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SECTION 1. SHORT TITLE. This Act may be cited as the ``Taxpayer Receipt Act''. SEC. 2. ITEMIZED FEDERAL TAX RECEIPT. (a) In General.--Chapter 77 of the Internal Revenue Code of 1986 is amended by adding at the end the following new section: ``SEC. 7529. FEDERAL TAX RECEIPT. ``(a) In General.--The Secretary shall send to every taxpayer who files an individual income tax return for any taxable year an itemized Federal tax receipt showing a proportionate allocation (in money terms) of the taxpayer's total tax payment for such taxable year among major expenditure categories for the fiscal year ending in such taxable year. The Federal tax receipt shall also include 2 separate line items showing the amount of Federal debt per legal United States resident at the end of such fiscal year, and the amount of additional borrowing per legal United States resident by the Federal Government in such fiscal year. ``(b) Total Tax Payments.--For purposes of subsection (a), the total tax payment of a taxpayer for any taxable year is equal to the sum of-- ``(1) the tax imposed by subtitle A for such taxable year (as shown on such taxpayer's return), plus ``(2) the tax imposed by section 3101 on wages received by such taxpayer during such taxable year. ``(c) Determination of Proportionate Allocation of Tax Payment Among Major Expenditure Categories.--For purposes of determining a proportionate allocation described in subsection (a), not later than 60 days after the end of any fiscal year, the Director of the Congressional Budget Office shall provide to the Secretary the percentage of Federal outlays for such fiscal year for the following categories and subcategories of Federal spending: ``(1) Social Security. ``(2) National defense: ``(A) Overseas combat operations. ``(3) Medicare. ``(4) Low-income assistance programs: ``(A) Housing assistance. ``(B) Food stamps and other food programs. ``(5) Other Federal health programs: ``(A) Medicaid, Children's Health Insurance Program, and other public health programs. ``(B) National Institutes of Health and other health research and training programs. ``(C) Food and Drug Administration, Consumer Product Safety Commission, and other regulatory health and safety activities. ``(6) Unemployment benefits. ``(7) Net interest on the Federal debt. ``(8) Veterans benefits and services. ``(9) Education: ``(A) K-12 and vocational education. ``(B) Higher education. ``(C) Job training and assistance. ``(10) Federal employee retirement and disability benefits. ``(11) Highway, mass transit, and railroad funding. ``(12) Mortgage finance (Federal National Mortgage Association, Federal Home Loan Mortgage Corporation, Federal Housing Administration, and other housing finance programs). ``(13) Justice and law enforcement funding, including Federal Bureau of Investigation, Federal courts, and Federal prisons. ``(14) Natural resources, land, and water management and conservation funding, including National Parks. ``(15) Foreign aid. ``(16) Science and technology research and advancement: ``(A) National Aeronautics and Space Administration. ``(17) Air transportation, including Federal Aviation Administration. ``(18) Farm subsidies. ``(19) Energy funding, including renewable energy and efficiency programs, Strategic Petroleum Reserve, and Federal Energy Regulatory Commission. ``(20) Disaster relief and insurance, including Federal Emergency Management Administration. ``(21) Diplomacy and embassies. ``(22) Environmental Protection Agency and pollution control programs. ``(23) Internal Revenue Service and United States Treasury operations. ``(24) Coast Guard and maritime programs. ``(25) Community Development Block Grants. ``(26) Congress and legislative branch activities. ``(27) United States Postal Service. ``(28) Executive Office of the President. ``(29) Other Federal spending. ``(d) Additional Major Expenditure Categories.--With respect to each fiscal year, the Director of the Congressional Budget Office shall include additional categories and subcategories of Federal spending for purposes of subsection (c), but only if, and only for so long as, each such additional category or subcategory exceeds 3 percent of total Federal outlays for the fiscal year. ``(e) Timing of Federal Tax Receipt.--A Federal tax receipt shall be made available to each taxpayer as soon as practicable upon the processing of that taxpayer's income tax return by the Internal Revenue Service. ``(f) Use of Technologies.--The Internal Revenue Service is encouraged to utilize modern technologies such as electronic mail and the Internet to minimize the cost of sending Federal tax receipts to taxpayers. The Internal Revenue Service shall establish an interactive program on its Internet Web site to allow taxpayers to generate Federal tax receipts on their own. ``(g) Cost.--No charge shall be imposed to cover any cost associated with the production or distribution of the Federal tax receipt. ``(h) Regulations.--The Secretary may prescribe such regulations as may be necessary to carry out this section.''. (b) Clerical Amendment.--The table of sections for chapter 77 of the Internal Revenue Code of 1986 is amended by adding at the end the following new item: ``Sec. 7529. Federal tax receipt.''. (c) Effective Date.--The amendments made by this section shall apply to taxable years beginning after the date of the enactment of this Act.

Taxpayer Receipt Act This bill amends the Internal Revenue Code to require the Department of the Treasury to provide every taxpayer who files an individual income tax return for any taxable year an itemized tax receipt showing: (1) the proportionate allocation of the taxpayer's payment in such year among major expenditure categories of the federal budget (e.g., social security, national defense, Medicare and other federal health programs, low-income assistance programs, unemployment benefits, net interest on the federal debt, and other federal programs); and (2) the amount of the federal debt at the end of the fiscal year and the amount of additional borrowing by the federal government in such fiscal year for each legal U.S. resident.

trinification @xcite refers to unified theories based on the gauge group @xmath1 , with gauge coupling equality imposed at a high scale , typically by a discrete symmetry that cyclically permutes the gauge group labels @xmath2 , @xmath3 , and @xmath4 . the higgs fields responsible for breaking @xmath5 to the standard model gauge group appear in the @xmath6-dimensional representation , @xmath7 the component fields @xmath8 transform as @xmath9 , @xmath10 s under the pair of gauge groups @xmath11 , @xmath12 , and @xmath13 , respectively . the theory thus specified has a simple moose representation , shown in fig . [ fig1 ] , with the component fields @xmath8 serving as the ` links ' that connect neighboring gauge group ` sites ' . this structure is reminiscent of a deconstructed higher - dimensional theory @xcite , aside from the fact that the link fields in eq . ( [ eq : higgs27 ] ) do not have the same purpose as in deconstruction , namely , to break chains of replicated gauge groups down to their diagonal subgroup . nevertheless , the structure of fig . [ fig2 ] suggests a natural generalization to trinified theories in which the group factors @xmath2 , @xmath3 , and @xmath4 are replicated @xmath14 times . we discuss this generalization in section [ sec : generalized ] . these theories also have a simple moose representation , and a gauge spectrum that can be interpreted via deconstruction . in particular , we will see that the gauge sector of the theory is a four - dimensional analog of the 5d trinified theory of ref . @xcite , in which gauge symmetry breaking effects are localized entirely on a boundary . such 5d theories have interesting properties @xcite , such as the logarithmic running of the gauge coupling difference @xmath15 , for @xmath16 , and a delay in the scale of unification above @xmath17 gev , the value obtained in the minimal supersymmetric standard model ( mssm ) . the construction of purely four - dimensional theories with such properties is clearly worthy of pursuit , and has lead to interesting results in the case of su(5 ) @xcite and so(10 ) @xcite unification . the present work complements this body of literature by introducing a new class of 4d unified theories that are closely related to the deconstruction of 5d trinified guts . that said , it will not be the purpose of this paper to present a literal deconstruction of the theories discussed in ref . rather , we proceed from a mostly 4d perspective and develop models that are viable and economical . for example , in determining the embedding of matter fields in the theory , we do nt follow the prescription of deconstruction at all , so that our 4d theory as a whole can not be mapped to a local 5d theory in the continuum limit . the higher - dimensional flavor of gauge unification is nonetheless retained leading to a new and interesting class of 4d unified theories . our paper is organized as follows . in section [ sec : generalized ] , we review conventional trinification and define a generalization to @xmath0 replicated su(3 ) groups . in section [ sec : spectrum ] , we study the gauge boson spectrum of the model , for arbitrary values of the localized symmetry - breaking vacuum expectation values ( vevs ) . in section [ sec : unification ] , we apply these results to study gauge coupling unification in this class of models . in section [ sec : matter ] , we describe how one may successfully include matter and light higgs fields , so the low - energy particle content is the same as in the mssm . in section [ sec : conc ] , we summarize our results and suggest directions for future study . 3.3 in conventional trinified theories @xcite are based on the gauge group @xmath18 , where @xmath19 indicates a semidirect product . the @xmath20 symmetry cyclically permutes the gauge group labels @xmath2 , @xmath3 and @xmath4 , ensuring a single unified coupling at the gut scale . the breaking of @xmath5 to the standard model gauge group requires a higgs field in the @xmath21-dimensional representation , @xmath22 where the numbers shown represent the su(3)@xmath23 , su(3)@xmath24 and su(3)@xmath25 representations , respectively . at least one such field must develop the vacuum expectation value , @xmath26 the presence of vevs only in the third row assures that su(2)@xmath24 remains unbroken , while nonvanishing @xmath27 and @xmath28 entries leave a single unbroken u(1 ) factor , generated by a linear combination of the diagonal generators of su(3)@xmath24 and su(3)@xmath25 . identifying this with hypercharge @xmath29 , one finds , @xmath30 note that su(3)@xmath31su(3)@xmath25 symmetry allows one to rotate away the vev @xmath32 in eq . ( [ eq : thevevs ] ) . therefore , it is usually assumed that at least two @xmath6 higgs fields with vacuum expectation values in the desired entries are present in the theory . we will return to this issue in sec . [ sec : matter ] . one can verify that this construction yields the standard gut - scale prediction for the weak mixing angle @xmath33 . let us focus on the structure of the gauge and unified - symmetry - breaking sectors of the theory . a conventional trinified theory can be represented by the moose diagram shown in fig . [ fig1 ] . for the sake of simplicity we display only a single higgs @xmath6 . the moose representation makes it clear that the @xmath6 is anomaly - free , which is relevant for the higgs representations since we assume supersymmetry . the @xmath20 symmetry is encoded in the symmetry of the moose under rotations by @xmath34 . 3.3 in now consider the generalization of this moose to @xmath0 gauge groups , as shown in fig . each link field transforms as a @xmath35 under consecutive su(3 ) groups , reading around the moose diagram clockwise . we assume that a generic link has vev @xmath36 where @xmath37 or @xmath4 . this breaks a chain of su(3 ) factors , namely su(3)@xmath38 for @xmath39 , down to its diagonal subgroup . the diagonal subgroups are precisely su(3)@xmath40su(3)@xmath31su(3)@xmath25 of conventional ( @xmath41 ) trinified theories . the three links which are not generic are identified with the links of the @xmath41 theory and have the corresponding expectation values . in particular , the links @xmath42 and @xmath43 have no vevs and serve to truncate a linear moose that contains unbroken su(3)@xmath23 . if the link @xmath44 also had no vev , we could make an analogous statement for su(3)@xmath24 and su(3)@xmath25 ; we assume , however , that this link has precisely the expectation value necessary to break su(3)@xmath45su(3)@xmath25 down to the electroweak gauge group of the standard model . thus , the total effect of the link vevs is to break @xmath46 below the scales @xmath47 , @xmath48 and @xmath32 . at this point , we have said nothing about the values of the @xmath0 gauge couplings . to maintain gauge unification , we assume that the theory defined by fig . [ fig2 ] is restricted by a @xmath20 symmetry that sets equal three sets of @xmath14 gauge couplings each , @xmath49 thus , we see that the moose in fig . [ fig2 ] is also symmetric under rotations by @xmath34 , like the @xmath41 theory . unification is maintained as in the @xmath41 theory since the couplings of the diagonal subgroups are given by @xmath50 for @xmath37 or @xmath4 . note that the vev of the @xmath51 link breaks both su(3)@xmath52 and the cyclic symmetry of the moose . it is important to note that we are agnostic as to whether the @xmath20 symmetry is a symmetry of the full theory , including the fermion representations , or is only an accidental symmetry of the gauge sector . the latter could be the case if , for example , all of the gauge couplings are equal at a high scale due to the dynamics of a more complete , high - energy theory . we will remain open to both possibilities in our subsequent model building . in the theory we have described thus far , the special links between @xmath53-@xmath54 , @xmath55-@xmath56 and @xmath57-@xmath58 contribute to the low - energy particle content of the theory . on the other hand , we wish only to have two light higgs doublets together with the matter content of the mssm . how we may arrange for this is discussed in sec . [ sec : matter ] . we first , however , address the less model - dependent issue of gauge unification , assuming that the low - energy matter and higgs content is that of the mssm . let us begin by discussing the spectrum of the @xmath59 gauge multiplets , for @xmath60 . this portion of the theory is a linear moose with @xmath14 unbroken su(3 ) factors . the contribution to the gauge boson mass matrix from a link spanning the @xmath61 and @xmath62 site is given by @xmath63,\ ] ] ( with @xmath64 ) leading to the @xmath65 mass squared matrix @xmath66 here we take all su(3 ) gauge couplings to be equal , and adopt this simplifying assumption henceforth . the mass spectrum given by eq . ( [ eq : cspec ] ) is that of a deconstructed 5d su(3 ) gauge theory , and is well known @xcite , @xmath67 where @xmath68 is the lattice spacing . the @xmath3 and @xmath4 sectors of the moose are more interesting due to the presence of the nontrivial vev at the @xmath53-@xmath54 link . let us define the @xmath69 gauge field as the @xmath70-component column vector @xmath71 \,\,\ , , \,\,\,\,\ , j = n+1-i \,\,\ , , \,\,\,\,\ , i=1\ldots n\ , . \label{eq : basis}\ ] ] if one were to excise the @xmath72 sector of the circular moose in fig . [ fig2 ] , and to bend it about the special link at @xmath53-@xmath54 , one would obtain a linear moose with @xmath14 sites , corresponding to gauge fields @xmath73 in eq . ( [ eq : basis ] ) . the symmetry breaking effects of the special link are confined to the @xmath74 lattice site . thus , we will be able to interpret our result as a deconstructed 5d theory with bulk su(3)@xmath31su(3)@xmath25 gauge symmetry broken at a boundary . since the @xmath3-@xmath3 and @xmath4-@xmath4 link fields give identical contributions to the su(3)@xmath24 and su(3)@xmath25 gauge boson mass matrices , respectively , we may express the mass matrix for the @xmath73 as @xmath75 where each entry represents a @xmath76 matrix in @xmath72 space . only the boundary contribution @xmath77 has a nontrivial structure in this space all others are proportional to an implicit identity matrix . the form of @xmath77 is precisely that of the @xmath72 gauge boson mass squared matrix in a conventional , @xmath41 trinified theory . let @xmath78 be the @xmath70-dimensional unitary matrix which diagonalizes @xmath77 : @xmath79 then the @xmath80 entry of eq . ( [ eq : lrspec ] ) may be diagonalized without affecting any of the others by letting @xmath81 , where @xmath82 is the unitary matrix @xmath83 since each @xmath70-dimensional sub - block is now - diagonalized , we end up with @xmath70 decoupled mass matrices , corresponding to the eigenvalues @xmath84 of @xmath77 : @xmath85 four of the eigenvalues of @xmath77 are zero , corresponding to the unbroken su(2)@xmath86u(1)@xmath87 gauge bosons , while the remaining @xmath88 are superheavy . for the massless states ( @xmath89 ) , eq . ( [ eq : simplerm ] ) reduces to eq . ( [ eq : cspec ] ) , as one would expect , and the mass spectrum is given by eq . ( [ eq : mspecsm ] ) . the massive gauge fields are more interesting . in this case , @xmath90 is nonvanishing and is of the order @xmath91 . we can find the mass spectrum in the @xmath92 case by exploiting a mechanical analogy . consider the system of masses @xmath93 and springs shown in fig . [ fig3]a . 5 in the equation of motion for the @xmath69 block is given by @xmath94 where @xmath95 has precisely the form of eq . ( [ eq : simplerm ] ) , with the identifications @xmath96 and @xmath97 . the squared frequencies of the normal modes of this mechanical system are precisely the eigenvalues of @xmath95 . notice that as @xmath98 is made large ( _ i.e. _ the massive gauge bosons of the last site in the moose are decoupled ) , the @xmath74 block in our spring system effectively becomes a fixed wall . we then obtain an @xmath99 mass matrix of the same form as eq . ( [ eq : simplerm ] ) with @xmath100 . this is exactly what we expect for the massive gauge modes when the @xmath74 site has a smaller gauge symmetry than the other sites in the moose ( see for example , ref . @xcite . ) the eigenvalues of @xmath95 may be found by considering the translationally invariant system shown in fig . [ fig3]b , and imposing boundary conditions that mimic the dynamics of the first and @xmath74 block of the system of interest . let @xmath101 represent the displacement of the @xmath69 block about its equilibrium position , where @xmath102 is the inter - block spacing . the fact that the first block has no spring to the left is equivalent to the boundary condition @xmath103 in the translationally invariant system . on the other hand , the effect of the spring with larger spring constant @xmath98 to the right of the @xmath74 block is replicated by the condition @xmath104 ) = -(\eta - 1 ) \ , \psi(an ) \,\,\ , . \label{eq : bcright}\ ] ] in other words , in the infinite system , one requires that the @xmath105 block moves so that the force on the @xmath74 block is indistinguishable from that of a stiffer spring connected to a wall . we may thus consider a normal mode solution to the infinite system of the form @xmath106 and determine the wave numbers @xmath107 allowed by these boundary conditions . we find that @xmath108 values of @xmath107 are determined by the transcendental equation @xmath109 leading to the eigenvalues @xmath110 here , @xmath111 represents the squared frequencies of the normal mode solutions in the mechanical system , and @xmath108 gauge boson squared masses in the problem of interest . the @xmath74 gauge boson mass , however , is not given by eqs . ( [ eq : telight ] ) and ( [ eq : mslight ] ) . the reason is that we have assumed that @xmath107 is real ; complex @xmath107 is perfectly consistent with the translation invariance of the infinite system ( see , for example , ref . taking @xmath112 , one finds another solution : @xmath113 with @xmath114 it is not hard to verify that eqs ( [ eq : telight ] ) , ( [ eq : mslight ] ) , ( [ eq : teheavy ] ) and ( [ eq : msheavy ] ) are correct . for example , a two - by - two matrix with @xmath115 and @xmath116 , has eigenvalues @xmath117 . the corresponding solutions to eqs . ( [ eq : telight ] ) and ( [ eq : teheavy ] ) are @xmath118 and @xmath119 , which yield precisely the same results via eqs . ( [ eq : mslight ] ) and ( [ eq : msheavy ] ) . the parameter @xmath90 allows us to interpolate between a number of familiar limits . for example , the choice @xmath120 yields the mass matrix for a gauge boson distributed among @xmath14 sites that receives no mass contribution from the @xmath105 link field . this is the case , for example , for the massive @xmath121 and @xmath29 bosons in an su(5 ) moose with @xmath122 sites , in which the gauge symmetry of the last site is taken to be su(3)@xmath40su(2)@xmath86u(1)@xmath87 . in this case , eq . ( [ eq : telight ] ) reduces to @xmath123)=0\ ] ] which is solved by @xmath124 this is consistent with the results of ref . @xcite , which presents the spectrum of a deconstructed 5d su(5 ) theory with unified symmetry broken explicitly at an orbifold fixed point . since we generally assume that @xmath125 , and hence that @xmath126 , a more relevant limit is the one in which @xmath127 . as we described earlier , this corresponds to a physical system in which the @xmath74 block has effectively become fixed . in this case , eq . ( [ eq : telight ] ) reduces to @xmath128)=0\ ] ] which is solved by @xmath129 as we expect , this result is simply eq . ( [ eq : exone ] ) with the replacement @xmath130 . for large values of @xmath14 , the expression for @xmath93 is approximately @xmath131 where we have identified the compactification scale @xmath132 . this is shifted relative to the gauge bosons with zero modes , which have the spectrum @xmath133 in the same limit . this is exactly the behavior we expect in the higgsless theory @xcite , obtained when when takes the boundary vevs @xmath134 . thus , the present work demonstrates how one may obtain a four - dimensional analog for the 5d higgsless trinified model described in ref . @xcite . with eqs . ( [ eq : mspecsm ] ) , ( [ eq : telight ] ) , ( [ eq : mslight ] ) , ( [ eq : teheavy ] ) , and ( [ eq : msheavy ] ) in hand , we have all the information we need to take into account the effect of finite boundary vevs on the gauge boson mass spectrum . we will use this result in our study of gauge unification in the following section . aside from the @xmath135 vector supermultiplets that we expect at each massive kk level of the deconstructed theory @xcite , we assume that the only other fields relevant for unification are the light matter and higgs fields of the mssm . we justify this assumption in sec . [ sec : matter ] , where we demonstrate how this can be arranged . we will find it convenient to express our results in terms of the differences @xmath136 where @xmath137 is the renormalization scale . since the theory of interest to us here represents a deconstructed version of the 5d trinified theory of ref . @xcite , the basic quantities of interest in studying gauge unification at the one loop level have the same form : @xmath138 @xmath139 @xmath140 here , @xmath141 and @xmath142 represent the mass levels corresponding to gauge fields with and without zero modes , respectively . these expressions are valid for @xmath143 , which we assume to be the lightest gauge field kk excitation ( recall that as @xmath127 , @xmath144 ) . the unification scale @xmath145 is identified with the scale at which the moose is reduced to the diagonal subgroup su(3)@xmath40su(3)@xmath31su(3)@xmath25 ; this is usually taken to be @xmath146 , the scale of the heaviest kk excitation . thus we require @xmath147 which determines the unification scale in terms of @xmath0 and @xmath90 . for arbitrary @xmath90 , eq . ( [ eq : ucond ] ) can be solved numerically ; for example , with @xmath148 and @xmath149 , one finds that @xmath150 is @xmath151 gev , as is shown in fig . [ fig4 ] . 4 in the changes in slope of @xmath152 and @xmath153 above @xmath154 correspond to vector multiplet mass thresholds . the one kink present above the unification scale corresponds to the mass threshold that decouples in the @xmath155 limit . one finds that the quality of unification in this example is given by @xmath156 note that the unification scale is above @xmath17 gev , the unification scale of conventional supersymmetric theories . since we are interested in @xmath157 , we will analyze the general case as an expansion in @xmath158 . the results we present below may be derived by taking into account the following simplifications , @xmath159 and @xmath160 which are valid if the renormalization scale is above all but the last mass threshold @xmath161 ( _ i.e. _ , the kink above the unification point shown in fig . [ fig4 ] is not included in the sums ) . then it follows that @xmath162 which clarifies the previously noted delay in unification by showing the scaling in @xmath14 and the weak dependence on @xmath90 , for @xmath90 large . one may also use eqs . ( [ eq : sumzero ] ) and ( [ eq : sumh ] ) to obtain a general expression for the quality of unification ( _ e.g. _ eq . ( [ eq : n6uq ] ) ) . one finds , @xmath163 where @xmath164 the function @xmath165 ranges approximately from @xmath166 to @xmath167 , for large @xmath90 , assuring reasonably accurate unification . 3.5 in we now show how one may construct tri - n - ified theories with the low - energy particle content of the mssm . our first example assumes that the @xmath20 symmetry applies to the theory as a whole , including the fermion representations , which makes achieving the desired low - energy theory nontrivial . let us consider a viable model for the next - to - minimal case of @xmath168 . we would first like to arrange for precisely two higgs doublet fields in the low - energy spectrum . we follow the approach of ref . @xcite and consider doublets living within @xmath6 and @xmath169 representations of the diagonal subgroup , and an additional higgs field in the @xmath170-dimensional representation , to arrange for doublet - triplet splitting . the higgs @xmath6 consists of the ` special ' links in the original circular moose , namely , the links between the sites @xmath53-@xmath171 , @xmath57-@xmath172 , and @xmath55-@xmath173 . the main purpose of these links was to cancel anomalies , and to provide for the breaking of the diagonal gauge group at a boundary . we add the @xmath169 as shown by the dashed lines in fig . [ fig5 ] . notice that to avoid anomalies , we have added spectator fields ; for example , the @xmath174 component requires three spectators with quantum numbers @xmath175 , for @xmath176 and three with quantum numbers @xmath177 . the links that acquire diagonal vevs generate mass terms for these spectators , @xmath178 where the @xmath179 are coupling constants . while the spectators are present at the unification scale , they do not alter the renormalization group analysis presented in the previous section . with both @xmath6 and @xmath169 higgs fields present in the theory , we can arrange for heavy masses for all the color - triplet components . doublet - triplet splitting may be obtained by adding the higgs representation @xmath180 . notice that the representation @xmath181 is anomaly free , so we do not require any additional spectator fields . we assume that only the @xmath182 component of the @xmath170 and the @xmath183 of the @xmath169 acquire gut - breaking vacuum expectation values , which again localizes the breaking of the diagonal subgroup to the @xmath53-@xmath171 link . these new vevs contribute to the the matrix @xmath77 in eq . ( [ eq : lrspec ] ) , but otherwise do not alter the discussion of section [ sec : unification ] . in addition , appropriate vevs in the @xmath170 and the @xmath169 prevent one from eliminating the desired symmetry - breaking effect of eq . ( [ eq : thevevs ] ) via a gauge transformation . calling the @xmath169 higgs @xmath184 , the superpotential terms relevant to doublet - triplet splitting are given by @xmath185 as described in ref . @xcite , a vev of the form @xmath186 allows one to make a doublet component of @xmath187 and a doublet component of @xmath188 light , provided that @xmath189 . the light components , which we identify as the two higgs doublets of the mssm are localized at the @xmath53-@xmath171 link . note that the down - type higgs doublet lives within the @xmath169 representation , which does not have a direct yukawa coupling with matter fields transforming in the @xmath21 . however , @xmath190 transforms as a @xmath6 , where @xmath191 is an ultraviolet cutoff . this combination provides for down - type higgs yukawa couplings via higher - dimension operators , suppressed relative to the up - type couplings by a factor of @xmath192 . we now must arrange for the embedding of three generations of matter fields , so that there are adequate couplings to the light , localized higgs doublets . a possible configuration is shown in fig . [ fig6 ] . 3.0 in here we have chosen to embed the matter fields so that the moose remains invariant under @xmath34 rotations . one could argue , therefore , that the @xmath20 symmetry forces the existence of three generations in this model . since the light higgs doublets are only present on the @xmath53-@xmath171 link , while the generations are delocalized we expect that yukawa couplings originate via higher - dimension operators , suppressed by powers of @xmath193 . for the model to be successful , these suppression factors must not be so great that we are prevented from achieving phenomenologically viable yukawa textures . let us identify the matter @xmath6 s by the sites that they connect , _ e.g. _ , @xmath194 transforms under the subset of gauge groups ( @xmath172,@xmath53,@xmath171 ) . then we identify the three generations as follows : @xmath195 given this choice , we see , for example , that the third generation yukawa couplings are not suppressed , @xmath196 while a purely second generation coupling @xmath197 involves a suppression factor of order @xmath198 . one therefore finds that the entries of the up quark yukawa matrix involve suppression factors summarized by @xmath199 where we have defined @xmath200 ; the down sector suppression factors are one power of @xmath192 higher . the tightest constraint on the size of these parameters comes from the strange quark yukawa coupling , which requires that @xmath201 . provided that this is satisfied , one may choose coupling matrices @xmath202 and @xmath203 to obtain the additional flavor suppression required to produce yukawa textures that are phenomenologically viable ( for example , compare to those found in ref . the reader can check that the same is true in the charged lepton sector as well . in addition , the @xmath6 s of matter fields contain exotic particle content that becomes heavy in minimal trinified theories due to the su(3)@xmath204-breaking vevs of the @xmath53-@xmath171 link . the same happens here , though there is some suppression due to the delocalization of the matter multiplets . since a generic link field transforms as @xmath205 , and it is possible to arrange @xmath206 , by elementary su(3 ) group theory , one has the necessary building blocks to reproduce _ any _ mass operator of the @xmath41 theory at some order in @xmath207 . note that the exotic fields in the @xmath21 form complete su(5 ) multiplets @xcite , so they can appear below the unification scale without substantially altering the conclusions of section [ sec : unification ] . while the previous model can accommodate the flavor structure of the standard model , it is not clear whether successful models can be constructed for larger @xmath14 . the assumption of the unbroken @xmath20 symmetry would force different generations to be widely separated if the number of sites is large . let us consider the possibility that the unified boundary condition on the gauge couplings has a dynamical origin and is not due to symmetry . equivalently , we may assume that the @xmath20 symmetry is an accidental symmetry of the gauge and higgs sector , but not of the matter fields . then we may place all three generations on a single set of gauge sites , namely , @xmath208-@xmath53-@xmath171 , for some @xmath61 . in this case , no suppression factors appear in the yukawa couplings , and the origin of the fermion mass hierarchy is completely decoupled from the physics of unification . while we keep the arrangement of higgs fields the same , we can add an additional three pairs of @xmath209 and @xmath210 spectator fields at each new gauge site ; in this way , all spectators will acquire gut - scale masses by coupling in pairs via an intermediate link field . for either the @xmath2 , @xmath3 or @xmath4-sector spectators , these interactions have the form @xmath211 using this construction , we can study models with many more gauge sites . the only limitation on the size of @xmath14 comes from the assumption that the su(3 ) gauge couplings @xmath212 remain perturbative . for the case of identical gauge couplings , @xmath212 is related to the gauge coupling of the diagonal subgroup , @xmath213 , by @xmath214 using our earlier renormalization group analysis , one finds numerically that the constraint @xmath215 translates to @xmath216 we have considered a natural generalization of trinification to theories with @xmath0 gauge groups . we have showed that the gauge and higgs sector of the theory can be interpreted as a deconstructed version of a 5d trinified theory with unified symmetry broken at a boundary ; we have studied the gauge spectrum in the deconstructed theory for arbitrary boundary higgs vevs . as in the 5d theory , the differences in inverse gauge couplings evolve logarithmically , and one finds successful unification at a scale higher than in the 4d mssm . since the unification scale grows as @xmath217 , unification may be delayed to @xmath218 gev before the gauge coupling of the replicated su(3 ) factors becomes nonperturbative . this might be compared to the result in the 5d theory , @xmath219 gev , which is the point at which the 5d planck scale and the unification scale coincide @xcite . we have also considered ways in which the light matter and higgs content of the mssm could be embedded in the ( rather large ) unified group . we first showed how doublet - triplet splitting could be arranged , via fine tuning , leaving light higgs doublets localized between two gauge sites in the original moose . the point here is not to solve the doublet - triplet splitting problem , but to present a viable zeroth - order framework in which such questions can be studied . with all symmetry breaking localized , we then considered the embedding of matter fields . assuming first that the unified boundary condition on the gauge couplings arises from a @xmath20 symmetry that rotates the moose by @xmath34 , one obtains symmetrical embeddings of the fermion multiplets within the moose ( _ c.f . _ , fig . [ fig6 ] ) . although these have no strict extra - dimensional interpretation , we have , roughly speaking , delocalized the fermion multiplets while keeping all the symmetry - breaking and light higgs fields at one point . we show for relatively small moose , one can arrange for sufficient overlaps via higher - dimension operators involving the link fields to account for fermion masses and inter - generational mixing . for larger moose , we assume instead that the unified boundary condition on the gauge couplings is simply present ( or alternately , the @xmath20 symmetry is an accidental symmetry of only the gauge and higgs sectors ) so that matter can be embedded asymmetrically . then the overlap between matter fields and light higgs fields can be made maximal and no restriction follows on the size of the moose . alternatively , such models provide the freedom to adjust matter - matter and matter - higgs overlaps in a way that can account in part for the flavor hierarchies of the standard model . this is one advantage of the models introduced here over minimal trinified scenarios . aside from demonstrating how one may deconstruct the 5d trinified theory described in ref . @xcite , we have arrived at at class of 4d theories that are interesting in their own right . this is not a surprise , as the same is true of deconstructed 5d theories based on su(5 ) symmetry that have been studied in the literature @xcite . the present work therefore provides a new framework for future study of a range of familiar issues , including the implementation of solutions to the doublet - triplet splitting problem , proton decay phenomenology , the origin of flavor via combined unified and horizontal symmetries , construction of explicit symmetry breaking sectors , _ etc_. models based on the idea of nonsupersymmetric triplicated trinification @xcite may also be worthy of study in this context . k. s. babu , x. g. he and s. pakvasa , phys . rev . d * 33 * , 763 ( 1986 ) . g. lazarides and c. panagiotakopoulos , phys . b * 336 * , 190 ( 1994 ) [ arxiv : hep - ph/9403317 ] . g. lazarides and c. panagiotakopoulos , phys . d * 51 * , 2486 ( 1995 ) [ arxiv : hep - ph/9407286 ] . k. s. choi and j. e. kim , phys . b * 567 * , 87 ( 2003 ) [ arxiv : hep - ph/0305002 ] ; j. e. kim , [ arxiv : hep - th/0301177 ] . s. willenbrock , phys . lett . b * 561 * , 130 ( 2003 ) [ arxiv : hep - ph/0302168 ] . g. r. dvali and q. shafi , phys . b * 339 * , 241 ( 1994 ) [ arxiv : hep - ph/9404334 ] . n. arkani - hamed , a. g. cohen and h. georgi , phys . lett . * 86 * , 4757 ( 2001 ) [ arxiv : hep - th/0104005 ] . c. t. hill , s. pokorski and j. wang , phys . d * 64 * , 105005 ( 2001 ) [ arxiv : hep - th/0104035 ] . c. d. carone and j. m. conroy , phys . d * 70 * , 075013 ( 2004 ) [ arxiv : hep - ph/0407116 ] . y. nomura , d. r. smith and n. weiner , nucl . b * 613 * , 147 ( 2001 ) [ arxiv : hep - ph/0104041 ] . c. csaki , g. d. kribs and j. terning , phys . d * 65 * , 015004 ( 2002 ) [ arxiv : hep - ph/0107266 ] . h. c. cheng , k. t. matchev and j. wang , phys . b * 521 * , 308 ( 2001 ) [ arxiv : hep - ph/0107268 ] . c. s. huang , j. jiang and t. li , nucl . b * 702 * , 109 ( 2004 ) [ arxiv : hep - ph/0407180 ] . c. csaki , c. grojean , h. murayama , l. pilo and j. terning , phys . d * 69 * , 055006 ( 2004 ) [ arxiv : hep - ph/0305237 ] . h. georgi , _ the physics of waves _ , englewood cliffs , n.j . , prentice hall , 1993 . c. csaki , j. erlich , d. z. freedman and w. skiba , phys . d * 56 * , 5209 ( 1997 ) [ arxiv : hep - th/9704067 ] . c. csaki , j. erlich , c. grojean and g. d. kribs , phys . d * 65 * , 015003 ( 2002 ) [ arxiv : hep - ph/0106044 ] . a. aranda , c. d. carone and r. f. lebed , phys . d * 62 * , 016009 ( 2000 ) [ arxiv : hep - ph/0002044 ] ; phys . b * 474 * , 170 ( 2000 ) [ arxiv : hep - ph/9910392 ] .

we consider a natural generalization of trinification to theories with @xmath0 su(3 ) gauge groups . these theories have a simple moose representation and a gauge boson spectrum that can be interpreted via the deconstruction of a 5d theory with unified symmetry broken on a boundary . although the matter and higgs sectors of the theory have no simple extra - dimensional analog , gauge unification retains features characteristic of the 5d theory . we determine possible assignments of the matter and higgs fields to unified multiplets and present theories that are viable alternatives to minimal trinified guts .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Private Investment in Housing Act of 2015''. SEC. 2. BUDGET-NEUTRAL DEMONSTRATION PROGRAM FOR ENERGY AND WATER CONSERVATION IMPROVEMENTS AT MULTIFAMILY RESIDENTIAL UNITS. (a) Establishment.--The Secretary of Housing and Urban Development (in this section referred to as the ``Secretary'') shall establish a demonstration program under which the Secretary may execute budget- neutral, performance-based agreements in fiscal years 2016 through 2019 that result in a reduction in energy or water costs with such entities as the Secretary determines to be appropriate under which the entities shall carry out projects for energy or water conservation improvements at not more than 20,000 residential units in multifamily buildings participating in-- (1) the project-based rental assistance program under section 8 of the United States Housing Act of 1937 (42 U.S.C. 1437f), other than assistance provided under section 8(o) of that Act; (2) the supportive housing for the elderly program under section 202 of the Housing Act of 1959 (12 U.S.C. 1701q); or (3) the supportive housing for persons with disabilities program under section 811(d)(2) of the Cranston-Gonzalez National Affordable Housing Act (42 U.S.C. 8013(d)(2)). (b) Requirements.-- (1) Payments contingent on savings.-- (A) In general.--The Secretary shall provide to an entity a payment under an agreement under this section only during applicable years for which an energy or water cost savings is achieved with respect to the applicable multifamily portfolio of properties, as determined by the Secretary, in accordance with subparagraph (B). (B) Payment methodology.-- (i) In general.--Each agreement under this section shall include a pay-for-success provision that-- (I) shall serve as a payment threshold for the term of the agreement; and (II) requires that payments shall be contingent on realized cost savings associated with reduced utility consumption in the participating properties. (ii) Limitations.--A payment made by the Secretary under an agreement under this section-- (I) shall be contingent on documented utility savings; and (II) shall not exceed the utility savings achieved by the date of the payment, and not previously paid, as a result of the improvements made under the agreement. (C) Third-party verification.--Savings payments made by the Secretary under this section shall be based on a measurement and verification protocol that includes at least-- (i) establishment of a weather-normalized and occupancy-normalized utility consumption baseline established pre-retrofit; (ii) annual third-party confirmation of actual utility consumption and cost for utilities; (iii) annual third-party validation of the tenant utility allowances in effect during the applicable year and vacancy rates for each unit type; and (iv) annual third-party determination of savings to the Secretary. An agreement under this section with an entity shall provide that the entity shall cover costs associated with third-party verification under this subparagraph. (2) Terms of performance-based agreements.--A performance- based agreement under this section shall include-- (A) the period that the agreement will be in effect and during which payments may be made, which may not be longer than 12 years; (B) the performance measures that will serve as payment thresholds during the term of the agreement; (C) an audit protocol for the properties covered by the agreement; (D) a requirement that payments shall be contingent on realized cost savings associated with reduced utility consumption in the participating properties; and (E) such other requirements and terms as determined to be appropriate by the Secretary. (3) Entity eligibility.--The Secretary shall-- (A) establish a competitive process for entering into agreements under this section; and (B) enter into such agreements only with entities that, either jointly or individually, demonstrate significant experience relating to-- (i) financing or operating properties receiving assistance under a program identified in subsection (a); (ii) oversight of energy or water conservation programs, including oversight of contractors; and (iii) raising capital for energy or water conservation improvements from charitable organizations or private investors. (4) Geographical diversity.--Each agreement entered into under this section shall provide for the inclusion of properties with the greatest feasible regional and State variance. (5) Properties.--A property may only be included in the demonstration under this section only if the property is subject to affordability restrictions for at least 15 years after the date of the completion of any conservation improvements made to the property under the demonstration program. Such restrictions may be made through an extended affordability agreement for the property under a new housing assistance payments contract with the Secretary of Housing and Urban Development or through an enforceable covenant with the owner of the property. (c) Plan and Reports.-- (1) Plan.--Not later than 90 days after the date of enactment of this Act, the Secretary shall submit to the Committees on Appropriations and Financial Services of the House of Representatives and the Committees on Appropriations and Banking, Housing, and Urban Affairs of the Senate a detailed plan for the implementation of this section. (2) Reports.--Not later than 1 year after the date of enactment of this Act, and annually thereafter, the Secretary shall-- (A) conduct an evaluation of the program under this section; and (B) submit to Congress a report describing each evaluation conducted under subparagraph (A). (d) Funding.--For each fiscal year during which an agreement under this section is in effect, the Secretary may use to carry out this section any funds appropriated to the Secretary for the renewal of contracts under a program described in subsection (a). Passed the House of Representatives July 14, 2015. Attest: KAREN L. HAAS, Clerk.

. Private Investment in Housing Act of 2015 (Sec. 2) Directs the Department of Housing and Urban Development (HUD) to establish a demonstration program under which, in FY2016 through FY2019, HUD may execute budget-neutral, performance-based agreements (for up to 12 years each) that result in a reduction in energy or water costs with appropriate entities to carry out projects for energy or water conservation improvements at up to 20,000 residential units in multifamily buildings participating in: Section 8 project-based rental assistance programs under the United States Housing Act of 1937, other than Section 8 (voucher program) assistance; supportive housing for the elderly programs under the Housing Act of 1959; or supportive housing for persons with disabilities programs under the Cranston-Gonzalez National Affordable Housing Act. Specifies requirements for payment under an agreement, which shall be contingent on documented utility savings, as well as for agreement terms, eligibility, geographical diversity, and funding for the program. Limits this demonstration program to properties subject to affordability restrictions, which may be through an affordability agreement under a new housing assistance payments contract with HUD, or through an enforceable covenant with the property owner, for at least 15 years after completion of any conservation improvements made under the program. Requires HUD to submit to specified congressional committees a detailed plan for the implementation of this Act. Authorizes HUD, for each fiscal year during which an agreement is in effect, to use any HUD appropriated funds for the renewal of contracts under the program.

therapeutic effects of various treatment options in burn wound healing have been one of the most controversial issues in wound care . aloe vera is an herbal medicine , which has wound healing effects on chronic wound . the present study was carried out to examine and compare the effect of aloe vera gel and nitrofurazone 2% on epithelialization and granulation tissue formation with respect to superficial second - degree burns . this is a randomized clinical trial and the sampling method was used based on pre - defined inclusion criteria . the sample size was 30 patients that were admitted to kerman burn center , including patients that had superficial burn in the symmetry limb , who were chosen based on depth burn and the qualifications needed for the study . one part of the burned area was dressed using ointment nitrofurazone 2% ( according to routine care in the hospital ) and the symmetry part was dressed using aloe vera gel . the tools for data collection included a demographic questionnaire , tools of bats - joints for checking epithelialization and granulation tissue . the burn wound epithelialization and granulation at the beginning of patient s admission and the first , second and third weeks after dressing were assessed and recorded . in patients treated with aloe vera gel , epithelialization and granulation tissue of burn wounds were remarkably earlier than those patients treated with nitrofurazone 2% ( p<0.05 ) . in conclusion , aloe vera gel enhanced epithelialization and granulation tissue of burn wounds in superficial second - degree burn patients better than nitrofurazone 2% . the mechanism of the remarkable efficacy of aloe vera gel in the epithelialization and granulation tissue of burn injuries may be explained by its hydrocolloid and moisturizing and anti - inflammatory effects .

background : therapeutic effects of various treatment options in burn wound healing have been one of the most controversial issues in wound care . aloe vera is an herbal medicine , which has wound healing effects on chronic wound . the present study was carried out to examine and compare the effect of aloe vera gel and nitrofurazone 2% on epithelialization and granulation tissue formation with respect to superficial second - degree burns.methods:this is a randomized clinical trial and the sampling method was used based on pre - defined inclusion criteria . the sample size was 30 patients that were admitted to kerman burn center , including patients that had superficial burn in the symmetry limb , who were chosen based on depth burn and the qualifications needed for the study . one part of the burned area was dressed using ointment nitrofurazone 2% ( according to routine care in the hospital ) and the symmetry part was dressed using aloe vera gel . the tools for data collection included a demographic questionnaire , tools of bats - joints for checking epithelialization and granulation tissue . the burn wound epithelialization and granulation at the beginning of patient s admission and the first , second and third weeks after dressing were assessed and recorded.results:in patients treated with aloe vera gel , epithelialization and granulation tissue of burn wounds were remarkably earlier than those patients treated with nitrofurazone 2% ( p<0.05).conclusion : in conclusion , aloe vera gel enhanced epithelialization and granulation tissue of burn wounds in superficial second - degree burn patients better than nitrofurazone 2% . the mechanism of the remarkable efficacy of aloe vera gel in the epithelialization and granulation tissue of burn injuries may be explained by its hydrocolloid and moisturizing and anti - inflammatory effects .

SECTION 1. BASELINE BASED ON PRIOR YEAR'S OUTLAYS. (a) President's Budget.--Section 1105(a)(5) of title 31, United States Code, is amended to read as follows: ``(5) except as provided in subsection (b) of this section-- ``(A) estimated expenditures and proposed appropriations for each function and subfunction in the current fiscal year; ``(B) estimated expenditures and proposed appropriations the President decides are necessary to support the Government for each function and subfunction in the fiscal year for which the budget is submitted; and ``(C) a comparison of levels of estimated expenditures and proposed appropriations for each function and subfunction in the current fiscal year and the fiscal year for which the budget is submitted, along with the proposed increase or decrease of spending in percentage terms for each function and subfunction;''. (b) Congressional Budget.--Section 301(e) of the Congressional Budget Act of 1974 (2 U.S.C. 632(e)) is amended by-- (1) inserting after the second sentence the following: ``The starting point for any deliberations in the Committee on the Budget of each House on the concurrent resolution on the budget for the next fiscal year shall be the estimated level of outlays for the current year in each function and subfunction. Any increases or decreases in the congressional budget for the next fiscal year shall be from those estimated levels.''; (2) striking paragraphs (2) and (3) and inserting the following: ``(2) a comparison of levels for the current fiscal year with proposed spending for the subsequent fiscal years along with the proposed increase or decrease of spending in percentage terms for each function and subfunction; ``(3) information, data, and comparisons indicating the manner in which and the basis on which the committee determined each of the matters set forth in the concurrent resolution, including information on outlays for the current fiscal year and the decisions reached to set funding for the subsequent fiscal years;''; (3) striking paragraph (8); (4) redesignating paragraph (9) as paragraph (8) and adding ``and'' at the end thereof; and (5) redesignating paragraph (10) as paragraph (9). (c) CBO Report to Committees.--The first sentence of section 202(f)(1) of the Congressional Budget Act of 1974 is amended to read as follows: ``On or before February 15 of each year, the Director shall submit to the Committees on the Budget of the House of Representatives and the Senate a report, for the fiscal year commencing on October 1 of that year, with respect to fiscal policy, including (A) estimated budget outlays in all functions and subfunctions for appropriated accounts for the current fiscal year and estimated budget outlays under current law for all entitlement programs for the next fiscal year, (B) alternative levels of total revenues, total new budget authority, and total outlays (including related surpluses and deficits), and (C) the levels of tax expenditures under existing law, taking into account projected economic factors and any changes in such levels based on proposals in the budget submitted by the President for such fiscal year.''. SEC. 2. SUNSETTING OF ENTITLEMENTS. (a) Reauthorization of Discretionary Programs and Unearned Entitlements.-- (1) Fiscal year 1994.--Effective October 1, 1993, spending authority for each unearned entitlement and high-cost discretionary spending program is terminated unless such spending authority is reauthorized after the date of enactment of this Act. (2) Fiscal year 1995.--Effective October 1, 1994, spending authority for each discretionary spending program (not including high-cost discretionary spending programs) is terminated unless such spending authority is reauthorized after the date of enactment of this Act. (3) Definitions.--For purposes of this section-- (A) the term ``unearned entitlement'' means an entitlement not earned by service or paid for in total or in part by assessments or contributions such as Social Security, veterans' benefits, retirement programs, and medicare; and (B) the term ``high-cost discretionary program'' means the most expensive one-third of discretionary program within each budget function account. (b) Point of Order.-- (1) In general.--It shall not be in order in the House of Representatives or the Senate to consider any bill, joint resolution, amendment, or conference report that includes any provision that appropriates funds unless such appropriation has been previously authorized by law. (2) Waiver or suspension.--This section may be waived or suspended in the House of Representatives or the Senate only by the affirmative vote of two-thirds of the Members, duly chosen and sworn. (c) Decennial Sunsetting.-- (1) First decennial census year.--Effective on the first day of the fiscal year beginning in the first decennial census year after the year 2000 and each 10 years thereafter, the spending authority described in subsection (a)(1) is terminated unless such spending authority is reauthorized after the last date the spending authority was required to be reauthorized under this section. (2) First decennial census year.--Effective on the first day of the fiscal year beginning in the year after the first decennial census year after the year 2000 and each 10 years thereafter, the spending authority described in subsection (a)(2) is terminated unless such spending authority is reauthorized after the last date the spending authority was required to be reauthorized under this section. SEC. 3. ELIMINATION OF EMERGENCY SPENDING FOR PURPOSES OF DISCRETIONARY CAPS. Section 251(b)(2)(D) of the Balanced Budget and Emergency Deficit Control Act of 1985 is repealed.

Amends Federal law to require both the President and the Congress to draft a budget based on estimates of current fiscal year spending, proposing increases or decreases based on this level (rather than on an estimated baseline). Amends the Congressional Budget Act of 1974 to require the Congressional Budget Office to use such a current fiscal year baseline in its report to the congressional budget committees, projecting growth for entitlement and discretionary spending based on current fiscal year spending. Terminates spending authority, effective October 1, 1993, for unearned entitlements and high-cost discretionary spending programs unless such spending authority is reauthorized. Terminates spending authority, effective October 1, 1994, for each discretionary spending program (not including high-cost discretionary spending programs) unless such spending authority is reauthorized. Provides for terminating such spending authorities after the year 2000 unless appropriately reauthorized.

the energetics of metal hydrides has recently become an issue of large scientific and technological interest , mainly because of the revived interest in these materials as potential hydrogen storage media @xcite . magnesium hydride ( mgh@xmath0 ) is a particularly interesting material , as it can store up to 7.6 % of hydrogen by weight , which is believed to be a large enough quantity for mobile applications , provided that all the hydrogen in the material can be made available when requested , of course . when heated above @xmath5c@xcite mgh@xmath0 decomposes into mg bulk and h@xmath0 gas , the reaction being endothermic with an enthalpy of decomposition of 76 kj / mole @xcite . conversely , mgh@xmath0 can be synthesised by combining mg bulk ( usually in form of a powder of micro - metre sized grains ) and h@xmath0 gas . the charging process can take many hours , because of a large energy barrier to dissociate the h@xmath0 molecule on the surface of magnesium @xcite . as it stands , mgh@xmath0 is not considered to be useful for hydrogen storage purposes , because of the high decomposition temperature ( ideal decomposition temperature should be in the range @xmath6c ) , and the slow kinetics of hydrogen intake . a number of attempts are being made to modify this material to improve its properties , including doping it with traces of transition metals @xcite , which have been shown to be very effective at reducing the activation energy for hydrogen dissociation @xcite , and also somewhat reduce the decomposition temperature of the hydride @xcite . a number of theoretical calculations have been performed on magnesium hydride and related systems ( see for example @xcite and references therein ; see also @xcite ) , the most recent ones based on the implementation of quantum mechanics known as density functional theory ( dft ) @xcite . although dft can often be reliable at predicting trends in the energetics of materials , it can be sometime in error when used to obtain absolute energies . in particular , as we show below , when applied to the calculation of the enthalpy of formation of mgh@xmath0 , the results are off by as much as 0.3 ev per formula unit , depending on the functional employed , and cohesive energies can be wrong by over 0.5 ev . quantum monte carlo ( qmc ) techniques @xcite are believed to be one possible way to improve beyond density functional theory . since they are many order of magnitudes more computationally demanding , the current database of properties of materials calculated with qmc is still rather small , however , the increase in computer power in the past few years is making now possible to perform increasingly more numerous calculations on real systems , and experience is being accumulated on the predictive power of this technique . here we have used qmc to calculate the structural properties of the mg and mgh@xmath0 crystals , together with their cohesive energies and the enthalpy of formation of mgh@xmath0 from mg bulk and h@xmath0 gas . we find excellent agreement with experiments for the structural properties of the two solids , as well as the cohesive energy of the mg solid . the enthalpy of formation of mgh@xmath0 is slightly overestimated , but the error is of the order of 1 kcal / mole , showing that qmc on this system can almost achieve chemical accuracy . density functional theory calculations have been performed with the vasp code @xcite . the interactions between the electrons and the ionic cores was described using the projector augmented method ( paw ) @xcite with the generalised gradient approximations known as pbe @xcite , pw91 @xcite or the local density approximation ( lda ) . the mg paw potential has a frozen ne core and an outermost cutoff radius for the valence orbitals of 1.06 . the h paw potential has a cutoff radius of 0.58 . single particle orbitals were expanded in plane waves with a plane - wave cutoff of 270 ev , and a cutoff of 1600 ev was used for the charge density . such a large cutoff in the charge density ( 4 times larger than the typical one used by default ) is necessary to obtain very accurate forces which are used to calculate the vibrational properties of the crystals . calculations were performed by requiring a self - consistency convergence on the total energy of @xmath7 ev per simulation cell . with these prescriptions convergence on the forces was at worse equal to 0.2 mev / , and one or two order of magnitudes smaller for most atoms in the simulation cell . brillouin zone integration was performed using * k*-point sampling , with 18x18x12 and 10x10x15 monkhorst - pack @xcite grids on the mg and mgh@xmath0 primitive cells respectively . with these densities of * k*-points the structural parameters are converged to better than 0.1 % , and the total energies to better than 1 mev / primitive cell . quantum monte carlo techniques have being extensively described elsewhere @xcite , so here we only report the main technical details used in this work . calculations have been performed using the casino code @xcite . diffusion monte carlo calculations have been performed using trial wavefunctions of the slater - jatrow type : @xmath8 where @xmath9 and @xmath10 are slater determinants of up- and down - spin single - electron orbitals , and @xmath11 is the so called jastrow factor , which is the exponential of a sum of one - body ( electron - nucleus ) , two - body ( electron - electron ) and three body ( electron - electron - nucleus ) terms , which are parametrised functions of electron - nucleus , electron - electron and electron - electron - nucleus separations , and are designed to satisfy the cusp conditions . the parameters in the jastrow factor are varied to minimise the variance of the local energy @xmath12 . imaginary time evolution of the schrdinger equation has been performed with the usual short time approximation , and the locality approximation @xcite . time step errors have been carefully analysed later in the paper . since the locality approximation introduces an uncontrollable error with respect to which the dmc energy is non - variational , we also tested the scheme of casula @xcite , which treats the non local part of the pseudopotential in a consistent variational scheme . we found that the zero time step extrapolation of the energies in the two scheme differed very little , which suggests that the errors in either case is rather small @xcite . however , we also found that the time step error is much smaller in the locality approximation in this particular case ( this may not be true in general for other systems ) , and therefore we decided to use the locality approximation throughout the work which allowed us to work with a larger time step . we used dirac - fock pseudopotentials ( pp ) for mg and h @xcite . the mg pp has a frozen ne core and a core radius of 1.43 , the h pp has a core radius of 0.26 . the single particle orbitals have been obtained by dft plane - wave ( pw ) calculations using the lda and a pw cutoff of 3400 ev , using the pwscf package @xcite . such a large pw cutoff is due to the very small h pp core radius , and was found to be necessary to reduce the variance of the local energy as much as possible . we then exploited the approximate equivalence between pw and b - splines @xcite to expand the single particle orbitals in a basis of b - spline , as described in ref . @xcite , using the natural b - spline grid spacing given by @xmath13 , where @xmath14 is the length of the largest vector employed in the pw calculations . we used a diffusion monte carlo time step of 0.05 a.u . , which was found to result in errors of about 2 mev / f.u . ( see below ) . with this time step the acceptance ratios were 99.2 and 99.7 % for the mgh@xmath0 and mg crystals respectively . total energies in the solids were obtained by correcting the raw dmc data with dft - lda calculations performed on the same cell size but a fully converged brillouin zone sampling , and then extrapolating these corrected dmc data to infinite size ( see below ) . the dmc calculations were performed using the ewald interaction to model electron - electron interactions . the number of walkers in the dmc simulations varied with the size of the systems , and was never less than 1280 . mg bulk has the hexagonal close packed structure , which is specified by a lattice parameter @xmath15 and the ratio @xmath16 of the vertical axis to one of the horizontal ones . the primitive cell contains two atoms , one at the origin and the other at ( 1/3,2/3,0.5 ) in lattice vectors units . the mgh@xmath0 solid has a tetragonal structure of rutile type ( see fig . [ fig : mgh2_struct ] ) , specified by a lattice parameter @xmath15 and the @xmath16 ratio . the primitive cell has two mg atoms , one at the origin and the other in the centre of the cell at ( 1/2,1/2,1/2 ) plus four hydrogen atoms at ( @xmath17x,@xmath17x,0 ) and ( 1/2@xmath17x,1/2@xmath18x,1/2 ) . the exact values of @xmath16 and x depend on pressure , and at ambient conditions are found to be @xmath19 and [email protected] @xcite . in order to compare the calculated structural parameters and cohesive energies with the experimental ones we need to study the vibrational properties of the crystals . this is because the experimental parameters are usually determined at ambient conditions , and room temperature thermal expansion for the mg and mgh@xmath0 solids is likely to be significant . we studied these vibrational properties within the quasi - harmonic approximation , which far from the melting temperatures provides accurate enough results for the thermal expansion of solids . this is certainly the case for the mg and mgh@xmath0 solids at room temperature . phonons have been calculated using the phon code @xcite , which implements the small displacement method @xcite to obtain the force constant matrix in crystals . the methods exploits the linearity relation between the displacement of the atoms from their equilibrium positions and the forces induced on all the atoms in the crystal , which holds in the harmonic approximation for small enough displacements . the method is applied by constructing a supercell which is a multiple of the primitive cell in the three spacial directions , then the atoms in the primitive cell are displaced by small amounts along three linearly independent directions and the forces induced on all the atoms in the supercell are used to construct the force constant matrix . symmetries can usually be used to reduce the total number of displacements needed , and also to symmetrise the force constant matrix @xcite . for bulk mg , which has the hexagonal closed packed crystal structure , only two displacements are needed , one in the basal plane and one orthogonal to it ( in fact , one single off symmetry displacements would be sufficient , although this would break the symmetry of the supercell and require a larger number of * k*-points in the dft calculation of forces ) . mgh@xmath0 has the tetragonal structure of rutile tio@xmath0 , with two mg and four h atoms in the primitive cell , and the total number of displacements needed in this case is 4 ( one could reduce the total number of displacements to 2 by sacrificing symmetries ) . if the supercell is large enough so that the forces on the atoms sitting near the edges are small , then the calculated force constant matrix becomes a good approximation of the exact one . magnesium bulk is a metal , and convergence of the force constant matrix with the size of the supercell is readily achieved : we found that with cell containing 36 atoms ( 3x3x2 ) the zpe is converged to within 0.1 mev / atom ( tested using supercells containing up to 150 atoms ) . however , mgh@xmath0 is an insulator , and long range coulomb interactions make convergence slower . nevertheless , we found that already by using a cell containing 72 atoms ( 2x2x3 supercell ) the zpe can be calculated with an accuracy of 0.5 mev / fu ( tests used supercells containing up to 576 atoms ) . all calculations were performed with dft - pbe . phonons calculated with the direct method described above may suffer from inaccuracies due to the size of the displacements and/or numerical noise in the calculated forces . to reduce the latter , one would like to maximise the size of the displacements , but too large displacements would cause departure from the harmonic regime . a compromise between these two opposite requirements then needs to be found , and this is usually achieved with displacement sizes of the order of a fraction of a percent of the inter - atomic distances . in order to test the size of the displacements we repeated the calculations using displacements of 0.067 , 0.04 , 0.02 , and 0.01 , and we found that even with the largest displacement the zpe energy is converged to less than 0.2 mev / atom in mg and 1 mev / fu in mgh@xmath0 . we then decided to use displacements of 0.04 . the fundamental vibrational frequency of the h@xmath0 molecule has been obtained by calculating the total energy of the h@xmath0 molecule in a large cubic box of size 13.5 for 5 different values of the h - h distance , ranging from @xmath21 to @xmath22 , where @xmath23 is the calculated equilibrium distance with dft - pbe . the 5 energies have been fitted to a parabola , providing a force constant of 33.35 ev / @xmath24 which corresponds to a stretching vibrational frequency of 127 thz ( only slightly lower that the experimental value of 131.8 thz @xcite ) , giving a zpe of 0.263 ev . initially , we performed dft calculations on the crystals with pbe , pw91 and lda . energy versus volume curves were fitted to a birch - murnaghan equation of state @xcite , which provided equilibrium volumes and bulk moduli . in the range of volumes considered , @xmath16 s do not change very much from their zero pressure values , and the structural parameters are essentially unchanged if @xmath16 is kept fixed . therefore , for simplicity we decided to fix @xmath16 to their calculated zero pressure values of 1.621 and 0.6682 for mg and mgh@xmath0 respectively . the mgh@xmath0 crystal has an additional degree of freedom , which defines the position of the h atoms in the lattice . this has also been optimised by fully relaxing the crystal at each different volume . these relaxations are essential in the calculation of phonons , because if the crystal is not in its ground state imaginary phonon frequencies appear . however , as far as the energy is concerned , the differences from calculations in which the h positions are kept at their zero pressure equilibrium values are undetectable . in table [ table1 ] we report the structural parameters of mg and mgh@xmath0 calculated with the three density functionals , and we report the results both at zero temperature ( with and without zpe ) and at room temperature . both mg and mgh@xmath0 are fairly soft materials , with bulk moduli of the order of 40 and 50 gpa . room temperature thermal pressure are about 1 and 1.8 gpa for mg and mgh@xmath0 respectively , which means volume thermal expansion is about 2% and 3.5% for the two solids . this is significant , and can not be ignored in a fair comparison with the experimental data . we also report in the same table the cohesive energies of the two solids . the experimental cohesive energy of mgh@xmath0 can be estimated by combining the cohesive energy of the mg crystal ( 1.51 ev / atom ) , the dissociation energy of the hydrogen molecule ( 4.48 ev / molecule ) and the enthalpy of formation of mgh@xmath0 from mg and h@xmath0 , whose value extrapolated at zero temperature is @xmath25 ev / fu @xcite , which therefore give a result of @xmath26 ev / fu . by comparing the calculated cohesive energies with the experimental ones it is clear that the three functionals provide quite scattered results , with the lda doing better on mgh@xmath27 and pbe doing better on mg . it is also apparent that errors can be significant , of up 0.6 ev for pbe . this error is well over 10 times a kcal / mole , which is the typical quantity cited as _ chemical accuracy_. lccccc & & & t + & & v@xmath28 , k@xmath28 & v@xmath28 , k@xmath28 & e@xmath29 & v@xmath28 , k@xmath28 + & & ( no zpe ) & ( with zpe ) & ( with zpe ) & + mg & & & & & + & lda & 21.59 , 40.6 & 21.80 , 39.3 & -1.74 & 22.14 , 36.4 + & pbe & 22.86 , 36.5 & 23.08 , 35.9 & -1.47 & 23.47 , 34.0 + & pw91 & 22.86 , 36.4 & 23.10 , 35.2 & -1.45 & 23.50 , 32.6 + & [ exp . ] & & & [ -1.51 ] & [ 23.24 , @xmath30 + & dmc & @xmath31 , @xmath32 & @xmath33 , @xmath34 & @xmath35 & @xmath36 , @xmath37 + + mgh@xmath0 & & & & & + & lda & 29.36 , 55.5 & 30.32 , 51.4 & -7.16 & 30.36 , 49.9 + & pbe & 30.84 , 51.1 & 31.92 , 45.8 & -6.17 & 32.03 , 43.5 + & pw91 & 30.72 , 51.5 & 31.79 , 46.4 & -6.27 & 31.89 , 43.9 + & [ exp . ] & & & [ @xmath38 & [ 30.49 , ] + & dmc & @xmath39 , @xmath40 & @xmath41 , @xmath42 & @xmath43 & @xmath44 , @xmath45 + + h@xmath0 & & & & & + & lda & & & -4.59 & + & pbe & & & -4.23 & + & pw91 & & & -4.25 & + & [ exp ] & & & [ -4.48 ] & + & dmc & & & @xmath46 & the dependence of the dmc energy on time step in the mgh@xmath0 crystal was studied by repeating simulations with a 2x2x3 supercell ( 72 atoms ) at time steps ranging from 0.005 to 0.15 a.u .. calculations were performed at the volume of 30.835 @xmath47/fu , and using the @xmath48 point ( 0.5,0.5,0.5 ) which is at one corner of the brillouin zone . for the mg crystal we used a 3x3x2 supercell ( 36 atoms ) , a volume of 22.785 @xmath47/atom and the h point ( 0.5,0.5,0.5 ) , also at one corner of the brillouin zone . results of total energy / fu for mgh@xmath0 and total energy / atom for mg are displayed in fig . [ fig : ts ] , from which it is evident that using a time step of 0.05 a.u . time step errors are well below 5 mev / fu . in fig . [ fig : ts ] we also display the results obtained with the scheme proposed by casula @xcite , and we observe that for short enough time steps the two sets of energies are very close , and extrapolate to roughly the same value in the limit of zero time step ( to less than 5 mev / fu ) . as mentioned earlier , this suggests that the error introduced with either scheme is very small . however , the locality approximation results in a much weaker dependence of the dmc energy on time step and this is what we used because it allowed us to work with much larger time steps . we note that for the mg crystal the time step error is much smaller , which in principle would allow us to work with larger time steps , however , for consistency , we used the same time step of 0.05 a.u . also for the mg crystal . to calculate the total energies of the mg atom and the h@xmath0 molecule we used trial wavefunctions obtained from plane wave calculations in which the mg atom or the h@xmath0 molecule was placed at the centre of a large cubic box with a side of 13.5 the dmc calculations were then performed using b - splines and no periodically boundary conditions . we display in fig . [ fig : tsatom ] the dmc energies as function of time step , from which we can obtain very accurate zero time step values . in the case of mg we also performed one calculation with the scheme of casula @xcite , which gave essentially the same energy . for the h@xmath0 molecule we display the binding energy calculated at the equilibrium distance of 0.75 , obtained by subtracting from the energy of the molecule twice the energy of the h atom , which is calculated to be 13.60635(5 ) both the energies of the h atom and the h molecule are in excellent agreement with the experimental data . in the mg crystal we studied the dependence of the dmc energy on the size of the simulation cell by repeating the calculations with 4x4x3 , 5x5x3 , 6x6x4 , 8x8x5 and 9x9x6 supercells , containing 96 , 150 , 288 , 640 and 972 atoms respectively . results are displayed in fig . [ fig : sizemg ] , where we show the total energies / atom @xmath49 as function of @xmath50 , with n the number of atoms in the simulation cell . on the same graph we also show the energies @xmath51 $ ] , where @xmath52 are the dft energies calculated with fully converged * k*-point sampling , and @xmath53 are the dft energies calculated with * k*-point samplings corresponding to the @xmath54-atom cells used in the dmc calculations . it is clear that the raw dmc energies @xmath49 are quite scattered and somewhat difficult to extrapolate to infinite size . this is due to the metallic nature of mg . however , the dft corrected energies @xmath55 are much better behaved , with data fitting quite well onto a straight line , which makes it possible to extrapolate to infinite size . in particular , we note that with no loss of accuracy we can also use only the calculations with the 4x4x3 , 5x5x3 and 6x6x4 supercells to extrapolate to essentially the same infinite size value . the calculations with these three supercell sizes were then repeated at 8 different volumes , between 21 and 25 @xmath47/atom . at each volume the dft corrected dmc results were extrapolated to infinite size and the results were fitted to a birch - murnaghan equation of state to obtain the structural parameters . we performed the fit by weighing each energy point @xmath56 point with @xmath57 , where @xmath58 is the standard error on @xmath56 . we report in table [ table1 ] the results obtained both at zero temperature ( with and without zero point energy ) and at room temperature . the latter are also shown in fig . [ fig : mg ] . the room temperature corrected dmc results slightly overestimate the equilibrium volume , and also underestimate the bulk modulus , but the calculated cohesive energy is in perfect agreement with the experimental data . for the mgh@xmath0 crystal size effects were studied using 2x2x3 , 3x3x4 , 4x4x6 and 5x5x7 supercells , containing 72 , 216 , 576 and 1050 atoms respectively . these tests were performed at the volume of 30 @xmath47/fu . the results for the four sizes studied are displayed in fig . [ fig : sizemgh2 ] , where we show total energies / fu @xmath49 as function of @xmath50 , as well as the dft corrected energies @xmath55 . in this case the dft corrections are much smaller , which is not surprising because of the large band gap in mgh@xmath0 . a small difference between the two sets of data can be observed for the smallest sizes , but it is clear that they both fit very well onto straight lines , which allows us to easily extrapolate the results to infinite size . in fact , in this case the extrapolated results for the two sets only differ by 5 mev / atom . the calculations were repeated at 7 different volumes between 28 and 32.5@xmath47/fu , and the dft corrected dmc results were then fitted with a birch - murnaghan equation of state to obtain the structural parameters . also in this case we used the inverse of the variances to weigh each point in the fit . we report in table [ table1 ] the results obtained both at zero temperature ( with and without zero point energy ) and at t = 260 k , which is the temperature at which the experimental data are reported @xcite . the high temperature results are also shown in fig . [ fig : mgh2 ] . it is clear that once thermal effects are added onto the calculations the agreement with the experimental equilibrium volume is in almost perfect agreement . the cohesive energy is slightly overestimated , but the error is only 0.06 ev , i.e. of the order of chemical accuracy . we can now calculate the enthalpy of formation of mgh@xmath0 from mg bulk and h@xmath0 in the gas phase by adding the cohesive energies of the mgh@xmath0 and mg crystals to the binding energy of the h@xmath0 molecule . we obtain enthalpy of formations of 0.82 , 0.47 and 0.57 ev / fu with lda , pbe and pw91 respectively , and with dmc we obtain the value @xmath59 ev / fu . the lda value is very accurate , but this is the result of large cancellations of errors in the cohesive energies of the crystals and the binding energy of the h@xmath0 molecule . the dmc result is only 0.06 ev higher than the experimental value of @xmath60 ev / fu , however in this case both the cohesive energies of the crystals and the binding energy of the h@xmath0 molecule are very accurate . we pointed out in this work the difficulty of using density functional theory to calculate the enthalpy of formation of mgh@xmath0 with high accuracy . we studied the effect of three different exchange - correlation functionals , pw91 , pbe and lda , and found that although the gga ones appear to work better on the mg solid , the lda gives better results on the mgh@xmath0 solid . it turns out , therefore , that is difficult to get a good dft value for the enthalpy of formation of mgh@xmath0 : the two gga functionals give an enthalpy of formation in error of more than 0.2 and 0.3 ev / fu respectively . the lda is the functional that does best , but for the wrong reason , because the cohesive energies of the crystals and the binding energies of the molecule are wrong by up to 0.4 ev / fu , and the enthalpy of formation is accurate only because of large cancellation of errors . diffusion monte carlo appears to deliver much better accuracy in general . we have shown that the dmc equilibrium volumes of mgh@xmath0 agrees perfectly with the experimental one , once high temperature thermal expansion is included in the calculations , and the equilibrium volume of mg is only slightly overestimated . the cohesive energy of mg is also predicted in perfect agreement with the experimental datum , and so is the binding energy of the h@xmath0 molecule . a small error is present in the cohesive energy of the mgh@xmath0 crystal , which determines the small inaccuracy in the enthalpy of formation , for which we find a dmc value of @xmath1 ev / fu . however , this is only 0.06 higher than the accepted experimental one of @xmath60 ev / fu , or @xmath3 kj / mole . this result is not very far from the lda value , but with the important difference that now all three terms that enter the enthalpy of formation are calculated accurately , and we do nt rely on fortunate cancellation of errors . although the dmc error is slightly larger than 1 kcal / mole , and therefore we can not claim _ chemical accuracy _ , we are not far from it , and therefore we argue that quantum monte carlo techniques have useful predictive power in the search of metal hydrides with workable decomposition temperatures . the computations were performed on the hpcx service , using allocations of time from nerc , and on hector . calculations have also been performed on the lcn cluster at university college london . this work was conducted as part of a euryi scheme award as provided by epsrc ( see www.esf.org/euryi ) . of course , it is possible that the casula scheme induces a large positive error in the dmc energy , and that by chance the error induced by the locality approximation is also positive and of the same size . however , since the two scheme are completely different , we believe that this is unlikely . f. birch , phys . rev . * 71 * , 809 ( 1947 ) . c. kittel , _ introduction to solid state physics _ , 7th ed . ( wiley , new york , 1996 ) . d. errandonea , y. meng , d. husermann , and t. uchida , j. phys . : condens . matter * 15 * , 1277 ( 2003 ) . bulk ( right panel ) as function of time step . dots and squares correspond to calculations performed with the locality approximation and with the scheme proposed by casula @xcite respectively.,title="fig:",width=336 ] bulk ( right panel ) as function of time step . dots and squares correspond to calculations performed with the locality approximation and with the scheme proposed by casula @xcite respectively.,title="fig:",width=336 ] molecule ( right panel ) as function of time step . calculations have been performed with the locality approximation . square : calculation performed with the scheme proposed by casula @xcite.,title="fig:",width=336 ] molecule ( right panel ) as function of time step . calculations have been performed with the locality approximation . square : calculation performed with the scheme proposed by casula @xcite.,title="fig:",width=336 ] , where n is the number of particles in the simulation cell . stars and squares correspond to raw and dft corrected ( see text ) results , solid line is a linear least square fit to the dft corrected results . , width=336 ] . dots correspond to dmc calculations extrapolated to infinite size , and include vibrational free energies calculated with dft - pbe . solid line is a least squares fit to a birch - murnaghan equation of state . , width=336 ] crystal as function of @xmath50 , where n is the number of particles in the simulation cell . stars and squares correspond to raw and dft corrected ( see text ) results , solid line is a linear least square fit to the dft corrected results.,width=336 ] crystal as function of volume @xmath63 . dots correspond to dmc calculations extrapolated to infinite size , and include vibrational free energies calculated with dft - pbe . solid line is a least squares fit to a birch - murnaghan equation of state . , width=336 ]

we have used diffusion monte carlo ( dmc ) calculations to study the structural properties of magnesium hydride ( mgh@xmath0 ) , including the pressure - volume equation of state , the cohesive energy and the enthalpy of formation from magnesium bulk and hydrogen gas . the calculations employ pseudopotentials and b - spline basis sets to expand the single particle orbitals used to construct the trial wavefunctions . extensive tests on system size , time step , and other sources of errors , performed on periodically repeated systems of up to 1050 atoms , show that all these errors together can be reduced to below 10 mev per formula unit . we find excellent agreement with the experiments for the equilibrium volume of both the mg and the mgh@xmath0 crystals . the cohesive energy of the mg crystal is found to be 1.51(1 ) ev , and agrees perfectly with the experimental value of 1.51 ev . the enthalpy of formation of mgh@xmath0 from mg bulk and h@xmath0 gas is found to be @xmath1 ev / formula unit , or @xmath2 kj / mole , which is off the experimental one of @xmath3 kj / mole only by @xmath4 kj / mole . this shows that dmc can almost achieve chemical accuracy ( 1 kcal / mole ) on this system . density functional theory errors are shown to be much larger , and depend strongly on the functional employed .

interacting magnetic nanostructured materials are currently the subject of intense research activity , driven by their fundamental interest and technological perspectives @xcite . numerous experimental and theoretical studies have been performed for various two - dimensional ( 2d ) @xcite and three - dimensional ( 3d ) @xcite arrangements of nanometer - size magnetic particles having different degrees of structural and magnetic disorder . the magnetic behaviour of these systems is determined by single - particle properties ( e.g. , particle moments , lattice and shape anisotropies , etc . ) , by the composition and morphology of the nanostructure , and in particular by the nature of the dominant interparticle interactions . the latter comprises especially the magnetic dipole coupling , which will be adressed in the present study . other interparticle interactions are , for example , the rudermann - kittel - kasuya - yosida ( rkky ) indirect exchange mediated by the conduction electrons of a metallic substrate , or the short - range direct exchange in case when the particles are in contact . the relative importance of single - particle versus interparticle contributions can be tuned experimentally at least to some extent by changing sample characteristics such as the particle - size distribution or the average interparticle distance . for low particle coverages the interactions can be treated as a perturbation to the single - particle properties . however , for dense particle ensembles the interparticle interactions become increasingly important and eventually dominate . in this interesting case the single - particle approach is no longer applicable and an explicit treatment of the interactions is unavoidable @xcite . a fundamental question in this context is to identify and understand the collectively ordered magnetic states which are induced by the interactions in such particle ensembles . a few basic properties of strictly periodic dipole - coupled systems are summarized . the ground state of a _ square _ lattice of equal - sized ( monodispersed ) particles is the so - called _ microvortex _ ( mv ) magnetic arrangement @xcite . this magnetic structure is characterized by the microvortex angle @xmath1 , where the angles of the particle magnetizations of a plaquette of four neighbouring particles are given by @xmath2 , @xmath3 , @xmath4 , and @xmath5 . in particular , multiples of @xmath6 represent _ columnar _ states , consisting of ferromagnetic rows or columns with alternating signs of magnetizations . evidently , the mv state has a vanishing net magnetization . the parallel or ferromagnetic ( fm ) state has a larger energy and is actually an unstable solution . the ordering of dipole - coupled spins is very sensitive to the lattice structure . for example , the honeycomb lattice has a ground state with a vanishing net magnetization which is similar to the mv state of the square lattice @xcite . in contrast , for the hexagonal lattice the ground state is ferromagnetic @xcite . despite the fact that the dipole interaction is not rotationally invariant , the ground state of these dipole - coupled periodic particle arrays are continuously degenerate with respect to a rotation of the mv angle @xmath1 or of the fm angle @xmath7 , respectively . this holds for classical spins at @xmath8 . thermal fluctuations , quantum fluctuations , or a structural disorder immediately lift these accidental ground state degeneracies of the periodic structures . the energy lowering associated to the symmetry breaking stabilizes the system in some particular magnetic order . therefore , the square and honeycomb lattices are said to show a so - called order - by - disorder effect @xcite . this implies that internal ( nontrivial ) degeneracies ( e.g. , the relative directions of magnetic sublattices ) are lifted by the presence of disorder , and that particular directions of the sublattice magnetizations are preferred . moreover , for a dipole - coupled square lattice the fluctuations induce a fourfold in - plane magnetic anisotropy . as shown by prakash and henley @xcite , the preferred in - plane magnetic orientations are the axial directions ( columnar states ) for thermal and quantum fluctuations , and the diagonal directions for a structural disorder induced by a small amount of vacancies . in addition , monte carlo calculations and interacting spin wave theory indicate that a magnetic ordering at finite temperatures exists for a dipole - coupled square spin lattice , since the magnetic excitations are not continuously degenerate @xcite . thus , the mermin - wagner theorem , which excludes an ordered state for a continuously degenerate 2d system at finite temperatures @xcite , is not effective in this case . notice that already the _ long - range _ character of the dipole interaction induces a collectively ordered magnetic state in a square lattice @xcite . structural disorder , which is usually present in real magnetic nanostructures , results for example from the size and shape dispersion , positional disorder , or random anisotropy axes . due to the nonuniform and competing nature of the magnetic couplings the magnetic ordering in disordered particle ensembles is similar to the one of a spin - glass @xcite . thus , many different metastable states exist , which are characterized by strong magnetic noncollinearities . an intriguing question in this context is whether the dipole interaction in _ disordered _ planar particle ensembles results in a collectively ordered magnetic state . several experiments on interacting , high - density ferrofluid systems indicate the onset of a collectively ordered state below a characteristic , concentration - dependent temperature . for example , at this temperature a critical slowing down of the magnetic relaxation is observed @xcite . furthermore , recent measurements on co islands on cu(001 ) exhibit a magnetic hysteresis and remanence in the temperature range up to 150 k also for coverages below the magnetic percolation threshold @xcite . due to the small size of the co islands these findings could not explained simply by single - particle blocking effects . note that the experimental determination of the ordering temperature is difficult , since the relaxation times are often very long . hence , it is of considerable interest to analyze how the magnetic order depends on the sample parameters which can be controlled in experiment . the purpose of this paper is the theoretical study of the low - energy properties of dipole - coupled magnetic particle ensembles forming inhomogeneous planar arrangements with various degrees of disorder ranging from a quasi - periodic square lattice to a random array . numerical simulations are performed in order to achieve a detailed microscopic description within the model . the low symmetry of the system and the complicated nature of the interaction seem to preclude simple analytical approaches . we focus on the strongly interacting case , neglecting single - particle anisotropies . special attention is paid to the role of disorder and noncollinear arrangements of the particle magnetic moments . in particular , we determine the energy distribution of metastable states and the average magnetic dipole energy for different coverages and types of disorder . furthermore , we investigate global and local order parameters as function of disorder , and compare our results with previous calculations @xcite . all calculations are performed at @xmath8 . the rest of the paper is organized as follows . the theoretical methods are outlined in section [ sec : theo ] . representative results for the magnetic arrangements , as well as for various magnetic properties are presented in section [ sec : res ] . a conclusion is given in section [ sec : conc ] . finally , in the appendix we report details for the extension of the dipole summation beyond the point - dipole approximation which takes into account effects resulting from the finite particle size . we consider a 2d rectangular unit cell in the @xmath9- plane with @xmath10 non - overlapping , disk - shaped magnetic particles . due to the strong direct exchange interaction and the small size of the particles under consideration , each particle @xmath11 can be viewed as a single magnetic domain ( stoner - wohlfarth particle ) @xcite . thus , a particle containing @xmath12 atoms carries a giant spin @xmath13 , where @xmath14 is the atomic magnetic moment . for simplicity , we restrict the particle magnetizations to be confined to the @xmath9 plane , the planar rotator @xmath15 is then characterized by the in - plane angle @xmath16 : @xmath17 . in this study no size dispersion is considered , i.e. , @xmath18 . for disk - shaped particles the particle radius @xmath19 is given by @xmath20 , where @xmath21 is the interatomic distance . unless otherwise stated , the present results refer to a unit cell containing @xmath22 particles with @xmath23 atoms each . the size of the unit cell is given by @xmath24 , with @xmath25 the average interparticle distance . for a planar array of circular particles the overall surface coverage is @xmath26 . four different types of the lateral particle arrangement have been considered : ( i ) a periodic square array , i.e. , the particle centers are located on the sites of a square lattice with lattice constant @xmath25 , ( ii ) a disturbed ( quasi - periodic ) array for which the particle centers deviate randomly from the square array , using a gaussian distribution @xmath27 with positional standard deviation @xmath28 , ( iii ) a diluted square particle lattice containing a number of vacancies @xmath29 with concentration @xmath30 , and ( iv ) a fully random distribution of non - overlapping particles within the unit cell . periodic boundary conditions are introduced in order to describe an infinitely extended planar particle ensemble . by considering a single unit cell a finite system can be realized as well . in this case the effect of boundaries will strongly dominate the resulting magnetic arrangement . for such particle ensembles we consider the dipole - dipole interaction between the magnetic moments @xmath15 , which can also be expressed in terms of a dipole field @xmath31 acting on @xmath15 due to all other particle magnetic moments : @xmath32 = - \frac{\mu_0}{2}\;\sum_i\ ; \bi{m}_i\;\bi{b}_i^\mathrm{dip } \ ; , \label{e1}\ ] ] where @xmath33 is the distance between the centers of particles @xmath11 and @xmath34 , and @xmath35 the vacuum permeability . the infinite range of the dipole interaction is taken into account by applying an ewald - type summation over all periodically arranged unit cells of the extended thin film @xcite . in addition to the usual point - dipole sum we consider the leading correction resulting from the finite particle size ( dipole - quadrupole interaction ) , which is outlined in detail in the appendix . this correction becomes comparable to the point - dipole sum for large particle coverages or small interparticle distances . the energy unit of the dipole coupling is given by @xmath36 , with @xmath14 in units of the bohr magneton @xmath37 . in this study we assume values appropriate to fe ( @xmath38 , @xmath39 ) , which yields @xmath40 k. the effects of single - particle anisotropies resulting from the spin - orbit interaction , the dipole interaction among atomic magnetic moments within each particle ( shape anisotropy ) , external magnetic fields , and finite temperatures are beyond the scope of the present study . starting from an arbitrary initial configuration @xmath41 of the magnetic directions , the total magnetic energy @xmath42 of the system is relaxed to the nearest local minimum , which often corresponds to a metastable state , by varying all in - plane angles @xmath16 of the particles using a conjugated gradient method @xcite . for example , the experimental situation of a remanent state after removal of an external magnetic field is simulated by choosing a fully aligned initial arrangement along a certain direction . we emphasize that the applied procedure is not intended to search preferently for the global energy minimum or ground state , which is the equilibrium state at @xmath8 . rather , at first we determine the energy distribution of the local minima for different degrees of structural disorder introduced in the planar particle array . a number of randomly chosen intital configurations @xmath41 is created and relaxed to a nearby local minimum . this metastable state is characterized by its energy @xmath42 and by its set of angles \{@xmath16}. a twofold ( uniaxial ) symmetry is always present due to time inversion symmetry , i.e. , the energy of a state does not change under the transformation @xmath43 performed simultaneously for all particles . these mirrored states are considered to be equivalent . the numbers of trials yielding relaxed states with energies falling into given energy intervals are monitored , and the corresponding energy histogram is determined . since the minimization procedure relaxes typically to the local energy minimum that is closest to the initial state , this frequency provides a measure of the _ catchment area , _ i.e. , the area of the energy valley belonging to that state in the high - dimensional configuration space . in order to account for the large number of local energy minima occurring in particle arrangements with structural inhomogeneities we determine the _ average dipole energy _ @xmath0 resulting from many different trials for the same particle array . in addition , we average @xmath0 over a number of different realizations of the unit cell , using the same global variables which characterize the particle ensemble ( coverage , standard deviation @xmath28 , etc . ) . for comparison , @xmath0 is also calculated for the same spatial setup by assuming a ferromagnetic state ( i.e. , @xmath44 ) and averaging over the fm angle @xmath7 . in case of a disturbed ( quasi - periodic ) square lattice , i.e. , if the particle numbering allows for the identification of a square plaquette of four neighbouring particles , we also determine the dipole energy for the microvortex magnetic arrangement , averaging over the mv angle @xmath1 . note that for a nonuniform particle ensemble these fm and mv magnetic arrangements do not correspond in general to local energy minima . for a _ random _ set of angles \{@xmath16 } one obtains @xmath45 which constitutes the natural energy reference . the deviations of the metastable low - energy magnetic arrangements from the mv state are quantified by the _ global _ and _ local microvortex order parameters _ @xmath46 and @xmath47 given by @xmath48^{1/2 } \ ; , \label{e1a } \\ m_\mathrm{mv}^\mathrm{local}(\sigma_r ) & = & \frac{1}{4}\bigg [ \bigg ( \sum_i^4(-1)^{i_y}\cos\phi_i\bigg)^2+\bigg(\sum_i^4 ( -1)^{i_x}\sin\phi_i\bigg)^2 \bigg]^{1/2 } \ ; , \label{e1b } \end{aligned}\ ] ] where @xmath49 and @xmath50 denote the numbering of the rows and columns corresponding to particle @xmath11 . clearly , a reference square lattice is prerequisitive . hence , we restrict ourselves to a quasi - periodic array or to a square array with vacancies for which @xmath49 and @xmath50 can be uniquely defined . these two order parameters differ by the sum @xmath11 running either over all @xmath51 particles of the unit cell or over the four neighbouring particles within a square plaquette . they have a simple geometrical interpretation as the projection of the magnetic configuration on the two linear independent columnar states having @xmath52 and @xmath6 , regardless of all possible rotations of the mv states within this plane . @xmath46 measures the mv order in the nanostructure , whereas @xmath47 measures the short range ordering . both quantities are averaged over an appropriate number of initial configurations for the same particle arrangement and over different realizations of the unit cell . in addition @xmath47 is averaged over all four - particle plaquettes within the unit cell . finally , another quantity characterizing the magnetic properties of nanostructured particle arrangements is the distribution of the microvortex angles @xmath1 . prakash and henley observed that the preferred mv angles for a square particle array with a small number of randomly distributed vacancies are the diagonal directions ( @xmath53 , etc . ) it is therefore interesting to investigate how the angular distribution of the microvortex angles depends on the type and degree of disorder . for this purpose different realizations of the nanostructure are created . for each particle setup the mv state with angle @xmath1 yielding the lowest energy is determined , and the corresponding frequencies for all angles are monitored . we consider a _ disturbed _ square particle array with standard deviation @xmath28 , and a _ diluted _ square particle lattice with a concentration @xmath30 of vacancies . it should be noted that for a small number of vacancies one obtains an appreciable dependence on the shape of the unit cell ( aspect ratio of the rectangle ) , since these vacancies are located effectively on a square or rectangular lattice due to the periodic boundary conditions . , ( b ) @xmath54 , and ( c ) @xmath55 , where @xmath25 refers to the average interparticle distance . the surface coverage amounts to @xmath56 % . the left columns refers to microvortex magnetic arrangements . relaxation of the magnetic moment directions using these arrangements as starting configurations yields the metastable solutions shown in the right columns . , width=491 ] first , figure 1 illustrates some representative low - energy magnetic arrangements of disordered particle arrays . with increasing disorder , characterized by the positional standard deviation @xmath28 , the magnetic configurations of the relaxed solutions become increasingly noncollinear . results are given for the magnetic states of a slightly disturbed ( @xmath57 ) , a moderately disturbed ( @xmath58 ) , and a strongly disturbed ( @xmath59 ) particle setup having all the same coverage @xmath56 % . both the optimal microvortex states and the relaxed solutions are shown . for @xmath57 the mv arrangement resembles quite closely the true solution , see figure 1(a ) . however , as can be seen in figure 1(b ) , already a moderate amount of positional disorder destroys the mv state . this is physically reasonable since the mv order is tightly connected to the presence of a square - lattice symmetry of the particle ensemble . the degree of the mv ordering will be quantified below . for large @xmath28 or for a random particle setup the resulting magnetic arrangement is dominated by the formation of chains and loops of magnetic moments with a correlated ` head - to - tail ' alignment of the particle magnetizations , see figure 1(c ) @xcite . this reflects the tendency of the dipole interaction to favour a locally demagnetized state with a vanishing or small net magnetization . + in figure 2 we present examples for the dipole energy distribution of metastable states of slightly and moderately disturbed particle setups shown in figures 1(a ) and ( b ) . these were obtained by considering 20000 random initial configurations @xmath41 and by assigning the energies of the relaxed states to energy intervals @xmath60 $ ] , with @xmath61 k. distinctly different energy distributions are observed for weak and strong disorder . for weak disorder [ e.g. , @xmath57 , see figure 2(a ) ] an _ asymmetric _ energy distribution is found . the lowest energy state is reached very often , in fact about @xmath62 % of the trials relax to that ground state for @xmath63 , and about @xmath64 % for @xmath57 . moreover , the ground state configuration resembles closely the mv state with an almost vanishing net magnetization . in addition , numerous metastable states are obtained , which energies are distributed over a relatively broad range , and which are reached far less frequently . in other words , for weak disturbances the catchment area of the ground state is much larger than the ones of the higher - energy states . it is interesting to note that the energy differences between the few states with the lowest energies are quite larger than those found for less stable magnetic arrangements . since these latter states often exhibit a finite net magnetization , one expects that an external magnetic field tends to stabilize these higher - energy metastable configurations . + already for moderate disorder @xmath58 the character of the energy distribution changes strongly . an almost _ symmetric , _ gaussian - like energy distribution is obtained around the average dipole energy @xmath0 , see figure 2(b ) . the number of metastable states has increased remarkedly . in fact , out of the considered 20000 random trials no single state is reached twice after relaxation . this is in particular true for the low - energy states which are obtained with a very small frequency [ see the encircled region in figure 2(b ) ] . for an even stronger disorder the small peak in the frequency distribution for the low - energy states disappears completely . since the total number of metastable states increases strongly with increasing disorder , the corresponding catchment areas decreases dramatically . the obtained large number of metastable states is consistent with experiments on ferrofluids , which show that after application and removal of an external magnetic field the same magnetic arrangement is seldomly reached for a second time @xcite . furthermore , from figure 2 one observes clearly that the average magnetic dipole energy @xmath0 decreases with increasing positional standard deviation @xmath28 . in figure 3 we present results for @xmath65 per particle as function of @xmath28 and for different particle coverages @xmath66 . a square lattice corresponds to @xmath67 . results for random particle setups are also shown . @xmath68 is calculated for the relaxed solutions as well as for the ferromagnetic and microvortex magnetic states averaged over the corresponding in - plane angles @xmath7 and @xmath1 . the obtained minimum values of @xmath68 are also displayed in order to illustrate the spread of the results around the average . whereas the energy distributions shown in figure 2 are determined from a _ single _ realization of the unit cell , here @xmath68 is in addition averaged over 20 different realizations . in figure 3(a ) , @xmath68 is shown for a coverage @xmath56 % . with increasing @xmath28 the average dipole energy _ decreases , _ i.e. , the respective magnetic binding energy _ increases _ with _ increasing disorder _ @xcite . for @xmath69 , @xmath68 approaches a constant value which corresponds , within the numerical dispersion of the data , to the average dipole energy for a _ random _ particle array . the decrease of the average energy is caused by the nonlinear dependence of the dipole interaction with respect to the interparticle distance @xcite . in fact , once disorder is introduced , the increase of @xmath0 for enlarged distances @xmath70 between some particle pairs is more than counterbalanced by a corresponding decrease for smaller distances between other pairs of particles . a similar behaviour is obtained for the ferromagnetic arrangement , albeit with a larger @xmath68 . in contrast , for the mv state the average energy exhibits a minimum as function of @xmath28 at @xmath71 , and approaches @xmath45 with increasing @xmath28 . relaxation in a disordered particle arrangement , see figure 1 , is thus crucial to the disorder induced reduction of @xmath68 . let us recall that the fm and mv arrangements usually do not correspond to local energy minima for @xmath72 . in figure 3(b ) we show @xmath68 of the relaxed solutions and for different particle coverages @xmath66 . first of all one observes that the overall dependence of @xmath0 on @xmath28 is not significantly affected by @xmath66 . increasing the interparticle spacing @xmath25 decreases the magnitude of the average dipole energy , which should scale in principle as @xmath73 . the dependence of @xmath0 on @xmath66 is depicted in figure 3(c ) for the relaxed solutions . indeed , the expected behaviour @xmath74 is obtained for weak positional disorder @xmath28 . however , for strong disorder and for small coverages a different concentration dependence is observed . it seems that the strong magnetic noncollinearities of the magnetic configurations render the simple scaling expectation no longer applicable . it would be therefore interesting to investigate in detail the energy scaling as function of coverage @xmath66 especially in the limit of strongly disturbed arrays of magnetic particles . note that the magnitude of the dipole energy is comparably small . this is a consequence of the disk - shaped particles assumed in our calculations . for compact sphere - shaped particles with the same radius @xmath19 as the disk - shaped ones , thus yielding the same surface coverage @xmath66 , the corresponding dipole energy will be significantly enhanced due to the larger number of atoms @xmath75 per spherical particle . moreover , similar as the positional disorder a particle - size dispersion yields noncollinear magnetic arrangements even if the particle centers form a periodic lattice . however , one observes that @xmath0 does not vary strongly with increasing size dispersion @xcite . furthermore , we discuss the crossover from a quasi - periodic to a random particle ensemble . in figure 4 we show the coverage dependence of the positional standard deviation @xmath76 , above which the average energy @xmath68 of a quasi - periodic particle arrangement reaches the limiting value of a random setup . one observes that @xmath76 decreases with increasing coverage @xmath66 , as can qualitatively explained by the following simple scaling consideration . the particles are scattered within a certain distance around the sites of the square lattice , the average scattering radius @xmath77 can be estimated by @xmath78 . for a given coverage @xmath66 the average dipole energy for a random particle setup is approximately reached for the _ crossover standard deviation _ @xmath76 for which @xmath77 plus the particle radius equals half of the average interparticle distance , @xmath79 using @xmath26 , one obtains @xmath80 in figure 4 , @xmath81 is compared with the inflection points of @xmath68 extracted from figure 3(b ) for various coverages @xmath66 . one observes that except for the largest considered coverage @xmath56 % a satisfactory agreement is obtained , which supports the validity of the previous scaling considerations . + results for the global and local microvortex order parameters @xmath46 and @xmath47 are presented in figure 5 , assuming two different types of disorder . in figure 5(a ) we consider a disturbed square particle lattice as function of the positional standard deviation @xmath28 for a coverage @xmath56 % , and in figure 5(b ) we vary the concentration of vacancies in an otherwise periodic array . the rather large dispersions of the mv order parameters result from many different initial arrangements and different realizations of the unit cell . locally the mv order is preserved even for strong disorder . for example , for @xmath55 which refers to an almost random particle array , see figure 3(a ) , we obtain @xmath82 , and @xmath83 for @xmath84 % . in contrast , positional disorder has a much stronger effect on @xmath85 . especially positional disturbances quickly destroy the long - range mv ordering in the square lattice . for instance , for a particle coverage @xmath56 % this occurs already for @xmath86 , which is consistent with the minimum of @xmath68 of the mv state , see figure 3(a ) . + + finally , we present results for the angular distribution of the microvortex angle @xmath1 for different degrees of disorder . we consider first the effect of _ vacancies _ in an otherwise periodic square particle lattice , as has been done previously by prakash and henley @xcite . according to these authors the preferred mv angles for a dipole - coupled square spin lattice with a small amount of vacancies correspond to the diagonal directions . indeed , as can be seen from figure 6 , a strong frequency of the diagonal mv angles @xmath87 and @xmath88 is obtained for low vacancy concentrations @xmath30 . the frequencies of these states decrease with increasing @xmath30 , and vanish for @xmath89 - 7 % . in addition to the diagonal states we also obtain a strong frequency of the mv angle along the axial directions ( columnar states ) with mv angles @xmath90 and @xmath91 . these states are also present for larger vacancy concentrations . we have investigated whether the angular distributions are affected by the finite size of the unit cell , in particular whether this could induce the pronounced frequencies of the columnar states . if this is true , the ratio of the frequencies of @xmath52 and @xmath6 is affected by a variation of the aspect ratio of the rectangular unit cell . we found that for not too small @xmath30 the dependence of the calculated frequencies for columnar and diagonal states as function of size and shape of the unit cell is quite weak . hence , our results indicate that the presence of a few vacancies induces a more complicated angular distribution of the mv angle . in any case , we would like to point out that at present we can not rule out completely the possibility that the pronounced frequencies of the columnar states might be caused by the finite size of the unit cell . concerning other types of disorder , we observe that for a _ disturbed _ square lattice characterized by the positional standard deviation @xmath28 there is no particular preference of the diagonal states . for this type of disorder only the columnar states exhibit a pronounced frequency as compared to the rest of the mv angles . the frequency peaks for columnar states decrease for increasing disorder and vanish above @xmath92 for the particle coverage @xmath56 % . a marked dependence of the angular distribution on the size and shape of the unit cell is not observed also for this type of disorder . to conclude this discussion , we would like to emphasize that the angular distributions presented in figure 6 were all obtained for a _ nonrelaxed _ mv state . we have also performed corresponding calculations for the _ relaxed _ solutions , and have determined the mv states which are closest to the noncollinear relaxed magnetic arrangements . in contrast to the results shown in figure 6 the corresponding angular histograms for the relaxed states exhibit a strong dependence on the size and shape of the unit cell . therefore , further investigations would be necessary in order to clarify this matter . in the present study we have investigated the low - energy properties of disordered planar arrays of magnetic nanoparticles interacting by the dipole coupling . different kinds of disorder have been considered . already small deviations from a square particle lattice lift the continuous degeneracy of the microvortex ground state . a strongly noncollinear magnetic order appears in the nanostructure which destroys the mv arrangement , as can be seen from the corresponding order parameter . we have shown that with an increasing disorder the energy distribution of the metastable states changes qualitatively . our results indicate that it should be very difficult to identify the ground state energy and its magnetic configuration for strongly inhomogeneous particle arrangements . this behaviour is typical for spin - glass systems or random magnets . a detailed investigation of the spin - glass hehaviour of the nanostructure is certainly worthlike . this would require the consideration of additional properties such as the nonlinear susceptibility and the time dependent correlation functions @xcite . it has been shown that the average magnetic dipole energy of an ensemble of magnetic particles decreases with increasing positional disorder . moreover , the average dipole energy @xmath0 of a quasi - periodic particle arrangement resembles the one of a random particle setup above the coverage - dependent crossover standard deviation @xmath81 . a simple scaling behaviour of @xmath81 has been derived , which reproduces quite accurately the coverage dependence of @xmath81 . structural disorder and strong magnetic noncollinearity effects result in a deviation from the straightforward scaling @xmath74 of the average dipole energy as function of the coverage . for a square particle lattice with a small vacancy concentration we found a preferred orientation of the microvortex angle @xmath1 along the diagonal directions . this is in agreement with the results obtained previously by prakash and henley @xcite . the pronounced frequency of this state decreases with an increasing vacancy concentration . however , we also find indications that the columnar states are particularly frequent . the difference with previous results could be related to the fact that isolated vacancies were considered in @xcite , whereas in the present study the vacancy concentration can not be chosen arbitrarily small . in contrast to the case of vacancy - induced disorder , for a disturbed square particle array characterized by the positional standard deviation @xmath28 a pronounced frequency is found only for the columnar but not for the diagonal states . the determination of @xmath0 allows to distinguish whether a magnetic particle ensemble can be considered as a weakly or a strongly interacting system . in the first case the interactions can be treated as perturbations to the single - particle couplings , whereas in the latter case they have to be considered explicitly . the present study can be easily extended in order to take into account single - particle anisotropies with distributions of their magnitudes and easy axes . the importance of collectively ordered magnetic states for strongly interacting particle systems has been pointed out . an increasing average binding energy @xmath93 favours magnetic ordering and should cause an increase of its critical spin - glass temperature . in this context the effect of disorder in the particle ensemble on the critical temperature is of considerable interest . also the magnetic relaxation will depend sensitively on the degree of disorder in such nanostructured systems . finite temperature effects can be introduced in the framework of a mean field approximation or by performing monte carlo simulations . magnetic hysteresis loops and susceptibilities can be derived by applying magnetic fields with different directions and strengths . the authors acknowledge support from cnrs ( france ) and from the eu growth project ammare ( contract number g5rd - ct-2001 - 00478 ) . we thank p. politi for fruitful discussions and for sending us his work prior to publication . in this appendix we determine the leading correction to the magnetic dipole interaction , see equation [ e1 ] , beyond the point - dipole sum . the finite extension of the particles for the most general case of arbitrary sizes and shapes is taken into account . for a hexagonal lattice the finite particle size has been considered already by politi and pini @xcite . first , the interaction between a particle pair is calculated . then a particle ensemble with an infinite lateral extension is modeled by means of a rectangular unit cell with periodic boundary conditions . consider a particle @xmath11 containing @xmath12 atoms on lattice sites @xmath94 with position vectors @xmath95 . the center of gravity of this particle is given by @xmath96 the finite size of particle @xmath11 is taken into account by the quadratic deviations with respect to its center , @xmath97 and similarly for @xmath98 and @xmath99 . these quantities depend on the size and shape of the particle and have the dimension of an area . furthermore , we define @xmath100 by @xmath101 hence , @xmath102 with @xmath103 . the factor @xmath104 appearing in the denominator of the dipole interaction energy , see equation [ e1 ] , is expanded to second order in @xmath105 , @xmath106 , and @xmath107 as @xmath108 now all different sums over the atomic sites @xmath94 of particle @xmath11 are performed up to this order . the non - vanishing terms are listed in the following equations [ e9][e18 ] . @xmath109\ , , \label{e9 } \\ \fl \sum_{k\in i}\frac{x_{ik}}{r_{ik}^5 } = \sum_{k\in i } \frac{x_{i0}+x_k}{r_{i0}^5(1+\varepsilon)^{5/2 } } \simeq \frac{n_i}{r_{i0}^5}\,x_{i0 } + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^3}{r_{i0}^2}-3\,x_{i0}\big){\mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{x_{i0}\,y_{i0}^2}{r_{i0}^2}-x_{i0}\big){\mathord{\langle}}y_i^2{\mathord{\rangle}}+ \big(7\,\frac{x_{i0}\,z_{i0}^2}{r_{i0}^2}-x_{i0}\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e10 } \\ \fl \sum_{k\in i}\frac{y_{ik}}{r_{ik}^5 } = \sum_{k\in i } \frac{y_{i0}+y_k}{r_{i0}^5(1+\varepsilon)^{5/2 } } \simeq \frac{n_i}{r_{i0}^5}\,y_{i0 } + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^2\,y_{i0}}{r_{i0}^2}-y_{i0}\big){\mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{y_{i0}^3}{r_{i0}^2}-3\,y_{i0}\big){\mathord{\langle}}y_i^2{\mathord{\rangle}}+ \big(7\,\frac{y_{i0}\,z_{i0}^2}{r_{i0}^2}-y_{i0}\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e11 } \\ \fl \sum_{k\in i}\frac{z_{ik}}{r_{ik}^5 } = \sum_{k\in i } \frac{z_{i0}+z_k}{r_{i0}^5(1+\varepsilon)^{5/2 } } \simeq \frac{n_i}{r_{i0}^5}\,z_{i0 } + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^2\,z_{i0}}{r_{i0}^2}-z_{i0}\big){\mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{y_{i0}^2\,z_{i0}}{r_{i0}^2}-z_{i0}\big){\mathord{\langle}}y_i^2{\mathord{\rangle}}+ \big(7\,\frac{z_{i0}^3}{r_{i0}^2}-3\,z_{i0}\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e12 } \\ \fl \sum_{k\in i}\frac{x_{ik}^2}{r_{ik}^5 } = \sum_{k\in i } \frac{x_{i0}^2 + 2x_{i0}\,x_k+x_k^2}{r_{i0}^5(1+\varepsilon)^{5/2 } } \simeq \frac{n_i}{r_{i0}^5}\big(x_{i0}^2+{\mathord{\langle}}x_i{\mathord{\rangle}}^2\big ) + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^4}{r_{i0}^2}-5\,x_{i0}^2\big ) { \mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{x_{i0}^2\,y_{i0}^2}{r_{i0}^2}-x_{i0}^2\big ) { \mathord{\langle}}y_i^2{\mathord{\rangle}}+ \big(7\,\frac{x_{i0}^2\,z_{i0}^2}{r_{i0}^2}-x_{i0}^2\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e13 } \\ \fl \sum_{k\in i}\frac{y_{ik}^2}{r_{ik}^5 } = \sum_{k\in i } \frac{y_{i0}^2 + 2y_{i0}\,y_k+y_k^2}{r_{i0}^5(1+\varepsilon)^{5/2 } } \simeq \frac{n_i}{r_{i0}^5}\big(y_{i0}^2+{\mathord{\langle}}y_i{\mathord{\rangle}}^2\big ) + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^2\,y_{i0}^2}{r_{i0}^2}-y_{i0}^2\big ) { \mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{y_{i0}^4}{r_{i0}^2}-5\,y_{i0}^2\big){\mathord{\langle}}y_i^2{\mathord{\rangle}}+ \big(7\,\frac{y_{i0}^2\,z_{i0}^2}{r_{i0}^2}-y_{i0}^2\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e14 } \\ \fl \sum_{k\in i}\frac{z_{ik}^2}{r_{ik}^5 } = \sum_{k\in i } \frac{z_{i0}^2 + 2z_{i0}\,z_k+z_k^2}{r_{i0}^5(1+\varepsilon)^{5/2 } } \simeq \frac{n_i}{r_{i0}^5}\big(z_{i0}^2+{\mathord{\langle}}z_i{\mathord{\rangle}}^2\big ) + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^2\,z_{i0}^2}{r_{i0}^2}-z_{i0}^2\big ) { \mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{y_{i0}^2\,z_{i0}^2}{r_{i0}^2}-z_{i0}^2\big ) { \mathord{\langle}}y_i^2{\mathord{\rangle}}+ \big(7\,\frac{z_{i0}^4}{r_{i0}^2}-5\,z_{i0}^2\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e15 } \\ \fl \sum_{k\in i}\frac{x_{ik}\,y_{ik}}{r_{ik}^5 } = \sum_{k\in i } \frac{x_{i0}\,y_{i0}+x_{i0}\,y_k+x_k\,y_{i0}+x_k\,y_k } { r_{i0}^5(1+\varepsilon)^{5/2 } } \nonumber \\ \fl \hspace*{1.5 cm } \simeq \frac{n_i}{r_{i0}^5}\,x_{i0}\,y_{i0 } + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^3\,y_{i0}}{r_{i0}^2}-3\,x_{i0}\,y_{i0}\big ) { \mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{x_{i0}\,y_{i0}^3}{r_{i0}^2}-3\,x_{i0}\,y_{i0}\big ) { \mathord{\langle}}y_i^2{\mathord{\rangle}}+\big(7\,\frac{x_{i0}\,y_{i0}\,z_{i0}^2}{r_{i0}^2}-x_{i0}\ , y_{i0}\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e16 } \\ \fl \sum_{k\in i}\frac{x_{ik}\,z_{ik}}{r_{ik}^5 } = \sum_{k\in i } \frac{x_{i0}\,z_{i0}+x_{i0}\,z_k+x_k\,z_{i0}+x_k\,z_k } { r_{i0}^5(1+\varepsilon)^{5/2 } } \nonumber \\ \fl \hspace*{1.5 cm } \simeq \frac{n_i}{r_{i0}^5}\,x_{i0}\,z_{i0 } + \frac{5}{2}\frac{n_i}{r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^3\,z_{i0}}{r_{i0}^2}-3\,x_{i0}\,z_{i0}\big ) { \mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{x_{i0}\,y_{i0}^2\,z_{i0}}{r_{i0}^2}-x_{i0}\,z_{i0}\big ) { \mathord{\langle}}y_i^2{\mathord{\rangle}}+\big(7\,\frac{x_{i0}\,z_{i0}^3}{r_{i0}^2}-3\,x_{i0}\ , z_{i0}\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , , \label{e17 } \\ \fl \sum_{k\in i}\frac{y_{ik}\,z_{ik}}{r_{ik}^5 } = \sum_{k\in i } \frac{y_{i0}\,z_{i0}+y_{i0}\,z_k+y_k\,z_{i0}+y_k\,z_k } { r_{i0}^5(1+\varepsilon)^{5/2 } } \nonumber \\ \fl \hspace*{1.5 cm } \simeq \frac{n_i}{r_{i0}^5}\,y_{i0}\,z_{i0 } + \frac{5n_i}{2r_{i0}^7}\bigg [ \big(7\,\frac{x_{i0}^2\,y_{i0}\,z_{i0}}{r_{i0}^2}-y_{i0}\,z_{i0}\big ) { \mathord{\langle}}x_i^2{\mathord{\rangle}}\nonumber \\ \fl \hspace*{1.5 cm } + \big(7\,\frac{y_{i0}^3\,z_{i0}}{r_{i0}^2}-3\,y_{i0}\,z_{i0}\big ) { \mathord{\langle}}y_i^2{\mathord{\rangle}}+\big(7\,\frac{y_{i0}\,z_{i0}^3}{r_{i0}^2}-3\,y_{i0}\ , z_{i0}\big ) { \mathord{\langle}}z_i^2{\mathord{\rangle}}\bigg]\ , . \label{e18}\end{aligned}\ ] ] a simple extension of the previous considerations allows to calculate to the same order the corresponding sums involved in the interaction between two extended particles @xmath11 and @xmath34 with sizes @xmath12 and @xmath110 . let @xmath111 denote the relative position vector between the particle centers . the non - vanishing sums in the interaction energy are given by equations [ e9][e18 ] after the replacements @xmath112 , @xmath113 , @xmath114 , @xmath115 , etc . , have been performed . concerning the summation over all atoms @xmath116 of particle @xmath34 , one obtains , for example , for equation [ e9 ] , @xmath117 \;. \label{e19}\end{aligned}\ ] ] thus , within this expansion the dipole interaction between particles @xmath11 and @xmath34 is expressed in terms of the distance @xmath118 between their centers and the quadratic deviations @xmath119 , @xmath120 , etc . , characterizing the sizes and shapes of the two particles . the point - dipole sum is recovered by setting @xmath121 , etc . the correction to the point - dipole sum is a dipole - quadrupole interaction , being of the order @xmath122 , i.e. , the ratio of the particle extensions and the square of the interparticle distance . evidently , the effect of finite particle sizes becomes more important the closer the particles are located . this is the case , for example , for a densely packed 3d ferrofluid or for a layered nanostructured particle ensemble with a large surface coverage . in figure 7 we compare the exact dipole interaction energy @xmath42 with the results obtained by using the point - dipole approximation with and without the dipole - quadrupole correction . @xmath123 for two square - shaped particles is shown as function of the distance @xmath124 between their centers . notice that the correction for nearby particles amounts to @xmath125 % of the point - dipole sum in this case . for simple particle geometries ( e.g. , disks , cubes , or spheres ) the quadratic deviations @xmath119 , etc . , can be calculated analytically . in case of spheres the dipole - quadrupole correction vanishes since a sphere has no quadrupole moment @xcite . let us now consider a planar particle ensemble infinitely extended in the @xmath9 plane . the unit cell has the size @xmath126 and consists @xmath51 particles . periodic boundary conditions are applied laterally , whereas the vertical extension along the @xmath127-direction is finite . the dipole interaction sum runs over all particle pairs within the same and between different unit cells . the position vectors connecting two particle centers are given by @xmath128 , with @xmath129 and @xmath130 integers . for such a periodic planar system an ewald summation technique can be applied by using a rapidly convergent 2d lattice summation @xcite . the following general sums over the unit cells need to be considered , @xmath131 the prime at the sum indicates that the term with @xmath132 is omitted . the different lattice sums appearing in equations [ e9][e18 ] can be obtained by an appropriate choice of the positive integers @xmath133 , @xmath134 , and @xmath135 . in general one has to distinguish between the cases @xmath136 and @xmath137 . the dipole field @xmath31 of particle @xmath11 , see equation [ e1 ] , has the components @xmath138\ , , \label{e21 } \\ \fl b_i^{y,\mathrm{dip}}=\mu_{at}\,\sum_j n_j \hspace{-0.2 cm } \sum_{l_x , l_y=-\infty}^\infty{}\hspace{-0.4cm}'\hspace{0.3 cm } \frac{1}{r^5}\bigg[(2y_{ij0}^2-x_{ij0}^2-z_{ij0}^2)\,m_j^y + 3\,x_{ij0}y_{ij0}\,m_j^x+3\,y_{ij0}z_{ij0}\,m_j^z\bigg]\ , , \label{e22 } \\ \fl b_i^{z,\mathrm{dip}}=\mu_{at}\,\sum_j n_j \hspace{-0.2 cm } \sum_{l_x , l_y=-\infty}^\infty{}\hspace{-0.4cm}'\hspace{0.3 cm } \frac{1}{r^5}\bigg[(2z_{ij0}^2-x_{ij0}^2-y_{ij0}^2)\,m_j^z + 3\,x_{ij0}z_{ij0}\,m_j^x+3\,y_{ij0}z_{ij0}\,m_j^y\bigg]\ , . \label{e23}\end{aligned}\ ] ] the unit vector @xmath139 determines the direction of the particle magnetic moment , with @xmath140 and @xmath141 the polar and azimuthal angles . introducing now the lattice sums @xmath142 and after some algebra one obtains for the three components of the dipole field @xmath143\,\big({\mathord{\langle}}x_i^2{\mathord{\rangle}}+{\mathord{\langle}}x_j^2{\mathord{\rangle}}\big ) \nonumber \\ \fl + \frac{5}{2 } \bigg[\big(14\,t_{ij}^{922}-2\,t_{ij}^{720}-7\ , t_{ij}^{904}+5\,t_{ij}^{702}+z_{ij0}^2\,(t_{ij}^{700}-7\,t_{ij}^{902 } ) -\frac{2}{5}\,t_{ij}^{500}\big)\,m_j^x \nonumber \\ \fl + ( 21\,t_{ij}^{913}-9\,t_{ij}^{711})\,m_j^y+z_{ij0}\,(21\,t_{ij}^{912 } -3\,t_{ij}^{710})m_j^z \bigg]\,\big({\mathord{\langle}}y_i^2{\mathord{\rangle}}+{\mathord{\langle}}y_j^2{\mathord{\rangle}}\big ) \nonumber \\ \fl + \frac{5}{2 } \bigg[\big(14\,z_{ij0}^2\,t_{ij}^{920}-2\,t_{ij}^{720 } -7\,z_{ij0}^2\,t_{ij}^{902}+t_{ij}^{702}+z_{ij0}^2\,(5\,t_{ij}^{700 } -7\,z_{ij0}^2\,t_{ij}^{900})-\frac{2}{5}\,t_{ij}^{500}\big)\,m_j^x \nonumber \\ \fl + ( 21\,z_{ij0}^2\,t_{ij}^{911}-3\,t_{ij}^{711})\,m_j^y+z_{ij0}\,(21\ , z_{ij0}^2\,t_{ij}^{910}-9\,t_{ij}^{710})\,m_j^z\bigg]\,\big ( { \mathord{\langle}}z_i^2{\mathord{\rangle}}+{\mathord{\langle}}z_j^2{\mathord{\rangle}}\big)\bigg\ } \ ; , \label{e24 } \\ \fl b_i^{y,\mathrm{dip}}=\mu_{at}\,\sum_j n_j \bigg\ { 3\,t_{ij}^{511}\,m_j^x+ \big(2\,t_{ij}^{502}-t_{ij}^{520}-z_{ij0}^2\,t_{ij}^{500}\big)\,m_j^y + 3\,z_{ij0}\,t_{ij}^{501}\,m_j^z \nonumber \\ \fl + \frac{5}{2 } \bigg[\big(14\,t_{ij}^{922}-2\,t_{ij}^{702}-7\ , t_{ij}^{940}+5\,t_{ij}^{720}+z_{ij0}^2\,(t_{ij}^{700}-7\,t_{ij}^{920 } ) -\frac{2}{5}\,t_{ij}^{500}\big)\,m_j^y \nonumber \\ \fl + ( 21\,t_{ij}^{931}-9\,t_{ij}^{711})\,m_j^x+z_{ij0}\,(21\ , t_{ij}^{921}-9\,t_{ij}^{701})\,m_j^z \bigg]\ , \big({\mathord{\langle}}x_i^2{\mathord{\rangle}}+{\mathord{\langle}}x_j^2{\mathord{\rangle}}\big ) \nonumber \\ \fl + \frac{5}{2 } \bigg[\big(14\,t_{ij}^{904}-10\,t_{ij}^{702}-7\ , t_{ij}^{922}+t_{ij}^{720}+z_{ij0}^2\,(t_{ij}^{700}-7\,t_{ij}^{902 } ) + \frac{4}{5}\,t_{ij}^{500}\big)\,m_j^y \nonumber \\ \fl + ( 21\,t_{ij}^{913}-9\,t_{ij}^{711})\,m_j^x+z_{ij0}\,(21\,t_{ij}^{903 } -9\,t_{ij}^{701})\,m_j^z \bigg]\,\big({\mathord{\langle}}y_i^2{\mathord{\rangle}}+{\mathord{\langle}}y_j^2{\mathord{\rangle}}\big ) \nonumber \\ \fl + \frac{5}{2 } \bigg[\big(14\,z_{ij0}^2\,t_{ij}^{902}-2\,t_{ij}^{702 } -7\,z_{ij0}^2\,t_{ij}^{920}+t_{ij}^{720}+z_{ij0}^2\,(5\,t_{ij}^{700 } -7\,z_{ij0}^2\,t_{ij}^{900})-\frac{2}{5}\,t_{ij}^{500}\big)\,m_j^y \nonumber \\ \fl + ( 21\,z_{ij0}^2\,t_{ij}^{911}-3\,t_{ij}^{711})\,m_j^x+z_{ij0}\ , ( 21\,z_{ij0}^2\,t_{ij}^{901}-9\,t_{ij}^{701})\,m_j^z\bigg]\,\big ( { \mathord{\langle}}z_i^2{\mathord{\rangle}}+{\mathord{\langle}}z_j^2{\mathord{\rangle}}\big)\bigg\ } \ ; , \label{e25 } \\ \fl b_i^{z,\mathrm{dip}}=\mu_{at}\,\sum_j n_j \bigg\ { \big(2\,z_{ij0}^2\,t_{ij}^{500}-t_{ij}^{520}-t_{ij}^{502}\big)\,m_j^z + 3\,z_{ij0}\,\big(t_{ij}^{510}\,m_j^x+t_{ij}^{501}\,m_j^y\big ) \nonumber \\ \fl + \frac{5}{2 } \bigg [ \big(14\,z_{ij0}^2\,t_{ij}^{920}-2\,z_{ij0}^2\,t_{ij}^{700 } -7\,t_{ij}^{940}+5\,t_{ij}^{720}-7\,t_{ij}^{922}+t_{ij}^{702 } -\frac{2}{5}\,t_{ij}^{500}\big)\,m_j^z \nonumber \\ \fl + z_{ij0}\,(21\,t_{ij}^{930}-9\,t_{ij}^{710})\,m_j^x + z_{ij0}\,(21\,t_{ij}^{921}-3\,t_{ij}^{701})\,m_j^y \bigg]\ , \big({\mathord{\langle}}x_i^2{\mathord{\rangle}}+{\mathord{\langle}}x_j^2{\mathord{\rangle}}\big ) \nonumber \\ \fl + \frac{5}{2 } \bigg[\big(14\,z_{ij0}^2\,t_{ij}^{902}-2\,z_{ij0}^2\ , t_{ij}^{700}-7\,t_{ij}^{904}+5\,t_{ij}^{702}-7\,t_{ij}^{922}+t_{ij}^{720 } -\frac{2}{5}\,t_{ij}^{500}\big)\,m_j^z \nonumber \\ \fl + z_{ij0}\,(21\,t_{ij}^{912}-3\,t_{ij}^{710})\,m_j^x+z_{ij0}\,(21\ , t_{ij}^{903}-9\,t_{ij}^{701})\,m_j^y \bigg]\ , \big({\mathord{\langle}}y_i^2{\mathord{\rangle}}+{\mathord{\langle}}y_j^2{\mathord{\rangle}}\big)\nonumber \\ \fl + \frac{5}{2 } \bigg[\big(z_{ij0}^2\,\big(14\,z_{ij0}^2\,t_{ij}^{900 } -10\,t_{ij}^{700}-7\,t_{ij}^{920}-7\,t_{ij}^{902}\big)+t_{ij}^{720 } + t_{ij}^{702}+\frac{4}{5}\,t_{ij}^{500}\big)\,m_j^z \nonumber \\ \fl + z_{ij0}\,(21\,z_{ij0}^2\,t_{ij}^{910}-9\,t_{ij}^{710})\,m_j^x + z_{ij0}\,(21\,z_{ij0}^2\,t_{ij}^{901}-9\,t_{ij}^{701})\,m_j^y \bigg]\,\big({\mathord{\langle}}z_i^2{\mathord{\rangle}}+{\mathord{\langle}}z_j^2{\mathord{\rangle}}\big)\bigg\ } \;. \label{e26}\end{aligned}\ ] ] the lateral extensions @xmath144 and @xmath145 of the unit cell and the components @xmath146 and @xmath147 of the interparticle distances within a unit cell are involved in a complicated manner in the lattice sums @xmath142 , whereas the dependence on the vertical distances @xmath148 appears explicitly . note that the contributions from mirror particles @xmath149 located in different unit cells are taken into account . the expressions for the dipole field components , equations [ e24 ] [ e26 ] , are simplified appreciably if all particles are located in the same plane ( @xmath136 ) . in this case @xmath150 , hence the @xmath127 component of the dipole field vanishes for an in - plane magnetization ( @xmath151 ) . as before , the point - dipole sum is recovered by setting @xmath152 , etc . the dipole energy @xmath42 per unit cell is obtained from equation [ e1 ] by performing the sum over all particles @xmath153 in the unit cell . 99 for a review see : dormann j l , fiorani d and tronc e 1997 _ adv . phys . _ * 98 * 283 sun s , murray c b , weller d , folks l and moser a 2000 _ science _ * 287 * 1989 ; respaud m et al . 1998 _ phys . b _ * 57 * 2925 ; giersig m and hilgersdorff m 1999 _ j. phys . d _ * 32 * l111 ; russier v , petit c , legrand j and pileni m p 2000 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( a ) _ * 189 * 527 jensen p j , unpublished pogorelov y g , private communication

the low - energy properties of two - dimensional ensembles of dipole - coupled magnetic nanoparticles are studied as function of structural disorder and particle coverage . already small deviations from a square particle arrangement lift the degeneracies of the microvortex magnetic configuration , and result in a strongly noncollinear magnetic order of the particle ensemble . the energy distribution of metastable states is determined . for a low degree of disorder a strongly asymmetric shape with a pronounced peak of the ground state energy results . in contrast , for a strong disorder a gaussian - like distribution is obtained . the average dipole coupling energy @xmath0 decreases with increasing structural disorder . the role of vacancies has been studied for a square particle array by determining the angular distribution of the preferred microvortex angle as function of the vacancy concentration . indications for a preferred angular direction along the axial as well as along the diagonal directions of the square array are revealed . a corresponding investigation for disturbed square arrays results in a different angular distribution . the effect of dipole - quadrupole corrections resulting from the finite size of the particles is quantified .

the full next - to - leading order ( nlo ) qcd corrections to hadroproduction of heavy flavors have been completed as early as 1988 @xcite . they have raised the leading order ( lo ) estimates @xcite but were still below the experimental results ( see e.g. @xcite ) . in a recent analysis theory moved closer to experiment @xcite . a large uncertainty in the nlo calculation results from the freedom in the choice of the renormalization and factorization scales . the dependence on the factorization and renormalization scales is expected to be greatly reduced at next - to - next - to - leading order ( nnlo ) this will reduce the theoretical uncertainty . furthermore , one may hope that there is yet better agreement between theory and experiment at nnlo . in fig . [ nnlo ] we show one generic diagram each for the four classes of gluon induced contributions that need to be calculated for the nnlo corrections to hadroproduction of heavy flavors . they involve the two - loop contribution ( fig . [ nnlo]a ) , the loop - by - loop contribution ( fig . [ nnlo]b ) , the one - loop gluon emission contribution ( fig . [ nnlo]c ) and , finally , the two gluon emission contribution ( fig . [ nnlo]d ) . we mention that there is an interesting subclass of the diagrams in fig . [ nnlo]c where the outgoing gluon is attached directly to the loop . one then has a five - point function which , when folded with the corresponding tree graph contribution , has to be calculated up to @xmath1 . in our work we have concentrated on the loop - by - loop contributions exemplified by fig . specifically , working in the framework of dimensional regularization , we are in the process of calculating @xmath2 results for all scalar massive one - loop one- , two- , three- and four - point integrals that are needed in the calculation of hadronic heavy flavour production . it should be clear from the flavour flow of the diagrams that , apart from the two mass scales set by the kinematics of the process there is only one explicit heavy mass scale in the problem . the integration is generally done by writing down the feynman parameter representation for the corresponding integrals , integrating over feynman parameters up to the last remaining integral , expanding the integrand of the last remaining parametric integral in terms of the dimensional parameter @xmath3 and doing the last parametric integration on the coefficients of the expansion . because the one - loop integrals exhibit infrared ( ir)/collinear ( m ) singularities up to @xmath4 one needs to know the one - loop integrals up to @xmath2 since the one - loop contributions appear in product form in the loop - by - loop contributions . the aim of our project is thus to compute all one - loop contributions to the two processes 1 . @xmath5 2 . @xmath6 up to @xmath2 . regarding the four classes of diagrams in fig.1 one might then say in a very loose sense that we are aiming to calculate one - fourth of the nnlo partonic contributions to heavy hadron production . nevertheless , calculating this one - fourth of the full problem already allows one to obtain a glimpse of the complexity that is waiting for us in the full nnlo calculation . this complexity does in fact reveal itself in terms of a very rich polylogarithmic structure of the laurent series expansion of the scalar one - loop integrals as will be discussed later on . in dimensional regularization there are three different sources that can contribute positive @xmath3powers to the laurent series of the one loop amplitudes . these are 1 . laurent series expansion of scalar one - loop integrals 2 . evaluation of the spin algebra of the loop amplitudes bringing in the @xmath7dimensional metric contraction @xmath8 3 . passarino veltman decomposition of tensor integrals involving again the metric contraction @xmath8 concerning the first item the @xmath2 calculation of the necessary one , two and three point one loop integrals for the loop by loop part of nnlo qcd calculation have now been completed by us . two of the three massive one loop four - point integrals have also been done leaving us with one remaining four - point integral which is presently being worked out . we hope to be able to present complete results on this part of the nnlo calculation in the near future @xcite . concerning the last two items ( spin algebra and passarino veltman decomposition ) there exist some partial results on this part of the nnlo calculation which will be given at the end of this presentation . apart from the present discussion of nnlo contributions to heavy hadron production the calculation of massive scalar loop integrals up to a given positive power of @xmath3 is of interest also in other contexts . for example , if the one loop integrals appear as subdiagrams in a given divergent feynman diagram one again needs to avail of the positive @xmath3powers of the subdiagram . this is of relevance for the calculation of two loop counter terms . another example is the reduction of a given set of loop integrals to master integrals by the integration by parts technique @xcite . in the reduction one may encounter explicit inverse powers of @xmath3 which implies that one has to evaluate the master integrals up to positive @xmath3 powers . [ cols="<,^,<,^,^,^,<",options="header " , ] in table 1 we provide a list of the one - loop scalar one , two , three and four point integrals that need to be evaluated up to @xmath2 in nnlo heavy hadron production . in column 2 the integrals are identified using the notation of @xcite . when writing down a laurent series expansion of these integrals in terms of @xmath3powers one needs to introduce a short hand notation for the integrals in order to keep the notation managable . our short hand notation for the integrals appears in column 3 . in column 5 we comment on their reality property and tick off those integrals that have been completed up to now . as mentioned before all one loop integrals have been done except for the four point integral @xmath9 involving three massive propagators . we have compared our results to results in the literature whenever possible and when these were accessible . we have found agreement . in column 4 , finally , we indicate which of our results are new . we mention that one also needs the imaginary parts of the amplitudes since the square of the amplitude contains also imaginary parts according to @xmath10 note , though , that the imaginary parts are only needed up to @xmath11 since the @xmath12 singularities in the imaginary parts of the one loop contributions are of @xmath13 only . the scalar four point integrals are the most difficult to calculate . they contain a very rich structure in terms of polylogarithmic functions . for example , the @xmath14coefficients of the laurent series expansion of the four point integrals contain logarithms and classical polylogarithms up to order four ( _ i.e. _ @xmath15 ) ( in conjunction with the @xmath16functions @xmath17 ) and products thereof , and a new class of functions which are now termed multiple polylogarithms @xcite . a multiple polylogarithm is represented by @xmath18 where the iterated integrals are defined by @xmath19 instead of using the multiple polylogarithms of goncharov we have chosen to write our results in terms of one - dimensional integral representations given by the integrals @xmath20 and @xmath21 where the @xmath22 take values @xmath23 and the @xmath24 s are combinations of the kinematical variables of the process . the numerical evaluation of these one - dimensional integral representations are quite stable . a comment on the length of our expressions is appropiate . the untreated computer output of the integrations is generally quite lengthy . the hard work is to simplify these expressions . we have written semi - automatic computer codes that achieve the simplifications using known identities among polylogarithms . all intermediate steps have been checked numerically . even after simplification , the final expressions are generally too long to be given in this presentation . as mentioned earlier on , we have compared our results to the results of other authors when they were available and have found agreement . in order to obtain the laurent series expansion of the full one loop amplitude one has to combine the laurent series expansion of the scalar one - loop integrals with the @xmath3expansion from the spin algebra calculation and the passarino veltman decomposition . this is the subject of a second paper which we are working on @xcite . as an example of such an amplitude result we present results on the contribution of the one loop gluon triangle graph to the process @xmath5 . we shall only list the @xmath25 and @xmath26terms for the triangle graph contribution since the finite and divergent pieces have been calculated before ( see e.g. @xcite ) . for the reduced gluon triangle amplitude @xmath28 with gluons and ghosts inside the triangle loop one obtains @xmath29 + 6 i ( t^a t^b - t^b t^a ) { \rm \hspace{-.1 in } } \not p_1 ( g^{\mu\nu } \nonumber \\ & & [ 9 b_5^{(1)}\!\!-\ ! 12 b_5^{(0)}\!\ ! + 9 c_4^{(1 ) } s\ ! - 8]/s + \ ! 8 p_2^{\mu } p_1^{\nu}\ , [ 3 b_5^{(0 ) } \nonumber \\ & & + 2]/s^2 ) ) - \varepsilon^2 ( b_s^{\mu\nu } [ 621 b_5^{(2)}\!\ ! + 36 b_5^{(1)}\!\ ! + 24 b_5^{(0 ) } \nonumber \\ & & + 162 c_4^{(2 ) } s + 16 ] + 6 i ( t^a t^b - t^b t^a ) { \rm \hspace{-.1 in } } \not p_1 ( g^{\mu\nu } \nonumber \\ & & [ 27 b_5^{(2)}\ ! - 36 b_5^{(1)}\ ! - 24 b_5^{(0 ) } + 27 c_4^{(2 ) } s - 16]/s \nonumber \\ & & + 8 p_2^{\mu } p_1^{\nu } [ 9 b_5^{(1 ) } + 6 b_5^{(0 ) } + 4]/s^2 ) ) \}/324 . \end{aligned}\ ] ] the one - loop triangle graph amplitude @xmath28 has been written in terms of the laurent series expansion of the two massless scalar two point and three point one loop integrals @xmath30 and @xmath31 listed in table 1 , where the laurent series expansions are defined by @xmath32 and @xmath33 where @xmath34 in our application . the born term amplitude @xmath35 appearing in ( [ glutri ] ) is defined by @xcite @xmath36 and the coefficient @xmath37 is given by @xmath38 after insertion of the appropiate coefficient functions @xmath39 and @xmath40 our results can be seen to fully agree with the results of the authors of @xcite who also calculated the gluonic one loop corrections to the three gluon vertex with one off - shell gluon . eq.([glutri ] ) gives an impression of the interplay of the three different sources of positive @xmath3powers in the amplitude calculation mentioned earlier on . note in particular that different orders of the laurent series coefficients of the scalar integrals enter at each order of the laurent series expansion of the full amplitude . we would like to thank the organizers of the 2004 loops and legs conference in zinnowitz , j. blmlein , s. moch and t. riemann , for having provided such a nice setting for the conference at the baltic sea together with a very lively and stimulating scientific athmosphere . 9 p. nason , s. dawson and r. k. ellis , nucl . * b303 * ( 1988 ) 607 ; _ ibid _ * b327 * ( 1989 ) 49 ; _ ibid _ * b335 * ( 1990 ) 260(e ) . w. beenakker , h. kuijf , w. l. van neerven and j. smith , phys . d * 40 * ( 1989 ) 54 ; w. beenakker , w. l. van neerven , r. meng , g.a . schuler and j. smith , nucl . phys . * b351 * ( 1991 ) 507 . m. glck , j.f . owens and e. reya , phys . d * 17 * ( 1978 ) 2324 ; + b. l. combridge , nucl . * b151 * ( 1979 ) 429 ; + j. babcock , d. sivers and s. wolfram , phys . rev . d * 18 * ( 1978 ) 162 ; + k. hagiwara and t. yoshino , phys . lett . * 80b * , ( 1979 ) 282 ; + l. m. jones and h. wyld , phys . d * 17 * ( 1978 ) 782 ; + h. georgi _ et al . ( n.y . ) * 114 * ( 1978 ) 273 . m. cacciari , s. frixione , m. l. mangano , p. nason , g. ridolfi , arxiv : hep - ph/0312132 . krner , z. merebashvili and m. rogal , `` laurent series expansion of massive scalar one - loop integrals to @xmath2 '' , to be published . k. g. chetyrkin and f. v. tkachov nucl . phys . * b192 * ( 1981 ) 159 ; + f. v. tkachov , phys . lett . * 100b * ( 1981 ) 65 . goncharov , math . lett . * 5 * ( 1998 ) , available at http://www.math.uiuc.edu/k-theory/0297 . krner , z. merebashvili and m. rogal , `` one loop amplitudes for @xmath5 and @xmath6 to @xmath2 '' , to be published . krner , z. merebashvili , phys . d * 66 * ( 2002 ) 054023 . davydychev , p. osland and o.v . tarasov , phys . d * 54 * ( 1996 ) 4087 ; * ibid * ( 1999)109901(e )

we report on the results of an ongoing calculation of massive scalar one - loop one- , two- , three- and four - point integrals up to @xmath0 which are needed in the nnlo calculation of heavy hadron production .

macrophages are plastic phagocytic cells that participate in innate and adaptive immunity , with important roles in the response against extra- and intracellular parasites , as well as in tissue homeostasis [ 1 , 2 ] . , macrophages contribute to mounting specific immunological responses for host defense , and the plasticity of macrophage phenotypes is modulated by the cytokine profile . tissue damage during inflammation increases the extracellular levels of otherwise intracellular molecules , resulting in damage - associated molecular patterns ( damps ) recognized by the immune system [ 35 ] . extracellular nucleotides , such as the atp released by dying cells and by activated immune cells during inflammation , are important danger signals involved in immune response , participating in both paracrine and autocrine signaling pathways . in inflammatory processes , high extracellular atp levels generated by tissue damage or secretion are recognized by the immune system as a danger signal , activating purinergic p2 receptors that contribute to a proinflammatory response . purinergic p2 receptors can be classified as ionotropic atp - gated ( p2x ) or g - protein coupled metabotropic ( p2y ) . extracellular atp ( eatp ) induces macrophage - mediated immune responses mainly through the activation of p2x7 receptors . these receptors have a ubiquitous distribution , although the highest levels of receptor expression are observed in immune cells of monocyte / macrophage origin . p2x7 receptor activation induces a myriad of intracellular events , including the production of nitric oxide ( no ) and of reactive oxygen species ( ros ) and the activation of phospholipase - d ( pld ) . these events are important for intracellular parasite killing , for the release of proinflammatory cytokines ( such as il-1 ) , and for inducing apoptosis [ 13 , 14 ] . the expression and function of p2x7 receptors are regulated by both pro- and anti - inflammatory stimuli . initially , p2x7 receptor activation in macrophages opens a plasma membrane cation channel that allows a substantial efflux of k , and influx of ca , with later formation of pores permeable to large molecules [ 16 , 17 ] . p2x receptor activation may also induce caspase-1 activation , interleukin il-1 release , apoptosis , phagolysosomal fusion , and the elimination of intracellular pathogens [ 14 , 18 , 19 ] . in murine macrophages , the mature il-1 secretion by the activation of p2x7 receptors is reduced by the incubation in a free - ca buffer . thus , murine macrophage release of mature il-1 depends on intracellular ca , confirming that ca signaling is essential for this p2x7 receptor function . schistosomiasis is a chronic inflammatory disease caused by schistosoma mansoni and it represents the second most common tropical parasitic disease related to socioeconomical factors . while migrating through the vascular system of infected mammalian hosts , parasites evolve from the schistosomula migratory form into adult worms , causing endothelial cell activation , immunological responses , and tissue damage . the disease starts with a th1-type immune response that gradually changes to a th2 profile [ 2124 ] . previous data suggest that the th2 stage begins four to six weeks after infection and is related to egg deposition by adult worms . macrophages play important roles in both phases of schistosomiasis . in the early phase of the disease , macrophages act as immune system effectors cells killing schistosomula and promoting tissue repair . after egg deposition , the immune response switches to a th2 profile that is involved in the formation of liver and colonic granulomas and fibrosis . the eggs are laid in mesenteric microcirculation and they may reach peritoneal cavity where the granulomas formed contain mainly macrophages . although granulomas are important to limit egg - derived potential cytotoxic products , macrophages isolated , for example , from hepatic granulomas , produce lipids mediators and free radicals that are potentially destructive to host tissues . among cytokines involved in schistosomiasis , transforming growth factor-1 ( tgf-1 ) is of particular interest , since high levels of this cytokine are released by peripheral blood mononuclear cells ( pbmcs ) from s. mansoni - infected mice . tgf- has an important role in immune modulation later during infection , limiting liver inflammation and favoring host survival [ 27 , 28 ] . recently , bhardwaj and skelly showed that s. mansoni expresses p2x7 receptors - like molecules and also enzymes responsible for the clearance of extracellular atp ( ectonucleotidases ) , suggesting that purinergic signaling is conserved in these parasites and is important for the host - parasite interplay . however , the impact of the chronic inflammation trigged by schistosomiasis on macrophage p2x7 receptor function remains unknown . here , we evaluated p2x7 receptor function and expression in macrophage from s. mansoni - infected mice . our data show that peritoneal macrophage p2x7 receptor function is attenuated during schistosomiasis and that this is associated with high peritoneal levels of tgf-1 , the important inflammatory mediator present in the chronic phase of the disease . we also show that tgf-1 downregulates p2x function in vitro , mimicking the effect of s. mansoni infection . the following primary antibodies were used in this work : rabbit polyclonal anti - p2x7 receptors ( apr-004 and apr-008 ; alomone labs , israel ) ; mouse monoclonal anti--actin ( santa cruz biotechnology , usa ) ; rat anti - f4/80 ( biolegend , usa ) ; rat anti - f4/80 fitc ( abd serotec , usa ) . atp , 3-o-(4-benzoyl)-atp ( bzatp ) , pmsf , sodium orthovanadate , aprotinin , leupeptin , bsa , ionomycin , and egta were from sigma chemical co. ( usa ) . fura-2-am was from molecular probes ( usa ) and a740003 was from tocris ( usa ) . rpmi , foetal bovine serum ( fbs ) , and penicillin / streptomycin solutions were from gibco brl ( usa ) . stock solutions were prepared in dmso ( 2.5 mm fura-2-am and 10 mm a740003 ) , water ( 10 mm bzatp ) , rpmi ( 5 ng / ml tgf-1 ) , or a buffered physiological saline solution ( 10 mm atp ) . the highest concentration of solvent used was 0.1% ( v / v ) . swiss , c57bl/6 ( wild type ) , and p2x7 receptor knockout ( p2x7 ko ) male mice were used in all procedures . swiss and c57bl/6 mice were obtained from the animal facility of the paulo de goes microbiology institute ( federal university of rio de janeiro , rio de janeiro , brazil ) . p2x7 ko mice ( originally from the jackson laboratory , usa , stock number 005576 ) were maintained in the transgenic animal house of the federal university of rio de janeiro . all mice were kept under a light / dark cycle of 12/12 h and with access to water and food ad libitum . all experiments were conducted in compliance with the ethical standards of our institution ( ethics committee of the federal university of rio de janeiro ; approved under the licenses dfbc - icb-011 and ibccf 154 ) and following both the guidelines of the national council on experimental animal control ( concea , brazil ) and the committee of care and use of laboratory animals ( national research council , united states ) . all efforts were made to minimize both animals suffering and the number of animals used , on the basis of valid statistical evaluation . in this work , we used the bh strain of s. mansoni , obtained from infected biomphalaria glabrata snails . swiss , c57bl/6 , and p2x7 ko mice ( 7 - 10 days old ) were infected percutaneously with approximately 80 cercariae from both genders , for 8 min , as previously described . animals were used in experiments at least 45 days after infection ( dpi ) to allow for full establishment of the infection . age - matched ( 60 to 80 days old ) uninfected swiss , c57bl/6 , and p2x7 ko mice were used as controls . c57bl/6 and p2x7 ko mice survival the peritoneal cavity was washed with 5 ml of sterile phosphate buffered saline ( pbs : 137 mm nacl , 8.1 mm na2hpo4 , 1.5 mm nah2po4 , and 2.7 mm kcl , ph 7.4 ) , and the peritoneal exudate was collected and centrifuged at 350 g , for 5 min , at 4c . the pellet was resuspended in 1 ml of pbs and used to perform total leukocyte counts ( cell viability , as estimated by trypan blue exclusion , was always 95% ) . for macrophages culture , cells were resuspended in 1 ml of rpmi-1640 medium containing 2 g / l sodium bicarbonate , 1 mm l - glutamine , 100 u / ml penicillin , and 100 g / ml streptomycin and plated in 35 mm petri dishes or on 6-well plates . after 1 h of incubation at 37c with 5% co2 , nonadherent cells were removed by vigorous washing , and rpmi-1640 medium with 10% heat - inactivated fbs was added to the cultures , which were kept at 37c with 5% co2 for 24 h until further use . to investigate macrophage responses to atp , freshly harvested peritoneal macrophages ( 10 cells ) from swiss ( uninfected or s. mansoni - infected ) or c57bl/6 ( wild type or p2x7 ko ) mice were treated with 0.1 , 0.5 , or 1 mm atp and 2.5 m ethidium bromide ( eb ) in pbs ( 15 min ; 37c ) . eb was used as a tracer for p2x7 receptor activation ( i.e. , cell permeabilization ) triggered by atp . after incubation with atp and eb , f4/80 positive cells were analyzed by flow cytometry ( 10,000 events / sample ) using a facscan system ( bd pharmingen , usa ) . , a marker was added based on a gate of the f4/80 positive macrophages population , which limited the basal fluorescence . the specific atp - induced permeabilization threshold was defined by comparison with the baseline profile of control cells not treated with atp ( i.e. , incubated with eb only ) . the specific permeabilization is the percentage of eb positive cells after atp stimulation in the f4/80 positive gated cells . alternatively , peritoneal macrophages were plated on 24-well plates ( 2 10 cells / well ) and , after 24 h , treated with 5 ng / ml tgf-1 or vehicle ( rpmi ) , for 24 h , at 37c and in 5% co2 . macrophages were washed in pbs ( ph 7.4 ) and then incubated with 1 mm atp and 5 m eb in buffer ( 145 mm nacl , 5 mm kcl , 1 mm mgcl2 , 1 mm cacl , and 10 mm hepes , ph 7.4 ) for 15 min at 37c to evaluate the p2x7 receptor activation . the ratio between permeabilized ( i.e. , eb positive ) and total cells was determined by direct counting of cells in five randomly chosen fields , using an axiovert 100 microscope ( karl zeiss , oberkochen , germany ) equipped with an olympus digital camera ( olympus american inc . the specific atp - induced permeabilization value ( in % ) was calculated by subtracting from the total % of permeabilized cells a value corresponding to the % of permeabilized cells in control samples not treated with atp ( i.e. , incubated with eb only ) . measurements of the intracellular ca concentration ( [ ca]i ) using fura-2-am were performed as previously described . briefly , macrophages were plated on glass bottom plates ( mattek , usa ) , at a density of 1 10 cells / plate , and maintained for 24 h at 37c , with 5% co2 . then , the medium was removed and the cells were incubated for 40 min with 2.5 m fura-2-am at room temperature . cells were subjected to alternate cycles of illumination with 340 nm and 380 nm excitation wavelengths , and the emission was measured at 500 nm . cells were washed twice with buffered physiological solution ( in mm : nacl 140 , kcl 5 , mgcl2 1 , cacl2 2 , glucose 5 , and hepes 5 , ph 7.4 ) and then stimulated with 100 m 3-o-(4-benzoyl)-atp ( bzatp ) ( at 37c ) in the absence or in the presence of 50 nm of the p2x7 receptor antagonist a740003 ( preincubated for 45 min , at 37c ) . after the maximum effect had been achieved , cells were treated with ca ionophore ( 10 m ionomycin ) and then with 6 mm egta to determine the molar concentration of ca according to the grynkiewicz equation . the estimation of tgf-1 levels in mouse peritoneal washes was performed using an elisa immunoassay kit ( peprotech , rocky hill , nj , usa ) , according to manufacturer 's instructions . for peritoneal wash collection , mice were euthanized with co2 and the peritoneal cavity was washed with 1 ml of sterile pbs . approximately 60% of the initial volume of pbs was recovered and centrifuged at 350 g for 5 min , at 4c . supernatants were collected and stored in liquid n2 until further use ( to determine tgf-1 content ) . peritoneal macrophages from control and infected mice ( 10 cells / well ) were treated with 5 ng / ml tgf- for 24 h , fixed with 4% paraformaldehyde and 4% sucrose for 10 min in pbs , washed , and incubated for 30 min with 50 mm ammonium chloride ( ph 8.0 ) . after three washes in pbs , samples were blocked in pbs with 10% fbs and 0.1% bsa for 30 min , washed twice in pbs , and incubated overnight with a rabbit polyclonal antibody that recognizes an extracellular epitope of p2x7 receptors ( apr-008 ; alomone labs , israel ; peptide kkgwmdpqskgiqtgrc , corresponding to amino acid residues 136152 of mouse p2x7 receptor ; extracellular loop ) diluted to 1 : 400 in pbs and 0.1% bsa . then , cells were washed and incubated with a rat anti - f4/80 antibody diluted to 1 : 50 in pbs and 0.1% bsa for 4 h , at 4c . samples were then labelled with secondary anti - rabbit - alexa 488 and anti - rat - alexa 546 antibodies diluted to 1 : 500 in pbs and 0.1% bsa for 1 h at 4c . after labelling , cells were mounted on slides using vectashield with dapi ( vector , burlingame , ca , usa ) and examined on a tcs - sp5 aobs confocal microscope ( leica microsystems , germany ) . , imagej , us national institutes of health , bethesda , maryland , usa , http://imagej.nih.gov/ij/ , 19972014 ) . the region of interest ( roi ) was delimited in each cell and the respective mean fluorescence intensity was measured based on the pixel intensity . 10 cells per image were evaluated and the fluorescent values were used for statistical analysis . data were also displayed in an orthogonal slice view that shows the raw pixel intensity values found mutually in each of three perpendicular planes . macrophages adhered to 6-well plates were washed with sterile pbs and lysed with 200 l ripa buffer ( 50 mm tris - hcl , ph 7.4 , containing 1% nonidet p40 , 0.25% sodium deoxycholate , 150 mm nacl , 1 mm edta , 1 mm pmsf , 1 mm sodium orthovanadate , 1 mm naf , 10 g / ml aprotinin , and 10 g / ml leupeptin ) . cell lysates were incubated at 4c for 30 min and centrifuged at 8,100 g , for 10 min , at 4c ; the pellets were discarded and the supernatant had their protein content determined by the lowry method . page gels ( 15 g protein / lane ) and then transferred to nitrocellulose membranes using a semidry transfer system . membranes were blocked for 1 h in tris - buffered saline ( tbs ) with 2% nonfat milk and then incubated overnight with rabbit anti - p2x7 receptors ( apr-004 ; alomone labs , israel ; 1 : 200 ; peptide ( c)kirkefpktqgqysgfkypy , corresponding to amino acid residues 576595 of p2x7 receptor intracellular , c - terminus ) or mouse monoclonal anti--actin ( 1 : 20.000 ) primary antibodies . after 3 washes in tbs - tween , membranes were incubated with hrp - conjugated anti - rabbit or anti - mouse secondary antibody ( 1 : 1.000 ) for 1 h and developed using enhanced chemiluminescence ( ecl ) . ponceau staining and labeling with a monoclonal anti--actin antibody were used as internal controls for protein loading . densitometry of protein bands was performed using the imagej software , and the values for relative amounts of protein were normalized to the -actin loading control . peritoneal macrophages from uninfected swiss mice ( treated with 5 ng / ml tgf-1 or with vehicle , for 24 h ) or from s. mansoni - infected mice were used to isolate total rna using the trizol reagent ( life technologies ) , according to the manufacturer 's instructions . total rna was quantified using an nd-1000 spectrophotometer ( nanodrop ) , and cdna was synthesized from 500 ng of total rna using the high capacity cdna reverse transcription kit with rnase inhibitor ( invitrogen ) . the sybr select master mix ( applied biosystems ) was used for qrt - pcr , to detect double - stranded dna synthesis . reactions were carried out in a final volume of 10 l , using 2 l of diluted cdna ( 1 : 10 ) and 300 nm of each of the reverse and forward primers . the following primers were used for qrt - pcr : for p2rx7 , 5 aatcggtgtgtttcctttgg 3 ( forward ) and 5 ccgggtgactttgtttgtct 3 ( reverse ) ; for actb , 5 tatgccaacacagtgctgtctgg 3 ( forward ) and 5 tactcctgcttgctgatccacat 3 ( reverse ) ; and for gapdh , 5 ggtcatcccagagctgaacg 3 ( forward ) and 5 ttgctgttgaagtcgcagga 3 ( reverse ) . reactions were performed in a 7500 fast real - time system ( applied biosystems ) , using the following pcr conditions : 5 min at 95c , followed by 40 cycles of 15 s at 95c , 35 s at 60c , and 15 s at 72c . at the end of cycling protocol , a melting - curve analysis ( with fluorescence measurements from 60 to 99c ) was performed . relative expression levels were determined using the sequence detection software v.2.0.5 ( applied biosystems ) , and the efficiency per sample was calculated using the linregpcr 11.0 software ( manufacturer).-actin and gapdh were used as internal controls to calculate relative p2rx7 mrna levels , by the comparative threshold cycle ( ct ) method with efficiency correction , using the mean qrt - pcr efficiency for each amplicon , as previously described [ 34 , 35 ] . differences between two or more groups were analyzed by student 's t - test or one - way analysis of variance ( anova ) followed by post hoc newman - keuls test , respectively , considering p < 0.05 . we used several approaches to examine the impact of the chronic inflammation triggered by s. mansoni infection on macrophage p2x7 receptor function . activation of p2x7 receptors by atp opens plasma membrane pores that allow molecules greater than 900 kda ( such as the fluorescent dye eb ) to enter the cells [ 17 , 36 ] . thus , we used atp - induced cell permeabilization ( as evidenced by staining with eb ) as a tool to compare the p2x7 receptor activation in peritoneal macrophage from infected and uninfected swiss mice . incubations with 0.11 mm atp induced cell permeabilization in macrophages from uninfected mice ; however , this effect was reduced in macrophages from infected mice ( figure 1(a ) ) . atp also induced permeabilization in macrophages from c57bl/6 wild type mice but , as expected , not in macrophages from p2x7 ko mice ( figure 1(b ) ) . we also used the potent p2x7 agonist bzatp to verify if p2x7 receptor activation increased the cytosolic ca concentration in macrophages from infected and uninfected swiss mice , since atp - induced ca influx is a hallmark of p2x7 activation . the basal levels of cytosolic ca ( before bzatp addition ) were similar in both groups ( figure 2(a ) ) . after treatment with 100 m bzatp , macrophages from uninfected mice showed a typical p2x7 receptors activation profile at 37c , characterized by a pronounced biphasic increase in intracellular ca levels ( figure 2(a ) ) . however , the p2x7 receptor - mediated ca influx was considerably less pronounced in macrophages from infected mice when compared to that observed in macrophages from uninfected mice ( figures 2(a ) and 2(b ) ) . we also assessed changes in intracellular ca in the presence of the selective p2x7 receptor antagonist a740003 . treatment with 50 nm a740003 did not alter basal intracellular ca levels , but it had a strong negative effect on the bzatp - induced ca influx , and this effect was similar in macrophages from both groups . these results confirmed that the increase in intracellular ca levels after addition of bzatp was due to p2x7 receptor activation . these data are in agreement with the reduction in atp - induced permeabilization observed in macrophages from infected mice ( figure 1(a ) ) and suggest that p2x7 receptor signaling is downregulated during schistosomiasis . moreover , in the chronic phase of schistosomiasis , there is a gradual increase of serum th2 cytokines . indeed , we observed a significant increase in tgf-1 levels in the peritoneal cavity of mice infected with s. mansoni ( figure 3 ) . to investigate if tgf-1 could modulate p2x7 receptor function in peritoneal macrophages similar to that described for monocytes , we harvested peritoneal macrophages from uninfected animals and treated these cells with 5 ng / ml tgf-1 for 24 h before assessing their sensitivity to atp - induced permeabilization ( using eb as a tracer ) . in the absence of atp , tgf-1 treatment did not induce cell permeabilization ; however , tgf-1 reduced the permeabilizing effect of 1 mm atp by approximately 50% , when compared to controls treated with atp only ( figure 4 ) . we also performed the permeabilization after 48 h of tgf- treatment and we observed that , even after 48 h , the p2x7-induced permeabilization was also reduced ( data not shown ) . the analysis of the concentration - response curve using different concentrations of tgf- showed that only the concentrations 5 ng / ml and 10 ng / ml were able to reduce the permeabilization intensity in macrophages ( data not shown ) . to evaluate whether the reduction in p2x7 receptors function observed in schistosomiasis and in tgf-1-treated cells was due , at least in part , to changes in p2x7 receptor expression , we quantified both p2x7 protein expression and the transcription from the p2rx7 locus by western blotting and qrt - pcr , respectively . we detected similar levels of p2x7 protein and mrna in macrophages from uninfected and infected groups ( figures 5(a ) and 5(c ) ) . moreover , the levels of p2x7 protein and mrna in macrophages from uninfected mice were not altered by treatment with 5 ng / ml tgf-1 for 24 h ( figures 5(b ) and 5(c ) ) . p2x7 receptors are targets of posttranslational modifications that regulate their insertion into plasma membrane , and the proinflammatory effects of p2x7 receptors ( including il-1 release and no and ros production ) depend on receptor localization at the cell surface . moreover , prolonged exposure of macrophages to atp may induce p2x7 receptors removal from the cell surface by internalization [ 39 , 40 ] . since the reduction in p2x7 function during s. mansoni infection was not due to decreases in protein or mrna levels , we hypothesized that changes in receptor structure or localization occurred during infection and downregulated receptor function , similar to that described for other p2x receptors . to test this hypothesis , we analyzed p2x7 receptor localization in nonpermeabilized f4/80 ( a common surface marker of mature macrophages ) positive macrophages from uninfected and s. mansoni - infected mice using an antibody that recognizes an extracellular p2x7 epitope . confocal microscopy analysis of anti - p2x7 labeled cells suggested that the levels of cell surface p2x7 receptors were reduced in macrophages from infected mice ( figures 6(a ) and 6(b ) ) . interestingly , there was also a reduction in cell surface p2x7 in macrophages from uninfected mice treated with tgf-1 ( figures 6(a ) and 6(b ) ) . relative quantification of the immunofluorescence data showed that there was a 1.6-fold decrease ( approximately ) in the intensity of cell surface p2x7 fluorescence in macrophages from infected mice , when compared to that observed in uninfected control mice ( figure 6(b ) ) . next , to evaluate the participation of p2x7 receptors during the disease , we infected c57bl/6 wild type and p2x7 ko mice and followed the progression of infection . the survival curves showed that mortality in p2x7 ko infected mice started at 28 dpi and reached 100% at 60 dpi . in contrast , no death was observed in c57bl/6 wild type mice ( figure 7 ) . the latter phenotype is present mainly in macrophages surrounding eggs within liver granulomas and was recently shown to be important in the control of tissue fibrosis . considering that schistosomiasis is a chronic inflammatory disease and that macrophages are involved in schistosomiasis pathogenesis , we sought to evaluate the function of p2x7 receptors in macrophages from mice infected with s. mansoni , since these receptors play an important role in inflammatory processes . here , we used a combination of atp - induced permeabilization and intracellular ca measurement assays to show that , during the chronic phase of schistosomiasis , there is a reduction in the atp - dependent p2x7 receptor function in macrophages ( figures 1 and 2 ) , similar to that observed in mesenteric endothelial cells using the same experimental model . while the function and expression of macrophage p2x7 receptors are positively regulated by proinflammatory cytokines such as ifn- [ 44 , 45 ] , gadeock and coworkers showed that the upregulation of p2x7 receptors in thp-1 monocytes is negatively regulated by tgf-. on the other hand , peripheral blood mononuclear cells ( pbmcs ) from s. mansoni - infected mice produce high levels of tgf- , and this cytokine is important to limit liver inflammation and favor host survival [ 27 , 28 ] . overall , these data are in agreement with our results also showing that the levels of peritoneal tgf-1 are increased in mice infected with s. mansoni ( figure 3 ) and that tgf-1 , in a concentration close to the ones observed in the serum of chronic patients , reduces by approximately 50% the p2x7-dependent macrophage permeabilization triggered by atp ( figure 4 ) , mimicking the attenuated p2x7 response observed during s. mansoni infection ( figure 1(a ) ) . taken together , these results support our hypothesis that the downregulation of p2x7 function observed in schistosomiasis is a result of the increase in tgf-1 levels during infection . regarding tgf- levels , despite the difference between the in vitro treatment concentration ( 5 ng / ml ) and the in vivo peritoneal measurement ( 100 pg / ml ) , we must consider that we injected 1 ml of pbs in the peritoneal cavity of infected animals before removing the body fluid for cytokine determination . therefore the samples were diluted , and , as a consequence , peritoneal tgf- levels in vivo may be higher than the estimation in vitro . moreover , previous data showed that individuals chronically infected with schistosomiasis have tgf- serum levels around 20 ng / ml and the serum level estimated in s. mansoni - infected mice ( 19.98 2.37 ng / ml ) is compatible with the value observed in patients . therefore we conclude that the tgf- concentration used in present work is compatible with the disease , and the peritoneal tgf- concentration in the infected animals is probably higher than estimated . finally , tgf- in the ng / ml range of concentration is able to modulate p2x7r function . western blotting and qrt - pcr data ( using whole cell lysates ) excluded the possibility that the reduction in p2x7 receptor function during s. mansoni infection or after treatment with tgf-1 resulted from decreased levels of p2x7 protein or mrna . in fact , immunofluorescence microscopy analysis of nonpermeabilized macrophages expressing f4/80 on their cell surface revealed that there was a lower density of surface p2x7 receptors in cells from infected mice compared to those from uninfected , control animals ( figure 6 ) . since total p2x7 protein levels were similar in both groups , we propose that there is reduction of p2x7 receptor in plasma membrane of macrophages from infected mice . the disappearance of immunoreactivity from plasma membrane could be related to some conformational changes of the receptor , an interaction with other proteins masking the extracellular epitope recognized by the antibody or the p2x7 receptor internalization . however , tgf- treatment in vitro mimicked both the reduced cell surface receptor expression and function observed in macrophages obtained from infected animals . consequently , a plausible explanation for the reduction in p2x7 function ( without corresponding decreases in total protein or mrna levels ) during chronic schistosomiasis could be related to a reduced cell surface expression of p2x7 receptor . despite the work of gadeock et al . , data investigating the link between tgf-1 and p2x7 receptors function and/or expression are still missing . since control macrophage treatment with tgf-1 mimicked the profile of cell surface p2x7 receptors expression and function observed in live macrophages obtained from infected mice , it is supposed that tgf-1 could be involved in the p2x7 receptors reduced function observed in the disease . to the best of our knowledge , this is the first report that shows a direct effect of tgf-1 on macrophage p2x7 receptor function . however , we do not exclude that other cytokines could contribute to the p2x7 reduced function in macrophages from s. mansoni - infected mice , since in the later phase of the disease beyond the increase of tgf- levels there is also the increase of il-4 , il-5 , il-10 , and il-13 .. moreover , it was shown that il-4 and il-10 also inhibit eb uptake in rat alveolar macrophage . furthermore , previous data showed that tgf- , il-10 , and il-4 inhibit macrophage cytotoxicity which could be an important strategy used by s. mansoni to evade macrophage - mediated immune destruction . patients with schistosomiasis may be more susceptible to secondary infections , and prior infection with schistosoma also increases the severity of secondary infections with leishmania , toxoplasma gondii , and salmonella . in addition , a previous report showed that macrophages from chronically infected mice have reduced phagocytic activity ; however , little is known about the mechanisms underlying this phenomenon . recently , wiley and gu showed that p2x7 receptors on the surface of monocytes / macrophages may act as scavenger receptors for bacteria in the absence of atp . therefore , the reduction of p2x7 receptor function in s. mansoni - infected animals could limit bacterial ( and possibly protozoal ) phagocytosis during schistosomiasis . this phenomenon might explain the increased susceptibility of patients infected with s. mansoni to secondary infections with other parasites and also the higher severity of secondary infections in these patients . kusner and adams showed that atp kills mycobacterium tuberculosis in human macrophages and that this effect depends on p2x7 receptor - mediated pld activation . this mechanism is also important for the atp - mediated killing of chlamydia trachomatis in murine peritoneal macrophages . moreover , our group showed that the acute infection of macrophages with chlamydia psittaci reduces p2x7 receptor - mediated cell permeabilization and ca influx , thus inhibiting macrophage apoptosis . considering that c. psittaci are obligatory intracellular parasites , this phenomenon could be an attempt to limit immunological responses by reducing atp - mediated apoptosis and , consequently , favoring parasite survival . an important new aspect of p2x7 receptors signaling highlighted in the present work is that the function of macrophage p2x7 receptors may also be modulated by the extracellular parasite s. mansoni . altogether , our data suggest that , during schistosomiasis , the function of macrophage p2x7 receptors is reduced and that tgf-1 plays a key putative role in the downregulation of receptor signaling . we hypothesize that macrophage purinergic receptors are differentially modulated during disease progression and that this phenomenon has a key role in the immune response against s. mansoni . in this context , our data show that p2x7 receptor knockout animals ( p2x7 ko ) are much more susceptible to death during s. mansoni infection than wt mice highlighting this p2 purinergic receptor and reinforcing the necessity of future studies exploring in deep its importance in s. mansoni - induced disease . given that purinergic signaling is also found in s. mansoni , understanding the interplay between host and parasite purinergic signaling pathways is now important to clarify if future therapeutic approaches targeting these signaling pathways would be useful against schistosomiasis . altogether , our data show that s. mansoni infection reduced p2x7 function in peritoneal macrophages during the chronic phase of the disease . furthermore , the peritoneal cavity of infected mice had increased levels of tgf-1 , and this cytokine reduced p2x7 receptor function in macrophages from uninfected mice . thus , immunomodulation by tgf-1 could limit p2x7-dependent inflammatory effects in macrophages from s. mansoni patients and may provide an explanation for the increased susceptibility of these patients to infections by others pathogens .

schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation . although p2x7 receptor signaling plays an important role in inflammatory responses mediated by macrophages , no reports have examined the role of p2x7 receptors in macrophage function during schistosomiasis . thus , we evaluated p2x7 receptor function in peritoneal macrophages during schistosomiasis using an atp - induced permeabilization assay and measurements of the intracellular ca2 + concentration . atp treatment induced significantly less permeabilization in macrophages from s. mansoni - infected mice than in control cells from uninfected animals . furthermore , p2x7-mediated increases in intracellular ca2 + levels were also reduced in macrophages from infected mice . tgf-1 levels were increased in the peritoneal cavity of infected animals , and pretreatment of control macrophages with tgf-1 reduced atp - induced permeabilization , mimicking the effect of s. mansoni infection . western blot and qrt - pcr data showed no difference in p2x7 protein and mrna between uninfected , infected , and tgf-1-treated groups . however , immunofluorescence analysis revealed reduced cell surface localization of p2x7 receptors in macrophages from infected and tgf-1-treated mice compared to controls . therefore , our data suggest that schistosomiasis reduces peritoneal macrophage p2x7 receptor signaling . this effect is likely due to the fact that infected mice have increased levels of tgf-1 , which reduces p2x7 receptor cell surface expression .

rare @xmath1 meson decays , induced by flavor changing neutral current ( fcnc ) @xmath2 transitions provide a promising ground for testing the structure of weak interactions . these decays which are forbidden in the standard model ( sm ) at tree level , occur at loop level and are very sensitive to the gauge structure of the sm . moreover , these decays are also quite sensitive to the existence of new physics beyond the sm , since loops with new particles can give considerable contribution to rare decays . the new physics effects in rare decays can appear in two ways ; one via modification of the existing wilson coefficients in the sm , or through the introduction of some operators with new coefficients . theoretical investigation of the @xmath3 decays are relatively more clean compared to their exclusive counterparts , since they are not spoiled by nonperturbative long distance effects , while the corresponding exclusive channels are easier to measure experimentally . some of the most important exclusive fcnc decays are @xmath4 and @xmath5 decays . the latter provides potentially a very rich set of experimental observables , such as , lepton pair forward backward ( fb ) asymmetry , lepton polarizations , etc . various kinematical distributions of such processes as @xmath6 @xcite , @xmath7 @xcite , @xmath8 @xcite and @xmath9 @xcite have already been studied . experimentally measurable quantities such as forward backward asymmetry , single polarization asymmetry , etc . , have been studied for the @xmath10 decay in @xcite . study of these quantities can give useful information in fitting the parameters of the sm and put constraints on new physics @xcite . it has been pointed out in @xcite that the study of simultaneous polarizations of both leptons in the final state provide , in principle , measurement of many more observables which would be useful in further improvement of the parameters of the sm probing new physics beyond the sm . it should be noted here that both lepton polarizations in the @xmath11 and @xmath12 decays are studied in @xcite and @xcite , respectively . as has already been noted , one efficient way of establishing new physics effects is studying forward backward asymmetry in semileptonic @xmath0 decay , since , @xmath13 vanishes at specific values of the dilepton invariant mass , and more essential than that , this zero position of @xmath13 is known to be practically free of hadronic uncertainties @xcite . the aim of the present work is studying the polarized forward backward asymmetry in the exclusive @xmath10 decay using a general form of the effective hamiltonian , including all possible forms of interactions . here we would like to remind the reader that the influence of new wilson coefficients on various kinematical variables , such as branching ratios , lepton pair forward backward asymmetries and single lepton polarization asymmetries for the inclusive @xmath14 decays ( see first references in @xcite ) and exclusive @xmath15 @xcite and pure leptonic @xmath16 decays @xcite have been studied comprehensively . recently , exiting results have been announced by the babar and belle collaborations for experimental study of the @xmath17 decay . as far as the results for the branching ratio of the @xmath10 decay measured by these collaborations are gives as ( b k^^+ ^- ) = \ { lc ( 11.5^+2.6_-2.4 0.8 0.2 ) 10 ^ -7 & @xcite , + + ( 0.88^+0.33_-0.29 ) 10 ^ -6 & @xcite . . the paper is organized as follows . in section 2 , using a general form of the effective hamiltonian , we obtain the matrix element in terms of the form factors of the @xmath18 transition . in section 3 we derive the analytical results for the polarized forward backward asymmetry . last section is devoted to the numerical analysis , discussion and conclusions . in this section we present the matrix element for the @xmath10 decay using a general form of the effective hamiltonian . the @xmath10 process is governed by @xmath19 transition at quark level . the effective hamiltonian for the @xmath19 can be written in terms of the twelve model independent four fermi interactions in the following form : [ e6301 ] h_eff v_tsv_tb^\ { c_sl |s i _ l b |^+ c_br |s i _ r b |^ + c_ll^tot |s_l _ b_l |_l ^_l + c_lr^tot |s_l _ b_l |_r ^_r + c_rl |s_r _ b_r c_rr |s_r _ b_r |_r ^_r + c_lrlr |s_l b_r |_l _ r + c_rllr |s_r b_l |_l _ r + c_lrrl |s_l b_r |_r _ l + c_rlrl |s_r b_l |_r _ l+ c_t |s _ b |^ + i c_te^ |s _ b | _ } , where @xmath20 and @xmath21 in ( [ e6301 ] ) are defined as l = , r = , and @xmath22 are the coefficients of the four fermi interactions . here , few words about the above hamiltonian are in order . in principle , @xmath23 , being a member of the standard model operators , as well as operators of the type @xmath24 , where @xmath25 represents a quark field , give contributions to the @xmath19 transition at one loop level . the hamiltonian given in eq . ( [ e6301 ] ) should be understood as an effective version of the most general one , where the above mentioned contributions are absorbed into effective wilson coefficients which depend on @xmath26 in general . the first two coefficients in eq . ( [ e6301 ] ) , @xmath27 and @xmath28 , are the nonlocal fermi interactions , which correspond to @xmath29 and @xmath30 in the sm , respectively . the following four terms with coefficients @xmath31 , @xmath32 , @xmath33 and @xmath34 are the vector type interactions . two of these interactions containing @xmath35 and @xmath36 do already exist in the sm in the form @xmath37 and @xmath38 . hence , representing @xmath35 and @xmath36 in the form c_ll^tot & = & c_9^eff - c_10 + c_ll , + c_lr^tot & = & c_9^eff + c_10 + c_lr , allows us to conclude that @xmath35 and @xmath36 describe the sum of the contributions from sm and the new physics . the terms with coefficients @xmath39 , @xmath40 , @xmath41 and @xmath42 describe the scalar type interactions . the remaining last two terms lead by the coefficients @xmath43 and @xmath44 , obviously , describe the tensor type interactions . the exclusive @xmath10 decay is described in terms of the matrix elements of the quark operators in eq . ( [ e6301 ] ) over meson states , which can be parametrized in terms of the form factors . obviously , the following matrix elements & & k^|s _ ( 1 _ 5 ) b b , + & & k^|s i _ q^ ( 1 _ 5 ) b b , + & & k^|s ( 1 _ 5 ) b b , + & & k^|s _ b b , are needed for the calculation of the @xmath10 decay . these matrix elements are defined as follows : + & & - _ ^ p_k^^q^ i _ ^(m_b+m_k^ ) a_1(q^2 ) + & & i ( p_b + p_k^)_(^q ) i q _ ( ^q ) , + + + & & 4 _ ^ p_k^^q^t_1(q^2 ) 2 i t_2(q^2 ) + & & 2 i ( ^q ) t_3(q^2 ) , + + + & & i _ \ { - 2 t_1(q^2 ) ^^(p_b + p_k^)^+ ( m_b^2-m_k^^2 ) ^ q^ + & & - ( ^q ) p_k^^q^ } . where @xmath45 is the momentum transfer and @xmath46 is the polarization vector of @xmath47 meson . in order to ensure finiteness of ( [ e6302 ] ) at @xmath48 , we assume that @xmath49 and @xmath50 . the matrix element @xmath51 can be calculated from eq . ( [ e6302 ] ) by contracting both sides of eq . ( [ e6302 ] ) with @xmath52 and using equation of motion . neglecting the mass of the strange quark we get [ e6305 ] k^(p_k^ , ) |s ( 1 _ 5 ) b b(p_b ) = . in deriving eq . ( [ e6305 ] ) we have used the relationship 2 m_k^ a_3(q^2 ) = ( m_b+m_k^ ) a_1(q^2 ) - ( m_b - m_k^ ) a_2(q^2 ) , which follows from the equations of motion . using the definition of the form factors , as given above , the amplitude of the @xmath10 decay can be written as + & & \ { |^(1-_5 ) + & & + |^(1+_5 ) + & & + |(1-_5 ) + |(1+_5 ) + & & + 4 |^ ( i c_t _ ) + & & + 16 c_te | _ , + + [ e6317 ] a_fb^lt m_b^2 , + + [ e6318 ] a_fb^tl m_b^2 + + [ e6319 ] a_fb^nt m_b^2 , + + [ e6320 ] a_fb^tn m_b^2 , + + [ e6321 ] a_fb^nn m_b^3 v , + + [ e6322 ] a_fb^tt m_b^3 v . in these expressions for @xmath53 , the first index in the superscript describes the polarization of lepton and the second index describes that of anti lepton . it should be noted here that , the double polarized @xmath54 asymmetry for the @xmath55 and @xmath56 decays are calculated in the supersymmetric model in @xcite . in this section we analyze the effects of the wilson coefficients on the polarized @xmath54 asymmetry . the input parameters we use in our numerical calculations are : @xmath57 and @xmath58 . for the values of the wilson coefficients we use @xmath59 and @xmath60 . it should be noted that the above presented value for @xmath61 corresponds only to short distance contributions . in addition to the short distance contributions , it receives long distance contributions which result from the conversion of @xmath62 to the lepton pair . in this work we neglect long distance contributions . the reason for such a choice is dictated by the fact that , in the sm the zero position of @xmath13 for the @xmath10 decay is practically independent of the form factors and is determined in terms of short distance wilson coefficients @xmath61 and @xmath63 ( see @xcite ) and @xmath64 . for the form factors we have used the light cone qcd sum rules results @xcite . as a result of the analysis carried out in this scheme , the @xmath26 dependence of the form factors can be represented in terms of three parameters as f(q^2 ) = , where the values of parameters @xmath65 , @xmath66 and @xmath67 for the @xmath18 decay are listed in table 1 . @xmath68 the new wilson coefficients vary in the range @xmath69 . the experimental value of the branching ratio of the @xmath70 decay @xcite and the bound on the branching ratio of the @xmath71 @xcite suggest that this is the right order of magnitude for the vector and scalar interaction coefficients . it should be noted here that the experimental results lead to stronger restrictions on some of the wilson coefficients , namely @xmath72 , @xmath73 , @xmath74 , @xmath75 , while the remaining coefficients vary in the range @xmath76 . since all existing experimental results are yet preliminary , we will vary all new wilson coefficients in the range @xmath76 . in fig . 1(2 ) we present the dependence of the @xmath77 on @xmath26 for the @xmath78 at four fixed values of @xmath79 . from these figures we see that nonzero values of the new wilson coefficients shift the zero position of @xmath77 corresponding to the sm result . when @xmath31 gets negative ( positive ) values , the zero position of @xmath77 shifts to the left ( right ) in comparison to that of the zero position in the sm . our analysis shows that the zero position of @xmath77 for the @xmath78 decay is practically independent of the existence of other wilson coefficients . for this reason we do not present the dependence of @xmath77 on @xmath26 at fixed values of the remaining wilson coefficients . figs . 3(5 ) and 4(6 ) depict the dependence of @xmath80 and @xmath81 on @xmath26 at four fixed values of @xmath82 . we observe from these figures that the zero positions of @xmath80 and @xmath81 are very sensitive to the existence of tensor interactions . more essential than is that in the sm case @xmath80 and @xmath81 do not have zero values . therefore , if zero values for the polarized @xmath80 and @xmath81 asymmetries are measured in the experiments in future , these results are unambiguous indication of the existence of new physics beyond the sm , more specifically , the existence of tensor interactions . in the case of @xmath83 decay , the zero position for the double polarization asymmetries @xmath53 is absent for most of the new wilson coefficients , and hence , it could be concluded to be insensitive to the new physics beyond the sm , or the value of @xmath53 is quite small , whose measurement in the experiments could practically be impossible . for this reason we do not present the dependencies of @xmath53 on @xmath26 at fixed values of @xmath22 for the @xmath83 decay . as is obvious from the explicit expressions of the forward backward asymmetries , they depend both on @xmath26 and the new wilson coefficients @xmath22 . as a result of this , it might be difficult to study the dependence of the polarized forward backward asymmetries @xmath53 on these parameters . however , we can eliminate the dependence of the polarized @xmath53 on @xmath26 by performing integration over @xmath26 in the kinematically allowed region , so that the polarized forward backward asymmetry is said to be averaged . the averaged polarized forward backward asymmetry is defined as _ fb^ij = . in fig . ( 7 ) , we present the dependence of @xmath84 on @xmath22 for the @xmath78 decay . the common intersection point of all curves corresponds to the sm case . we observe from this figure that , @xmath84 has symmetric behavior on its dependence on @xmath43 and @xmath44 with respect to zero position , and remains smaller compared to the sm result . the only case for which @xmath85 occurs for the positive values of the vector interaction coefficients . therefore , if we measure in the experiments @xmath86 , it is a direct indication of new physics beyond the sm , and this departure is to be attributed solely to the existence of vector type interactions . the situation is even more conformative for the @xmath83 case . in figs . ( 9 ) and ( 10 ) , we present the dependencies of @xmath84 and @xmath87 on the new wilson coefficients @xmath22 . from fig . ( 9 ) we observe that , with respect to the zero value of the wilson coefficients , @xmath84 increases if @xmath88 and @xmath34 increase , while it decreases when @xmath40 increases . from fig . ( 9 ) we see that the dependence of @xmath87 on the tensor interaction is stronger . when @xmath89 and @xmath32 are negative ( positive ) and vary from @xmath90 to zero ( from zero to @xmath91 ) @xmath87 decrease ( increase ) . additionally , we observe that with increasing values of @xmath33 and @xmath34 , @xmath87 increases . this figure further depicts that @xmath87 , for practical purposes , is not sensitive to the existence of scalar interactions . on the other hand , @xmath92 and @xmath93 are very sensitive to the presence of tensor and scalar interactions ( see figs . ( 10 ) and ( 11 ) ) . it is clear from these results that several of the polarized forward backward asymmetries show sizable departure from the sm results and they are sensitive to the existence of different type of interactions . therefore , study of these observables can be very useful in looking for new physics beyond the sm . obviously , if new physics beyond the sm exists , there hoped to be effects on the branching ratio besides the polarized @xmath13 . keeping in mind that the measurement of the branching ratio is easier , one could find it more convenient to study it for establishing new physics . but the intriguing question is , whether there could appear situations in which the value of the branching ratio coincides with that of the sm result , while polarized @xmath13 does not . in order to answer this question we study the correlation between the averaged , polarized @xmath94 and branching ratio . in further analysis we vary the branching ratio of @xmath95 between the values @xmath96 $ ] , which is very close to the sm calculations . note that , we do not take into account the experimental results on branching ratio since they contain large errors , and it would be better to wait for more improved experimental results . our conclusion for the @xmath97 decay , in regard to the above mentioned correlated relation , is as follows ( remember that , the intersection of all curves corresponds to the sm value ) : * for @xmath84 , such a region is absent for all @xmath22 , * for @xmath98 , such a region does exist for @xmath99 and @xmath44 ( see fig . ( 13 ) ) . the situation is much more attractive for the @xmath100 decay . in figs . ( 14)(18 ) , we depict the dependence of the averaged , forward backward polarized asymmetries @xmath84 ; @xmath101 ; @xmath102 ; @xmath92 and @xmath93 , on branching ratio . it follows from these figures that , indeed , there exist certain regions of the new wilson coefficients for which , mere study of the polarized @xmath13 can give promising information about new physics beyond the sm . in summary , in this work we present the analysis for the forward backward asymmetries when both leptons are polarized , using a general , model independent form of the effective hamiltonian . our work verifies that the study of the zero position of @xmath84 can give unambiguous conformation of the new physics beyond the sm , since when new physics effects are taken into account , the results are shifted with respect to their zero positions in the sm . moreover , we find that the polarized @xmath13 is quite sensitive to the existence of the tensor and vector interactions . finally we obtain that there exist certain regions of the new wilson coefficients for which , only study of the polarized forward backward asymmetry gives invaluable information in establishing new physics beyond the sm . 99 c. q. geng and c. p. kao , _ transverse lepton polarization in @xmath10 _ , _ phys . * d 57 * ( 1998 ) 4479 ; 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( 1 ) * the dependence of the double lepton polarization asymmetry @xmath77 on @xmath26 at four fixed values of @xmath31 , for the @xmath97 decay . + + * fig . ( 2 ) * the same as in fig . ( 1 ) , but at four fixed values of @xmath32 . + + * fig . ( 3 ) * the dependence of the double lepton polarization asymmetry @xmath80 on @xmath26 at four fixed values of @xmath99 , for the @xmath97 decay . + + * fig . ( 4 ) * the same as in fig . ( 3 ) , but for @xmath81 . + + * fig . ( 5 ) * the same as in fig . ( 3 ) , but at four fixed values of @xmath44 . + + * fig . ( 6 ) * the same as in fig . ( 4 ) , but at four fixed values of @xmath44 . + + * fig . ( 7 ) * the dependence of the averaged forward backward double lepton polarization asymmetry @xmath84 on the new wilson coefficients @xmath22 , for the @xmath97 decay . + + * fig . ( 8) * the same as in fig . ( 7 ) , but for the @xmath100 decay . + + * fig . ( 9 ) * the same as in fig . ( 8) , but for the averaged forward backward double lepton polarization asymmetry @xmath87 . + + * fig . ( 10 ) * the same as in fig . ( 8) , but for the averaged forward backward double lepton polarization asymmetry @xmath98 . + + * fig . ( 11 ) * the same as in fig . ( 8) , but for the averaged forward backward double lepton polarization asymmetry @xmath92 . + + * fig . ( 12 ) * the same as in fig . ( 8) , but for the averaged forward backward double lepton polarization asymmetry @xmath93 . + + * fig . ( 13 ) * parametric plot of the correlation between the averaged forward backward double lepton polarization asymmetry @xmath87 and the branching ratio for the @xmath97 decay . + + * fig . ( 14 ) * parametric plot of the correlation between the averaged forward backward double lepton polarization asymmetry @xmath84 and the branching ratio for the @xmath100 decay . + + * fig . ( 15 ) * the same as in fig . ( 14 ) , but for the the correlation between the averaged forward backward double lepton polarization asymmetry @xmath87 and the branching ratio . + + * fig . ( 16 ) * the same as in fig . ( 15 ) , but for the the correlation between the averaged forward backward double lepton polarization asymmetry @xmath142 and the branching ratio . + + * fig . ( 17 ) * the same as in fig . ( 16 ) , but for the the correlation between the averaged forward backward double lepton polarization asymmetry @xmath92 and the branching ratio . + + * fig . ( 18 ) * the same as in fig . ( 17 ) , but for the the correlation between the averaged forward backward double lepton polarization asymmetry @xmath93 and the branching ratio .

we study the polarized lepton pair forward backward asymmetries in @xmath0 decay using a general , model independent form of the effective hamiltonian . we present the general expression for nine double polarization forward backward asymmetries . it is shown that , the study of the forward backward asymmetries of the doubly polarized lepton pair is a very useful tool for establishing new physics beyond the standard model . 16.3 true cm 23.0 true cm -0.8 true in 0.00 true in 0^*0 5_5 s_s^ ? ? o _ ^0 _ pacs numbers : 13.20.he , 12.60.i , 13.88.+e

cancer remains as a life - threatening disease and a leading cause of death as its control has been difficult . although , a range of conventional therapies based on chemotherapy , surgery , and radiotherapy are available , these approaches are in many cases of limited efficacy . moreover , current anticancer regimens are frequently associated with significant levels of toxicity and the emergence of drug resistance . one major challenge to relieve cancer burden is to develop highly effective drugs with specificity on cancers but little or no side effects on normal mammalian cells . many research projects have been focused on developing new chemotherapies either by exploring the anticancer ability of novel compounds or by assessing drugs conventionally used in other clinical diseases . natural products have been found to be a relevant source of novel and potent bioactive compounds with minimal side effects in vivo . plant derivatives have been known to be effective against a range of diseases with broad antimicrobial activity , and some have also exhibited significant antitumor activity . one of the promising compounds is artemisinin , a naturally occurring antimalarial with anticancer properties . artemisinin and its derivatives , which are commonly used in malaria therapy , have also potent anticancer activity in the nano- to - micromolar range in sensitive and drug- or radiation - resistant cell lines [ 35 ] . importantly , artemisinin is one of the very few drugs that have been widely used as antimalarials but has no significant side effects or clinical resistance , although tolerance has been reported . recently , growing amount of research has focused on the mechanisms underlying the action and response to artemisinin - like drugs . in this review , we will revisit some of the key issues in the development of artemisinin and its analogs as anticancer agents to better understand the mechanisms of their antitumor effects from the insights of new gained knowledge . by considering the benefits , limitations , and current and future development of artemisinins , we can then identify emerging questions and address future research needs in this promising field of cancer drug discovery . this endoperoxide compound is extracted from the chinese herb qinghaosu ( artemisia annua or annual wormwood ) which was used for treating fevers for over two millennia . despite its efficacy , the prototype drug , artemisinin , has pharmacokinetic limitations . naturally , artemisinin has low solubility in water or oil , poor bioavailability , and a short half - life in vivo ( ~2.5 h ) [ 9 , 10 ] . to overcome some of these problems , three generations of artemisinin - like endoperoxides including semisynthetic derivatives and fully synthetic compounds so far , two generations of semisynthetic derivatives of artemisinin such as artesunate , arteeter , artemether , and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability ( figure 1 ) . semisynthetic artemisinins are obtained from dihydroartemisinin ( dha ) , the main active metabolite of artemisinin [ 11 , 12 ] . the first generation of semisynthetic artemisinins includes arteeter and artemether , the lipophilic artemisinins , whereas artesunate is the water soluble derivative [ 11 , 12 ] . artemisone , a second - generation artemisinin , has shown improved pharmacokinetic properties including longer half - life and lower toxicity . so far , artesunate is the derivative that is commonly used in the antimalarial combination therapy . fully synthetic artemisinin derivatives have also been designed by preserving the peroxide moiety which confers potent drug activity . these compounds are easily synthesized from simple starting materials , thus being currently under intense development [ 1417 ] . in the malaria parasite , the endoperoxide moiety of artemisinin has been shown to be pharmacologically important and responsible of the antimalarial activity [ 18 , 19 ] . the endoperoxide bond is thought to be activated by reduced heme ( fpfeii ) or ferrous iron ( feii ) , leading to cytotoxic carbon - centered radicals which are highly potent alkylating agents . however , the precise mechanism of action and primary target of artemisinin remain under study . in plasmodium , it has been postulated that artemisinin may target organelles such as the mitochondrion , endoplasmic reticulum , and the digestive vacuole ( reviewed in ) . some postulated molecular targets include heme alkylation , protein alkylation , ca atpase ( serca ) inhibition , membrane damage , and loss of mitochondrial potential ( reviewed in ) . despite the continuous debate on artemisinin activation and specific targets , supporting evidence points that heme or ferrous iron is required for potent activity . , artemether has an exquisite action against the tegument ; this activity is also enhanced by iron . interestingly , the potent anticancer action of artemisinin can also be attributed to the endoperoxide bond ( red square in figure 2 ) and shares the same parasitical chemical base . lack of the endoperoxide moiety does not completely abrogate anticancer activity but significantly reduces cytotoxicity to only fiftieth compared to those compounds with the trioxane ring [ 2628 ] . residual anticancer activity may be associated with an alternative peroxide - independent mechanism . in a general consensus , iron and heme or heme - bound proteins have been involved in the bioreductive activation of artemisinin [ 2931 ] . in most of the systems , preloading of cancer cells with iron or iron - saturated holotransferrin ( diferric transferrin ) triggers artemisinin cytotoxicity [ 3235 ] with an increase in artemisinin activity up to 100-fold in some cell lines . moreover , artemisinins tagged to iron - carrying compounds exhibit greater activity compared with that of artemisinin alone [ 3739 ] . recently , it was shown that chemical modulation using succinylacetone , a heme synthesis inhibitor , decreases dha cytotoxicity in hl-60 ( human promyelocytic leukemia cells ) . this was consistent with previous studies showing that induction of heme oxidase followed by downregulation of the heme synthesis genes may also inhibit cytotoxicity of novel artemisinin dimers in the same cancer line . similarly , iron and heme metabolism may have a relevant role in the selective antitumor activity of artemisinin . continued proliferation and growth of malignant cells require higher iron metabolism to achieve processes of cell survival . therefore , cancer cells exhibit an increase in transferrin receptors ( tfr ) which are responsible for the iron uptake and regulation of intracellular concentrations . levels of expression of tfr in cancer cells may vary depending on the cell line . however , they differ substantially from normal cells leading to a high selectivity index of artemisinin and its derivatives . reported that leukemia ( ccrf - cem ) and astrocytoma ( u373 ) cells express tfr in 95% and 43% of the cell population , whereas normal monocytes only account for approximately 1% [ 42 , 43 ] . it has been hypothesized that iron - activated artemisinin induces damage by release of highly alkylating carbon - centered radicals and radical oxygen species ( ros ) ( figure 2 ) [ 28 , 35 ] . radicals may play a role in the cell alterations reported in artemisinin - treated cancer cells such as enhanced apoptosis , arrest of growth , inhibition of angiogenesis , and dna damage ( figure 2 ) . several studies have also associated artemisinin toxicity with impaired cytokinesis , enhanced levels of oxidative stress , inhibition of tumor invasion , migration , and metastasis ( reviewed in ) . tumor cells have enhanced vulnerability to ros damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase , catalase , and gluthatione peroxidase compared to that of normal cells [ 45 , 46 ] . hence , increasing oxidative stress is a common anticancer mechanism of antitumor agents . in addition , the selectivity of artemisinin may be boosted by preferential targeting of cancer biomarkers or overexpressed cancer genes and proteins which are not detectable in normal differentiated tissues . as in plasmodium , although artemisinin - induced alterations in some tumor cells are consistent , it is not clear if this toxicity resides in defined molecular targets . drug concentrations required to have an effect on cancer cells are often higher than those inducing toxicity in malaria parasites . artemisinin , dha , artesunate , and artemether exhibit 48 h ic50s ( fifty percent inhibitory concentration ) up to 15 nm in malaria parasites [ 49 , 50 ] , whereas their anticancer activity is cell - line dependent and ic50s fluctuate between 0.5 and 200 m . the exquisite sensitivity of malaria parasites to artemisinin points to the presence of specific parasitic targets . by contrast , in cancer cells , the artemisinin effect seems to be rather mediated by more general mechanisms through generation of ros . however , it has been suggested that ros - mediated damage may be triggered by an initiating event in the vicinity of artemisinin activation . microscopy analyses in artesunate - treated cells have shown early oncosis - like morphological changes at subcellular structures in which ros generation may be triggered . microarray analyses found that the action of artemisinin seems to be modulated by the expression of oxidative stress enzymes including catalase , thioredoxin reductase , superoxide dismutase and the glutathione s - transferase family [ 5 , 52 ] . artemisinin - sensitive cells have downregulated oxidation enzymes whereas overexpression of these molecules renders cancer cells less sensitive . direct evidence in the hl-60 cell line has revealed that early and rapid generation ( 1 h ) of ros has been associated with apoptosis induction and artemisinin - induced damage . conversely , the action of artemisinin in several experimental systems has been reverted in presence of the antioxidant agents , n - acetyl cysteine , and 1,2-dihydroxybenzene-3,5-disulfonic acid ( tiron , an iron scavenger ) , which resulted in a delay in cell death [ 40 , 52 , 53 ] . a recent study has demonstrated that generation of ros in artesunate - treated hela cells ( 16 h ) occurring before cytotoxicity is being detected ( 48 h ) , suggesting that this may be the starting event in artemisinin - induced damage . the electron transfer chain ( etc ) in the mitochondrion has been proposed to play a role in the generation of ros , however substantial cytotoxicity is still detected in hela cells devoid of etc indicating that other sources of ros may be available in the cells . indeed , emerging evidence has postulated that oxidative stress in breast cancer cells is initially generated in the lysosome as consequence of iron - activated artesunate in a process similar to that suggested in malaria parasites . thus , activation of the mitochondrial intrinsic apoptotic pathway is a downstream event leading to cell death ( figure 2 ) . in this model , artemisinins may be negatively controlling heme synthesis and further increase cytotoxicity . despite the growing evidence of ros - mediated damage in many cell systems [ 31 , 33 , 35 , 54 ] particularly , novel artemisinin dimers seem to exert antitumor action with little or no ros generation , however the underlying mechanism of cytotoxicity is still under study . it also remains unclear if artemisinins - induced necrosis may be a ros - independent mechanism of cell death . the antineoplastic toxicity of artemisinins appears to be also modulated by calcium metabolism [ 40 , 5557 ] , endoplasmic reticulum ( er ) stress [ 33 , 40 ] , and the expression of the translationally controlled tumor protein , tctp , a binding calcium protein which has been also postulated as a parasite target . although the expression of the tctp gen , tctp , was initially correlated with cancer cell response to artemisinins , a functional role for tctp in the artemisinin action has yet to be found . as for malaria parasites , the role of sarcoendoplasmic ca atpase ( serca ) as artemisinin target in cancer cells has also been explored . previous evidence has revealed that treatment with 10 m artemisinin increases calcium concentrations as a result of serca inhibition . however , studies on the mechanism of action of two artemisinin dimers have shown that potent ros - mediated induced er - stress after treatment was independent of serca inhibition . interestingly , the behavior of a highly active artemisinin dimer and thapsigargin , a well - known serca inhibitor , seems to be similar but mediated by different molecular events . nevertheless the er appears to be a relevant site for artemisinin action as in hepg2 cells a fluorescent derivative has been shown to preferentially accumulate in this cell compartment . it is also possible that the underlying mechanisms mediating artemisinins cytotoxicity may vary upon specific hallmarks or shifting characteristics in cancer cell lines ( table 1 ) . this will be only possible to elucidate if the molecular events involved in countering malignant cell proliferation are investigated in different cell lines under similar conditions . significant antitumor activity of artemisinin and licensed semisynthetic artemisinin derivatives has been documented in vitro and in animal models . considerable research has been focused on the most active compounds , namely , dha and artesunate . one study that tested 55 cell lines from the developmental therapeutics program of the national cancer institute ( nci ) showed that artesunate displays inhibitory activity against leukemia , colon , melanoma , breast , ovarian , prostate , central nervous system ( cns ) , and renal cancer cells . dihydroartemisinin has also remarkable antineoplastic activity against pancreatic , leukemic , osteosarcoma , and lung cancer cells . moreover , artemisone has shown better activity than artemisinin and considerable synergistic interactions with other anticancer agents . artemisinin has been found to act either directly by inducing dna damage ( genotoxicity ) or indirectly by interfering with a range of signaling pathways involved in several hallmarks of malignancy . however , direct dna damage is only described in specific systems , while indirect effects are more commonly refereed in the literature . in pancreatic cells ( panc-1 ) interestingly , low doses of artesunate were associated with oncosis - like cell death , whereas higher concentrations induce apoptosis . extend and type of damage seem to depend on the phenotype and the origin of cell line , and it may also vary in a time- and dose - dependent manner ( table 1 ) . notably , higher sensitivity to artesunate was observed in rapidly growing cell lines when compared with slow growing cancer cells . alternatively , dha , artesunate , and artemether are likely to modulate genes and proteins coordinating growth signals , apoptosis , proliferation capacity , angiogenesis and tissue invasion , and metastasis . a complex network of interactions through different pathways may enhance the anticancer effect of these endoperoxide drugs leading to cancer control and cell death ( table 2 ) . in normal cells , cyclin - dependent kinases ( cdk ) normal growth relies on the ability to translate signals in order to replicate and divide in an effective manner . uncontrolled proliferation in cancer cells is the result of mutations inducing amplification of growth signals , deregulation of checkpoints , and loss of sensitivity to growth inhibitors . artemisinin and its semisynthetic derivatives are able to effectively induce cell growth arrest in cancer lines either by disrupting the cell cycle kinetics or by interfering with proliferation - interacting pathways . dihydroartemisinin and artesunate are very potent growth inhibitors with multiple studies pointing to dha as the most potent anticancer artemisinin - like compound ( dha > artesunate > arteeter > artemether ) [ 5 , 66 ] . recently , artemisone has shown impressive antitumor efficacy in 7 cells lines including melanoma and breast cancer cells . artemisinin compounds have been shown to exert cytostatic and cytotoxic action on cancer cells [ 63 , 67 ] . artemisinin - induced growth arrest has been reported at all cell cycle phases ; however , arrest at g0/g1 to s transition seems to be more commonly affected ( table 2 ) . arrest at all cell cycle phases at the same time has been interpreted as a cytostatic effect . disruption of the cell cycle at g2/m was observed after dha treatment in osteosacorma , pancreas , leukemia and ovarian cancer cells ( table 2 ) . similarly , artesunate interferes with g2 in osteosarcoma , ovarian , and other different cancer lines ( table 2 ) . the underlying mechanisms of artemisinins - induced growth arrest include alterations in the expression and activity of regulatory enzymes of the cell cycle , such as cdk2 - 4 and -6 and d type cyclins ( g1-to - s - phase transition ) or cdk1 , and a - type cyclin ( g2/m ) [ 7072 ] . the antiproliferative action of artemisinin induces downregulation of cdk transcription , inhibition of cdk promoters or increase of p21 , p27 , and cdk inhibitor ( table 2 ) . inhibition of proliferation may be also attributed to downregulation of interacting proteins targeting multiple pathways . it has been shown that dha treatment in pancreatic cells ( bxpc3 , aspc-1 ) inhibits viability by decreasing levels of proliferating cell nuclear antigen ( pcna ) and cyclin d with parallel increase in p21 . another study in the same system shows that dha counters nf-b factor activation leading to inhibition of its targets in the proliferation ( c - myc , cyclin d ) and apoptotic pathways ( bcl2 , bcl - xl ) . downregulation of survivin , a protein modulating apoptosis and g2/m cell cycle progression , was observed after treatment with dha in lung cancer cells ( spc - a1 ) . a similar effect was described by qiang et al . in artesunate- treated osteosarcoma cells . in prostate cancer , dha induces cell cycle arrest by disrupting the interaction of sp1 ( specificity protein 1 ) and the cdk4 promoter . in addition one work has identified artesunate as a topoisomerase ii , an inhibitor which inhibits growth by interaction with multiple pathways . overall , artemisinins seem to be interfering with several pathways that are common to different cancer entities . apoptosis is a widely studied mechanism in antitumor therapy as its manipulation is an effective strategy for cancer control . this cellular process is mediated by a balance between the bcl2 family genes , the proapoptotic bax , and the antiapoptotic bcl2 and their effects on the mitochondria [ 97 , 98 ] . an increase in the bax / bcl2 ratio induces the release of cytochrome c followed by sequential activation of caspases and culminating with cell death . apoptosis is a common and rapid artemisinin - induced effect observed in many cancer and cell lines . treatment with 200 m dha in leukemia cells induced apoptosis after 1 hour of exposure . artemisinin sensitivity has been correlated to the level of expression of antiapoptotic ( bcl2 ) and proapoptotic genes ( bax ) in a cancer cell line [ 61 , 97 , 99 ] ( table 1 ) . in general , hence , mitochondrial membrane damage is thought to have a pivotal role in the cascade of cell death events . many studies have revealed that artemisinin - like compounds induce apoptosis by modulating the bax / bcl2 ratio [ 33 , 44 , 54 , 63 , 75 , 77 , 78 , 86 , 99 ] . consistent with these observations , dha and artesunate , in a panel of osteosarcoma cells , caused cytochrome c release , bax overexpression , increase in bax / bcl2 ratio [ 44 , 73 ] , and activation of caspases 3 and 9 . dha also activates caspase 8 and decreases the levels of cdc25b , cyclin b1 , and nf-b . in the same system , artesunate exposure depletes survivin which has also been involved in the apoptotic dha response in lung cancer cells . similar events have been described in hepatoma cancer lines treated with dha , particularly in this system dha and the prototype drug artemisinin seem to have similar potency . a microarray analysis has correlated the expression levels of c - myc with enhanced dha - induced apoptosis . leukemia ( hl-60 ) and colon cancer cells ( hct116 ) expressing high levels of c - myc are significantly more sensitive to the dha proapoptotic action . moreover , knockdown of c - myc in hct116 depleted dha - associated cell death . downregulation of c - myc may also correlate with induced g1 arrest in this cell line . studies in metastatic melanoma ( a375 , g361 cell line ) and jurkat t lymphoma cells have associated the elevated apoptotic action of dha with upregulation of noxa ( a proapoptotic protein ) , caspase 3 activation , and oxidative stress [ 79 , 80 ] . in lung cells , the apoptotic effect of dha occurs with increasing calcium concentration and activation of p38 [ 56 , 57 ] . in some studies alterations on molecules acting on the extrinsic apoptotic pathway dha seems to increase the transcription of the cell death receptor 5 ( dr5 ) promoter and induces dr5 in different prostate cancer lines . in fact , a combination treatment with trail , a dr5 ligand , strongly enhances dha proapoptotic action by up to 35% on this system . artemisinins usually promote apoptosis rather than necrosis in most of the systems , however in some cases both apoptosis and necrosis have been reported . induction of apoptosis is a major benefit of artemisinins ' antitumor action as it prevents the collateral effects of inflammation and cell damage caused by necrosis . artemisinin - induced necrosis has been associated with low levels of atp and defective apoptotic mechanisms in some cell lines . the ability of malignant cells to invade has been associated with high mortality and morbidity in cancer patients . the spread of cancer cells to other organs is a process in which malignant cells readily invade through the extracellular matrix , reach and survive in the bloodstream , and finally seed at distant organs . to achieve invasion , the cancer cell requires the loss of expression or function of e - cadherin , a calcium - binding transmembrane molecule involved in cell - cell adhesion . a range of genes encoding extracellular matrix processing proteases , motility factors , and adhesion proteins are also acting at different steps in the metastatic process . recently , pai-1 and timp-1 known as endogenous protease inhibitors have also been shown to be involved in cancer metastasis . an invaluable benefit of artemisinin is its relevant antimigratory activity in highly aggressive and invasive cancer entities [ 56 , 59 , 88 , 91 ] . antimetastatic activity of artemisinins has been correlated with modified expression of the matrix metalloproteinases ( mmp ) gene family and their effects on v3 integrins . in hepatoma cells ( hepg2 and smmc 7721 ) , treatment with 12.5 m artemisinin depleted migration linked to a decrease in mmp2 with concomitant increase in timp-2 . inhibition of metastasis is achieved as artemisinin increases cell - cell adhesion by enhancing e - cadherin activity and cdc42 activation . in addition , it has been found that some cancer cells may have specific proteins cointeracting at different pathways . for example , in non - small cell lung cancer and fibrosarcoma , dha treatment induced low levels of mmp2 , mmp7 , or mmp9 driven by ap-1 and nf-b transactivation or inactivation . previous studies have shown that mmp2 is regulated by sp-1 transcription factor activity , moreover dha - induced disruption of sp-1 molecular interactions has been postulated as a crucial event for dha regulation effects on different pathways . other investigations have found that in mouse lung lewis cancer , lymphoid node metastasis and lymphangiogenesis were retarded by artemisinin - mediated inhibition of vascular endothelial growth factor c ( vgf - c ) . as malignant tissues grow , metastases and solid tumors require extra blood supply for thriving and survival . thus , cancer cells induce neovascularisation by regulating proteins and pathways involved in the generation and restructure of new vasculature . angiogenesis process leads to enhanced proliferation of endothelial cells through induction of vascular endothelial growth factor ( vegf ) , fibroblast growth factor ( fgf ) , its receptors , and cytokines . this event occurs via multiple mechanisms including hypoxia - driven activation of expression of hif-1 and the aryl hydrocarbon receptor nuclear translocator ( arnt ) . angiogenesis control is mediated by angiostatin , endostatin , thrombospondin , timps , pai-1 , and others . due to their role in tumor survival , the proangiogenic factors and the molecules involved in their regulatory networks are relevant drug targets . a microarray - based study revealed that artemisinins , artesunate and other derivatives inhibit neovascularisation by modulating gene expression of angiogenic factors . artemisinins responses seem to be mediated by downregulation of growth factors ( vegf , fgf ) [ 82 , 106 ] , hif-1 , new vessel mediator angiogenin ( ang ) , the cysteine - rich angiogenic inducer ( cyr61 ) , some metalloproteinases ( mmp9 , mmp11 , and bmp1 ) , and collagens . in parallel , artemisinins- induced upregulation of angiogenesis inhibitors was observed . these findings have been supported by experimental investigation in different systems , unveiling other molecular interactions . exposure of human umbilical vein endothelial cells to 50 m dha prevents angiogenesis by depleting the levels of the vegf flt-1 and kdr / flk-1-receptors . similar effects were reproduced in lymphatic endothelial cells and lewis lung carcinoma [ 78 , 84 ] . in pancreatic cells ( bxpc-3 ) and balb / c nude mice , dha induced inhibition of nf-b dna binding and downregulation of its angiogenic - related targets such as vegf , il-8 , cox2 , and mmp9 . reduced levels of nf-b have been previously associated with proliferation and metastasis inhibition [ 33 , 81 , 90 , 94 ] suggesting that nf-b regulation may be a key role in the multimodal action of dha in this system . nf-b is a crucial factor regulating multiple processes and it has a key role in the anticancer drug response . it is activated by dna damage and it is a mediator of apoptosis resistance in response to drug pressure . artesunate has shown its ability to revert cellular transitions allowing re - differentiation of tissues by negative control of wnt - signaling pathway . notably , artesunate has been found to be more effective in less differentiated cell lines . one major obstacle for a successful anticancer therapy is the development of resistance over time . a leading cause of drug resistance is the drug efflux generated by overexpression of membrane protein pumps , which results in ineffective low drug concentrations . anticancer activity of artemisinins has shown to be unaffected in otherwise resistant and multiresistant cancer cells . one study using the 55 nci cell lines and microarray analysis revealed that genes related with resistance to the established anticancer drugs such as mdr1 ( pgp ) , mrp1 , and bcrp showed no impact on the activity of artemisinins . this was substantiated when no effects on the artesunate growth inhibition profile were observed in multidrug resistance hl-60 cell lines overexpressing mrp-1 and bcrp - overexpressing cells , suggesting that antitumor activity of artemisinin is preserved when resistance to other agents is present . artemisinins are effective in a broad range of resistant cancer lines including doxorubicin , metrotexate , and hydroxyurea - resistant lines with no cross - resistance . further investigation has shown that artesunate proapoptotic effect is not affected in a doxorubicin - resistant leukemia cell line ; instead artesunate potentiates doxorubicin apoptotic effects . in another study , anticancer potency of artesunate is preserved in chemoresistant and chemosensitive neuroblastoma cell lines and primary neuroblastoma cultures . in this system , sensitivity to artesunate was not affected in vincristin , doxorubicin , cisplastin , topotecan , mephalan , and ectoposide - adapted cells with ic50s ranging from 1.42.7 m similar to that of the parent sensitive cell line . only one cell line showed low sensitivity to artesunate which was related to low ros formation and increased expression of gluthatione cysteine ligase ( gcl ) . depletion of glutathione mediated by a gcl inhibitor improved artesunate sensitivity in this cell line . p - glycoprotein ( pgp ) or p53 attenuation did not affect sensitivity to artesunate . dha has shown the lowest ic50 in some cell lines such as cholangiocarcinoma ( cl-6 ) and hepatocarcinoma ( hep g2 ) compared to other anticancer agents ; moreover , upregulation of mdr1 , mrp1 - 2 , or mrp3 shows no effect on potency . lack of cross resistance between anticancer agents and artemisinins might be based on different mechanisms of drug action and/or resistance . most of the conventional anticancer agents are nucleoside analogs , whereas artemisinins action is thought to be mediated by a ros - dependent mechanism . furthermore , in erythromyelogenous leukemia and human small cell lung cancer , artemisinins show no significant inhibition towards pgp or mrp1 , thus in principle overexpression of protein pump may not affect artemisinin 's potency . in another system however , artemisinin ( the prototype drug ) increases doxorubicin resistance by upregulating mdrp through a mechanism that will be discussed later . existing anticancer therapies predominantly target cancer proliferation either with chemotherapeutic agents , ionizing radiation or direct toxicity on growth factor signaling pathways . in a combination therapy for cancer , the antineoplastic action of artemisinin may contribute to an independent antitumor activity with no additional side effects . the benefits of combining artemisinins with other anticancer agents have been investigated showing that multifactorial action of artemisinin in different pathways may improve overall activity ( synergism ) . it has been reported that resistant cancer cell lines become sensitive by adding artemisinin to the conventional treatment ( chemosensitization ) . interestingly , dha and artesunate have exhibited the strongest chemosensitizing / synergistic effects [ 4 , 110 ] , whereas the prototype drug artemisinin shows only additive and antagonistic interactions ( table 3 ) . dha significantly improves the anticancer effect of gemcitabine , an anticancer drug used in pancreatic cancer which develops resistance over time . in vitro and in vivo analysis in pancreatic cells demonstrated a dha - induced increase in growth inhibition and apoptosis by 4- and 2-fold , respectively , compared with those obtained with gemcitabine alone . a dual action of dha in potentiating gemcitabine activity and possibly counteracting resistance has been attributed to dha inhibition of gemcitabine- induced nf-b activation and subsequent action on its targets . a similar effect has been shown in hepatoma cancer cell lines irrespective of their p53 status . dha synergistically enhances tumor growth inhibition by 45% when in combination with gemcitabine , whereas artemisinin , the prototype , only induces additive effects . consistent with this observation , a greater antitumor activity was observed when dha was used in a combination with cyclosphosphamide in murine lewis lung carcinoma cell line or in combination with cisplatin in non - small cell lung cancer a549 in mice . in rat c6 glioma cells , addition of 1 m dha increased by 177% the cytotoxic effect of temozolomide , a dna - alkylating agent used in the treatment of brain cancer . further investigation found that dha promotes apoptotic and necrotic activity of temozolomide through ros generation . recently , an enhancement of artesunate anticancer activity has been observed in different combination regimens . a striking synergy was achieved in combinations of artesunate and the immunomodulator drug , lenalidomide . however , the benefits of an artemisinin combination therapy need to be carefully dissected . therapeutic effects are influenced by the mode of action of the drugs and multiple interactions in particular systems and schedules . recently , gravetth et al . showed that gemcitabine has only additive effects when combining gemcitabine and artemisone in colon and breast cancer cells . in cancer colon cells ( ht-29 ) , it has been suggested that artemisinin may impair doxorubicin activity possibly by countering the doxorubicin effect on nf-b inhibition . the same authors have reported artemisinin - induced resistance in the same system through a different mechanism . thus , it has been postulated that artemisinin exposure inhibits serca with subsequent accumulation of calcium . as a result , by contrast , pretreatment with a calcium chelator reverted the cells to a sensitive phenotype . notably , dha and artesunate have not been evaluated in this system ; it remains to be elucidated whether the most potent chemosensitizers have similar effects on this cell line . so far , artesunate or dha in combination with doxorubicin and pirarubicin showed chemosensitizing effect in leukemia and human - small - cell cancer - resistant cell lines , but no further increase of sensitivity was observed in the sensitive parent cell lines . overall , this evidence suggests that dha and artesunate have remarkable ability to potentiate antitumor agents and to counter tumor resistance . u373 mg , dha treatment inhibits the radiation - induced expression of gst with concomitant ros generation . a combination treatment with dha has been shown to be more effective than radiation or dha alone . the adjuvant effect of artemisinin in other cancer treatments including hyperbaric oxygen has also been reported . a salient feature of artemisinin is that artemisinin resistance in vitro or in the field has yet to be confirmed after 30 years of use as an antimalarial . clinically , tolerance has been reported in patients with therapeutic failure . however , in vitro tolerant strains are usually unstable and only develop after several years of continuous drug exposure . the multimodal action of artemisinins at different cancer pathways might also predict a delay of induced resistance in malignant cells . indeed , only few cell lines have shown intrinsic low sensitivity or no response to artemisinin or its derivatives . for example , artemisinin ( the prototype drug ) seems to be less active in breast cancer cells ( mcf-7 ) and gastric cancer ( mkn ) . some studies in breast cancer cells have suggested that artemisinin response may be mediated by estrogen receptors ( er and er ) which are involved in cell proliferation ( reviewed in ) . interestingly , it has been documented that in breast cancer cells , disruption of iron metabolism may enhance potency of doxorubicin and cisplatin . the low response to artemisinin has been also associated with overexpression of bmi-1 in highly metastatic nasopharyngeal cancer cell lines ( cne-1 , cne-2 ) . a recent study found some levels of cross resistance to artesunate and dha in a unique cisplatin chemo - resistant cell line . this effect was partially reverted by l - buthionine - s , r - sulfoximine , an inhibitor of the antioxidant glc . however , in vitro resistance has already been developed under experimental conditions . microarray and experimental studies using knockouts and transfected cells indicate that upregulation of the tumor suppressor p16 and the antioxidant protein , catalase , may confer resistance to artesunate independent of the p53 status . recently , concerns have arisen after baechmeier et al . showed that a 24 h preincubation with 20 m artesunate induces resistance in highly metastatic breast cancer cells . pretreated mda - mb-231 metastatic cells were completely refractory to further artesunate treatment , whereas a similar treatment in mda - mb-468 , a non - metastatic cell line , renders less sensitive cells . further investigation on the mechanism of artesunate - acquired resistance indicates that upregulated transcription of nf-b , ap-1 , and nmp-1 overcome artesunate apoptotic and antimetastatic action and allows tumor progression . it is not clear , however , whether artesunate - induced resistance and loss of sensitivity are preserved after long - term cell subculturing . it also remains to elucidate if other semisynthetic endoperoxides may induce a similar effect or whether a combinational therapy may delay or revert the effect on cell lines bearing this phenotype . this problem may be overcome by enhancing anticancer activity and thus reducing toxic drug concentrations . neurotoxicity has been reported in animal studies in a dose- and time - dependent manner ( 7 days ) [ 118120 ] . the toxicity of artemisinin - like compounds has been associated with long - term availability , whereas short - term peak concentrations are not toxic . thus , rapid elimination of artemisinin in oral formulations is safer than slow - release or oil - based intramuscular formulations [ 6 , 121 ] . remarkably , although artemisinins derivatives have been widely used as antimalarials , their toxicity in humans have been shown to be negligible . in cancer therapy , artemisinin may have multiple benefits as it can be used in combination with no additional side effects , but also it enhances potency and reduces doses of more toxic anticancer partners . clinical doses used in malaria treatment after administration of 2 mg / kg in patients rise plasma concentrations of 2640 + 1800 g / ml ( approximately 6.9 4.7 mm ) which can be considered up to 3 orders of magnitude higher than those artemisinin concentrations with antitumor activity . it becomes relevant to closely monitor the safety of long - term artemisinin - based therapies as severe side effects may be highly unusual but significant . so far , artemisinin treatments for as long as 12 months have been reported with no relevant side effects [ 30 , 122 , 123 ] . however , an extremely rare case of toxic brainstem encephalopathy was described in a patient after a 2-week herbal / artemisinin combination ( 400 mg ) regimen for breast cancer . brainstem neurotoxicity has been reported in animal studies and associated with long - term ( > 28 days ) and high - dose treatments . recently , a fatal case of overdosing in a child who was taking antimalarial treatment was reported . antitumor activity of artemisinin has also been documented in human trials and individual clinical cases [ 30 , 122 ] . artemether and artesunate have been used in cancer therapy with good tolerability and lack of significant side effects . artesunate was successfully used in the treatment of laryngeal squamous cell carcinoma and substantially reduced the size of the tumor ( by 70% ) after two months of treatment . furthermore , artesunate increased survival and substantial metastasis reduction when used in combination with standard chemotherapy in patients with malignant skin cancer . another report describes a beneficial improvement in a patient with pituitary macroadenoma who was treated with artemether for 12 months . artemether has longer half - life and easily crosses the blood - brain barrier which is crucial for brain tumor treatment . similarly , a clinical trial in 120 patients with advanced non - small cell lung cancer has shown that artesunate in combination with a chemotherapy regimen of vinorelbine and cisplatin elevated 1-year survival rate by 13% with a significant improvement in disease control and time to progression . another trial in uk in colorectal adenocarcinoma to evaluate anticancer action and tolerability of artesunate was completed last year , but the results have not been published . imperative need of highly effective compounds with enhanced pharmacological properties has led to the design of novel endoperoxide compounds with selective toxicity toward cancer cells . considerable progress has been made in the design of novel compounds with enhanced potency at the nanomolar range , increased selectivity , and low toxicity in vitro . independent of stereo- or region - chemistry , strong inhibition was influenced by the functional group attached to the triazole ring . substituted compounds with a penthyl benzene group showed the highest antiproliferative activity ranging from 0.07 to 0.39 m 72 h ic50 in 6 cancer lines . recently , feng et al . synthesized a series of dihydroartemisinin derivatives via an aza - michael addition reaction with high selectivity index and ic50 in the nanomolar range against hela cells ( 0.37 m ) . in a series of deoxoartemisinins and carboxypropyldeoxoartemisinins , different from their antiparasitic activity , it has been found that dimeric and trimeric artemisinin derivatives display much higher antitumor activity than their monomeric counterparts . in the last decade , an increase in the number of outputs in artemisinin dimeric compounds with anticancer activity has been observed . these compounds have shown ic50 ranging from 0.014 to 6 m [ 130 , 131 ] . potent anticancer toxicity has been correlated with the nature of the linker and with lipophilicity or electrophilic substitutions . posner et al . developed a series of artemisinin - trioxane derivate dimers from which two phosphate esters displayed nanomolar growth inhibitory values in the nci 60 human cell line screen . further investigation in vitro showed that in hl-60 cells , these compounds are more potent than doxorubicin , whereas their strongly anti - parasitic monomeric counterparts showed no anticancer activity . as suggested by the authors , two trioxane units in addition to the nature of the linker may be relevant in conferring potent anticancer activity . homodimers of artesunic acid have also nanomolar inhibitory values when tested in chemo - resistant and sensitive leukemia cells . notably , the artesunic dimer seems to be 6-fold more potent in the multiresistant pgp overexpressing cells ( cem / adr500 ) than in its sensitive counterparts . anticancer activity was attributed to apoptosis induction , arrest of cell cycle at g0/g1 , and ros generation . in prostate cancer cells ( lncap , tramp cia , and c2h ) , two c10 non - acetal trioxane dimers displayed a 3-fold increase in potency compared to doxorubicin ( 17 - 18 nm versus 45.3 nm resp . ) . the dimers induced arrest at g0/g1 mediated by decreasing cyclin d1 , cyclin e , cdk2 , and an increase in p21 and p27 in many studies , there has been an emphasis on the nature and stereochemistry of the dimer linker which may influence anticancer activity . however , it has also been shown that the linker by its own is inactive . have described that an artemisinin dimer exhibits up to 30-fold more activity than artemisinin in prostate cancer lines . this dimer selectively exerted highly antigrowth potential and apoptosis in c4 - 2 ( a cell line derived from lncap ) and lncap cells compared to artemisinin . an enhanced anticancer activity seems to be given by the stereoisomery of the linker . in another study , c12 non - acetal dimers and one trimer of deoxoartemisinin showed similar potency to that of the conventional anticancer drugs against many cell lines . the linker with one amide or one sulfur - centered 2 ethylene groups was essential for potent anticancer activity . diastomeric - cholic - acid - derived 1,2,4,5-tetraoxanes were also tested and found to have high anticancer activity against human melanoma ( fem x ) , and cervix cancer ( hela ) cis stereoisomers were twofold more active . the authors further suggested that an amide terminus in the linker confers increased anticancer activity . interestingly , beckman et al . showed that the stereochemistry of the ether linkage of the dimers , of dihydroartemisinin ( didha ) , and dihydrodeoxyartemisinin ( the respective endoperoxide lacking dimer ) was as important for antitumor activity as the endoperoxide moiety . dimers were tested against 60 cells from 9 different cancers showing that although in general the didha was more active than dihydrodeoxyartemisinin toward anticancer growth , asymmetrical dimers of either didha or dihydrodeoxyartemisinin were similarly toxic . the mechanism underlying the antiproliferative action of the artemisinin - derived dimers needs further study . recently , a series of potent artemisinin - like derivatives of easy synthesis and anticancer activity has been identified . these compounds also exhibit relevant antiangiogenic properties as judged by studies in a zebrafish model . it is important to recall that some limitations of artemisinins such as short half - life ( between 1 and 5 hours [ 136 , 137 ] ) , limited affordability , and solubility need to be further addressed . although semisynthetic compounds have partially overcome these issues , they still rely on the availability of natural precursors . in malaria , some trioxolanes and ozonides with remarkable improved pharmacokinetics are under clinical development . recently , it has been found that synthetic trioxolanes with enhanced pharmacokinetic properties may exhibit a similar toxicity than artesunate in schistosomas . given that artemisinins may be potentially used as anticancer drugs and possibly in other parasitic and viral infections , the development of novel compounds with enhanced pharmacokinetic properties and targeted anticancer actions is also paramount . although novel semisynthetic artemisinins have shown substantial antineoplastic activity , there is still limited information regarding the cytotoxicity of fully synthetic endoperoxides . a triol substituted compound has displayed prominent antitumor action in vivo toward melanoma ( lox imvi ) and ovarian ( igrov1 ) cancer in nanomolar concentrations ( lc50 60 nm ) . other authors have synthesized compounds with dual action ( antimalarial / anticancer effect ) . these deoxycholic - acid-(dca-)and cholic acid ( ca)derived mixed tetraoxanes are cytotoxic at very low concentrations and particularly potent against melanoma cancer ( lox imvi , lc50 up to 69 nm ) . this drug class has shown many biological activities , in particular , strong anticancer growth activity . supporting evidence indicates that artemisinin - like compounds may be a therapeutic alternative in highly metastatic and aggressive cancers with no long - term effective therapy [ 44 , 61 ] and commonly developing drug resistance . furthermore , antimalarial endoperoxides may act synergistically with other anticancer drugs with no additional side effects . the ability of artemisinins to kill cancer cells through multiple and heterogeneous molecular events has been well documented . however , some questions about the molecular base of artemisinin - induced cell death need further study . growing research has been focusing on determination of the mechanism of bioactivation and molecular events underlying the artemisinin effects . however , how the antitumor activity is exerted following artemisinin activation is still not well understood . so far , the precise molecular events involved in how , when , and where ros production is initially triggered in cancer cells remain to be defined . in addition , the relevance of any ros- independent mechanism should be also addressed ; these might not be obvious but possibly important for artemisinin cytotoxicity in some cancer cells . some other aspects such as the direct dna damage induced by artemisinin - like compounds and the role of p53 status in genotoxicity need to be further analysed . one relevant aim in anticancer therapy is cotargeting multiple pathways minimizing shifting cell hallmarks and side effects . whereas it remains important to characterize the anticancer effects of existing and novel artemisinins derivatives , research also needs to be focused on unveiling the mechanisms of cytotoxicity by identifying their relation to a particular cancer biomarkers and molecules . artemisinins seems to regulate key players participating in multiple pathways such as nf-b , survivin , noxa , hif-1 , and bmi-1 . these molecules and others are to be revealed , which in turn may be involved in drug response , drug interactions , mechanisms of resistance , and collateral effects in normal cells . a better understanding of common mechanisms under similar conditions in different cell systems will greatly aid the development of targeted artemisinin derivatives . this will improve artemisinins cytotoxicity by lowering ic50 , emerging of resistance , drug associated toxicity , and potentiating drug interactions . it is important to connect the molecular interactions and the regulatory effects of artemisinin on the cancer hallmarks and particularly in those tumors with poor prognosis . some cancer cell biomarkers may be potentially useful to predict success on an artemisinin - based treatment in specific systems . furthermore , novel endoperoxide compounds and combinational therapies can be addressed to target or cotarget markers of carcinoma progression and prevent invasiveness and metastatic properties in highly recurrent and aggressive tumors or advanced stage cancers . although the benefits of artemisinins in the clinical setting have been already assessed , specific interactions with established chemotherapy need to be further dissected in different cancer cells and their phenotypes . this will be crucial to implement clinical trials and treatment of individual cases . in this it is important to note that the prototype drug , artemisinin , seems to modulate responses leading to antagonistic interactions with other anticancer drugs . however , whereas it may be useful to have the prototype drug as a control in vitro , its pharmacokinetic properties may differ from the semisynthetic artemisinins . therefore , artemisinin antagonistic reactions and resistance must be cautiously validated using different semisynthetic derivatives . so far , artemether has been shown to share similar anticancer properties than dha and artesunate . the study of how artemisinin drives tumor control may become even more complex as immunological hallmarks are also involved in the generation of tumors . immunological hallmarks in cancer cells include the ability to induce chronic inflammatory response , evasion of tumor recognition , and ability to induce tolerance . whether artemisinin may participate in the mechanisms involved in these events has yet to be determined . overall , the real potential and benefits of the artemisinin drug class remain yet to be uncovered . the imminent possibility of artemisinins being included in the arsenal of anti cancer drugs has opened the door for challenging research in this area , one that seems to fulfill many expectations .

improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells . artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity . in primary cancer cultures and cell lines , their antitumor actions were by inhibiting cancer proliferation , metastasis , and angiogenesis . in xenograft models , exposure to artemisinins substantially reduces tumor volume and progression . however , the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects . the primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated . the aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Canceling Loans to Allow School Systems to Attract Classroom Teachers Act''. SEC. 2. ADDITIONAL QUALIFIED LOAN AMOUNTS FOR STUDENT LOAN FORGIVENESS AND LOAN CANCELLATION. (a) FFEL Loans.--Section 428J of the Higher Education Act of 1965 (20 U.S.C. 1078-10) is amended-- (1) in subsection (c)-- (A) in paragraph (1), by striking ``$5,000'' and inserting ``$17,500''; and (B) by adding at the end the following: ``(3) Priority.--The Secretary shall repay the loan obligations for elementary school or secondary school teachers who meet the requirements of subsection (b) on a first-come first-served basis, subject to the availability of appropriations, but shall give priority in providing loan repayment under this paragraph for a fiscal year to teachers who-- ``(A)(i) are employed as special education teachers whose primary responsibility is to teach or support children with disabilities (as defined in section 602 of the Individuals with Disabilities Act); and ``(ii) as certified by the chief administrative officer of the public or nonprofit private elementary school or secondary school in which the borrower is employed, are teaching children with disabilities (as defined in section 602 of the Individuals with Disabilities Act) that correspond with the borrower's training and have demonstrated knowledge and teaching skills in the content areas of the elementary school or secondary school curriculum that the borrower is teaching; or ``(B) are employed as teachers of mathematics or science in local educational agencies that are determined by a State educational agency under section 2141 of the Elementary and Secondary Education Act of 1965 to have failed to make progress toward meeting the annual measurable objectives described in section 1119(a)(2) of such Act for 2 consecutive years.''; and (2) by adding at the end the following: ``(i) Authorization of Appropriations.--There are authorized to be appropriated to carry out this section such sums as may be necessary for fiscal year 2003 and each of the 4 succeeding fiscal years.''. (b) Direct Loans.--Section 460 of the Higher Education Act of 1965 (20 U.S.C. 1087j) is amended-- (1) in subsection (c)-- (A) in paragraph (1), by striking ``$5,000'' and inserting ``$17,500''; and (B) by adding at the end the following: ``(3) Priority.--The Secretary shall cancel loan obligations under this section for elementary school or secondary school teachers who meet the requirements of subsection (b) on a first-come first-served basis, subject to the availability of appropriations, but shall give priority in canceling loan obligations under this section for a fiscal year to teachers who-- ``(A)(i) are employed as special education teachers whose primary responsibility is to teach or support children with disabilities (as defined in section 602 of the Individuals with Disabilities Act); and ``(ii) as certified by the chief administrative officer of the public or nonprofit private elementary school or secondary school in which the borrower is employed, are teaching children with disabilities (as defined in section 602 of the Individuals with Disabilities Education Act) that correspond with the borrower's training and have demonstrated knowledge and teaching skills in the content areas of the elementary school or secondary school curriculum that the borrower is teaching; or ``(B) are employed as teachers of mathematics or science in local educational agencies that are determined by a State educational agency under section 2141 of the Elementary and Secondary Education Act of 1965 to have failed to make progress toward meeting the annual measurable objectives described in section 1119(a)(2) of such Act for 2 consecutive years.''; and (2) by adding at the end the following: ``(i) Authorization of Appropriations.--There are authorized to be appropriated to carry out this section such sums as may be necessary for fiscal year 2003 and each of the 4 succeeding fiscal years.''.

Canceling Loans to Allow School Systems to Attract Classroom Teachers Act - Amends the Higher Education Act of 1965 to provide for additional amounts of student loan forgiveness and cancellation for certain elementary and secondary school teachers. Directs the Secretary of Education, in making such additional repayments and cancellations, to give priority to teachers of: (1) special education; (2) children with disabilities; or (3) mathematics or science in local educational agencies that have failed to make progress toward meeting annual measurable objectives.

Image caption Yarsagumba is a fungus which has grown into the mummified body of a caterpillar A court in Nepal has found six men guilty of murdering seven rivals in a fight over a rare caterpillar fungus highly prized as an aphrodisiac. The men from the northern district of Manang were all given life sentences. Thirteen other villagers got two years in jail for their part in the murders. Another 21 defendants were acquitted. Foraging for the fungus is a major source of income for poor Himalayan communities. A kilo can fetch tens of thousands of dollars in China. The so-called "Himalayan viagra" case had made headlines in Nepal. Men from the village of Nar high up in mountains close to the Tibetan border were charged with brutally taking the law into their own hands. "Evidence showed that the six were directly involved in the murder while the rest had provided indirect help," local court official Shambhu Baral told AFP news agency. He said those given two-year sentences had already served their time. Jealousy and crime The court heard how in June 2009 the Nar villagers formed a posse and murdered seven outsiders from low-lying Gorkha district who had come to harvest "yarsagumba". Image caption The makeshift prison that defendants were kept in Yarsagumba is the term used in Nepal to describe the mummified body of the Himalayan bat moth caterpillar that has been invaded by the fungus Cordyceps sinensis. It is considered a medicinal mushroom in Oriental medicines and is famous throughout the Himalayas. Many poor villagers see it as a vital source of income. Only two of the Gorkha farmers' bodies were found, thrown down a deep ravine. The local police chief told the BBC he believed the villagers dug up the other five when they realised they were being investigated, cut them into pieces and disposed of them in a fast-flowing river. The trial was concluded in 2010 but verdicts were delayed for months, says the BBC's Joanna Jolly. Sentences were passed on Monday, but the Manang area is so remote it took until Tuesday for the news to emerge. Our correspondent says although the caterpillar fungus has brought wealth to the region, it has also brought jealousy and crime and many locals regard it as a curse. ||||| Uttam Babu Shrestha Yarsagumba, the world’s most expensive medicinal fungus, is in serious decline in Nepal because of over-harvesting, researchers warn in a study due to appear in the journal Biological Conservation1. Known as ‘Himalayan Viagra' because of its supposed libido-boosting powers, the fungus can fetch as much as US$100 per gramme on the Chinese market, making it pricier than gold. The exotic species is often regarded as a symbol of wealth and power in China, and as the country’s economy has boomed, the fungus “has enjoyed unprecedented popularity”, says one of the study’s co-authors, Kamaljit Bawa, a conservation biologist at the University of Massachusetts in Boston. Based on estimates of the volume of trade2 and average retail prices, Uttam Babu Shrestha, the study's lead author, puts the global market at betwen $5 billion and $11 billion per year. The high price and rising demand are driving a fungus gold rush in poverty-stricken rural communities in Himalayan countries, but the impact on biodiversity and ecosystems has received little attention until now, says Bawa. Native to the meadows of the Himalayas and Tibetan plateau at 3,000–5,000 metres above sea level, yarsagumba (Ophiocordyceps sinensis) is prescribed in traditional Chinese and Tibetan medicine for a wide range of conditions including impotence, asthma and cancer. The peculiar life cycle of the fungus has also earned it the names 'winter worm, summer grass' and 'caterpillar fungus'. In late summer, the fungus spores infect moth larvae that live in the soil. The fungus grows inside the caterpillar, mummifying it and steering it into a position a few centimetres below the soil surface, with the head pointing upwards. Just before winter sets in and the soil freezes, a small bud forms and pushes up out of the caterpillar's head. The following spring, a brownish fruiting body — a mushroom — emerges from the soil. Gold rush In an attempt to assess the effects of collecting the fungus in Nepal, the study’s authors interviewed more than 200 harvesters in Dolpa, western Nepal, a region that is home to 60,000 harvesters and contributes about 40% of the total fungus yield in the country. They found that the annual trade fell by more than 50% from its 2009 peak to 2011, with most harvesters believing that it had become more difficult to find the fungus. “The villagers spend more time in the field but are getting fewer fungi,” Shrestha says. The decline in the abundance of the fungus may have prompted harvesters to pick all of the fungi they could find, says Shrestha. The researchers found that about 94% of the fungi collected by the villagers had not yet reached reproductive maturity, which is when spores form and disperse into the soil. “This would probably reduce the yield in the following year,” he says. “There is a similar trend in other Himalayan countries, such as China, India and Bhutan,” says Liu Xingzhong, a mycologist in the Chinese Academy of Sciences’ Institute of Microbiology in Beijing. On the Tibetan plateau, for instance, the fungus harvest per unit area has dropped by 10–30% compared with three decades ago. Harvest regulation If the caterpillar fungus disappears, says Liu, it could lead to an uncontrolled proliferation of the larvae and moths, triggering a series of changes in the fragile mountain ecosystems. And because hundreds of harvesters typically work in a limited area, they too could damage the ecosystem with their digging tools and by compacting the soil, says Shrestha. Bawa speculates that other factors may also be contributing to the decline of the fungus — in particular, rising temperatures and less snow in the eastern Himalayas as a result of climate change. Bawa says that the study’s findings indicate a need for long-term monitoring and management plans for sustainable harvest of the fungus. The harvest season, for instance, should be shortened to allow enough fungi to mature and spread their spores. A rotational system for the harvest should also be implemented, so that the meadow has the chance to recover from human impact, he says. Without such regulations, “we will soon see the end of the fungus boom”, says Shrestha. “It will have devastating consequences for the ecosystems and local economy.” ||||| Siwang, Nepal - An $11bn gold rush is under way in the remote highlands of Nepal to exploit the world’s most valuable fungus fabled for its aphrodisiac and medicinal properties. Trade in yarsagumba - dubbed the "Himalayan Viagra" for its supposed libido-boosting powers - has boomed since the end of a ban opened up the Chinese market where it is highly prized. Yet researchers now warn that uncontrolled collection of the unique species could trigger devastating changes in the fragile mountain ecosystem and destroy the local economy. Harvest season At 2,500 metres above sea level and two days’ trek from the nearest town with paved roads, the normally sleepy mountain hamlet of Siwang is shaken by hectic activity. Porters load belongings into their doka - Nepalese wicker baskets traditionally carried on the forehead - and entire families prepare for the harvest season. "I go with my brother, wife and children - the children are more likely to find yarsagumba because they have better sight and nimble fingers to search for it," says villager Ganesh Pun, 38. "Only little children and old people who can’t see or move very well remain in the village." Like Pun, half of the residents of the hamlet will climb to 4,000 meters in the search for yarsagumba, which is native to the meadows of Nepal, India, Bhutan and the Tibetan plateau at up to 5,000 metres above sea level. For more than 500 years, this exotic specimen has been coveted in the Asiatic market due to its aphrodisiac and medicinal properties. "Ophiocordyceps sinensis [its scientific name] is an important nourishing tonic," explains Jit Narajan Sah, assistant professor at the Institute of Forestry of Tribhuvan University. "It regulates the normal functioning of various part of the body and strengthens the immune and circulatory system. "It has traditionally been used for impotence, backache and to increase sperm and blood production." Fungal spores colonise larvae that live in the soil during summer rains and, after mummifying them over winter, a mushroom grows from each caterpillar’s head to emerge from the soil. The fungus is then harvested before the monsoon season, between May and June, when tens of thousands of tents invade the vast plateau in Rukum and Dolpa, which becomes home to 60,000 harvesters and generates 40 percent of the country’s yarsagumba yield. The power to boost the libido attributed to the fungus has made it highly prized in the Chinese market and it has become a key source of income for poor Nepalese villages. "Yarsagumba is very mysterious. Some could search for it in a square metre and won’t find it," says Dham Bahadour Gorbuga, 45, also from Siwang. "Sometimes, we can’t collect a single one in a working week, but some other times we’re able to get 50 of them on the same day." Gorbuga describes the difficulties of harvesting at high altitude: "The path is very narrow and steep, the weather conditions are terrible: we suffer from altitude sickness, fatigue and dizziness. "But it’s only for a couple of weeks and this money help us support our families." Price differential Siwang villagers have organised their own committee to coordinate the harvest and control access to the fields, which establishes annual quotas and charges collectors an entry fee. Raj Kumar Pun, a trader in the neighbouring village of Maikut, said entry fees have been increasing every year, and traders also have to pay government royalties. "Back in the 90s, the price for a piece of yarsagumba was only a rupee or two, as my father used to sell it," he said. The exotic species made no official contribution to Nepal’s economy until 2001 because its collection, use and sale was banned by the government. But once the ban was lifted, the boom began and trade in the "Himalayan Viagra", mostly in unprocessed form, increased exponentially. The government now earns substantial revenue of about 5.1 million rupees from the trade, according to the International Centre for Integrated Mountain Development (ICIMOD). Yet a huge price differential exists between the local and international market meaning those who gather the fungus earn only a small share from the trade. A middle man in Siwang buys the harvest for 1.7 million rupees ($18,000) per kilo and sells it for up to 3 million rupees ($31,600) in Nepal’s capital Kathmandu, but by the time the yarsagumba reaches Shanghai, it can fetch as much as $100 per gramme. Over-exploitation Scientists are also warning about over-exploitation of this resource as the market for it has boomed. A study published last year in the magazine Biological Conservation suggested China’s rapid economic growth has increased the value of yarsagumba’s global market to between $5bn and $11bn per year. However, scientific research reported by Nature magazine reveals that alongside the growing trade in yarsagumba, the harvest has decreased in recent years. Researchers link this decline to the lack of regulations governing what is harvested and warn that without controls the yarsagumba boom could end by triggering devastating changes in the fragile mountain ecosystem. The absence of regulation not only allows over-harvesting but is also reinforcing the inequalities among those profiting from this trade Ragu Chitra, a herb trader from Kathmandu, described problems that exist in a black market for the fungus. "A trader had yarsagumba worth 5 million rupees stolen last year when a gang went to his place pretending to be police," Chitra said. "He had to give it all because he didn’t have a licence." Robbery and crimes related to the trade in the coveted fungus have made headlines, and in 2011 a Nepalese court condemned six men to life sentences for murdering harvesters. Collecting at high altitudes can also be hazardous - four children from Siwang School have become orphans after the harvest season. The school will be closed during harvesting as half of its children trek with their families to the buki or Himalayan pastures. Siwang’s villagers will continue to harvest at more than 4,000 meters, aware that there is a fine line between luck and misfortune. But the hunt for this natural treasure does not deter many - Gorbuga is now in his tenth year searching for the world’s most valuable fungus. "The mountain is unforgiving - a villager died because a block of ice struck him and swiped him away," he said. "I was there when everything happened and we couldn’t ever find him." Follow Angel L. Martinez on Twitter: @AngelLMartinez

– It's June in Nepal, so tens of thousands of people are scouring the nation's remote highlands for so-called "Himalayan Viagra"—a fungus said to boost libidos and ease health woes. But harvesting is a risky job that doesn't pay much compared to the fungus' value on the open market, Al Jazeera reports. Why risky? Not only are the mountain paths steep and narrow, killing the occasional harvester, but the fungus is worth enough to attract crime. Six men were given life sentences in 2011 for killing harvesters, the BBC reports, and the Himalayan Times reports that thieves stormed a harvesters' tent on Friday and stole more than $410,000 worth of fungus. Called Yarsagumba, the fungus has been popular for more than 500 years, but Nepal's decision in 2001 to legalize its collection, use, and sale may have led to ecologically destructive over-harvesting. Because the fungus grows inside of caterpillars, heavy collection (60,000 are now harvesting the nation's midwestern region) could destroy caterpillar populations and allow moths and larvae to proliferate, Nature reports. On the plus side, harvesters make decent money for a couple of weeks' work, and buyers reportedly enjoy the benefits. "It regulates the normal functioning of various parts of the body and strengthens the immune and circulatory system," says a Nepalese professor. "It has traditionally been used for impotence, backache, and to increase sperm and blood production." (For more on fungus, read about North Korea's claim to a new sports drink.)

migraine is a primary headache that is characterized by mostly unilateral pulsating head pain , is aggravated by routine physical activity , and is associated with nausea and/or photophobia and phonophobia ( headache classification committee of the international headache , 2013 ) . migraine may be accompanied by a variety of autonomic , cognitive , and emotional disturbances ( grassini and nordin , 2015 ) . epidemiological studies have documented its high prevalence and high socio - economic and personal impact . migraine has a 1-year prevalence of 14% in the general population ( vos et al . , 2012 ) and 9.3% in china ( yu et al . , 2012 ) . it was ranked as the sixth greatest cause of disability worldwide in the global burden of disease survey 2013 ( 2015 ) . it is generally believed that migraine is abnormal brain function that depends on the activation and sensitization of the trigeminovascular pathway ( borsook and burstein , 2012 , noseda and burstein , 2013 ) . cortical spreading depression ( csd ) is the electrophysiological correlate of migraine aura ( ferrari et al . , 2015 , pietrobon and moskowitz , 2013 ) . questions remain , however , concerning the mechanisms of initiation , continuation , and termination of migraine . neuroimaging has led to advances in the understanding of primary headache mechanisms , and to better identification of the causes of headache , as well as the structures that are responsible for initiation of the pain . co - localization of structural changes ( i.e. , an increase in voxel - based morphometry [ vbm ] ) as well as changes in localized brain activity characterized using positron emission tomography ( pet ) have been found in the same area of the brain ( hypothalamus ) in cluster headache patients ( may et al . , 1999 ) . hypothalamus is undoubtedly crucial for the pathogenesis of the trigeminal autonomic syndromes , so anatomical co - localization of functional and structural changes ( especially increase in gm ) raises the possibility that the observed changes may be causal as opposed to a consequence of pain ( may , 2009 ) . combined analysis of structural and functional changes in migraine may be urgent to elaborate the pathophysiological mechanism . because of the episodic nature and unpleasantness of migraine attacks , imaging during spontaneous migraine has proven difficult . therefore , most magnetic resonance imaging ( mri ) studies of migraine have focused on the migraineurs between attacks , during the so - called interictal phase . in recent years , grey matter ( gm ) morphology based on mr , particularly vbm , has been carried out on migraineurs . vbm involving statistical voxel - wise testing of the local concentration of gm is a whole - brain method for analysis of automatically pre - processed structural high - resolution mri data ( draganski and may , 2008 ) . some researchers have meta - analyzed vbm studies in migraine , but they did not combine them with functional changes and had not taken frequency of migraine attacks into account ( dai et al . , 2015 , wenting hu et al . , 2015 ) . variations like nociceptive , olfactory and visual stimuli in the methods used complicate a meta - analysis of all studies showing brain regions with atypical activation in migraine sufferers ( chen et al . , 2015 , schwedt et al . , 2015 ) interictal cutaneous pain thresholds are lower in migraine patients compared to controls , so we chose articles used nociceptive stimuli for a meta - analysis ( schwedt et al . , 2011 , weissman - fogel et al . , 2003 ) . here , we systematically summarize and meta - analyze the voxel - wise changes and functional changes in gm in patients with migraine . combined with previously published studies on pain disorders i ) are there concordant structural changes in the foci ( increase or decrease ) in migraine ? iii ) what can be deduced from gm changes in migraine ? we describe how these studies have helped our understanding of the anatomy and biology of migraine , discuss their limitations , and propose avenues for future research using mri to study migraine . we searched pubmed and embase for manuscripts published between january 1985 and november 2015 using the following search terms : ( mri or magnetic resonance imaging ) and migraine and structur * for vbm analysis . search words : ( fmri or functional magnetic resonance imaging ) and ( migraine disorders or ( migraine and disorders ) or migraine ) were used for functional studies . literatures were screened from the title , abstract , intensive reading full - text . we limited the search to studies published in the english language and where the subjects were human . we also examined the references of relevant primary articles and review articles to identify studies that may have been missed in the search . the meta - analysis included only articles ( i ) that evaluated the association of grey matter changes and migraine based on a case - control or cohort design ; ( ii ) that contained information on the sample sizes , disease conditions ; ( iii ) patients with migraine were diagnosed according to the international classification of headache disorders ( ichd ) ; ( iv ) reported whole - brain results of changes in stereotactic coordinates ; v ) nociceptive stimuli ( either heat or ammonia ) were used for functional studies and ( vi ) used thresholds for significance corrected for multiple comparisons or uncorrected with special extent thresholds . we excluded the following : a ) non - original studies ; b ) studies in which the field of view was confined to a restricted region of the cortex ; c ) studies in which the comparisons between patients with migraine and healthy subjects did not include changes in gm ; d ) comorbidity with other diseases ; e ) migraine - like syndromes that were secondary to other diseases ; f ) articles that concerned other types of headache or a special subtype of migraine ( like vestibular migraine ) ; g ) articles that reported no significant results ; h ) articles in which there was no healthy control ( hc ) group or no comparison with hc ; i ) studies with unspecified vbm analyses ; j ) grey matter functional changes due to other stimuli ( like visual or olfactory ) or combined with other tasks or intervention ; k ) only functional connectivity was conducted ; l ) resting - state functional studies in migraineurs ; m ) duplicate articles ; and n ) case reports . the two authors ( zj and sy ) independently extracted data from each study using a predefined data extraction form , any lack of clarity or disagreement was resolved through discussion . the investigators abstracted data from each study to obtain information on author , publication year , sample size , characteristics of the study population ( age , gender ) , types of migraine , disease information and technical details ( mri scanner , region studied , timing , methods and main findings ) . we used ginger ale 2.3.5 ( http://www.brainmap.org/ ) to evaluate the presence of common patterns of gm alterations . ginger ale is a brainmap application that can be used to perform an ale meta - analysis on coordinates in a talairach or mni space . ale is probably the most widely used algorithm for coordinate - based meta - analyses . the approach treats activation foci reported in neuroimaging studies as spatial probability distributions centered at given coordinates rather than as single points . for each voxel , ginger ale estimates the cumulative probabilities that at least one study reports activation for that locus . ale maps are then obtained by computing the union of activation probabilities for each voxel . differentiation between true convergence of foci and random clustering is tested using a permutation procedure ( eickhoff et al . , 2009 , laird et al . , 2005 , turkeltaub et al . , 2012 ) . with version 2.0 , ginger ale switched the ale methods from fixed effects to random effects , and incorporated variable uncertainty based on the sample size ( eickhoff et al . , 2012 ) . a random effects model assumes a higher than chance likelihood of consensus between different experiments , but not in relation to activation variance within each study . during an ale analysis , each activation focus is modeled as the center of a gaussian probability distribution , and is used to generate a modeled activation ( ma ) map for each study . where we used data that were not expressed in talairach coordinates , these were transformed into talairach space using icbm2tal , as implemented in ginger ale 2.3.5 ( lancaster et al . , 2007 a very conservative threshold of p < 0.001 was chosen , and the minimum cluster size was 100 mm . all of these steps combined help to control for publication bias with regard to reported foci . we searched pubmed and embase for manuscripts published between january 1985 and november 2015 using the following search terms : ( mri or magnetic resonance imaging ) and migraine and structur * for vbm analysis . search words : ( fmri or functional magnetic resonance imaging ) and ( migraine disorders or ( migraine and disorders ) or migraine ) were used for functional studies . literatures were screened from the title , abstract , intensive reading full - text . we limited the search to studies published in the english language and where the subjects were human . we also examined the references of relevant primary articles and review articles to identify studies that may have been missed in the search . the meta - analysis included only articles ( i ) that evaluated the association of grey matter changes and migraine based on a case - control or cohort design ; ( ii ) that contained information on the sample sizes , disease conditions ; ( iii ) patients with migraine were diagnosed according to the international classification of headache disorders ( ichd ) ; ( iv ) reported whole - brain results of changes in stereotactic coordinates ; v ) nociceptive stimuli ( either heat or ammonia ) were used for functional studies and ( vi ) used thresholds for significance corrected for multiple comparisons or uncorrected with special extent thresholds . we excluded the following : a ) non - original studies ; b ) studies in which the field of view was confined to a restricted region of the cortex ; c ) studies in which the comparisons between patients with migraine and healthy subjects did not include changes in gm ; d ) comorbidity with other diseases ; e ) migraine - like syndromes that were secondary to other diseases ; f ) articles that concerned other types of headache or a special subtype of migraine ( like vestibular migraine ) ; g ) articles that reported no significant results ; h ) articles in which there was no healthy control ( hc ) group or no comparison with hc ; i ) studies with unspecified vbm analyses ; j ) grey matter functional changes due to other stimuli ( like visual or olfactory ) or combined with other tasks or intervention ; k ) only functional connectivity was conducted ; l ) resting - state functional studies in migraineurs ; m ) duplicate articles ; and n ) case reports . the two authors ( zj and sy ) independently extracted data from each study using a predefined data extraction form , any lack of clarity or disagreement was resolved through discussion . the investigators abstracted data from each study to obtain information on author , publication year , sample size , characteristics of the study population ( age , gender ) , types of migraine , disease information and technical details ( mri scanner , region studied , timing , methods and main findings ) . we used ginger ale 2.3.5 ( http://www.brainmap.org/ ) to evaluate the presence of common patterns of gm alterations . ginger ale is a brainmap application that can be used to perform an ale meta - analysis on coordinates in a talairach or mni space . ale is probably the most widely used algorithm for coordinate - based meta - analyses . the approach treats activation foci reported in neuroimaging studies as spatial probability distributions centered at given coordinates rather than as single points . for each voxel , ginger ale estimates the cumulative probabilities that at least one study reports activation for that locus . ale maps are then obtained by computing the union of activation probabilities for each voxel . differentiation between true convergence of foci and random clustering is tested using a permutation procedure ( eickhoff et al . , 2009 , laird et al . , 2005 , turkeltaub et al . , 2012 ) . with version 2.0 , ginger ale switched the ale methods from fixed effects to random effects , and incorporated variable uncertainty based on the sample size ( eickhoff et al . , 2012 ) . a random effects model assumes a higher than chance likelihood of consensus between different experiments , but not in relation to activation variance within each study . during an ale analysis , each activation focus is modeled as the center of a gaussian probability distribution , and is used to generate a modeled activation ( ma ) map for each study . where we used data that were not expressed in talairach coordinates , these were transformed into talairach space using icbm2tal , as implemented in ginger ale 2.3.5 ( lancaster et al . , 2007 ) . a very conservative threshold of p < 0.001 was chosen , and the minimum cluster size was 100 mm . all of these steps combined help to control for publication bias with regard to reported foci . lots of studies have been performed on grey matter ( structural or functional ) changes in migraine patients , but the results were not consistent and different areas were found in them . after a careful screen , we identified 8 clinical studies that used vbm to assess changes in gm regions in migraineurs and controls , containing a total of 390 subjects ( 191 patients and 199 controls ) . the patient group was comprised of 24 men and 167 women , where 155 cases of migraine were without aura and 36 were with aura . the clinical manifestations and technical details of the structural changes on migraine are listed in table 1 , table 2 . the studies we analyzed compared the whole brain grey matter volume ( gmv ) of 191 migraine patients ( mean age : 37.94 years ) , and 199 healthy controls ( mean age : 36.71 years ) . there were no significant age or gender differences between the patients with migraine and the hc subjects ( t - test ; p < 0.05 ) . the relationship between changes in gmv and frequency of attack and disease duration were also performed in five out of the eight studies ( kim et al . , 2008 , four of them assessing the correlation of gm changes with clinical data through multiple comparison or pearson correlation test , we chose them for subtraction meta - analysis to explore the correlation of gmv changes with frequency of attack and disease duration ( kim et al . , 2008 , rocca et al . , 2006 , schmitz et al . , 2008a , valfre et al . , 2008 ) . as they are correlation analysis , the concept estimated frequency of migraine attacks ( frequency of migraine attacks or duration of the disease ) was used and a dichotomous grouping based on disease duration -related gmv changes may present the complete picture of development in migraine ( deramus and kana , 2015 , kim et al . , 2008 , nellessen et al . , 2015 ) . using these data , group analyses were performed between patients with migraine and hc subjects , lower estimated frequency of migraine attacks and higher estimated frequency of migraine attacks patients , respectively . only one study included chronic migraine , and the number of migraines with aura was small ; hence , a group analysis among migraine subtypes was not possible . five functional mri studies used nociceptive stimuli were included to assess functional changes in the whole brain gm regions in migraine patients containing a total of 189 subjects ( 93 patients and 96 controls ) . 32 men and 61 women were contained in patient group . the clinical manifestations and technical details of the functional changes on migraine can be found in table 3 , table 4 . there was no significant gender difference between the migraineurs and the hc subjects ( t - test ; p < 0.05 ) . age information are not available in some researches , however , gender and age were exactly matched in each study . although pag increase was found in one study ( rocca et al . , 2006 ) the ale results showed that , compared with hc , migraine was associated with a common core set of decreases in gm volume in the bilateral inferior frontal gyri , the right precentral gyrus , the right cerebellar culmen , the left middle frontal gyrus and the left cingulate gyrus ( see fig . 2 and table 5 ) . changes in the volume of gm in the right claustrum , left cingulated gyrus , right anterior cingulate , amygdala , and left parahippocampal gyrus were negatively related to the estimated frequency of attack ( see fig . 3 and table 6 ) . in individual studies , both activated and deactivated areas were found in migraineurs . several areas containing the bilateral lentiform nucleus , putamen and claustrum , the right precentral gyrus , the right midbrain , the right postcentral gyrus , the left limbic lobe and the left cingulate gyrus were activated in the migraine patients after ale analysis . there were also area deactivations in the left precentral gyrus and the right superior temporal gyrus in the migraineurs ( shown in fig . 4 and table 7 ) . genome - wide association studies of migraine have revealed that genetics are involved in migraine ( anttila et al . , 2010 , chasman et al . , 2011 , freilinger et al . , 2012 ) ; however , only limited variance can be explained by genetics . environmental factors , such as stress , weather , hormonal fluctuations , sleep disturbances , meal skipping , and sensory overload , are clearly involved in migraine ( kelman , 2007 , levy et al . , 2009 ) . whatever the cause , imaging during migraine pain has led to a shift from vascular hypotheses of migraine pathophysiology to neurovascular or central nervous system ( cns ) theories . mri is a non - invasive procedure with the potential to determine a morphological basis of neurological diseases , as well as to investigate functional structural relationships . in idiopathic or primary headaches , including migraine , tension - type headaches , and cluster headaches , the accepted view is that these conditions are due to abnormal brain function that occurs with normal brain structure . patients with chronic tension - type headaches exhibit a decrease in gm volume in the structures that are responsible for transmitting pain ( schmidt - wilcke et al . , 2005 ) . data on cluster headaches describe an increase in the volume of gm in the hypothalamus which is associated with functional areas involved during acute headache attacks ( may et al . , 1999 ) . in recent years , there have been a number of studies on gm morphology using mr ( especially vbm ) to investigate the mechanisms of initiation , continuation and termination of migraine ( hougaard et al . , lots of researches also be conducted on gm function in migraine patients used various methods . nevertheless , single imaging study carries several limitations , including small sample sizes , low reliability and its inherent subtraction logic which is only sensitive to differences between conditions ( feredoes and postle , 2007 , price et al . , 2005 ) ale treats activation foci , assesses the overlap between foci based on modelling them as probability distributions centered at the respective coordinates and finds agreement across subject groups . either way , single study results are driven by dataset 's foci as well as how they are grouped . ale was widely applied to meta - analyze the structural and functional brain changes of various neuropsychiatric disorders , such as autism spectrum disorders , alzheimer 's disease , anhedonia , idiopathic dystonia and physiological conditions , such as aging and touch ( chapleau et al . , 2016 , deramus and kana , 2015 , di et al . , 2014 , lokkegaard et al . , 2016 , morrison , 2016 , nickl - jockschat et al . , after ale meta - analysis of structural and functional changes in the gm in migraine patients , combined with previous studies in pain disorder , our study demonstrates : i ) migraine was associated with a common core set of decreases in the volume of gm in the bilateral inferior frontal gyri , the right precentral gyrus , the left middle frontal gyrus and the left anterior cingulate gyrus ; changes in the volume of gm in the cingulated gyrus were negatively related to the estimated frequency of headache attack ; ii ) the precentral gyrus and the cingulate gyrus were also over - activated in interictal migraineurs during nociceptive stimuli ; and iii)structural changes in the frontal gyrus may predispose a person to pain , and the cingulate gyrus may accumulate damage due to the repeated occurrence of migraine ; functional activation in the precentral and postcentral gyrus , the limbic region , the basal ganglia and the right midbrain may be associated with pain processing and associated symptoms in migraine patients . brain function activation in primary headache syndromes contains two groups : areas generally involved in pain processing , such as the somatosensory , cingulate , thalamus et al . ; and areas specifically activated in primary headaches , such as the hypothalamus , which is activated in cluster headache attacks ( may et al . , 1999 ) . one review of stimulus - induced brain activation in migraine found atypical brain responses to sensory stimuli , an absence of the normal habituating response between attacks , and atypical functional connectivity of sensory processing regions ( schwedt et al . , 2015 ) . migraine sensory hypersensitivities may be induced by a combination of enhanced sensory facilitation and reduced inhibition in response to sensory stimuli ( russo et al . , 2012 , schwedt et al . , 2014 ) , as well as reduced or absent habituation to stimuli interictally ( burstein et al . , 2010 ) . they may also contribute to a transformation from episodic to chronic migraine ( moulton et al . , 2008 ) . a concordant activation was found in the somatosensory , cingulate , limbic lobe , basal ganglia and midbrain in migraine patients in our study . all these areas are related to pain processing , modulation and associated symptoms ( like emotional disturbances ) in migraineurs . the activation areas of somatosensory , basal ganglia and midbrain coincided with previous studies and further confirms that activation and sensitization of the trigeminovascular pathway are involved in migraine pathophysiology ( dasilva et al . , 2007 , noseda and burstein , 2013 , schulte and may , 2016 , stankewitz et al . , 2011 ) . studies of changes in brain function during the ictal phase may improve our understanding of migraine mechanisms . , 2001 , welch et al . , 1998 ) , and others exposed migraine subjects to attack triggers in order to initiate migraine ( afridi et al . , 2005b , cao et al . , 2002 , maniyar et al . , 2014 ) . during the premonitory phase of nitroglycerin - triggered migraine attacks , the following areas of the brain were found to be activated : the posterolateral hypothalamus , the brainstem , and various cortical areas , including the occipital , temporal , and prefrontal cortices ( maniyar et al . , 2014 ) . studies that captured the onset of migraine found an increase in the signal from the brainstem ( bahra et al . , 2001 ) . comparisons of ictal images with interictal scans revealed significant activation in the anterior and posterior cingulate , as well as the cerebellum , thalamus , insula , prefrontal cortex , temporal lobes , and dorsal pons during migraine ( afridi et al . , 2005a ) . several studies found that , following treatment of the migraine with sumatriptan and suboccipital stimulator therapy , the dorsal pons remained active ( bahra et al . , 2001 , matharu et al . , 2004 ) . taken together , these studies show that the brainstem is continuously activated during a migraine , and that this may be specific to migraine and it may act as a generator of migraine . a longitudinal fmri study on a migraine patient found that hypothalamic activity increases towards the next migraine attack and shows altered functional coupling with the spinal trigeminal nuclei and the dorsal rostral pons during the preictal day and the pain phase ( schulte and may , 2016 ) . combined with previous study , this may indicate that the real driver of attacks might be the functional changes in hypothalamo brainstem connectivity ( maniyar et al . , 2014 ) . if there are concordant structural changes , especially increases in the gmv , these areas may be the cause of migraine . mri studies of patients with migraine have consistently shown a distributed pattern of morphological brain abnormalities characterized by regions of decreased and increased gmv ( jin et al . , 2013 , kim et al . , 2008 , , 2012a , rocca et al . , 2006 , schmidt - wilcke et al . , 2008a , schmitz et al . , 2008b , valfre et al . , 2008 ) . the role of such abnormalities in the pathogenesis of this condition remains a matter of debate ; histological measures , such as neuronal density , do not correlate with vbm gm probability maps ( eriksson et al . , 2009 ) , and changes in cerebral blood flow produce this may reflect alterations in the dendritic complexity or changes in the number of synapses , or simply changes in water content . an increase in gmv may reflect structural brain plasticity as a result of exercise and learning ( may , 2009 ) . a decrease in gmv suggest that the central reorganization processes in chronic pain syndromes may involve degeneration of anti - nociceptive brain areas . indeed , relationships between decreases in gmv and disease duration or attack frequency have been reported ( kim et al . , 2008 , liu et al . , 2013 , , 2012a , rocca et al . , 2006 , schmidt - wilcke et al . however , some changes in gmv are not correlated with clinical manifestation , suggesting that they may predispose a person to migraine ( liu et al . , 2013 ) . in our study , one study without significant result was excluded , it was conducted in 2003 and the possibility may be the differences existed in migraine patients included and image pre - processing procedures ( matharu et al . , 2003 ) . we found a set of decreases in the gmv in the bilateral inferior frontal gyri , the right precentral gyrus , the left middle frontal gyrus and the left anterior cingulate gyrus in migraine . our finding of reliable structural alterations in homologous regions associated with pain processing highlights the importance of these areas in the pathogenesis of migraine . we also found changes in gmv in the right claustrum , the left cingulate gyrus , the right anterior cingulate , the amygdala , and the left parahippocampal gyrus , which were negatively related to the frequency of headache attacks . our result further indicate that the gmv changes related to the frequency of headache attacks may occur as a consequence of repeated brain insults during migraine attacks . decreases in gmv in the frontal gyri were not related to the frequency of headache attacks . the frontal cortex is one of the most important areas associated with brain abnormalities in migraine patients . the role of the frontal lobe in pain processing has been established in several recent morphological studies , including subjects with chronic back pain ( apkarian et al . , 2004 ) , fibromyalgia , irritable bowel syndrome , and phantom pain atrophy in the prefrontal cortex ( may , 2008 ) . it has recently been reported that significant gm atrophy of the frontal lobe is associated with migraine in pediatric patients , but is not correlated with the disease duration or frequency of attacks ( rocca et al . , 2014 ) . a recent longitudinal mri study using vbm investigated changes in gm related to medication withdrawal in a group of patients with medication overuse headache ( riederer et al . , 2013 ) . patients with clinical improvement showed a significant reversal of the changes in gm in some regions , and patients without treatment response had less gm in the orbitofrontal cortex . it appears that a decrease in gmv in the frontal gyrus may predispose a person to pain conditions , and may be predictive of poor response to treatment . pet studies have shown that the limbic regions ( the cingulate cortex , amygdala , and parahippocampal gyrus ) are activated during migraine attacks ( afridi et al . , 2005b , matharu et al . , 2004)and cluster headache attacks ( may et al . , 1999 , may et al . these areas of the brain are also believed to be involved in emotional , cognitive , and autonomic functions ( may , 2006 , morgane et al . , 2005 , alterations in cerebral structures that modulate the affective components of pain that are found in migraine suggest a possible neurobiological mechanism , which may explain the link between chronic migraine and psychiatric disturbances ( buse et al . , 2013 , minen et al . , 2016 ) . decreases in gmv in the cingulate cortex were also found in patients with chronic back pain ( schmidt - wilcke et al . , 2006 ) , chronic phantom pain ( henry et al . , 2011 ) , and chronic tension - type headaches ( schmidt - wilcke et al . , 2005 ) . these changes are correlated with disease duration and attack frequency , and may result in brain damage accumulated due to repeated occurrences of pain - related processes , and are not specific to migraine . for better understanding the neuroanatomical and functional brain changes in migraine patients , there are several studies performed on the concurrent functional and structural cortical alterations in migraine ( hubbard et al . higher thickness in the post - central gyrus in the higher frequency of attack ( hf ) correlated with the observed stronger functional activation , suggested adaptation to repeated sensory drive ( maleki et al . , 2012a ) . decreased dorsal anterior cingulate cortex was correlated with increased functional connectivity between several regions indicate that frequent nociceptive input has modified the structural and functional patterns of the frontal cortex in migraine ( jin et al . , 2013 ) . concordant structural and functional changes in hippocampal in lower frequency of attack ( lf ) group relative to the hf and hc groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency ( maleki et al . , 2013 ) . in our study , no gmv increase was found , so the generator of migraine can not been deduced . increased activation in precentral gyrus and cingulate during nociceptive stimuli opposed to gmv decrease might represent increased effort , possibly due to disorganization of these areas and/or the use of compensatory strategies involving pain processing in migraine . we did not find structural changes in gm in areas that were specifically activated in migraine ( i.e. , the brainstem , hypothalamus ) . however , this negative finding does not imply that the brainstem and hypothalamus are not involved in the pathophysiology of migraine . because most of the studies included in our meta - analysis used whole - brain detection ( only in one study was the brainstem subjected to a small - volume correction , but this employed a 1.5-t mri scanner ) , and the gm volume of the brainstem is relatively small further studies are therefore warranted that focus on the brainstem volume using 3.0-t or 7.0-t mri scanners in order to determine whether there are any significant changes in the volume of the brainstem . at the same time , ale provides a way of applying statistical thresholds to large sets of coordinate data , in order to identify the most consistently - existed and reproducible loci across many studies , the result can provide a priori hypotheses for further experimental testing . however , it filters out less robust or infrequently - reported foci that may have a greater dependence on the details of individual studies . longitudinal and combination of structural and functional imaging studies may be needed to better understand the anatomy of migraine . as animal models are available in migraine and their life spans are short , a longitudinal imaging study can also be completed in rodents and brains can be collected ex - vivo for further analysis . there are no established protocols for imaging studies , and image pre - processing procedures , such as smoothing , registration , the choice of small volume corrections , imaging modalities , and data analysis , differed among studies . the headache characteristics ( i.e. , attack frequency and disease duration ) as well as the hc choices were also inconsistent . our meta - analysis was subject to publication bias because unpublished studies and studies without any significant clusters reported were not included , the studies were limited to those published in english and where the subjects were human . the ale meta - analysis was based on pooling of stereotactic coordinates with significant differences rather than on the raw data from the included studies ; this may have limited the accuracy of the results . nevertheless , previous studies suggested that no individual study could significantly bias the results of ale meta - analyses after including the sample size and number of reported foci into ale algorithm , changing from fixed - effects to random - effects inference , and revising for multiple comparison correction ( eickhoff et al . , 2012 , eickhoff et al . , 2009 , turkeltaub et al . , 2012 ) . the inclusion criteria for fmri were nociceptive stimulation in order to allow for analysis , regardless of stimulation site or stimulus type ( e.g. , hand , forehead , heat , and ammonia ) . the result makes clear that the simultaneous activation and deactivation of the relevant regions are implicated in responses to a range of nociceptive stimuli . the sex ratio was not concordant with the prevalence of migraine , and sex differences in brain structure may be present ( maleki et al . , 2012b ) . there were few chronic migraineurs , and the sample may not be broadly representative of migraineurs overall . migraineurs frequently have several comorbid conditions ( e.g. , anxiety and mood disorders , altered lifestyles , and drug use that might directly contribute to morphological changes ) ; this was not considered in our study . brain function activation in primary headache syndromes contains two groups : areas generally involved in pain processing , such as the somatosensory , cingulate , thalamus et al . ; and areas specifically activated in primary headaches , such as the hypothalamus , which is activated in cluster headache attacks ( may et al . , 1999 ) . one review of stimulus - induced brain activation in migraine found atypical brain responses to sensory stimuli , an absence of the normal habituating response between attacks , and atypical functional connectivity of sensory processing regions ( schwedt et al . , 2015 ) . migraine sensory hypersensitivities may be induced by a combination of enhanced sensory facilitation and reduced inhibition in response to sensory stimuli ( russo et al . , 2012 , schwedt et al . , 2014 ) , as well as reduced or absent habituation to stimuli interictally ( burstein et al . , 2010 ) . they may also contribute to a transformation from episodic to chronic migraine ( moulton et al . , 2008 ) . a concordant activation was found in the somatosensory , cingulate , limbic lobe , basal ganglia and midbrain in migraine patients in our study . all these areas are related to pain processing , modulation and associated symptoms ( like emotional disturbances ) in migraineurs . the activation areas of somatosensory , basal ganglia and midbrain coincided with previous studies and further confirms that activation and sensitization of the trigeminovascular pathway are involved in migraine pathophysiology ( dasilva et al . , 2007 , noseda and burstein , 2013 , schulte and may , 2016 , stankewitz et al . , 2011 ) . studies of changes in brain function during the ictal phase may improve our understanding of migraine mechanisms . , 2005a , bahra et al . , 2001 , welch et al . , 1998 ) , and others exposed migraine subjects to attack triggers in order to initiate migraine ( afridi et al . , 2005b , cao et al . , 2002 , maniyar et al . , 2014 ) . during the premonitory phase of nitroglycerin - triggered migraine attacks , the following areas of the brain were found to be activated : the posterolateral hypothalamus , the brainstem , and various cortical areas , including the occipital , temporal , and prefrontal cortices ( maniyar et al . , 2014 ) . studies that captured the onset of migraine found an increase in the signal from the brainstem ( bahra et al . , 2001 ) . comparisons of ictal images with interictal scans revealed significant activation in the anterior and posterior cingulate , as well as the cerebellum , thalamus , insula , prefrontal cortex , temporal lobes , and dorsal pons during migraine ( afridi et al . , 2005a ) . several studies found that , following treatment of the migraine with sumatriptan and suboccipital stimulator therapy , the dorsal pons remained active ( bahra et al . , 2001 , matharu et al . , 2004 ) . taken together , these studies show that the brainstem is continuously activated during a migraine , and that this may be specific to migraine and it may act as a generator of migraine . a longitudinal fmri study on a migraine patient found that hypothalamic activity increases towards the next migraine attack and shows altered functional coupling with the spinal trigeminal nuclei and the dorsal rostral pons during the preictal day and the pain phase ( schulte and may , 2016 ) . combined with previous study , this may indicate that the real driver of attacks might be the functional changes in hypothalamo brainstem connectivity ( maniyar et al . , 2014 ) . if there are concordant structural changes , especially increases in the gmv , these areas may be the cause of migraine . mri studies of patients with migraine have consistently shown a distributed pattern of morphological brain abnormalities characterized by regions of decreased and increased gmv ( jin et al . , 2013 , kim et al . , 2008 , maleki et al . , 2012a , rocca et al . , 2006 , schmidt - wilcke et al . , 2008 , schmitz et al . , 2008a , schmitz et al . , 2008b , valfre et al . , 2008 ) . the role of such abnormalities in the pathogenesis of this condition remains a matter of debate ; histological measures , such as neuronal density , do not correlate with vbm gm probability maps ( eriksson et al . , 2009 ) , and changes in cerebral blood flow produce this may reflect alterations in the dendritic complexity or changes in the number of synapses , or simply changes in water content . an increase in gmv may reflect structural brain plasticity as a result of exercise and learning ( may , 2009 ) . a decrease in gmv suggest that the central reorganization processes in chronic pain syndromes may involve degeneration of anti - nociceptive brain areas . indeed , relationships between decreases in gmv and disease duration or attack frequency have been reported ( kim et al . , 2008 , , 2012a , rocca et al . , 2006 , schmidt - wilcke et al . however , some changes in gmv are not correlated with clinical manifestation , suggesting that they may predispose a person to migraine ( liu et al . , 2013 ) . in our study , one study without significant result was excluded , it was conducted in 2003 and the possibility may be the differences existed in migraine patients included and image pre - processing procedures ( matharu et al . , 2003 ) . we found a set of decreases in the gmv in the bilateral inferior frontal gyri , the right precentral gyrus , the left middle frontal gyrus and the left anterior cingulate gyrus in migraine . our finding of reliable structural alterations in homologous regions associated with pain processing highlights the importance of these areas in the pathogenesis of migraine . we also found changes in gmv in the right claustrum , the left cingulate gyrus , the right anterior cingulate , the amygdala , and the left parahippocampal gyrus , which were negatively related to the frequency of headache attacks . our result further indicate that the gmv changes related to the frequency of headache attacks may occur as a consequence of repeated brain insults during migraine attacks . decreases in gmv in the frontal gyri were not related to the frequency of headache attacks . the frontal cortex is one of the most important areas associated with brain abnormalities in migraine patients . the role of the frontal lobe in pain processing has been established in several recent morphological studies , including subjects with chronic back pain ( apkarian et al . , 2004 ) , fibromyalgia , irritable bowel syndrome , and phantom pain atrophy in the prefrontal cortex ( may , 2008 ) . it has recently been reported that significant gm atrophy of the frontal lobe is associated with migraine in pediatric patients , but is not correlated with the disease duration or frequency of attacks ( rocca et al . , a recent longitudinal mri study using vbm investigated changes in gm related to medication withdrawal in a group of patients with medication overuse headache ( riederer et al . , 2013 ) . patients with clinical improvement showed a significant reversal of the changes in gm in some regions , and patients without treatment response had less gm in the orbitofrontal cortex . it appears that a decrease in gmv in the frontal gyrus may predispose a person to pain conditions , and may be predictive of poor response to treatment . pet studies have shown that the limbic regions ( the cingulate cortex , amygdala , and parahippocampal gyrus ) are activated during migraine attacks ( afridi et al . , 2005b , matharu et al . , 2004)and cluster headache attacks ( may et al . , 1999 , may et al . these areas of the brain are also believed to be involved in emotional , cognitive , and autonomic functions ( may , 2006 , morgane et al . , 2005 , peyron et al . , 1999 ) . alterations in cerebral structures that modulate the affective components of pain that are found in migraine suggest a possible neurobiological mechanism , which may explain the link between chronic migraine and psychiatric disturbances ( buse et al . decreases in gmv in the cingulate cortex were also found in patients with chronic back pain ( schmidt - wilcke et al . , 2006 ) , chronic phantom pain ( henry et al . , 2011 ) , and chronic tension - type headaches ( schmidt - wilcke et al . , 2005 ) . these changes are correlated with disease duration and attack frequency , and may result in brain damage accumulated due to repeated occurrences of pain - related processes , and are not specific to migraine . for better understanding the neuroanatomical and functional brain changes in migraine patients , there are several studies performed on the concurrent functional and structural cortical alterations in migraine ( hubbard et al . higher thickness in the post - central gyrus in the higher frequency of attack ( hf ) correlated with the observed stronger functional activation , suggested adaptation to repeated sensory drive ( maleki et al . decreased dorsal anterior cingulate cortex was correlated with increased functional connectivity between several regions indicate that frequent nociceptive input has modified the structural and functional patterns of the frontal cortex in migraine ( jin et al . , 2013 ) . concordant structural and functional changes in hippocampal in lower frequency of attack ( lf ) group relative to the hf and hc groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency ( maleki et al . , no gmv increase was found , so the generator of migraine can not been deduced . increased activation in precentral gyrus and cingulate during nociceptive stimuli opposed to gmv decrease might represent increased effort , possibly due to disorganization of these areas and/or the use of compensatory strategies involving pain processing in migraine . we did not find structural changes in gm in areas that were specifically activated in migraine ( i.e. , the brainstem , hypothalamus ) . however , this negative finding does not imply that the brainstem and hypothalamus are not involved in the pathophysiology of migraine . because most of the studies included in our meta - analysis used whole - brain detection ( only in one study was the brainstem subjected to a small - volume correction , but this employed a 1.5-t mri scanner ) , and the gm volume of the brainstem is relatively small further studies are therefore warranted that focus on the brainstem volume using 3.0-t or 7.0-t mri scanners in order to determine whether there are any significant changes in the volume of the brainstem . at the same time , ale provides a way of applying statistical thresholds to large sets of coordinate data , in order to identify the most consistently - existed and reproducible loci across many studies , the result can provide a priori hypotheses for further experimental testing . however , it filters out less robust or infrequently - reported foci that may have a greater dependence on the details of individual studies . longitudinal and combination of structural and functional imaging studies may be needed to better understand the anatomy of migraine . as animal models are available in migraine and their life spans are short , a longitudinal imaging study can also be completed in rodents and brains can be collected ex - vivo for further analysis . first , we consider limitations that are common to imaging studies . there are no established protocols for imaging studies , and image pre - processing procedures , such as smoothing , registration , the choice of small volume corrections , imaging modalities , and data analysis , differed among studies . the headache characteristics ( i.e. , attack frequency and disease duration ) as well as the hc choices were also inconsistent . our meta - analysis was subject to publication bias because unpublished studies and studies without any significant clusters reported were not included , the studies were limited to those published in english and where the subjects were human . the ale meta - analysis was based on pooling of stereotactic coordinates with significant differences rather than on the raw data from the included studies ; this may have limited the accuracy of the results . nevertheless , previous studies suggested that no individual study could significantly bias the results of ale meta - analyses after including the sample size and number of reported foci into ale algorithm , changing from fixed - effects to random - effects inference , and revising for multiple comparison correction ( eickhoff et al . , 2012 , eickhoff et al . , 2009 , turkeltaub et al . , 2012 ) . the inclusion criteria for fmri were nociceptive stimulation in order to allow for analysis , regardless of stimulation site or stimulus type ( e.g. , hand , forehead , heat , and ammonia ) . the result makes clear that the simultaneous activation and deactivation of the relevant regions are implicated in responses to a range of nociceptive stimuli . the sex ratio was not concordant with the prevalence of migraine , and sex differences in brain structure may be present ( maleki et al . there were few chronic migraineurs , and the sample may not be broadly representative of migraineurs overall . migraineurs frequently have several comorbid conditions ( e.g. , anxiety and mood disorders , altered lifestyles , and drug use that might directly contribute to morphological changes ) ; this was not considered in our study . whole - brain vbm studies identified consistent widespread reduction in the gmv in migraine , specifically in the frontal cortex and the cingulate gyrus . the cingulate gyrus and the parahippocampal gyrus were related to the estimated frequency of headache attacks . frontal cortex and cingulate gyrus were over - activated in interictal phase during nociceptive stimuli . these changes in gm may be related to the mechanisms of pain processing and the associated symptoms of migraine , such as cognitive dysfunction , emotional problems , and autonomic dysfunction . the limbic regions may accumulate damage due to repeated occurrences of pain - related processes . further studies are required to determine how these changes can be used to monitor disease progression or exploited in therapeutic interventions . supplementary material 1structural neuroimaging data in nifti format.image 1supplementary material 2structural neuroimaging data related to headache durations in nifti format.image 2supplementary material 3functional neuroimaging data in nifti format.image 3supplementary material 4structural interactive plots.image 4supplementary material 5structural interactive plots related to headache durations.image 5supplementary material 6functional interactive plots.image 6 structural neuroimaging data in nifti format . structural neuroimaging data related to headache durations in nifti format . functional neuroimaging data in nifti format . structural interactive plots .

objectivesto summarize and meta - analyze studies on changes in grey matter ( gm ) in patients with migraine . we aimed to determine whether there are concordant structural changes in the foci , whether structural changes are concordant with functional changes , and provide further understanding of the anatomy and biology of migraine.methodswe searched pubmed and embase for relevant articles published between january 1985 and november 2015 , and examined the references within relevant primary articles . following exclusion of unsuitable studies , meta - analysis were performed using activation likelihood estimation ( ale).resultseight clinical studies were analyzed for structural changes , containing a total of 390 subjects ( 191 patients and 199 controls ) . five functional studies were enrolled , containing 93 patients and 96 controls . ale showed that the migraineurs had concordant decreases in the gm volume ( gmv ) in the bilateral inferior frontal gyri , the right precentral gyrus , the left middle frontal gyrus and the left cingulate gyrus . gmv decreases in right claustrum , left cingulated gyrus , right anterior cingulate , amygdala and left parahippocampal gyrus are related to estimated frequency of headache attack . activation was found in the somatosensory , cingulate , limbic lobe , basal ganglia and midbrain in migraine patients.conclusiongm changes in migraineurs may indicate the mechanism of pain processing and associated symptoms . changes in the frontal gyrus may predispose a person to pain conditions . the limbic regions may be accumulated damage due to the repetitive occurrence of pain - related processes . increased activation in precentral gyrus and cingulate opposed to gmv decrease might suggest increased effort duo to disorganization of these areas and/or the use of compensatory strategies involving pain processing in migraine . knowledge of these structural and functional changes may be useful for monitoring disease progression as well as for therapeutic interventions .

in the past two decades , the function of matrix metalloproteinases ( mmps ) in the central nervous system ( cns ) has gained much attention . mmps are calcium ( ca ) dependent zinc ( zn ) containing endopeptidases produced in latent forms . once activated , they participate in the regulation of diverse physiological and pathological processes . mmps are involved in the degradation of extracellular matrix ( ecm ) components , remodeling of tissues , shedding of cell surface receptors , and processing of various signaling molecules . mmps are essential for brain development due to their association with important neurophysiological functions , such as synaptic plasticity [ 2 , 3 ] and long - term potentiation [ 4 , 5 ] . in the adult brain under normal conditions , increased expression of mmps is observed in a variety of pathological conditions , including neurodegenerative diseases such as alzheimer 's disease ( ad ) , parkinson 's disease ( pd ) , amyotrophic lateral sclerosis ( als ) , huntington 's disease ( hd ) , and multiple sclerosis ( ms ) and in neuroinflammatory conditions such as traumatic brain injury , stroke , and meningitis . as part of the neuroinflammatory response , mmp activity at cns barriers contributes to the increase in permeability by altering the properties of ecm and tight junctions . this results in aggravation of neuroinflammation - induced brain damage . on the other hand , activation of mmps is known to help in tissue repair , angiogenesis , and neurogenesis . in this review , mmps , together with adamlysins and astacins , belong to metzincins , a family of zn - dependent , ca - containing endopeptidases ( 24 members in mammals ) . mmps are multidomain proteins consisting mostly of the following domains : n - terminal signal peptide ( which is cleaved in the secretory pathway ) , propeptide ( which maintains latency of mmps ) , catalytic domain ( holds the zn ion ) , hinge region ( connecting sequences ) , and c - terminal hemopexin - like domain ( required for substrate and timp recognition ) ( figure 1 ) . besides these common domains , some mmps have alternative peptide structures and different additional domains . mmps are produced as zymogens ( pro - mmp ) that are activated by other enzymes or free radicals through the cysteine switch mechanism . the thiol group of a cysteine residue in the n - terminal prodomain binds to and blocks the active - site zn atom ; activation occurs when the thiol group is blocked or removed . it has been shown that mmps play an important role in various physiological and pathological processes in the body . it acts as an adhesion site for various cells and serves as a storage site for different signaling molecules , growth factors , and proteins in general , thus influencing development and migration of the cells . ecm consists mainly of glycosaminoglycans , proteoglycans , and fibrous proteins ( collagen , laminin , and fibronectin ) . mmp cleavage of ecm influences cell migration , embryogenesis , and other processes during development as well as in the adult organism . in the brain , mmps are involved in tissue remodeling after injury , neurogenesis , axonal growth , angiogenesis , cns barrier disruption , myelinogenesis , and demyelination . additionally , mmps play an active role in immune processes by cleaving various molecules , including growth factors , death receptors , chemokines , and cytokines [ 9 , 10 ] . for example , several mmps can activate tumor necrosis factor ( tnf ) [ 1115 ] and transforming growth factor - beta ( tgf- ) , while other mmps degrade interleukin-1 ( il-1 ) . ultimately , mmp cleavage of chemokines and cytokines can lead to either pro- or anti - inflammatory processes . based on their domain organization , mmps are classified into four major subgroups : ( 1 ) gelatinases ( mmp-2 , mmp-9 ) , ( 2 ) matrilysins ( mmp-7 , mmp-26 ) , ( 3 ) archetypal mmps , and ( 4 ) furin - activated mmps ( figure 1 and table 1 ) . the archetypal mmps contain different types : stromelysins ( mmp-3 , mmp-10 ) , collagenases ( mmp-1 , mmp-8 , mmp-13 ) , and other mmps ( mmp-12 , mmp-18 , mmp-20 , mmp-27 ) . similarly , the furin - activated mmps are divided in secreted mmps ( mmp-11 , mmp-21 , mmp-28 ) ; type - i transmembrane mmps ( mmp-14 , mt1-mmp , mmp-15 , mt2-mmp , mmp-16 ( mt3-mmp ) , and mmp-24 ( mt5-mmp ) ) , type - ii transmembrane mmps ( mmp-23 ) , and gpi - anchored mmps ( mmp-17 ( mt4-mmp ) , mmp-25 ( mt6-mmp ) ) . mmps are modulated on several levels : transcriptional activation , removal of the prodomain , interaction with ecm components , and inhibition by endogenous inhibitors such as tissue inhibitors of metalloproteinases ( timps ) . timps are proteins of 2128 kda which bind the active site of mmps in a one - to - one ratio [ 7 , 20 ] . besides timps , also -2 macroglobulin and receptor mediated endocytosis can prevent activated mmps from exerting their effects . proinflammatory cytokines ( e.g. , tnf and il-1 ) and several growth factors can initiate an intracellular signaling cascade leading to the activation of ap-1 , nf - kb , or ets transcription factors , with consequent mmp transcription . on the level of mmp - zymogen activation , mostly serine proteases and other mmps are involved in initiating proteolytic cleavage of the prodomain ; for example , mmp-3 can cleave pro - mmp-9 . additionally , high levels of reactive oxygen species ( ros ) and reactive nitrogen species can induce activation of mmps . it has been observed that mmps in the cns are secreted by microglia , astrocytes , and neurons . in physiological conditions , mmps are either absent or present at undetectable levels in the mature brain , and deregulation of their activity could shift the balance and induce perpetuation of chronic inflammation . this has been shown in different peripheral chronic diseases , such as atherosclerosis and rheumatoid arthritis [ 25 , 26 ] , and neuroinflammatory diseases , such as cerebral ischemia , stroke , and bacterial meningitis . mmps are known to be involved in cns barrier maintenance and to increase the permeability of the barriers in inflammation . the proposed mechanism involves degradation of ecm components ( e.g. , laminin and collagen ) , which normally support cellular structures and limit the passage of different molecules and cells into the blood through the barriers [ 2830 ] . additionally , increased mmp activity is known to negatively affect tight junction functionality at the cns barriers [ 3033 ] . alternatively , several mmps have been shown to activate proinflammatory cytokines and free radicals , which enhances inflammation and subsequently induces disruption of the cns barriers [ 27 , 34 , 35 ] . mmps are secreted upon inflammation , for example , by peripheral neutrophils , which thereby contribute to aggravation of the inflammation and disruption of the barriers . compromise of cns barrier integrity due to activation of mmps has been observed in cerebral ischemia , traumatic brain injury ( tbi ) , and other diseases associated with neuroinflammation . in this review , we focus on the role of different mmps in the major neurodegenerative diseases , ad , pd , als , hd , and ms ( figure 2 ; tables 2 and 3 ) . during the previous century , prolongation of the human lifespan led to an increase in the proportion of elderly people in the population , which has given rise to an increased incidence of age - related diseases such as neurodegenerative disorders . neurodegenerative diseases share common features , such as progressive loss of neurons and deterioration of the structure and function of the central and/or peripheral nervous system . these chronic illnesses impose a heavy economic and social burden and affect both patients and caregivers . since all neurodegenerative diseases are incurable , the outcome in most cases is death . worldwide , 47 million people are living with ad and other dementias , including more than 5 million in the united states alone , where the number is expected to rise to 7.1 million in 2025 . furthermore , there are large numbers of patients with other neurodegenerative diseases , including ad , pd , als , hd , ms , and frontotemporal dementia . the major problem in the management of neurodegenerative diseases is the lack of adequate information on their pathogenesis and absence of mechanism - based treatments . however , interaction of genetic and environmental factors , as well as advanced age , is known to contribute to disease onset . generally , all neurodegenerative diseases share certain molecular and cellular mechanisms , including protein aggregation and formation of inclusion bodies . the traditional classification of neurodegenerative disorders is based on clinicopathological features and has been formulated through consensus criteria , that is , a set of diagnostic criteria on which experts in the field agree , along with specific molecular characteristics . this traditional classification was established during the early stages of the research on neurodegenerative diseases and was based on a rather small number of cases . one of the categories used for classification is the presence of certain molecules in brain lesions associated with the disorder , for example , -amyloid ( a ) for ad and -synuclein for pd . for several neurodegenerative diseases , mutations in specific genes have been found , for example , presenilin genes ( psen 1 and 2 ) for ad . however , in certain cases diagnosis is difficult due to the coincidence of clinicopathological features of several neurodegenerative diseases [ 9799 ] . nowadays , with the increasing amount of molecular and genetic data and the continuing efforts to find other common characteristics of neurodegenerative diseases , questions have arisen about the distinction between these diseases , making their classification even more problematic [ 99101 ] . the early classifications divided neurodegenerative diseases into either taupathies ( including ad , pick 's disease ( pid ) , argyrophilic grain disease ( agd ) , progressive supranuclear palsy ( psp ) , corticobasal degeneration ( cbd ) , and ftdp-17 ) and synucleinopathies ( including pd , dementia with lewy bodies ( dlb ) , and multiple system atrophy ( msa ) ) . today , different , nosological classifications of neurodegenerative diseases exist , taking into account clinical presentation , affected brain regions and cell types , altered proteins involved in the pathogenesis of the disease , genetics , and possible overlaps between diseases [ 96 , 103 ] . neuroinflammation is defined as inflammation of nervous tissue , which occurs as a biological response to different signals , such as infection , cns injury , autoimmunity , and toxic compounds . although it is initiated primarily as a beneficial reaction of the cns to the harmful stimulus , it could eventually aggravate the disease . neuroinflammation is characterized by the initiation of a cascade of events , including production of cytokines and chemokines accompanied by the release of free radicals and proteases , resulting in a chronic inflammatory state in the organism . four cns barriers separate blood from cns parenchyma to block entrance of immune cells and various molecules into the brain from the periphery : blood - brain barrier ( bbb ) , blood - cerebrospinal fluid barrier ( bcsfb ) , arachnoid barrier , and blood - spinal cord barrier ( bscb ) [ 104 , 105 ] . all cns barriers are dynamic structures that allow passage of immune - related molecules and cells upon specific stimuli ( e.g. , proinflammatory cytokines ) [ 106 , 107 ] . furthermore , immune functions in the brain are conveyed by microglia , innate immune cells that are constitutively present in the brain , but astrocytes can secrete many molecular mediators of the immune response . microglia are of myeloid origin and normally reside in a ramified , resting state in the cns , where they monitor the surrounding environment in the brain and spinal cord . opposite to immune cells in the periphery , microglia are predominantly involved in limiting inflammation . when triggered by various immunological stimuli , microglia morphologically transform into ameboid cells and start to proliferate and secrete inflammatory mediators [ 109 , 110 ] . besides , they start to mimic antigen presenting cells ( apc ) , which are immune cells in the periphery , by upregulating major histocompatibility complex ( mhc ) class ii and becoming phagocytic . the presence of the mhc is important for prolongation of the immune response in the cns . it has been shown that microglia are involved in neuron survival , neurogenesis , facilitation of brain repair via guidance of stem - cell migration to the site of inflammation or injury , and clearance of cell debris . nevertheless , when overactive , microglia can inflict severe damage to the brain by excessive production of molecules such as mmps , proinflammatory cytokines and chemokines , and cytotoxic molecules such as ros and nitric oxide ( no ) [ 116118 ] . they also produce different inflammatory mediators , including cytokines , chemokines , and complement components . for example , both microglia and astrocytes secrete il-2 and il-1 , thereby stimulating cd4 + t helper cells to produce gm - csf , which contributes to perpetuation of the inflammation processes by recruitment of cd11b - positive myeloid cells . also t cells can secrete cytokines and mmps that are known to disrupt the bbb and permit the entry of immune cells from periphery , converting acute inflammation into a chronic inflammatory state . although microglia have been implicated in neurodegenerative diseases , the mechanisms responsible for activating microglia are unknown . all neurodegenerative diseases are multifactorial and caused by complex interactions of genetic and environmental factors . by far the most prominent risk factor for most neurodegenerative diseases is aging , so the prevalence of these disorders is high above the age of 65 years . aging is influenced by interaction and balance between various protective and harmful factors over the lifespan of an individual . these factors include genetics , nutrition , psychosocial influences , and exposure to toxic compounds . however , it is not yet clear how aging acts on the development of neurodegenerative diseases and other age - related diseases . two of the most prominent characteristics of aging are immunosenescence ( deterioration of immune responses ) and inflammaging ( presence of chronic low grade inflammation ) [ 124 , 125 ] . physiological aging is associated with a progressive increase in the number of activated microglial cells in the brain and spinal cord [ 126128 ] accompanied by transition from normal microglial morphology to microglial dystrophy . it has been shown that aged microglia secrete il-1 and increase mhc class ii expression . low - level systemic inflammation during aging has also been linked to the presence of active microglia and increased proinflammatory cytokines levels in the brain [ 132134 ] . one of the characteristics of aging is accumulation of advanced glycation end products ( age ) , which are also elevated in ad . activation of the receptor for age ( rage ) leads to release of proinflammatory cytokines and free radicals , further contributing to inflammatory processes . nevertheless , changes in the physiological balance between mmps and timps have been related to age - related vascular diseases . one theory of aging suggests that vascular - derived insults initiate and/or contribute to aging and to some of the age - related diseases , such as ad [ 137 , 138 ] . in a comparative study , rna expression of 22,626 genes was monitored in the heart and cerebellum of young and aged mice of several strains . two potential biomarkers of aging present in both structures were identified : complement component c4 and timp-2 . using magnetic resonance imaging , romero et al . found that upregulation of mmp-9 was associated with aging and circulating levels of mmp-9 and timp-1 in patients with brain ischemia and aging . liu et al . observed that mmp-12 increased in the aging brain and that mmp-12 deficiency led to a reduction of neuroinflammaging . this finding is linked to aggravation of neuroinflammation associated with aging via the induction of the migration of bone marrow derived microglia to the brain . furthermore , safciuc et al . showed that microvessels in the brain of aged rats exhibit decreased mmp-2 activity and appearance of mmp-9 . its prominent characteristics include brain atrophy , caused by neuronal cell death , and decreased dendritic arborization in the cerebral cortex and other subcortical areas . the hallmarks of ad include presence of amyloid plaques and neurofibrillary tangles , which are linked to cerebral atrophy . amyloid plaques , also called senile plaques , appear in brain parenchyma as extracellular deposits consisting of a fibrils of 3743 amino acids , originating from alternative processing of app protein . although a deposition is considered a signature lesion for ad , it also occurs in down 's syndrome , possibly due to triple multiplication of amyloid precursor protein ( app ) , as well as in certain cases of dementia with lewy bodies [ 145 , 146 ] . additionally , occurrence of a pathology has been observed in several other neurodegenerative diseases , such as pd , pick 's disease ( pid ) , progressive supranuclear palsy ( psp ) , and corticobasal degeneration , as well as in als . besides , deposition of a occurs in the cerebral vasculature in both cerebral amyloid angiopathy ( caa ) and in 90% of patients with ad . a originates from the transmembrane protein app , which undergoes amyloidogenic processing by -secretase to produce -c terminal fragments ( ctfs ) . these fragments are cleaved by -secretase to release a in the extracellular space and app intracellular domain ( aicd ) into the cytoplasm . in the physiological nonamyloidogenic pathway , these fragments are cleaved by -secretase , resulting in the cytoplasmic peptide fragment aicd and the extracellular p3 peptide . in contrast to a peptides , p3 peptides have a low propensity to assemble into stable oligomers and they have no known harmful effects on brain cells . it has been shown that some of the members of the metalloproteinase family , including the adam ( a disintegrin and metalloproteinase ) proteins adam-17 ( also called tumor necrosis factor--converting enzyme or tace ) , adam-9 and adam-10 , can cleave app at the -secretase cleaving site . a oligomers are nonfibrillar structures , and further aggregation of a oligomers results in the formation of protofibrils and eventually fibrils . a deposits are typically surrounded by dystrophic neurites , reactive astrocytes , and activated microglia , forming dense - core plaques in the brain parenchyma . also considered hallmarks of ad are neurofibrillary tangles ( nft ) , intercellular deposits of a hyperphosphorylated form of tau protein . physiologically , tau protein plays a role in the assembly and stabilization of microtubules in neurons . cases of dementia with abundance of nfts and a few amyloid plaques have been classified as a nonspecific type of neurodegenerative disorders , called nft dementia . however , the etiology of ad is complex , and neither a nor nft alone should be considered responsible for the disease manifestations . therefore , other proposed mechanisms and manifestations of the disease should also be taken into account . some authors point to the role of an imbalance in ros formation and cellular antioxidant activity in ad . the idea is that overproduction of free radicals could be a driving force behind neurodegeneration , and given the large number of possible stressors , such as aging , inflammation , hypoxia , and cerebral hypoperfusion , there is ample opportunity for overproduction of free radicals . on the other hand , advocates of the inflammatory hypothesis propose a central role for activated microglia nearby amyloid plaques in the brain . their notion is that activated microglia produce large amounts of inflammatory cytokines and chemokines , which sustain a chronic inflammation in the brain that ultimately leads to neuronal cell death . furthermore , it has been shown that besides the established direct neurotoxic effect , a can exert indirect proinflammatory effects via microglial activation , which results in secretion of no , tnf , and superoxides [ 167 , 168 ] . interestingly , clustering of activated microglia around a aggregates has been observed even before the development of ad symptoms [ 169171 ] . in view of the relationship between mmps and ad ( figure 3 ) and in order to distinguish ad from vascular dementia , bjerke et al . proposed mmp-9 and timp-1 as biomarkers of ad , next to t - tau , p - tau , a142 , and white matter lesions . strikingly , a correlation between cognitive impairment and mmp-9 activity was observed in patients with mild cognitive impairment . in agreement with that correlation , mmp-9 expression was shown to be induced in ad patients in neuronal cytoplasm , neurofibrillary tangles , amyloid plaques , and vascular tissue , as well as in astrocytes upon a stimulation . additionally , mmp-9 was found in pyramidal neurons of the brains of ad patients , and near amyloid plaques and it was shown that mmp-9 is able to cleave a140 . moreover , yan et al . showed that mmp-9 can degrade a fibrils in vitro , as well as amyloid plaques in brain slices from app / ps1 mice . using intracerebroventricular ( icv ) injections of different a peptides in animal models , mizoguchi et al . showed an increase in mmp-9 activity in hippocampus , related this increase to a-induced cognitive impairment , and confirmed the results using mmp inhibitors and mmp-9 knockout mice . notably , another study showed that mmp-3 , by remodeling the ecm , is crucial for synaptic plasticity and learning . it has been shown that mmp-9 can act through nmda receptor signaling via an integrin 1 dependent pathway . li et al . showed in primary astrocyte cultures insignificant levels of mmp-9 in medium after treatment with a oligomers , accompanied with a decrease in mmp-2 activity . on the contrary , in the brain of app / ps1 ad mice , they observed increased mmp-2 and proinflammatory cytokine levels . they proposed that a can decrease the expression and activation of mmp-2 in astrocytes directly , while stimulating microglia to produce proinflammatory cytokines , which in turn again induce mmp-2 expression and aggravate the disease . , no elevation of mmp-2 activity was observed in ad patients . in a transgenic mouse model of ad , expression of mmp-2 and mt1-mmp , a potent mmp-2 activator , was found in reactive astrocytes around amyloid plaques , and higher levels of a142 increased the production of mmp-3 , mmp-12 , and mmp-13 in microglia . additionally , mmp-12 exacerbates the cascade of proteolytic processes by subsequent activation of other mmps such as mmp-2 and mmp-3 . looked into the effects of a on endothelial cells and bbb integrity and linked this to mmp activity . they observed increased bbb permeability in cultured endothelial cells linked to decreased zonula occludens-1 ( zo1 ) levels , one of the major components of tjs . moreover , there was an increase in mmp-9 and mmp-2 activity , and broad - spectrum mmp inhibition reversed the a-induced bbb disruption . additionally , they confirmed these results in a transgenic mouse model of ad by showing enhanced immunoreactivity of mmp-9 near cerebral capillaries and alterations in tight junction components . the proposed mechanism of a activity is through activation of rage , which is physiologically expressed on endothelial cells and activates the intracellular calcineurin ( can ) signaling pathway , which ultimately results in activation of mmps and tj cleavage . in the same year , another group showed that interaction of a with rage induces mmp-2 via the erk and jnk pathways in brain endothelial cells . besides aging , the most prominent genetic risk factor for developing late onset ad is the presence of apolipoprotein e 4 allele ( apoe 4 ) in the genome . the group of zlokovic reported that , both in transgenic mice and in humans , apoe 4 leads to bbb breakdown by activating the proinflammatory cyclophilin a ( cypa)/mmp-9 pathway in brain pericytes , which are important components of the neurovascular unit and guardians of bbb integrity [ 61 , 174 ] . this eventually results in degradation of the bbb tight junctions and basement membrane proteins [ 61 , 174 ] . as far as the role of stromelysins in ad is concerned , mmp-3 levels were significantly upregulated in plasma , similar to what was observed in csf of ad patients . in contrast , mlekusch and humpel observed downregulation of mmp-3 and mmp-2 in csf of ad patients , but it should be noted that these patients had lower a levels . in other studies , it has been shown that mmp-3 is expressed in microglia , astrocytes , and endothelial cells in the brain , as well as near senile plaques in ad . deb and gottschall showed that mmp-3 was induced and its activity increased in astrocyte and neuronal cell cultures upon a140 stimulation . as reported for mmp-9 moreover , a correlation was found between mmp35a and apoe 4 alleles , and the presence of both is a risk factor for developing ad . interestingly , we recently reported that icv injection of a142 oligomers induces loss of barrier integrity at the blood - csf barrier , and this was linked to increased mmp-3 expression and mmp activity . moreover , the a142 oligomer - induced leakage of the bcsfb could be prevented by a broad - spectrum mmp inhibitor and did not occur in mmp-3 deficient mice . leake et al . reported a notable increase in mmp-1 in brain of ad patients . found upregulated microglial / macrophage expression in tissues from ad patients , as well as in a mouse model of ad . finally , levels of timp-1 and c - reactive protein ( crp ) were found to be increased in ad patients , and they decreased remarkably after treatment with acetylcholinesterase inhibitors ( acheis ) , one of the few available therapies of ad . pd is the second most prevalent neurodegenerative disease and the most common neurodegenerative movement disorder , with an estimated 710 million people worldwide suffering from it . like ad , its prevalence increases with age , and due to the severity and long duration of the disease , its costs in the us alone are estimated at 25 billion dollars per year . a prominent characteristic of pd is the presence of intracellular protein inclusions called lewy bodies in affected brain areas . these inclusions are formed of fibrillar , misfolded proteins composed of -synuclein , parkin , synphilin , synaptic vesicle proteins , and neurofilaments . interestingly , inclusions similar to lewy bodies were found in 22% of cases of familial ad , and they occur also in dementia with lewy bodies ( dlb ) and in multiple system atrophy ( msa ) . another hallmark of pd is selective and progressive loss of dopaminergic neurons in substantia nigra pars compacta . the substantia nigra , being part of basal ganglia together with the striatum , globus pallidus , and subthalamic nucleus , modulates motor activity in the brain . thus , due to dopaminergic neuron cell death , one of the clear manifestations of the disease is loss of control over movements , resting tremor , bradykinesia , and rigidity . additionally , pd is accompanied by sensory dysfunction , mood and sleep disorders , dementia , and partial autonomic nervous system impairment . this multifactorial disorder is known to be influenced by genetic factors , such as multiplication or missense mutations in the -synuclein gene , which is a major risk factor for familial pd . additionally , mutations in parkin , pink1 , and lrrk2 have been identified as possible causes of other cases of familial pd [ 186 , 187 ] . nevertheless , most cases of pd are sporadic , and the onset of the disease has been shown to be caused by complex interaction of environmental and genetic factors . thus , some hypotheses propose that neuroinflammation could play a pivotal role in promotion and aggravation of the disease [ 188190 ] . studies on postmortem tissue of pd patients , as well as in vivo imaging , revealed astrogliosis , overactivation of microglia , and infiltration of peripheral immune cells into brain regions affected by pd [ 191195 ] . in pd patients , active microglia have been observed in most of the regions with lewy bodies , and in vivo imaging revealed microglial activation throughout the different stages of the disease , indicating chronic microglial activation . the substantia nigra seems to be particularly susceptible to inflammation due to the presence of the largest number of microglia in this brain area , so relevant stimuli lead to the activation of large numbers of microglia . in agreement with these findings , activated microglia have been found in substantia nigra in patients with sporadic or familial pd [ 196 , 198 ] as well as after exposure of humans to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( mptp ) . the same effect was seen in the substantia nigra and striatum in animal models of pd based on mptp injection [ 199202 ] . microglial activation was also found in other pd models and in other brain regions in pd patients , including putamen , hippocampus , transentorhinal cortex , cingulate cortex , and temporal cortex . hirsch and hunot described early microglial activation after mptp injection , followed by later neuronal cell death and infiltration of t cells and astrogliosis . other evidence for the role of microglia in pd comes from studies using anti - inflammatory drugs to inhibit microglial activation , which was protective against neurodegeneration induced by mptp or 6-ohda . active microglia are known to secrete inflammatory mediators , and accordingly , increased proinflammatory cytokine levels were increased in the substantia nigra [ 206 , 207 ] and csf in pd . furthermore , il-1 and il-6 were found to be elevated in csf of parkinson 's disease patients [ 209 , 210 ] . it has been speculated that prolonged overactivation of microglia and production of proinflammatory cytokines could lead to neuronal degeneration in pd [ 207 , 211 ] . it is also speculated that oxidative stress could be generated from dopaminergic metabolism , mitochondrial dysfunction , and microglial activation , which could be influenced beforehand by various toxins and mutations in parkin , pink1 , dj-1 , or htra1 , which are important for physiological mitochondrial functioning . other evidence for the involvement of active microglia in triggering neurodegeneration of dopaminergic neurons in the substantia nigra comes from studies on injection of lipopolysaccharide ( lps ) systemically or directly in the substantia nigra [ 213215 ] . this could be explained by specific susceptibility of dopaminergic neurons to oxidative stress due to the presence of tyrosine hydroxylase and monoamine oxidase , which are ros - generating enzymes , as well as excessive production of easily oxidized cytosolic dopamine [ 217 , 218 ] . however , it is speculated that initial neurotoxic insult to dopaminergic neurons results in the release of certain factors that activate microglia and convert them from beneficial into harmful . it has been shown that damaged dopaminergic neurons can activate microglia by releasing -synuclein and neuromelanin , causing them to produce ros . mmp-3 , produced by neurotoxin - stressed dopaminergic neurons , seems to be a self - sufficient player in microglial activation in the absence of any other inflammatory molecule . it has been suggested that this mechanism plays an important role in apoptosis . on the one hand , mmp-3 could cleave the connections between apoptotic cells and ecm , thereby facilitating subsequent phagocytosis . on the other hand , it could activate microglia , leading to the release of cytokines and receptors for phagocytosis of apoptotic cells . in an in vitro study , kim et al . additionally , they hypothesized that both active mmp-3 and catalytically active recombinant mmp-3 could activate microglia to produce proinflammatory cytokines , which in turn aggravate neuronal apoptosis of damaged cells , leading to further induction of apoptosis in neighboring dopaminergic neurons . this hypothesis is supported by postmortem studies describing progressive dopaminergic neuronal degeneration in humans and monkeys treated with mptp for 10 years [ 65 , 221 ] . using mmp-3 deficient mice and a broad spectrum mmp inhibitor , it has been shown that depletion of mmp-3 can significantly reduce mptp - induced degeneration of nigrostriatal dopaminergic neurons in the brain . furthermore , mmp-3 activated microglia produce superoxide , known to be involved in facilitation of dopaminergic neuronal cell death in vitro [ 222 , 223 ] and in vivo . using sirna , also upregulated mmp-9 activity , produced by neurons and microglia , was found in both striatum and substantia nigra after mptp treatment , and pharmacologic inhibition of mmps protected against mptp neurotoxicity . earlier , the same group analyzed postmortem brain tissue from pd patients and found no change in the activities of mmp-9 and mmp-1 in substantia nigra , cortex , or hippocampus , whereas mmp-2 was significantly reduced in the substantia nigra . additionally , they showed that mmp-9 was localized primarily in neurons and mmp-2 in astrocytes and microglia . in the same study , timp-2 levels did not change , whereas timp-1 was upregulated in substantia nigra but not in the cortex and hippocampus . the increase in mmp-9 expression in substantia nigra was later confirmed by annese et al . the data showed that mmp-9 is expressed in reactive microglia and astrocytes , pinpointing mmp-9 as a key molecule for the onset of neuroinflammation in pd . experiments done in mmp-9 deficient mice confirm that active glia diminish neuronal survival since decreased numbers of active microglia correlated with increased numbers of functional dopaminergic neurons . in a primate model of pd ( mptp - injected macaques ) , an increase in mmp-9 labeled striatal neurons and astrocytes was also found . bbb leakage was found in animal models of pd solely in brain regions and was associated with microglial activation and dopaminergic neurodegeneration [ 225 , 226 ] . recent evidence suggests that the proteolytic activity of mmps might be involved in alteration of -synuclein protein conformation , thus contributing to aggregation , lewy body formation , and microglial activation . in an in vitro study on a dopaminergic neuronal cell line , sung et al . observed mmp - dependent proteolysis of -synuclein , followed by increased aggegate formation . in this process , mmp-3 was particularly efficient , but mmp-1 , mmp-2 , and mmp-14 showed similar properties . levin et al . further studied the mmp - specific -synuclein cleavage and showed that both mmp-1 and mmp-3 mediate increased -synuclein aggregation in comparison to trypsin and proteinase k . als , also known as lou gehrig 's disease , is characterized by degeneration of motor neurons in the brain , brainstem , and spinal cord . all voluntary muscles are affected , and the muscle weakness and atrophy are followed by paralysis , and finally respiratory failure and death . some other neurodegenerative diseases share similar etiology , such as progressive lateral sclerosis ( pls ) , progressive muscular atrophy ( pma ) , als dementia , and als frontal lobe dementia . interestingly , one - third of all als patients exhibit symptoms or pathology resembling those of ad . ( 2.08 people per 100,000 in europe ) , and the prevalence is mostly in people between the ages of 45 and 65 years . familial occurrence of the disease is only 510% of all als cases , and the cause of the sporadic form of als is still unknown . some familial and sporadic cases are caused by mutation in the gene for copper - zinc superoxide dismutase 1 ( sod1 ) . additionally , als is associated with protein inclusions composed mostly of transactive response dna - binding protein 43 ( tdp-43 ) in the cytoplasm in the affected areas of the brain and spinal cord . however , occurrence of tdp-43 is not characteristic of only als but was found in several patients with frontotemporal lobar degeneration with tdp proteinopathy ( ftld - tdp ) , as well as in frontotemporal dementia , ad , and some other neurodegenerative diseases . the etiology of the disease is unknown , but various mechanisms have been proposed , including neuroinflammation , glutamate excitotoxicity , oxidative stress damage and mitochondrial dysfunction , protein misfolding and aggregation , and deficits in neurotrophic factors . besides , in als , active microglia were also observed in brain areas such as motor cortex , pons , dorsolateral prefrontal cortex , and thalamus . interestingly , activation of microglia was correlated with progression of the disease . in the in vitro work of swarup et al . , microglia overexpressing tdp-43 increased their secretion of proinflammatory cytokines upon lps treatment in comparison to wild type microglia . one of the theories suggests that bbb and bscb breakdown could contribute to the motor neuron damage , due to the importance of these barriers in maintenance of homeostasis in the cns . indications of the involvement of mmps , key players in barrier alteration , come from early studies on neocortex and spinal cord of als patients , in which mmp-2 was found in astrocytes , and mmp-9 was found in pyramidal neurons in the motor cortex and motor neurons in the spinal cord . additionally , mmp-2 activity was decreased in motor cortex whereas mmp-9 activity was increased in spinal cord . since bscb disruption in als [ 237239 ] is accompanied by downregulation of mrna for tight junction proteins , miyazaki et al . speculated that mmp-9 is involved in barrier disruption . another group showed reduced mmp-9 activity during disease progression , with the peak at the onset of als , and described a similar profile for mmp-2 . two separate groups found significant increases in both pro - mmp-9 and active mmp-9 in serum of als patients relative to healthy controls [ 242 , 243 ] . reported that in mild cases of als , expressions of mt - mmp-1 , mmp-2 , mmp-9 , and timp-1 are elevated in serum compared to csf , where mt - mmp-1 , mmp-2 , and timp-1 were upregulated or unchanged while mmp-9 levels were decreased . furthermore , fang et al . found increased levels of mmp-9 in csf from patients suffering from rapidly progressing als . they speculated that this finding is associated with progression of the disease , poor survival of the patients , and neuronal degeneration . nevertheless , mmp-2 showed a slow but progressive decrease with the development of the disease . in the study by kaplan et al . , diminishing mmp-9 function by genetic , viral , or pharmacological intervention was shown to prolong survival in a sod1 mouse model of als . moreover , mmp-9 was preexpressed only in fast motor neurons , which have been shown to be particularly susceptible to degeneration in patients suffering from als . these results show that mmp-9 is a key player in the onset of the disease and point to it as a therapeutic target . kaplan et al . focused on the early stage of the disease and expression of mmp-9 by neurons , whereas kiaei et al . studied later stages of the disease and observed expression of mmp-9 by activated microglia , giving support to the hypothesis that the pathology is mediated by cytokines secreted by microglia . since the depletion of mmp-9 gene does not rescue transgenic sod1 mice from death , als indeed has complex background . there are about 2.5 million cases worldwide , with approximately 400,000 in the us alone , and ms is twice as common in women as in men . in contrast to most neurodegenerative disorders that are prevalent in aged individuals , ms occurs in people between 20 and 45 years of age . the cause of the disease is unknown , but genetic and environmental factors contribute to its development . interestingly , epidemiological studies revealed a correlation with smoking , exposure to uvb radiation , and intake of unsaturated fatty acids . ( 1 ) relapsing - remitting ms ( rrms ) occurs in about 85% of patients suffering from ms . the disease alternates between remission ( periods of improvement ) and relapses ( periods of deterioration ) . ( 2 ) secondary progressive ms ( spms ) , which is characterized by continuous worsening of the symptoms , affects some patients suffering from rrms . ( 3 ) primary progressive ms ( ppms ) is manifested in about 10% of ms patients . ( 4 ) progressive - relapsing ms ( prms ) is the rarest type , present in less than 5% of patients . although it is progressive from the beginning , it shows relapses occasionally , but without periods of remission . at onset , rrms is characterized as a neuroinflammatory state . however , with the progression of the disease and occurrence of relapses , certain residual disability develops . over ten years , most patients enter spms , which is then observed more as neurodegeneration state resulting in permanent disability . although inflammation is considered as primary in ms , this disease is recently being acknowledged as a neurodegenerative disorder too because of recent findings . it has been observed that disability related to ms is correlated with axonal damage and neuronal cell loss more than with inflammation . the new hypothesis that emerged resembles the previously proposed mechanism for the other neurodegenerative disorders : perpetuated inflammation leads to triggering of neurodegenerative processes . interestingly , certain case reports have noted patients suffering from ms and als at the same time . in ms , the bbb is disrupted , leading to peripheral blood leukocyte infiltration , followed by focal degradation of myelin , and finally axonal disruption and neuronal cell loss . it has been shown that the bbb function in ms is lost in both relapsing - remitting and progressive phases . nevertheless , bbb dysfunction is a temporary event , although recurrence is highly possible . in fact , local bbb changes that follow the pattern of the lesions help diagnose ms by observing brains using magnetic resonance imaging ( mri ) with contrast agents that easily leak into the affected parts of the brain . some of the data suggest that bbb breakdown precedes infiltration of the immune cells , but this event is not definitively the primary cause of lesion formation . . showed in a common animal model of ms called experimental autoimmune encephalomyelitis ( eae ) that occludin dephosphorylation preceded visible signs of disease onset , which indicates that bbb breakdown is one of the first events in ms . it is known that in ms , various brain and immune cells can secrete mmps , thus contributing to the bbb breakdown [ 260 , 261 ] . cossins et al . observed expression of mmp-7 by macrophages and mmp-9 in blood vessels in active lesion sites of postmortem brain samples . another group confirmed this finding and also showed expression of mmp-3 in endothelial cells , mmp-1 , mmp-2 , mmp-3 and mmp-9 in macrophages , and to a lesser extent in astrocytes , around active and necrotic lesions . examined csf samples from patients suffering from both rrms and ppms and found an increase in mmp-9 in all the rrms cases throughout both phases of the disease . however , in ppms patients , mmp-9 was increased in only about half of the samples and in significantly smaller amounts than in the relapsing - remitting form . they argued that this points out that t - cells and macrophages are responsible for the secretion of mmp-9 in ms . additionally , they proposed that constant elevation of mmp-9 throughout the progress of the disease could contribute to the surrounding tissue damage and neuronal cell loss . in their work using the eae model , kieseier et al . showed that the increase in mmp-9 and mmp-7 expression in blood vessels and parenchyma strongly correlated with the peak of the disease . elevated levels of mmp-9 were also observed in serum of ms patients , together with an increase in timp-1 and timp-2 . in the same study , the authors pointed out an association of these increases with the number of lesions observed by mri . however , the study of waubant et al . found increased levels of mmp-9 in serum but no elevation of timp-1 levels . also , by univariant analysis they found that an increase in mmp-9 and a decrease in timp-1 levels preceded the appearance of new lesions . another group compared the mrna levels of mmp-1 , mmp-3 , mmp-7 , mmp-9 , mmp-14 , and timp-1 in blood monocytes of ms patients with those of controls . they found that all except mmp-14 were upregulated . in an interesting study by althoff et al . using the eae model , transgenic mice that constitutively express timp-1 in the cns had a normal phenotype but eae symptoms were diminished . interestingly , other studies done using the eae model showed limited bbb restoration and amelioration of the clinical picture after administration of broad - spectrum mmp inhibitors [ 90 , 265 ] . finally , mmp-9 knockout mice were shown to be less susceptible to induction of eae . besides the occurrence of the leakage , the bbb also becomes activated , meaning that cells making up the bbb , including endothelial cells , astrocytes , and potentially pericytes , start expressing and secreting various factors involved in the recruitment and functioning of leukocytes . constant leukocyte migration occurs through the bbb in active ms lesions and this migration is normally strictly regulated by a number of molecules , such as cell adhesion molecules ( cam ) , integrins , cytokines , and chemokines . the leukocyte infiltration further aggravates bbb breakdown , as shown in in vitro studies . in one in vitro study , interferon treatment downregulated mmp-9 expression and abolished mmp-2 expression , thereby diminishing subsequent migration of t - cells . newman et al . showed that microinjection of activated mmps into white matter leads to axonal injury . of the several mmps tested , the most potent was mmp-9 , followed by mmp-2 , and finally mmp-7 . the proposed mechanism of mmp action is via degradation of the ecm , since mmps have an established role in the apoptosis of different cell types by the same mechanism . additionally , mmp - activated axonal degeneration was hardly observed in peripheral nervous system , possibly due to the presence of resilient ecm and higher timps expression . it has been speculated that this could be a cause of reduced remyelination and decreased number of mature oligodendrocytes in mmp-9 and mmp-9/-12 null mice . huntington 's disease ( hd ) is an inherited neurodegenerative disorder that decreases muscle coordination and mental ability . the disease has been linked to a mutation on chromosome 4 in a gene coding for a protein called huntingtin ( htt ) . while the exact role of htt is not clear yet , it has been speculated that proteolysis of mutant htt participates in the pathology . besides caspases and calpains acting as proteases in hd miller et al . have shown that knocking down mmp-10 , mmp-14 , and mmp-23 in cultured striatal cells expressing mutant htt diminishes toxicity . additionally , mmp-10 can directly cleave htt , and the production of toxic htt fragments is reduced upon silencing of mmp-10 . analysis of deceased patients with hd revealed an increase in mmp-9 in comparison to controls , as well as upregulation of cytokine levels ( il-6 , il-8 ) in cortex and cerebellum . in striatum , the main area affected in hd , only ccl2 and il-10 were upregulated . other evidence for involvement of mmp-9 in hd comes from the 3-nitropropionic acid animal model of the disease . the authors showed that mmp-9 is accountable for the bbb disruption that occurs in the disease . moreover , significantly elevated levels of mmp-9 were found in plasma of patients suffering from hd , as well as in the r6/2 mouse hd model . the authors proposed mmp-9 ( along with il-6 , vegf , and tgf- ) as a potential biomarker of hd . as far as timps are concerned , lorenzl et al . found increased timp-1 and timp-2 levels in csf of patients suffering from hd . as far as other neurodegenerative diseases are concerned , different mmps were found to be dysregulated in people suffering from dementias . decreased levels of timp-2 were found in serum of patients with frontotemporal dementia , and downregulated timp-1 was shown in patients with vascular dementia . intriguingly , patients with vascular dementia have been noted to have higher levels of mmp-9 in csf even compared to patients suffering from ad . in csf from patients suffering from creuztfeldt - jakob disease , a rare type of dementia , there were increased levels of pro - mmp-9 and active mmp-2 , as well as timp-1 and timp-2 . for decades , conventional wisdom has taught us that mmps play a pivotal role in the dissemination of cancer : they degrade the connective tissue between the cells and allow the cancer cells to leak from the primary site of tumor formation . during the past decade , more than a dozen of mmps have been shown to be involved in progression of neurodegenerative disorders , thereby opening up the possibility of therapeutically targeting mmps . in most neurodegenerative disorders , neuroinflammation is observed either before or during the development of the pathological characteristics of the disease . during neuroinflammation , mmps often increase the permeability of the cns barriers by destroying the stability of the tight junction proteins or degrading the ecm , which in turn leads to infiltration of immune cells into the brain and cell death . on the other hand , in certain neurodegenerative diseases such as ad and mmps , and , in particular , mmp-3 and mmp-9 , were shown to degrade a plaques [ 50 , 58 ] , justifying the view of mmps as a double - edged sword . therefore , drugs that inhibit mmps could have unforeseen effects that need to be well understood and avoided before we employ them for therapy ( figure 4 ) . mmp expression is usually triggered by an inflammatory stimulus ( e.g. , infection , burns , or protein aggregates ) , which induces an inflammatory cascade . at this stage , anti - inflammatory drugs will be effective in eliminating the expression or activation of mmps . subsequently , the available synthetic broad - spectrum inhibitors might be used to inhibit mmps ( table 3 ) . however indeed , selective mmp inhibition might avoid the unwanted side effects of broad - spectrum mmp inhibition . mmp inhibitors can be broadly classified as macromolecular inhibitors ( including timps and monoclonal antibodies ) and both synthetic and natural small molecules [ 280 , 281 ] . in general , early studies conducted using broad spectrum mmp inhibitors such as batimastat on mice injected with human cancer cells gave compelling results of extending the life of the mice from six- to sevenfold , thereby paving the way for the potential use of mmp inhibitors in other diseases . mmp inhibitors yielded beneficial results in animal studies of lung inflammatory diseases , multiple sclerosis , meningitis [ 283285 ] , vascular dementia , stroke , acute cerebral ischemia [ 287 , 288 ] , and sepsis [ 1 , 15 , 289 , 290 ] . finally , interfering with the substrates downstream of mmps might also have therapeutic value . the potential use of mmp inhibitors in ad is very speculative and is based on the seemingly beneficial effect of mmp-9 , due to its role in degradation of amyloid plaques and hence its contribution to the clearance of a from the brain . furthermore , it has been reported that mmp-2 can cleave a at the -secretase site . in another similar study , it was reported that mmp-2 also can cleave full - length app , indicating that it can produce -apps at the plasma membrane or degrade a in the ecm , which leads to reduction of a burden in the brain . in contrast to those reports , other authors were unable to show a similar mmp-2 activity , but they found that mmp-2 might possess -secretase like activity , which might shift the balance towards the amyloidogenic pathway . mice deficient in mmp-2 or mmp-9 appeared to have higher levels of a than wild type animals . likewise , treatment with the broad - spectrum mmp inhibitor gm6001 resulted in an increase in a in transgenic mice overexpressing the swedish variant of app . in an in vitro study , gm6001 was shown to block the a-induced alterations in zo-1 expression and bbb permeability . similarly , gm6001 was also able to prevent the a oligomer - induced degradation of the blood - csf barrier integrity . moreover , in another study on a transgenic mouse model of ad , it was reported that inhibition of mmps with gm6001 reduced the oxidative stress associated with caa . timps , the endogenous inhibitors of mmps , were found to be localized near the a plaques and neurofibrillary tangles of ad - affected brain samples . it has been speculated that mmps and timps contribute to the evolution of these lesions . similarly , it has been shown that mmps are produced in excess at lesion sites by the immune cells surrounded by the effected regions , and that timps might be localized in these places as well to control the activity of mmps . thus , to validate mmps and timps as possible candidates for therapeutics development , it is important to investigate whether they are amyloidogenic or prevent a accumulation . this is mainly because of potential harmful side effects of broad spectrum mmp inhibitor activities , which pose a big hurdle . as far as therapeutic opportunities of mmp inhibition in pd are concerned , lorenzl et al . reported the expression of mmps such as mmp-1 , mmp-2 , and mmp-9 and also timp-1 and timp-2 in substantia nigra of postmortem pd brain samples . hence , mmp inhibitors might hold promise for management of pd because death of dopaminergic neurons seems to be linked with release of mmps . apoptotic dopaminergic neurons release mmp-3 , which in turn activates microglia in vitro , indicating that mmp-3 could serve as a signaling molecule as well . the activated microglia release proinflammatory cytokines , such as tnf , that lead to neuronal cell death . treatment of mouse mesencephalic cells with tetrahydrobiopterin ( bh4 ) , a selective dopaminergic neuronal toxin , decreased cell survival . however , when cells were exposed to a selective mmp-3 inhibitor , nngh ( n - isobutyl - n-[4-methoxyphenylsulfonyl]-glycylhydroxamic acid ) , cell survival was extended via the decrease of tnf- release from activated microglial cells . similarly , several hypotheses were proposed regarding the role of mmps in the development of als . reported that by crossing g93a sod1 mice with mmp-9 knockout mice , immunoreactivity was increased and expression of mmp-9 was elevated in spinal cord tissue of g93a sod1 mice , a model of familial als . reduced mmp-9 activity was shown to prolong survival in the als mouse model expressing mutant sod1 , pointing to mmp-9 as a potential therapeutic target . generally , mmp-9 stimulates neuronal tnf- by cleaving it from its membrane - bound form , and it also contributes to neuronal cell death by activating other proinflammatory cytokines . abnormally high levels of mmp-9 and possible degradation of the matrix components contribute to als progression . there are several reports on the use of synthetic mmp inhibitors to ameliorate the symptoms of eae , and protease inhibitors were used to treat eae as early as 1982 . mmp activity was shown to increase threefold in the csf in two acute models of eae . broad - spectrum mmp inhibitors such as gm6001 [ 87 , 89 ] , ro31 - 9790 , uk221,316 , d - penicillamine , and bb1101 were shown to be beneficial in eae . mmp-9 was shown to be elevated at the lesion sites and in the csf of ms patients . similarly , association of mmp-9 with the disruption of the bbb was also reported in mri studies . when gm6001 was administered after the clinical onset of the disease , it inhibited the development of eae , and it also reversed the clinical symptoms in sjl / j mice . it was also speculated that mmp inhibition results in restoration of damaged bbb , thereby decreasing the inflammation rather than inhibiting demyelination . in a similar study by hewson et al . , using ro31 - 9790 reduced the clinical signs in the eae model of ms when given on the day of disease induction or three days after induction . ro31 - 9790 was less effective in controlling the disease in animals with more severe clinical signs . bb1101 , another broad - spectrum inhibitor , reduced disease severity in lewis rats and reversed acute symptoms in sjl / j mice . bb1101 was also shown to be effective in chronic relapsing eae in sjl / j mice , in which bb1101 treatment reduced the glial scar and demyelination . further , b1101 treatment shifted the cytokine profile from a proinflammatory to an anti - inflammatory state . an antirheumatic drug , d - penicillamine , was also shown to partially protect against eae in sjl / j mice , but in chronic relapsing eae in biozzo mice , treatment with d - penicillamine resulted in attenuation of disease progression after disease induction . the therapeutic efficacy of minocycline , a semisynthetic derivative of tetracycline , was tested in mog35_55 peptide - induced eae in c57bl/6 mice . it reduced both the activity and expression of mmp-9 in t - cells and reduced disease severity . in the same study , interestingly , an antioxidant molecule , -lipoic acid , was found to be beneficial in suppressing eae and reducing disease severity after disease induction . this effect was linked with reduced infiltration of t cells into the cns , which led to speculation that -lipoic acid could be inhibiting mmp-9 . so far , no molecular mechanism has been identified to explain how mmp inhibition ameliorates ms disease symptoms , but it is speculated that broad - spectrum mmp inhibition inhibits transmigration of immune cells into the cns via the bbb . that would result in reduced demyelination and reduced levels of tnf through inhibition of adam17 . therefore , novel strategies are needed to harness the ability of neuroprotective mechanisms to slow down or stop the progression of the disease in order to prolong the healthy lifespan of patients . more basic research is required to fully understand the diverse roles of mmps in the pathophysiology of neurodegenerative diseases in order to design specific mmp inhibitors and therapeutic strategies for these chronic diseases of the nervous system . although the potential causes and etiology of neurodegenerative diseases remain largely elusive , mmps clearly have a pivotal role in the progression of neurodegenerative diseases such as ad , pd , als , hd , and ms , and their functions in these diseases seem to be much more complex than previously thought . targeting mmps will be of much interest for the treatment of these disorders . in most clinical cases , hence , it is necessary to explore the role of the different mmps in depth to be able to develop more therapeutic options . more than a dozen mmps were shown to be involved in neurodegenerative diseases , including mmp-2 , mmp-3 , and mmp-9 , and they seem to be important players in most of the diseases mentioned in this review . the mechanisms of action by which they contribute to the aggravation of neurodegenerative diseases are slowly starting to unfold . mmps participate in a common pathway of pathological changes in the cns homeostasis , that is , accumulation of proinflammatory molecules or aggregated proteins and peptides , leading to increased permeability of cns barriers and consequently to cell death . on the other hand , the dual roles of mmps hinder efforts to use broad - spectrum mmp inhibitors as therapeutics . however , a strong indication that selective mmp inhibitors could have therapeutic opportunities already exists . consequently , investigation of mmps and timps as potential biomarkers and therapeutics in neurodegenerative diseases needs to be continued .

neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system ( cns ) functionality . it has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases . matrix metalloproteinases ( mmps ) , a protein family of zinc - containing endopeptidases , are essential in ( neuro)inflammation and might be involved in neurodegeneration . although mmps are indispensable for physiological development and functioning of the organism , they are often referred to as double - edged swords due to their ability to also inflict substantial damage in various pathological conditions . mmp activity is strictly controlled , and its dysregulation leads to a variety of pathologies . investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases . here , we review mmps and their roles in neurodegenerative diseases : alzheimer 's disease ( ad ) , parkinson 's disease ( pd ) , amyotrophic lateral sclerosis ( als ) , huntington 's disease ( hd ) , and multiple sclerosis ( ms ) . we also discuss mmp inhibition as a possible therapeutic strategy to treat neurodegenerative diseases .

ferromagnetism and superconductivity are antagonistic to each other s orders , however their interplay can be realized when the two interactions are spatially separated . in this case the coexistence of the two orderings is due to the proximity effect @xcite , @xcite , @xcite . experimentally this situation can be realized in superconductor/ ferromagnet ( s / f ) hybrid structures . the role of the andreev reflection is central to the proximity effect since it provides the mechanism for converting single electron states from a normal ( n ) or ferromagnetic metal to cooper pairs in the superconducting condensate @xcite , @xcite . during the andreev reflection process the electron incoming to the n / s ( f / s ) interface is reflected as a hole and a charge @xmath4 is transferred across the interface . as a result a long - range electron - hole coherence is induced into the non - superconducting material . the andreev reflection manifests itself in the subgap conductance , i.e. the conductance for voltages smaller than the superconducting gap @xmath1 . in diffusive n / s systems the subgap conductance shows the zero bias anomaly peak due to the impurity confinement and the electron - hole interference at the fermi level @xcite , @xcite , @xcite . at a s / f interface the mechanism of andreev reflection is modified compared to the n / s hybrid structures since the incoming electron and reflected hole belong to different spin bands @xcite . thus , one expects a suppression of the andreev ( subgap ) current by increasing the exchange field @xmath0 , which is a measure of the spin - splitting at the fermi level . recently it was shown by the authors that this intuitive picture does not hold always @xcite . if the voltage exceeds some critical value the andreev current of a tunnel ferromagnet/ insulator/ superconductor ( fis ) structure is enhanced by a small exchange field @xmath5 reaching a maximum at @xmath6 at zero temperature . if one keeps the voltage low but now increase the temperature , the andreev current ( as well as the full current at this temperature ) shows a peak at @xmath2 . all these novel features were exhaustively discussed in @xcite . finally it was shown that the subgap conductance of a fis junction at low temperatures and small exchange fields @xmath5 has a peak at @xmath3 @xcite , @xcite . thus its measurement can be used to determine the strength of a weak exchange or zeeman - like field in the hybrid structure . the latter can be not only the intrinsic exchange field of a ferromagnetic alloy @xcite but also a spin - splitting field created in the normal metal by a magnetic induction @xmath7 ( in which case @xmath8 , where @xmath9 is the bohr magneton ) or by a proximity to the ferromagnetic insulator material @xcite . all these predictions were made in @xcite for the mono - domain fis hybrid system . the purpose of this work is to consider hybrid structure with a multi - domain ferromagnetic metal . we present a quantitative analysis of the electron transport in fis tunnel structures where a ferromagnetic layer consist of two magnetic domains with arbitrary direction of magnetization ( so called `` superconducting spin - valve '' @xcite ) . we show that in this case the aforementioned features of the andreev current and subgap conductance occur at the value of the `` effective field '' , which is the field acting on the cooper pairs in the multi - domain ferromagnetic region , averaged over the decay length of the superconducting condensate into a ferromagnet @xcite . the model of a sf@xmath10f@xmath11n junction we are going to study is depicted in fig . [ model ] and consists of a ferromagnetic bilayer f@xmath10f@xmath11 of thickness @xmath12 connected to a superconductor ( s ) and a normal ( n ) reservoirs along the @xmath13 direction . we consider the diffusive limit , i.e the elastic scattering length @xmath14 is much smaller than the decay length of the superconducting condensate into a ferromagnet @xmath15 and the superconducting coherence length @xmath16 , where @xmath17 is the diffusion coefficient and @xmath0 is the value of the exchange field ( we set @xmath18 and for simplicity we assume the same @xmath17 in the whole structure ) . we also assume that the f@xmath10f@xmath11 and f@xmath11n interfaces are transparent , while the sf@xmath10 is a tunnel barrier . thus , the two ferromagnetic layers are kept at the same potential as the voltage - biased normal reservoir . the f@xmath10f@xmath11 bilayer can either model a two domain ferromagnet or an artificial hybrid magnetic structure . the magnetization of the f@xmath10 layer is along the @xmath19 direction , while the magnetization of the f@xmath11 layer forms an angle @xmath20 with the one of the layer f@xmath10 . both magnetization vectors lie in the @xmath21 plane . correspondingly the exchange field vector in the f@xmath10 is given by @xmath22 , and in the f@xmath11 layer by @xmath23 , where the angle @xmath20 takes values from 0 ( parallel configuration ) to @xmath24 ( antiparallel configuration ) . f@xmath11n junction . the interface at @xmath25 corresponds to the insulating barrier ( thick black line ) . interfaces at @xmath26 and @xmath27 are fully transparent . @xmath20 is the angle between the magnetization directions of f@xmath10 and f@xmath11 . ] under these conditions , the microscopic calculation of the electric current through the structure requires solution of the quasiclassical equation for the @xmath28 keldysh - green function @xmath29 in the keldysh @xmath30 nambu @xmath30 spin space in the f@xmath10f@xmath11 bilayer @xcite , @xcite , @xmath31 , \quad \breve{g}^2 = 1 , \quad \breve{g } = \begin{pmatrix } \check{g}^r & \check{g}^k \\ 0 & \check{g}^a \end{pmatrix}.\ ] ] here @xmath32 is the hamiltonian , @xmath33 is the matrix spectral current , @xmath34 are the pauli matrices in spin space and @xmath35 in nambu space . the @xmath36 , @xmath37 and @xmath38 indices stand for the retarded , advanced and keldysh components ( we use the symbols @xmath39 for @xmath28 and @xmath40 for @xmath41 matrices ) . in eq . ( [ usadel3d ] ) we neglect the inelastic collision term , assuming @xmath42 to be smaller than the inelastic relaxation length @xcite . in the f@xmath10 region @xmath43 and the equation eq . ( [ usadel3d ] ) has the form @xmath44.\ ] ] in the f@xmath11 region @xmath45 and it is convenient to introduce green s functions rotated in spin space @xcite , @xmath46 the rotated function @xmath47 is then determined by eq . ( [ usadel ] ) . the eq . ( [ usadel ] ) should be complemented by boundary conditions at the interfaces . as mentioned above , we assume that the f@xmath10f@xmath11 and f@xmath11n interfaces are transparent and therefore the boundary conditions at @xmath48 read @xmath49 at @xmath25 , the sf@xmath10 interface is a tunnel barrier , where the boundary conditions are given by the relation @xcite , @xmath50_{x=0}.\ ] ] here @xmath51 is the green function of a bulk bcs superconductor defined as @xmath52 @xmath53 is the diffusive transparency parameter @xcite , @xmath54 , and @xmath55 is the dynes parameter @xcite . in our calculations we set small @xmath56 where @xmath57 is the superconducting gap at zero temperature . below we omit @xmath55 in analytical expressions for simplicity . the electric current through the structure is given by the following expression @xcite , @xcite , @xmath58 where @xmath59 . by neglecting non - equilibrium effects , the keldysh component of green s function is related to the retarded and advanced ones by @xmath60 where @xmath61 and @xmath62 are correspondingly the equilibrium quasiparticle distribution functions and the temperature . below we express the advanced green functions through the retarded ones using the general relation @xmath63 @xcite . in particular , we are interested in the andreev current , i.e. the current for voltages smaller than the superconducting gap due to andreev processes at the sf@xmath10 interface . it is given by the expression @xcite , @xcite , @xmath64 where @xmath65 is the condensate spectral function , @xmath66 is the heaviside step function and the function @xmath67 is the singlet component of @xmath68 at @xmath69 . this equation is used throughout the article to determine the andreev transport . we neglect the contribution to the andreev current due to the partial andreev reflection at the energies above the superconducting gap . in the case of strong enough tunnel barrier at @xmath25 this contribution leads to negligible corrections @xcite . because of the low transparency of the tunnel sf@xmath10 barrier , the proximity effect is weak and the retarded green function can be linearized ( we omit the superscript @xmath36 ) , @xmath70 where @xmath68 is the @xmath71 anomalous green function in the spin space ( @xmath72 ) that obeys the linearized equation , @xmath73 where @xmath74 stands for the anticommutator . the general solution of this equation has the form @xmath75 where @xmath76 is the singlet component and @xmath77 are the triplet components with respectively zero and @xmath78 projections on the spin quantization axis @xcite . solving eq . ( [ linearized ] ) in the f@xmath10 layer we obtain for the components of eq . ( [ f ] ) , [ f_i ] @xmath79 where @xmath80 , @xmath81 are the boundary values of @xmath82 at @xmath25 ( @xmath83 stands for @xmath84 ) and the characteristic wave vectors are @xmath85 in the f@xmath11 layer the general solution has the form , @xmath86,\ ] ] where @xmath87 are the components of the rotated green function , eq . ( [ gauge ] ) . using the boundary conditions at the f@xmath10f@xmath11 interface , eqs . ( [ bc1]-[bc11 ] ) we obtain a set of six linear equations for the six coefficients @xmath81 and @xmath88 , that can be solved straightforwardly . in particular we are interested in @xmath89 which enters the equation for the andreev current , eq . ( [ ia ] ) . since the analytical expression is cumbersome we do not present it here . first we briefly review the novel features of the andreev current for a mono - domain sifn structure ( @xmath90 ) , discussed in @xcite . at zero temperature we observe the enhancement of the andreev current at high enough voltages above some critical value , see fig . [ fig1 ] ( a ) , solid black line . the andreev current first increases by increasing @xmath0 , reaches a maximum at @xmath6 , and then decays by further increase of the exchange field . the enhancement of the andreev current is due to the competition between two - particle tunneling processes and decoherence mechanisms . sharp suppression of the andreev current at @xmath6 occurs when the electron - hole coherence length @xmath91 is cut off by the decay length of superconducting condensate into a ferromagnet , @xmath15 . another feature of the andreev current , predicted in @xcite is the peak at @xmath2 which can be observed only at finite temperatures . the relative height of this peak increases with temperature and voltage , see figs . [ fig1 ] ( c ) and ( d ) , solid black line . in case of large enough values of @xmath92 and @xmath62 , we observe both the enhancement of the andreev current by increasing @xmath0 and the peak at @xmath2 , see fig . [ fig1 ] ( b ) , solid black line . the peak can be observed only for high enough temperatures when the upper limit of the integration in eq . ( [ ia ] ) is @xmath1 ( at zero temperature the upper limit is @xmath93 ) . then the integrand in eq . ( [ ia ] ) has a `` dangerous point '' at @xmath94 . this peak can be observed by measuring the full electric current through the junction as the single particle current is almost independent on @xmath0 . note that for the values of temperature used in our calculations @xmath95 . now let us reconsider these features for the two - domain situation in case of @xmath96 ( dashed blue lines in fig . [ fig1 ] ) and @xmath97 ( dash - dotted red line in fig . [ fig1 ] ) . the thickness of the f layers is chosen to be @xmath98 and @xmath99 , @xmath100 short enough for the superconducting condensate penetrates both ferromagnetic layers and @xmath101 long enough for the full development of the proximity effect in f@xmath10f@xmath11 bilayer ( at small values of @xmath101 the andreev current is suppressed by the proximity of the normal reservoir at @xmath102 ) @xcite . firs of all , we see that increasing @xmath20 the features ( peaks at @xmath103 ) smear and their amplitude reduces . for @xmath97 we do not see any more the enhancement of the andreev current . secondly , we see shift of these peaks to the larger values of @xmath0 , which is explicitly seen for @xmath96 . the peak at @xmath6 is shifted to the right ( fig . [ fig1 ] ( a ) , dashed blue line ) as well as the peak at @xmath2 ( fig . [ fig1 ] ( d ) , dashed blue line ) . this can be explained as follows . the superconducting condensate penetrates both ferromagnetic layers and feel the `` effective exchange field '' @xmath104 acting on the cooper pairs , averaged over the length @xmath105 @xcite . the @xmath106 is gradually reduced as @xmath20 increases from @xmath107 to @xmath24 . as before the andreev current peak is at @xmath108 which in the case of a finite @xmath20 corresponds to larger values of the bare @xmath0 , therefore we observe shift of the andreev current peak to the right . let us now calculate the subgap differential conductance @xmath109 at zero temperature . it is known that for a diffusive nis junction the differential conductance at low temperatures has a peak at @xmath110 and a zero bias anomaly ( zba ) peak due to the impurity confinement and the electron - hole interference at the fermi level @xcite , @xcite , @xcite . it occurs at zero bias since for @xmath111 the electron is perfectly retro - reflected as a hole during the andreev reflection process . thus the electron and the reflected hole interfere along the same trajectory and the interference effect strongly enhance the subgap conductance at zero bias @xcite . for the fis structures with @xmath5 the zba peak is now shifted to the finite voltage @xmath3 @xcite , @xcite , see fig . [ fig2 ] , solid black lines . this can be described as follows . upon entering of the cooper pair into the ferromagnetic metal the spin up electron in the pair lowers its potential energy by @xmath0 , while the spin down electron raises its potential energy by the same amount . in order for each electron to conserve its total energy , the spin up electron must increase its kinetic energy , while the spin down electron must decrease its kinetic energy , to make up for these additional potential energies in f @xcite . therefore the electron - hole pair in f has now the momentum mismatch , i.e. the electron is not perfectly retro - reflected . however , if @xmath3 there is a possibility for exact retro - reflection ( and interference along the trajectory ) of an electron to a hole with a same kinetic energy equal to the fermi energy . in case of the two - domain ferromagnetic metal we now have the zba shift to the `` effective exchange field '' @xmath112 . the `` effective field '' is smaller than the bare @xmath0 , @xmath113 , and therefore we observe the shift of the differential conductance peak to the left . we can explicitly see this for @xmath96 ( fig . [ fig2 ] , dashed blue lines ) . for @xmath97 the situation is more complicated as the effective exchange field is rather small in the antiparallel configuration . for @xmath98 we observe a broad zba peak at @xmath111 for @xmath97 for both values of @xmath114 and @xmath115 ( fig . [ fig2 ] , dash - dotted red lines ) . for @xmath116 the maximum is shifted from the zero bias , see fig . [ fig3 ] , dash - dotted red lines . in the end we notice that siffn structures with two - domain ferromagnetic interlayer show interesting behavior of the heat current through the structure @xcite . it is known that in nis tunnel junctions the flow of electric current is accompanied by a heat transfer from the normal metal into the superconductor @xcite , @xcite . this happens due to the selective tunneling of high - energy quasiparticles out of the normal metal in presence of the superconducting energy gap @xmath1 . the heat transfer through nis junctions can be used for the realization of a microcooler , and the important problem is to overcome possible limitations of its cooling performance . some of the limitations arise from the fact that nonequilibrium quasiparticles injected into the superconducting electrode accumulate near the tunneling interface @xcite , @xcite . this problem can be solved by imposing a local thermal equilibrium in the superconductor electrode by means of a `` quasiparticle trap '' , i.e. an additional normal metal layer covering the superconductor electrode @xcite , @xcite . another fundamental limitation arise from the andreev reflection processes : the andreev current @xmath117 does not transfer heat through the n / s interface but rather generates the joule heating @xmath118 which fully dissipates in the normal electrode and dominates quasiparticle cooling at low temperatures @xcite , @xcite . in order to reduce this factor it was proposed to add a ferromagnetic interlayer in the nis structure to suppress the andreev current and enhance the heat current and cooling performance @xcite . from our studies we can conclude that the ferromagnetic interlayer with small enough exchange field will rather enhance the andreev current and suppress the heat current ( cooling power ) through the structure . one need ferromagnet with an exchange field ( bare or effective in multi - domain case ) larger than the superconductor gap @xmath1 to suppress the andreev reflection processes and enhance the cooling performance . the @xmath20-dependence of the heat current in siffn structures was discussed in @xcite . to summarize , we have studied the andreev current and the subgap conductance behavior in siffn hybrid structures with arbitrary direction of magnetization of the f layers . we have revisited all novel features predicted recently in the mono - domain sif system in the presence of a small spin - splitting field @xmath0 @xcite , namely the andreev current peaks at @xmath6 at @xmath119 and at @xmath2 for high enough temperature , and the differential conductance peak at @xmath3 . we have shown that in the two - domain case the aforementioned features occur at the value of the `` effective exchange field '' @xmath113 , which is the field acting on the cooper pairs in the multi - domain ferromagnetic region , averaged over the decay length of the superconducting condensate into a ferromagnet , @xmath105 . increasing @xmath20 from @xmath107 to @xmath24 one gradually reduce the effective field @xmath106 . we also briefly discuss the heat transport and electron cooling in the considered structures . this work was supported by the spanish ministry of economy and competition under project fis2011 - 28851-c02 - 02 , the basque government under upv / ehu project it-366- 07 , the `` topological quantum phenomena '' ( no.22103002 ) kakenhi on innovative areas , a grant - in - aid for scientific research ( no . 22710096 ) from mext of japan , and jsps institutional program for young researcher overseas visits . the work of a.o . was supported by the csic and the european social fund under jae - predoc program . e. v. bezuglyi , a. s. vasenko , v. s. shumeiko , and g. wendin : phys . b * 72 * , 014501 ( 2005 ) ; e. v. bezuglyi , a. s. vasenko , e. n. bratus , v. s. shumeiko , and g. wendin : _ ibid . _ * 73 * , 220506(r ) ( 2006 ) d. golubev and a. vasenko : in _ international workshop on superconducting nano - electronics devices _ , ed . by j. pekola , b. ruggiero , and p. silvestrini ( kluwer academic , dordrecht 2002 ) , p. 165 ; [ arxiv:1204.2719 ]

the andreev current and the subgap conductance in a superconductor/ insulator/ ferromagnet ( sif ) structure in the presence of a small spin - splitting field show novel interesting features @xcite . for example , the andreev current at zero temperature can be enhanced by a spin - splitting field @xmath0 , smaller than the superconducting gap @xmath1 , as has been recently reported by the authors . also at finite temperatures the andreev current has a peak for values of the spin - splitting field close to the superconducting gap , @xmath2 . finally , the differential subgap conductance at low temperatures show a peak at the bias voltage @xmath3 . in this paper we investigate the andreev current and the subgap conductance in sff structures with arbitrary direction of magnetization of the f layers . we show that all aforementioned features occur now at the value of the `` effective field '' , which is the field acting on the cooper pairs in the multi - domain ferromagnetic region , averaged over the decay length of the superconducting condensate into a ferromagnet . we also briefly discuss the heat transport and electron cooling in the considered structures .

recent experiments have shown that it is possible to study unitary nonequilibrium dynamics in quantum systems on long time scales @xcite . one important result of these investigations has been the observed lack of thermalization . the reason for this non - thermal behaviour is attributed to the near integrability of the system . this observation has motivated recent studies of the non - equilibrium properties of integrable quantum model hamiltonians @xcite . the interest in this topic is also motivated by its relevance to a variety of experimental situations , including cold atoms @xcite , penning traps @xcite and josephson - junction arrays @xcite . there are many ways in which it is possible to drive a system out of equilibrium . quantum quenches , and coupling to baths with different temperatures ( or potentials ) are the most common protocols . while in the quench scenario the focus is on the unitary dynamics of the full system , in the second case one usually deals with an effective description of the dynamics of the subsystem only . different out - of - equilibrium dynamics have nevertheless similar characteristics , for example the presence of currents ( of particles , energy , or heat ) . in this work , we study an ising - like model system driven out of equilibrium with a quantum quench in the presence of an energy current . in the usual quench protocol the system is prepared in the ground - state in the absence of any current , and subsequently the dynamics drives it to some excited state . the model hamiltonian we consider here allows for the study of two different new situations : a quench from the ground - state in the presence of an energy current , and a quench from an initial excited state in the absence of an energy current . the two scenarios are associated with different hamiltonians which , in a sense , are dual to each other . to characterize the system s behaviour we focus our attention on the entanglement entropy ( ee ) , as measured by the von neumann entropy , which is a central quantity in the characterization of nonequilibrium quantum dynamics @xcite . the structure of the paper is the following : in sec.ii we introduce and describe the properties of the model hamiltonian , in sec.iii we consider the static properties of ee for this model , and in sec.iv we study the dynamics of entanglement following a quench . finally , we states our conclusions . in the appendix the reader can find more details of the calculations . we consider an ising spin chain in transverse field @xmath0 , with an additional dzyaloshinskii - moriya ( dm ) interaction @xmath1 . the total hamiltonian @xmath2 is defined as follows @xmath3 , \label{eq : ham}\ ] ] where @xmath4 is the external magnetic field , and @xmath5 is the coupling parameter determining the strength of the dm interaction . such an anisotropic interaction is present in many low - dimensional materials with the necessary crystal symmetry , and it originates from spin - orbit coupling @xcite . furthermore , the dm interaction is of relevance in quantum information theory , since it plays an important role in the physics of quantum dots @xcite , and in fault - tolerant quantum computation @xcite . adding the dm term to @xmath0 does not affect the solvability of the model @xcite , and interestingly enough it provides the system with a richer phase diagram . these features have been used in @xcite to study the effective out - of - equilibrium quantum dynamics of the model . @xmath6 can be viewed as a current term . the reason for this is the following . the equation of motion for the local energy density of @xmath0 , defined by @xmath7 @xmath8.\ ] ] one can write the time derivative of the energy current as the divergence of the energy current @xmath9 with @xmath10 it thus follows that @xmath6 is precisely the sum over all sites of the local currents @xmath11 . therefore , the ground - state expectation value of @xmath6 @xmath12 becomes an order parameter indicating the presence of an energy current . once the total hamiltonian has been diagonalized , which can be done with the usual jordan - wigner and bogoliubov transformations @xmath13 the effect of the dm interaction is clearly observed at the single - particle level . the single - particle spectrum is given by @xmath14 with @xmath15 the momentum of the quasi - particle . as can be seen in the above expression and in fig.[fig : spectrum ] , the dm interaction makes the spectrum non - symmetric with respect to @xmath16 . note that the ground state of the hamiltonian including the dm interaction is the same for all values of @xmath5 in the interval @xmath17 $ ] . in particular this means that , within this range of values , the ising model in a transverse field @xmath0 and the system described by eq.[eq : ham ] have the same ground state . beyond @xmath18 ( with @xmath19 ) the fermi sea starts to be populated by the modes in between the zeros of the single particle spectrum ( i.e. between @xmath20 and @xmath21 in fig.[fig : spectrum ] ) . this implies that the ground state is not anymore that of @xmath0 . furthermore , since the dm term commutes with the rest of the hamiltonian , at the many - body level when @xmath18 we must have a level crossing between the ground state of @xmath0 and some previously excited hamiltonian eigenstates . fig.[fig : phase ] shows the phase diagram of the model @xcite . there are three regions : ferromagnetic , polarized paramagnetic , and the so - called current phase , characterized by @xmath22 . the current phase is gapless , and the two - point correlation functions show a power - law behaviour with an oscillatory amplitude : @xmath23 where @xmath24 is a non - universal function and @xmath25 @xcite . in the following , we study the entanglement properties of this model , and subsequently we analyze new quench protocols for this spin system . . we show the spectrum for 4 different values of @xmath26 , while keeping @xmath27 fixed . see also figures in @xcite . ] plane of the model in eq.[eq : ham ] . the dotted line is a critical line where the model shows the same universal properties of the quantum ising model in transverse field . see also figures in @xcite . ] in this section we show how entanglement can be used to characterize the different phases of the model . to measure the ee , we consider a bipartition of the spin chain into two subsystems a and b. for this setup a good measure of ee between the two partitions is given by the von neumann entropy @xmath28 , where @xmath29 is the ground - state reduced density matrix of the subsystem a with @xmath30 spins . it is known that for critical one - dimensional systems the ee scales logarithmically in the subsystem size , with a prefactor given by the central charge of the associated conformal field theory ( cft ) , @xmath31 where @xmath32 is the central charge and @xmath33 is a non - universal constant @xcite . on the other hand , in the non - critical region of the phase diagram , the entanglement entropy saturates to a value which depends on the correlation length @xmath34 , @xmath35 both eq.[eq : critscaling ] and eq.[eq : noncritscaling ] characterize the ground - state properties of ee for one - dimensional systems . apart from the ground state it is also of interest to investigate entanglement properties of excited states . recently , two works have appeared on this topic . in @xcite it has been shown that there are excited states for which the logarithmic scaling of ee can have prefactors different from the ground state , and that for some excited states the scaling can be extensive in the subsystem size , instead of logarithmic . in @xcite the authors have studied the connection between ee for excited states and properties of the associated cft not contained in the central charge . the ee of excited states is of interest also in the context of quantum quenches since in this setting the system is unitarily driven from the initial ground state to an excited state . the hamiltonian in eq.[eq : ham ] naturally fits in this set of problems . following the discussion from the previous section the model we are considering allows us to study the ee of some excited states of @xmath0 , simply by tuning the coupling constant associated with the dm term . the excitations we can consider in this way are characterized by the modes in between the zeros of the single particle spectrum that get populated when @xmath36 and @xmath37 ( [ eq : spectrum ] ) . for these states the ee can be evaluated analogously to the ground state of @xmath0 ( see also @xcite for related analytical study ) . vs @xmath38 at @xmath39 for different @xmath26 . the scaling behavior changes from @xmath40 on the critical line separating the ordered and disordered phase to @xmath41 inside the current - carrying phase . ] let us consider in detail the entanglement properties of the different phases shown in fig.[fig : phase ] . first , we compare the scaling of the entanglement in the non - current - carrying critical regions and in the region where an energy current is present . fig.[fig : scaling ] shows the result of the simulations for the scaling behaviour of the ground - state ee with @xmath42 and @xmath43 . for all values of @xmath44 $ ] one observes the same scaling result . in the non - current - carrying region critical states are present only on the @xmath43 line of the phase diagram . on this line , separating the ferromagnetic and polarized paramagnetic phases , the ground state of the system is the same as in @xmath0 . this implies that the ee scaling is logarithmic with a prefactor of @xmath45 , and @xmath46 . note that also the entire current - carrying phase ( @xmath47 and @xmath48 ) is gapless , and in this sense critical . at any point in this phase we observe logarithmic scaling of the ee in the subsystem size . this is consistent with the discussion in the previous section on the algebraic decay of the two point correlation function . interestingly , the prefactor of the logarithmic scaling of ee in the current phase is twice as large as the prefactor in the non - current phase . this doubling reflects the increased number of zeros in the single - particle spectrum , consistent with the results of @xcite . in fact , when @xmath47 the ground state of eq.[eq : ham ] is the filled fermi sea of modes in between @xmath49 and @xmath50 ( see fig.[fig : spectrum ] ) . since the ground - state in the current phase is effectively an excited eigenstate of @xmath0 , we could expect a scaling of ee that is extensive in the system size , as shown in @xcite for excited states . the reason why this is not the case is due to the nature of the single - particle spectrum , which at most can have two zeros ( see fig.[fig : spectrum ] ) , and thus does not satisfy the requirements found in @xcite for an extensive scaling of ee . the dm interaction in the hamiltonian affects also the sub - leading term in the scaling of ee @xmath51 . deriving the analytical form of the sub - leading order term @xmath52 is complicated . nonetheless , one can investigate this term numerically . in fig.[fig : sublead ] we see that @xmath53 is constant on the critical line @xmath43 with @xmath54 . as soon as @xmath55 and @xmath56 , @xmath53 increases , but becomes almost constant for large @xmath26 . also @xmath53 is maximum at @xmath57 , and @xmath53 is minimum at the critical point @xmath58 . from the behaviour of @xmath53 we can conclude that a given block has the highest entanglement when all the negative modes ( @xmath59 ) in the fermi sea are filled . consequently ee increases with higher values of the energy current . we now consider the differences between the critical lines shown in the phase diagram ( fig.[fig : phase ] ) , separating different phases . the only second - order quantum phase transition is found along at the @xmath43 line ( with @xmath60 ) , which corresponds to the ising quantum phase transition ( see fig . [ fig : iiqpt ] ) . on the hand the boundaries of the current - carrying phase with both the paramagnetic and the ferromagnetic phases are characterized by a level crossing . this translates into a sudden jump in ee ( see fig.[fig : iiqpt ] and fig.[fig : iqpt ] ) . the value of ee is always higher in the current carrying phase because of the presence of long - range correlations that decay algebraically . the plots in fig.[fig : iiqpt ] and fig.[fig : iqpt ] show that controlling the dm term can be used as an entanglement switch . the amount of entanglement can be driven by the dm coupling term or the magnetic field , which are controllable parameters in optical lattices @xcite . . ( upper panel ) @xmath53 vs. @xmath26 at different @xmath61 ; ( lower panel ) @xmath53 vs. @xmath61 at different @xmath26 . ] vs. @xmath61 at @xmath62 for different @xmath26 . ( upper panel ) static entanglement along the transition between the ordered ferromagnetic and the disordered paramagnetic phase . the peak signals the presence of long - range correlations at the critical point , which is a signature of a second - order quantum phase transition . ( lower panel ) static entanglement along the transition between the disordered paramagnetic and the current - carrying phase . the sudden change in entanglement followed by the absence of a peak at the critical point is a signature of the first - order quantum phase transition . ] vs. @xmath26 at @xmath62 for different @xmath61 . the plots for @xmath27 corresponds to the static entanglement along the transition between the ordered ferromagnetic and the current - carrying phase . this is a first order quantum phase transition which occurs at @xmath63 ( analogously for @xmath43 ) . the plots for @xmath64 and @xmath65 correspond to the static entanglement along the transition between the disordered and the current - carrying phase . this is a first order qpt which occurs at @xmath66 . ] in this section , we focus on the quench dynamics of the ee . quenching provides a way to excite a system , initially prepared in the ground state , and to subsequently study the non - equilibrium dynamics of the model ( in the following , we denote with a subscript @xmath67 the value of the parameters describing the initial hamiltonian ) . as stated previously , the model in eq.[eq : ham ] is of interest because it combines two different mechanisms typically used to drive a system out of equilibrium : quantum quenching , and the coupling to a field originating a current in the system . furthermore the inclusion of the dm term allows us to study a model hamiltonian where the energy current can be controlled and used in the quench protocol . in our setup , the quench can either involve the magnetic field @xmath61 , the dm coupling @xmath26 or a combination of the two . since the dm term commutes with the hamiltonian , a quench in @xmath5 leaves the system in one of its eigenstates , providing a trivial evolution of the ee . on the other hand , quenches in the magnetic field give more interesting behaviours . if the quench is done with the initial state prepared in a region with no current the results are similar to those found in @xcite , where quenches for the @xmath0 were considered . this is due to the fact that , in the absence of a current , the ground - state wave function initially is identical to that of @xmath0 , and the time evolution is not affected by the presence of the dm term ( see the derivation of eq.[eq : timecorrelation ] in the appendix for a proof of this ) . more interestingly , if the quench involves an initial state inside the current phase , new non - trivial behaviours can be expected , since the ground state now is radically different . it is important to notice that the dm coupling enters only in the specification of the initial state , whereas the evolution can be effectively described by the hamiltonian without the dm term . the calculations showing that this is in fact the case can be found in the appendix . vs. the time steps , with @xmath62 , @xmath68 , @xmath69 for different @xmath61 . note that the extent of the initial linear regime depends on the particular evolving hamiltonian . ] we first compare the evolution of the ee for different quenches inside the current - carrying phase . fixing the coupling constant of the dm term , and quenching only the external magnetic field we obtain the results shown in fig.[fig : quincurr1 ] . one always has an initial ballistic evolution of the ee , which grows linearly in time ( measured in units where the speed of the elementary excitation is unity ) and saturates at some point . quite interestingly , the saturation time ( hence also the rate at which entanglement is initially building up ) depends on the particular evolving hamiltonian . this way we can control the time needed to generate the maximal asymptotic amount of entanglement . this property is relevant also from a computational point of view . in fact , dmrg - like schemes , used for the simulation of the time evolution of quantum systems , can take advantage of the lower rate at which entanglement is generated . knowing the regions in the phase diagram where such rates are lower can provide more efficient time simulations . as far as we know this is a new feature that is not present in other quench protocols considered so far in the literature . the other aspect that is important to notice in fig.[fig : quincurr1 ] is the special role played by the line @xmath43 in the phase diagram , which turns out to provide the maximum asymptotic ee for different quench parameters . this can be understood by mapping the quench for @xmath70 to a quench protocol for @xmath0 only . as stated in the previous section , the entanglement evolution with respect to @xmath71 is identical to the evolution with respect to @xmath72 . furthermore , the ground state of @xmath73 , the initial hamiltonian in the quench protocol is also an excited eigenstate of @xmath74 , because of the commutativity of the dm term with the total hamiltonian . from this dual perspective the effect of the current is that of effectively quenching an excited eigenstate without the current term . for the ising model , a quench from @xmath75 yields the maximum value of @xmath76 when quenched to @xmath43 , because the energy gap closes at @xmath43 , and hence a large number of zero energy excitations can be produced . while the asymptotic value of ee depends on the particular excited state at the beginning of the quench . . @xmath77 vs. the time steps with @xmath62 , @xmath78 to @xmath43 for different @xmath79 . ] fig.[fig : quincurr2 ] shows results of simulations for quenches with increasing values of the dm field in the current - carrying phase . the asymptotic value of the ee decreases with increasing @xmath26 . this is consistent with the phenomenological picture provided in @xcite , and with the fact that if the system starts in an excited state , the available number of unoccupied modes that can be occupied after the quench is smaller than in the case of having the ground state as an initial state . furthermore , fig.[fig : quincurr2 ] shows that the time at which the ee saturates does not depend on @xmath5 , and consequently does not depend on the particular initial hamiltonian eigenstates ( as long as it is not an eigenstate of the evolving hamiltonian ) . the line with @xmath80 in fig.[fig : quincurr2 ] shows that very deep into the current phase quenching does not create entanglement . in fact , when @xmath81 quenching the magnetic field is just a small perturbation to the hamiltonian , which then approximately stays in the ground state . vs. the time steps inside the current - carrying phase for different block sizes @xmath38 . quenching is done from @xmath82 to @xmath39 with @xmath83 . ] finally , we verify that the presence of an energy current does not affect the extensive nature of the asymptotic value of ee ( fig.[fig : l ] ) , and its proportionality with the quench size ( fig.[fig : quenchsize ] ) . vs. the time steps for quenches to @xmath43 from various @xmath84 inside the current - carrying phase at @xmath85 . we have studied the static and dynamic properties of the entanglement entropy in the ising spin chain with a transverse field and a dzyaloshinskii - moriya interaction . the model is characterized by the presence of an energy current for certain regions of the phase diagram . concerning the static properties we have analyzed the transitions between phases with no energy current and the phase where an energy current is present . the transition is captured by a discontinuity of ee as a function of the parameters , and by a distinguishable scaling behaviour in the current - carrying and non - current - carrying regions . in particular , the leading logarithmic term of the ee scaling with respect to the system size has a prefactor in the current - carrying region which is twice as large compared to the second order ising critical line . concerning the behaviour of the entanglement evolution following a quench , the model in eq.[eq : ham ] allows us to study new quench protocols . the usual schemes consider quenches from an initial ground state . this scenario , for the model in eq . [ eq : ham ] , effectively corresponds to a quench from an initially excited state of the ising spin chain in transverse field ( without dm interaction ) . the main result of this analysis shows that the ballistic picture presented in @xcite is still valid , although with a significantly different aspect . in particular the entanglement saturation time in the current - carrying phase depends on the details of the evolving hamiltonian . this is an indication of the role played by the evolving hamiltonian on the propagation of excitations . this result is of relevance in tuning the dynamics of the system in regions with a different rate for the propagation of entanglement . furthermore it also provides a characterization of the regions in the phase diagram that can be simulated more efficiently with dmrg - like techniques . from a general point of view , the model in eq . 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j. p. keating , and f. mezzadri , commun . phys . , * 252 * 543 ( 2004 ) ; v. eisler , and z. zimbors , phys . a * 71 * , 042318 ( 2005 ) . m. greiner et al . , nature * 472 * , 307 ( 2011 ) ; k. sengupta , s. powell , and s. sachdev , phys . rev . a * 69 * , 053616 ( 2004 ) . * appendix . * in this appendix we give a detailed description of the steps involved in first evaluating the entanglement entropy of the hamiltonian in eq.[eq : ham ] , and then calculating its time evolution . after the standard sequence of jordan - wigner and bogoliubov transformations the hamiltonian is in the diagonal form @xmath86 , with @xmath87 . + the density matrix of the subsystem od size l , embedded in a system of size n , can be obtained tracing out the rest of the system @xmath88 where @xmath89 is a normalization constant and @xmath90 is a quadratic hermitian operator @xmath91 @xmath92 can be diagonalized via a generalized bogoliubov transformation . the reduced density matrix has the form @xmath93 \label{}\ ] ] using @xmath94 , we get @xmath95 . this gives the final form of the density matrix as @xmath96 defining @xmath97 , we can write @xmath98 and also @xmath99\nonumber\\ & = \pi_{q=1}^l(\frac{1+\nu_q}{2}-\nu_qd_q^\dag d_q)\nonumber\\ & = \bigotimes_{q=1}^l\rho_q.\end{aligned}\ ] ] using the fact that @xmath100 , one has for the entanglement entropy @xmath101\nonumber\\ & = -\sum_{q=1}^l(\frac{1+\nu_q}{2}\ln\frac{1+\nu_q}{2}+\frac{1-\nu_q}{2}\ln\frac{1-\nu_q}{2 } ) . \label{}\end{aligned}\ ] ] we have to calculate @xmath102 , from which we can obtain the block entropy . @xmath102 is given by the expectation value of @xmath103 and @xmath104 @xmath105 we define four @xmath106 column vector : @xmath107 , @xmath108 , @xmath109 and @xmath110 where @xmath111 , and similarly for @xmath112 . the previous bogoliubov transformations can be expressed in a compact matrix notation as @xmath113 and @xmath114 where @xmath115 and @xmath61 are l@xmath116l matrices . in terms of expectation values we have @xmath117 let us now consider a quantum quench protocol . initially the system is prepared in the ground state of an hamiltonian @xmath118 , and suddenly one of the parameters is changed , and the new hamiltonian is denoted by @xmath119 . the quasi - particle operator vector @xmath120 is associated with @xmath118 , and the vector @xmath121 is associated with @xmath119 . similarly for @xmath122 , which is associated with bare vacuum fermions . define also the matrix @xmath123 , where @xmath124 are the pauli matrices , and @xmath125 . it can be easily seen that @xmath126 , and @xmath127 , with @xmath128 a parameter of the bogoliubov transformation @xcite . from which we can write @xmath129 . when a quench takes place , the time evolution of the fermion operators is given by @xmath130 . we can write @xmath131 , where @xmath132 notice that the energy spectrum of the hamiltonian in eq.[eq : ham ] is not symmetric , which means that in general @xmath133 . in order to evaluate the two - point correlation functions we consider different cases when the initial state of the system is in the non - current - carrying region we have @xmath134 if the initial state of the system is in the current - carrying phase and @xmath135 , where @xmath136 and @xmath137 are the zeros of the spectrum then @xmath138 for @xmath139 lying between @xmath140 and @xmath141 we have @xmath142 a compact way of expressing eq.[b1 ] , eq.[b2 ] , and eq.[b3 ] is given by @xmath143 finally we can write @xmath144 notice that the above expression is the same if we consider @xmath145 , with @xmath146 the single particle spectrum of eq.[eq : ham ] , or if we consider @xmath145 , with @xmath146 the single particle spectrum of the ising hamiltonian without the dm term . this can be seen with a direct calculation . for example , one entry of the above correlation matrix is given by @xmath147 \sin{\theta_k } \sin \left(\theta'_k-\theta_k\right),\end{aligned}\ ] ] where @xmath148 and @xmath149 . the argument of @xmath150 appears only in the argument of the trigonometric function in such a way that the dm contribution is irrelevant ( see eq.[eq : spectrum ] ) . this proves that the time evolution of the correlation matrix in eq.[eq : timecorrelation ] , with respect to the ground - state of eq.[eq : ham ] , is the same as the time evolution of the correlation matrix with respect to the ising hamiltonian in transverse field , with respect to an excited state of the ising hamiltonian .

we study the ising spin chain with a dzyaloshinskii - moriya interaction focusing on the static and dynamic properties of the entanglement entropy , following a quantum quench . we show that the effects of the additional anisotropic interaction on the phase diagram and on the dynamics of the system are captured by the properties of the entanglement entropy . in particular , the model provides a way to study the quench dynamics in a system with an energy current . we consider quenches starting from an initial excited state of the ising spin chain , and we analyze the effects of different initial conditions .

the effect of the electric field on the exciton recombination energy is used to probe the properties of the electron and hole confinement in separate self - assembled quantum dots @xcite through a strong deformation of the carrier wave functions . for vertically coupled quantum dots@xcite the electric field oriented in the growth direction leads to a redistribution of the carriers between the dots.@xcite typical electric field applied for vertically coupled quantum dots is of the order of 20 - 30 kv / cm , i.e. , by an order of magnitude smaller than the one used to probe the confinement potential@xcite of a single dot . therefore , such experiments on the electric - field effect for coupled dots resolve rather the properties of the molecular coupling than the fabrication dependent details of the confinement in separate dots . moreover , the charge redistribution induced by the electric field between the different dots have naturally a much stronger energy effect than deformation of the wave functions inside each of the dots . due to these features , previous simple modeling@xcite ( done in parallel with the experimental work@xcite ) using a square well vertical and harmonic lateral confinement@xcite led to the correct description of the observed @xcite electric field induced dissociation of the electron - hole pair in an avoided crossing of dark and bright energy levels.@xcite it also successfully predicted@xcite non - trivial features of the photoluminescence spectrum observed during the negative trion dissociation by the electric field.@xcite a vertical electric field was used very recently@xcite to verify the growth process of intentionally strongly asymmetric double quantum dots . in this paper we demonstrate that the horizonal electric field ( perpendicular to the growth direction ) can be useful to estimate the non - perfect vertical alignment of the dots and to determine the direction of the horizontal shift between them . to account for the horizontal field effects we replaced the harmonic lateral profile of our previous model@xcite by a quantum well and developed a computational approach for treating excitons in systems with no axial symmetry and for an arbitrary electric field direction . the vertical electric field - induced redistribution of charge carriers is smooth only for the electron which tunnels much more effectively between the dots and is responsible for the most characteristic experimental features of the spectrum . @xcite similarly , it is the electron redistribution between the dots due to a rotation of a weak horizontal field that allows for the detection of the non - perfect alignment , the hole charge being only shifted within the separate dots . therefore , we decided to use for simplicity the single band model to describe the hole . the paper is organized as follows , section ii describes the computational approach , our numerical results are given in section iii , and section iv contains the summary and conclusions . we work in the single valence band approximation , for which the hamiltonian of the electron - hole pair is @xmath0 with @xmath1 , @xmath2 - electron and hole coordinates , @xmath3 , @xmath4 - effective band masses for the electron and the hole , @xmath5 the dielectric constant , and @xmath6 is the electric field . the electron confinement potential of the double dot system is taken in the form of a sum of double disk - shaped quantum wells with smooth walls ( see fig . [ pot ] ) @xmath7 here @xmath8 stands for the radius of a single dot , @xmath9 is half of its height , the dots centers are placed symmetrically with respect to the origin at points @xmath10 ( the spacer layer is then equal to @xmath11 ) , @xmath12 and @xmath13 are the lower and upper dot depths , respectively . for simplicity we take the same size of both dots , the inevitable asymmetry between them ( due to size difference , indium composition , nonsymmetric strain , etc . ) can for the limited purpose of the present paper be effectively taken into account by applying different depths of the dots . the confinement potential for the hole is of the same form , only with depths @xmath14 , @xmath15 replacing @xmath12 and @xmath13 . the bottom of the conduction band of the barrier material ( gaas ) is taken as the reference energy for electrons , and the top of the gaas valence band as the reference level for the holes , i.e. , the eigenvalues of ( 1 ) have to be shifted up by the gaas band gap to give the photon energy measured in a luminescence experiment . we previously@xcite demonstrated , that for an interacting electron - hole pair both the energy spectrum and the particle distribution are nearly the same when the asymmetry of the double well is exclusively introduced for one of the particles , since it is translated by the interaction into an asymmetry for the other particle . in this paper we assume that the dot situated on the negative side of the @xmath16 plane is deeper by 10 mev for both the electron and the hole @xmath17 mev , @xmath18 mev , and @xmath19 mev , @xmath20 mev is taken the same as in our previous paper@xcite assuming that the dots embedded in a pure gaas matrix are made of ga@xmath21in@xmath22as alloy with @xmath23 . accordingly@xcite we take @xmath24 , @xmath25 , and @xmath26 . the size parameters are taken from ref.@xcite , diameter @xmath27 nm and height @xmath28 nm ( therefore @xmath29 nm ) . the schroedinger equation with hamiltonian ( 1 ) is solved using the exact diagonalization ( configuration interaction ) approach keeping a complete account of the electron - hole correlation . as the basis for the electron - hole pair we take products of single - electron states and single - hole states @xmath30 where @xmath31 , @xmath32 are the single - electron and single - hole wave functions of state @xmath33 and @xmath34 , respectively . the single - particle wave functions are obtained in the multicenter basis of displaced gaussian functions , @xmath35,\end{aligned}\ ] ] where @xmath36 are the linear variational parameters , @xmath37 and @xmath38 are the nonlinear variational parameters describing the strength of @xmath39 gaussian around point @xmath40 , whose coordinates are variational parameters by themselves . we took 11 basis functions for each of the dots : one situated at the dot center @xmath41 , eight around it within the plane of confinement @xmath42 , on a circle with optimized diameter . two additional centers are placed above and below the center of each dot @xmath43 with @xmath44 optimized variationally . addition of more centers outside the plane of confinement or including more centers within it does not improve the results significantly . in the configuration basis ( 3 ) we include all the single - particle wave functions obtained in a diagonalization of the electron and the hole hamiltonians each in a basis of form ( 4 ) ( with position of centers and other nonlinear parameters optimized separately for the electron and hole ) , which eventually yields 484 _ localized _ basis functions to treat the exciton . the recombination probability for the exciton state with wave function @xmath45 is calculated from the envelope wave function as @xmath46 two - dimensional version of the multicenter basis was previously used for laterally coupled dots.@xcite our study@xcite on electron systems in a single circular dot performed with a similar technique showed that the superposition of gaussians very well approximates the angular momentum eigenstates . the effect of the unperfect alignment of the dots for the exciton stark effect due to the electric field oriented in the growth direction is presented in fig . [ h10pz ] . the figure shows the dependence of the exciton spectra on the vertically oriented electric field for the barrier thickness @xmath47 nm ( @xmath48 nm ) . for the dots aligned vertically ( a ) as well as for the offset between the axes of @xmath49 nm ( b ) and @xmath50 nm ( c ) at @xmath51 we observe two bright lines ( thickness of lines is set proportional to the recombination probability ) . the particle distribution for the bright states is displayed in fig . [ 510 ] . [ 510](a ) shows the cross section ( @xmath52 ) of the electron and hole probability density distributions ( obtained through integration of the two - particle probability density in the coordinates of the other particle ) for both the bright states at @xmath51 . we notice that in these states the hole is entirely localized in one of the dots , and the electron tends to accompany the hole . in the ground - state the electron is entirely localized in the deeper ( lower ) dot . in the excited bright state , the electron is predominantly localized in the upper dot , but a small part of the electron wave function leaks to the other ( deeper ) dot . for thinner spacer layer @xmath53 nm ( @xmath54 nm ) a leakage of the electron density to the dot without the hole appears in the ground state [ fig . [ 510](b ) ] , and in the excited state it is strengthened . note , that in the excited state the hole density maximum is displaced to the left within the upper dot following the electron density noticeably shifted to the lower dot . the vertically oriented electric field @xmath55 tends to push the electron to the upper ( shallower ) dot . in the ground state near @xmath56 kv / cm we see [ cf . [ h10pz](a - c ) ] an avoided crossing of the bright energy level with both carriers in the deeper dot with a dark energy level of separated carriers ( hole stays in the lower dot , the electron is transferred to the upper one ) . the crossing is avoided due to the electron tunnel coupling between the dots . in the upper bright state - no avoided crossing is observed for @xmath55 , the positive electric field stabilizes the electron in the upper dot . on the other hand , for the upper bright energy level , the negative electric field of smaller absolute value ( around 10 kv / cm ) is enough to transfer the electron from the upper to the lower ( deeper ) dot which results in an avoided level crossing similar to the one appearing in the ground - state [ see the upper avoided crossing at left of @xmath51 in fig . [ h10pz](a - c ) ] . we see that for the displaced axes of the dots [ figs . [ h10pz ] ( b - c ) ] the dependence of the spectra on the vertical electric field is qualitatively similar to the perfect alignment case [ fig . [ h10pz](a ) ] but with an avoided level crossings width which is smaller due to the suppressed electron tunnel coupling as the barrier thickness in increased . pronounced qualitative differences of the spectra for aligned and not aligned dots appear in case the electric field is oriented horizontally . [ h_10px](a ) shows the spectrum for perfectly aligned dots . for both the bright states ( with both carriers localized in the same dot ) the electric field separates the electron and the hole within each dot pushing the carriers at its opposite sides , which leads to a decreased recombination probability and a decreased energy . the first excited state , which is dark and twice degenerated at @xmath51 , corresponds to both carriers in the deeper dot , but with a hole excitation ( of @xmath57 type ) . the horizontal electric field lifts the degeneracy of the @xmath57 energy level of the hole . the electron ( left panel ) and the hole ( right panel ) density for @xmath56 kv / cm applied in the @xmath58 direction is shown in fig . [ 010gora ] for the ground - state and the two lowest - energy excited states with @xmath57-excitations of the hole . the plot was made in @xmath59 coordinates for the plane of confinement of the lower dot @xmath60 [ all the three states correspond to carriers totally localized in the lower dot cf . upper panels of fig . [ 510](a ) ] . the lower dark energy state with @xmath57-hole excitation has a nodal surface at the plane @xmath52 , and the parity with respect to this plane is conserved when the field is applied in the @xmath58-direction ( see the panel of fig . [ 010gora ] for the first excited state ) , hence the zero recombination probability for all @xmath61 . the other @xmath57-level , higher in energy becomes bright at larger @xmath61 , when the hole parity with respect to the direction perpendicular to the field is destroyed ( see the panel of fig . [ 010gora ] for the second excited state ) . we note that in all the three states , for @xmath56 kv / cm the electron density is not perturbed by the horizontally applied field , but its effect on the hole ( for which the confinement is weaker ) is clearly visible . for non - perfectly aligned dots the component of the electric field parallel to the direction of their relative horizontal displacement redistributes the carriers between the dots . the low - energy spectrum plot for @xmath49 nm ( @xmath62 still equal to 10 nm ) contains 4 bright energy levels denoted by 1 , 2 , 3 , and 4 in fig . [ h_10px](b ) . the modification of the carrier distribution by the electric field in these states is shown in fig . [ 5_10fp ] . in the ground state [ for @xmath51 both carriers in the lower dot - see fig . [ 510](a ) ] the electron passes to the right ( shallower ) dot near @xmath63 kv / cm . on the other hand , in the excited state which is bright at @xmath51 and marked by 2 in fig . [ h_10px ] both carriers are localized in the upper shallower dot . the electron is transferred to the left dot ( lower and deeper ) for the field around @xmath64 kv / cm . both these electron transfers ( ground state at + 60 kv / cm and excited bright state at -30 kv / cm ) are associated with avoided crossings of bright and dark energy levels . these avoided crossings become smaller for an offset of 10 nm between the axes of the dots , the case presented in fig . [ h_10px](c ) . fig . [ h8px ] shows the spectra for stronger interdot coupling ( @xmath54 nm ) . compared to @xmath48 nm case , the weak - field extrema of the energy levels are shifted more distinctly off the @xmath51 point due to a larger value of the built - in dipole moment resulting from the shift of the electron density related to the tunnel coupling [ see fig . [ 510](b ) and notice opposite shifts for the extrema of two lowest bright energy levels and much larger value of the dipole moment for the excited state ] . the dipole moment ( @xmath65 is proportional to the difference in the mean positions of the electron and the hole . the impact of the horizontal field ( @xmath58 ) on the spatial position of particles in the ground - state is plotted for @xmath54 nm in fig . [ positions ] . for perfect alignment @xmath66 [ fig . [ positions](a ) ] the field applied in @xmath58 direction does not affect the @xmath67 position of the particles , although one can notice a shallow minimum for the electron at @xmath51 . the horizontal field slightly strengthens the electron confinement within each of the dots thus enhancing the interdot vertical coupling and weakly shifting the electron towards the upper dot . [ positions](a ) shows a stronger reaction of the horizontal position of the hole than of the electron , which was already noted in the context of fig . [ 010gora ] . for non - perfect alignment [ @xmath49 nm , [ positions](b ) ] the horizontal field ( @xmath58 ) leads to a very strong dependence of the vertical positions ( @xmath67 ) of the particles . for @xmath55 the electron is transferred to the dot at right and is shifted to the top while hole is stabilized in the left dot . due to the electron tunnel coupling the electron position is continuous and a smooth function of @xmath61 . on the contrary the ground - state values of the hole position have a strong jump at @xmath68 kv / cm , where the crossing of energy levels appear in the ground - state [ cf . [ h8px](a ) ] . note that also the electron positions are modified during this jump - the electron , localized in the lower ( left ) dot tends to follow the hole when it leaves to the upper ( right ) one . [ obroty ] shows the low - energy exciton spectrum for a fixed , rather small , length of the electric field of @xmath56 kv / cm as function of the angle @xmath45 that it forms with the @xmath58 axis , @xmath69 . the upper panel of the figure corresponds to @xmath48 nm and the lower to @xmath54 nm . the plots from left to right are calculated for offsets @xmath70 and 15 nm ( for perfectly aligned dots @xmath66 the spectra are independent of @xmath45 ) . already for the smallest offset [ figs . [ obroty ] ( a - b ) ] we notice that the ground state energy is minimal when the field is oriented to the right ( @xmath71 ) , i.e. , when it tends to transfer the electron to the shallower right dot , and maximal when the field is oriented to the left ( tends to keep the electron in the deeper left dot ) . for the excited bright state ( when both carriers tend to remain in the shallower right dot ) , the energy is maximal when the field pushes the electron to the right ( reduced penetration of the electron to the other - deeper dot ) and minimal in the opposite case ( enhanced tunneling to the other dot ) . the energy dependence of the excited bright state on @xmath45 is stronger than for the ground state . this is due to the larger electron tunnel coupling for the excited state [ see fig . [ 510 ] ] . the electron is simply more willing to pass to the deeper dot . for a larger offset of @xmath49 [ obroty](c - d ) ] the dependencies of the bright energy levels on the angle @xmath45 preserve their character but become more pronounced . the electron and hole densities in the @xmath52 plane are plotted in fig . [ ffobroty ] for the two lowest - energy bright energy levels of fig . [ obroty](d ) and for opposite field orientation . they are to be compared to the @xmath51 case displayed in fig . [ 510](b ) , which shows that in the absence of the field the probability to find the electron in the upper dot for the ground state was smaller than the probability to find the electron in the lower one in the excited bright state . field of 20 kv / cm at @xmath71 ( @xmath61 oriented in @xmath58 direction ) reverses this relation , as the field shifts more of the electron to the upper dot when in the ground state and removes the electron from the lower dot when in the excited state . a shift of the hole distributions to the left and the squeeze of the distribution to the left side of the dot is also visible . for the electric field oriented along the @xmath72 direction ( @xmath73 ) the electron distribution of the carriers between the dots is similar to the @xmath51 case . for the field oriented antiparallel to the @xmath58 axis ( @xmath74 ) the electron is almost entirely localized in the left dot when in the ground state and almost completely so when in excited state . the anti - locking of the energy extrema as function of @xmath45 for the two lowest bright states observed in figs . [ obroty ] ( a - d ) at the electric field orientation matching the direction of the shift between the dots can be explained in the following way . the electric field leads to a decrease of the energy levels through the separation of the electron and hole charges [ see eq . ( 1 ) ] . in the ground state [ see fig . [ ffobroty ] ] the field at the angle @xmath71 ( @xmath75 direction ) enhances the separation stimulating the electron to leave the hole [ hence the energy minimum see fig . 9(d ) ] , and at @xmath74 ( @xmath76 direction ) prevents the electron - hole separation ( hence the maximum ) . in the excited bright state the effect of the field on the carrier separation is opposite . for the excited state the modulation of the recombination probability is more pronounced , the electron coupling and the electron switching between the dots is stronger , hence the more pronounced energy dependence on @xmath45 [ fig . 9(d ) ] . for the offset of dot axes equal to the radii @xmath50 nm figs . [ obroty](e - f ) the excited bright energy level is involved in an avoided crossing with a dark energy level . for even larger offset @xmath77 nm figs . obroty](g - h ) an avoided crossing appears also in the ground state . the appearance of these anticrossings is due to the stronger energetic effect of constant @xmath61 for increased @xmath78 . in summary , we have shown that for vertically coupled dots their non - perfect alignment does not qualitatively influence the exciton stark effect of the electric field oriented in the growth direction . although for perfectly aligned dots the horizontal electric field only deforms the electron and hole density within each of the dots , for non - perfect alignment it leads to a redistribution of the particles between the dots , i.e. , in the direction perpendicular to the field . we demonstrated that due to the relatively strong electron tunnel coupling and strong electron confinement within each of the dots the horizontal electric field can be used to tune the electron distribution in the vertical direction only weakly affecting the electron charge distribution within each of the dots . on the other hand , due to a weaker hole confinement the horizontal field distinctly affects the hole distribution within each of the dots , and the hole transfer between the dots is rapid due to negligible tunnel coupling . we have shown that a rotation of the electric field vector within the plane of confinement can be used to detect the non - perfect alignment . to determine the direction of the horizontal shift between the non - aligned dots , and to estimate the length of the shift , they can be observed from the exciton photoluminescence spectrum . fry , i.e. itskevich , d.j . mowbray , m.s . skolnick , j.j . finley , j.a . barker , e.p . oreilly , l.r . wilson , i.a . larkin , p.a . maksym , m. hopkinson , m. al - khafaji , j.p.r . david , a.g . cullis , g. hill , and j.c . clark , phys . 84 * , 733 ( 2000 ) . j.a . barker and e.p . oreilly , phys . b * 61 * , 13840 ( 2000 ) . q. xie , a. madhukar , p. chen , and n.p . kobayashi , phys . * 75 * , 2452 ( 1995 ) . krenner , m. sabahtil , e.c . clark , a. kress , d. schuh , m. bichler , g. absteiter , and j.j . finley , phys . lett . * 94 * , 057492 ( 2005 ) . stinaff , m. scheibner , a.s . bracker , i.v . pomonarev , v.l . korenev , m.e . ware , m.f . doty , t.l . reinecke , and d. gammon , science * 311 * , 636 ( 2005 ) . krenner , e.c . clark , t. nakaoka , m. bichler , c. scheurer , g. absteiter , and j.j . finley , phys . lett . * 97 * , 076403 ( 2006 ) . bracker , m. scheibner , m.f . doty , e.a . stinaff , i.v . pomonarev , j.c . kim , l.j . whitman , t.l . reinecke , and d. gammon , cond - mat/0609147 , appl . phys . lett . in print . b. szafran , t. chwiej , f. m. peeters , s. bednarek , j. adamowski , and b. partoens , phys . b * 71 * , 205316 ( 2005 ) . similar potential model was also used for the magnetic - field related avoided - crossings by y.b . lyanda - geller , t.l . reinecke , and m. bayer , phys . b * 69 * , r161308 ( 2004 ) as well as in a work for exciton complexes in the in - plane magnetic field by d. bellucci , f. troiani , g. goldoni and e. molinari , phys . rev . b * 70 * , 205332 ( 2004 ) . for a previous theoretical view on the stark effect in vertically coupled dots see w. sheng and j - p . leburton , phys . * 88 * , 167401 ( 2002 ) ; k.l . janssens , b. partoens , and f.m . peeters , phys . b * 65 * , 233301 ( 2002 ) . a couple of theoretical papers on the exciton dissociation by the electric field with results qualitatively identical to ref @xcite have appeared very recently , cf . w. chu and j.l . zhu , appl . . lett . * 89 * , 053122 ( 2006 ) and m.h . degani , g.a . farias , and p.f . farinas , appl . . lett . * 89 * , 152109 ( 2006 ) . b. szafran , f. m. peeters , and s. bednarek , phys . b * 70 * , 205318 ( 2004 ) . b. szafran , f. m. peeters , s. bednarek , and j. adamowski , phys . b * 69 * , 125344 ( 2004 ) .

we study the effect of an electric - field on an electron - hole pair in an asymmetric system of vertically coupled self - assembled quantum dots taking into account their non - perfect alignment . we show that the non - perfect alignment does not qualitatively influence the exciton stark effect for the electric field applied in the growth direction , but can be detected by application of a perpendicular electric field . we demonstrate that the direction of the shift between the axes of non - aligned dots can be detected by rotation of a weak electric field within the plane of confinement . already for a nearly perfect alignment the two - lowest energy bright exciton states possess antilocked extrema as function of the orientation angle of the horizontal field which appear when the field is parallel to the direction of the shift between the dot centers .

dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort , visual disturbance , [ 13 ] , and tears film instability with potential damage to the ocular surface . it is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface [ 4 , 5 ] . chronic exposure to cigarette smoke is harmful to ocular tissues through ischemic or oxidative mechanisms . this study aimed to investigate the relation between passive smoking and dry eye in children . this cross - sectional clinical study was carried out from june 2008 to december 2009 . we started with 300 children ( 512 years old ) presenting with eye discomfort to the ophthalmology clinics . the hospital serves patients from eastern cairo which has the same degree of social and environmental status . after exclusion of a big list of direct causes of eye discomfort ( 188 patients ) , the remaining 112 children ( 60 males and 52 females with a mean age of 7.28 1.31 for males and 7.51 1.25 years for females ) were assessed for eye dryness both clinically and by tests for tear film status . this group of children was then classified into two major groups : group 1 without eye dryness ( 32 patients ) and group 2 with eye dryness ( 80 patients ) . passive smoking was assessed in the 112 children based on history of exposure and confirmed with urinary cotinine and urinary cotinine creatinine values . exclusion criteria areactive smokers;conjunctivitis;contact lens users;history of ocular surgery in the last 6 months;systemic diseases such as diabetes mellitus and collagen disorders;those with atopy or allergic diseases;drugs as antihistaminics and atropine with its similar agents . history of ocular surgery in the last 6 months ; systemic diseases such as diabetes mellitus and collagen disorders ; those with atopy or allergic diseases ; drugs as antihistaminics and atropine with its similar agents . group 1 without eye dryness ( 32 patients ) comprised 14 patients with hypermetropia , 8 patients with astigmatism , 6 patients with emotional instability , and 4 patients with sleep disturbances . correction of the underlying cause was followed by disappearance of the eye discomfort in all cases with errors of refraction , 3 cases with emotional instability that was associated with other depressive manifestations who were referred to pediatric psychiatrist ( mother death in one patient , separation of parents in 2 patients ) , and 2 cases with sleep disturbances ( inverted sleep rhythm and short interval of sleep ) . after approval of the local ethics committee , informed consents were taken from parents or guardians of those children . all included children were subjected to detailed history taking with special emphasis on pattern and degree of exposure to smokers . past history of recurrent conjunctivitis , respiratory allergy , or infections was taken as well . detailed ocular history was taken including foreign body sensation ( sandy ) , irritation , discomfort , eye itching , and discharge . we looked at nyctalopia , hemeralopia , or xerophthalmia as signs of vitamin a deficiency . the tests were carried out in sequence , starting with tear film ( tbut ) done for three times with calculation of mean of the three readings [ 9 , 10 ] . the next test was examination of the cornea by fluorescein staining ( table 1 ) with scoring according to . this sequence of testing was adopted to minimize any error due to reflex tearing [ 9 , 10 ] . breakup time test was done by putting a fluorescein filter paper in the lower fornix and asking the patient to blink , the interval between the last complete blink and the appearance of the first corneal black spot in the stained tear film was measured three times , and the mean value of the measurements was calculated . schirmer-1 test was done without topical anaesthesia bilaterally , by the standardized strips of filter paper placed in the lateral canthus away from the cornea and left in place for 5 min with the eyes closed . a tbut value of less than 10 seconds and schirmer-1 test value of less than 5 mm were considered as abnormal . we conducted statistical analysis using the statistical package for the social sciences ( spss software , version 15 ) . quantitative variables were expressed as mean sd , and whereas qualitative variables were given as numbers and percentage . student 's t - test was used to assess the statistical significance of differences between two groups . regression analysis was done to assess the different factors that can increase the risk of dry eye . dry eye was found in 80 children among 112 ones presenting with symptoms suggestive of dryness . the present study showed that age and body mass index were not significantly different between children with dry eye and those without dryness . the passive smoking was documented in 62 male and 14 female children with an age range of 612 years ( 7.35 1.25 years ) . the nonexposed group comprised 18 male and 18 female children with an age range of 512 years ( 7.31 1.22 years ) . the number of smoked cigarettes to which the child was exposed per day and the duration of exposure of the child to passive smoking was significantly higher in children with dry eye ( 17.70 14.19 and 10.00 3.77 hours , resp . ) compared to those without ( 0.652 2.55 and 0.70 2.38 hours , resp . ) urinary cotinine and cotinine / creatinine ratio was significantly higher in children with dry eye ( 66.64 15.71 g / l and 210.17 48.36 ng / mg , resp . ) compared to those with nondry eye ( 15.03 8.11 g / l and 50.62 22.72 ng / mg , resp . ) ( p values of < 0.0001 ) ( table 2 ) . signs of vitamin deficiency were not significantly different between children with dry eye and those without ( table 3 ) . moreover , passive smoking in the males with eye dryness was more intense than in females with ccr being significantly higher in males ( 260.12 56.14 ng / mg ) than in females ( 192.56 23.45 ng / mg ) with a p value < 0.001 . dry eye score showed significant positive correlation with the number of cigarettes , duration of smoking , urinary cotinine and urinary cotinine / creatinine ratio . however , it was not significantly correlated with age or body mass index ( table 4 ) . multiregression analysis ( r of 0.827 ) showed that the most important determinants of dry eye in this study was ccr ( beta = 0.786 and p = 0.006 ) and number of cigarettes per day ( beta = 0.337 and p = 0.002 ) ( table 5 ) . the diagnosis of dry eye was confirmed in the majority of children presenting with symptoms of dry eye . dry eye disease in children can occur in association with a number of congenital , autoimmune , endocrine , and inflammatory disorders , or under certain environmental and nutritional conditions . dry eye was more commonly encountered among male children than females ( p = 0.003 ) . body mass index as a reflection of the nutritional status was not different between children with dry eye compared to those without . similarly , signs of vitamin deficiency were not significantly different between children with dry eye and those without . the urinary cotinine and cotinine / creatinine ratio made an objective validation of the history of passive smoking . the credibility of these parameters was ensured in a previous work . in the present study , 76 patients were exposed to smoking , and their passive exposure to cigarette smoking was proved by the high values of urinary cotinine and urinary cotinine / creatinine ratio . this may be attributed to the common habit that males usually join adults more frequently than female children in our community . passive smoking assessed as number of smoked cigarettes near to the child per day and the duration of exposure of the child to passive smoking as well as laboratory findings of urinary cotinine and cotinine / creatinine ratio showed higher results in children with dry eye compared to children without dry eye . moreover dry eye score had significant positive correlation with smoking parameters . the multiregression analysis showed that passive smoking represented by ccr and number of cigarettes per day was the most important determinant of eye dryness in this group of children . these results are supplemented by the work of matsumoto et al . who found that tbut was 11.95.8 seconds in active smokers and 14.95.5 in nonsmokers . moreover , they found that schirmer-1 test results were lower in smokers compared to nonsmokers . found that the mean tbut was 5.3 seconds and the mean schirmer-1 test value was 10.8 mm in active smokers , which were significantly lower than those values of nonsmokers . yoon et al . also found that tear film but and basal tear secretion in smokers were significantly lower than in nonsmokers . matsumoto et al . reported similar results . regarding the fluorescein staining score , yoon et al . , contrary to our results , found that fluorescein staining score in smokers ( 0.40 0.77 ) was not different from that of controls ( 0.38 0.80 ) . although there are no previous reports concerning relation of passive smoking to the eye dryness of children , yet many studies on adults showed that active smoking is a significant risk factor for eye dryness whether done on general population or performed as hospital - based ones [ 1723 ] . we can conclude that passive smoking is a commonly encountered risk factor of dry eye among the young children .

purpose . adult active smoking is a risk factor for dry eye . we hypothesize that passive smoking in children can also produce the same effects . methods . we included 112 school children presenting with eye discomfort . assessment of eye dryness and its severity levels depending on symptoms of dry eye , visual symptoms , tear breakup time ( tbut ) , schirmer-1 test , and corneal fluorescein staining were done for all of them . exposure to cigarette smoking was assessed by history - taking and urinary cotinine levels . results . dry eye was found in 80/112 children . passive smoking was documented in 76/112 children . number of cigarettes to which the child was exposed per day and the duration of exposure to passive smoking were significantly higher in children with dry eye compared to those without . urinary cotinine , and cotinine / creatinine ratio ( ccr ) was significantly higher in children with dry eye compared to those without dry eye . multiregression analysis showed that the most important determinants of dry eye were ccr and number of cigarettes / day . conclusion . passive smoking represents a significant risk factor of dry eye in children comparable to that shown with active adult smoking . male children are more prone to this effect .

Efforts by police to negotiate a peaceful end to a siege of a cafe in the heart of Sydney's CBD are continuing well into the night. Police said they are dealing with an armed man, who has been holding an undisclosed number of hostages at the Lindt Chocolat Cafe in Martin Place since about 9.45am. Face of terror: Suspected gunman with one of the hostages. Photo: Steven Siewert Police Commissioner Andrew Scipione told an evening media conference that police were in contact with the suspected gunman, adding that "we are only dealing with one location". Advertisement "Our plan, our only goal tonight is to get those people who are currently caught in that building, out of there," Mr Scipione said. "Rest assured, we are doing all we can to set you free." NSW Premier Mike Baird advised people who normally work in the exclusion zone around Martin Place to prepare to "work from home" on Tuesday, implying authorities are preparing for protracted negotiations. A Lindt cafe worker flees to safety. Photo: AP Mr Scipione declined to comment on a question about the lights being turned off in the cafe. He added that "police will be out there" to ensure communities were given "confidence". "Clearly, reprisal attacks are something that should not happen," Mr Scipione said. Tom Steinfort, a Channel Nine journalist tweeted a picture of a rabbi, priest and imam holding a prayer session in Lakemba, in Sydney's south-west: Two hostages run to safety outside the Lindt cafe. Photo: Mark Metcalfe/Getty Images " @tomsteinfort: An Imam,Rabbi & priest have held joint prayer session for the hostages at Lakemba Mosque #sydneysiege pic.twitter.com/auO34D9RwT — ❤Ruba Gs (@GsRuba) December 15, 2014 A group of 40 groups representing NSW's Islamic community issued a statement expressing their "utter shock and horror at the unprecedented scenes" from Martin Place. "We reject any attempt to take the innocent life of any human being, or to instill fear and terror into their hearts," the statement said. "This is a time for all Australians to stand together and support each other." The location of the cafe and its proximity to buildings of note nearby. Australians are responding to the call, taking to social media site Twitter with the hashtag, #illridewithyou to rally support for Muslim members of the community. Five hostages escape Earlier, five hostages managed to flee the cafe, hours after the gunman first holed himself up in the store and forced hostages to display an Islamic flag. A screengrab apparently showing a jihadi flag being flown inside the Lindt Chocolat Cafe. Photo: Channel Seven Police Commissioner Scipione said that he understood one of the hostages who got out subsequently went to hospital, but that was for a pre-existing condition, not a injury from today's ordeal. He declined to discuss the motive of the armed man, or whether the five who had fled had been released or had managed to escape. Police have cordoned off an exclusion zone around the building. Apart from the affected area, people should go about their usual business in the city, police said. NSW Deputy Police Commissioner Catherine Burn addresses the media on Monday afternoon. Photo: Kate Geraghty Hostages 'rotated' Earlier, Chris Reason, a journalist from Channel Seven which occupies a nearby building, said in posts to social media site Twitter that the gunman appeared to be rotating hostages, forcing them to stand against windows for as long as two hours at a time. From inside Martin Place newsroom, we've counted around 15 hostages - not 50 - mix of women, men, young, old - but no children. — Chris Reason (@ChrisReason7) December 15, 2014 Armed police at Martin Place. Photo: Daniel Munoz/Fairfax Media Mr Reason said the gunman could be seen clearly, wearing "a white shirt, black cap, unshaven, holds [possible] pump action shotgun". From inside Martin Place we can see the faces of hostages - pained, strained, eyes red and raw. One young am with head in hands — Chris Reason (@ChrisReason7) December 15, 2014 Five hostages escape Police with guns drawn in Martin Place in a screengrab. Photo: Channel Seven Deputy Police Commissioner Catherine Burn told a separate evening media conference the situation involved "negotiation" with the armed person. She said the approach was to deal with the situation "peacefully." "It might take a bit of time but that is our approach," Ms Burn said. "We will be working into the night if this situation continues and we will be looking at arrangements for tomorrow." Police have requested that media outlets do not report the gunman's demands. This article has been updated to remove earlier references to the reported demands. Crowds hurry away. Photo: Peter Rae Earlier, two female cafe workers ran from the building at about 5pm. Three men escaped about an hour earlier. The women, appeared to be aged in their 20s, ran out of the cafe a few seconds apart and into the arms of police officers. One of the two appeared to collapse as she rounded the corner from Martin Place into Elizabeth Street. They fled from an office foyer on Martin Place that adjoins the cafe. Both were wearing brown Lindt aprons. Television footage of the men showed two of them running from the front of cafe on Martin Place. A third, dressed in what appeared to be a Lindt uniform, is shown escaping out a side door on Phillip Street. A heavily armed police officer left the building after the men. Police negotiators have made contact: Burn Martin Place Siege exclusion zone Photo: NSW government At an earlier media briefing, Deputy Police Commissioner Burn confirmed three male hostages had made it out. "We do not have any information to suggest anyone has been harmed at this stage," she said. "Police negotiators have had contact and will continue to have contact." She also said police could not confirm how many people remained inside the Lindt cafe in Martin Place, but it was fewer than 30. At that earlier briefing, Ms Burn said police did not yet know why the gunman was taking the action he has. "Those motivations are not known and it would not be good to speculate," she said. "We know have numerous police working on who this person is and what those motivations might be." Lockdown Sydney's CBD has been in lockdown since the siege began at about 9.45am on a sparklingly sunny Monday morning. In extraordinary and terrifying scenes, hostages could be seen through the cafe's windows with their hands held in the air, while heavily armed police surrounded the building. A number of hostages were being forced to hold an Islamic flag against the window. The flag appears to be a Shahada flag, not an Islamic State flag, but is associated with Islamist and jihadist movements. Thousands of workers across the city were sent home early and some of the city's major buildings evacuated. They include the Opera House, the State Library, Channel Seven, the NSW parliamentary executive offices, the NSW Supreme Court's criminal courts, the Downing Centre, and several city legal chambers. An unknown number of staff and customers are being held at gunpoint inside the cafe. It was earlier reported that 20 hostages were being held. Baird, Abbott and Shorten speak NSW Premier Baird said: "We are being tested today in Sydney." "The police are being tested, the public is being tested, but whatever the test we will face it head-on and we will remain a civil, democratic society," he said. "All my thoughts and prayers are with those members of the public affected by the situation in Martin Place and the NSW Police who are trained to deal with these events." In a nationally televised address, Prime Minister Tony Abbott said he could think of "almost nothing more distressing, more terrifying than to be caught up in such a situation". "Our hearts go out to these people," he said. "We have to appreciate that, even in a society such as ours, there are people who would wish to do us harm. "Australia is a peaceful, open and generous society. Nothing should ever change that and that's why I would urge all Australians today to go about their business as usual." He said the National Security Committee of Cabinet has convened for briefings on the situation. Opposition Leader Bill Shorten said Australians were shocked "but we won't be shaken". "At times like this it is more critical than ever that the Australian community be solid, stick together and be united," he said. Blue sports bag A woman is believed to have raised the alarm at 9.44am when she saw a man outside the cafe carrying a blue sports bag with a gun inside. Just before 12.30pm, police tackled a man to the ground about 200 metres from the cafe and a police officer was seen with his foot on what appeared to be a small black handgun. However, police later said the arrest was not related to the siege. The cafe is right in the middle of the banking and retail district, and is usually packed with Christmas shoppers at this time of year. The federal government has been warning for months that a terrorist attack in Australia could happen. Channel Seven evacuated The Channel Seven newsroom, which faces Martin Place, was evacuated, along with the Macquarie Bank and Westpac offices in the area. The Martin Place studio is Seven's main newsroom and is home to breakfast show Sunrise and The Morning Show, which was on air when news of the siege broke about 9.45am. The network was originally running a live-stream of the siege, but was asked to take it down for security reasons. It is unknown if any Seven staff are among the hostages. Channel Seven has shifted its network operations to Melbourne during the siege. State Parliament, which is one block away from the cafe, has also been closed to the public, while David Jones' flagship store in the city was also evacuated. Office workers as far away as Circular Quay reported that they were being sent home just before midday. Police said office workers on Hunter, George, Elizabeth and Macquarie streets bordering Martin Place had been told to stay indoors and away from open windows. Anyone outside that area was free to leave their buildings. Trains between Central and Bondi Junction were initially stopped, but the Transport Management Centre said services resumed about 10.45am. However, Martin Place train station has been closed and trains are not stopping there. A spokesman for federal Transport Minister Warren Truss said: "The airspace over the Sydney CBD is not in shut down. There are choppers in the air and air traffic is being rerouted according. At this stage no impact on the air traffic network." The Department of Education and Communities' Safety and Security Unit has notified public schools of the hostage situation. All schools have been asked to assume "white level" lockout, which means no school group is to leave the school grounds. Journalist in shop Journalist Chris Kenny, who was in the Lindt cafe about 20 minutes before the siege began, said he understood the automatic glass sliding doors had been disabled. "I did speak to a couple of people who saw a bit more of this unfold than I did," he said. "One woman said she tried to go into the shop just after I came out with my takeaway coffee but the doors wouldn't open. "So obviously whoever is doing this has disabled the automatic glass sliding doors to stop anyone else going in and she said immediately she could see there was a weapon. "She mentioned it being taken out of a blue bag and people were straight away asked to put up their hands." A man who gave his name only as Bruno said he'd worked in the cafe for six months. "I was supposed to start at 10am," he said while visibly shaken. That was about 15 minutes after the siege started and he was unable to get inside. Ray Hadley Broadcaster Ray Hadley claimed on Monday to have spoken on the phone to one of the hostages. Hadley said on 2GB that the male hostage was "remarkably calm" when relaying information over the phone from the gunman about 1pm on Monday. Hadley said he could hear the gunman talking in the background during the phone conversation. The gunman wanted the hostage to speak live on radio, a demand that Hadley said he refused. There have since been reports that Hadley has spoken to the hostage again. In September this year, police conducted a series of major anti-terrorism raids across Sydney. Following those raids, police alleged Islamic extremists were planning to behead a person in Martin Place in Sydney's CBD. Shortly after the siege began, the US Consulate sent an "emergency message" to its citizens warning them to stay away from Martin Place. The message read: "US citizens are strongly encouraged to review your personal security plan, remain aware of your surroundings including local events, and monitor local news stations for updates. Maintain a high level of vigilance and take appropriate steps to enhance your personal security." Lawyers, courts evacuated The NSW Supreme Court's criminal courts on King Street in the CBD have been evacuated, as has have scores of staff from the NSW Crown Solicitor's office. A number of prominent barristers' chambers have also been evacuated, including the Seventh Floor Garfield Barwick Chambers in Martin Place and the Wentworth Chambers. Other legal chambers such as Sir Owen Dixon have been locked down, along with dozens of government and commercial buildings in the blocks surrounding the siege, including the Reserve Bank and the NSW Department of Transport. Some staff say they have been moved out of their offices to the "safe" side of their buildings, away from the café. A NSW Police motorcyclist was involved in an accident with another vehicle just after 11am on the Cahill Expressway, resulting in the closure of some approaches to the bridge. The motorcyclist was treated by paramedics before the road reopened a short time later. Police guns drawn. Crowds pushed further back. All unfolding directly across from 7 newsroom. Frightening. Up to dozen people inside. — Chris Kenny (@chriskkenny) December 14, 2014 Police clear Martin Place between Elizabeth and Macquarie. Customers still hands up against window - police in vests swarm - more on way. — Chris Kenny (@chriskkenny) December 14, 2014 Hold up of some kind in Lindt coffee shop. Just after I walked out. People with arms in air against window. Horrible. Stay away. — Chris Kenny (@chriskkenny) December 14, 2014 - with AAP, James Robertson, Paul Bibby, Tim Elliot, Emma Partridge and Peter Hannam ||||| Siege situation in Martin Place 7News reporter Chris Reason was relocated back to the Martin Place newsroom, the closest view of the Lindt cafe building where an unconfirmed number of hostages are being held by an alleged gunman. Reason confirmed he could see a clear view of the alleged gunman wearing a "white shirt, black cap" and that he was "unshaven, holds poss pump action shotgun." He saw the hostages being supplied with food. The faces of hostages were seen to be "pained, strained, eyes red and raw", Reason wrote, one "with head in hands". Most of the CBD remains in lockdown as police continue their operation. 7News has also learned of some of the alleged gunman's demands, however NSW Police have asked that we do not make them public at this stage. Police have allowed me back into Martin Place newsroom - gunman is clear - white shirt, black cap, unshaven, holds poss pump action shotgun — Chris Reason (@ChrisReason7) December 15, 2014 From inside Martin Place newsroom, we've counted around 15 hostages - not 50 - mix of women, men, young, old - but no children. — Chris Reason (@ChrisReason7) December 15, 2014 From inside Martin Place we can see the faces of hostages - pained, strained, eyes red and raw. One young am with head in hands — Chris Reason (@ChrisReason7) December 15, 2014 All the hostages now huddled at one end of Lindt Cafe, one is covering the window at that end with an apron — Chris Reason (@ChrisReason7) December 15, 2014 All the hostages now huddled at one end of Lindt Cafe, one is covering the window at that end with an apron Hostages have been pressed against the window of the cafe in front of horrified witnesses. Photo: 7News — Chris Reason (@ChrisReason7) December 15, 2014 ||||| They ran with terror etched in their faces, fleeing from a gunman before collapsing, tearful, shocked and relieved into the safe arms of police. For two women who fled from the siege at the Lindt cafe in the heart of Sydney their ordeal was over - as it was for three men who made their own frantic escape an hour earlier. But more people remain hostages of a shotgun-wielding man who barged into the Martin Place chocolate cafe on Monday morning, locked the doors and forced his victims to hold a black Islamic flag up to the window. Hundreds of heavily armed police continue to hold an intense security cordon around the cafe on Monday evening and central Sydney remains in lockdown as negotiators try to secure the safe release of the hostages. Nearly 12 hours into the siege, NSW Police Commissioner Andrew Scipione said the 'best negotiators in the world' were working to secure the safe release and end the ordeal. 'Our only goal tonight and for as long as this takes is to get those people that are currently caught in that building out of there safely,' he said. Police are keeping a tight lid on details of the situation and the gunman, who has forced hostages to contact media outlets and relay his demands. Commissioner Scipione said police were in communication with the gunman but refused to reveal how. 'Suffice to say we have got contact with him,' he told media. The commissioner also declined to confirm whether the five who had fled the cafe had escaped or been released. Also unconfirmed is how many people are being held hostage and whether the gunman - seen through the cafe windows wearing a black headband inscribed with white lettering - is acting alone. 'We know it's at least one,' he said. The shocking siege has turned Martin Place and surrounding streets - Sydney's government, legal and financial heart - into a ghost city with roads empty of pedestrians and travelled only by speeding police and emergency vehicles with lights flashing. A huge, highly coordinated operation is under way and Commissioner Scipione said he would commit as many police to the operation as needed. Office workers were evacuated from buildings during the day via ladders, out of windows and down fire escapes. One of the hostages to flee the siege was Lindt cafe worker Elly Chen, whose escape, caught by cameras gathered at the distant barricades, evoked an outpouring of relief from friends on her Facebook page. Another man who got out was taken to St Vincents Hospital to be treated for a pre-existing condition and was in a satisfactory condition. Lights were turned off in the cafe on Monday night. Social media has been employed by the gunman, with reports hostages have been directed to relay his demands via Facebook accounts and to contact media outlets, however police have urged the gunman to speak directly to negotiators. The gunman, who calls himself 'the brother', had reportedly demanded a flag of terrorist organisation Islamic State, made bomb threats and wants to speak with Prime Minister Tony Abbott. The siege has grabbed attention around the world with US President Barack Obama briefed and leaders from the United Kingdom, New Zealand and Canada expressing their concerns for the hostages. In a statement, Mr Abbott said he had received messages of support from a number of international leaders. 'It is a day which has tested us but so far, like Australians in all sorts of situation, we have risen to the challenge,' he said. Australia's national terror alert level was lifted to High in September just before two people were charged in raids in Sydney amid reports there was a plot to behead a member of the public in Martin Place. Mr Abbott said at the time there was no specific information behind the decision. Earlier Read below how the siege unfolded in Sydney - all times are in AEDT. Sky News will provide updates online and on Foxtel Channel 601 if the situation changes overnight and throughout Tuesday. 9.55pm &amp;amp;amp;amp;amp;nbsp; 9.15pm Here's the official map of the Martin Place exclusion zone, which will be in place tomorrow. Workers inside this area have been asked to work from home on Tuesday. 9pm Australians are taking to Twitter to head off anti-Islamic sentiment and offering to escort Muslims on public transport. They're using the hashtag #illridewithyou, which is currently trending. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 8.45pm The lights remain off inside the Lindt cafe, with police standing in darkness next to a fire door from which at least one hostage earlier escaped. 8.30pm NSW Police Commissioner Andrew Scipione and NSW Premier Mike Baird have given an update in Sydney. Mr Baird confirmed an exclusion zone will remain in place around Martin Place on Tuesday, and workers in that zone will be asked to work from home. 'I am proud of how we have responded as a city, state and nation – but my thoughts remain with those that are caught in this event,' he said. The police commissioner reiterated that police would not be discussing tactics, how the five hostages escaped or how many remain inside the cafe. 'Our only goal tonight, for as long as it takes, is to get those people that are currently caught in that building out of there safely,' he said. He said one escaped hostage had gone to hospital for a pre-existing condition, but otherwise no one had been injured. On the location of the threat, he said police were only dealing with one location at this stage. 8.20pm Australia's Muslim community has released a statement denouncing the day's events. 8.05pm &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 7.45pm Channel Seven's Chris Reason has a view into the cafe from Seven's Martin Place studio, and has been tweeting what he can see. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 7.30pm The Police Commissioner and the Premier will give an update at 8.15pm AEDT. 7.10pm A summary of the facts we have at the moment: The siege began at the Lindt Cafe in Sydney's Martin Place at about 9.44am, when members of the public called police after seeing a man with a gun enter the cafe. The siege has now been going for more than nine hours. Five hostages have escaped, but police aren't saying how many remain inside the cafe. Seven News reporter Chris Reason claims there are about 15, a mix of men and women, but no children. Hundreds of police are at the scene, with tactical officers watching the doors the hostages used to escape. Police have confirmed they are in touch with the gunman, but they aren't revealing what he has told them or what his motivations may be. A large exclusion zone remains in place in the Sydney CBD, and trains are not stopping at Martin Place station. 7pm NSW Police Deputy Commissioner Catherine Burn has updated the media on the siege, saying police are prepared to continue dealing with the situation into the night. 'Everything has to be about the safety of the people at the location.' 'The aim is a peaceful resolution.' She said the public should remain aware and vigilant, but that police focus was on Martin Place tonight. 6.30pm Prime Minister Tony Abbott has given a brief, pre-recorded statement describing the siege as 'very disturbing' and 'profoundly shocking'. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 6pm Sky News correspondent Chris Kenny describes how he narrowly missed being caught up in the siege. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 5.55pm The gunman has reportedly told hostages he has planted four bombs. He said two bombs are in the cafe and the others are elsewhere in the CBD, Network Ten reports. Network Ten says it has spoken with two hostages inside the cafe, who were hysterical as they relayed the man's demands. 5.30pm Here's the situation as of 5.30pm AEDT: Five hostages have escaped the central Sydney cafe where a gunman has been holding up to 30 hostages. Two women raced to the safety of police officers at around 5pm after three men fled the scene just over an hour earlier. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; Police believe there is only one gunman conducting the Martin Place cafe siege which started at around 10am. NSW deputy police commissioner Catherine Burn earlier said police were still trying to work out the gunman's motivation. Ms Burn said the number of hostages in the Martin Place cafe was not clear but it was fewer than 30. NSW deputy police commissioner Catherine Burn said police have established contact with the gunman. 'Police negotiators have had contact and they continue to have contact,' Ms Burn said. A heavy security cordon remains in place over a large part of the Sydney CBD with roads closed and large numbers of uniformed police and heavily armed riot and tactical officers in place. Authorities are on alert similar to a terrorist attack with an Islamic flag pressed to the window inside the Lindt chocolate cafe earlier on Monday. Prime Minister Tony Abbott has met with the national security committee of cabinet. 'We have to appreciate that even in a society such as ours, there are people who would wish to do us harm,' Mr Abbott said. 'I would urge all Australians today to go about their business as usual.' NSW Police Commissioner Andrew Scipione wouldn't confirm if it was a terrorism-related event, although he said police have moved to a 'footing' similar to dealing with a terrorist attack. Earlier on Monday, there were distressing images of cafe customers and employees with their arms in the air inside the cafe. 'We are continuing to secure and make sure we are doing all we can to bring this to a peaceful outcome,' Mr Scipione said. The flag appears to be the Shahada flag which has on it in Arabic the Islamic testimony of faith affirming belief in the oneness of God and the acceptance of Muhammad as his messenger. While it is a religiously significant flag respected by mainstream Muslims around the world, it has also been recently adopted by extremist groups such as the Al Qaeda linked al-Nusra Front which is active in Syria and Lebanon. Security agencies believe there are Australians in Syria fighting for the terrorist group. Martin Place, the heart of the Australian financial industry, has been shut down with workers stuck inside the police cordon and told not to go near the office windows. Businesses have been cleared out with Reserve Bank of Australia employees only being let out five hours after the start of the siege. Police are expected to give an update at 6.30pm AEDT. 5pm Two women have just been seen running from the building, both wearing Lindt aprons. Five hostages in total have now escaped the siege. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 4.40pm A hostage has been seen walking in front of the cafe's windows while displaying a flag with Arabic writing on it. A similar flag was held up against the cafe windows earlier in the day. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 4.05pm Dep Commissioner Burn said police had made contact with the hostage taker, but could not say exactly how many hostages remained inside. She did say it was not as high as 30. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 'We clearly are dealing with a situation that is unfolding and it's happening as we speak and the most important thing is the safety of those hostages and I wouldn't want to do anything that may impact on the safety of those hostages. 3.55pm Police have confirmed three people escaped the Lindt cafe a short time ago. Deputy Police Commissioner, Specialist Operations, Catherine Burn said the first priority was the wellbeing of the people who escaped, after which police would question them to gain more information about the situation inside the cafe. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; Police do not know how the hostages escaped, and have not revealed any further details about the gunman. A 'safety site' has been set up in Hyde Park to provide information to the public about the ongoing siege situation. 3.45pm There are reports three people have been seen running from the Lindt cafe. Armed police can be seen next to an open fire door, with weapons pointed at the front door of the cafe. 3.30pm A little more detail on that phone call from a hostage to 2GB personality Ray Hadley. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; Deputy Police Commissioner, Specialist Operations, Catherine Burn is expected to give an update shortly. 3pm The Grand Mufti of Australia has denounced the siege in a statement released a short time ago. 2.55pm 2.45pm Broadcaster Ray Hadley claims to have spoken to a hostage inside the cafe on two occasions today. Speaking on 2GB, Hadley said he had spoken to a 'remarkably calm' male hostage about 1pm AEDT, and that the hostage taker had demanded the hostage speak live on the radio, a demand Hadley refused. 'I told the hostage it would not be in his best interest or my best interest to allow that to happen because I'm not a trained negotiator, I don't have any expertise in this, there are people who will talk to both the hostages and the person holding the hostages and they will be knowing what to do,' he said. Victorian Premier Daniel Andrews has also addressed the media, saying that while there were no specific threats being monitored by Victorian police, extra officers would be on patrol in Melbourne and surrounds today. 2.30pm Here's the full press conference from the Premier and Police Commissioner from earlier this afternoon. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 2pm Speaking at a press conference in Sydney, NSW Premier Mike Baird urged Sydney residents to go about their business as usual. 'I have full confidence in the police commissioner and the NSW police – they are the world’s best,' he said. 'Be aware, be vigilant and be patient. Our thoughts and prayers are with those caught up in the situation.' The police commissioner confirmed there was 'an armed offender holding an undisclosed number of hostages'. 'We are very contained and have tight restrictions around that location. The city is still operating and will continue to operate unless we need to change that.' 'Transport arrangements are in place for people to leave the city.' He said police had yet to make contact with the hostage taker. 'My advice is that we haven’t had contact with the armed individual at this stage,' he said, but there was 'at least one' gunman inside the cafe. Police had taken a number of calls from the public, and were looking into the meaning of a flag held up against the cafe's window earlier this morning. 'At this stage we are looking into what it stands for, but it’s probably best that I don’t take that any further,' he said. 1.50pm Words of support are coming in from international leaders. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 1.45pm An update on public schools - only schools within 1km of the Sydney CBD are implementing mandatory lockouts, other schools can choose to implement a lockout if they feel it necessary. 1.40pm &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 1.20pm All public schools in NSW have been asked to assume a 'white level' lockout, which means no school group is to leave the school grounds. 1.05pm NSW Police Commissioner Andrew Scipione will address the media at 1.30pm AEDT. 1pm The Prime Minister has urged Australians to go about their business as usual. 'The ordinary business of government must go on and it will go on,' he said, adding that the mid-year financial outlook would be released today as planned. He described the scene as a 'disturbing incident' and said there were 'some indications' it was politically motivated. US President Barack Obama has reportedly been briefed on the siege. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 12.50pm There are about 200 bystanders between Martin Place and Castlereagh Street watching anxiously. Workers trapped in buildings inside the police cordon have been told to stay away from the windows. Justin Doyle, who works in a legal office inside the cordon, said colleagues were 'all very scared'. 'Police have told them to stay where they are and do as they're told,' he said. Around 11.50am, police officers placed a ladder up against a window on the first floor of an office on the Elizabeth Street side of the same building. People then began climbing out onto an awning. Martin Place is home to several prominent buildings, including NSW Premier Mike Baird's office, the Reserve Bank of Australia, Westpac Bank and the Commonwealth Bank headquarters as well as the US embassy and Network Seven. The Supreme Court, Sydney Hospital, NSW Library, NSW parliament are all located nearby. Lebanese Muslim Association President Samier Dandan says Australian Muslim leaders are meeting online now to see if the community can help. 'If there's something that the Australian Muslim community can do to assist, we are there,' he told ABC. Elsewhere, the Sydney Opera House has reopened after an earlier report of a suspicious package. 12.35pm &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; 12.30pm Opposition Leader Bill Shorten has also released a statement. 'Our thoughts and prayers today are with the innocent people involved in this morning’s incident in Martin Place, Sydney. Our thoughts are also with their families who are seeing this incredibly distressing situation unfold, along with the rest of Australia. I have full confidence in the skill and professionalism of our police and security agencies. I have spoken to Prime Minister Tony Abbott this morning and offered him the Opposition’s full support at this time. Australians can be assured that we are one when it comes to keeping Australians safe.' The Prime Minister is due to speak at a press conference in Canberra shortly. 12.20pm AAP reports a man has been arrested 200 metres from the siege scene, and may have been carrying a gun. 12.15pm &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; Midday Several sites around the CBD have now been evacuated, including: Channel Seven building at Martin Place The Opera House NSW parliamentary executive offices The State Library The NSW Supreme Court's criminal courts Sydney Airport has also confirmed there are no changes to flights, and the airspace around the airport remains open. 11.55am Statement from NSW Police: 'There is a police operation underway at Martin Place. Police and emergency services have responded and a number of streets around the area have been closed. The Martin Place train station is also shut. Police are dealing with an armed incident and specialist officers are attempting to make contact those inside a café. Some nearby offices have been evacuated as a precaution. Anyone else in the area encompassing Hunter, George, Elizabeth and Macquarie streets bordering Martin Place is directed to remain indoors and away from open windows. Anyone in the vicinity but outside that area is free to leave their buildings. Police urge members of the public to remain calm and note that an appropriate police presence is in place.' Police urge the media to be responsible in their reporting. Speculation can cause unnecessary alarm. We will attempt to keep you updated and Police will release more information when it has been confirmed. 11.40am An update on transport and road closures in Sydney as the siege continues. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; There's also been a statement released by the NSW Premier, Mike Baird: 'All my thoughts and prayers are with those members of the public affected by the situation in Martin Place and the NSW Police who are trained to deal with these events. I have spoken to Police Commissioner Andrew Scipione and have full confidence the NSW Police are working effectively to resolve the situation. I will provide further information as appropriate.' 11.30am The Prime Minister's Office has just put out a statement: 'New South Wales Police and the Australian Federal Police are currently responding to a reported hostage-taking incident in Martin Place in Sydney. I have spoken with NSW Premier Mike Baird and offered him all possible Commonwealth support and assistance. The National Security Committee of Cabinet has also convened for briefings on the situation. This is obviously a deeply concerning incident but all Australians should be reassured that our law enforcement and security agencies are well trained and equipped and are responding in a thorough and professional manner. We will provide regular updates as further information becomes available.' 11.20am The office of the Deputy Prime Minister has said the airspace above Sydney is not shut down. 'The airspace over the Sydney CBD is not shut down. There are choppers in the air and air traffic is being rerouted according. At this stage no impact on the air traffic network.' 11.15am Fairfax Media reports police are saying there has been an 'incident' at the Sydney Opera House, but no further details are available. The US Consulate has sent the following emergency message to US citizens in Australia: 'US Consulate Sydney informs US citizens of a security incident involving at least one armed person at Lindt Chocolate Café in Martin Place in Sydney. New South Wales and Australian Federal police are addressing the threat. Please avoid the area around Martin Place until further notice. 'US citizens are strongly encouraged to review your personal security plan, remain aware of your surroundings including local events, and monitor local news stations for updates. Maintain a high level of vigilance and take appropriate steps to enhance your personal security.' 11.05am Fairfax Media reports that Channel Seven's Sean Berry told ABC Radio's 702 that police have asked them not to film, so their live coverage is no longer rolling. 11am There are up to 13 hostages inside the cafe, News Corp and Channel Seven are reporting. Train services have resumed on the Eastern Suburbs and Illawarra line, but trains are not stopping at Martin Place. 10.45am There are now reports the airspace above Sydney's CBD has been shut down, and the Sydney Opera House evacuated. Earlier Workers in nearby buildings, including the Seven Network, have been ordered to evacuate the area. NSW government offices, including Premier Mike Baird's, are in the vicinity of the cafe. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;nbsp; A black flag with white writing on it, thought to be an Islamic flag, is being displayed from the window of the cafe. ||||| There were scenes of grief at the site of the Martin Place siege, as mourners hugged and consoled each other in front of hundreds of floral tributes to the hostages who lost their lives. Groups of people hugged and cried as they gathered at the site where Lindt cafe manager Tori Johnson and barrister Katrina Dawson died following the 17-hour siege. The PM visited the scene this afternoon among hundreds of mourners. (9NEWS) () Hundreds have laid flowers at the scene, including Prime Minister Tony Abbott, Police Commissioner Andrew Scipione, NSW Premier Mike Baird and Australia's most senior Muslim cleric, the Grand Mufti Dr Ibrahim Abu Mohammed. Mr Abbott visited the memorial and signed the condolence book with his wife Margaret. Aerial photos of the flowers at the memorial. (9NEWS) () In a press conference this evening, Mr Abbott described the hostages as "decent" people going about their ordinary lives. He said the nation had been thoroughly impressed with the police operation and thanked Sydney for its response to the tragedy. "Every Sydneysider can feel quietly proud of the way this city has handled one of the most difficult 36 hours in our history," he said. "Australia will always be a free and open and generous society." It is believed some were friends of the victims. (9NEWS) () Cafe manager Tori Johnson was one of the people killed in the siege. Supplied) () The Homicide Squad will investigate the three deaths after the siege, which will be treated as a critical incident. Johnson's parents Ken and Rosemary have remembered him as "their beautiful boy" in a statement released via radio host Ben Fordham. "We are so proud of our beautiful boy Tori, gone from this earth but forever in our memories as the most amazing life partner, son and brother we could ever wish for," the statement read. "We'd like to thank not only our friends and loved ones for their support, but the people of Sydney; Australia and those around the world for reaching out with their thoughts and prayers." Barrister Katrina Dawson. (Supplied) () The couple also offered their "heartfelt sorrow for the family of Katrina Dawson". Dawson, 38, died of a heart attack on the way to hospital after police stormed the cafe about 2am. Four of the hostages were staff members from the nearby Westpac bank who had dropped into the cafe for their morning coffee. Sheik Man Haron Monis has been named as the gunman. (AAP) (AAP) Night falls over Martin Place, as a captor holds hostages at gunpoint. (9NEWS) () Fordham called into 2GB this morning to tell listeners the Johnson family had requested he read out the statement on air. He said he was a "mate of a mate" of Dawson's father. Read the full statement released by Tori Johnson's family here. Five of the hostages were taken to hospital for treatment to injuries suffered during the gunfight. - A 75-year-old woman suffered a gunshot wound to the shoulder and is now in a stable condition. - A 52-year-old woman suffered a gunshot wound to the foot and is now in a stable condition. - A 43-year-old woman suffered a gunshot wound to the leg and is in a stable condition. - Two pregnant women, aged 35 and 30 respectively, were assessed for "health and welfare purposes" and are now in a stable condition. - A 39-year-old police officer, believed to be a sergeant, suffered minor facial injures from shotgun pellets. He was treated at hospital and discharged. Police Commissioner Andrew Scipione said police stormed the cafe after hearing "a number of gunshots from inside". "To the people of Sydney, this was an isolated incident… it was an act of an individual and should not change how we go about our business," Commissioner Scipione told reporters this morning. He praised the hostages for their courage during the ordeal. Sheik Man Haron Monis during one of his recent court appearances. (AAP) (AAP) "They were just buying a cup of coffee and got caught up in this affair... they were caught up in this room and needed to make hard decisions," he said. He also confirmed no explosives were found inside the building, despite some earlier reports. Two escapees from the Lindt cafe were reportedly shaken by the ordeal. (Nine) () Dawson was a well respected lawyer who worked for a firm on Phillip Street and had dropped into the cafe to grab a coffee before starting work yesterday. The NSW Bar Association has paid tribute to Dawson. "Katrina was one of our best and brightest barristers who will be greatly missed by her colleagues and friends of the NSW Bar," association president Jane Needham SC said in a statement. "She was a devoted mother of three children and a valued member of her floor and of our community." She also topped her bar exams and is the sister of well-known media barrister Sandy Dawson. Johnson had worked at the Lindt Cafe for more than two years and had reportedly worked in the service industry in the US and Australia. The dramatic events of early this morning brought to a head a siege which had paralysed the city from 10am yesterday morning when the self-styled Muslim cleric Monis took the group of 17 people hostage. Iranian-born Monis was shunned by the mainstream Muslim community for his radical views and was on bail at the time of the attack in relation to the murder of his ex-wife. He first came to the attention of police when he penned letters to the families of dead Australian soldiers seven years ago. He had also been charged with more than 50 allegations of indecent and sexual assault, reported to have occurred while he operated as "spiritual healer". The PM and his wife signed the condolences book. (9NEWS) () On Friday, his latest appeal in relation to the sending of letters to deceased Australia soldiers was dismissed by the High Court. Monis escaped jail time over the incident was sentenced to 300 hours of community service and placed on a two-year good behaviour bond in September 2013. He had been quiet for nine hours in the lead up to the storming of the building when a man sprinted from the cafe with his hands raised. After dropping to the ground he was frisked by police and taken away. Another group of five then ran out the door to safety. A bang from inside the building was heard and was quickly followed by a second loud report when a seventh hostage ran into the arms of police. Police opened the door and used live ammunition and several stun grenades. The seventh hostage was then ushered away before more gunfire erupted. NSW Premier Mike Baird has called for calm following the incident. "In the past 24 hours, this city has been shaken by a tragedy we'd never thought possible – we are a peaceful and harmonious society which is the envy of the world," he said this morning. "We must go about our useful business, we must work, we must talk to our family, we must talk to our friends. A hostage is seen going to the front door of the Lindt cafe to switch off the lights. (Getty) () "But we must come together… we are stronger together and we will get through this." It is believed 11 people escaped or were rescued, after five escaped yesterday afternoon. "What ISIL has done recently is actually claim credit for a number of these lone actor attacks even if there is no intelligence, let alone evidence, to indicate that it had a connection to these individuals," security expert Neil Fergus, who is the chief executive of Intelligent Risks, said. "It has even claimed responsibility on the internet for the attack in Melbourne involving the stabbing of two police officers and the death of the perpetrator." "So it will again try to use this type of tragic event to [spread] its message. One of the first hostages to escape raises his hands as he approaches armed police. (Getty) () "They will try to claim it is one of their terrorist events and the reality is that we've got a very disturbed criminal individual who has carried out this attack with some very murky political agenda but it will now go into the litany of these lone wolf attacks that seem to have been occurring around the globe in recent months." Police said their operation had now concluded but the matter would now be handed to the Professional Standards Command, which handle all police shootings. Forensic officers remain at the scene and it is understood Monis' body has not been removed from the building. Heavily armed police are also still at the scene and a bomb detection robot was earlier seen entering the building. The families of those being held captive had gathered at a nearby St James building earlier in the evening. After the gunfire erupted, they paced the stairs at the front of the building, as police tried to usher them inside. HOSTAGE-TAKER: Radical cleric named as siege mastermind THE FAMILIES: Anxious wait for families gathered in CBD SURVIVOR'S TALE: The horror of being taken hostage #ILLRIDEWITHYOU: Twitter campaign sprouts during siege Prime Minister Tony Abbott and his wife Margaret pay their respects. (9NEWS) () TUESDAY IN TOWN: What commuters, workers can expect today Throughout the night, hostages had been huddled in the cafe in the darkness. The gunman had earlier rotated the hostages for around two hours at a time for stints pressed against the glass windows of the shop. The gunman was reportedly "extremely agitated" after the escape of five hostages yesterday afternoon and was seen shouting at the remaining hostages. One of the hostages to flee the siege was Lindt cafe worker Elly Chen, whose escape, caught by cameramen gathered at the distant barricades, evoked an outpouring of relief from friends on her Facebook page. A male escapee was taken to St Vincents Hospital to be treated for shock and a pre-existing heart condition and was in a satisfactory condition. Social media had been employed by the gunman, with reports hostages have been directed to relay his demands via Facebook accounts and to contact media outlets, however police had urged the gunman to speak directly to negotiators. The shocking siege turned Martin Place and surrounding streets - Sydney's government, legal and financial heart - into a ghost town with roads empty of pedestrians and travelled only by speeding police and emergency vehicles with lights flashing. Office workers were evacuated from buildings during the day via ladders, out of windows and down fire escapes. Earlier, two hostages had contacted 9NEWS with demands from the gunman. The view from the air of the Martin Place memorial. (9NEWS) () 9NEWS reporter Mark Burrows says it was "upsetting in the extreme" to speak with two hostages, both women, inside the cafe this afternoon, who both contacted the station's newsroom at the demand of the gunman. Burrows said he could hear the gunman in the background "clearly ... outlining his demands", which 9NEWS refused to air in cooperation with authorities. Burrows said the first woman "sounded remarkably calm as she detailed (the gunman's) demands". She asked Burrows to pass on a message to her husband, who also remarked that his wife was "always so cool in a crisis". The second woman Burrows spoke to was "agitated" that nothing seemed to be happening, the journalist said. "She also relayed more of his demands but he (the gunman) would not come to the phone," Burrows said. "It was upsetting in the extreme to hear these women talking ... women who should be at home with their families ... who are now plunged into a deadly situation." The alarm was raised about 9.45am after onlookers reported a man with a shotgun taking hostages in the cafe. In the first hours of the siege, hostages were forced to hold what appeared to be an Islamic flag, identified as a Shahada flag, in the cafe window reading: "There is no god worthy of worship except Allah and Muhammad is his messenger." The flag is used by the group Jabhat al-Nusra - which preaches jihad and has links to terror groups ISIS and Al Qaeda. Mr Abbott condemned the act but shied away from labelling it terrorism. "He (the offender) sought to cloak his action in the symbolise of the ISIL death cult," he said. "These events do demonstrate that any country as free, as open, generous and safe as ours is vulnerable to acts of politically motivated violence. There were emotional scenes at Martin Place as hundreds paid their respects to those who died. (9NEWS) () "But we are ready to deal with these people, professionally and with the full force of the law." Australia's national terror alert level was lifted to high in September just before two people were charged in raids in Sydney amid reports there was a plot to behead a member of the public in Martin Place. Mr Abbott said at the time there was no specific information behind the decision. © Nine Digital Pty Ltd 2018 ||||| Story highlights The hostages who died are identified as Katrina Dawson and Tori Johnson All of those injured are described by police in stable condition "It will take time to clarify exactly what happened ... and why," PM says The gunman's social media postings reflect a radical Sunni extremist theology The deadly siege of a central Sydney cafe has ended but the investigation is just beginning. Australian authorities stormed the cafe where a self-styled Muslim cleric had been holding hostages early Tuesday, killing the gunman. They moved in some 16 hours after the siege began, after hearing gunfire inside the Lindt Chocolate Cafe, New South Wales police Commissioner Andrew P. Scipione told reporters. Two of the 17 hostages initially held by the gunman died, according to Scipione. They were later identified as Katrina Dawson, 38, and Tori Johnson, 34. Other people were injured, including a police officer who suffered a wound to the face from gunshot pellets. All were described by police to be in stable condition. "Understandably, there is a lot of speculation, but it will take time to clarify exactly what happened ... and why," Australian Prime Minister Tony Abbott told reporters Tuesday. Man Haron Monis. What did the gunman want? Why did he choose the cafe as his target? "There is nothing more Australian than dropping in at the local cafe for a morning coffee, and it's tragic beyond words that people going about their everyday business should have been caught up in such a horrific incident," Abbott said. He offered his condolences to people caught in the attack and to their loved ones. "These events do demonstrate that even a country as free as open as generous and as safe as ours is vulnerable to acts of politically motivated violence," the Prime Minister said. "But they also remind us that Australia, and Australians are resilient and we are ready to respond." Gunman had violent history JUST WATCHED Australian PM: Hearts go out to hostages Replay More Videos ... MUST WATCH Australian PM: Hearts go out to hostages 02:47 JUST WATCHED How the Sydney hostage siege unfolded Replay More Videos ... MUST WATCH How the Sydney hostage siege unfolded 02:38 JUST WATCHED Police: Hostage safety is our top priority Replay More Videos ... MUST WATCH Police: Hostage safety is our top priority 03:43 The gunman was identified as Man Haron Monis by an official with direct knowledge of the situation. According to his social media posts, the hostage-taker appears to have embraced a radical Sunni theology. Abbott told reporters that the gunman was already well-known to authorities, and that he had a "long history of violent crime, infatuation with extremism and mental instability." Before the raid, Monis had demanded a flag and phone call with Abbott, CNN affiliate Sky News Australia reported. He made the demands through hostages who contacted media organizations, Sky News reported. Some hostages had also reportedly posted messages to social networking sites and the YouTube online video service. Police urged media early Tuesday not to show the videos. Monis, also known as Sheikh Haron, pleaded guilty in 2013 to writing letters to relatives of Australian service members saying they were "Hitler's soldiers," according to Australian media reports. He was believed to be acting alone, and he didn't appear to be part of a broader plot, additional U.S. law enforcement and intelligence sources said. How the siege unfolded Hundreds of police officers, including snipers, surrounded the cafe in Sydney's central business district shortly after the gunman took over the building at 10 a.m. Monday (6 p.m. ET Sunday). Chilling images from Australian media showed people, believed to be hostages, with their hands pressed against the cafe's windows. They were holding up a black flag with Arabic writing on it reading, "There is no God but God and Mohammed is the prophet of God." Photos: Photos: Sydney cafe siege Photos: Photos: Sydney cafe siege Sydney cafe siege – A message of condolence is written on the pavement at Martin Place, Sydney on Wednesday, December 17. #illridewithyou became a trending hashtag on Twitter during the siege, expressing solidarity with Australian Muslims in the wake of deadly siege at the Lindt Cafe in Sydney. Hide Caption 1 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – A woman walks past flowers placed by people as a mark of respect for the victims of Martin Place siege on Tuesday, December 16. Hide Caption 2 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Members of the Muslim community show their respect at Martin Place on December 16. Hide Caption 3 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Prime Minister Tony Abbott arrives with his wife Margaret to pay their respects at Martin Place on December 16. Hide Caption 4 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Australian flags fly at half mast on Sydney Harbour Bridge on December 16 following the fatal siege. Hide Caption 5 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – An injured hostage is carried to an ambulance from a cafe in Sydney on December 16. Gunfire erupted early Tuesday as police stormed the Lindt Chocolate Cafe, where a gunman had been holding hostages since Monday morning. Hide Caption 6 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Hostages run toward police officers on December 16. Hide Caption 7 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – A police officer and a paramedic escort a hostage away from the scene of the siege on December 16. Hide Caption 8 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – An injured hostage is wheeled to an ambulance after shots were fired during the raid on the cafe. Hide Caption 9 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Two armed police officers stand ready to enter the cafe on December 16. Hide Caption 10 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – A hostage stands by the front entrance of the cafe as she turns off the lights on Monday, December 15. Hide Caption 11 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – A hostage runs toward police on December 15. She was one of five people seen fleeing the cafe. Hide Caption 12 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Police gather near the cafe on December 15. Hide Caption 13 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Hostages behind the cafe's window hold up a black flag with Arabic script on December 15. Hide Caption 14 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – A police officer listens to a radio on December 15. Hide Caption 15 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Two hostages make it to safety outside the cafe on December 15. Hide Caption 16 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – A police sniper walks to his vehicle on December 15. Hide Caption 17 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – A journalist reports on the situation in Sydney. Hide Caption 18 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Armed police are seen outside the cafe on December 15. Hide Caption 19 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – People rush past armed police near the cafe on December 15. Hide Caption 20 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Police close a street near the scene on December 15. Hide Caption 21 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Police officers talk at the scene on December 15. Hide Caption 22 of 23 Photos: Photos: Sydney cafe siege Sydney cafe siege – Armed police patrol near the Sydney Opera House. Major landmarks in Sydney were evacuated as police responded to the hostage situation. Hide Caption 23 of 23 JUST WATCHED Australian Police: We have had contact Replay More Videos ... MUST WATCH Australian Police: We have had contact 03:12 JUST WATCHED Anatomy of the Sydney hostage situation Replay More Videos ... MUST WATCH Anatomy of the Sydney hostage situation 01:57 Five hostages sprinted out of the cafe toward heavily armed police officers several hours into the standoff, sending the gunman into a tirade, according to an Australian reporter. Chris Reason, a correspondent for CNN affiliate Seven Network, said the gunman became "extremely agitated" when he realized what had happened and "started screaming orders" at the remaining hostages. Reason said he could see the gunman pacing past the cafe's windows from his vantage point at the network's nearby offices. He described the man as unshaven, wearing a white shirt and black cap and carrying a shotgun. As night fell, lights went out in the cafe, Reason reported. After a tense night, police could be seen early Tuesday throwing flash-bang grenades into the cafe in video aired by Seven Network. Gunfire erupted amid the chaos. A national security source in the United States said that a team of Australian special forces troops and police had entered the Lindt Chocolate Cafe from two directions and killed the gunman. Video captured medics working on some people and others being carried away on stretchers. On Tuesday, the hostages who died were identified as Dawson and Johnson. JUST WATCHED Remembering the victims killed in Sydney Replay More Videos ... MUST WATCH Remembering the victims killed in Sydney 01:28 "Katrina was one of our best and brightest barristers who will be greatly missed by her colleagues and friends at the NSW Bar," the New South Wales Bar Association said in a statement. "She was a devoted mother of three children and a valued member of her floor and of our bar community. Our thoughts are with her family at this time." Johnson's family also released a statement. It read, in part: "We are so proud of our beautiful boy Tori, gone from this Earth but forever in our memories as the most amazing life partner, son and brother we could ever wish for."

– Ominous developments in Sydney, where an unknown number of people are being held hostage in a chocolate shop and cafe: A gunman has contacted multiple media outlets and demanded both an ISIS flag and a phone call to Australian Prime Minister Tony Abbott, according to Sky News Australia, and the lights in the cafe have now been switched off. Five hostages have escaped, but authorities, who have been in contact with what is now believed to be a lone gunman, aren't sure how many people remain in the Lindt Chocolat Cafe, CNN reports. Witnesses say there are around 15 hostages and the gunman is forcing them to stand pressed to the cafe glass for two-hour stints, reports 9News, which has been contacted by two hostages to relay the gunman's demands. According to Ten Eyewitness News, which has also spoken to hostages, the gunman says he has planted four bombs—two in the cafe and two elsewhere in downtown Sydney. In other developments: More than 11 hours after the siege began, police say that the gunman is continuing to negotiate with them and have warned against reprisal attacks on Muslims, the Sydney Morning Herald reports. "Our plan, our only goal tonight is to get those people who are currently caught in that building out of there," New South Wales Police Commissioner Andrew Scipione told reporters. "Rest assured, we are doing all we can to set you free." Staff at 7News were able to observe the gunman from their offices. They say the gunman has what appears to be a pump-action shotgun, became "extremely agitated" when he realized five hostages had escaped, and the faces of remaining hostages appear "pained, strained, eyes red and raw." A coalition of 40 Australian Islamic groups has issued a statement expressing "utter shock and horror at the unprecedented scenes." An exclusion zone has been set up around the cafe in the heart of Sydney's central business district, and the premier of New South Wales says people who normally work there should prepare to work from home tomorrow.

Image copyright AFP Image caption A worker collects ashes after cremation. File photo The ashes of cremated Catholics cannot be kept at home, scattered or divided among family members, the Vatican has announced in new guidelines. The two-page instruction by the Vatican's department on doctrine said ashes of the dead must be kept in "sacred places" such as cemeteries. It also stressed that the Roman Catholic Church still preferred burials over cremations. The Vatican allowed cremation in 1963 but has always frowned on the practice. It also stressed at the time that cremation must not suggest a denial of faith about resurrection. Countering 'new ideas' "It is not permitted to scatter the ashes of the faithful departed in the air, on land, at sea or in some other way, nor may they be preserved in mementos, pieces of jewellery or other objects," said the instruction by the Vatican's Congregation for the Doctrine of the Faith. "These courses of action cannot be legitimised by an appeal to the sanitary, social, or economic motives that may have occasioned the choice of cremation." The Vatican said it was issuing the new guidelines to counter "new ideas contrary to the Church's faith" that had become widespread since 1963. It said the Church could not "condone attitudes or permit rites that involve erroneous ideas about death, such as considering death as the definitive annihilation of the person, or the moment of fusion with Mother Nature or the universe, or as a stage in the cycle of regeneration, or as the definitive liberation from the 'prison' of the body". The guidelines reiterated that Catholics who chose to be cremated "for reasons contrary to the Christian faith" must be denied a Christian funeral. The Vatican also stressed that "the Church continues to prefer the practice of burying the bodies of the deceased, because this shows a greater esteem towards the deceased". Pope Francis had already approved the guidelines, the Vatican said. Shortage of burial land fears - BBC's Religious Affairs correspondent Martin Bashir Fearing the impact of naturalistic ideas about the circle of life, where the body is regarded as no different to other physical matter, the Vatican has decided to clarify its position on what should happen to the remains of the dead. Cardinal Gerhard Muller, the head of the Church's powerful Congregation for the Doctrine of the Faith, said ashes of those cremated should be committed to a cemetery or another consecrated place. But Britain and some other western countries face a shortage of land in which to bury bodies. There are concerns this announcement will not only place financial burdens on Catholic families but also increase the pressure on cemeteries, half of which are expected to run out of space within the next 20 years. ||||| CONGREGATION FOR THE DOCTRINE OF THE FAITH Instruction Ad resurgendum cum Christo regarding the burial of the deceased and the conservation of the ashes in the case of cremation 1. To rise with Christ, we must die with Christ: we must “be away from the body and at home with the Lord” (2 Cor 5:8). With the Instruction Piam et Constantem of 5 July 1963, the then Holy Office established that “all necessary measures must be taken to preserve the practice of reverently burying the faithful departed”, adding however that cremation is not “opposed per se to the Christian religion” and that no longer should the sacraments and funeral rites be denied to those who have asked that they be cremated, under the condition that this choice has not been made through “a denial of Christian dogmas, the animosity of a secret society, or hatred of the Catholic religion and the Church”.[1] Later this change in ecclesiastical discipline was incorporated into the Code of Canon Law (1983) and the Code of Canons of Oriental Churches (1990). During the intervening years, the practice of cremation has notably increased in many countries, but simultaneously new ideas contrary to the Church’s faith have also become widespread. Having consulted the Congregation for Divine Worship and the Discipline of the Sacraments, the Pontifical Council for Legislative Texts and numerous Episcopal Conferences and Synods of Bishops of the Oriental Churches, the Congregation for the Doctrine of the Faith has deemed opportune the publication of a new Instruction, with the intention of underlining the doctrinal and pastoral reasons for the preference of the burial of the remains of the faithful and to set out norms pertaining to the conservation of ashes in the case of cremation. 2. The resurrection of Jesus is the culminating truth of the Christian faith, preached as an essential part of the Paschal Mystery from the very beginnings of Christianity: “For I handed on to you as of first importance what I also received: that Christ died for our sins in accordance with the scriptures; that he was buried; that he was raised on the third day in accordance with the scriptures; that he appeared to Cephas, then to the Twelve” (1 Cor 15:3-5). Through his death and resurrection, Christ freed us from sin and gave us access to a new life, “so that as Christ was raised from the dead by the glory of the Father, we too might walk in newness of life” (Rm 6:4). Furthermore, the risen Christ is the principle and source of our future resurrection: “Christ has been raised from the dead, the first fruits of those who have fallen asleep […] For as in Adam all die, so also in Christ shall all be made alive” (1 Cor 15:20-22). It is true that Christ will raise us up on the last day; but it is also true that, in a certain way, we have already risen with Christ. In Baptism, actually, we are immersed in the death and resurrection of Christ and sacramentally assimilated to him: “You were buried with him in baptism, in which you were also raised with him through faith in the power of God, who raised him from the dead” (Col 2:12). United with Christ by Baptism, we already truly participate in the life of the risen Christ (cf. Eph 2:6). Because of Christ, Christian death has a positive meaning. The Christian vision of death receives privileged expression in the liturgy of the Church: “Indeed for your faithful, Lord, life is changed not ended, and, when this earthly dwelling turns to dust, an eternal dwelling is made ready for them in heaven”.[2] By death the soul is separated from the body, but in the resurrection God will give incorruptible life to our body, transformed by reunion with our soul. In our own day also, the Church is called to proclaim her faith in the resurrection: “The confidence of Christians is the resurrection of the dead; believing this we live”.[3] 3. Following the most ancient Christian tradition, the Church insistently recommends that the bodies of the deceased be buried in cemeteries or other sacred places.[4] In memory of the death, burial and resurrection of the Lord, the mystery that illumines the Christian meaning of death,[5] burial is above all the most fitting way to express faith and hope in the resurrection of the body.[6] The Church who, as Mother, has accompanied the Christian during his earthly pilgrimage, offers to the Father, in Christ, the child of her grace, and she commits to the earth, in hope, the seed of the body that will rise in glory.[7] By burying the bodies of the faithful, the Church confirms her faith in the resurrection of the body,[8] and intends to show the great dignity of the human body as an integral part of the human person whose body forms part of their identity.[9] She cannot, therefore, condone attitudes or permit rites that involve erroneous ideas about death, such as considering death as the definitive annihilation of the person, or the moment of fusion with Mother Nature or the universe, or as a stage in the cycle of regeneration, or as the definitive liberation from the “prison” of the body. Furthermore, burial in a cemetery or another sacred place adequately corresponds to the piety and respect owed to the bodies of the faithful departed who through Baptism have become temples of the Holy Spirit and in which “as instruments and vessels the Spirit has carried out so many good works”.[10] Tobias, the just, was praised for the merits he acquired in the sight of God for having buried the dead,[11] and the Church considers the burial of dead one of the corporal works of mercy.[12] Finally, the burial of the faithful departed in cemeteries or other sacred places encourages family members and the whole Christian community to pray for and remember the dead, while at the same time fostering the veneration of martyrs and saints. Through the practice of burying the dead in cemeteries, in churches or their environs, Christian tradition has upheld the relationship between the living and the dead and has opposed any tendency to minimize, or relegate to the purely private sphere, the event of death and the meaning it has for Christians. 4. In circumstances when cremation is chosen because of sanitary, economic or social considerations, this choice must never violate the explicitly-stated or the reasonably inferable wishes of the deceased faithful. The Church raises no doctrinal objections to this practice, since cremation of the deceased’s body does not affect his or her soul, nor does it prevent God, in his omnipotence, from raising up the deceased body to new life. Thus cremation, in and of itself, objectively negates neither the Christian doctrine of the soul’s immortality nor that of the resurrection of the body.[13] The Church continues to prefer the practice of burying the bodies of the deceased, because this shows a greater esteem towards the deceased. Nevertheless, cremation is not prohibited, “unless it was chosen for reasons contrary to Christian doctrine”.[14] In the absence of motives contrary to Christian doctrine, the Church, after the celebration of the funeral rite, accompanies the choice of cremation, providing the relevant liturgical and pastoral directives, and taking particular care to avoid every form of scandal or the appearance of religious indifferentism. 5. When, for legitimate motives, cremation of the body has been chosen, the ashes of the faithful must be laid to rest in a sacred place, that is, in a cemetery or, in certain cases, in a church or an area, which has been set aside for this purpose, and so dedicated by the competent ecclesial authority. From the earliest times, Christians have desired that the faithful departed become the objects of the Christian community’s prayers and remembrance. Their tombs have become places of prayer, remembrance and reflection. The faithful departed remain part of the Church who believes “in the communion of all the faithful of Christ, those who are pilgrims on earth, the dead who are being purified, and the blessed in heaven, all together forming one Church”.[15] The reservation of the ashes of the departed in a sacred place ensures that they are not excluded from the prayers and remembrance of their family or the Christian community. It prevents the faithful departed from being forgotten, or their remains from being shown a lack of respect, which eventuality is possible, most especially once the immediately subsequent generation has too passed away. Also it prevents any unfitting or superstitious practices. 6. For the reasons given above, the conservation of the ashes of the departed in a domestic residence is not permitted. Only in grave and exceptional cases dependent on cultural conditions of a localized nature, may the Ordinary, in agreement with the Episcopal Conference or the Synod of Bishops of the Oriental Churches, concede permission for the conservation of the ashes of the departed in a domestic residence. Nonetheless, the ashes may not be divided among various family members and due respect must be maintained regarding the circumstances of such a conservation. 7. In order that every appearance of pantheism, naturalism or nihilism be avoided, it is not permitted to scatter the ashes of the faithful departed in the air, on land, at sea or in some other way, nor may they be preserved in mementos, pieces of jewelry or other objects. These courses of action cannot be legitimized by an appeal to the sanitary, social, or economic motives that may have occasioned the choice of cremation. 8. When the deceased notoriously has requested cremation and the scattering of their ashes for reasons contrary to the Christian faith, a Christian funeral must be denied to that person according to the norms of the law.[16] The Sovereign Pontiff Francis, in the Audience granted to the undersigned Cardinal Prefect on 18 March 2016, approved the present Instruction, adopted in the Ordinary Session of this Congregation on 2 March 2016, and ordered its publication. Rome, from the Offices of the Congregation for the Doctrine of the Faith, 15 August 2016, the Solemnity of the Assumption of the Blessed Virgin Mary. Gerhard Card. Müller Prefect + Luis F. Ladaria, S.I. Titular Archbishop of Thibica Secretary

– Keeping the cremated ashes of a loved one in an urn on your mantel is officially against the rules for Catholics. New guidelines from the Vatican state that ashes must never be scattered or kept by family members, but held in a "sacred place" like a cemetery, reports the BBC. This "prevents the faithful departed from being forgotten, or their remains from being shown a lack of respect," as well as "any unfitting or superstitious practices," the Catholic Church says. It adds it cannot "condone attitudes or permit rites that involve erroneous ideas about death, such as considering death as the definitive annihilation of the person … or as a stage in the cycle of regeneration." If a person requests "cremation and the scattering of their ashes for reasons contrary to the Christian faith, a Christian funeral must be denied," the Vatican adds, noting a burial is preferred "to express faith and hope in the resurrection of the body."

SECTION 1. SHORT TITLE; TABLE OF CONTENTS. (a) Short Title.--This Act may be cited as the ``Deborah Sampson Act''. (b) Table of Contents.--The table of contents for this Act is as follows: Sec. 1. Short title; table of contents. TITLE I--PEER-TO-PEER ASSISTANCE Sec. 101. Pilot program on peer-to-peer assistance for women veterans separating or newly separated from service in the Armed Forces. Sec. 102. Expansion of capabilities of Women Veterans Call Center to include text messaging. Sec. 103. Provision of reintegration and readjustment services to veterans and family members in group retreat settings. TITLE II--LEGAL AND SUPPORTIVE SERVICES Sec. 201. Department of Veterans Affairs public-private partnership on legal services for women veterans. Sec. 202. Additional amount for Supportive Services for Veteran Families grant program to support organizations that have a focus on providing assistance to women veterans and their families. TITLE III--NEWBORN CARE Sec. 301. Extension of period of eligibility for care for newborn children from the Department of Veterans Affairs. Sec. 302. Source of amounts for medically necessary travel paid by the Department of Veterans Affairs in connection with care for newborn children. TITLE IV--ELIMINATING BARRIERS TO ACCESS Sec. 401. Women Veterans Retrofit Initiative. Sec. 402. Staffing of women's health primary care providers at medical facilities of the Department of Veterans Affairs. Sec. 403. Staffing of Women Veteran Program Manager program at medical centers of the Department of Veterans Affairs. Sec. 404. Additional funding for primary care and emergency care clinicians in Women Veterans Health Care Mini-Residency Program. TITLE V--DATA COLLECTION AND REPORTING Sec. 501. Requirement for collection and analysis of data on Department of Veterans Affairs benefits and services and disaggregation of such data by sex and minority status. Sec. 502. Report on availability of prosthetics for women veterans from the Department of Veterans Affairs. Sec. 503. Requirement for Department of Veterans Affairs Internet website to provide information on services available to women veterans. Sec. 504. Sense of Congress on changing motto of Department of Veterans Affairs to be more inclusive. TITLE I--PEER-TO-PEER ASSISTANCE SEC. 101. PILOT PROGRAM ON PEER-TO-PEER ASSISTANCE FOR WOMEN VETERANS SEPARATING OR NEWLY SEPARATED FROM SERVICE IN THE ARMED FORCES. (a) Pilot Program Required.--Commencing not later than January 1, 2018, the Secretary of Veterans Affairs shall carry out a pilot program to assess the feasibility and advisability of facilitating peer-to-peer assistance for women veterans who are separating or newly separated from service in the Armed Forces. (b) Peer-to-Peer Assistance.--Peer-to-peer assistance under the pilot program shall consist of the following: (1) Provision of information about services and benefits provided under laws administered by the Secretary of Veterans Affairs. (2) Employment mentoring. (c) Duration.--The Secretary shall carry out the pilot program during the three-year period beginning on the date of the commencement of the pilot program. (d) Emphasis.--In carrying out the pilot program, the Secretary shall emphasize facilitating peer-to-peer assistance for women described in subsection (a) who suffered sexual trauma while serving in the Armed Forces, have post-traumatic stress disorder or suffer from another mental health condition, or are otherwise at risk of becoming homeless. (e) Outreach.--As part of the pilot program, the Secretary conduct a program of outreach to inform women veterans about the pilot program and the assistance available under the pilot program. (f) Coordination.-- (1) With government and community organizations.--Under the pilot program, the Secretary shall facilitate engagement and coordination with such community organizations, State and local governments, institutions of higher education, chambers of commerce, local business organizations, organizations that provide legal assistance, and other organizations as the Secretary considers appropriate to facilitate the transition of women described in subsection (a) into their communities. (2) With transition assistance program.--To the degree practicable, the Secretary shall coordinate facilitation of assistance under the pilot program with the program carried out under section 1144 of title 10, United States Code. (g) Authorization of Appropriations.-- (1) In general.--There are authorized to be appropriated to the Secretary such funds as may be necessary to carry out the pilot program. (2) Limitation.--Of the amounts appropriated under paragraph (1), the Secretary may not expend more than $100,000 on training and developing training materials for peer counselors. SEC. 102. EXPANSION OF CAPABILITIES OF WOMEN VETERANS CALL CENTER TO INCLUDE TEXT MESSAGING. The Secretary of Veterans Affairs shall expand the capabilities of the Women Veterans Call Center of the Department of Veterans Affairs to include a text messaging capability. SEC. 103. PROVISION OF REINTEGRATION AND READJUSTMENT SERVICES TO VETERANS AND FAMILY MEMBERS IN GROUP RETREAT SETTINGS. (a) In General.--Section 1712A of title 38, United States Code, is amended-- (1) in subsection (a)(1)(B)-- (A) in clause (ii), by redesignating subclauses (I) and (II) as items (aa) and (bb); (B) by redesignating clauses (i) and (ii) as subclauses (I) and (II); and (C) in the matter preceding subclause (I), as redesignated by subparagraph (B), by striking ``Counseling'' and inserting ``(i) Counseling''; and (D) by adding at the end the following new clause: ``(ii)(I) Except as provided in subclause (IV), counseling furnished to an individual under subparagraph (A) may include reintegration and readjustment services described in subclause (II) furnished in group retreat settings. ``(II) Reintegration and readjustment services described in this subclause are the following: ``(aa) Information on reintegration of the individual into family, employment, and community. ``(bb) Financial counseling. ``(cc) Occupational counseling. ``(dd) Information and counseling on stress reduction. ``(ee) Information and counseling on conflict resolution. ``(ff) Such other information and counseling as the Secretary considers appropriate to assist the individual in reintegration into family, employment, and community. ``(III) In furnishing reintegration and readjustment services under subclause (I), the Secretary shall offer women the opportunity to receive such services in group retreat settings in which the only participants are women. ``(IV) An individual referred to in subparagraph (C)(v) may receive reintegration and readjustment services under subclause (I) only if the individual receives such services with a family member described in subclause (I) or (II) of such subparagraph.''. (b) Request for Services.--Subsection (a)(2) of such section is amended-- (1) by striking ``Upon'' and inserting ``(A) Upon''; (2) by striking ``paragraph (1)(B)'' and inserting ``paragraph (1)(B)(i)''; and (3) by adding at the end the following new subparagraph: ``(B) Upon the request of an individual described in paragraph (1)(C), the Secretary shall furnish the individual reintegration and readjustment services in group retreat settings under paragraph (1)(B)(ii).''. TITLE II--LEGAL AND SUPPORTIVE SERVICES SEC. 201. DEPARTMENT OF VETERANS AFFAIRS PUBLIC-PRIVATE PARTNERSHIP ON LEGAL SERVICES FOR WOMEN VETERANS. (a) Partnership Required.--The Secretary of Veterans Affairs shall establish a partnership with at least one nongovernmental organization to provide legal services to women veterans. (b) Focus.--The focus of the partnership established under subsection (a) shall be on the 10 highest unmet needs of women veterans as set forth in the most recently completed Community Homelessness Assessment, Local Education and Networking Groups for Veterans (CHALENG for Veterans) survey. SEC. 202. ADDITIONAL AMOUNT FOR SUPPORTIVE SERVICES FOR VETERAN FAMILIES GRANT PROGRAM TO SUPPORT ORGANIZATIONS THAT HAVE A FOCUS ON PROVIDING ASSISTANCE TO WOMEN VETERANS AND THEIR FAMILIES. Section 2044(e) of title 38, United States Code, is amended-- (1) in paragraph (1)-- (A) in subparagraph (E), by striking ``2017'' and inserting ``2016''; and (B) by adding at the end the following new subparagraph: ``(F) $340,000,000 for each of fiscal years 2017 and 2018.''; and (2) by adding at the end the following new paragraph: ``(4) Not less than $20,000,000 shall be available under paragraph (1)(F) for the provision of financial assistance under subsection (a) to organizations that have a focus on providing assistance to women veterans and their families.''. TITLE III--NEWBORN CARE SEC. 301. EXTENSION OF PERIOD OF ELIGIBILITY FOR CARE FOR NEWBORN CHILDREN FROM THE DEPARTMENT OF VETERANS AFFAIRS. Section 1786(a) of title 38, United States Code, is amended, in the matter preceding paragraph (1), by striking ``seven days'' and inserting ``14 days''. SEC. 302. SOURCE OF AMOUNTS FOR MEDICALLY NECESSARY TRAVEL PAID BY THE DEPARTMENT OF VETERANS AFFAIRS IN CONNECTION WITH CARE FOR NEWBORN CHILDREN. Section 1786 of title 38, United States Code, is amended by adding at the end the following new subsection: ``(c) Source of Amounts for Travel.--Amounts paid by the Department for medically necessary travel in connection with health care services furnished under this section shall be derived from the Medical Services appropriations account of the Department.''. TITLE IV--ELIMINATING BARRIERS TO ACCESS SEC. 401. WOMEN VETERANS RETROFIT INITIATIVE. (a) In General.--The Secretary of Veterans Affairs shall retrofit existing medical facilities of the Department of Veterans Affairs with fixtures, materials, and other outfitting measures to support the provision of care to women veterans at such facilities. (b) Plan.--Not later than 180 days after the date of the enactment of this Act, the Secretary shall submit to the Committee on Veterans' Affairs of the Senate and the Committee on Veterans' Affairs of the House of Representatives a plan to address deficiencies in environment of care for women veterans at medical facilities of the Department. (c) Authorization of Appropriations.--There is authorized to be appropriated to the Secretary $20,000,000 to carry out subsection (a) in addition to amounts otherwise made available to the Secretary for the purposes set forth in such subsection. SEC. 402. STAFFING OF WOMEN'S HEALTH PRIMARY CARE PROVIDERS AT MEDICAL FACILITIES OF THE DEPARTMENT OF VETERANS AFFAIRS. The Secretary of Veterans Affairs shall ensure that each medical facility of the Department of Veterans Affairs has not fewer than one full-time or part-time women's health primary care provider whose duties include, to the extent possible, providing training to other health care providers of the Department on the needs of women veterans. SEC. 403. STAFFING OF WOMEN VETERAN PROGRAM MANAGER PROGRAM AT MEDICAL CENTERS OF THE DEPARTMENT OF VETERANS AFFAIRS. (a) In General.--The Secretary of Veterans Affairs shall ensure that the Women Veteran Program Manager program of the Department of Veterans Affairs is supported at each medical center of the Department with a Women Veteran Program Manager and a Women Veteran Program Ombudsman. (b) Training.--The Secretary shall ensure that the staff required under subsection (a) receive the proper training to carry out their duties. SEC. 404. ADDITIONAL FUNDING FOR PRIMARY CARE AND EMERGENCY CARE CLINICIANS IN WOMEN VETERANS HEALTH CARE MINI-RESIDENCY PROGRAM. (a) In General.--There is authorized to be appropriated to the Secretary of Veterans Affairs $1,000,000 for each fiscal year for the Women Veterans Health Care Mini-Residency Program of the Department of Veterans Affairs to provide opportunities for participation in such program for primary care and emergency care clinicians. (b) Treatment of Amounts.--The amounts authorized to be appropriated under subsection (a) shall be in addition to amounts otherwise made available to the Secretary for the purposes set forth in such subsection. TITLE V--DATA COLLECTION AND REPORTING SEC. 501. REQUIREMENT FOR COLLECTION AND ANALYSIS OF DATA ON DEPARTMENT OF VETERANS AFFAIRS BENEFITS AND SERVICES AND DISAGGREGATION OF SUCH DATA BY SEX AND MINORITY STATUS. The Secretary of Veterans Affairs shall-- (1) collect and analyze data on each program of the Department of Veterans Affairs that provides a service or benefit to a veteran, including the program carried out under section 1144 of title 10, United States Code; (2) disaggregate such data by sex and minority status, when the data lends itself to such disaggregation; and (3) publish the data collected and analyzed under paragraph (1), except for such cases in which the Secretary determines that some portions of the data would undermine the anonymity of a veteran. SEC. 502. REPORT ON AVAILABILITY OF PROSTHETICS FOR WOMEN VETERANS FROM THE DEPARTMENT OF VETERANS AFFAIRS. Not later than one year after the date of the enactment of this Act, the Secretary of Veterans Affairs shall submit to the Committee on Veterans' Affairs of the Senate and the Committee on Veterans' Affairs of the House of Representatives a report on the availability from the Department of Veterans Affairs of prosthetics made for women veterans, including an assessment of the availability of such prosthetics at each medical facility of the Department. SEC. 503. REQUIREMENT FOR DEPARTMENT OF VETERANS AFFAIRS INTERNET WEBSITE TO PROVIDE INFORMATION ON SERVICES AVAILABLE TO WOMEN VETERANS. (a) In General.--The Secretary of Veterans Affairs shall survey the Internet websites and information resources of the Department of Veterans Affairs in effect on the day before the date of the enactment of this Act and publish an Internet website that serves as a centralized source for the provision to women veterans of information about the benefits and services available to them under laws administered by the Secretary. (b) Elements.--The Internet website published under subsection (a) shall provide to women veterans information regarding all of the services available in the district in which that the veteran is seeking such services, including, with respect to each medical center and community-based outpatient clinic in the applicable Veterans Integrated Service Network-- (1) the name and contact information of each women's health coordinator; (2) a list of appropriate staff for other benefits available from the Veterans Benefits Administration, the National Cemetery Administration, and such other entities as the Secretary considers appropriate; and (3) such other information as the Secretary considers appropriate. (c) Updated Information.--The Secretary shall ensure that the information described in subsection (b) that is published on the Internet website required by subsection (a) is updated not less frequently than once every 90 days. (d) Outreach.--In carrying out this section, the Secretary shall ensure that the outreach conducted under section 1720F(i) of title 38, United States Code, includes information regarding the Internet website required by subsection (a). (e) Derivation of Funds.--Amounts used by the Secretary to carry out this section shall be derived from amounts made available to the Secretary to publish Internet websites of the Department. SEC. 504. SENSE OF CONGRESS ON CHANGING MOTTO OF DEPARTMENT OF VETERANS AFFAIRS TO BE MORE INCLUSIVE. In is the sense of Congress that the Secretary of Veterans Affairs should change the motto of the Department of Veterans Affairs to be more inclusive.

Deborah Sampson Act This bill directs the Department of Veterans Affairs (VA) to carry out a three-year pilot program to assess the feasibility of peer-to-peer assistance for women veterans who are separating or newly separated from the Armed Forces), with emphasis placed on women who suffered service-related sexual trauma or who are at risk of becoming homeless. Additionally, the VA shall: expand the women veterans call center to include a text messaging capability; establish a partnership with at least one nongovernmental organization to provide legal services to women veterans based upon their 10 highest unmet needs; retrofit VA medical facilities with fixtures, materials, and other outfitting measures to support the care of women veterans; ensure that each VA medical facility has at least one full-time or part-time women's health primary care provider; expand to 14 days VA post-delivery care services for women veterans who are receiving maternity care in a VA or VA-contracted facility; ensure that the women veteran manager program is supported at each VA medical center with a program manager and an ombudsman; collect, analyze, and publish data on each VA service or benefit program and disaggregate such data by sex and minority status; and publish an Internet website that serves as a centralized information source for women veterans' benefits and services. The bill makes funds available for: (1) primary care and emergency care clinicians' participation in the women veterans health care mini-residency program, and (2) organizations that focus on providing assistance to women veterans and their families. The bill: (1) provides for reintegration and readjustment services to veterans and family members in group retreat settings, and (2) expresses the sense of Congress that the VA's motto should be more inclusive.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Medicare Prescription Drug Improvement Act''. TITLE I--IMPROVEMENT OF MEDICARE PRESCRIPTION DRUG BENEFITS SEC. 101. PERMITTING THE NEGOTIATION OF FAIR PRICES FOR MEDICARE PRESCRIPTION DRUGS ON BEHALF OF MEDICARE BENEFICIARIES. Section 1860D-11 of the Social Security Act, as added by section 101(a) of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (Public Law 108-173), is amended by striking subsection (i) (relating to noninterference) and by inserting the following: ``(i) Authority to Negotiate Prices With Manufacturers.--In order to ensure that beneficiaries enrolled under prescription drug plans, MA-PD plans, and qualified retiree prescription drug plans pay the lowest possible price, the Secretary shall have authority similar to that of the Secretary of Veterans Affairs, Secretary of Defense, and the heads of other Federal agencies and departments that purchase prescription drugs in bulk to negotiate contracts with manufacturers of covered part D drugs, consistent with the requirements and in furtherance of the goals of providing quality care and containing costs under this part.''. SEC. 102. ELIMINATION OF GAP IN COVERAGE OF PRESCRIPTION DRUG BENEFITS. (a) In General.--Section 1860D-2(b) of the Social Security Act (42 U.S.C. 1395w-102(b)), as added by section 101(a) of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (Public Law 108-173), is amended by striking paragraph (3) and inserting the following: ``(3) Repealed.''. (b) Conforming Amendments.-- (1) Section 1860D-2 of the Social Security Act (42 U.S.C. 1395w-102) is amended-- (A) in subsection (a)(2)(A)(i)(I), by striking ``, or an increase in the initial coverage limit with respect to covered part D drugs''; (B) in subsection (b)(2)(A), by striking ``and up to the initial coverage limit under paragraph (3)''; (C) in subsection (b)(4)(C)(i)-- (i) by striking the comma after ``paragraph (1)'' and inserting ``and''; and (ii) by striking ``, and for amounts for which benefits are not provided because of the application of the initial coverage limit described in paragraph (3)''; (D) in subsection (c)(1), by striking subparagraph (C); and (E) in subsection (d)(1)(A), by striking ``or an initial coverage limit (described in subsection (b)(3))''. (2) Section 1860D-4(a)(4)(B) of such Act (42 U.S.C. 1395w- 104(a)(4)(B)) is amended to read as follows: ``(B) when prescription drug benefits are provided under this part, a notice of the benefits in relation to the annual out-of-pocket threshold for the current year.''. (3)(A) Section 1860D-14(a) of such Act (42 U.S.C. 1395w- 114(a)) is amended-- (i) in paragraph (1), by striking subparagraph (C) and redesignating subparagraphs (D) and (E) as subparagraphs (C) and (D), respectively; (ii) in paragraph (2), by striking subparagraph (C) and redesignating subparagraphs (D) and (E) as subparagraphs (C) and (D), respectively; and (iii) in paragraph (4)(A) in the matter preceding clause (i), by striking ``paragraph (1)(D)(ii)'' and inserting ``paragraph (1)(C)(ii)''. (B) Section 1860D-14(c)(1) of such Act (42 U.S.C. 1395w- 114(c)(1)) is amended in the second sentence by striking ``subsections (a)(1)(D) and (a)(2)(E)'' and inserting ``subsections (a)(1)(C) and (a)(2)(D)''. (C) Section 1860D-15(e)(1)(B) of such Act (42 U.S.C. 1395w- 115(e)(1)(B)) is amended by striking ``paragraphs (1)(D) and (2)(E)'' and inserting ``paragraphs (1)(C) and (2)(D)''. (4)(A) Section 1860D-41(a)(6) of such Act (42 U.S.C. 1395w- 151(a)(6)) is amended by striking paragraph (6) and redesignating paragraphs (7) through (18) as paragraphs (6) through (17), respectively. (B) Section 1860D-1(a)(1)(A) of such Act (42 U.S.C. 1395w- 101(a)(1)(A)) is amended by striking ``1860D-41(a)(14)'' and inserting ``1860D-41(a)(13)''. (c) Effective Date.--The amendments made by this section shall take effect as if included in the enactment of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (Public law 108-173). TITLE II--IMPORTATION OF PRESCRIPTION DRUGS SEC. 201. SHORT TITLE. This title may be cited as the ``Pharmaceutical Market Access Act of 2004''. SEC. 202. IMPORTATION OF PRESCRIPTION DRUGS. (a) Nullification of Certain Amendments Made by Public Law 108- 173.--The Federal Food, Drug, and Cosmetic Act is amended-- (1) in section 804 (21 U.S.C. 384), by amending the section to read as if section 1121(a) of Public Law 108-173 had not been enacted; (2) in section 301 (21 U.S.C. 331), by amending the section to read as if section 1121(b)(1) of Public Law 108-173 had not been enacted; and (3) in section 303 (21 U.S.C. 333), by amending the section to read as if section 1121(b)(2) of Public Law 108-173 had not been enacted. (b) Importation of Prescription Drugs.--Section 804 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 384), as amended by subsection (a)(1) of this section, is amended-- (1) in subsection (a)-- (A) by striking ``The Secretary'' and inserting ``Not later than 180 days after the date of the enactment of the Pharmaceutical Market Access Act of 2003, the Secretary''; and (B) by striking ``pharmacists and wholesalers'' and inserting ``pharmacists, wholesalers, and qualifying individuals''; (2) in subsection (b)-- (A) by amending paragraph (1) to read as follows: ``(1) require that each covered product imported pursuant to such subsection complies with sections 501, 502, and 505, and other applicable requirements of this Act; and''; (B) in paragraph (2), by striking ``, including subsection (d); and'' and inserting a period; and (C) by striking paragraph (3); (3) in subsection (c), by inserting ``by pharmacists and wholesalers (but not qualifying individuals)'' after ``importation of covered products''; (4) in subsection (d)-- (A) by striking paragraphs (3) and (10); (B) in paragraph (5), by striking ``, including the professional license number of the importer, if any''; (C) in paragraph (6)-- (i) in subparagraph (C), by inserting ``(if required under subsection (e))'' before the period; (ii) in subparagraph (D), by inserting ``(if required under subsection (e))'' before the period; and (iii) in subparagraph (E), by striking ``labeling''; (D) in paragraph (7)-- (i) in subparagraph (A), by inserting ``(if required under subsection (e))'' before the period; and (ii) by amending subparagraph (B) to read as follows: ``(B) Certification from the importer or manufacturer of such product that the product meets all requirements of this Act.''; and (E) by redesignating paragraphs (4) through (9) as paragraphs (3) through (8), respectively; (5) by amending subsection (e) to read as follows: ``(e) Testing.-- ``(1) In general.--Subject to paragraph (2), regulations under subsection (a) shall require that testing referred to in paragraphs (5) through (7) of subsection (d) be conducted by the importer of the covered product, unless the covered product is a prescription drug subject to the requirements of section 505C for counterfeit-resistant technologies. ``(2) Exception.--The testing requirements of paragraphs (5) through (7) of subsection (d) shall not apply to an importer unless the importer is a wholesaler.''; (6) in subsection (f), by striking ``or designated by the Secretary, subject to such limitations as the Secretary determines to be appropriate to protect the public health''; (7) in subsection (g)-- (A) by striking ``counterfeit or''; and (B) by striking ``and the Secretary determines that the public is adequately protected from counterfeit and violative covered products being imported pursuant to subsection (a)''; (8) in subsection (i)(1)-- (A) by amending subparagraph (A) to read as follows: ``(A) In general.--The Secretary shall conduct, or contract with an entity to conduct, a study on the imports permitted pursuant to subsection (a), including consideration of the information received under subsection (d). In conducting such study, the Secretary or entity shall evaluate the compliance of importers with regulations under subsection (a), and the incidence of shipments pursuant to such subsection, if any, that have been determined to be misbranded or adulterated, and determine how such compliance contrasts with the incidence of shipments of prescription drugs transported within the United States that have been determined to be misbranded or adulterated.''; and (B) in subparagraph (B), by striking ``Not later than 2 years after the effective date of final regulations under subsection (a),'' and inserting ``Not later than 18 months after the date of the enactment of the Pharmaceutical Market Access Act of 2003,''; (9) in subsection (k)(2)-- (A) by redesignating subparagraphs (D) and (E) as subparagraphs (E) and (F), respectively; and (B) by inserting after subparagraph (C) the following: ``(D) The term `qualifying individual' means an individual who is not a pharmacist or a wholesaler.''; and (10) by striking subsections (l) and (m). SEC. 203. USE OF COUNTERFEIT-RESISTANT TECHNOLOGIES TO PREVENT COUNTERFEITING. (a) Misbranding.--Section 502 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 352; deeming drugs and devices to be misbranded) is amended by adding at the end the following: ``(w) If it is a drug subject to section 503(b), unless the packaging of such drug complies with the requirements of section 505C for counterfeit-resistant technologies.''. (b) Requirements.--Title V of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351 et seq.) is amended by inserting after section 505B the following: ``SEC. 505C. COUNTERFEIT-RESISTANT TECHNOLOGIES. ``(a) Incorporation of Counterfeit-Resistant Technologies Into Prescription Drug Packaging.--The Secretary shall require that the packaging of any drug subject to section 503(b) incorporate-- ``(1) overt optically variable counterfeit-resistant technologies that are described in subsection (b) and comply with the standards of subsection (c); or ``(2) technologies that have an equivalent function of security, as determined by the Secretary. ``(b) Eligible Technologies.--Technologies described in this subsection-- ``(1) shall be visible to the naked eye, providing for visual identification of product authenticity without the need for readers, microscopes, lighting devices, or scanners; ``(2) shall be similar to that used by the Bureau of Engraving and Printing to secure United States currency; ``(3) shall be manufactured and distributed in a highly secure, tightly controlled environment; and ``(4) should incorporate additional layers of non-visible covert security features up to and including forensic capability. ``(c) Standards for Packaging.-- ``(1) Multiple elements.--For the purpose of making it more difficult to counterfeit the packaging of drugs subject to section 503(b), manufacturers of the drugs shall incorporate the technologies described in subsection (b) into multiple elements of the physical packaging of the drugs, including blister packs, shrink wrap, package labels, package seals, bottles, and boxes. ``(2) Labeling of shipping container.--Shipments of drugs described in subsection (a) shall include a label on the shipping container that incorporates the technologies described in subsection (b), so that officials inspecting the packages will be able to determine the authenticity of the shipment. Chain of custody procedures shall apply to such labels and shall include procedures applicable to contractual agreements for the use and distribution of the labels, methods to audit the use of the labels, and database access for the relevant governmental agencies for audit or verification of the use and distribution of the labels.''.

Medicare Prescription Drug Improvement Act - Amends title XVIII (Medicare) of the Social Security Act to repeal provisions prohibiting the Secretary of Health and Human Services from interfering with the negotiations between drug manufacturers and pharmacies and prescription drug plan sponsors. Grants the Secretary authority similar to that of the Secretary of Veterans Affairs, Secretary of Defense, and the heads of other Federal agencies and departments that purchase prescription drugs in bulk to negotiate contracts with manufacturers of covered Medicare part D (Voluntary Prescription Drug Benefit Program) drugs. Eliminates the initial coverage limit on the maximum costs that may be recognized for payment purposes (including the annual deductible) with respect to prescription drug benefits. Pharmaceutical Market Access Act of 2004 - Amends the Federal Food, Drug and Cosmetic Act to: (1) repeal certain sections of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 relating to importation of prescription drugs from Canada. and (2) restore previous law. Amends such restored law to direct the Secretary to promulgate regulations allowing qualifying individuals (in addition to pharmacists and wholesalers) to import covered products. Repeals the mandate that the Secretary require that a foreign seller specify the original source of the product and the amount of each lot of the product originally received. Amends provisions regarding the testing of imported covered products. Declares that specified tests shall not be required unless the importer is a wholesaler. Requires such tests to be conducted by the importer-wholesaler unless a product is a prescription drug subject to the provisions of this Act pertaining to counterfeit-resistant packaging. Classifies prescription drugs as misbranded if they do not incorporate specified counterfeit-resistant technologies in packaging. Directs the Secretary to require that the packaging of any subject drug incorporate specified overt optically variable counterfeit-resistant technologies.

over the past decades , the syntheses of superheavy elements and their lifetime measurement have been explored with a variety of methods . the heavy elements with @xmath4 have been successfully synthesized at gsi @xcite . elements along with @xmath5 have been produced at jinr - flnr , dubna @xcite . last year , two isotopes of a new element with atomic number @xmath6 were synthesized in the fusion reactions between @xmath7ca projectiles and radioactive @xmath8bk target nuclei whose @xmath0 chains terminated by spontaneous fission was observed in dubna @xcite , which fills the gap between the elements 116 and 118 . the element 114 was independently confirmed recently by the lbnl in the usa @xcite and gsi @xcite . a superheavy element isotope @xmath9 was observed in lbnl last year @xcite , and an isotope of @xmath10 has been identified at riken , japan @xcite . thus up to now superheavy elements with @xmath11 have been synthesized in experiment and consequently they offer the possibility to study the heaviest known nuclei with greater detail . however , their is no consensus among theorists with regard to what should be the next doubly magic nucleus beyond @xmath12pb . nearly all of modern calculations predict the existence of a closed neutron shell at @xmath13 . however , they differ in predicting the atomic number of the closed proton shell . for instance , the macroscopic - microscopic model predicts the shell gap at @xmath14 @xcite . the microscopic skyrme - hartree - fock models give @xmath15 @xcite and the relativistic mean - field calculations suggest @xmath16 @xcite . the magic numbers @xmath17 and @xmath18 were predicted from the discontinuity of the volume integral at shell closures @xcite . a tremendous progress in experiments and the development of the radioactive ion beam facilities have made it possible to reach the island of superheavy elements . the heaviest shn decay primarily by the emission of @xmath0-particle terminated by spontaneous fission . therefore , in recent experiments , @xmath0 decay has been indispensable for the identification of new nuclides . because the experimentalists have to evaluate the values of the @xmath0 decay half - lives , during the experimental design , it is quite important and necessary to investigate the @xmath0 decay of shn theoretically . although @xmath0 decay is very useful for the study of the nuclei , a quantitative description of them with a satisfying accuracy is difficult . the @xmath0 decay was firstly interpreted as a consequence of quantum penetration of @xmath0-particle by gamow in 1928 . at present , many theoretical approaches have been being used to describe the @xmath0 decay , such as the cluster model @xcite , the density - dependent m3y ( ddm3y ) effective interaction @xcite , the generalized liquid drop model ( gldm ) @xcite , the coulomb and proximity potential model @xcite , the superasymmetric fission model @xcite , the umadac method @xcite , the coupled channel approach @xcite and the universal curves for @xmath0 and cluster radioactivities in a fission theory @xcite . some physically plausible formulas also were employed to calculate the @xmath0 decay half - lives directly @xcite . interestingly , the superasymmetric fission theory for @xmath0 and cluster decay has been extended by some authors to study metallic cluster physics @xcite , which is an example of using the nuclear methods in nanophysics . the half - life is extremely sensitive to the @xmath0 decay @xmath19 value and an uncertainty of 1 mev in @xmath19 value corresponds to an uncertainty of @xmath0-decay half - life ranging from @xmath20 to @xmath21 times in the heavy element region @xcite . in this work , with the experimental @xmath19 values , we carry out the half - life calculations for the recently synthesized shn by employing a relationship between the @xmath0 decay half - lives of neighboring shn that are established based on some simple semi - empirical formulas . differently from our approach , theoretical estimates for the lifetimes by calculating the quantum mechanical tunneling probability in a wkb framework is widely performed for the @xmath0 decay along with other physically analogical decay processes . it is pointed out that the wkb approximation works well at energies well below the barrier height @xcite . as a matter of fact , the accuracy of the wkb approximation also depends on the shape of the potential barrier as well as the decay energy . in this work , we obtain the penetrability with a different method and show the applicability of the wkb approximation in @xmath0 , proton and cluster radioactivity . this paper is organized as follows : in section 2 , a brief discussion of the method and the calculated results along with the corresponding discussions for the half - lives of shn are presented . the applicability of the wkb approximation for @xmath0 decay , proton and cluster emission are discussed in section 3 . finally , a brief summary is provided in section 4 . we start from royer s @xcite and viola - seaborg semi - empirical ( vss ) formulas @xcite . the royer s formula is given by @xmath22 where @xmath19 is in mev and the parameter set varies for four types : @xmath23 , @xmath24 , @xmath25 for even(@xmath26)-even(@xmath27 ) , @xmath28 , @xmath29 , @xmath30 for even - odd , @xmath31 , @xmath32 , @xmath33 for odd - even and @xmath34 , @xmath35 , @xmath36 for odd - odd nuclei @xcite . in our previous work , this formula has been extended by taking into account the centrifugal barrier to describe unfavored @xmath0 decay . for odd - mass nuclei , it is possible that some decays involve non - zero @xmath37 values . however , as no experimental evidence is available for the spin - parity of the levels involved in the decay , we have not included the centrifugal barrier in the present calculations . the vss formula is given by @xmath38 instead of using the original set of constants by viola and seaborg , recent values @xmath39 , @xmath40 , @xmath41 , @xmath42 being valid for the nuclei of four types are used @xcite . @xmath43 accounts for the hindrances associated with odd proton and odd neutron numbers but does not take an effect in our calculations . once the half - life of a nucleus @xmath44 ( reference nucleus ) is known , the half - life of an other nucleus @xmath45 ( target nucleus ) with the same type can be derived . the difference of the logarithms of half - life is written with eq . ( [ a ] ) as @xmath46 and with eq . ( [ b ] ) as @xmath47 therefore , the half - life of the nuclei @xmath45 can be obtained from @xmath48 with the help of its neighboring nucleus @xmath44 . the two formulas can validate each other to obtain more compelling results . now we focus on two simple cases . one is that the two nuclei are in an isotope chain for which eqs . ( [ c ] ) and ( [ d ] ) can be further simplified , and the other is that the two nuclei belong to an @xmath0 decay chain . we estimated the @xmath0 decay half - lives of recently synthesized shn @xmath45 with the help of the reference nuclei @xmath49 and @xmath50 by employing eqs . ( [ c ] ) and ( [ d ] ) without taking into account the uncertainty of the experimental @xmath19 values . the results are presented in table 1 compared with experimental data . the results obtained with the ddm3y effective interaction and the gldm are also shown for comparison . the third column marks the experimental @xmath0 decay half - lives , and the columns 4 and 5 are the estimated ones from eq . ( [ c ] ) based on the royer s formula and from eq . ( [ d ] ) based on the vss formula , respectively . the first half is obtained with the reference nuclei @xmath49 and the second half are obtained with the reference nuclei @xmath50 . on an average , the ddm3y results are slightly larger than the experimental data while the gldm values are lower than the measured ones . in fact , the ddm3y effective interaction and gldm are very successful because of the appropriate treatment on the microscopic level in the ddm3y calculation and the quasimolecular shape in the gldm in consideration of the difficulty in accurate half - life calculation . our calculated values are in very good agreement with the experimental measurements which indicates our method is a very effective approach to investigate the half - lives of @xmath0 decay when the experimental @xmath19 values are given though it is very simple in theoretical framework compared to the ddm3y and gldm . the two approaches based on the royer s formula and vss formula give nearly the same results implying the reliability of our method to a certain extent . the half - life of @xmath51113 is underestimated by one order of magnitude with the present method and the gldm , which are possibly due to nonzero angular momentum transfer or some nuclear structure effects such as the dramatic deformation changes as suggested in ref . @xcite and the influence of a possible neutron shell gap at @xmath52 on its daughter nucleus . in ref . @xcite , it is suggested that @xmath52 is a neutron shell gap in certain region within relativistic mean field models . this nuclide warrants further experimental measurements with higher statistics . apart from calculating the decay half - life , the present method is also a useful approach to validate the experimental measurements . the recently observed shn still await confirmation by other laboratories , which is not easy because the new shn form an isolated island that is not linked through @xmath0 decay chain with known nuclei . therefore , the theoretical confirmations become important and necessary . since the half - lives of the reference nuclei are taken from the experimental values , that the estimated results with eqs . ( [ c ] ) and ( [ d ] ) are in excellent agreement with the experimental values suggests that the experimental half - lives are themselves consistent with each other which confirms the reliability of the experimental observations and measurements to a great extent . in order to further confirm the above conclusions drawn from table 1 and the predictive power of eqs . ( [ c ] ) and ( [ d ] ) , a relationship between the @xmath0 decay half - lives of the nuclei belonging to an @xmath0 decay chain is investigated here and the estimated half - lives of shn @xmath45 are listed in table 2 . the columns 4 and 5 are the estimated half - lives from eqs . ( [ c ] ) and ( [ d ] ) with the help of their daughter nuclei @xmath53 while the columns 6 and 7 are the estimated ones with the help of their parent nuclei @xmath54 respectively . the well agreement between the evaluated values with the experimental ones further indicates the predictive power of eqs . ( [ c ] ) and ( [ d ] ) along with the reliability of the experimental measurements . of course , the uncertainties in the measured values are large because of the experimental difficulties and poor statistics . and our approach underestimates the @xmath0 decay half - life of @xmath55111 as the ddm3y and gldm . the reason for that is just the same as that for @xmath51113 mentioned above . although the main shell effect has been included in the @xmath19 value to evaluate the half - life , the preformation probability is also affected obviously by the shell effect @xcite , which will lead to a large deviation of eqs . ( [ a ] ) and ( [ b ] ) together with eqs . ( [ c ] ) and ( [ d ] ) for the nuclei around the magic numbers . however , as shown in table 2 , the half - lives of element 114 and the isotones @xmath56 are very well reproduced by applying eqs . ( [ c ] ) and ( [ d ] ) . in other words , it does not exhibit any evidence to show that @xmath57 and @xmath56 are shell closures in this region . finally , we predict the @xmath0 decay half - lives of the nuclei belonging to an @xmath0 decay chain starting from @xmath58 without experimental values by employing eqs . ( [ c ] ) and ( [ d ] ) . they are listed in table 3 which may be useful for future experimental measurements . the theoretical half - lives from eq . ( [ c ] ) and eq . ( [ d ] ) agree very well with each other which additionally confirms again the validity of our approach . the deviation in the predicted values for @xmath59115 may be large since the experimental @xmath19 value has a large uncertainty of 0.41 mev . the @xmath19 value for this nuclide needs to be measured with a higher accuracy . for other still unknown shn , one can make predictions for the @xmath0 decay half - lives with the decay energies calculated from the atomic mass evaluation of audi _ et al_. @xcite as a substitute since the agreement with the experimental data on the mass of the known heaviest elements is very satisfactory , or from a formula for the @xmath0-decay energy @xcite . we turn now to the applicability of the wkb approximation for @xmath0 decay . the interaction potential @xmath60 is the sum of the nuclear potential @xmath61 , coulomb potential @xmath62 and the centrifugal barrier . we approximate the nuclear potential by @xmath63 $ ] , with @xmath64 fm , @xmath65 fm , @xmath66 $ ] mev , @xmath67 the mass number of the emitted particle , @xmath68 the neutron , proton , and mass numbers of the parent nucleus respectively . here the single particle potential is taken from ref . the coulomb potential is given by the point - like plus uniformly charged sphere method with a parent nucleus radius @xmath69 fm @xcite . as an example , the barrier for @xmath70po@xmath71pb@xmath72 is shown in figure 1(a ) . here only the barrier is considered and we divide the barrier into a sequence of square barriers , as shown in figure 1(b ) . in principle , the barrier ranging from @xmath73 to infinity should be taken into account for the calculation yet it is unpractical . therefore , we cut off the barrier at a sufficiently large distance of @xmath74 fm and the potential barrier is divided into @xmath75 parts with a step of @xmath76 without loss of accuracy . the wave function @xmath77 ( @xmath78 ) of the emitted particle with @xmath19 value in these @xmath79 regions can be written as @xmath80 with @xmath81 , @xmath82 and @xmath83/2 $ ] . the wave function outside of the barrier is given by @xmath84 with @xmath85 where @xmath86 and @xmath87 are the amplitude of incident wave and transmitted wave , respectively . by using the connection condition of wave function , one can deduce the transmission amplitude and reflection amplitude for the @xmath79th square barrier @xmath88 a_{1,n+1 } , \\ a_{2,n } & = & \frac{1}{2}\left ( 1-\frac{k_{n+1}}{k_{n}}\right ) \exp \left [ i\left ( k_{n+1}+k_{n}\right ) r_{n}\right ] a_{1,n+1},\end{aligned}\ ] ] and for the @xmath89th ( @xmath90 ) square barrier @xmath91,\]]@xmath92.\ ] ] the penetration probability is given by @xmath93 normalization wo nt help - this is not a normalizable state . we choose @xmath94 , and then the @xmath86 can be recured according to the above formulas and hence one can obtain the penetrability . as a matter of fact , our method is a kind of numerical method to solve one - dimensional schrdinger equation for unbound state , in which the differential equation is translated to recursion formulas . before we perform the calculation for @xmath0 , proton and cluster radioactivity , we have checked this method with a soluble example @xmath95 for which the exact analytic transmission probability is known @xcite . it is found that the result with this method completely coincides with the analytic one , which confirms the reliability of this method . taking this method as a standard , one can test whether the wkb approximation works well or not . in the wkb approximation , the formula @xmath96,\ ] ] is employed to evaluate the penetrability , and one can estimate the relative deviation @xmath97 of this wkb method . as a semiclassical approximation , there exist two classical turning points @xmath98 and @xmath99 in wkb method . the penetration only performs between @xmath98 and @xmath99 and the effects of the regions i and iii of potential barrier in figure 1(a ) are neglected . however , according to quantum mechanics , the particle can be also reflected back in the region iii with some probability . additionally , the wkb method also brings some errors when one evaluates the penetrability from @xmath98 to @xmath99 ( the region ii ) and it can not deal with these @xmath19 values being near or larger than the top of the barriers in principle while our fully quantum mechanical approach has no such a drawback . we select @xmath0 decay events with @xmath100 , and the experimental @xmath19 values are taken from refs . @xcite . for @xmath0 decay , the @xmath101 values have been presented in figure 2 . the wkb approximation underestimates the penetration probability by about @xmath102 . it is not possible to calculate the @xmath0 decay half - life theoretically with a high accuracy within the framework of barrier penetration because the preformation factor is very difficult to be estimated microscopically and the @xmath0-daughter interaction has not yet been well determined . from this point of view , the wkb approximation thus works well in investigations of @xmath0 decay especially for shn since the experimental half - lives of shn tend to have a large uncertainty . indeed , because the deviation is nearly a constant in the whole mass region , this constant error can be compensated by other quantities such as a phenomenological assault frequency in actual calculations within the wkb framework . in an analogous way , we investigate the deviation of the wkb approximation for proton and cluster radioactivity . the study of the nuclei far away from the @xmath103-stable line has attracted world wide attention from both the experimental and theoretical points of view . in the case of very proton - rich nuclei , it is expected to observe the proton emission experimentally @xcite . since around 1980 , the cluster radioactivity was observed in experiments with daughter nuclei being almost closed - shell spherical nuclei around @xmath12pb . the proton and cluster emission can be treated as simple quantum tunneling effects through a potential barrier just as the @xmath0 decay @xcite . we select cluster emitters with emitted particles from @xmath104c to @xmath105si and spherical proton emitters , for which the experimental @xmath19 values are taken from refs . figure 3(a ) shows the relative deviation @xmath101 of the wkb method for the proton radioactivity of spherical proton emitters . as can be seen , the wkb method underestimates the penetrability by @xmath106 and again the deviation does not fluctuate with a large amplitude as that for @xmath0 decay . figure 3(b ) presents the relative deviation @xmath101 of the wkb method for cluster radioactivity . it indicates the wkb approximation works well for the cluster emission with a deviation by only @xmath107 . the @xmath101 is found to be insensitive to the nuclear potential @xmath61 for these three decay modes which indicates the conclusion we draw here is universal . to summarize , the @xmath0 decay half - lives of newly synthesized shn have been investigated in terms of the correlation between the half - lives of @xmath0 decay . the results of the present calculations with this relationship based on the royer s and vss formulas are in excellent agreement with the experimental data which indicates the predictive power of our method . according to the present calculations , an important conclusion is that the experimental half - lives are themselves consistent with each other confirming the reliability of the experimental observations and measurements to a great extent . for the nuclei @xmath51113 and @xmath55111 , the half - lives from the theoretical estimations are underestimated by one order of magnitude possibly due to nonzero angular momentum transfer or some nuclear structure effects . the half - lives of the synthesized shn does not exhibit any evidence to show that @xmath57 and @xmath56 are shell closures in the considered region according to our analysis . the other task of the present work was to test the applicability of the wkb approximation for quantum mechanical tunneling probabilities . we calculated the barrier penetrability for @xmath0 decay , proton and cluster emission accurately with the recursion formulas by dividing the potential barrier into a sequence of square barriers , which is a numerical method to solve one - dimensional schrdinger equation for unbound state , and the results are compared with those of the wkb approximation . it is found that the wkb method produces relative deviations by about @xmath102 for @xmath0 decay of heavy and superheavy nuclei , @xmath108 for proton emission and @xmath107 for cluster radioactivity . also , in consideration of the deviations being nearly constants in each decay mode , indeed , the wkb approximation works well for these decays . jianmin dong is thankful to prof . jianzhong gu and hongfei zhang for providing useful help . this work is supported by the national natural science foundation of china ( grant nos . 10875151 , 10575119 , 10975190 and 10947109 ) , the major state basic research developing program of china under grant nos . 2007cb815003 and 2007cb815004 , the knowledge innovation project ( kjcx2-ew - n01 ) of chinese academy of sciences , cas / safea international partnership program for creative research teams ( grant no . cxtd - j2005 - 1 ) , the funds for creative research groups of china ( grant 11021504 ) and the financial support from dfg of germany . oganessian , et al . c 69 ( 2004 ) 021601(r ) ; yu . oganessian , et al . c 70 ( 2004 ) 064609 ; yu . ts . oganessian , et al . c 72 ( 2005 ) 034611 ; yu . ts . oganessian , et al . c 74 ( 2006 ) 044602 ; yu . ts . oganessian , et al . c 76 ( 2007 ) 011601(r ) . k. p. santhosh , sabina sahadevan , r. k. biju , nucl . phys . a 825 ( 2009 ) 159 ; k. p. santhosh and r. k. biju , j. phys . g : nucl . part . 36 ( 2009 ) 015107 ; k. p. santhosh , r. k. biju and antony joseph , j. phys . g : nucl . part . 35 ( 2008 ) 085102 . v. yu . denisov and a. a. khudenko , at . data nucl . data tables 95 ( 2009 ) 815 ; v. yu . denisov and a. a. khudenko , phys . c 81 ( 2010 ) 034613 ; v. yu . denisov and a. a. khudenko , phys . rev . c 82 ( 2010 ) 059901(e ) .

the @xmath0 decay half - lives of recently synthesized superheavy nuclei ( shn ) are calculated by applying a new approach which estimates them with the help of their neighbors based on some simple formulas . the estimated half - life values are in very good agreement with the experimental ones , indicating the reliability of the experimental observations and measurements to a large extent as well as the predictive power of our approach . the second part of this work is to test the applicability of the wentzel - kramers - brillouin ( wkb ) approximation for the quantum mechanical tunneling probability . we calculated the accurate barrier penetrability for alpha decay along with proton and cluster radioactivity by numerically solving schrdinger equation . the calculated results are compared with those of the wkb method to find that wkb approximation works well for the three physically analogical decay modes . # 1 # 1 # 1#2 jianmin dong@xmath1 , wei zuo@xmath2 , werner scheid @xmath3 1 . research center for hadron and csr physics , lanzhou university and institute of modern physics of cas , lanzhou 730000 , china 2 . institute of modern physics , chinese academy of sciences , lanzhou 730000 , china 3 . graduate university of chinese academy of sciences , beijing 100049 , china 4 . school of nuclear science and technology , lanzhou university , lanzhou 730000 , china 5 . institute for theoretical physics , justus - liebig - university , d-35392 giessen , germany 6 . china institute of atomic energy , p. o. box 275(18 ) , beijing 102413 , people s republic of china _ pacs _ : 27.90.+b , 21.10.tg , 23.60.+e , 23.50.+z , 23.70.+j _ keywords _ : superheavy nuclei ; half - lives ; @xmath0-decay ; proton radioactivity ; cluster emission

Humblebragging is irritating; this, you know. But the truth about that special, noxious blend of whining and boasting is that it also doesn’t even appear to work the way that humblebraggarts think it does, in that it doesn’t successfully get the intended message across, according to a new working paper from a team of Harvard Business School researchers. Sometimes, you’re better off just regular-bragging. The researchers, Ovul Sezer, Francesca Gino, and Michael I. Norton, tested people’s perception of humblebragging across five separate experiments. In one, they asked 302 people to imagine the person who said one of three statements: a complaint (“I am so bored”), a brag (“People mistake me for a model”), or a humblebrag (“I am so bored of people mistaking me for a model”). They were then asked to rate how much they liked this person, judging from this one statement, and how sincere the person seemed. Overall, the study participants liked the complainers the best, and then the braggers; in last place, perhaps not surprisingly, were the humblebraggers. The participants also rated the complainers as most sincere and the humblebraggers as least sincere, which gets at one reason humblebragging is so obnoxious: It comes off as inauthentic. In another experiment, the researchers showed that humblebragging isn’t an effective way to get your point across when compared to straightforward bragging. To test this, they had 201 people either read a brag (“I get hit on all the time”) or a humblebrag (“Just rolled out of bed and still get hit on all the time, so annoying.”); each group was asked to rate how attractive they’d guess the person behind the statement was. The findings showed that people consistently rated humblebraggers as less attractive than the braggers — 4.34 out of 7 for the humblebraggers, as compared to 4.91 for the braggers (a significant difference, though admittedly not a huge one). Humblebragging, then, the researchers conclude, a self-promotion strategy you're better off avoiding. “Faced with the choice to (honestly) brag or (deceptively) humblebrag,” they write, “would-be self-promoters should choose the former — and at least reap the rewards of seeming sincere.” ||||| Working Paper | HBS Working Paper Series | 2017 Humblebragging: A Distinct—and Ineffective—Self-Presentation Strategy by Ovul Sezer, Francesca Gino and Michael I. Norton Abstract Self-presentation is a fundamental aspect of social life, with myriad critical outcomes dependent on others’ impressions. We identify and offer the first empirical investigation of a prevalent, yet understudied self-presentation strategy: humblebragging. Across seven studies including a week-long diary study and a field experiment, we identify humblebragging—bragging masked by a complaint or humility—as a common, conceptually distinct, and ineffective form of self-presentation. We first document the ubiquity of humblebragging across several domains, from everyday life to social media. We then show that both forms of humblebragging—complaint-based or humility-based—are less effective than straightforward bragging, as they reduce liking, perceived competence, and compliance with requests. Despite being more common, complaint-based humblebrags are less effective than humility-based humblebrags and are even less effective than simply complaining. We show that people choose to deploy humblebrags particularly when motivated both to elicit sympathy and impress others. Despite the belief that combining bragging with complaining or humility confers the benefits of each strategy, we find that humblebragging confers the benefits of neither, instead backfiring because it is seen as insincere. Keywords: Humblebragging; impression management; sincerity; liking; competence; interpersonal perception; Self-presentation; Perception; Marketing; Trust; Personal Development and Career; Language: English Format: Print 79 pages SSRN Read Now

– Masking a brag with false modesty—known as a "humblebrag" in today's parlance—may seem like an effective way to boast about your achievements without seeming like, well, an egotistical jerk. But a working paper from Harvard Business School researchers finds exactly the opposite, noting that people may be better off simply bragging and self-promoting without shame than adopting a veneer of faux humility, the Science of Us reports. Even complainers fared better than humblebraggers in the study because they were viewed as more "sincere." The researchers conducted five separate experiments to test how people perceived humblebragging. In one of the experiments, 300 or so people were asked to rate hypothetical people who made the following three statements: "I am so bored" (complaint), "People mistake me for a model" (explicit brag), and the everyone-wishes-they-had this-problem remark of "I am so bored of people mistaking me for a model" (humblebrag). Not only did the participants rate the complainers as the most authentic (braggers came in second), but they also imagined the humblebraggers to be less attractive than the braggarts. "Despite people's belief that combining bragging and complaining confers the benefits of both self-promotion strategies, humblebragging fails to pay off," the researchers conclude. (One writer thinks celebrities are the worst humblebraggers.)

critical properties of structurally disordered magnets remain a problem of great interest in condensed matter physics , as far as real magnetic crystals are usually non - ideal . commonly , in the theoretical studies , as well as in the mc simulations , one considers point - like uncorrelated quenched non - magnetic impurities @xcite . however , in real magnets one encounters non - idealities of structure , which can not be modeled by simple point - like uncorrelated defects . indeed , magnetic crystals often contain defects of a more complex structure : linear dislocations , planar grain boundaries , three - dimensional cavities or regions of different phases , embedded in the matrix of the original crystal , as well as various complexes ( clusters ) of point - like non - magnetic impurities @xcite . therefore , a challenge is to offer a consistent description of the critical phenomena influenced by the presence of such complicated defects . different models of structural disorder have arisen as an attempt to describe such defects . in this paper we concentrate on the so - called long - range - correlated disorder when the point - like defects are correlated and the resulting critical behaviour depends on the type of this correlation . several models have been proposed for description of such a dependence @xcite , a subject of extensive analytical and numerical @xcite treatment . a common outcome of the above studies is that although the concentration of non - magnetic impurities is taken to be far from the percolation threshold , in the region of weak dilution , the impurities make a crucial influence on an onset of ordered ferromagnetic phase . given that the pure ( undiluted ) magnet possesses a second - order phase transition at certain critical temperature @xmath0 , an influence of the weak dilution may range from the decrease of @xmath0 to the changes in the universality class and even to the smearing off this transition @xcite . moreover , the critical exponents governing power low scaling in the vicinity of @xmath0 may depend on the parameters of impurity - impurity correlation . to give an example , the harris criterion , which holds for the energy - coupled uncorrelated disorder @xcite is modified when the disorder is long - range correlated @xcite . in particular , when the impurity - impurity pair correlation function @xmath1 decays at large distances @xmath2 according to a power law : @xmath3 the asymptotic critical exponents governing magnetic phase transition ( and hence the universality class of the transition ) do change if @xcite @xmath4 where @xmath5 is the correlation length critical exponent of the undiluted magnet . the above condition ( [ 2 ] ) holds for @xmath6 , @xmath7 being the space ( lattice ) dimension . for @xmath8 the usual harris criterion @xcite is recovered and condition ( [ 2 ] ) is substituted by @xmath9 . the fact , that the power of the correlation decay might be a relevant parameter at @xmath6 can be easily understood observing an asymptotics of the fourier transform @xmath10 of @xmath1 at small wave vector numbers @xmath11 . from ( [ 1 ] ) one arrives at @xmath12 , which for @xmath6 leads to a singular behaviour at @xmath13 . as far as the small @xmath11 region defines the criticality , the systems with @xmath6 are good candidates to manifest changes in the critical behaviour with respect to their undiluted counterparts . on contrary , impurity - impurity correlations at @xmath8 do not produce additional singularities with respect to the uncorrelated point - like impurities , therefore they are referred to as the short - range correlated . in turn , the disorder characterized by eq . ( [ 1 ] ) with @xmath6 is called the long - range correlated . there are different ways to model systems with the long - range - correlated disorder governed by eq . ( [ 1 ] ) . the most direct interpretation relies on the observation that the integer @xmath14 in eq . ( [ 1 ] ) corresponds to the large @xmath2 behaviour of the pair correlation function for the impurities in the form of points ( @xmath15 ) , lines ( @xmath16 ) , and planes ( @xmath17 ) @xcite . since the last two objects extend in space , the impurities with @xmath6 sometimes are called the extended ones . note that the isotropic form of the pair correlation function ( [ 1 ] ) demands random orientation of such spatially extended objects . non - integer @xmath14 sometimes are treated in terms of a fractal dimension of impurities , see e.g. @xcite . besides energy - coupled disorder , the power - low correlation decay ( [ 1 ] ) is relevant for the thermodynamic phase transition in random field systems @xcite , percolation @xcite , scaling of polymer macromolecules at presence of porous medium @xcite , zero - temperature quantum phase transitions @xcite . our paper was stimulated by the observations of obvious discrepancies in the state - of - the - art analysis of criticality in three - dimensional ising magnets with the long - range - correlated disorder governed by eq . ( [ 1 ] ) . indeed , since for the pure @xmath18 ising model @xmath19 @xcite , the long - range correlated disorder should change its universality class according to eq . ( [ 2 ] ) . whereas both theoretical and numerical studies agree on the validity of extended harris criterion ( [ 2 ] ) and bring about the new universality class @xcite , the numerical values of the critical exponents being evaluated differ essentially . we list the values of the exponents found so far by different approaches in table [ tab1 ] and refer the reader to the section [ ii ] for a more detailed discussion of this issue . here , we would like to point out that presently the results of each of existing analytical approaches ( refs . @xcite and @xcite ) is confirmed by only one numerical simulation ( refs . @xcite and @xcite , respectively ) . to resolve such a bias , we perform mc simulations of a @xmath18 ising model with extended impurities and evaluate critical exponents governing ferromagnetic phase transition . as it will become evident from the further account , our estimates for the exponents differ from the results of two numerical simulations performed so far @xcite and are in favour of a non - trivial dependency of the critical exponents on the peculiarities of long - range correlations decay . lllll reference & @xmath20 & @xmath21 & @xmath22 & @xmath23 + + weinrib , halperin , @xcite & 1 & 2 & 1/2 & 0 + prudnikov _ et al . _ , @xcite & 0.7151 & _ 1.4449 _ & _ 0.3502 _ & -0.0205 + ballesteros , parisi , @xcite@xmath24 & 1.012(10 ) & _ 1.980(16 ) _ & _ 0.528(7 ) _ & 0.043(4 ) + @xcite@xmath25 & 1.005(14 ) & _ 1.967(23)_&_0.524(9 ) _ & 0.043(4 ) + prudnikov _ et al . _ , @xcite@xmath24 & 0.719(22 ) & _ 1.407(24 ) _ & 0.375(45 ) & _ 0.043(93 ) _ + @xcite@xmath25 & 0.710(10 ) & 1.441(15)&0.362(20 ) & _ -0.030(7 ) _ + the outline of the paper is the following . in the next section we make a brief overview of the results of previous analysis of the 3d ising model with long - range - correlated impurities paying special attention to the former mc simulations . details of our mc simulations are explained in sections [ iii ] and [ iv ] . there , we formulate the model and define the observables we are interested in . we analyze statistics of typical and rare events taking the magnetic susceptibility as an example in section [ iv ] . the numerical values of the exponents are evaluated there by the finite - size scaling technique . section [ v ] concludes our study . currently , there exist two different analytical results for the values of critical exponents of the 3d ising model with long - range - correlated impurities . the first one is due to weinrib and halperin , who formulated the model of a @xmath26-vector magnet with quenched impurities correlated via the power law ( [ 1 ] ) @xcite . they used the renormalzation group technique carrying out a double expansion in @xmath27 , @xmath28 , considering @xmath29 and @xmath30 to be of the same order of magnitude , and estimating values of the critical exponents to the first order in this expansion . further , they conjectured the obtained first order result for the correlation length critical exponent @xmath31 to be an exact one and to hold for any value of spin component number @xmath26 provided that @xmath32 . by complementing eq . ( [ 3 ] ) with the first order value of the pair correlation function critical exponent , @xmath33 @xcite , the other critical exponents can be obtained via familiar scaling relations . for @xmath34 the exponents are listed in table [ tab1 ] . the second theoretical estimate was obtained by prudnikov _ @xcite in the field theoretical renormalization group technique by performing renormalization for non - zero mass at fixed space dimension @xmath18 . their two - loop calculations refined by the resummation of the series obtained bring about a non - trivial dependence of the critical exponents both on @xmath26 and on @xmath14 . we list their values of the exponents for @xmath35 and @xmath34 in the second row of table [ tab1 ] . in particular , one observes that the correlation length exponent @xmath20 obtained in ref . @xcite differs from the value predicted by ( [ 3 ] ) by the order of 25 % . as for the reason of such discrepancy the authors of ref . @xcite point to a higher order of the perturbation theory they considered together with the methods of series summation as well as to taking into account the graphs which are discarded when the @xmath36-expansion is being used . let us note however , the qualitative agreement between the above analytical results : both renormalization group treatments , refs . @xcite and @xcite , predict that the new ( long - range - correlated ) fixed point is stable and reachable for the condition considered and hence the 3d ising model with long - range - correlated impurities belongs to a new universality class . these are only the numerical values of the exponents which call for additional verification . in such cases one often appeals to the numerical simulations . indeed , two simulations were performed , and , strangely enough , the results again split into two groups : whereas the simulation of ballesteros and parisi @xcite is strongly in favour of the theoretical results of weinrib and halperin , the simulation of prudnikov _ et al . _ @xcite almost exactly reproduces former theoretical results of this group @xcite as one can see from table 1 . there , we give the results for the exponents obtained in simulations complementing them by those that follow if one uses familiar scaling relations ( the last are shown in italic ) . since our own study will rely on the simulation technique as well , we describe an analysis performed in refs . @xcite in more details . in ref . @xcite the simulations were done for two different types of the long - range - correlated disorder referred by the authors as the gaussian and the non - gaussian one . in the first case , the point - like defects are scattered directly on the sites of a 3d simple cubic lattice according to the desired decay of the pair correlation function ( [ 1 ] ) , @xmath34 . in the second case , the defects form the lines directed along the randomly chosen axes and , as was mentioned before , their impurity - impurity pair correlation function should also decay at large @xmath2 as @xmath37 ) . the mc algorithm used in ref . @xcite is a combination of a single - cluster wolff method and a swendsen - wang algorithm . after a fixed number of a single - cluster updates one swendsen - wang sweep is performed . the procedure was called a mc step ( mcs ) . the number of single cluster flips was chosen such that the autocorrelation time @xmath38 was typically 1 mcs . for thermalization of the system @xmath39 mcss were performed and then various observables were measured . the simulation was done on the lattice of sizes @xmath40 and @xmath41 . then @xmath39 mcss have been used for measurements on @xmath42=20000 different samples for @xmath43 and on @xmath42=10000 samples for @xmath44 . the procedure seems to be quite safe . values of the critical exponents @xmath20 and @xmath23 obtained in ref . @xcite in the case of gaussian disorder ( point - like long - range - correlated defects ) are given in table [ tab1 ] for the impurities concentrations @xmath45 , @xmath46 . it was stated in the paper , that for the non - gaussian disorder ( lines of defects ) the estimates of the exponents are comparable with analytic calculations of weinrib and halperin @xcite . in ref . @xcite the mc simulation of the critical behavior of the three - dimensional ising model with long - range - correlated disorder at criticality was performed by means of the short - time dynamics and the single - cluster wolff method . randomly distributed defects had a form of lines and resembled the `` non - gaussian disorder '' of ref . however , in contrast to ref . @xcite , a condition of lines mutual avoidance was implemented . according to ref . @xcite , a situation when crossing of the lines of defects is allowed is not described by the weinrib - halperin model . in the short - time critical dynamics method , the concentration of spins was chosen @xmath45 and the cubic lattices of sizes @xmath47 were considered . as a mc method was used a metropolis algorithm . resulting numbers for the exponents are given in the 5th row of table [ tab1 ] . additional simulations in the equilibrium state were performed in ref . @xcite to verify the reliability of results obtained by means of the short - time critical dynamics . the single - cluster wolff algorithm was used for simulation and a finite size scaling for evaluation of the critical exponents . one mcs was defined as 5 cluster flips , @xmath48 mcss were discarded for equilibration and @xmath49 for measurement . disorder averaging was typically performed over @xmath48 samples . again , the procedure seems to be safe . the values of critical exponents obtained in the simulations are quoted in the 6th row of table [ tab1 ] . with the above information at hand we started our numerical analysis as explained in the forthcoming sections . we consider a @xmath18 ising model with non - magnetic sites arranged in a form of randomly oriented lines ( see fig . [ fig_1 ] ) . the hamiltonian reads : @xmath50 where @xmath51 means the nearest neighbour summation over the sites of a s.c . lattice of linear size @xmath52 , @xmath53 is the interaction constant , ising spins @xmath54 , @xmath55 is the occupation number for the @xmath56-th site and periodic boundary conditions are employed . non - magnetic sites ( @xmath57 ) are quenched in a fixed configuration and form lines , as shown in fig . [ fig_1 ] . concentration @xmath58 of the magnetic sites is taken to be far above the percolation threshold . [ fig_1 ] shows one possible configuration for non - magnetic impurity lines . during the simulations , one generates a large number of such disorder realizations this is done in our study using the following procedure . the lines of impurities are generated one by one , each along randomly chosen axis and the final disorder realization is accepted with the probability @xmath59 using rejection method . here @xmath60 is a required value for the concentration of magnetic sites and @xmath61 is the dispersion of the resulted gaussian distribution in @xmath58 ( see fig . [ hist ] ) . the average value for the impurity concentration is equal to @xmath62 . in the simulations presented here we paid special attention to the width of this distribution and consider both broad and narrow cases , see sections [ ivb ] and [ ivc ] ) . the observables saved during each step of the mc simulations for a given disorder realization will be the instantaneous values for the internal energy @xmath63 and magnetisation @xmath64 per spin , defined as @xmath65 @xmath66 where number of magnetic sites is @xmath67 , total number of sites is @xmath68 . using the histogram reweighting technique @xcite we compute the following expectation values at the critical temperature region for a given disorder realization : @xmath69 as functions of an inverse temperature @xmath70 . in ( [ 99 ] ) the angular brackets @xmath71 stand for the thermodynamical averaging in one sample of disorder . for a given disorder configuration , one can evaluate the temperature behaviour of the magnetic susceptibility @xmath72 and magnetic cumulants @xmath73 , @xmath74 : @xmath75 in order to refer to the physical quantities , the observables are to be averaged over different disorder configurations , denoted hereafter by an overline : @xmath76 . two ways of averaging can be found in the literature , which we will consider for the case of finding the maximum value for the susceptibility . at each disorder realization an individual curve for the susceptibility @xmath72 as a function of the temperature @xmath77 is obtained ( using histogram reweighting technique ) . in the first method of averaging , depicted in fig . [ fig_11],a the maximal values of each individual curves are averaged over all disorder realizations . this type of averaging , referred hereafter as _ averaging a _ , will be denoted as @xmath78 . \a ) _ averaging a _ b ) _ averaging b _ an alternative method is shown in fig . [ fig_11],b : at first one performs a configurational averaging of the susceptibility , i.e. the single averaged curve is evaluated for @xmath79 . then the maximal value for this curve , @xmath80 , is found . hereafter , this method will be referred as _ averaging b_. both _ averaging a _ and _ averaging b _ will be exploited in our analysis . to evaluate the critical exponents , a number of characteristics will be used with known finite size scaling : * _ averaging a _ : @xmath81 here , @xmath78 , @xmath82 , and @xmath83 are the averaged over disorder configurations maximal values of the magnetic susceptibility and magnetic cumulants temperature derivatives . the value @xmath84 is calculated for the temperature that corresponds to the magnetic susceptibility maximum . * _ averaging b _ : + @xmath85 + @xmath86 + where @xmath87 note , that quantities ( [ 111a ] ) are ill - defined if _ averaging a _ is considered . moreover , as one can see from the definitions ( [ 22a ] ) , ( [ 22b ] ) there are different ways to define magnetic cumulants for the disordered system ( see refs . @xcite for more discussion ) . we performed our numerical simulations using the swendsen - wang cluster algorithm . the main reason is , that with the diluted system one often performs simulations at the temperature which is far from the native phase transition point of each particular disorder realization . as the result , the single clusters can be of rather small size and the wolff one algorithm , used by us before @xcite is found to be less effective . the following set of lattice sizes @xmath88 ( @xmath89 in some cases ) is used and performing the finite - size - scaling analysis is performed . the magnetic site concentration is chosen to be @xmath45 which is far from the percolation threshold and this also allows comparison with the previous simulations @xcite . another reason for such a choice is that for the 3d ising model with uncorrelated impurities the correction to scaling terms were found to be minimal at @xmath45 @xcite , ( obviously , this does not mean that @xmath45 minimizes correction - to - scaling terms at any level of impurities correlation ) . the number of samples ranges from @xmath90 to @xmath48 for all lattice sizes . the simulations are performed at the finite - size critical temperature @xmath91 which is found from the maximum of magnetic susceptibility @xmath72 at each lattice size @xmath52 and the reweighting technique for the neighbouring temperatures is used . note , that in refs . @xcite all simulation were performed at the critical temperature of an infinite system . similarly to our other previous papers @xcite we start simulation from estimating the critical temperature of a finite - size system as a function of the lattice size @xmath52 , @xmath91 . for the smallest lattice size @xmath92 , the preliminary simulation is performed at @xmath93 first ( @xmath94 is the critical temperature for the pure system ) . the @xmath95 is located then from the maximum of the susceptibility . at the same time , we estimate various autocorrelation times to control the error due to time correlations . for the next larger lattice size , e.g. @xmath96 , preliminary simulation is performed at @xmath95 and then @xmath97 is located again from the maximum of the susceptibility at @xmath96 . the process is repeated for all lattice sizes . in this way we estimate @xmath91 and the energy autocorrelation time @xmath98 . the results are given in table [ tab2 ] . one can see that the finite size system critical temperature obtained via _ averaging a _ differs from those obtained via and _ averaging b_. the difference is not too large , the next simulations were performed at the critical temperature obtained by _ averaging a_. in evaluation of the critical indices we followed the standard finite - size - scaling scheme as described e. g. in ref . the estimates for the correlation length , magnetic susceptibility , and spontaneous magnetization critical exponents @xmath20 , @xmath21 and @xmath22 can be obtained from the fss behaviour of the following quantities : * _ averaging a _ : @xmath99 in eqs . ( [ 111b ] ) , ( [ 111c ] ) , the correction - to - scaling terms have been omitted . taking them into account the fss behaviour of the quantity @xmath100 attains the form : @xmath101 where @xmath102 is the leading exponent , @xmath103 is the correction - to - scaling exponent , and @xmath104 is a correction - to - scaling amplitude . hereafter , we perform the finite - size - scaling analysis in several ways . first , assuming the correction - to - scaling terms to be small we will fit the data for the observables to the leading power laws ( [ 111b ] ) , ( [ 111c ] ) only . besides that , we will also perform the fits with correction - to - scaling terms ( [ 111d ] ) as explained below . in this section , applying the above described formalism , we give preliminary estimates of the critical exponents . as we will see , the estimates for the same exponent obtained on the base of fss of different quantities differ from each other . moreover , similar differences arise when the results obtained via _ averaging a _ and _ averaging b _ are compared . we will discuss possible reasons for such behaviour and will analyze them further in the forthcoming section . the starting point of the analysis performed in this section is connected with the fact that at the same concentration of impurities , different samples vary configurationally ( geometrically ) as well as in their thermodynamical characteristics . in systems with uncorrelated dilution these variations are also present ( see e.g. ref . @xcite ) although , as we will see below , these are less pronounced than in the case of the long - range - correlated disorder . moreover , although the mean concentration of magnetic sites is well - defined for an ensemble samples ( and chosen to be @xmath45 ) , the concentration of magnetic sites in each sample vary from the mean one . such deviations are caused by possible intersections of impurity lines in different samples , besides not for all lattice sizes one can reach given concentration of impurities by an integer number of lines . therefore , to start an analysis one has to make a choice of a set of sample specifying allowed values of the concentration dispersion . we start an analysis by dealing with the set of samples that are characterized by dispersion of concentrations @xmath105 . the sample - to - sample variations increase with the increase of the lattice size . as an example , we show in fig . [ fig2 ] the values of the susceptibility for a given disorder realization calculated via _ averaging a _ ( @xmath78 , fig . 3a-3c ) and _ averaging b _ ( @xmath106 , fig . 3d-3f ) for three typical lattice sizes @xmath107 . each point in these plots represents the data obtained for a given sample ( i.e. given disorder realization ) . solid lines are made up of the average values , where at each @xmath108 the averaging is done on the interval @xmath109 . one can see that the averages saturate at @xmath108 larger than two hundred samples . from this in particular one can conclude that considered here number of samples @xmath110 is quite sufficient for further analysis . one observes that for some samples @xmath78 and @xmath106 differ significantly from the average values . when this is the case , we will call such an event a rare one . the values that are close to the maximal one will be referred to as typical events . we would like to stress that for _ averaging b _ for the lattice size @xmath111 most of rare events produce the values for the susceptibility below the average value , while for @xmath112 the situation is reversed , see figure [ fig2 ] . at @xmath113 the distribution of rare events is aproximately symmetric . the situation is more homogenous for the _ averaging a_. the averaging over too small number of disorder realizations leads to typical ( i.e. most probable ) values instead of averaged ones . indeed , as can be seen in fig . [ fig3 ] for @xmath112 , the probability distributions of @xmath78 and @xmath106 possess long tails of rare events with larger values of susceptibility . the samples which correspond to the rare events give a large contribution to the average and shift it far from the most probable values . the value of @xmath106 calculated with the complete probability distribution in shown in fig . [ fig3 ] by a dashed line ( blue on - line ) . another characteristic value shown in fig . [ fig3 ] by lines ( solid ) are the median values @xmath114 , defined as the values of @xmath72 where the integrated probability distributions are equal to 0.5 . a distance between the average and median values may serve to quantify the asymmetricity of the probability distribution . figures [ fig5a ] and [ fig6a ] show contributions of typical and rare events to the temperature behaviour of the observables under discussion . as an example of typical events , we plot in fig . [ fig5a ] the magnetic susceptibility @xmath72 , binder s cummulant @xmath74 , and magnetisation @xmath115 selecting the samples where susceptibilities have the same values as @xmath116 at @xmath117 for the largest lattice size @xmath112 . few examples of rare events corresponding to large values of @xmath72 are shown in fig . [ fig6a ] . the bold lines in the figures show averages over all disorder realizations ( all samples ) . the thin lines ( color on - line ) correspond to different samples , as shown in the legends to the plots [ fig5a]a , [ fig6a]a . it follows from the above analysis that the rare events are obviously present in the random variables distributions and give a contribution to the average values of physical quantities . law to choose the samples during the mc experiment ( as it was done at the initial phase of our analysis , see ref . @xcite ) modifies the distribution . such modifying leads to different results for the exponents . we thank the referee for the comments on this point . ] before passing to evaluation of the critical exponents let us recall that as it was noted at the beginning of section [ v ] we perform the simulations for the samples with varying concentration of magnetic sites , keeping the mean concentration equal to @xmath45 and limiting dispersion of concentrations by @xmath105 ( [ probp ] ) . following refs . @xcite it is natural to call such situation the grand canonical disorder. afterwards , in section [ ivc ] we will consider the case of canonical disorder , when we will choose the samples much more close in the concentration of magnetic sites ( taking @xmath118 ) . in the finite - size - scaling technique @xcite , the critical exponents are calculated by fitting the data set for the observables evaluated at various lattice sizes to the power laws ( [ 111b ] ) , ( [ 111d ] ) as was already mentioned in section [ iii ] . this procedure will be used for the evaluation of the critical exponents @xmath20 , @xmath22 , and @xmath21 based on the observables measured during the mc simulations . corresponding finite - size - scaling plots are shown in figs . [ fig5 ] , [ fig7 ] , the numbers are given in table [ tab3 ] . in fig . [ fig5 ] , we give the log - log plots of the maximum values of the configurationally averaged derivatives of binder cumulants @xmath119 and @xmath120 . the scaling of these quantities is governed by the correlation length critical exponent @xmath20 , see eqs . ( [ 111b ] ) . [ fig7 ] shows the size dependence of the configurationally averaged magnetic susceptibility @xmath78 ( fig . [ fig7]a ) and magnetisation @xmath84 ( fig . [ fig7]b ) . these values are expected to manifest a power - law scaling with exponents @xmath121 and @xmath122 , see eq . ( [ 111b ] ) .

we analyze a controversial topic about the universality class of the three - dimensional ising model with long - range - correlated disorder . whereas both theoretical and numerical studies agree on the validity of extended harris criterion ( a. weinrib , b.i . halperin , phys . rev . b 27 ( 1983 ) 413 ) and indicate the existence of a new universality class , the numerical values of the critical exponents found so far differ essentially . to resolve this discrepancy we perform extensive monte carlo simulations of a 3d ising model with non - magnetic impurities being arranged in a form of lines along randomly chosen axes of a lattice . the swendsen - wang algorithm is used alongside with a histogram reweighting technique and the finite - size scaling analysis to evaluate the values of critical exponents governing the magnetic phase transition . our estimates for these exponents differ from both previous numerical simulations and are in favour of a non - trivial dependency of the critical exponents on the peculiarities of long - range correlations decay . , , , random ising model , long - range - correlated disorder , monte carlo , critical exponents 05.10.ln , 64.60.fr , 75.10.hk

multiple sclerosis is a chronic inflammatory disease in which autoreactive lymphocytes induce inflammatory damage to myelin sheaths of the central nervous system ( cns ) . the morphologic hallmarks of multiple sclerosis are demyelination , inflammation , axonal damage , and gliosis with loss of oligodendrocytes and neurons . treatment options have widened in the last decade , leading to fingolimod ( fty270 ) approval as the first oral agent proved to be effective in reducing relapse rate and disability progression in relapsing remitting multiple sclerosis ( rrms ) . fingolimod acts as a sphingosine-1-phosphate receptor ( s1pr ) modulator retaining pathogenic autoreactive t cells in the lymph nodes and preventing their infiltration into the cns [ 14 ] . in addition , some studies suggest that fingolimod biological activity would be underpinned , to some extent , by its direct interaction with neural cells expressing s1pr [ 5 , 6 ] . the efficacy of oral fingolimod was investigated in two large phase 3 clinical trials comparing oral fingolimod doses of 0.5 mg and 1.25 mg once daily in rrms [ 710 ] . the fty720 research evaluating effects of daily oral therapy in multiple sclerosis ( freedoms ) trial showed significant efficacy of fingolimod in reducing the annualized relapse rate ( arr ) , the risk of disability progression , and the number of new or newly enlarging brain lesions on magnetic resonance imaging ( mri ) [ 7 , 8 , 10 ] . the second pivotal trial ( trial assessing injectable interferon versus fty720 oral in relapsing - remitting multiple sclerosis , transforms ) confirmed preliminary results , as fingolimod proved to be effective in reducing the arr and mri disease activity measures but failed to slow disability progression , compared to interferon beta 1-a . in phase 2 , phase 3 , and extension studies , fingolimod exhibited a relatively good safety and tolerability profile . most commonly reported adverse events in the fingolimod group were mild infections , mainly of the lower respiratory tract , increased alanine aminotransferase levels , bradycardia , first and second degree atrioventricular blocks at the time of first administration , hypertension , macular edema , mild decrease in lung function , and lowering of peripheral blood lymphocyte count , as expected from the mechanism of action of fingolimod [ 1113 ] . the european medicines agency ( ema ) approved fingolimod as a single agent disease modifying therapy in patients with unsatisfactory disease control despite treatment with a beta interferon or in treatment - nave patients with rapidly evolving severe multiple sclerosis , providing a second - line treatment option in highly active rrms . a recent observational population study showed similar efficacy of fingolimod compared with natalizumab on clinical measures , as defined by arr and risk of disability progression , in an unselected rrms cohort . the aim of this prospective postmarketing multicenter observational study was to evaluate the clinical efficacy of fingolimod in rrms patients in a real clinical practice setting . we report prospectively collected data from 142 patients diagnosed with rrms according to mcdonald criteria , in three multiple sclerosis centers throughout central and southern italy , starting fingolimod treatment . baseline demographic and clinical data are reported in table 1 . out of 142 patients , 95 ( 66.9% ) were female ; mean age was 39.56 9.11 years ( 39.63 8.15-year males , 39.53 9.59-year females ) with a mean disease duration of 11.37 6.74 years ( 11.01 6.13-year males , 10.62 7.44-year females ) . mean duration of the fingolimod treatment was 14.95 9.15 months ( range 133 months ) . thirty - four patients ( 23.94% ) received fingolimod 24 months , 47 patients ( 33.09% ) received fingolimod between 12 and 23 months , 33 patients ( 23.23% ) received fingolimod between 6 and 11 months , and 28 patients ( 19.71% ) received fingolimod between 1 and 5 months . patients were included in accordance with the italian drug agency ( aifa ) eligibility criteria for reimbursement of the drug . criteria included patients on previous immunomodulant treatment for at least 12 months who had experienced at least one relapse in the last year with at least 9 t2 lesions at mri or an increased lesion burden or at least one gadolinium - enhanced lesion or patients with severe multiple sclerosis with a fast progression / evolution , even if not previously treated with immunomodulant treatments , with 2 relapses with accumulation of disability during the last year , and with new t2- or gadolinium - enhanced lesions on mri , compared with a previous mri examination conducted during the previous 12 months . patients switching from natalizumab to fingolimod were also recruited and started treatment after a wash - out period of three months . all these patients discontinued natalizumab due to safety concerns for positive jcv status and overall treatment duration longer than 24 months , despite being clinically and radiologically stable under natalizumab treatment . patients underwent complete cardiac evaluation before starting fingolimod in order to exclude heart rate and atrioventricular conduction alterations . moreover , a continuous electrocardiographic monitoring for six hours after the administration of the first dose was performed in all patients . every hour , ophthalmologic evaluation with optical coherence tomography was performed at baseline , at 3 and 6 months and every 6 months thereafter , in order to monitor potential adverse events such as macular oedema . neurological examination and edss assessment were performed at baseline and during follow - up visits . imaging data were collected at mri facilities of the participating sites and reviewed by experienced neuroradiologists . mri imaging was performed at 1.5 t and at least axial flair , t2 weighted , and t1 gadolinium - enhanced sequences were obtained for all exams . mri scans were analyzed for new or newly enlarging t2 lesions and gadolinium enhancing lesions . the study was approved by the azienda sanitaria locale avezzano - sulmona - l'aquila ethics committee and conducted in conformance with the ethical principles of the declaration of helsinki . written informed consent was obtained from all patients . the main end points were the proportion of patients free from clinical relapses ; from confirmed disability progression , as defined by sustained increase of 1.0 point in the edss score ( or 1.5 points if the baseline was < 1.0 ) confirmed after 12 weeks ; from new or newly enlarging t2 lesions ; from gadolinium enhancing lesions ; from any disease activity , as defined by the occurrence of relapse or confirmed disease progression or new disease activity at mri . arr and edss score variations at 6 , 12 , 18 , and 24 months with respect to basal values were also considered . an intention to treat analysis was planned . continuous variables were reported as means , standard deviations and range while discrete data were reported in contingency tables as absolute and relative frequencies . the cox multivariate model was used to test the influence of prognostic factors ( age , sex , duration of the disease , number of previous treatments , edss score before fingolimod start , number of contrast - enhancing lesions at mri before fingolimod start , previous immunosuppressant treatments , and previous natalizumab treatment ) . furthermore , the appearance of events during the study was performed by the kaplan - meier ( product - limit ) survival analysis . in the overall population , the cumulative proportion of patients free from clinical relapse was 88.1% ( figure 1 ) . figure 2 shows the cumulative proportion of patients free from clinical relapse with respect to prior exposure to natalizumab . patients without previous natalizumab exposure had improved relapse - free survival compared with those previously treated with natalizumab ( 90.5% versus 77.9% ; p = 0.021 ) . mean time to relapse was 29.6 months ( 95% confidence interval [ ci ] , 28.02531.202 ) . time to first relapse significantly decreased in patients receiving previous natalizumab treatment ( 23.767 2.218 versus 30.411 0.778 ; p = 0.021 ) . values decreased from 1.14 to 0.14 at 6 months , to 0.11 at one year , and to 0.09 at 2 years of treatment ( p < 0.0001 ) . at 6 months of follow - up , arr was significantly associated with the number of relapses in the year preceding the start of fingolimod treatment ( p = 0.049 ) and with the previous use of natalizumab ( p = 0.018 ) . no associations were found at 12 and 24 months . as shown in figure 3 , the cumulative proportion of patients free from confirmed edss progression was 69.0% . during the study period , mean edss score decreased from 2.7 1.1 at baseline to 2.5 1.1 at 18 months ( p = 0.13 ) . edss evaluation at 24 months disclosed a trend toward further decrease , though sample size was too small to reach statistical significance ( 2.7 1.1 versus 2.3 0.9 ; p = 0.501 ) . mean time to confirmed edss progression was 28.6 months ( 95% ci , 26.930.3 ) . subgroup analysis failed to show any difference in time to disability progression for patients undergoing previous natalizumab treatment . multivariate regression analysis showed no correlation between the risk of disability progression and age , gender , disease duration , number of previous treatments , previous immunosuppressant therapies , edss at baseline , previous contrast enhancing lesions , or previous natalizumab treatment . mri scans were obtained at baseline in all patients and in all 81 and 34 patients that reached 12 and 24 months of follow - up , respectively . as shown in figure 4 , time to recurrence of new t2 lesions was 25.8 months , on average ( 95% ci , 23.827.9 ) . multivariate regression analysis found that edss score at baseline was the only predictor of new or newly enlarging t2 lesion occurrence , as edss score at baseline was significantly lower in patients with new t2 lesions on follow - up mri ( p = 0.016 ) . mean time to the appearance of a new enhancing lesion was 28.9 months ( 95% ci , 27.230.7 ) . new contrast enhancing lesions were more common in patients undergoing previous natalizumab treatment ( 26.7% versus 15.3% , p = 0.046 ) . as shown in figure 6 , the cumulative proportion of patients free from any disease activity was 41.9% . multivariate regression analysis revealed lower edss score at baseline as the only predictor of disease activity recurrence after fingolimod start ( p = 0.018 ) . all patients were discharged at the end of the 6 hours of monitoring , but 8 patients ( 5.6% ) needed 2 hours of extended monitoring due to asymptomatic bradycardia . no significant modification of arterial pressure values was also registered . during the follow - up however , headache was reported by 25 patients ( 17.6% ) , diarrhea by 7 patients ( 4.9 ) , and arterial hypertension by 3 patients ( 2.1% ) . therapy was stopped in 13 patients ( 9.1% ) . in 7 patients ( 4.9% ) the interruption was due to lack of efficacy , in 2 patients ( 1.4% ) it was due to general intolerance , and in 3 patients ( 2.1% ) it was stopped due to the patient 's decision , and one patient ( 0.7% ) was lost to follow - up . in this prospective multicenter clinical practice study , fingolimod treatment was effective in providing freedom from disease activity and preventing clinical relapse in patients with rrms . after starting fingolimod , the cumulative proportion of patients free from clinical relapse throughout the follow - up was 88.1% , and 69.0% of patients remained free from disability progression . disability progression rates curves disclosed a trend toward further improvement over time . cumulatively during the study period , almost half of patients were free from any disease activity , that is , no relapses , no disability progression , no new or enlarged t2 lesions , and no gadolinium enhancing lesions . of interest , relapse rates were higher in patients with prior natalizumab treatment compared with patients without previous natalizumab exposure ( relapse - free survival 77.9% versus 90.5% , resp . ) . although prior receipt of natalizumab was associated with a shorter time to first relapse , there was no difference in time to disability progression between patients who had or had not undergone prior natalizumab treatment . it is a widely held notion that natalizumab withdrawal is associated with possible severe disease reactivation occurring within the first three or up to seven months after natalizumab discontinuation . rather than rebound activity , early relapses are likely to be underpinned by the clearance of natalizumab biological effect prompting recurrence of disease activity . hence , higher relapse rate and new gadolinium enhancing lesions at 6 months after switching from natalizumab to fingolimod could be possibly driven by early disease recrudescence of disease activity . recent studies suggest that a wash - out period as short as 4 to 4 weeks should be preferable in order to prevent severe disease reactivation after switching from natalizumab to fingolimod . nevertheless , our population underwent a three - month wash - out period as required by regulatory agencies in order to prevent potential safety issues from overlapping immunomodulatory effects . while no direct comparisons are intended , it is of interest to review the findings observed in phase 3 clinical trials of fingolimod and natalizumab in patients with rrms . the pivotal phase 3 clinical trials , freedoms and transforms , each of which enrolled over 1000 patients , showed that fingolimod at doses of 0.5 mg and 1.25 mg once daily significantly reduced arr and mri disease activity compared with placebo ( freedoms ) and interferon beta-1a ( transforms ) in patients with rrms . in the 24-month freedoms study , fingolimod also slowed disability progression , whereas no significant reductions in disability progression had emerged during the 12 months of the transforms study . during the 24-month period of the freedoms study , fingolimod reduced the risk of disability progression confirmed at three months ( 17.7% fingolimod 0.5 mg ; 16.6% fingolimod 1.25 mg ; 24.1% placebo ) . both fingolimod doses also showed a reduction in the aggregate annualized relapse rate ( 0.18 fingolimod 0.5 mg , 0.16 fingolimod 1.25 mg ) versus placebo ( 0.40 ) , representing relative reductions in annualized relapse rate of 54% and 60% , respectively . in the transforms study the annualized relapse rate was 0.16 in the 0.5 mg fingolimod group and 0.20 mg in the 1.25 mg fingolimod group versus 0.33 in the interferon group . in the pivotal affirm phase 3 trial of intravenous natalizumab , the 2-year relapse - free rate was 72.41% in the natalizumab group , compared with 46.35% with placebo . in a clinical practice setting , results from 343 consecutive patients with rrms who started treatment with natalizumab at 12 italian multiple sclerosis centers have recently been reported . over 42 months of follow - up , the cumulative proportion of patients free from relapse was 68% , 93% were free from edss progression , and 77% were free from mri activity . there was a reduction of arr of approximately 90% over the follow - up period , compared with the year preceding the start of natalizumab treatment . meanwhile , in a recent observational cohort study of 427 rrms patients receiving either fingolimod or natalizumab , the risk of disability progression was lower in the fingolimod versus natalizumab group ( 87.39% versus 82.7% , resp . ) and a greater proportion of patients receiving fingolimod was relapse - free at 12 months ( 75.79% fingolimod versus 71.73% natalizumab ) . the relapse rate was substantially reduced in both treatment groups within three months of commencing treatment and remained at similar low levels in each group throughout follow - up . similarly , edss was unchanged or improved in similar proportions of both groups and remained stable over 12 months of follow - up . treatment with fingolimod was well tolerated , and no patients had any severe adverse events . however , headache was the most common adverse event reported ( 17.6% ) . during the study , no concerns with cardiac function were encountered , and no patients had clinically significant bradycardia . the main focus of our study was to provide real world efficacy data from patients representative of the italian relapsing - remitting multiple sclerosis population meeting the eligibility criteria of the aifa for treatment with fingolimod . although direct comparisons can not be made , our results in a real world clinical practice setting are to great extent in line with those observed in large clinical trials . our findings yield further information to the growing body of evidence for the use of fingolimod in multiple sclerosis in europe . a recent review article summarized data on the efficacy and safety of fingolimod in patients eligible for therapy according to the european union label to provide practical guidance on the use of fingolimod in the clinic . in addition to pooled data from clinical trials , the review examined findings from recent european studies of real - world patient populations and concluded that , unlike some newer oral therapies for multiple sclerosis , fingolimod has a well - established safety and efficacy profile . until additional long - term data on fingolimod are available , clinicians should implement appropriate routine patient monitoring measures to guide and optimize treatment benefits and to minimize adverse events . we acknowledge that patients enrolled in our post - marketing study were quite heterogeneous in terms of follow - up length , ranging from 1 to 33 months ; nevertheless mean follow - up was 14.95 months , and follow - up data were available for at least 57% and 23.9% of patients at 12 and 24 months , respectively . we decided to analyze data of all enrolled patients since literature data indicated an early action of fingolimod due to its mechanism of action [ 15 ] . moreover , we included patients starting fingolimod after treatment with natalizumab who are at high risk of relapse in the first months of therapy . we also acknowledge that data from patients with prior natalizumab treatment might have yielded mixed results in regard to previous disease activity and duration . yet , the aim of our investigation was to perform a clinical study in real world setting as to provide efficacy data from a sample of patients representative of the overall population treated with fingolimod . in our study , fingolimod positively influenced the course of rrms in terms of degree of reduction of relapse , stabilization of edss , and reduction of mri activity . our data , showing no disease activity in about 50% of patients , confirmed the results of clinical trials .

objective . the aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting . methods . one hundred forty - two subjects with relapsing - remitting multiple sclerosis ( rrms ) were enrolled in three multiple sclerosis centers throughout central and southern italy between january 2011 and september 2013 . after enrollment , regular visits and edss assessment were scheduled every 3 months , and mri scan was obtained every 12 months . patients were followed up from 1 to 33 months ( mean 14.95 9.15 months ) . the main efficacy endpoints included the proportion of patients free from clinical relapses , from disability progression , from magnetic resonance imaging activity , and from any disease activity . results . out of 142 patients enrolled in the study , 88.1% were free from clinical relapse and 69.0% were free from disability progression ; 68.5% of patients remained free from new or newly enlarging t2 lesions and 81.7% of patients were free from gadolinium enhancing lesions . overall the proportion of patients free from any disease activity was 41.9% . conclusions . our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with rrms .

splenic infarction is an uncommon medical condition most commonly associated with a hypercoagulable state or a cardiovascular etiology . the typical presentation includes a left upper quadrant abdominal pain radiating to the left shoulder . the association with cirrhosis is rare and only a few cases have been reported to date . we describe the case of an elderly female patient with known history of primary biliary cirrhosis presenting for left upper quadrant abdominal pain secondary to splenic infarction . a 67-year - old female presented for a 1-day history of left upper quadrant abdominal pain . she described the pain as moderate , sharp , and radiating to her left shoulder . there was no history of fever , chills , abnormal bowel movements , nausea , or vomiting . her past medical history was remarkable for cirrhosis secondary to primary biliary cirrhosis complicated by hepatic encephalopathy and ascites . she denied recent trauma , previous miscarriage , deep vein thrombosis , or embolic disease . laboratory results on admission were comparable to previous routine blood draws done 2 months earlier and were the following : hemoglobin 10.3 g / dl , hematocrit 32% , platelet count 55 10/l , white blood cell count 9.1 10/l , international normalized ratio 1.5 , aspartate aminotransferase 39 iu / l , alanine aminotransferase 35 iu / l , alkaline phosphatase 151 iu / l , total bilirubin 2 mg / dl , total protein 5.6 g / dl , and albumin 2.3 g / dl . ekg , chest x - ray , and cardiac enzymes were all within normal range . computed tomography ( ct ) scan of the abdomen with contrast revealed cirrhotic morphology of the liver , large varices in the right lower quadrant , and numerous wedge - shaped areas of hypoenhancement extending to the periphery of the spleen concerning for splenic infarcts ( fig . doppler ultrasound of the spleen confirmed the presence of infarcts with preserved flow within the main splenic artery . further evaluations were performed to rule out other secondary causes of spontaneous splenic infarcts including a hypercoagulable workup , autoimmune disease markers , and an echocardiogram . follow - up at 2 months showed consistent resolution of her clinical symptoms and signs . splenic infarction is an uncommon cause of abdominal pain that usually occurs as a result of occluded splenic artery or one of its branches with a clot or an infected embolus . most common symptoms include left - sided abdominal pain , fever , nausea , and vomiting . in many cases , splenic infarction can be the primary presentation of an underlying condition . in about two - thirds of the cases , splenic infarction is reported as a result of a hypercoagulable state including hematologic malignancies or a cardiovascular etiology ( intracardiac thrombus , bacterial endocarditis ) . other less common causes include infectious mononucleosis , sickle cell disease , gaucher disease , wandering spleen , sepsis , pancreatitis , infiltrative diseases , and collagen - vascular diseases . spontaneous splenic infarct secondary to cirrhosis and portal hypertension has been rarely described in the literature [ 4 , 5 , 6 , 7 , 8 ] . one large case series of patients with splenic infarcts reported that only 3 out of 152 patients were secondary to portal hypertension . in case of underlying cirrhosis , splenic infarction has been reported after cyanoacrylate injection for gastric fundal varices , splenic artery ligation , liver transplantation , and histoacryl embolization . also , iatrogenic infarction may occur due to splenic artery spasm after intraarterial infusion of vasopressin for gastrointestinal bleed . spontaneous splenic infarction secondary to portal hypertension is due to hemodynamic changes rather than the occlusion of the splenic artery . the exact mechanism is unclear , although it is postulated that congestive splenomegaly resulting in greater oxygen requirements by the spleen combined with a decrease in the oxygen - carrying capacity of the blood caused by anemia results in anoxia and infarction of the spleen . also , cirrhosis often results in a hypercoagulable state . the probable mechanism of splenic infarction in our patient with primary biliary cirrhosis and portal hypertension is anoxia . contrast ct scan is currently the best noninvasive test to diagnose splenic infarctions and to rule out other pathologies that have a similar presentation . the diagnosis of splenic infarction in our case was made by ct scan and doppler ultrasound . conservative management often yields good results and consists of pain control and other supportive measures . splenectomy is only required in case of persistent symptoms or complications including splenic pseudocyst , abscess , or hemorrhage . the rate of resolution of splenic infarcts is unknown ; however , a few case reports documented complete resolution of infarcts due to infective endocarditis and atrial fibrillation on follow - up imaging . in one case with underlying cirrhosis , a defect was still present 6 months later suggesting different resolution rates depending on the underlying etiology keeping a high index of suspicion is appropriate in the presence of predisposing conditions including cirrhosis , left upper quadrant pain , and abdominal tenderness without a clear source .

spontaneous splenic infarction has been rarely reported as a complication of cirrhosis and portal hypertension . we describe the case of a 67-year - old female with past medical history of primary biliary cirrhosis presenting for a 1-day history of left upper quadrant pain . investigations were in favor of splenic infarcts secondary to portal hypertension . the patient improved with conservative management and no recurrence was noted on further follow - up . splenic infarction must be kept in mind when a patient with cirrhosis presents with left upper quadrant abdominal pain without a clear source .

the incidence of complex congenital heart disease is approximately 8.21/1000 live births in canada , with involvement of the right ventricular outflow tract ( rvot ) of approximately 10% . generally , initial rvot reconstruction is performed by patch , but due to the absence of a sufficient functioning pulmonary valve , the right ventricle will be volume - overloaded and dilate over time . the volume overload of the right ventricle is usually well tolerated , but over time it might lead to decreased exercise tolerance , dyspnea , arrhythmia , symptoms of heart failure , and , eventually , sudden death . at the time of ventricle dilatation , a valve conduit is chosen to reconstruct the rvot , since today s available valve conduits degenerate over time in absence of regeneration or growth potential [ 46 ] . the ideal would be a living autologous valve with regeneration , remodelling , and growth potential , implanted with minimal invasiveness , without tissue distortion or compromising valve function . tissue engineering techniques allows us to construct valves with remodelling , regeneration , and growth potential , but these valves have only limited availability for clinical use and are conventionally implanted . in 2000 . began using glutaraldehyde - fixed bovine jugular veins mounted on balloon - expandable stainless stents to be percutaneously implanted . these valves were initially implanted in patients with pulmonary valve stenosis , but nowadays pulmonary valve regurgitations can also be treated with these valves if the current annulus size is still suitable and not over - dilated . general disadvantages of the current clinically available transcatheter valves are availability for selected cases , high rate of stent fractures , and increased risk of endocarditis during follow - up . glutaraldehyde treatment is not an optimal option in congenital heart disease treatment because there is lack of growth potential as well as increased risk for early deterioration . the aim of the present study was to evaluate the implantation of a newly designed injectable te pulmonary heart valve with a self - expandable nitinol stent to reconstruct the rvot . all experiments were performed in accordance to the principles of laboratory animal care prepared by the national society of medical research , and the guide for the care and use of laboratory animals prepared by the institute of laboratory animal resources and published by the national institute of health ( nih , revised 1996 ) . the study was approved by the institutional review and ethics committee at the university of leipzig . details on decellularization of porcine pulmonary heart valves were previously reported . in brief , fresh porcine pulmonary heart valves were obtained from the slaughterhouse . after preparation and carefully trimming the muscle tissue to a minimum , the valves were placed in antibiotic solutions until decellularization with deoxycholic acid ( sigma chemical co , st . the decellularized pulmonary valves were sutured into a self - expendable nitinol stent ( pfm medical ag , koeln , germany ) with a diameter of 16 mm ( figure 1a , 1b ) . this size was chosen because the diameter of the pulmonary valve annulus was preoperatively measured , adding 10% to ensure optimal fitting of the injectable te heart valve into the pulmonary valve annulus . seven healthy pigs between 6 and 9 months of age with a median weight of 28 kg ( range 2631 kg ) were included in this study . all animals were pre - medicated and , after general anesthesia was induced , mechanical ventilation was started . a median sternotomy or limited lateral thoracotomy was performed to implant the injectable te pulmonary heart valve . one purse - string suture was placed at the level of the right ventricular outflow tract . after crimping the valve for at least 30 min , an introducer was used to implant the injectable te pulmonary heart valve ( figure 2 ) . the implanted valve was studied by epicardial echocardiographic examination ( vivid ; ge healthcare , munich germany ) , invasive pressure , and angiographic measurements . finally , 46 h after implantation , the animals were sacrificed and the injectable te heart valves were explanted , rinsed , and subjected to gross examination and histopathological analysis . , fresh porcine pulmonary heart valves were obtained from the slaughterhouse . after preparation and carefully trimming the muscle tissue to a minimum , the valves were placed in antibiotic solutions until decellularization with deoxycholic acid ( sigma chemical co , st . the decellularized pulmonary valves were sutured into a self - expendable nitinol stent ( pfm medical ag , koeln , germany ) with a diameter of 16 mm ( figure 1a , 1b ) . this size was chosen because the diameter of the pulmonary valve annulus was preoperatively measured , adding 10% to ensure optimal fitting of the injectable te heart valve into the pulmonary valve annulus . seven healthy pigs between 6 and 9 months of age with a median weight of 28 kg ( range 2631 kg ) were included in this study . all animals were pre - medicated and , after general anesthesia was induced , mechanical ventilation was started . a median sternotomy or limited lateral thoracotomy was performed to implant the injectable te pulmonary heart valve . one purse - string suture was placed at the level of the right ventricular outflow tract . after crimping the valve for at least 30 min , an introducer was used to implant the injectable te pulmonary heart valve ( figure 2 ) . the implanted valve was studied by epicardial echocardiographic examination ( vivid ; ge healthcare , munich germany ) , invasive pressure , and angiographic measurements . finally , 46 h after implantation , the animals were sacrificed and the injectable te heart valves were explanted , rinsed , and subjected to gross examination and histopathological analysis . the injectable te heart valve was guided by fluoroscopy ( figure 3 ) and successfully delivered in all animals , except in 1 were the valve migrated due to the discrepancy between the implanted valve and the native pulmonary valve annulus . angiography and epicardial echocardiography proved that all injectable te heart valves were competent , and no trans- or paravalvular leakage was seen in any of the 6 successful implantations ( figure 4 ) . invasive pressure measurement showed a median maximum pressure gradient of 4 mm hg ( range 35 mm hg ) and median maximum pressure gradient of 8 mm hg ( range 612 mm hg ) , confirmed by epicardial echocardiographic examination . during follow - up , none of the valves migrated and hemodynamic behavior of the implanted valves was stable . gross examination of the injectable te heart valve showed pliable leaflets without tears or bleeding . the leaflets were all intact and showed no thrombus formation ( figure 5a , 5b ) . histopathological examination showed a preserved extracellular matrix with absence of any tissue damage due to the delivery system or implantation process ( figure 6a6d ) . today s treatment options for complex congenital rvot disease are not yet optimal and need to be improved . allografts are still an excellent option , but availability is limited ; therefore , alternative materials are used such as glutaraldehyde - fixed conduits to correct congenital malformation of the rvot in neonates and infants . . showed similar survival rates for patients treated with allografts and xenografts , but freedom of re - operation was different for both groups , at 28% for xenografts versus 62% for allografts these xenografts showed serious deterioration during long - term follow - up , such as sclerosis and calcification . in a more recent study by vitanova et al . , different types of conduits for rvot reconstruction were compared in patients below the age of 1 year . they showed similar rates of freedom for reoperation for allografts , contegra , and hancock conduits at 38.18.3% , 38.011.3% , and 20.37.5% , respectively ( p=0.4 ) . the hancock conduit , however , was associated with a significantly higher rate of thrombosis ( p=0.01 ) and the patients receiving a contegra conduit developed faster conduit regurgitation or stenosis than patients with allografts ( p=0.01 ) . nevertheless , all these heart valve substitutes have no growth potential . new technologies are therefore needed that are free of glutaraldehyde , to allow tissue remodelling . tissue engineering could overcome this problem , which clinically started with autologous endothelial cell seeded grafting . one reason for this could be the different origins of tissue used for the extracellular matrix . excellent clinical results are achieved with human - origin tissue . another issue is the performed decellularization process itself , which can be very different and has enormous influence on the extracellular matrix . conventional surgical implantation techniques have been used for these te heart valves , but it would be desirable to implant these valves minimally invasively by using a catheter . percutaneous pulmonary valve implantation ( ppvi ) was started in 2000 by bonhoeffer et al . in patients with degenerated conduits within the rvot , showing initially limited benefit . nordmeyer et al . reported a high number of stent fractures , which can be dramatically reduced by performing pre - stenting using a strong stent or performing a valve - in - valve procedure . after modifications were done , this treatment option become promising , but only for selected patients . an additional patient group those with pulmonary valve regurgitation of different etiology could also benefit from this method . prospective randomized studies on the optimal timing for intervention of pulmonary valve regurgitation are not currently available . today , cardiac magnetic resonance imaging ( cmri ) is the criterion standard for diagnosing ventricular function , mass , and volumes , which is also important in evaluating the postoperative development of right ventricular volume reduction and cardiac improvement , resulting in better exercise tolerance . the improvement of right ventricular function after pulmonary valve implantation , however , did not decrease death in recent studies . cmri examination will also provide additional information of value in avoiding fatal complications of percutaneous pulmonary valve implantation by left coronary occlusion , which can occur immediately after or hours after the procedure has been completed ( 33 ) . mckenzie et al . showed comparative data of surgical pulmonary valve replacement to ppvi , showing freedom of reoperation was 94% , and in the expanded melody valve trial freedom of re - intervention was 53% . if ppvi is advocated in patients because it is less invasive and is suggested to be done at an earlier stage , modification of materials is needed to achieve this . kiefer et al . showed changes of the extracellular matrix , which were related to the crimping time . however , in a subcutaneous rat model , which is a passive screening model for calcification , there were no sign of increased tissue calcification . therefore , examinations in a large circulating animal model are needed to investigate the impact of tissue crimping on leaflet durability and calcification during long - term follow - up . the present study was performed by using a decellularized porcine extracellular matrix in the porcine model , which simulates the situation of implanting a decellularized allograft in humans . to implant this injectable te heart valve into the pulmonary position using a limited thoracotomy , the valve does not need to be extensively crimped . to implant an injectable te heart valve percutaneously additionally , because the decellularization of the pericardial tissue stays very pliable , and due to the absence of glutaraldehyde to cross - link , no tissue rupture can occur . the present feasibility study shows that injectable te heart valves can be implanted safely and that crimping for the delivery process can be safely performed without tissue distortion . long - term follow - up will be needed to evaluate functionality and absence of tissue distortion to eventually expand the use of this less invasive approach in humans . this feasibility study was performed to evaluate the influence of delivery procedure on an injectable te heart valve . however , due to the limitation of the acute setting of these experiments , long - term implantation studies will be needed to evaluate the injectable te heart valve behavior under permanent burden . this feasibility study was performed to evaluate the influence of delivery procedure on an injectable te heart valve . however , due to the limitation of the acute setting of these experiments , long - term implantation studies will be needed to evaluate the injectable te heart valve behavior under permanent burden . transcatheter implantation of an injectable te heart valve seems to be feasible , without tissue distortion due to the delivery procedure .

backgroundtranscatheter pulmonary valve replacement is currently performed in clinical trials , but is limited by the use of glutaraldehyde - treated bioprostheses . this feasibility study was performed to evaluate delivery - related tissue distortion during implantation of tissue - engineered ( te ) heart valves.material/methodsthe injectable te heart valve was mounted on a self - expanding nitinol stent ( n=7 ) and delivered into the pulmonary position in 7 pigs , ( weight 26 to 31 kg ) , performing a sternotomy or limited lateral thoracotomy . prior to implantation , the injectable te heart valves were crimped and inserted into an applicator . positioning of the implants was guided by fluoroscopy , and after careful deployment , angiographic examination was performed to evaluate the correct delivered position . hemodynamic measurements were performed by epicardial echocardiography . finally , the animals were sacrificed and the injectable te heart valves were inspected by gross examination and histological examination.resultsorthotopic deliveries of the injectable te heart valves were all successful performed , expect in 1 where the valve migrated due to a discrepancy between pulmonary valve annulus size and injectable te valve size . angiographic evaluation ( n=6 ) showed normal valve function , supported by epicardial echocardiography in which no increased flow velocity was measured , neither trans- nor paravalvular regurgitation . histological evaluation demonstrated absence of tissue damage from the delivery process.conclusionstranscatheter implantation of an injectable te heart valve seems to be possible without tissue distortion due to the delivery system .

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Activity Based Total Accountability Act of 2010''. SEC. 2. FINDINGS AND PURPOSE. (a) Findings.--The Congress finds as follows: (1) The Federal Government sends hundreds of billions of dollars to the States each and every year. (2) In Fiscal Year 2008, among the money sent to the States were $267 billion for health care, $53 billion for transportation, $47 billion for housing and urban development, $36 billion for education, and $27 billion for agriculture. (3) States receive money from the Federal Government through grants, loans, loan guarantees, property, cooperative agreements, interest subsidies, insurance, food commodities, and direct appropriations, among others means. (4) Every State spends money for common activities such as health care, transportation, housing, education, agriculture and other issues, yet some States are more effective than others when spending these Federal taxpayer dollars. (5) Taxpayers, legislators, and agencies should be able to objectively and reliably share data comparing apples-to-apples performance measurements that identify what government does and what it really costs. (6) Activity-based total accountability will show which States are the most effective with taxpayer dollars and lead to competition among States. (7) States demonstrating that they are more efficient with tax dollars by having lower activity costs will serve as models for others to ensure that there is more accountability for how tax dollars are spent and to ensure that the taxpayer is getting the best value for their dollar. (b) Purpose.--The purpose of this Act is to improve the policymaking process and government accountability at the State level by requiring annual accountings from State governments in a format that uses total accountability measures, including unit-cost data. SEC. 3. STATE FISCAL ACCOUNTING REPORTS. (a) In General.--Not later than 15 days before the end of a Federal fiscal year, each State government that receives Federal financial assistance in that Federal fiscal year shall submit a State fiscal accounting report for the Federal fiscal year to the Director of the Office of Management and Budget (hereinafter in this Act referred to as the ``Director''). (b) Contents of Report.--Each State fiscal accounting report shall include-- (1) a one-page summary that lists the total funding and expenditures of each budget entity of the State government; and (2) for each budget entity of the State government, a unit- cost summary for the Federal fiscal year. (c) Publication of Reports.--The Director shall publish each report received under this section on an Internet Web site of the Director not later than 30 days after receiving that report. SEC. 4. STANDARDIZATION OF STATE FISCAL ACCOUNTING REPORTS. (a) Standardization of Reports.--The Director shall ensure that each State fiscal accounting report is in such standardized form as the Director may prescribe. Such form shall permit the comparison of the information contained in a State fiscal accounting report with the information contained in every other State fiscal accounting report. (b) Initial Reports.--Not later than 180 days after the date of enactment of this Act, each State government that is required to submit a report under section 3 shall submit to the Director a description of the programs and other activities carried out by each budget entity of that State government over that fiscal year, including such information on those programs or activities as the Director may require. (c) Classification System.--Based on the descriptions submitted under subsection (b) and on what the Director determines to be the most relevant data available (including data from the most recent census), the Director shall by rule do the following: (1) Establish a uniform system for classifying such programs and activities within categories (hereinafter in this Act referred to as ``agency activities'') identified by the Director. (2) For each agency activity, identify conduct (hereinafter in this Act referred to as an ``activity unit'') that, in the determination of the Director, constitutes a completed instance of such agency activity. (3) For each agency activity, identify, to the extent practicable, performance measures for that agency activity, and, in publishing a report under section 3(c), link electronically such performance measures to that agency activity. SEC. 5. UNIT-COST SUMMARY. Each unit-cost summary for a budget entity of a State government shall be in such form as the Director may prescribe, be one page long, and include the following: (1) A statement of funds available, as described under section 6. (2) For each agency activity that the budget entity began, attempted, continued, or completed, a line-item listing as described under section 7. (3) A reconciliation of funds available with adjusted expenditures as described under section 8. SEC. 6. STATEMENT OF FUNDS AVAILABLE. (a) In General.--A statement of funds available shall identify-- (1) in accordance with subsection (b), each source of funds available for expenditure or obligation by the budget entity and the amount of such funds; and (2) the sum of all amounts identified under paragraph (1). (b) Identification of Sources.--In identifying the sources of funds available for expenditure or obligation by the budget entity, the budget entity shall include the following: (1) All funds made available by State appropriations laws. (2) Any Federal financial assistance provided by a Federal department or agency. (3) Any other sources the Director determines appropriate. SEC. 7. AGENCY ACTIVITY LINE ITEM LISTINGS. (a) In General.--A line item listing for an agency activity shall-- (1) identify-- (A) the agency activity; (B) in accordance with subsection (b), the total amount of funds that the budget entity expended in carrying out the agency activity; (C) the number of activity units of the agency activity the budget entity began, attempted, continued, or completed; and (D) the unit-cost of the agency activity, determined in accordance with subsection (c); and (2) describe as many of the following as are relevant to the agency activity: (A) What conduct constitutes an activity unit. (B) Each purpose for which the budget entity engaged in that agency activity. (C) Each person that is an intended beneficiary of that agency activity. (b) Special Rules for Determination of Expenditures.-- (1) Allocation of expenditures for certain agency activities.--If the Director determines that there is an agency activity for which no method of measuring the accomplishment of the agency activity exists, an expenditure for that agency activity must be consistently allocated to what is, in the determination of the Director, a sufficiently similar agency activity for which such a method exists. (2) Payments to contractors or subordinate entities included.--An identification of the total amount of funds that a budget entity expended shall include any amounts paid to a contractor or subordinate entity. (c) Determination of Unit-Cost.-- (1) In general.--The unit-cost of an agency activity shall be determined in accordance with the following formula: m UC = --------------------------------------. q (2) Definition of terms in formula.--For purposes of the formula in paragraph (1)-- (A) UC is the unit-cost of the agency activity; (B) m is the amount described in subsection (a)(1)(B); and (C) q is the number described in subsection (a)(1)(C). SEC. 8. RECONCILIATION OF FUNDS AVAILABLE WITH ADJUSTED EXPENDITURES. (a) In General.--A reconciliation of funds available with adjusted expenditures shall-- (1) identify the adjusted expenditures of the budget entity; and (2) explain any difference between the adjusted expenditures and the sum of all funds available for expenditure or obligation by the budget entity (determined in accordance with section 6). (b) Determination of Adjusted Expenditures.-- (1) In general.--The adjusted expenditures of the budget entity shall be determined in accordance with the following formula: AE = EXP + PT + REV. (2) Definition of terms in formula.--For purposes of the formula in paragraph (1)-- (A) AE is the adjusted expenditures; (B) EXP is the sum of all expenditures by the budget entity for agency activities; (C) PT is the sum of all pass-throughs identified by the budget entity under subsection (c); and (D) REV is the sum of all reversions identified by the budget entity under subsection (c). (c) Identification of Pass-Throughs and Reversions.--A budget entity may identify an amount as a pass-through or a reversion if the amount satisfies criteria established by the Director. SEC. 9. NONCOMPLIANCE. If the Director determines that a State government has failed, with respect to a Federal fiscal year, to file a sufficient and timely State fiscal accounting report under this Act, the Director shall so inform the head of each Federal department or agency. Each such head shall withhold 10 percent of any Federal financial assistance provided to the State government for the next Federal fiscal year. SEC. 10. RULES. The Director is authorized to make such rules as may be necessary to carry out this Act. SEC. 11. DEFINITIONS. In this Act: (1) The term ``State government'' means the government of each of the several States, the District of Columbia, and any commonwealth, territory, or possession of the United States. (2) The term ``budget entity'' means a State agency or the State judiciary. (3) The term ``agency activity'' means major operational activities carried out by a budget entity. (4) The term ``Federal financial assistance'' has the meaning given such term in section 7501 of title 31, United States Code, and also includes any other amounts that the Director determines appropriate.

National Activity Based Total Accountability Act of 2010 - Requires each state government that receives federal financial assistance in a federal fiscal year to submit a state fiscal accounting report for such fiscal year to the Director of the Office of Management and Budget (OMB) that includes: (1) a one-page summary listing the total funding and expenditures of each budget entity of the state government; and (2) a unit-cost summary for each such entity that includes a statement of funds available, a line-item listing for each agency activity that the entity began, attempted, continued, or completed, and a reconciliation of funds available with adjusted expenditures. Sets forth formulae for determining unit-cost and adjusted expenditures. Requires the Director to: (1) publish each report on an OMB website; (2) ensure that such state reports use a standardized form that permits the comparison of information; (3) establish a uniform system for classifying programs and activities; (4) identify conduct for each agency activity that constitutes a completed instance of such activity; and (5) identify performance measures for each agency activity. Requires the Director to inform each federal agency if a state fails to file such report and requires the agency to withhold 10% of any federal financial assistance provided to such state for the next fiscal year.

Tragic “Fast & Furious” actor Paul Walker left his entire $25 million estate to his only child, according to a report Tuesday. Walker’s father, also called Paul, who was named executor of the estate, filed his son’s will in a Los Angeles court that leaves every penny of his son’s fortune to 15-year-old Meadow Walker. The late Paul Walker's daughter, Meadow, is shown leaving home with a couple of friends as she continues to mourn her father's tragic death. (Raef-Ramirez/AKM-GSI) The action movie star, who died in a fiery November car crash in Santa Clarita, Calif., appointed his mother, Cheryl, as Meadow’s guardian, according to court papers obtained by TMZ. Paul Walker, who died in a November car crash, has left $25 million to his 15-year-old daughter Meadow, pictured, but nothing to his girlfriend, Jasmine Pilchard-Gosnell, or other family members. (Chiva/INFphoto.com) Walker, 40, apparently left nothing to other family members or his girlfriend, Jasmine Pilchard-Gosnell, 23, who began dating the actor when she was 16. First responders are seen here gathering evidence near the wreckage of the Porsche that crashed in November, killing actor Paul Walker. (Dan Watson/AP) Meadow grew up in Hawaii, where she lived with her mother, Rebecca Soteros. The girl had been living with her father in California at the time of his death. From right, Paul Walker Sr. and his son Cody arrange details for actor Paul Walker's funeral. (Hector Campos/Splash News) A court hearing is set for later this month on a petition Paul Walker Sr. filed asking to grant his son’s wishes to make Cheryl Walker the guardian of Meadow. Paul Walker Sr., left, and his son Cody, right, brother of the late Paul Walker, are shown outside a Georgio Armani BH as the actor's funeral approached. (Hector Campos/Splash News) It was unclear Tuesday if Soteros planned to object to the arrangement. Paul Walker's mother, Cheryl, is spotted taking out the trash and bringing in the mail at her home in Los Angeles, Calif. (Mariotto/INFphoto.com) Meadow Walker was present Nov. 30 when her father and his pal, race car driver Roger Rodas, went for a spin in a Porsche Carrera GT and crashed into a light pole and tree at more than 100 mph. Paul Walker's tearful girlfriend, Jasmine Pilchard-Gosnell, made a highly emotional visit to his Santa Barbara home shortly after the actor's death in a fiery car crash. (Splash News) Just before the deadly crash, Walker and his daughter attended a fund-raiser for his Reach Out Worldwide charity. In May, actor Paul Walker attended the 'Fast & Furious 6' world premiere in London. The movie franchise's seventh installment is still on track for release in 2015. (Stuart C. Wilson/Getty Images for Universal Pictures) Days before his death, Walker told friends he was the happiest he’d ever been since his daughter came to live with him. “We’re matching up sweet!” Walker told reporters of his relationship with Meadow. “She’s been with her mom her whole life and she wants a relationship with her pops. It’s working out really well right now.” Following the tragedy, Meadow Walker called her father “My REAL life hero!” in a Facebook post. “When I was little he taught me to walk, taught me to smile and taught me to never give up,” she wrote. “I loved him even before I knew what love was.” Born in Glendale, Calif., Paul Walker portrayed undercover FBI agent Brian O’Conner in five “Fast & Furious” movies. Walker was filming the seventh installment of the wildly successful franchise when he was killed. The film is still scheduled to be released in 2015. “They’re having to rewrite, they’re having to do whatever they’re having to do to deal with the situation,” actor Kurt Russell — who will star in “Fast & Furious 7” — said last month at the Sundance Film Festival. “Listen, it’s catastrophic.” Sign up for BREAKING NEWS Emails privacy policy Thanks for subscribing! ||||| Paul Walker's Will $25 Million Estate Curious Language Paul Walker's Will ... $25 Million Estate -- Curious Language EXCLUSIVE was worth $25 million when he died and there seems to be some possibility of a family conflict ... this, based on new documents obtained by TMZ.We've obtained a copy of Paul Walker's will. Walker left his entire estate -- $25 mil -- to his 15-year-old daughter Meadow.Paul's dad -- the named executor -- filed Paul's will with the court. Paul's dad has petitioned the court to appoint Paul's mother -- Cheryl -- guardian of Meadow. What's more, Paul's dad wants Cheryl to be the guardian of the $25 mil. This is exactly what Paul wanted under the will.Now Meadow lives with her mom, Rebecca Soteros. If Paul gets his last wish, grandma will become Meadow's guardian. It's unclear if Rebecca approves, but it's definitely strange that Paul wanted his mom to be guardian since Meadow lives with Rebecca.A court hearing is scheduled for later this month.

– Paul Walker's entire $25 million estate is going to his 15-year-old daughter, Meadow. But TMZ notes an interesting twist: Paul's dad was named executor, and he petitioned the court to appoint Paul's mom as Meadow's guardian. Paul's mom would then also be the guardian of the $25 million, which TMZ reports is what Walker's will dictates. It's interesting because Meadow lives with her mom, so it's rather odd that Walker would have wanted someone else (his mom) to be her guardian. A court hearing will be held later this month. Also interesting: Walker apparently left nothing to other family members or his girlfriend of seven years, the New York Daily News reports.

organophosphorus agents are used in agriculture as pesticides and are stocked by the military as chemical warfare agents . seizures , respiratory arrest , and death are explained by a cascade of reactions that begins with inhibition of acetylcholinesterase . although acetylcholinesterase in red blood cells and butyrylcholinesterase in plasma are established biomarkers of organophosphorus ester ( op)1 exposure , additional biomarkers are being sought . albumin has the potential to serve as a new biomarker of op exposure ( 1,2 ) . albumin has been reported to covalently bind diisopropylfluorophosphate ( dfp ) , sarin , soman , cyclosarin , tabun , 10-fluoroethoxyphosphinyl - n - biotinamido pentyldecanamide ( fp - biotin ) , chlorpyrifos oxon ( cpo ) , and dichlorvos ( 26 ) and to hydrolyze cpo , paraoxon ( 7,8 ) , and o - hexyl o-2,5-dichlorophenyl phosphoramidate ( 9 ) . mass spectrometry has identified tyrosine 411 of human albumin as the site for covalent attachment of op nerve agents and op pesticides ( 6 ) . a second site for covalent attachment of soman was suggested by experiments that found more fluoride ion released than could be accounted for by one site in albumin ( 3 ) . pretreatment of albumin with decanoate , a lipid that binds to the tyr 411 subdomain , inhibited incorporation of 91% of h - dfp , leaving open the possibility that 9% of the h - dfp bound to other sites ( 10 ) . crystallization trials of cpo - labeled human albumin yielded gelatinous soft amorphous crystals , further suggesting the likelihood that more than one site was labeled and that labeling was not uniform . the goal of this study was to determine if sites in addition to tyr 411 could make a covalent bond with op and to identify the labeled residues . 1abbreviations : cpo , chlorpyrifos oxon ; dfp , diisopropylfluorophosphate ; fp - biotin , 10-fluoroethoxyphosphinyl - n - biotinamido pentyldecanamide ; op , organophosphorus ester ; lc / ms / ms , liquid chromatography tandem mass spectrometry ; maldi - tof - tof , matrix - assisted laser desorption tandem time - of - flight mass spectrometry . abbreviations : cpo , chlorpyrifos oxon ; dfp , diisopropylfluorophosphate ; fp - biotin , 10-fluoroethoxyphosphinyl - n - biotinamido pentyldecanamide ; op , organophosphorus ester ; lc / ms / ms , liquid chromatography tandem mass spectrometry ; maldi - tof - tof , matrix - assisted laser desorption tandem time - of - flight mass spectrometry . our starting premise was that op bound exclusively to tyr 411 of human albumin . for certain studies the sample was checked by mass spectrometry to confirm the site of op labeling , and to our surprise , we found several cpo - labeled peptides . our studies with human plasma were initiated with the goal of identifying op - labeled proteins in human plasma . fp - biotin was used for studies with plasma because biotinylated peptides are readily purified by binding to immobilized avidin beads ( 1,11 ) . fp - biotin ( mw 592.32 ) was custom synthesized in the laboratory of dr . charles m. thompson at the university of montana ( missoula , mt ) ( 12 ) . west chester , pa ; met-674b ) was dissolved in ethanol and stored at 80 c . dfp , a liquid with a concentration of 5.73 m , was from sigma ( d0879 ) . soman from ceb ( vert - le - petit , france ) was dissolved in isopropanol . a proteome partitioning kit , proteomelab igy-12 high capacity in spin column format contained igy antibodies directed against the 12 most abundant proteins in human plasma ( beckman coulter # a24331 s0510903 ) including albumin , igg , fibrinogen , transferrin , iga , igm , hdl ( apo a - i and apo a - ii ) , haptoglobin , -1-antitrypsin , -1-acid glycoprotein , and -2-macroglobulin . cibacron blue 3ga agarose ( sigma , c1535 ) bound 1020 mg of human albumin per ml of gel . porcine trypsin ( promega , madison , wi ; v5113 sequencing grade modified trypsin ) at a concentration of 0.4 g/l in 50 mm acetic acid was stored at 80 c . louis , mo ; p6887 from porcine gastric mucosa ) was dissolved in 10 mm hcl to make a 1 mg / ml solution and stored at 80 c . monomeric avidin agarose beads ( # 20228 ) were from pierce co. neutravidin agarose beads ( # 29202 ) were from thermo scientific ( rockford , il ) . human plasma ( edta anticoagulant ) was from an adult male , who had fasted overnight before donating blood . two hundred microliters of human plasma were fractionated into low and high abundance proteins by processing 20 l of plasma at a time on the beckman coulter proteome igy spin column depletion kit . of this , 123 l was labeled with fp - biotin , 123 l was used as a negative control , and the remainder was used for determination of protein concentration . a 123 l aliquot of the high abundance fraction was treated with 1.25 l of 20 mm fp - biotin for 48 h at 37 c at ph 8.0 . excess fp - biotin was removed by dialysis against 2 4 l of 10 mm ammonium bicarbonate . proteins , in 8 m urea , were reduced with 5 mm dithiothreitol and alkylated with 40 mm iodoacetamide . the samples were diluted to reduce the concentration of urea to 2 m. proteins were digested with a 1:50 ratio of trypsin to protein at 37 c overnight . the trypsin was inactivated by heating the sample in a boiling water bath for 10 min . it was necessary to inactivate trypsin because trypsin could have destroyed the avidin protein used in the next step . fp - biotinylated peptides were purified by binding to 0.5 ml of monomeric avidin beads . the column was washed with water to remove salts , and fp - biotinylated peptides were eluted with 10% acetic acid . the eluate was dried in a vacuum centrifuge in preparation for mass spectrometry . an albumin - depleted plasma sample was prepared by binding 0.6 ml of human plasma to 2 ml of cibacron blue and collecting the protein that eluted in 10 ml of 10 mm triscl , ph 8.0 , containing 0.3 m nacl . the protein was desalted , concentrated to 0.5 ml , and labeled with 100 m fp - biotin at 37 c for 16 h in 10 mm ammonium bicarbonate . the labeled protein was denatured in 8 m urea , reduced with dithiothreitol , carbamidomethylated with iodoacetamide , and desalted on a spin column . the entire sample was digested with 40 g of trypsin ( promega ) at 37 c overnight . the fp - biotinylated tryptic peptides were bound to 0.1 ml of neutravidin beads , washed with high salt buffers and water , and eluted with 45% acetonitrile and 0.1% formic acid . five micrograms of the high abundance fp - biotinylated peptides purified with monomeric avidin beads was analyzed on the qstar elite liquid chromatography tandem mass spectrometry ( lc / ms / ms ) system with proteinpilot 2.0 software at the applied biosystems laboratories ( framingham , ma ) . a second 5 g aliquot from the same protein preparation , a negative control sample , and the neutravidin purified peptides were analyzed by lc / ms / ms on the qtrap 2000 mass spectrometer ( applied biosystems ) at the university of nebraska medical center with analyst 1.4.1 software . the digest was dried in a vacuum centrifuge and dissolved in 5% acetonitrile and 0.1% formic acid to make 0.5 g/l . a 10 l aliquot was injected into the hplc nanocolumn ( # 218ms3.07515 vydac c18 polymeric rev - phase , 75 m i.d . peptides were separated with a 90 min linear gradient from 0 to 60% acetonitrile at a flow rate of 0.3 l / min and electrosprayed through a nanospray fused silica emitter ( 360 m o.d . , 75 m i.d . , 15 m taper , new objective ) directly into the qtrap 2000 , a hybrid quadrupole linear ion trap mass spectrometer . an ion spray voltage of 1900 v was maintained between the emitter and the mass spectrometer . information - dependent acquisition was used to collect ms , enhanced ms , and ms / ms spectra for the three most intense peaks in each cycle , having a charge of + 1 to + 4 , a mass between 400 and 1700 m / z , and an intensity > 10000 counts per s. all spectra were collected in the enhanced mode , that is , using the trap function . precursor ions were excluded for 30 s after one ms / ms spectrum had been collected . collision energies between 20 and 40 ev were determined automatically by the software , based on the mass and charge of the precursor ion . the mass spectrometer was calibrated on selected fragments from the ms / ms spectrum of glu - fibrinopeptide b. ms / ms spectra were submitted to mascot for identification of labeled peptides and amino acids ( 13 ) . mascot identified fp - biotinylated y*lyeiar ( score 17 ) , hpy*fyapellffak ( score 14 ) , and mpcaedy*lsvvlnqlcvlhek ( score 15 ) but none of the other fp - biotinylated peptides . the others were identified by manually searching the ms / ms data files using the extracted ion chromatogram feature of the analyst software . the scores were low because the software did not recognize the characteristic fragments of fp - biotin at 227 , 312 , and 329 . it also did not recognize the 591 ion of fp - biotin or the fp - biotin - tyrosine immonium ions at 708 and 691 or fragments containing dehydroalanine in place of serine . the ions that mascot did not recognize were often very intense . the mascot modification file is an open source software called unimod . the fp - biotin modification on serine , threonine , and tyrosine access to the modification is freely available to all mascot users in the variable modifications menu under the name fp - biotin . peptides yielding fp - biotin fragments at 227 , 312 , and 329 amu were identified using the extracted ion chromatogram feature of abi s analyst software . neutral loss of fragments of fp - biotin were identified by manual inspection of ms / ms spectra . a 0.5 l aliquot of essentially salt - free samples was spotted on a maldi target plate , air - dried , and overlaid with 0.5 l of 10 mg / ml -cyano-4-hydroxy cinnamic acid in 50% acetonitrile and 0.1% trifluoroacetic acid . ms spectra were acquired using a maldi - tof - tof 4800 ( applied biosystems ) , with a laser power of 3000 v , in positive reflector mode . the mass spectrometer was calibrated against des - arg - bradykinin ( 904.468 da ) , angiotensin 1 ( 1296.685 da ) , glu - fibrinopeptide b ( 1570.677 da ) , and neurotensin ( 1672.918 da ) ( cal mix 1 from applied biosystems ) . a 5 l aliquot of 10 mg / ml albumin was diluted with 5 l of 1% trifluoroacetic and digested with 2 l of 1 mg / ml porcine pepsin for 12 h at 37 c . the digest was diluted with 50% acetonitrile and 0.1% trifluoroacetic acid to give a final protein concentration of about 0.5 mg / ml . a 0.5 l aliquot was spotted on the maldi target plate , dried , and overlaid with 0.5 l of 10 mg / ml -cyano-4-hydroxy cinnamic acid . ms spectra were acquired with the laser set at 3000 v and were saved to data explorer . when the saved spectrum was opened in data explorer , the cluster areas appeared in an output window . percent op - labeled tyr 411 was calculated by dividing the cluster area of the labeled peptide by the sum of the cluster areas for the unlabeled and labeled peaks . the unlabeled peptides were vrytkkvpqvstptl ( 1717.0 amu ) and lvrytkkvpqvstptl ( 1830.1 amu ) . after covalent bond formation with cpo , these masses increased by 136 amu to become 1853.0 and 1966.1 amu . after covalent bond formation with fp - biotin , these masses increased by 572.3 to become 2289.3 and 2402.4 amu . at the time that we prepared cpo - labeled human albumin , we knew that tyr 411 was labeled by cpo and had no reason to suspect that other residues might also be labeled . cpo dissolved in ethanol was added to an albumin solution in 10 mm ammonium bicarbonate , ph 8.3 , and 0.01% sodium azide in six additions over a 1 month period . the labeling efficiency was poor when the albumin concentration was 500 mg / ml , so the albumin was diluted to 35 mg / ml , and then to 5 mg / ml , and finally to 1 mg / ml . the final ratio was 7.7 mol of albumin to 146 mol of cpo . during the 1 month labeling time , the decision to add more cpo was based on the percent tyr 411 labeled . no further additions of cpo were made after 85% of the tyr 411 had been labeled . the labeled albumin was dialyzed against 10 mm potassium phosphate , ph 7.0 , and 0.01% azide and processed for lc / ms / ms analysis in the qtrap mass spectrometer . the conditions reported to label 1 mol of albumin with 1 mol of dfp were used ( 10 ) . human albumin ( 1.8 mg / ml ) in 10 mm triscl , ph 8.0 , was treated with a 20-fold molar excess of dfp for 2 h at room temperature . the reaction was stopped by the addition of solid urea to 8 m and boiling for 10 min in the presence of 10 mm dithiothreitol . the experiment was repeated with fp - biotin , soman , and cpo . a 15 m solution of albumin in 10 mm triscl ph 8.0 was treated with 150 m fp - biotin or 150 m soman or 150 m cpo for 2 h at 22 c . samples with intact disulfides were digested with pepsin and analyzed by maldi - tof . carbamidomethylated tryptic peptides were analyzed by lc / ms / ms . tryptic peptides labeled with fp - biotin were also purified on monomeric avidin beads eluted with 50% acetonitrile and 0.1% formic acid and analyzed by maldi - tof - tof . the stability of cpo - labeled tyr 411 in human albumin was tested at ph 1.5 , 7.4 , and 8.3 after incubation for up to 7 months at 22 and 80 c . albumin labeled on 97% of tyr 411 with diethoxyphosphate was prepared by incubating 1 mg / ml human albumin ( 15.6 m ) in 10 mm triscl , ph 8.0 , and 0.01% sodium azide with 118 m cpo for 2.5 days at 22 c . excess cpo was removed by dialysis of the 8.5 ml solution against 2 4 l of 10 mm ammonium bicarbonate , ph 8.3 , and 0.01% azide . the ph of 2.6 ml of the dialyzed cpo - albumin was adjusted to ph 1.5 by adding 2.6 ml of 1% trifluoroacetic acid . half of the sample was stored at room temperature , and half was divided into 40 l aliquots and stored at 80 c . the ph was adjusted to ph 7.4 by dialyzing 3.3 ml of the cpo - albumin preparation against 4.5 l of 10 mm potassium phosphate , ph 7.4 , and 0.01% azide . to avoid freezethaw artifacts , samples intended for storage at 80 c were divided into 20 l aliquots so that each tube was thawed only once . the ph of 2.6 ml of cpo - albumin was brought to ph 8.3 by dialysis against 10 mm ammonium bicarbonate and 0.01% sodium azide , ph 8.3 . samples to be stored at 80 c were divided into 65 tubes each containing 20 l . after various times , a tube was removed from 80 c storage , and the entire contents were digested with pepsin . the digests were analyzed by maldi - tof , and % labeled tyr 411 was calculated from cluster areas as described above . the sample stored at 80 c in ph 7.4 buffer was analyzed by lc / ms / ms to determine whether sites in addition to tyr 411 were labeled . the cpo - albumin was denatured , reduced , carbamidomethylated , and digested with trypsin in preparation for lc / ms / ms . five tyrosines and two serines in human albumin were labeled with fp - biotin including tyr 138 , tyr 148 , tyr 401 , tyr 411 , tyr 452 , ser 232 , and ser 287 ( table 1 ) . covalent binding to tyrosine or serine results in loss of the fluoride ion from soman , dfp , and fp - biotin and of the aromatic ring from cpo , so that the added mass is 162.2 for soman , 164.1 for dfp , 136.0 for cpo , and 572.3 for fp - biotin . a 227 amu ion is produced by cleavage between carbon 16 and the adjacent nitrogen . a 329 amu ion is produced by cleavage between carbon 10 and the adjacent nitrogen . the 312 amu ion is produced by loss of the amine from the 329 ion . residue numbers in accession # gi : 3212456 are for the mature albumin protein and do not include the 24 amino acid signal peptide . supporting ms / ms spectra for these assignments are in figures 26 . a peptide labeled with fp - biotin had ions at 227 , 312 , and 329 atomic mass units ( amu ) resulting from fragmentation of fp - biotin ( 12 ) . two ions characteristic of covalent binding of fp - biotin to the hydroxyl group of tyrosine are the immonium ion of tyrosine - fp - biotin at 708 amu and its partner ion at 691 amu , produced by loss of nh3 . the 708 and 691 amu masses are prominent in figure 2a , b but barely visible in figure 3a , b . an additional complexity in figure 2a is the presence of ions that had lost a 329 or 226 amu fragment from fp - biotin . ( a ) tyr 411 in peptide ytk and ( b ) tyr 138 in peptide ylyeiar are covalently modified by fp - biotin . the characteristic fragments of fp - biotin at 227.2 , 312.4 , and 329.3 amu are present . ions characteristic of fp - biotin modification on tyrosine are the immonium ion at 708 amu and the immonium ion minus 17 at 691 amu . support for modification of the first tyrosine rather than the second in ylyeiar is the mass of ions a2 , b2 , and a2 . the doubly charged parent ion in panel a had a mass of 492.2 amu . the triply charged parent ion in panel b had a mass of 500.9 m / z the fp - biotin tyrosine immonium ion is at 708.5 ; after neutral loss of 226 , its mass is 482.9 . ( b ) tyr 401 in peptide qncelfeqlgeyk is covalently modified by fp - biotin . the triply charged parent ion in b has a mass of 744.2 m / z . ms / ms spectrum of albumin peptide labeled with fp - biotin on tyrosine 452 . internal fragmentation at proline yielded the 458.2 ion for pc(cam)ae and the 573.2 ion for pc(cam)aed . the characteristic fragments of fp - biotin at 227.2 , 312.2 , and 329.4 are present . after loss of an amine , the fp - biotin tyrosine immonium ion has a mass of 691.4 amu . ( a ) ms / ms spectrum of albumin peptide labeled with fp - biotin on ser 287 . the evidence for modification on serine is the presence of a b - ion series for the dehydroalanine form of the peptide , designated . the 591.4 amu ion is fp - biotin released from serine where the fluoride ion has been replaced by a hydroxyl group . release of the entire op accompanied by formation of dehydroalanine is a characteristic of op bound to serine . internal fragmentation at proline yielded masses at 284.0 for pad , 369.1 for psla , and 397.2 for padl . fragmentation in the mass spectrometer eliminates the op from serine and simultaneously converts serine to dehydroalanine . the masses in figure 2a are consistent with the sequence ytk where the added mass of 572 amu from fp - biotin is on tyr . the complete y - ion series is present ( y1 , 147.0 amu , lys ; y2 , 248.4 amu , lysthr ; and the doubly charged , fp - biotinylated parent ion ) . peaks at 227.2 , 312.4 , 329.4 , 691.3 , and 708.5 amu are indicative of the presence of fp - biotinylated tyrosine . the remaining major peaks are consistent with various fp - biotinylated tyrosine fragments missing pieces of the fp - biotin moiety . additional evidence for labeling on tyr 138 rather than on tyr 140 was the presence of the a2 ion at 821.4 amu , the b2 ion at 849.2 amu , the a1 ion at 354.8 , and the a2 ion at 411.4 m / z ( figure 2b ) . if the fp - biotin had been attached to tyr 140 , the masses would have been a2 = 249 , b2 = 277 , a1 = 68 , and a2 = 125 amu . masses at 708.2 and 691.3 amu for fp - biotinylated tyrosine confirm the presence of fp - biotinylated tyrosine in the peptide . analysis of the missed cleavage peptide kylyeiar supports labeling on tyr 138 ( data not shown ) . evidence for labeling on tyr 148 rather than on tyr 150 is the presence of the b4 ion at 1118.5 amu , the a4 ion at 545.4 amu , and the b4 ion at 559.3 m / z . the total mass of the b4 fragment ( 1117.6 amu ) is equal to the fragment hpyf ( 545 amu ) plus the added mass from fp - biotin ( 572 amu ) . of the four residues in the b4 fragment , tyr 148 is the most reasonable candidate for labeling . fragment masses for b5 and b6 also support labeling of tyr 148 rather than tyr 150 . an extensive y - ion series ( y2y8 ) supports the assignment of this peptide . masses at 227.3 , 312.2 , and 329.4 indicate the presence of fp - biotin . a similar analysis was made for peptides rhpyfyapellffak and hpyfyapellffakr , which differ from hpyfyapellffak by virtue of missed cleavages ( data not shown ) . peptide qncelfeqlgeyk in figure 3b is fp - biotinylated on tyr 401 as demonstrated by the y2 ion at 882.5 amu , the y3 ion at 1011.5 amu , the y4 ion at 1068.5 amu , and the y5 ion at 1181.8 amu . the y2 mass is equal to the sum of lys ( 147 amu ) , tyr ( 163 amu ) , and the added mass of fp - biotin ( 572 amu ) . a variety of larger , multiply charged y - ion fragments support the labeling assignment . fragments at 227.2 , 312.2 , and 329.3 amu indicate the presence of fp - biotin in the peptide . the best evidence in support of this interpretation is the doubly charged mass at 720.4 m / z , which is consistent with the b7 ion plus the added mass from fp - biotin . masses at 227.2 , 312.2 , and 329.4 indicate the presence of fp - biotin . masses at 691.4 and 708.4 amu indicate the presence of fp - biotinylated tyrosine in this peptide . a missed cleavage form of this peptide , rmpcaedylsvvlnqlcvlhek , was also analyzed , and the results support labeling of tyr 452 ( data not shown ) . existence of an fp - biotinylated serine is indicated by the major peak at 591.4 amu . this is a characteristic mass from fp - biotin that appears as the result of -type elimination of fp - biotin from a serine adduct ( figure 5b ) , during collision - induced dissociation in the mass spectrometer ( 12 ) . the complementary peptide fragment arising from this fragmentation contains a dehydroalanine in place of serine . the masses of a b - series ( b5b12 ) containing a dehydroalanine residue support the elimination of fp - biotin from serine . of the residues in the b5 fragment ( shcia ) , serine at position 287 is a candidate for fp - biotinylation . the cysteine might have been considered a target for labeling , but the overall mass of the fragment is consistent with carbamidomethylation on the cysteine . a y - ion series ( y4y15 ) additional support for the presence of fp - biotin in the peptide comes from characteristic masses at 312.1 and 329.2 amu . the absence of the characteristic mass at 227 amu is common for fp - biotinylated serine . the ms / ms spectrum for peptide aefaevsk labeled by fp - biotin on ser 232 is in figure 6 . the b- and peaks not assigned by protein pilot included six dehydroalanine fragments as well as the 591 amu ion of fp - biotin and the 227 , 312 , and 329 amu fragments of fp - biotin . these additional peaks strongly support the conclusion that ser 232 of albumin was labeled by fp - biotin . this labeled peptide was detected by the sensitive qstar elite mass spectrometer but not by the qtrap 2000 mass spectrometer . no fp - biotinylated peptides were found in the control plasma that had not been treated with fp - biotin . ms / ms spectrum of albumin peptide labeled with fp - biotin on ser 232 . the peak at 591.3 is fp - biotin released from serine , carrying a hydroxyl group in place of fluorine . four y - ions ( y2 , y3 , y4 , and y5 ) carry fp - biotin on serine , whereas six y - ions ( y3y8 ) have lost fp - biotin as well as a molecule of water , thus converting serine to dehydroalanine . the present method identified 7 fp - biotin - labeled albumin peptides but no fp - biotin - labeled peptides from any other protein . a western blot hybridized with streptavidin alexafluor-680 showed many fp - biotinylated bands in human plasma treated with fp - biotin under our conditions ( data not shown ) . however , the fp - biotinylated butyrylcholinesterase peptide was not found with the present methods . fp - biotinylated peptides from proteins other than albumin are difficult to detect in the presence of the overwhelmingly high concentration of albumin . even after depletion of albumin with cibacron blue , the concentration of albumin was still too high to allow detection of other fp - biotinylated peptides . human plasma contains 5 mg of butyrylcholinesterase and 50000 mg albumin per l. in experiments not described in this report , we found op - labeled butyrylcholinesterase in human plasma only after the butyrylcholinesterase had been purified by binding to procainamide affinity gel , thus eliminating more than 95% of the albumin . prolonged labeling of pure human albumin with cpo resulted in labeling of six tyrosines : y138 , y150 , y161 , y401 , y411 , and y452 ( table 2 ) . four of these sites were also labeled by fp - biotin ( y138 , y401 , y411 , and y452 ) . the hpyfyapellffak peptide was labeled on tyr 150 by cpo , whereas it was labeled on tyr 148 by fp - biotin . a new peptide ykaafteccqaadk was labeled by cpo ( figure 7 ) and not by fp - biotin . additional ms / ms spectra for cpo - labeled peptides are in the supporting information ( figures s1s5 ) . peptide kylyeiar was carbamylated on the n - terminal lys by degradation products in urea , adding a mass of 43 . the finding that seven tyrosines and two serines make a covalent bond with op led to the question of which amino acid reacts most readily with op . to answer this question , we duplicated the conditions reported to label one molar equivalent of human albumin with dfp ( 10 ) . maldi - tof analysis of pepsin - digested , dfp - treated human albumin suggested that 80% of tyr 411 was labeled with dfp . ms / ms analysis of a tryptic digest of carbamidomethylated dfp - treated albumin confirmed that tyr 411 in peptide y*tk was labeled . in addition , less than 10% of peptide efnaetftfhadict*ls*ek was labeled ( on residues t515 and s517 ) . albumin treated with fp - biotin for 2 h and digested with pepsin had 52% of its tyr 411 labeled in peptide vry*tkkvpqvstptl as calculated by maldi - tof mass spectrometry ( figure 8) . the carbamidomethylated , trypsin - digested preparation analyzed by lc / ms / ms confirmed that tyr 411 in peptide y*tk was labeled with fp - biotin . peptide hpy*fyapellffak was labeled on tyr 148 with fp - biotin but to less than 10% . a third method to identify fp - biotinylated peptides was purification on monomeric avidin beads followed by maldi - tof - tof analysis . this method yielded only one fp - biotinylated peptide , the y*tk peptide labeled on tyr 411 . maldi - tof spectrum of pepsin - digested albumin to show labeling of tyr 411 by fp - biotin . pepsin digestion of albumin yields two unlabeled peptides at 1717.2 ( vrytkkvpqvstptl ) and 1830.3 ( lvrytkkvpqvstptl ) amu , both containing tyr 411 . both peptides have a mass shift of 572.3 after reaction with fp - biotin , yielding the peaks at 2289.6 and 2402.7 amu . about 50% of the tyr 411 is labeled as calculated from cluster areas of the labeled and unlabeled peaks . soman - treated albumin ( 150 m soman for 2 h ) analyzed by maldi - tof and lc / ms / ms yielded only one labeled peptide . albumin treated with cpo for 2 h before digestion with pepsin or trypsin and analyzed by maldi - tof and lc / ms / ms was labeled on tyr 411 . in addition , less than 5% of thr 566 in peptide et*cfaeegkk and less than 5% of thr 236 and thr 239 in peptide lvt*dlt*kvhtecchgdllecaddr were labeled . support for the conclusion that tyr 411 is the most op reactive residue in albumin comes from ref ( 2 ) . williams incubated the albumin fraction of human plasma with radiolabeled sarin , digested with trypsin , purified the radiolabeled peptides by hplc , and analyzed by lc / ms / ms . it was noted that serine and threonine residues were labeled in addition to tyrosine when samples had been incubated at ph 8.08.3 for 248 h but were not found in samples incubated at ph 8.3 for a month . in contrast , op - labeled tyrosines were found even after 1 month of incubation at ph 8.3 . our stability study of cpo - labeled albumin confirmed that the tyr 411 adduct was stable ( figure 9 ) . incubation at ph 7.4 and 22 c resulted in almost no loss of the cpo label on tyr 411 after 7 months . in contrast , about half of the label was lost after 3.6 months at ph 8.3 and 22 c . the cpo - labeled tyr 411 was stable at ph 1.5 and 22 c and was stable at all ph values when the labeled albumin was stored at 80 c . these results suggest that op - labeled serine and threonine adducts are unstable as compared to op - labeled tyrosine . the ph of the dialyzed albumin was adjusted to 1.5 , 7.4 , and 8.3 . after various times of storage , samples were digested with pepsin and % labeling of tyr 411 was calculated from cluster areas of labeled and unlabeled peptides in the maldi - tof mass spectrometer . cpo - labeled tyr 411 was stable at ph 1.5 and 7.4 when cpo - albumin was stored at 22 c ( top panel ) , and it was stable at all ph values when cpo - albumin was stored at 80 c ( bottom panel ) . storage of cpo - albumin at ph 8.3 at 22 c resulted in release of half of the diethoxyphosphate group from tyr 411 after 3.6 months . the crystal structure in figure 10 shows the five tyrosines and two serines that become labeled by fp - biotin . these residues are located on the surface of the albumin molecule where they are available for reaction with op . crystal structure of human albumin showing surface location of tyr 138 , tyr 148 , tyr 401 , tyr 411 , tyr 452 , ser 232 , and ser 287 . the picture was made with pymol software using the structure in pdb code 1bm0(28 ) . human albumin has 18 tyrosines and 24 serines but only five tyrosines and two serines made a covalent bond with fp - biotin . their special reactivity may be explained by a nearby arginine or lysine that stabilizes the ionized hydroxyl of tyrosine or serine . although tyr 411 is the most op reactive residue in human albumin , an additional eight amino acids were labeled when the op concentration was high and the reaction time was prolonged . the reaction with fp - biotin at ph 8.0 resulted in the labeling of five tyrosines and two serines in albumin . cpo labeled six tyrosines ( two of which were different from those labeled by fp - biotin ) and no serines . we agree with means and wu ( 10 ) that about 90% of the label is on tyr 411 and 10% is on other residues . the pka of the tyrosine hydroxyl group is 10.1 and of the serine hydroxyl group is approximately 16 , based on comparison to ethanol ( 15 ) . in the absence of special activation , less than 1% of the tyrosines and less than 0.000001% of the serines would be expected to be ionized at ph 8.0 . ionized forms react preferentially with op , so the reactivity of tyrosine and especially of serine with op would be expected to be poor at ph 8 . the special reactivity of tyr 411 suggests that the pka of this particular tyrosine has been lowered . means and wu identified an op reactive residue in albumin that had a pka of 8.3 ( 10 ) . our results show that albumin is an op scavenger , undergoing a covalent reaction with op . as such a significant amount of op can be bound by albumin because the concentration of albumin in serum is high ( 0.6 mm ) , even though the rate of reaction with op is slow ( 3 ) . tyrosines with an abnormally low pka are involved directly or indirectly in the catalytic activity of numerous enzymes including glutathione s - transferase ( 16 ) , asparaginase ( 17 ) , -lactamases ( 18 ) , and old yellow enzyme ( 19 ) . lowering the pka of tyrosines in albumin by modifying their environment , either by mutagenesis or by chemical modification of vicinal residues , would increase the reactivity of albumin with op . specific nitration of tyrosine by tetranitromethane was found to lower the pka of tyrosine to 6.8 ( 20 ) . another nitration reagent of tyrosine , peroxynitrite , was found to increase the catalytic activity of a few enzymes ( 21 ) . thus , specific nitration of tyrosine residues in albumin could also lead to a gain in reactivity of this protein , increasing its scavenging properties . when soman or dfp are bound to acetylcholinesterase or butyrylcholinesterase , the op loses an alkyl group in a process called aging ( 2225 ) . an aged soman - labeled peptide would have an added mass of 78 rather than 162 ; an aged dfp - labeled peptide would have an added mass of 122 rather than 164 ; an aged cpo - labeled peptide would have an added mass of 108 rather than 136 . human albumin covalently labeled with soman or sarin and treated with sodium fluoride to release the op yielded intact soman and sarin . soman - tyrosine adducts isolated from nerve agent - treated guinea pigs contained the pinacolyl group of soman . the absence of aging is a special advantage for op - albumin as a biomarker because it allows for a more precise identification of the op . in contrast , soman and sarin exposure can not be distinguished when the biomarker is cholinesterase , where aging of op adducts occurs rapidly . guinea pigs treated with the nerve agents soman , sarin , cyclosarin , or tabun have nerve agent - labeled albumin in their blood ( 2 ) . the tabun - tyrosine and soman - tyrosine adducts were detected in blood 7 days postexposure , indicating that the adducts are stable . the adducts had not undergone aging and had not been released from tyrosine by treatment of the guinea pigs with oxime . mice treated with a nontoxic dose of fp - biotin by intraperitoneal injection had fp - biotinylated albumin in blood and muscle ( 1 ) . these examples show that op binds covalently to albumin under physiological conditions and that op - albumin adducts could therefore be useful as biomarkers of op exposure ( 27 ) . our results suggest that op exposure could be monitored by mass spectrometry of op - albumin adducts or with antibodies against op - albumin adducts . the surface location of the op - binding sites in albumin suggests that these epitopes may be available for reaction with antibodies . this is in distinct contrast with acetylcholinesterase and butyrylcholinesterase where the op binding site is buried deep within the molecule , making it unavailable to antibodies . antibodies to op - albumin would be primarily against op - labeled tyr 411 because tyr 411 is the most reactive residue at low op concentrations . therefore , only two antibodies would be needed for detection of exposure to common op pesticides . the studies described here support investigation into whether albumin could be engineered to become a more efficient op scavenger .

tyrosine 411 of human albumin is an established site for covalent attachment of 10-fluoroethoxyphosphinyl - n - biotinamidopentyldecanamide ( fp - biotin ) , diisopropylfluorophosphate , chlorpyrifos oxon , soman , sarin , and dichlorvos . this work investigated the hypothesis that other residues in albumin could be modified by organophosphorus agents ( op ) . human plasma was aggressively treated with fp - biotin ; plasma proteins were separated into high and low abundant portions using a proteome partitioning antibody kit , and the proteins were digested with trypsin . the fp - biotinylated tryptic peptides were isolated by binding to monomeric avidin beads . the major sites of covalent attachment identified by mass spectrometry were y138 , y148 , y401 , y411 , y452 , s232 , and s287 of human albumin . prolonged treatment of pure human albumin with chlorpyrifos oxon labeled y138 , y150 , y161 , y401 , y411 , and y452 . to identify the most reactive residue , albumin was treated for 2 h with dfp , fp - biotin , chlorpyrifos oxon , or soman , digested with trypsin or pepsin , and analyzed by mass spectrometry . the most reactive residue was always tyr 411 . diethoxyphosphate - labeled tyr 411 was stable for months at ph 7.4 . these results will be useful in the development of specific antibodies to detect op exposure and to engineer albumin for use as an op scavenger .

After weeks of publicly complaining that Senate Democrats were going easy on Neil Gorsuch, liberal activists are close to securing a successful filibuster of President Donald Trump’s Supreme Court pick. But they’re not stopping there. Activists are now vowing to make Republicans pay a political price if they decide to rip up Senate rules to push Gorsuch through with a simple majority vote. And if Majority Leader Mitch McConnell does kill the Supreme Court filibuster to confirm Gorsuch, liberals say they’ll still come out on top — having further emboldened a base that wants Democrats to brook no compromise with Trump. Story Continued Below “Democrats showing they can unify [against Gorsuch] helps energize the grass roots,” MoveOn.org Washington director Ben Wikler said in an interview. “If Republicans decide to go nuclear, that will further energize the resistance movement. The only bad path here is for Democrats to flee the fight.” Simply getting to this point is a victory for the left, which began the Supreme Court battle frustrated with Senate Democrats and bluntly urging them to "do better" as Gorsuch appeared on track for easy confirmation. But over the past two weeks, as liberals kept nudging Senate Minority Leader Chuck Schumer's caucus to push back harder, Democrats have abandoned their reluctance to commit to a filibuster. The shift can be largely credited to the aggressive campaign from liberal groups, though a number of Democrats also became inclined to favor a filibuster after they found Gorsuch's answers far too noncommittal during his marathon confirmation hearing. Most GOP senators have signaled they’re ready to back McConnell on a critical vote to unilaterally change Senate rules. But a handful have remained skeptical enough to fuel speculation among Gorsuch foes that the Kentucky Republican may be short of the votes. Amid continuing talk of a last-minute deal to preserve the filibuster for Supreme Court picks, liberals are starting to publicly prod Republicans to explain why they would change the Senate rules. “I don’t always see eye to eye with these folks, but some of them are expressing caution about changing the norms of the Senate,” said Ilyse Hogue, president of the abortion-rights group NARAL Pro-Choice America. “So we’ll see. I don’t know that they have 51 votes yet — but that’s on them to prove, not me.” As the Senate drew closer to a possible "nuclear option" scheduled for the end of next week, few Republicans were optimistic about defusing the tension. “The Democrats, they know better,” Sen. Bob Corker (R-Tenn.) told reporters. “But their base, you understand, won’t allow them to do the right thing.” Corker referenced liberal protesters gathering outside Schumer’s Brooklyn apartment earlier this year as a reason that “he’s making these arguments about [Gorsuch] being extreme. We all know that’s not true.” Senate Democrats don't share some liberal activists' skepticism that McConnell will muscle through a rules change that promises to further poison relations in the polarized Senate — and which could spark blowback for his party when the GOP next loses the White House. But Democrats do agree with one strategic move by their base: They're starting to press Republicans to own their decision to end filibusters for Supreme Court nominees, not just talk about it. “Everybody’s talking about whether Gorsuch gets confirmed — and that’s essential and right in front of us,” Sen. Brian Schatz (D-Hawaii) said in an interview. “But the broader question, in the sweep of history is: What happens to the Senate? And that’s in the hands of just a handful of Republicans, not us.” "There are enormous implications of changing the rules of the Senate in order to force an unpopular Supreme Court justice through," adds Chris Murphy (D-Conn.). "I hope Republicans think about the consequences of what they’re thinking about doing." For the moment, Democrats' progress towards a viable filibuster is attracting outsized attention on Capitol Hill. Politico's count stood at 36 Senate Democrats ready to block Gorsuch after Sen. Claire McCaskill of Missouri made a pivotal announcement of her opposition on Friday. Sens. Heidi Heitkamp of North Dakota and Joe Manchin of West Virginia are the only Democrats in the yes column. On Monday, left-leaning groups, including Sen. Bernie Sanders' Our Revolution, plan to send a message to Democrats who are considering joining Heitkamp and Manchin. They have organized a petition publicly imploring the Democratic Senatorial Campaign Committee to withhold support from any Democratic senator who backs Gorsuch. The most reliable politics newsletter. Sign up for POLITICO Playbook and get the latest news, every morning — in your inbox. Email Sign Up By signing up you agree to receive email newsletters or alerts from POLITICO. You can unsubscribe at any time. Once Schumer's caucus gets to 41 confirmed votes to block Gorsuch, the focus will shift to Republicans who remain less than publicly committed to supporting the so-called nuclear option to change the rules — including Corker and Sens Susan Collins of Maine and John McCain of Arizona. Liberal activist groups are pushing as hard as possible to move scrutiny to the GOP whip count, touting a poll they commissioned that shows 69 percent of all voters — and even four in 10 Trump backers — oppose Republican changes to Senate filibuster rules. "McConnell has very cunningly kept all the attention off his conference for this whole arc," said one liberal strategist working on the Gorsuch nomination, describing moderate Republicans as "leaning into it, bluffing" on where they stand. "He does an excellent job of giving the impression that getting the votes to change the rules isn’t a problem." McConnell, for his part, is well aware of the pressure Democrats are facing from liberal groups opposed to Gorsuch. "This isn’t about the nominee at all," McConnell said on the floor earlier this week. "It’s about a few on the left whose priority is to obstruct this Senate and this president, whenever and wherever they can. Months after the election, they’re still in campaign mode calling for Senate Democrats to obstruct and resist." But with McConnell's guarantee that Gorsuch will be confirmed by April 7, liberals are warning Republicans of the potential midterm-election ramifications of jamming Gorsuch onto the court. Hogue, of NARAL, said anti-Gorsuch rallies spearheaded by her group on Saturday would be aimed as much at Republicans as at Democrats. "It’s really important for people to remember that if this judge is confirmed, especially if Republicans change the rules to get Trump’s guys in, it won’t be theory in 2018," Hogue said. "This guy will have ruled. It will be a Gorsuch court — and it most likely will have ruled on some of Trump’s agenda." ||||| Washington (CNN) As the Senate prepares to vote this week on Neil Gorsuch's nomination, it's unclear yet whether Republicans will have enough votes to end an expected Democratic filibuster. Republicans, who have a 52-48 majority, need a total of eight Democrats to get to 60 -- the critical number required to end the filibuster. If they don't reach 60, they can still get around that filibuster, but it would require taking a highly controversial step to change the Senate rules, a move also known as the nuclear option Republicans already have three Democrats who will vote with them to end the filibuster, so they need five more of the remaining eight undecided Democrats -- as of Sunday -- to do the same and reach that 60 number. All eyes will be on those undecideds this week. It's a diverse mix that includes senior Democrats who've been in the chamber for decades to first-term senators. Most are up for re-election, but a majority of that group is considered fairly safe in their respective states. Here's a look at the nine undecided Democrats and what they've said recently about Gorsuch: Sen. Pat Leahy (Vermont) -- Having been elected to office in 1975, Leahy is the most senior Democrat in the Senate. He tweeted Monday that he's generally "never inclined to filibuster" a Supreme Court nominee, even though he stated he doubts he can support Gorsuch in the end. Leahy, a member of the Judiciary Committee, later expressed strong concern about Republicans using the nuclear option, something they'd only do if enough Democrats didn't join them to break the filibuster. Sen. Mark Warner (Virginia) -- Warner has been a bit busy with his other job as the top Democrat on the Senate intelligence committee . He told reporters earlier this week that he was still reading up on Gorsuch but was concerned about what he called Gorsuch's "evasive answers" in his hearings last week. Sen. Chris Coons (Delaware) -- Coons is also a member of the Judiciary Committee and has a record of working across the aisle on legislation. He, too, has expressed concern about a change in the Senate rules and has been a part of informal conversations to find a way to avert a course that leads to the nuclear option. Still, Coons appeared highly disappointed in some of Gorsuch's answers last week, and he said on MSNBC that he doubts Gorsuch will be able to get the 60 votes needed to advance through the process. Sen. Michael Bennet (Colorado) -- Bennet has been quiet this week about how where he'll fall on the filibuster. Bennet hails from the same state as Gorsuch and introduced the federal judge at his hearing last week, along with the state's other senator, Republican Cory Gardner. But Bennet made it clear that he was introducing Gorsuch out of tradition and that he wasn't necessarily signaling how he'd vote. Sen. Dianne Feinstein (California) -- Feinstein is the top Democrat on the Senate Judiciary Committee and another high ranking Democrat in the Senate, having served since 1992. She said she was disappointed with many of Gorsuch's answers at the hearing and felt he wasn't forthcoming enough. The committee meets again Monday to vote on whether to send Gorsuch to the full Senate (with Republicans outnumbering Democrats on the committee, it's expected Gorsuch will pass). Feinstein told reporters this week that she would wait until next week to make her decision known on the filibuster and how she would vote on Gorsuch's confirmation vote. Sen. Ben Cardin (Maryland) -- Like Feinstein, Cardin also hasn't announced whether he'll run for re-election. He told CNN this week that he plans to vote against Gorsuch's nomination in the end, but he hasn't made a decision on whether he'll vote to maintain the filibuster. "I'm waiting to see what the Republican leadership (does), how they present the nomination on the floor and how they work with the Democrats. There's still a lot of anxiety out there because of the way they handled the (Merrick) Garland (Supreme Court) nomination. So I will wait to see how they handle this nomination before deciding what I will do on procedural votes." Sen. Bob Menendez (New Jersey) -- Menendez also hasn't announced a 2018 run but he has reportedly started raising campaign funds. Like Feinstein and Cardin, he's considered safe if he decides to run. The New Jersey senator told reporters that he's still deciding on Gorsuch, but "when I come to a conclusion on how I'm voting on Gorsuch, I'll decide on how I'm voting in the whole process." Independent Sen. Angus King (Maine) -- While King is an independent, he's considered part of the Democratic caucus. He's been fairly quiet about Gorsuch of late. His seat is also considered safe in 2018. ||||| FILE - In this Feb. 4, 1939, file photo, Felix Frankfurter, the new associate justice of the United States Supreme Court, poses in his judicial robe for his portrait in Washington. Supreme Court nominations... (Associated Press) FILE - In this Feb. 4, 1939, file photo, Felix Frankfurter, the new associate justice of the United States Supreme Court, poses in his judicial robe for his portrait in Washington. Supreme Court nominations became politically contentious about 222 years ago when the Senate voted down George Washington’s... (Associated Press) WASHINGTON (AP) — Wondering when Supreme Court nominations became so politically contentious? Only about 222 years ago — when the Senate voted down George Washington's choice for chief justice. "We are in an era of extreme partisan energy right now. In such a moment, the partisanship will manifest itself across government, and there's no reason to think the nomination process will be exempt from that. It hasn't been in the past," University of Georgia law professor Lori Ringhand said. This year's brouhaha sees Senate Democrats and Republicans bracing for a showdown over President Donald Trump's nominee, Neil Gorsuch. It's the latest twist in the political wrangling that has surrounded the high court vacancy almost from the moment Justice Antonin Scalia died in February 2016. Each side has accused the other of unprecedented obstruction. Republicans wouldn't even hold a hearing for Merrick Garland, President Barack Obama's nominee. Democrats are threatening a filibuster, which takes 60 votes to overcome, to try to stop Gorsuch from becoming a justice. If they succeed, Republicans who control the Senate could change the rules and prevail with a simple majority vote in the 100-member body. As she lays out in "Supreme Court Confirmation Hearings and Constitutional Change," the book she co-wrote, Ringhand said, "There were more rejected nominees in the first half of the nation's history than in the second half. That controversy has been partisan in many cases, back to George Washington." "Confirmations have been episodically controversial," said Ringhand, who is the Georgia law school's associate dean. "The level of controversy has ebbed and flowed." John Rutledge, a South Carolinian who was a drafter of the Constitution, was the first to succumb to politics. The Senate confirmed Rutledge as a justice in 1789, a post he gave up a couple of years later to become South Carolina's chief justice. In 1795, Washington nominated Rutledge to replace John Jay as chief justice. By then, Rutledge had become an outspoken opponent of the Jay Treaty, which sought to reduce tensions with England. A year after ratifying the treaty, the Senate voted down Rutledge's nomination. The rejected chief justice was partly a victim of his own design. He was among the drafters who insisted Congress should have a role in the Supreme Court appointment process, rather than leave it solely to the president, historian Henry Abraham wrote in his history of high court appointments, "Justices, Presidents, and Senators." Rutledge was not the last to get close to the lifetime appointment to the court only to see it yanked away. The most recent were Garland and former White House counsel Harriet Miers, whose nomination by President George W. Bush was withdrawn under pressure from conservatives. In between, President John Tyler broke with the Whigs who controlled the Senate and couldn't even get a vote for three nominees. A fourth was rejected and only one of Tyler's choices ever made it to the court. A quarter-century later, following the Civil War, the Republican-dominated Congress actually abolished a Supreme Court seat rather than act on a nomination by President Andrew Johnson. Even some who have made it to the court endured difficult confirmations. Justice Clarence Thomas faced questions about former colleague Anita Hill's claims that he sexually harassed her. Justice Felix Frankfurter's loyalty to the United States was questioned because of his birth in Austria, his Judaism and his affiliation with the American Civil Liberties Union. But American politicians don't tend to look back so far. Democrats fixate on 1968, the last year of the Johnson administration, when Republicans and southern Democrats came together to filibuster the nomination of Abe Fortas to be chief justice. Republicans point to 1987, when Democrats led the way in rejecting Ronald Reagan's nomination of Robert Bork for the high court. The 58-42 vote against Bork came after a full hearing and Senate debate. Still, it's understandable for the public to see the Gorsuch fight as the product of a recent change in American politics. Barbara Perry, a University of Virginia expert on the presidency, said she spoke about the confirmation process recently in Charlottesville, Virginia. "A woman stood up and said, 'When did the court become so political?'" Perry recalled. Around the founding of the country, she and a colleague replied, "or at least since we've had two political parties." ||||| By Steven T. Marshall, Attorney General for the State of Alabama. This article was released to coincide with National Crime Victims' Rights Week, observed during the first week in April, to honor the victims of crime and to promote their rights. As I watched the U.S. Senate Judiciary Committee's confirmation hearings for Supreme Court nominee Neil Gorsuch, I couldn't help but be struck by the weightiness of today's divided Court and how just one new justice can change the landscape of law enforcement. The impact that the Supreme Court's decisions have on law enforcement at the state and local level is substantial and affects our prosecutors, police officers, and my own office in carrying out our most basic day-to-day duties in the administration of justice. Though there are a myriad of law enforcement issues hanging delicately in the balance with the Court's current makeup, one stands out amongst them all--the death penalty. Before his death, Justice Antonin Scalia--an ardent defender of the constitutionality of the death penalty and the states' ability to impose it--was demonstrably frustrated with the Court's "incremental abolition" of the punishment. As a textualist, he could not make heads or tails of any justice's proposition that the death penalty was flatly unconstitutional, since it is specifically referred to in the text of the Constitution. Nor could he take seriously the role of the Court as the "sole arbiter of our Nation's moral standards," a role he believed it created for itself as to the death penalty through its evolving Eighth Amendment (cruel and unusual punishment) analysis. In a 2015 speech, Justice Scalia remarked that he wouldn't be surprised if the death penalty were struck down altogether by the Court. His untimely death, coupled with the fact that at least two sitting justices believe that the death penalty is unconstitutional in any circumstance, guarantee that the next Supreme Court justice will play a monumental role in the coming decades of death penalty jurisprudence. If the Court continues on its current trajectory, we will more often see it pressuring states to adapt to its "evolving standards of decency," than see the justices defer to the sovereignty of the states on matters that were once considered plainly within their purview to decide. Alabama has been no stranger to death penalty litigation before a divided U.S. Supreme Court. At times, our success or failure has come down to one vote, regardless of how ironclad the evidence of guilt was. In 2016 alone, an evenly divided Court kept our state from executing two heinous criminals, to the dismay of victims' families who'd endured decades of appeals and expected to see justice served. The Court has received hundreds of failed habeas petitions from Alabama's death row inmates, and has even ruled on whether our method of execution was "cruel and unusual"--ironic, when you consider the kinds of deaths that the victims died. Our Capital Litigation Division has handled SCOTUS appeals from the likes of an individual who brutally murdered a woman with a hand tool and then chased around her two small children with a kitchen knife until he also murdered them; another who shot and killed six of his ex's family members, waiting all day for them to come home to be murdered one by one; or another who randomly beat and killed an elderly couple with a crowbar after entering their house under the guise of needing to use the telephone. Undoubtedly, our state has a strong interest in the Court's preservation of our right to levy the death penalty in appropriate cases. Of course, the death penalty is just one of the critical matters that has reached the purview of the U.S. Supreme Court and impacts the work of law enforcement. While Judge Gorsuch's opinions certainly do not indicate hostility to the death penalty generally, how he would rule on these and related questions of criminal law is, to some degree, unknown. The best that we, as members of law enforcement and as citizens, can ask or hope for from judges at any level is that they remain faithful to the Constitution and to the rule of law--and I believe that Judge Gorsuch will. Such a commitment must be more adamantly required of the judiciary at large, as it is indispensable to our law-and-order society.

– Merrick Garland never got a hearing, and Neil Gorsuch looks headed for a highly partisan showdown this week that could see the first successful filibuster of a Supreme Court nominee since the 1960s and Senate rules rewritten as Republicans try to put him in the seat that's been empty since Antonin Scalia died more than a year ago. But if you're wondering how we came to this bitter moment of partisan divide over President Trump's pick for the job for life, the AP takes a long look back and finds that we came by it honestly—the first Supreme Court nominee voted down by the Senate was the pick of none other than George Washington, who tapped John Rutledge 222 years ago to succeed John Jay as chief justice. "There were more rejected nominees in the first half of the nation's history than in the second half," says an expert. A look around the landscape as Gorsuch heads for a vote: Democrats Joe Manchin and Heidi Heitkamp announced late last week that they would break party lines to vote for Gorsuch's confirmation, CNN reports. That means Republicans need six more Democrats to defect in order to end their expected filibuster and avoid invoking the nuclear option. CNN takes a look at the 10 Democrats currently sitting on the fence; six are up for re-election. Liberals are licking their chops at the thought of a successful filibuster, reports Politico. "If Republicans decide to go nuclear, that will further energize the resistance movement," a MoveOn.org activist says. "The only bad path here is for Democrats to flee the fight." Writing at Al.com, Alabama AG Steven Marshall opines that Gorsuch could be the deciding vote on the fate of the death penalty—and it's not entirely clear where he would land.

in the last years , the kinetics of aggregation has been widely studied @xcite . it has been studied experimentally in a large number of systems like aqueous metal colloids @xcite , silicon tetramethoxyde @xcite and tetraethoxyde @xcite , alumino - silcates @xcite , colloidal silica @xcite , polystyrene @xcite , and oil in water emulsions @xcite . using small - angle scattering techniques it has been suggested that some of these systems @xcite grow like diffusion - limited cluster - cluster aggregation ( dlca ) @xcite . numerically , the gelation process in dlca has been investigated by analyzing the cluster size distribution and the mean cluster size , as a function of the time @xmath11 using both the smoluchowski equation @xcite and the dlca model in 2 dimensions @xcite . on the other hand , recently @xcite it has been shown that , when the volumic fraction @xmath4 , or concentration , is greater than a characteristic gel concentration @xmath12 , dlca model leads to a homogeneous gelling network of connected fractal clusters of mean size @xmath2 . in some systems @xcite where fractal clusters grow separately until obtaining a system of connected fractal clusters at large @xmath11 , the wave - vector - dependent scattering function @xmath1 exhibits a maximum in the wave vector @xmath7-value ( which is inversely proportional to @xmath2 ) at a given time @xmath11 . this maximum can be interpreted as a crossover between the fractal regime ( intermediate @xmath13-values where @xmath14 ) and the homogeneous regime ( small @xmath13-values ) . moreover , some very interesting relations on the @xmath15 curve ( see below equations 7 ) have been established on various systems @xcite . since scaling relation are known to be of wide applications ( `` universality '' ) it is worth studying them here . another interesting experimental results @xcite reveal that the gyration radius @xmath16 ( which is proportional to @xmath2 ) saturates close to @xmath3 , the time where the system can be considered as a gelling network . in this paper , we present some new results obtained from our numerical study of the gelation process using diffusion limited cluster - cluster aggregation in a box @xcite , where a sufficiently large initial concentration has been considered in order to obtain a gelling network of connected clusters at the end of the aggregation process . we have calculated numerically the mean number of particles per cluster @xmath10 and their mean size @xmath2 as a function of time @xmath11 as well as the correlation function @xmath0 , and the scattering function @xmath1 . we show that there exists a crossover at @xmath3 such that , for @xmath6 , @xmath2 increases when @xmath11 increases , and for @xmath17 , the characteristic length @xmath2 remains constant and equal to its value obtained near @xmath3 . the location of this crossover is pushed toward the low-@xmath11 values when @xmath4 increases . for @xmath18 the normalized gel time @xmath19 does not change . additionally , the maximum of the @xmath1 curve , @xmath20 , increases as @xmath21 where @xmath22 is an apparent fractal dimension . we report on the discrepancies between the actual fractal dimension @xmath9 and @xmath22 for large @xmath4-values . finally , we discuss the qualitative agreement between our simulations and some experiments . we have modelized the gelation process considering a three dimensional off - lattice extension of the original diffusion cluster - cluster aggregation model @xcite as in ref . @xcite where we have shown that such a model is well adapted to describe the aerogel structure . during the aggregation process , we can naturally define a `` monte - carlo '' time @xmath23 which is increased by an arbitrary constant amount @xmath24 at each iteration . due to the use of formula ( 3 ) of ref . @xcite to choose the aggregates , the actual `` physical '' time @xmath11 should be increased by the amount @xmath25 related to @xmath26 by : @xmath27 in our calculation the time unit has been arbitrarily fixed by setting @xmath28 . using scaling arguments , it can be established that the whole system remains invariant if length , mass and time are conveniently rescaled simultaneously @xcite . changing the average mass @xmath10 by a factor @xmath29 , the distance should be rescaled by @xmath30 and , using a general mean - field argument to evaluate the average time it takes for all clusters to pair up , the time should be rescaled by @xmath31 , giving : @xmath32 with @xmath33 for @xmath34 and @xmath35 this reasoning gives @xmath36 . in figure 1 we show the time evolution of the mean number of particles per cluster @xmath10 for three different concentrations . when @xmath37 @xmath10 is roughly proportional to @xmath11 as expected from equation ( 2 ) . however , for @xmath38 this dependence is only observed at short times ( for @xmath39 ) . at large times ( for @xmath40 ) if one still assumes @xmath41 , one should consider a very large exponent @xmath42 . note that in refs . @xcite , equation ( 2 ) was obtained under the hypothesis that the entire system remains space and time scaling invariant . this hypothesis is no longer valid when a gel is formed since the system becomes homogeneous for distances larger than @xmath2 @xcite and if one tries to define its global fractal dimension it should be taken as the dimension of space . qualitatively , the observed increase of @xmath43 can be understood as a consequence of the increase of the fractal dimension . an earlier work by gonzalez @xcite suggests the same conclusion . in his paper it is shown that when @xmath9 increases from 1.87 to 2.05 , @xmath43 increases from 1.3 to 2.5 when using a cluster - cluster aggregation model with a sticking probability @xmath44 varying from 0.5 to 0.005 , reaching the chemically - limited cluster - cluster aggregation ( clca ) model @xcite , also called reaction - limited cluster - cluster aggregation ( rlca ) @xcite . an increasing @xmath43-value with @xmath9 was also found in another clca model also recently proposed by gonzalez @xcite . the distance that a cluster must travel before colliding with another cluster decreases when @xmath4 increases so that both the gel time @xmath3 , when it exists ( i. e. for @xmath45 ) , and the time at the end of the aggregation process @xmath46 should decrease as @xmath4 increases . this is well observed in figure 2 where @xmath3 and @xmath46 have been plotted as a function of @xmath4 in a log - log plot . for @xmath47 we observe that @xmath46 is roughly inversely proportional to @xmath4 while , for @xmath45 , both @xmath3 and @xmath46 decrease roughly as @xmath48 ( @xmath12 is determined as explained in ref . the latter result can be simply understood if one assumes that when @xmath45 the scaling relation ( 2 ) holds up to @xmath49 where the system is made of clusters of mean size @xmath2 containing @xmath50 particles . the concentration being related to @xmath2 by @xmath51 ( see ref . @xcite ) , the relation ( 2 ) with @xmath52 gives : @xmath53 the observed exponent of -1.75 corresponds to @xmath54 a value larger but quite close to the expected value of the fractal dimension of dlca clusters . we point out that in our model @xmath12 decreases as @xmath55 as showed elsewhere @xcite , and from equation ( 3 ) one can deduce that @xmath56 when @xmath57 . from figure 2 we also find that the ratio @xmath19 is almost independent on @xmath4 , for @xmath18 . this implies that the time taken by smaller clusters to stick to the gelling network remains a finite fraction of the total time . the two - point correlation function @xmath0 can be calculated by choosing a given path @xmath58 , and calculating the number @xmath59 of interparticle distances lying between @xmath60 and @xmath61 , taking care of the periodic boundary conditions when investigating regions outside of the box . in order to normalize @xmath0 to unity when r tends to infinity , @xmath0 was defined as follows : @xmath62 the static structure factor , or scattering function , @xmath1 in a system containing identical particles with mean volume fraction @xmath4 is given by @xcite : @xmath63 in theory one should take @xmath64 and @xmath65 . but , as explained in detail in refs . @xcite we have calculated @xmath66 from the formula : @xmath67 which gives a @xmath66 value very close to one that insures that @xmath68 when @xmath69 . on the other hand , @xmath70 was chosen equal to @xmath71 , to avoid boundary artifacts due to the periodic boundary conditions considered in our problem . using equation ( 4 ) , we have calculated @xmath0 at all times @xmath11 during the aggregation process ; we have observed that all the @xmath0 curves exhibit a delta peak at @xmath72 , a discontinuity at @xmath73 and a minimum at @xmath74 , that correspond to the typical short and long range features of dlca aggregates @xcite . in figure 3 we have plotted several @xmath0 curves for @xmath75 at four different @xmath11 emphasizing the region near the minimum in order to show that its location ( which defines the characteristic size @xmath2 of the aggregates ) is shifted to higher @xmath60-values when @xmath11 increases . the function @xmath0 was averaged up to 20 independent simulations , and the box size @xmath5 was taken equal to 103 . figure 4 shows @xmath2 as function of @xmath76 for four different values of @xmath4 . from equation ( 2 ) , one expects that @xmath2 should increase as @xmath77 for @xmath6 . however , for concentrations close to @xmath12 this power law is only verified for @xmath78 . for @xmath11 smaller than but close to @xmath3 one observes a crossover regime with a smaller slope which extends down to smaller times when @xmath4 is smaller . this smaller slope might be due to the interpenetration of clusters which becomes important as @xmath11 approaches @xmath3 . the cluster size @xmath2 saturates for @xmath17 suggesting that , in this regime , the remaining free small clusters diffuse towards the gelling network on which they stick without changing the mean size of the large connected clusters . however , during this regime , the density of clusters increases and therefore their fractal dimension should become larger . this can be checked in figure 5 where we have plotted the fractal dimension @xmath9 as a function of @xmath4 . the upper curve ( open squares ) correspond to the true fractal dimension , i.e. the one estimated in real space from the power law behavior @xmath79 , for @xmath80 . in figure 6 we show typical @xmath1 curves at different times . these curves exhibit the three regimes explained elsewhere @xcite , damped oscillations at large @xmath13-values @xmath81 , a power law @xmath14 at the intermediate @xmath13-values , and a vanishing regime for @xmath82 . in this figure we clearly see that @xmath7 is shifted to lower @xmath13-values as @xmath11 increases . this is in agreement with the results of figure 4 if one considers that @xmath7 is proportional to @xmath83 ( as found for @xmath84 in ref . additionally , it has been shown @xcite that the scaled scattering function @xmath85 and the position of the peak @xmath7 are related by : @xmath86 where @xmath87 is a time - independent scaling function . in spinodal decomposition @xmath88 , while in other growth problems @xmath89 @xcite . in our case , as showed in inset in figure 6 , the best collapse is obtained with @xmath90 which roughly corresponds to our previous estimate of the fractal dimension . also , this scaling behavior can be deduced by considering that the maximum of the scattering function @xmath20 is roughly proportional to the mean number of particles per cluster @xcite : @xmath91 implying : @xmath92 in figure 7 we show a log - log plot of @xmath93 versus @xmath20 . for convenience we have reported the results for @xmath94 by estimating @xmath2 from the minimum of @xmath0 since in such estimation the errors are smaller than estimating @xmath7 directly from @xmath1 . as expected from equation ( 7b ) a quasi linear behavior is found for the four concentrations reported in the figure . by performing a linear regression we have estimated the exponents of ( 7b ) which have been reported in table i together with the related fractal dimension that we call @xmath95 . in this table we have also reported the values @xmath22 obtained from the slopes of the respective @xmath1 curves at the last stage of the aggregation process as well as the actual fractal dimension @xmath9 obtained from @xmath0 . it is shown that , while @xmath9 increases , @xmath95 and @xmath22 decrease when @xmath4 increases , as already seen on figure 5 . similar discrepancies between @xmath9 and @xmath22 were observed by amar et al . @xcite in a sub - monolayer molecular beam epitaxy model in which the aggregation regime was described by a system of connected fractal clusters . these discrepancies between @xmath9 and @xmath22 might be explained by the fact that for @xmath96 the single scattering theory considered here is not completely justified@xcite . note that , for @xmath45 one has @xmath97 for distances larger than @xmath2 , while for @xmath98 the final system is a single fractal aggregate , with @xmath99 as showed elsewhere @xcite . in this section we would like to discuss our results in comparison with several experiments . small - angle neutron - scattering ( sans ) experiments in the sol - gel process of alumino - silicates have been performed by pouxviel et al . @xcite showing that the radius of gyration @xmath16 saturates when @xmath11 approaches @xmath3 ( see figure 2 of ref . these authors have considered three different composition samples prepared under basic conditions and they obtained a fractal dimension @xmath100 as in the dlca case . therefore , their results are in agreement with our numerical simulations . another interesting study has been reported in ref . @xcite , where small - angle light - scattering experiments have been performed on polystyrene spheres diluted in a water - heavy - water mixture ; it has been shown that @xmath101 scale as @xmath102 , where @xmath103 is equal to -0.58 ( close to the exponent reported in table i ) , at early stage of the growth process , and at larger @xmath11 values it has been found that @xmath103 becomes close to ( -1/3 ) the typical value for spinodal decomposition . they conclude that at early stage of spinodal decomposition the growth is dominated by dlca . similar kind of analysis has been recently done by hobbie et al.@xcite concerning sans experiments in a hydrogen - bonded polymer blend . but in their experiments they found @xmath104 a value consistent with diffusion limited particle - cluster aggregation @xcite . other interesting results have been reported by bibette et al . they have performed small angle light scattering experiments in monodisperse droplets of water emulsions in oil . they have suggested that the emulsion growth is like diffusion - limited cluster - cluster aggregation , obtaining @xmath100 . we have extracted the @xmath105 points from their curves of figure 2 in ref . @xcite , that we have compared with the points obtained from our simulation when using the same @xmath4 value as in the experiments ( @xmath75 ) . in figure 8 we show the good agreement with the experiments , obtaining the same increasing behavior of @xmath105 as a function of @xmath11 . in conclusion , in this work we have shown that numerical simulations of dlca model in a box can account for the growth process of several experimental systems . on the other hand , our numerical calculation of @xmath1 during the dlca process is an original investigation that extends previous numerical analysis of this growth process @xcite , leading to the theoretical explanation of additional interesting properties during the aggregation process and confirming some predictions made in some experimental studies . in particular the power law given in equation ( 7b ) and the shape of our @xmath1 curves are experimentally observed . similar calculations with the clca model are in progress in order to interpret some experiments which are more likely explained by such kind of growth process . .for four concentrations considered in the simulations , we have reported the respective exponents ( @xmath106 ) from equation ( 7b ) and the related fractal dimensions @xmath95 , which is compared with the apparent fractal dimension @xmath22 measured from the slope of the @xmath1 curve and the `` true '' fractal dimension @xmath9 as deduced from @xmath0 . [ cols="^,^,^,^ , > " , ]

the pair - correlation function @xmath0 and its fourier transform , the structure factor @xmath1 , are computed during the gelation process of identical spherical particles using the diffusion - limited cluster - cluster aggregation model in a box . this numerical analysis shows that the time evolution of the characteristic cluster size @xmath2 exhibits a crossover close to the gel time @xmath3 which depends on the volumic fraction @xmath4 . in this model @xmath3 tends to infinity when the box size @xmath5 tends to infinity . for systems of finite size , it is shown numerically that , when @xmath6 , the wave vector @xmath7 , at which @xmath1 has a maximum , decreases as @xmath8 , where @xmath9 is an apparent fractal dimension of clusters , as measured from the slope of @xmath1 . the time evolution of the mean number of particles per cluster @xmath10 is also investigated . our numerical results are in qualitative agreement with small angle scattering experiments in several systems .

Amazon's net shipping costs jumped 19% to $1.21 billion in the fourth quarter. More revenue from larger Prime subscriptions may help cover this huge and stubborn expense - as long as users don't cancel Employees select and dispatch items in the huge Amazon 'fulfilment centre' warehouse on Thursday in Peterborough, England. (Photo: Oli Scarff, Getty Images) SAN FRANCISCO - Amazon.com said it may raise the annual price of its popular Prime subscription by as much as $40 as the world's largest Internet retailer battles higher shipping costs. During a conference call with analysts on Thursday, following disappointing quarterly results, Amazon said it may increase the cost of Prime in the U.S. by $20 to $40. The service, which includes free two-day shipping on most products from Amazon.com, currently costs $79 a year in the U.S. Amazon has become the dominant online retailer by focusing on getting products delivered to customers quickly and cheaply. However, as fuel prices have climbed, the company has struggled to keep a lid on the cost of making those deliveries. Amazon said on Thursday that its net shipping costs jumped 19% to $1.21 billion in the fourth quarter. That was 4.7% of net sales, up from 4.5% a year earlier. Expenses like this contribute to the company's wafer-thin profit margins, which have been a concern on Wall Street for years. "They can't keep losing so much. This is their profit margin," said Colin Gillis, an analyst at BGC Partners. "Drones aside, they have to find a way to get the package from the warehouse to the user in a timely way but also in a cost-effective way." Amazon may lose some Prime subscribers, especially if the annual cost goes above $100. However, Gillis and other analysts expect the impact to be limited. "Where are these customers going to go? I want some competition because they've got me hooked on Prime. Hello Walmart or Alibaba, somebody else please step up," Gillis said "They will use some Prime members, but most people will probably take it," he added. "Pricing power!" Colin Sebastian, an analyst at RW Baird, wrote in an email to USA TODAY when asked why Amazon would make such a move. He expects few Amazon customers to cancel their Prime subscriptions. "Why would they cancel?" he added. "Keep in mind that a lot of Prime paying members allow family members to use the service as well." That may reduce the impact of a price increase, because the benefits of the subscription are spread among more customers. Read or Share this story: http://usat.ly/1bDJAk0 ||||| Amazon may raise the price of its Prime membership by up to $40 for U.S. customers, the company said today during its quarterly earnings call. Amazon’s Prime membership is an annual subscription that gives frequent shoppers “free” 2-day shipping on any item sold through the retail giant or one of its affiliate sellers. Prime members also gain access to Amazon’s Kindle e-book library-lending program and the Prime Instant Video service, which contains a collection of movies and TV shows that members can stream for free. Membership currently costs $79 per year, and the company hasn’t increased the price in nearly a decade. During the earnings call, the company said it was looking into boosting the price of Prime membership by $20 to $40 in the next year or so. Amazon said the reason for the increase has to do with rising costs of shipping items as well as the fuel cost associated with it. It’ll be interesting to see how customers react to a price increase. A $120 annual fee for Prime may turn off those that are only occasional Amazon shoppers. That’s assuming the company isn’t successful in making its Prime Instant Video and library-lending services more appealing on their own. However, if it can make Prime Instant Video as appealing as a Netflix subscription, consumers may not get sticker shock. One possibility is that Amazon switches from charging annually for Prime, to charging either monthly or quarterly. My guess is that Amazon has distanced itself from this option because it makes it much easier for customers to compare what they purchased over the month versus the cost of membership. Amazon CFO Thomas Szkutak shied away from whether the company would be open to breaking off its video service as a standalone subscription during the earnings call. I can’t imagine this would ever be an option since the video service’s main purpose is to get more people signed up for Prime, as VentureBeat previously reported. (I could possibly see the company breaking out an option where you might pay less for a membership that gives you only free 2-day shipping.) The company didn’t offer an exact date for when Prime membership prices would increase. ||||| Jeff Bezos, CEO of Amazon, during a 2012 news conference in Santa Monica, Calif. (Photo: Joe Klamar, AFP/Getty Images) Shares of Amazon tumbled after-hours on news that the e-tail giant missed earnings estimates by a wide margin, though sales saw a big jump over the key holiday season. Amazon stock is tanking 10.6% in after-hours trading, to $360.25. The company's earnings report dropped shortly after the closing bell of regular trading -- after the Seattle-based company had gained 4.9% for the day. Revenue for the fourth quarter came in at $25.59 billion, well below the anticipated $26.06 billion. The actual earnings per share was 51 cents -- well under the Street's estimate of 66 cents. Net sales increased 20% in the last three months of 2013 over the $21.27 billion the company took in over the same period the previous year. Read or Share this story: http://usat.ly/1bDjA8D

– Amazon Prime may cost you more in the near future—quite a lot more, in fact. Thanks to rising fuel and shipping costs, the company revealed in yesterday's quarterly earnings call that it's looking into bumping up the current $79 subscription fee $20 to $40 in the next year or so, VentureBeat reports. It would be the first price hike for the annual membership—which comes with "free" 2-day shipping plus access to Prime Instant Video and the Kindle's library-lending program—in nearly a decade. USA Today reports that Amazon's stock took a 10.6% hit in after-hours trading yesterday after the company reported Q4 revenue of $25.59 billion, a good deal below the expected $26.06 billion; net shipping costs increased 19% to $1.21 billion for the quarter. "They can't keep losing so much. This is their profit margin," an analyst tells USA Today. "Drones aside, they have to find a way to get the package from the warehouse to the user in a timely way but also in a cost-effective way." He suspects most subscribers will likely swallow the price hike—"Where are these customers going to go?" VentureBeat notes, however, that a $120 price tag might turn off only occasional buyers. A way around that? It suggests making Prime Instant Video as tempting as Netflix.

CLOSE Sen. Rand Paul discusses tax reform at UPS training center Marty Pearl, Special to the CJ Sen. Rand Paul, R-Ky., speaks to supporters gathered at The Champions of Liberty Rally in Hebron, Ky., Friday, Aug. 11, 2017. Paul was joined at the fundraising event by Kentucky Gov. Matt Bevin, and U.S. Reps Thomas Massie, R-Ky., and Jim Jordan, R-Ohio. (Photo: Bryan Woolston, AP) Police say they've arrested a man who intentionally assaulted U.S. Sen. Rand Paul, causing a minor injury. Rene Boucher, 59, of Bowling Green, is charged with one count of fourth-degree assault and is being held in the Warren County Detention Center, according to a news release from Kentucky State Police. Police responded to a report of an assault at Paul's residence just before 3:30 p.m. Friday. They determined Boucher had intentionally assaulted the junior senator, according to the release. It was not immediately clear what injury Paul suffered. More Courier Journal headlines ► House still doesn't have the votes to pass the pension reform bill ► Hoover remains House speaker with 'support' of GOP caucus ► Check out these events in Louisville over the weekend A spokeswoman for Paul's office said in an email that the senator was "blindsided." "Senator Paul was blindsided and the victim of an assault," it stated. "The assailant was arrested and it is now a matter for the police. Senator Paul is fine." The investigation is ongoing. KSP spokesman Jeremiah Hodges said the FBI was on scene to investigate whether the assault was politically motivated, but was unable to elaborate on the status of that investigation. David Habich, a spokesman for the FBI, said the agency was aware of the incident concerning Senator Paul. "We are working with our state and local partners to determine if there was a violation of federal law," Habich said. Voter records from March 2017 show Rene Boucher had registered as a Democrat. A jail website shows that Boucher was booked Friday night just before 9 p.m. He's being held on $5,000 bond and there is no court date set. Reach reporter Darcy Costello at [email protected] or 502-582-4834. Read or Share this story: http://www.courier-journal.com/story/news/crime/2017/11/04/man-accused-assaulting-senator-rand-paul/832626001/ ||||| Close Get email notifications on Don Sergent daily! Your notification has been saved. There was a problem saving your notification. Whenever Don Sergent posts new content, you'll get an email delivered to your inbox with a link. Email notifications are only sent once a day, and only if there are new matching items. ||||| Sen. Rand Paul suffered a minor injury when a man allegedly assaulted him at his home in Warren County, Kentucky, on Friday afternoon, according to state authorities. Kentucky State Police say 59-year-old Rene Boucher has been charged with fourth-degree assault and booked into Warren County Detention Center, after he "intentionally" assaulted Paul, "causing a minor injury." "On Friday, November 3, 2017 at 3:21 p.m., KSP Troopers responded to the residence of Rand Paul in Warren County, in reference to a report of an assault," Kentucky State Police said in a news release. "Upon their arrival, it was determined that Rene Boucher had intentionally assaulted Paul causing a minor injury." Warren County Regional Jail Kentucky State Police Master Trooper Jeremy Hodges said he could not release details of the assault because of security issues. Hodges did say that Boucher is an acquaintance of Paul. CBS affiliate WNKY reports that Boucher is a neighbor of Paul's. Hodges said Boucher would have faced more serious charges if had he used a weapon or if Paul had been injured seriously. "If he was using any type of a dangerous instrument, then it would have been a felony charge," Hodges said by telephone Saturday. According to WNKY, the the FBI believe that the attack was politically motivated. A spokesperson for Paul said he is "fine," and was "blindsided" by the assault. "Senator Paul was blindsided and the victim of an assault. The assailant was arrested and it is now a matter for the police. Senator Paul is fine," Kelsey Cooper, a spokesperson for Paul, told media outlets. WBKO, a local TV station in Kentucky, first reported the incident. Local authorities are conducting an investigation. A court date has not yet been set for Boucher, according to booking records. Paul, Kentucky's junior senator since 2011, is known for his libertarian leanings and fiscal conservatism. He is an ophthalmologist by trade. Paul was present at the congressional baseball practice shooting in June that seriously injured House Majority Whip Rep. Steve Scalise, R-Louisiana. CBS News' Kathryn Watson contributed to this report.

– Sen. Rand Paul suffered a minor injury Friday afternoon when he was assaulted at his Kentucky home, the Courier-Journal reports. A spokesperson for Paul says he was "blindsided" by the attacker just before 3:30pm. The nature of Paul's injury is unclear, but the spokesperson says he is "fine." Police arrested 59-year-old Rene Boucher in connection with the attack. He was charged with fourth-degree assault, a misdemeanor punishable by up to a year in jail, the Bowling Green Daily News reports. Further charges are possible. CBS News notes it's unclear what connection, if any, there is between Paul and Boucher and whether the assault happened inside or outside Paul's home. An address on file with the county lists Boucher as living in a gated community just east of Paul's home in Bowling Green.

Trump-backed Rep. Ellmers becomes first GOP incumbent to lose primary In this May 19, 2016, file photo, Rep. Renee Ellmers listens while facing off with Greg Brannon and Rep. George Holding during the 2nd District Republican primary debate at WRAL studio in Raleigh, N.C. (Photo: Travis Long, AP) North Carolina Rep. Renee Ellmers became the first Republican incumbent to lose a primary on Tuesday just days after Donald Trump endorsed her. Trump backed Ellmers in a robocall that went out on Saturday calling her a “fighter” who could help him get things done in Washington. It was his first official congressional endorsement. But on Tuesday, she lost in a primary to Rep. George Holding after redistricting forced the two North Carolina incumbents to compete for the seat. Ellmers suffered when Susan B. Anthony List, a group dedicated to electing anti-abortion Republicans to office, endorsed her opponent. SBA was upset when Ellmers attempted to stall a 20-week abortion bill that had the caveat that a woman subject to rape or incest would have to report it to authorities to qualify for an exemption from the ban. Ellmers' loss also came the same day as a video of her telling a North Carolina Republican woman that she had gained some weight. “You’re eating a little bit too much pork barbecue. Whoo!” Ellmers said as she walked past. Former American Idol star Clay Aiken, who lost his challenge to Ellmers in the 2014 election, wasted no time weighing in on the results. Read or Share this story: http://usat.ly/1t7jcyl ||||| (CNN) North Carolina Republican Rep. Renee Ellmers went out with a bang Tuesday when she mocked the weight of a party activist who didn't support her re-election campaign during a stop at a polling place. Ellmers, who lost a primary for her House seat in North Carolina's Second District to a challenger backed by conservative groups Tuesday, told a former GOP official she had "gained some weight," when she stopped to vote earlier that day. The loss is also of note because Ellmers was opposed by conservative groups, but backed by presumptive Republican presidential nominee Donald Trump, who recorded robocalls on her behalf. "You're eating a little bit too much pork barbecue," Ellmers said to Maggie Sandrock, a poll worker and former chairwoman of the Harnett County Republican Party. Video of the insult was caught by WNCN, a CBS affiliate in Raleigh. According to Sandrock, Ellmers' comments was not just a little ribbing between friends. Sandrock supported her challenger, Rep. George Holding, after years of previously backing Ellmers. Holding and Ellmers ended up facing off because of redistricting. Read More

– North Carolina Rep. Renee Ellmers, who was Donald Trump's first official congressional endorsement, lost her primary contest Tuesday after calling a former supporter fat, USA Today reports. According to WNCN, Ellmers was caught on video telling a woman at a polling place that she had "gained some weight." Ellmers added: "You're eating a little bit too much pork barbecue. Whoo!" The woman on the wrong end of those comments was Maggie Sandrock, an ex-GOP chair and former Ellmers supporter who had backed Ellmers' opponent. Despite a Trump robocall sent out Saturday, Ellmers became the first GOP incumbent to lose a primary this election. When reached later by WNCN, Ellmers doubled down on her comments: "Yeah, she's put on a little weight." Sandrock took the insult in stride. "Typical Renee," she says. "She has become a mean girl on steroids in my view." Sandrock tells CNN she wasn't surprised by Ellmers' behavior. "She took everything really personally," Sandrock says. "She has been known to lash out when confronted with constituents who don't agree with her or if they challenge her position." She says Ellmers is still a friend "but certainly not a good one." Redistricting had forced Ellmers to run against another GOP incumbent, who received the support of conservative groups.

it has long been recognized that heart failure and renal impairment frequently coexist and that functional decline in one organ system is often associated with a parallel decline in the other . in the past decade , the term cardiorenal syndrome ( crs ) has been used to describe this complex process . although initially described as a state in which therapy to relieve congestive symptoms of heart failure is limited by further decline in renal function , newer definitions and classification schemes have tried to capture the bidirectional feedback processes and complex pathophysiological interactions which exist between the heart and the kidneys . the crs is not simply renal dysfunction as a result of a low - flow state induced by depressed cardiac function but rather a complex clinical syndrome in which hemodynamic abnormalities , neurohormonal activation , inflammation and oxidative stress cause dysfunction of both organ systems through symbiotic pathways . in recognition of these complex interactions , ronco and colleagues recently presented a classification system for crs ( table 1 ) . it is well recognized that an individual can simultaneously exhibit the pathophysiological characteristics of multiple types of crs and that this classification scheme is not meant to discretely categorize patients into subgroups . as our understanding of the underlying mechanisms of crs has progressed , so has our recognition of the magnitude of the problem and of its prognostic significance . in adhere , a national registry of more than 100 000 nonselected patients admitted to hospital with acute decompensated heart failure , 31% of patients had chronic renal insufficiency , 20% had serum creatinine levels > 2.0 mg / dl , and 5% were receiving dialysis . furthermore , even moderate renal insufficiency is associated with increased mortality in patients with symptomatic or asymptomatic lv dysfunction or heart failure with preserved systolic function ; creatinine clearance predicts mortality independent of ejection fraction or functional capacity . in the studies of left ventricular dysfunction ( solvd ) trials , decline in gfr was independently associated with increased risk of mortality in patients with heart failure , regardless of baseline renal function . in patients admitted to hospital with heart failure , worsening renal function during admission predicts in - hospital mortality , complications , and longer duration of hospitalization . on the other hand , cardiovascular disease including heart failure is common in patients with renal failure , and cardiovascular death is the leading cause of mortality among renal cohorts . pharmacologic therapies for heart failure are often limited by adverse effects on renal function . although angiotensin converting enzyme inhibitors ( aceis ) , angiotensin ii receptor blockers ( arbs ) , and aldosterone antagonists all prolong survival in heart failure patients [ 1116 ] , they are relatively contraindicated in patients with unstable renal function and may cause acute declines in glomerular filtration rate ( gfr ) . furthermore , most trials evaluating the efficacy of these therapies in heart failure excluded patients with evidence of significant renal dysfunction . similarly , loop diuretics , which have never been demonstrated to improve outcomes in heart failure , are the mainstay of symptomatic treatment for volume overload and are frequently associated with a decline in renal function . moreover , there is emerging data to suggest an increase in mortality with the use of these agents . pharmacological therapy centered on neurohormonal blockade remains first - line therapy for the majority of patients with systolic left ventricular dysfunction [ 1820 ] . however , for those with advanced functional symptoms and depressed lv function , despite optimization of evidence - based hf therapies , cardiac resynchronization therapy may provide additional morbidity and mortality benefits . in up to 30% of patients with heart failure , intraventricular conduction delay produces mechanical dyssynchrony , resulting in inefficient ventricular contraction and negative remodeling . biventricular pacing may restore synchronous contraction of the interventricular septum and lv free wall with resultant improvement in lv geometry and function . cardiac resynchronization therapy ( crt ) improves symptoms , functional classification , echo parameters ( including left ventricular ejection fraction and end - systolic volume , mitral regurgitation severity , and interventricular mechanical delay ) and prolongs survival in patients with intraventricular conduction delay ( qrs complex width > 120 ms ) , lvef 35% , and new york heart association ( nyha ) class iii - iv symptoms [ 2124 ] . as such , each of the major societies ' guidelines recommends crt in this patient population [ 1820 ] . our understanding of the impact of crt on renal function in patients with crs has been limited by the exclusion of patients with renal failure from many randomized , clinical trials . the miracle trial was a double - blinded , randomized and placebo - controlled trial in which patients with nyha class iii or iv symptoms , qrs duration 130 ms , lvef 35% , and lv end - diastolic diameter 55 mm underwent implantation of a crt device and were randomized to device on ( treatment group ) or device off ( control group ) . patients were excluded from the trial if their serum creatinine was > 3.0 mg / dl . in a retrospective analysis of the miracle trial , boerrigter and colleagues assessed the effect of crt on estimated gfr ( egfr ) in patients falling into three categories : normal or increased egfr ( 90 ml / min/1.73 m ) , mildly reduced egfr ( 60 egfr < 90 ml / min/1.73 m ) , and moderately reduced egfr ( 30 egfr 60 ml / min/1.73 m ) . crt significantly improved egfr compared to control in patients with moderately reduced egfr , but it had no effect in patients with normal , increased or mildly decreased egfr . in patients with a baseline egfr 60 ml / min/1.73 m , there were fewer patients in the treatment group than in the control group who experienced worsening renal function . adelstein and colleagues demonstrated that compared to standard defibrillator ( sd ) therapy , crt - defibrillator ( crt - d ) implantation was associated with improved renal function , as well as improved survival and improved lv systolic function on echocardiogram , in patients with baseline gfr 3059 ml / min/1.73 m . patients with gfr 30 ml / min/1.73 m showed improved renal function but not improved survival after crt - d implantation , while renal function deteriorated in those with gfr 60 ml / min/1.73 m. although the authors did not specifically address the reason for the decline in this latter group , they did hypothesize that preserved renal function may be a surrogate for relatively compensated heart failure . the decline in gfr in this group could reflect the risks associated with device implantation ( see below ) or simply the natural progression of the cardiorenal syndrome , superimposed on minimal hemodynamic benefit of crt at the level of the kidney . in another study , patients who were responders to crt ( those who demonstrated any improvement in lvef after crt implantation ) showed mild improvement in gfr , while those who were nonresponders showed a decline in renal function . as in other studies , this effect was even more pronounced in patients with baseline egfr < 60 ml / min . perhaps as a result of this , prescription of acei and arb therapy increased in acei and arb therapies have a well - established survival benefit in hf patients , regardless of gfr , and the ability to offer them to patients may contribute to the overall benefit of crt . in a similar study by fung and colleagues , patients with a 10% reduction in lv end - systolic volume ( lvesv ) after crt implantation maintained stable renal function , while those who failed to show improvement in lvesv had a significant decline in gfr . from the limited data available , it appears that crt - implantation , particularly when associated with improved lv function , is associated with improved renal function in patients with baseline renal impairment . the proposed mechanisms by which crt may improve renal function are based on our current understanding of the pathophysiology of renal failure in the broader context of the cardiorenal syndrome . historically , it was believed that renal failure was a result of renal hypoperfusion , in turn , due to reduced cardiac output and diuretic - induced intravascular volume depletion . more recently , it has been recognized that elevated central venous pressure may play an equally or even more important role in the progression of renal failure among hf patients . increased right - sided filling pressures ultimately lead to renal congestion , reduced renal perfusion pressure , and direct ischemic injury as a result of increased interstitial pressure in the renal medulla [ 31 , 32 ] . crt may mitigate these processes , in part due to improved cardiac output [ 24 , 33 ] and increased mean arterial pressure [ 22 , 34 ] . it also leads to reductions in central venous pressure , and therefore , may improve renal perfusion by improving both neurohormonal activation may also play a role in the pathogenesis of the cardiorenal syndrome . heart failure is clearly associated with activation of the sympathetic nervous system ( sns ) , the renin - angiotensin - aldosterone system ( raas ) and cardiac natriuretic peptides . although the specific roles of these messenger pathways at the level of the kidney are still being elucidated , there is indirect evidence to suggest that interruption of both renal sympathetic innervation and of raas activation may produce beneficial renal effects . although catecholamine levels are not reduced with crt , sympathetic nerve activity is diminished [ 35 , 36 ] , suggesting decreased adrenergic tone with crt . in addition , long - term crt is associated with reduced raas activity and stabilization of nt - probnp levels in patients who demonstrate reverse lv remodeling but not in those who do not reverse remodel . taken together , these findings suggest that in addition to the benefits achieved through direct hemodynamic effects , crt may positively impact renal function by interrupting deleterious neurohormonal pathways that are hypothesized to be culprit in the pathophysiology of heart failure . baseline renal function may predict response to crt both in terms of mortality and other clinically important endpoints . shalaby and colleagues retrospectively studied 330 patients receiving crt and found that those in the highest tertile of serum creatinine ( 1.43.0 mg / dl ) had the highest mortality rate ( 28.7% versus 14.0% in other tertiles , p = .008 ) as well as the highest rate of the combined endpoint of mortality and heart failure hospitalization ( 41.6% versus 21.5% , p = .001 ) . when studied as a continuous variable , each 0.1 mg / dl increase in creatinine was associated with an 11% increase in mortality and a 7% increase in the combined endpoint . several other studies have similarly demonstrated that renal function is an independent predictor of survival [ 39 , 40 ] and survival - free from heart transplantation or ventricular assist device ( vad ) [ 41 , 42 ] in patients receiving crt and that the mortality benefit achieved with crt - d over standard defibrillator therapy may be attenuated or lost at low egfr . the change in gfr following crt implantation may also predict long - term outcomes . fung and colleagues were able to demonstrate that patients whose renal function remained stable at 3 months after crt implantation had lower all - cause mortality and lower combined mortality and hf hospitalization than those whose renal function declined . interestingly , in the same study , the group of patients who responded to crt as characterized by lv reverse remodeling had worse renal function at baseline than the group who did not respond . other investigators have shown that lv mass may decrease and 6-minute walk distance may increase after crt implantation in patients with egfr < 60 ml / min/1.73 m to a greater extent than in patients with egfr 60 ml / min/1.73 m . these findings may reflect the fact that while renal insufficiency is associated with a poor overall prognosis that can not be completely reversed with current therapies , patients with reduced gfr have the most to gain from reversal of the neurohormonal and hemodynamic disturbances associated with heart failure . while there are many potential benefits to crt in patients with the crs , no procedure is entirely without risks . implantation of the left ventricular lead typically requires contrast administration in order to locate the ostium of the coronary sinus and to define coronary venous anatomy . contrast - induced nephropathy ( cin ) , typically defined as an elevation in serum creatinine of 25% following intravenous contrast administration , is frequently reported after other procedures such as coronary angiography and is associated with adverse outcomes including mortality . major risk factors for cin include preexisting renal dysfunction , diabetes mellitus , congestive heart failure , volume of contrast used , female sex , and mean arterial pressure < 100 mmhg [ 4345 ] . in one study , cin occurred in 10 of 68 patients ( 14% ) undergoing crt implantation ; three of these patients required hemofiltration , and one died . the incidence of cin was higher ( 63% ) in patients with baseline creatinine 200 umol / l , and cin was associated with longer duration of hospital stay ( 19 versus 4 days , p < .01 ) . epicardial lv lead placement , via an open surgical procedure , has been proposed as an alternative in patients with renal insufficiency . although this approach is more invasive than catheter - based transvenous lead placement and is associated with longer icu stay , it avoids the use of intravenous contrast dye and may be equally effective . crs is an important clinical syndrome affecting a large proportion of patients with primary heart failure , primary kidney disease , or both and is associated with a poor prognosis . many pharmacologic therapies used in the management of heart failure have the potential to worsen renal function , particularly in patients who already have baseline renal insufficiency . cardiac resynchronization therapy is an additional tool which can be used to manage this complex patient population ; crt may have the added benefit of specifically targeting many of the underlying pathophysiological mechanisms which are felt to be central to the propagation of crs and data suggest that it may also be an effective means of treating heart failure while improving renal function in this population . crs patients are at particularly high risk of mortality and other adverse events and they may remain at higher risk than isolated hf patients when treated with crt , but the limited amount of available data suggests that they are still able to obtain some benefit from this therapy . more studies of crt in this specific population , and in the individual subtypes of crs , as well as the inclusion of crs patients in large clinical trials , will allow a greater understanding of its impact on this important disease .

the cardiorenal syndrome ( crs ) is a complex clinical syndrome in which dysfunction of either the heart or the kidneys affects the functioning of the other organ system . many therapies used in heart failure have further detrimental effects on renal function . cardiac resynchronization therapy ( crt ) is a relatively new form of device therapy that reduces morbidity and mortality in patients with heart failure . this review will discuss the effects of crt on renal function in patients with crs , the impact of baseline renal function on response to crt , and potential risks associated with crt in this unique population .

the problem of electromagnetic ( em ) wave propagation and related phenomena in relativistic plasmas has attracted considerable attention in the recent past . from the nonthermal emission of the high - energy radiation coming from a variety of compact astrophysical objects it has become possible to deduce the presence of a population of relativistic electrons in the plasma created in the dense radiation fields of those sources [ 1 ] . the principal components of these plasmas could be either relativistic electrons and nonrelativistic ions ( protons ) , or relativistic electron - positron ( e - p ) pairs . relativistic e - p dominated plasmas may be created in a variety of astrophysical situations . electron - positron pair production cascades are believed to occur in pulsar magnetospheres [ 2 ] . the e - p plasmas are also likely to be found in the bipolar outflows ( jets ) in active galactic nuclei ( agn ) [ 3 ] , and at the center of our own galaxy [ 4 ] . in agns , the observations of superluminal motions are commonly attributed to the expansion of relativistic e - p beams in a pervading subrelativistic medium . this model implies copious pair production via @xmath0 interactions creating an e - p atmosphere around the source . the actual production of e - p pairs due to photon - photon interactions occurs in the coronas of agn accretion disks , which upscatter the soft photons emitted by the accretion disks by inverse compton scattering . the presence of e - p plasma is also argued in the mev epoch of the early universe . in the standard cosmological model , temperatures in the mev range ( @xmath1 ) prevail up to times @xmath2 after the big bang [ 5 ] . in this epoch , the main constituent of the universe is the relativistic e - p plasma in equilibrium with photons , neutrinos , antineutrinos , and a minority population of heavier ions . contemporary progress in the development of super strong laser pulses with intensities @xmath3 has also made it possible to create relativistic plasmas in the laboratory by a host of experimental techniques [ 6 ] . at the focus of an ultrastrong laser pulses , the electrons can acquire velocities close to the speed of light opening the possibility of simulating in the laboratory the conditions and phenomena that , generally , belong in the astrophysical realm [ 7 ] . elucidation of the electromagnetic wave dynamics in a relativistic plasmas will , perhaps , be an essential tool for understanding the radiation properties of astrophysical objects as well as of the media exposed to the field of superstrong laser radiation . although the study of wave propagation in relativistic plasmas has been in vogue for some time , it is only in the recent years that the nonlinear dynamics of em radiation in e - p dominated plasmas [ 8 ] has come into focus . the enhanced interest stems from two facts : 1 ) e - p plasmas seem to be essential constituents of the universe , and 2 ) under certain conditions , even an ultrarelativistic electron - proton plasma can behave akin to an e - p plasma [ 9 ] . wave self - modulation and soliton - formation is , perhaps , one of the more interesting and significant signatures of the overall plasma dynamics . the existence of stable localized envelop solitons of em radiation has been suggested as a potential mechanism for the production of micropulses in agn and pulsars [ 10 ] . in the early universe localized solitons are strong candidates to explain the observed inhomogeneities of the visible universe [ 11,12 ] . in e - p plasmas , there does not exist a general satisfactory theory for the generation of soliton like structures by ultrastrong high - frequency em fields of arbitrary spatio - temporal shape . relative complexity of the fully relativistic equations ( hydrodynamic or kinetic ) has limited their solutions essentially to one - dimensional systems . a summary of the salient results is : in unmagnetized e - p plasmas , high - frequency pressure of the em pulse pushes e - p pairs in the direction of its propagation thus creating a density hump in the region of the field localization . the effective refractive index of medium decreases in this region and as a result localized soliton - formation is not supported by the medium . ( the increase in the refractive index due to the relativistic nonlinearity related with the particles high - frequency motion is not enough to cope with the decrease caused by the above mentioned effect ) . in refs.[11 , 13 ] it has been argued that localized solitons can be formed if the interaction between the em field and acoustic phonons is taken into account- the envelope solitons propagating with subsonic velocities may , then , emerge . in magnetized e - p plasma , larger classes of soliton solutions are possible - typical examples may be found in refs.[14 ] . however , it is conceivable that soliton solutions obtained in a one dimensional formulation will turn out to be unstable in higher dimensions . it is , therefore , a matter of utmost priority that we explore the possibility of finding stable multidimensional soliton solutions in e - p plasmas . dynamics of @xmath4 envelope solitons of arbitrary strong em fields in e - p plasma with a small fraction of heavy ions has been analyzed in ref.[12 ] . it was shown that , in a transparent e - p plasma , em pulses with @xmath5 ( where @xmath6 and @xmath7 respectively , the characteristic longitudinal and transverse spatial dimensions of the field ) , may propagate as stable , nondiffracting and nondispersing objects ( light bullets ) with large density bunching . it was further shown in ref . [ 15 ] that these bullets are exceptionally robust : they can emerge from a large variety of initial field distributions , and are remarkably stable . in these studies , the em field is pulse - like with longitudinal localization much stronger than the transverse ; the localization is brought about by the charge separation electric field ( usually absent in a pure e - p plasma ) created by the presence of a small population of ions . in the present paper we explore another mechanism for localization - we will show that the in the pure e - p plasma , the thermal pressure can provide the confining glue just as the charge separation electric field did for an e - p plasma contaminated with ions . we will also deal with a complimentary manifestation of the radiation field- the beam ( @xmath8 ) rather than the pulse ( @xmath9 ) . assuming the plasma to be transparent to the beam , and applying a fully relativistic hydrodynamical model , we demonstrate the possibility of beam self - trapping leading to the formation of stable @xmath10 solitonic structures . the high - frequency pressure force of the em field ( tending to completely expel the pairs radially from the region of localization ) is overwhelmed by the thermal pressure force which opposes the radial expansion of the plasma creating conditions for the formation of the stationary self - guiding regime of beam propagation . in this paper the word relativistic connotes two distinct regimes : the plasma becomes relativistic when either the directed fluid velocity approaches the speed of light or the thermal energy per particle is of the order of , or larger than the rest mass energy . since both these paths to relativity are encountered in the astrophysical as well as laboratory plasmas ( produced and accelerated by intense laser pulses ) , we will investigate a fully relativistic hydrodynamical model . if the velocity distribution of the particles of species @xmath11 ( @xmath12 where @xmath13,@xmath14 , and @xmath15 denote respectively electrons , positrons and heavy ions ( protons ) ) is taken to be a local relativistic maxwellian , the hydrodynamics of such fluids is described by [ 16 ] : @xmath16 where @xmath17 $ ] is the hydrodynamic four - velocity with @xmath18 as the three - velocity , @xmath19 is the relativistic factor , @xmath20 is the four - current , @xmath21 is the electromagnetic field tensor , and @xmath22 is the enthalpy per unit volume @xmath23 here @xmath24 and @xmath25 are the particle invariant rest mass and temperature , respectively , @xmath26 is the density in the laboratory frame of the fluid of species @xmath11 . the pressure @xmath27 , and @xmath28 , where @xmath29 and @xmath30 are , respectively , modified bessel functions of the second and third order and @xmath31 . the factor @xmath32 has the following asymptotes , @xmath33 for @xmath34 ( non - relativistic ) and @xmath35 for @xmath36 ( highly relativistic ) . the set of equations ( 1)-(2 ) may be written in the standard form : @xmath37 @xmath38 where @xmath39 is the hydrodynamical momentum , @xmath40 and @xmath41 are the electric and magnetic fields , and @xmath42 is the comoving derivative . the hydrodynamical velocity @xmath18 and the relativistic @xmath43 are related to the momentum by the standard relations : @xmath44 and @xmath45 . it is interesting to note from eqs . ( 3)-(4 ) that the fluid inertia is modified by the temperature ; the expression @xmath46 denotes the effective mass of the particle . for ultrarelativistic temperatures ( @xmath47 ) , the effective mass turns out to be @xmath48 . thus the particles forget their rest mass and the plasma turns into a kind of photon gas . if an ultrarelativistic plasma is in thermodynamical equilibrium with the high - frequency photon gas ( @xmath49 ) , one should also take into account the radiation pressure @xmath50 [ 17 ] . in this paper this effect will be neglected . we must also bear in mind that for extremely relativistic regimes , the model eqs.(3)-(4 ) fail to adequately describe the plasma dynamics since heavy particle production has been neglected . this shortcoming will impose an upper limit on the temperature for the validity of the model .. note that in the context of early universe , the epoch in which the e - p plasma is dominant , has a characteristic temperature @xmath51 and @xmath52 . since the particle masses are just a few times larger than their rest mass at these temperatures , the e - p plasma can still be considered as a two component fluid rather than a photon gas . the equation of state directly follows from the self - consistency of eqs.(3 ) and ( 4 ) . taking the scalar product of eq.(4 ) with @xmath18 and comparing it with eq.(3 ) , we can derive @xmath53 . after straightforward manipulation , the equation can be easily integrated to yield @xmath54 where the arbitrary constant @xmath55 must be defined by the initial state . using @xmath56 eq.(5 ) reduces to the adiabatic equation of state : @xmath57 for nonrelativistic temperatures , eq.(6 ) yields the usual result for a monoatomic ideal gas ( @xmath58 , where @xmath59 is the density in the rest frame of fluid element ) and for ultrarelativistic temperatures one obtains the equation of state for the photon gas ( @xmath60 ) . we would like to emphasize that the @xmath43 factor appearing in eq.(6 ) is related to the coherent or directed motion of fluid elements whose origin may lie either in an initial macroscopic flow or in the motion imparted by intense em radiation . to complete the picture we must couple the plasma equations of motion with maxwell equations : @xmath61 @xmath62 @xmath63 @xmath64 where @xmath65 are , respectively , the charge and current densities . the system of eqs.(3)-(11 ) along with the continuity equation ( for each species ) @xmath66 represents a closed set of equations which describe propagation of em radiation in relativistic multicomponent plasmas . the above system can be manipulated further to reveal interesting structural properties . to begin with , eqs.(5)-(6 ) can be cast in the form @xmath67 which , when substituted into eq.(4 ) , converts it to @xmath68\ ] ] where @xmath69 is the so called generalized vorticity . taking the curl of eq.(14 ) , we find that the evolution equation for @xmath70 @xmath71\ ] ] is of the standard vortex dynamics form . although the system of eqs.(14)-(16 ) can be traced to early publications ( see for instance ref.[18 ] ) , their consequences are yet to be fully worked out . an immediate consequence , for instance , is the appropriate equivalent of kelvin s theorem- the flux of generalized vorticity @xmath72 is frozen - in through a comoving area . the system yields the following set of relativistic beltrami- bernoulli equations for equilibrium [ 19 ] : @xmath73 @xmath74 where @xmath75 are constants and @xmath76 is the scalar potential . the relevance of these equilibria for astrophysics is the subject matter of a forthcoming paper . for the current effort , we apply eqs.(14)-(16 ) for wave processes in an unmagnetized plasma . from eq.(16 ) it follows that if the generalized vorticity is initially zero ( @xmath77 ) everywhere in space , it remains zero for all subsequent times . we assume that before the em radiation is switched on , the generalized vorticity of the system is zero . in this case the equation of motion may be written as : @xmath78 where the temperature dependent momentum @xmath79 and @xmath80 are defined by : @xmath81 @xmath82 the condition of vanishing generalized vorticity connects @xmath83 with the magnetic field : @xmath84 it is remarkable that in eq.(19 ) the magnetic part of the lorentz force is formally absent ; this fact greatly simplifies analytical manipulations . it is equally remarkable that our equations which describe the dynamics of a hot relativistic plasma are structurally similar to equations used in the theoretical treatment of different aspects of ultrastrong laser interaction with a cold plasma [ 20 ] . this similarity becomes even more evident when we study the interaction of short em pulse with relativistic electron - ion plasmas . if the pulse is assumed to be shorter than the characteristic time for ion response ( i.e. inverse of ion langmuir frequency ) , the ion motion may be ignored , and the electric field may be found from the electron part of eq.(19 ) , @xmath85 substituting this expression into poisson s eq.(3 ) ( which now reads as @xmath86 , where @xmath87 is the equilibrium ion density ) we find the electron density @xmath88 where @xmath89 is the plasma frequency . using eqs.(22)-(24 ) , eq.(7 ) reduces to : @xmath90 @xmath91 = 0\ ] ] which , along with the equation of state ( @xmath92 ) @xmath93 constitutes the simplified system to which the entire set of maxwell and relativistic hydrodynamic equations for an the electron -ion plasma have been reduced . an equation similar to eq.(25 ) was derived in the cold plasma limit in ref.[21 ] . however , there are important differences : a ) due to the temperature dependence of @xmath94 in eq.(21 ) , the factor @xmath95 and the momentum @xmath96 are no more related by simple relations as they do for a cold case , and b ) to incorporate the temperature variation in the system we must add the equation of state ( 26 ) . though eqs.(25)-(26 ) form a more complicated system than what we have for the cold plasma , we believe that many results obtained in the cold plasma limit can find appropriate analogies in the hot relativistic- temperature case . detailed studies of the nonlinear dynamics of the electron - ion plasma is beyond the intended scope of the current paper and some new results will be presented separately elsewhere . in the next part of the current paper , we concentrate on the nonlinear dynamics of em beams in e - p dominated plasmas . in this section we apply our general formulation to the problem of self - trapping of em beams in pure e - p plasmas with relativistic temperatures . for notational convenience , we replace the subscripts ( e ) and ( p ) by superscripts @xmath97 , and @xmath98 . we assume that the equilibrium state of the plasma is characterized by an overall charge neutrality @xmath99 , where @xmath100 and @xmath101 are the unperturbed number densities of the electrons and positrons in the far region of the em beam localization . in most mechanisms for creating e - p plasmas , the pairs appear simultaneously and due to the symmetry of the problem it is natural to assume that @xmath102 , where @xmath103 and @xmath104 are the respective equilibrium temperatures . we shall assume that for the radiation field of interest , the plasma is underdense and transparent , i.e. , @xmath105 , where @xmath106 is the mean frequency of em radiation and @xmath107 is the plasma frequency . since both species are mobile , the e - p dynamics can not be reduced to just one vector equation similar to eq.(25 ) . we will display the entire set in terms of potentials ( the coulomb gauge @xmath108 will be used ) , @xmath109 and the dimensionless quantities @xmath110 , @xmath111 , @xmath112 , @xmath113 , @xmath114 , @xmath115 , and @xmath116 . suppressing the label- tilde , we may arrive at the dimensionless equations , @xmath117 @xmath118 @xmath119 @xmath120 @xmath121 with @xmath122 and @xmath123 . the species equation of state is : @xmath124 where @xmath125\ ] ] of various techniques that could be invoked to investigate eqs.(28)-(34 ) to study the self - trapping of high - frequency em radiation propagating along the @xmath126- axis , we choose the method presented in the excellent paper by sun et al . [ 22 ] . the method is based on the multiple scale expansion of the equations in the small parameter @xmath127 . assuming that all variations are slow compared to the variation in @xmath128 , we expand all quantities @xmath129 as @xmath130 where @xmath131 denote the directions of slow change , and @xmath132 . we further assume that the high - frequency em field is circularly polarized , @xmath133 here @xmath134 is the slowly varying envelope of the em beam , @xmath135 and @xmath136 denote unit vectors , and @xmath137 is the complex conjugate . we now give a short summary of the steps in the standard multiple- scale methodology ( ref.[22 ] ) . to the lowest order in @xmath127 , we obtain the following . the transverse ( to the direction of em wave propagation @xmath126 ) component of eq.(28 ) reduces to @xmath138 and for the longitudinal components we get : @xmath139 equations ( 29)-(31 ) yield @xmath140 , where @xmath141 is the perpendicular laplacian in @xmath142 . these relations imply that @xmath143 and @xmath144 do not depend on the fast variable @xmath145 . for the self - trapping problem , we can assume that @xmath146 [ 22 ] . from eq.(38 ) , and from the lowest order continuity eq . ( 32 ) , we obtain : @xmath147 , i.e. , @xmath148 and @xmath149 also do not depend on the fast variable @xmath145 . to the next order ( in @xmath127 ) , the transverse component of eq.(28 ) reads : @xmath150 averaging over the fast variable @xmath145 we obtain @xmath151 yielding the trivial solution @xmath152 and @xmath153 . note that from eqs.(30 ) and ( 33 ) , we can deduce that @xmath154 and @xmath155 . thus , as one would expect , the low frequency motion of the e - p plasma is driven by the ponderomotive pressure ( @xmath156 ) of the high - frequency em field and this force , being same for the electrons and positrons , does not cause charge separation . it is also evident that due to the symmetry between the electron and positron fluids , their temperatures , being initially equal , will remain equal during the evolution of the system . the relation between the em field and the temperature can be found using the equation @xmath157 obtained above . using eqs.(36)-(37 ) and by choosing the @xmath158 by requiring that at infinity @xmath159 and @xmath160 , we derive @xmath161 it follows from eq.(40 ) that the present hydrodynamical model , which describes the nonlinear waves in e - p plasma , is valid for @xmath162 . in our opinion the origin of this restriction lies in the inadequacy of the basic model , and is not solely due to a failure of the perturbation technique used above . when this condition is violated , the em waves are overturned and they will cause multistream motion of the plasma ( i.e. wave breaking takes place ) . in such a situation , one must resort to kinetic description for studying the nonlinear wave motion . notice however that the function @xmath163 if @xmath164 but rapidly increases with increase of @xmath165 thus providing room for @xmath166 to reach from weak to relativistic values . we are now ready to deal with the equation for the slowly varying envelope @xmath167 of the em beam . to the lowest order in @xmath127 , one finds from eq.(29 ) @xmath168 for deriving this equation , we used the relation @xmath169 , and @xmath170 which follows from eq.(33 ) . substituting eq.(36 ) into eq.(41 ) we find : @xmath171a=0\ ] ] where subscripts for variables ( @xmath172 ) are dropped for simplicity . we also assumed without loss of generality that @xmath173 , which in dimensional units coincides with the linear dispersion relation of the em wave in an e - p plasma , namely : @xmath174 provided that @xmath175 . thus , the dynamics of em beams in hot relativistic e - p plasma has become accessible within the context of a generalized nonlinear schrdinger equation ( nse ) ( 43 ) . in this section we seek the localized 2d soliton solutions of eq.(43 ) , and analyze the stability of such solutions . making the self - evident re - normalization of variables @xmath176 , @xmath177 , eq.(43 ) can be written as : @xmath178 where @xmath179 represents the generalized nonlinearity . the companion equation ( 40 ) can be viewed as a transcendental algebraic relation between @xmath180 and @xmath181 . thus we conclude that @xmath182 is a function of @xmath181 ( @xmath183 . we note that eq.(44 ) can be written in the hamiltonian form @xmath184 , where @xmath185 $ ] and @xmath186 . the hamiltonian structure implies that eq.(44 ) conserves the hamiltonian @xmath187 in addition to the power ( photon number ) @xmath188 . unfortunately , it is not possible , in general , to derive an explicit analytic relation @xmath183 for arbitrary value of @xmath165 . some qualitative deductions readily follow . equation ( 40 ) shows that the presence of em radiation reduces the temperature @xmath180 . since @xmath189 , from eq.(42 ) we conclude that the plasma density is also reduced in the region of the em field localization which is in accordance with adiabatic motion of the plasma . for higher strength of the em field , a complete expulsion of plasma i.e. plasma cavitation can take place ( @xmath190 ) ; this has been predicted in ref.[23 ] . thus the nonlinearity function @xmath182 shows a saturating character with the increase of em field strength ( note that present model is valid provided latexmath:[$% a plot of @xmath182 versus @xmath181 for @xmath192 . one can see that the nonlinearity function indeed saturates at high intensity . versus @xmath181 for @xmath193.,width=264 ] for small temperatures , we can even obtain an analytic expression for the function @xmath194 . remembering @xmath195 , assuming @xmath196 , and by using eq.(42 ) along with the asymptotic expansions @xmath197 and @xmath198 , we derive for the nonlinearity function : @xmath199 equations ( 44)-(45 ) admit a stationary , nondiffracting axially symmetric solution of the form @xmath200 where @xmath201 and @xmath202 is the nonlinear wave - vector shift . the radially dependent envelope @xmath203 obeys an ordinary nonlinear differential equation : @xmath204 where @xmath205 . this equation corresponds to a boundary value problem with the boundary conditions : @xmath206 has its maximum @xmath207 at @xmath208 , and @xmath209 as @xmath210 . we remind the reader that it has been shown in a seminal paper of vakhitov and kolokolov [ 24 ] that such solutions exist for arbitrary saturating nonlinearity functions @xmath182 , provided that the eigenvalue @xmath202 satisfies @xmath211 , where @xmath212 is a maximal value of the nonlinearity function . equation ( 46 ) admits an infinity of discrete bound states characterized by @xmath213 zeros at finite @xmath214 . we consider only the lowest - order nodeless solution of eq.(46 ) , i. e. ground state that is positive and monotonically decreasing with increasing @xmath214 . in the asymptotic region the solution must decay as @xmath215 . our nonlinearity function @xmath182 has a maximum @xmath216 found at @xmath217 , i. e. at the maximally allowed strength of the field . as a consequence the upper bound of the propagation constant @xmath218 must satisfy @xmath219 . numerical simulations show that the amplitude of the ground state solution @xmath220 is a growing function of @xmath202 ( see fig.2 ) and it acquires its maximum value ( @xmath221 ) at @xmath222 . as a function of @xmath202 , the eigenvalue . the plasma temperature @xmath223.,width=264 ] the solution represents a trapped , localized em solitary beam . the beam becomes wider at low amplitudes . the stability of the solitonic solutions can be investigated using the criterion of vakhitov and kolokolov [ 24]- the soliton is stable against small , arbitrary perturbations if @xmath224 , where @xmath225 is the power of the trapped mode : @xmath226 versus @xmath202 ( @xmath227).,width=264 ] in fig.3 we plot the numerically obtained solutions of @xmath225 for various @xmath228 . since the curve has positive slope everywhere , the corresponding ground state solution is stable for @xmath229 . notice that the power of the solitary beam always exceeds a certain critical value @xmath230 . we also know that @xmath225 must be bounded from above ( @xmath231 ) . for arbitrary temperatures , explicit form of @xmath183 can not be found . however , due to its saturating character , solutions with properties similar to the small temperature case ( which can be explicitly solved ) could be expected . using relations ( 34 ) , ( 40 ) and ( 42 ) , we numerically find a stationary solution of eq.(44 ) for arbitrary @xmath165 . for convenience we use following representation of vector potential @xmath232 , where @xmath233 . though the maximum value of @xmath206 is still restricted by the condition @xmath234 , the amplitude of vector potential @xmath235 can reach a considerable value . for ultrarelativistic temperatures , @xmath236 , we have @xmath237 and since @xmath238 the soliton solution with ultrarelativistic strength of em field is possible . here we present results of simulations for @xmath239 ( i.e. @xmath240 ) . versus @xmath202 for @xmath239.,width=264 ] in fig.4 we plot the amplitude of the ground state solution @xmath207 versus the propagation constant @xmath202 . the solution exists provided @xmath241 . the profiles of the field @xmath203 the plasma density @xmath242 and the temperature @xmath243 are exhibited in fig.5 for @xmath244 . , plasma temperature @xmath180 and density @xmath245 versus @xmath214 for @xmath239.,width=264 ] one can see that in the region of field localization , the plasma temperature and density is reduced . similar plots could be obtained for all allowed values of @xmath202 . when @xmath246 , plasma cavitation takes place , i.e. at @xmath247 the plasma density and temperature tends down to zero . appearance of zero temperature is not surprising since the corresponding region is the plasma vacuum ; all particles are gone away . versus @xmath202 ( @xmath239).,width=264 ] the dependence of @xmath225 on @xmath202 is presented in fig.6 . one can see that the curve @xmath248 has a positive slope and according to vakhitov and kolokolov criterion , the corresponding solitary solutions are stable against small perturbations . the detailed dynamics of arbitrary field distribution must be studied by direct simulations of eq.(44 ) . we can learn much , however , from the recent extensive elucidations of the dynamical properties of the solutions of nse with saturating nonlinearity . it seems that the general features of evolution are not sensitive to the details of the saturating nonlinearity ( see for instance [ 15 , 25 ] and references therein ) . for all such systems the beam will monotonically diffract if the beam power is below a critical value ( @xmath249 ) , and it will be trapped if @xmath250 and the hamiltonian @xmath251 is negative . in the latter case , the beam parameters will oscillate near the equilibrium , ground state values . this oscillations monotonically decrease with increase @xmath126 due to the appearance of the radiation spectrum . for larger @xmath126 , the oscillations are damped out , and the formation of the soliton in its ground state takes place . if the initial profile of the beam is close to the equilibrium one , the beam quickly reaches the ground - state equilibrium , and propagates for a long distance without distortion of its shape . the initial beam , even when its parameters ( i.e. amplitude , effective width and phase ) are quite far from equilibrium , will either focus or defocus to the ground state , exhibiting damped oscillations around it . as a consequence the beam reaches an equilibrium with its final power slightly smaller than the initial . such an evolutionary scenario may not hold for very intense beams with @xmath252 ; the beam may then break up into filaments due to a modulation instability . however , each filament , will tend to evolve towards its own equilibrium state corresponding to the power it carries . thus , the ground - state equilibrium seems to be an attractor . our own studies indicate that eq.(44 ) , with the nonlinearity particular to the problem at hand , reproduces the general expected behavior described above . however we find that the soliton formation requires the initial beam power to be in the range @xmath253 . for @xmath254 , the multistream motion of the plasma prevents the system from settling in a steady state . we have investigated the nonlinear propagation of strong em radiation in a relativistic , unmagnetized two - fluid plasma . the treatment is fully relativistic- in the coherent or directed motion as well as in the random or thermal motion of the plasma particles . the assumption that prior to the switching of the field - plasma interaction , the generalized vorticity is zero , greatly simplifies the system of relativistic fluid equations . in particular , in the electron - ion dominated plasma , under well defined conditions the system of maxwell -fluid equation ( eqs.(25)-(26 ) ) turns out to be structurally similar to the one obtained for a cold plasma . consequently we would expect that results already established in cold plasma limit can find appropriate analogy in the hot plasma case . we presented a somewhat detailed study of em beam propagation in transparent e - p plasmas . applying a reductive perturbation technique , the system of relativistic maxwell- fluid equations is reduced to a 2d nonlinear schrdinger equation with a saturating nonlinearity . we found that if the strength of the em field amplitude is below the wave breaking limit , the beam can enter the self - trapped regime resulting in the formation of stable , self - guided @xmath10 solitonic structures . the beam - trapping owes its origin to the thermal pressure ( which opposes the ponderomotive pressure ) - naturally such trapping regimes are not accessible in the relativistic but cold plasma limit . in the region of beam trapping , the plasma density as well as its temperature is reduced and under certain conditions these parameters can be reduced considerably ( i.e. plasma cavitation takes place ) . the fact that relativistically hot e - p plasmas are capable of sustaining high amplitude localized structures of high amplitude electromagnetic fields should be a result of considerable importance to an understanding of the complex radiative properties of different astrophysical objects where such plasmas are known to exist . the work of z y is partially supported by toray science foundation , the work of v i b was partially supported by the intas georgian call-97 , and s m m s work was supported by the u.s . department of energy contract no . de - fg03 - 96er-54346 . p. mszros and m.j . rees , apj * 418 * , l59 ( 1993 ) ; 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interaction of an intense electromagnetic ( em ) beam with hot relativistic plasma is investigated . it is shown that the thermal pressure brings about a fundamental change in the dynamics - localized , high amplitude , em field structures , not accessible to a cold ( but relativisic ) plasma , can now be formed under well- defined conditions . examples of the trapping of em beams in self - guiding regimes to form stable 2d solitonic structures in a pure e - p plasma are worked out .

SECTION 1. REAUTHORIZATION AND ENHANCEMENT OF JOHANNA'S LAW. (a) In General.--Section 317P(d)(4) of the Public Health Service Act (42 U.S.C. 247b-17(d)(4)) is amended by inserting after ``2009'' the following: ``, $16,500,000 for the period of fiscal years 2010 through 2012, and such sums as are necessary for each subsequent fiscal year''. (b) Collaboration With Nonprofit Gynecologic Cancer Organizations.--Section 317P(d) of such Act (42 U.S.C. 247b-17(d)) is amended by adding at the end the following new paragraph: ``(5) Collaboration with nonprofit gynecologic cancer organizations.--In carrying out the national campaign under this subsection, the Secretary shall collaborate with the leading nonprofit gynecologic cancer organizations, with a mission both to conquer ovarian cancer nationwide and to provide outreach to State and local governments and communities, for the purpose of determining the best practices for providing gynecologic cancer information and outreach services to varied populations.''. SEC. 2. DEMONSTRATION PROJECTS REGARDING OUTREACH AND EDUCATION STRATEGIES RELATING TO GYNECOLOGIC CANCER. (a) In General.--Section 317P of the Public Health Service Act (42 U.S.C. 247b-17) is amended by adding at the end the following new subsection: ``(e) Demonstration Projects Regarding Outreach and Education Strategies.-- ``(1) In general.--The Secretary shall carry out a program to make grants to nonprofit private entities for the purpose of carrying out demonstration projects to test different outreach and education strategies to increase the awareness and knowledge of women and health care providers with respect to gynecologic cancers, including early warning signs, risk factors, prevention, screening, and treatment options. Such strategies shall include strategies directed at women and their families, physicians, nurses, and key health professionals. ``(2) Preferences in making grants.--In making grants under paragraph (1), the Secretary shall give preference to-- ``(A) applicants with demonstrated expertise in gynecologic cancer education or treatment or in working with groups of women who are at especially high risk of gynecologic cancers; and ``(B) applicants that, in the demonstration project funded by the grant, will establish linkages between physicians, nurses, and key health professionals, hospitals, payers, and State health departments. ``(3) Application for grant.--A grant may be made under paragraph (1) only if an application for the grant is submitted to the Secretary and the application is in such form, is made in such manner, and contains such agreements, assurances, and information as the Secretary determines to be necessary to carry out this subsection. ``(4) Certain requirements.--In making grants under paragraph (1)-- ``(A) the Secretary shall make grants to not fewer than five applicants, subject to the extent of amounts made available in appropriations Acts; and ``(B) the Secretary shall ensure that information provided through demonstration projects under such grants is consistent with the best available medical information. ``(5) Report to congress.--Not later than 6 months after the date of the enactment of this subsection and annually thereafter, the Secretary shall submit to the Congress a report that-- ``(A) summarizes the activities of demonstration projects under paragraph (1); ``(B) evaluates the extent to which the projects were effective in increasing early detection of gynecologic cancers and awareness of risk factors and early warning signs in the populations to which the projects were directed; and ``(C) identifies barriers to early detection and appropriate treatment of such cancers. ``(6) Authorization of appropriations.-- ``(A) In general.--For purposes of carrying out this subsection, there is authorized to be appropriated in the aggregate $15,000,000 for the period of fiscal years 2010 through 2012 and such sums as are necessary for each subsequent fiscal year. ``(B) Administration, technical assistance, and evaluation.--Of the amounts appropriated under subparagraph (A), not more than 9 percent may be expended for the purpose of administering this subsection, providing technical assistance to grantees under this subsection, and preparing the report under paragraph (5).''. (b) Conforming Amendment.--Subsection (d)(3)(A) of such section is amended by inserting ``(other than subsections (e))'' after ``this section''.

Amends the Public Health Service Act to extend through FY2012 the current authorization of appropriations for the national public awareness campaign for gynecologic cancers (Johanna's law). Authorizes appropriations in subsequent fiscal years at levels necessary to carry out such campaign. Requires the Secretary of Health and Human Services (HHS) to: (1) collaborate with nonprofit gynecologic cancer organizations to determine the best practices for providing gynecologic cancer information and outreach services to varied populations; and (2) make grants to nonprofit private entities to carry out demonstration projects to test outreach and education strategies to increase the awareness and knowledge of women and health care providers regarding gynecologic cancers.

it is well established that quantum mechanics of a non - relativistic particle and paraxial wave optics in dielectric media shear strong formal similarities ( see , for instance , @xcite ) . owing to such similarities , the temporal evolution of a quantum particle ( e.g. an electron in an atom or in a crystal ) can be mimicked by means of light propagation in suitably - designed photonic structures . quantum - optical analogies have seen in recent years a renewed and increasing interest , both theoretically and experimentally , mainly motivated by the possibility offered by optics to visualize at a macroscopic level certain coherent phenomena , originally proposed for quantum systems , which may be of difficult access or of controversial interpretation in the quantum context ( see , e.g. , @xcite and references therein ) . in particular , recent works theoretically proposed and experimentally demonstrated the optical analogues of some important coherent phenomena encountered in atomic and molecular physics , such as coherent population transfer @xcite , electromagnetically - induced transparency @xcite , and population trapping in the continuum @xcite . the latter effect has been extensively investigated in atomic physics in connection , for instance , with the problem of autoionization of an atom by ultraviolet radiation or in laser - induced continuum structures ( see @xcite and references therein ) . in the simplest case , population trapping in the continuum describes decay suppression of two discrete states coupled to a common and unstructured continuum : as a single bound state coupled to the continuum decays in an irreversible way and population is transferred into the continuum , under certain conditions coupling of the continuum with the additional other bound state may partially or totally suppress the decay of states owing to a destructive interference effect which was first studied by fano for radiative transitions to autoionizing states in atoms @xcite . fano - like resonances in photonic systems have been considered in several recent works as well @xcite , with a main focus on the scattering ( transmission ) properties of the structures . these previous studies in optics have mostly considered propagation of classical light in coupled guiding structures , disregarding the quantum nature of light . for classical light , destructive interference among different tunneling paths is responsible for the existence of bound states in the continuum , similarly to fano interference in atomic physics . however , when few photons or nonclassical beams are used to excite the photonic structures , light propagation may show interference effects of quantum nature . since long time , coupled waveguides are known to behave similarly to beam splitters ( see , for instance , @xcite ) and to show strictly quantum features when nonclassical light propagates through them , such as two - photon hong - ou - mandel quantum interference originally demonstrated for beam splitters @xcite . like beam splitters @xcite , coupled waveguides offer the possibility to transfer nonclassical properties of light and to generate entangled states @xcite . with recent technological advances in the realization of high - quality low - loss integrated photonic structures and nonclassical light sources , such possibilities are nowadays realities . high - fidelity hong - ou - mandel quantum interference and integrated optical realizations of other key quantum photonic circuits have been recently demonstrated in silicon - based waveguide couplers @xcite . in another recent experiment , bromberg et al . @xcite showed nontrivial photon correlations in coupled waveguide arrays and observed them using classical intensity correlation measurements . the possibility offered by experimentalists to test quantum aspects of light in integrated optic networks motivates to extend previous studies of quantum - optical analogies from the classical to the quantum level , highlighting interference effects of purely quantum nature . for instance , a recent theoretical study of optical bloch oscillations and zener tunneling in optical lattices @xcite showed that propagation of nonclassical light in the lattice may reveal certain particle - like aspects of light and quantum interference phenomena . + in this work we investigate classical and quantum interference effects of light in an optical analogue of coherent population trapping , based on two optical channel waveguides side coupled to a common slab waveguide recently proposed in ref.@xcite . for classical light ( coherent states ) , such system realizes in optics a simple analogue of destructive fano interference with suppression of light leakage from the channel waveguides ( analogous to two discrete states ) into the slab waveguide ( the analogue of the continuum ) . when the description of light propagation is made at the quantum level , photon pair excitation reveals strictly quantum features , such as the tendency of photons to bunch when decaying into the continuum . let us consider propagation of quasi - monochromatic and paraxial light wave packets at carrier frequency @xmath0 in a weakling guiding dielectric structure , with optical axis @xmath1 and refractive index profile @xmath2 , composed by two straight and parallel single - mode and equal channel waveguides w@xmath3 and w@xmath4 , side - coupled to a slab waveguide s as shown in fig.1(a ) . in the paraxial , weak guidance and quasi - monochromatic approximations , the electric field can be written as @xmath5 , where the envelope @xmath6 varies slowly with respect to @xmath1 and @xmath7 over one wavelength @xmath8 and one optical cycle @xmath9 . neglecting nonlinearities and group - velocity dispersion , the slow evolution of the electric field envelope @xmath10 along the paraxial @xmath1 direction is governed by the scalar wave equation @xmath11 where @xmath12 is the reference propagation constant , @xmath13 is the substrate refractive index , @xmath14 is the group velocity of light , and @xmath15/n_s$ ] . the electric field envelope @xmath6 has been normalized such that the cycle - averaged total energy of the electromagnetic field ( see , e.g. , @xcite ) is given by @xmath16 at the entrance plane @xmath17 , light is typically injected into either one , or in both , the channel waveguides w@xmath3 and w@xmath4 , in the form of either monochromatic waves or wave packets with spatial profiles tailored to match their fundamental modes . owing to evanescent coupling with the slab waveguide s , light leakage into the continuous set of modes of the slab is generally found , however for certain geometric settings a trapping state may exist , corresponding to destructive interference between different tunneling paths into the continuum @xcite . at a classical level , light propagation in the waveguides is well captured in the framework of a coupled mode equation approach , as previously shown in ref.@xcite . after introduction of the spectral decomposition @xmath18 , from eq.(1 ) it follows that the spectral amplitude @xmath19 satisfies the wave equation @xmath20 let us indicate by @xmath21 and @xmath22 the fundamental modes of waveguides w@xmath3 and w@xmath4 , and by @xmath23 the continuous set of modes of the slab waveguide s with the normalization conditions @xmath24 and @xmath25 , where @xmath26 . let us search for a solution to eq.(3 ) in the form @xmath27 \exp(i \omega z / v_g ) . \nonumber\end{aligned}\ ] ] the evolution equations of modal amplitudes @xmath28 , @xmath29 and @xmath30 then read @xcite @xmath31 where : @xmath32 is the coupling amplitude between modes @xmath33 and @xmath34 ; @xmath35 is the coupling amplitude between modes @xmath36 and @xmath34 ; and @xmath37 , @xmath38 are the propagation constant shifts of modes @xmath34 and @xmath39 , respectively , from the reference value @xmath40 . in their present form , eqs.(5 - 7 ) are analogous to the dynamical equations describing the quantum mechanical decay of two bound states w@xmath3 and w@xmath4 into a common continuum s [ see fig.1(b ) ] , provided that the temporal dynamics of the quantum mechanical problem is replaced by the paraxial propagation in space of light waves . the two bound states , with the same energy , are embedded in the continuum provided that @xmath38 falls inside the continuous spectrum @xmath41 , a condition which is satisfied whenever the refractive index change @xmath42 in the slab waveguide is smaller than the index change @xmath43 in the two channel waveguides ( see @xcite for more details ) . note that , if waveguides w@xmath3 and w@xmath4 are symmetrically placed at opposite sides from the slab waveguide s as shown in fig.1(a ) , the coupling coefficients @xmath32 and @xmath35 are the same , i.e. @xmath44 , and in this case a trapped state does exist , as discussed in ref.@xcite . although trapped states in the continuum may also exist when the waveguides w@xmath3 and w@xmath4 are horizontally displaced or placed at different distances from the slab waveguide @xcite , in this work we will consider the simplest symmetric case shown in fig.1(a ) . if one of the two channel waveguides , say e.g. w@xmath4 , were removed , light initially injected into waveguide w@xmath3 would decay into the slab waveguide , a phenomenon fully analogous to the quantum mechanical decay of a bound state coupled to a continuum . in the markovian approximation , valid for weak coupling and for a nearly unstructured continuum , the decay is well described by an exponential law . the presence of waveguide w@xmath4 generally modifies the decay behavior and , under certain conditions , the decay can be suppressed owing to a destructive fano - like interference of different decay channels . full or fractional suppression of the decay is related to the appearance of a trapped ( or dark ) state in the continuum . to derive the decay laws of light waves in the channel waveguides w@xmath3 and w@xmath4 , we follow a standard procedure @xcite , detailed for instance in ref.@xcite , and eliminate the amplitudes @xmath30 of continuous modes by a formal integration of eq.(7 ) with the initial condition @xmath45 . this yields a set of two coupled integro - differential equations for the amplitudes @xmath28 and @xmath29 of discrete modes . in the weak coupling limit and assuming a nearly unstructured continuum , the markovian approximation can be made and the following reduced equations for amplitudes @xmath28 and @xmath29 are derived @xmath46 where @xmath47 \tau \}\ ] ] is the decay rate of the single channel waveguide into the continuum . the solution to eqs.(8 ) reads explicitly @xmath48 where @xmath49\\ s_{12}(z ) & = & -\frac{1}{2 } \exp(-i \delta \beta_0 z ) \left[1-\exp(-2 \sigma z ) \right ] \\ s_{22}(z ) & = & s_{11}(z ) \ ; , \;\ ; s_{21}(z)=s_{12}(z).\end{aligned}\ ] ] note that , in the quasi - monochromatic approximation assumed in this work , the matrix coefficients @xmath50 are independent of frequency @xmath51 . to understand the appearance of the optical analogue of population trapping , let us consider the monochromatic case , with the only nonvanishing spectral component at @xmath52 , and two different input excitations , corresponding the former to single waveguide excitation and the latter to simultaneous excitation of the two channel waveguides . in the former case , assuming for instance @xmath53 and @xmath54 , one obtains @xmath55 where the last term on the right hand side of eq.(15 ) accounts for the light field tunnelled into the slab waveguide and @xmath56 ia a suitable superposition of continuous modes @xmath23 normalized such that @xmath57 then holds . note that , after a propagation distance @xmath1 a few times the decay length @xmath58 , one has @xmath59 and @xmath60 , i.e. half of the injected light power has decayed into the slab , whereas the other half of light power is equally distributed into the two channel waveguides . the fact that the decay is not complete ( fractional decay ) indicates that a bound state embedded in the continuum does exist . when both waveguides w@xmath3 and w@xmath4 are initially excited with coherent fields of equal amplitudes but opposite sign , i.e. @xmath61 , one obtains @xmath62 \exp(-i \delta \beta_0 z)$ ] , i.e. the decay into the slab waveguide is fully suppressed . this is due to a destructive interference effect between different decay channels when @xmath63 [ see eqs.(7 ) and ( 8) ] and to the existence of a trapped state embedded in the continuum . numerical examples of fractional light decay for single waveguide excitation , and of full decay suppression for simultaneous waveguide excitation in the trapped state , as obtained by a direct numerical analysis of eq.(1 ) in the monochromatic regime , are shown in fig.2 . in the simulations , we assumed circular channel waveguides with a gaussian index core profile of radius @xmath64 ( at @xmath65 ) , and a step - index slab waveguide of thickness @xmath66 . equation ( 1 ) has been integrated by a standard split - step pseudospectral method with absorbing boundary conditions @xcite . + generalization of light propagation in the non - monochromatic case simply follows from the superposition principle . for instance , if waveguides w@xmath3 and w@xmath4 are excited at the input plane by two pulses with envelopes @xmath67 and @xmath68 , from eqs.(4 ) , ( 10 ) and ( 11 ) it follows that the field envelope @xmath69 can be cast in the form @xmath70u_1(\rho)+ \nonumber \\ + \left [ s_{12}(z)r_1 \left(t-\frac{z}{v_g } \right)+s_{22}(z)r_2 \left(t-\frac{z}{v_g } \right ) \right]u_2(\rho)+\psi_s\end{aligned}\ ] ] where @xmath71 is the fractional part of the field tunnelled into the slab waveguide . in particular , let us consider two coherent pulses with the same envelope but phase reversed and delayed by an interval @xmath72 , i.e. @xmath73 and @xmath74 . in this case , interference effects , leading to light trapping in waveguides w@xmath3 and w@xmath4 and full suppression of leakage into the slab waveguide s ( @xmath75 ) , occurs for @xmath76 or , approximately , for a delay @xmath72 much smaller than the characteristic pulse duration @xmath77 . for @xmath72 larger than @xmath77 , the two wave packets are not overlapped and behave as independent beams , leading to fractional decay . the latter scenario is also observed if the two pulses are temporally overlapped @xmath78 but incoherent , i.e. their phase difference changes randomly in time . to describe propagation of nonclassical light in the coupled waveguide system , the classical paraxial wave field @xmath6 in eq.(1 ) or , similarly , the classical c - numbers @xmath79 , @xmath29 and @xmath30 in eqs.(5 - 7 ) , have to be replaced by quantum - mechanical operators satisfying suitable commutation relations , and different quantization procedures may be adopted . a first approach , which is well suited when the classical problem is formulated in terms of coupled - mode equations ( 5 - 7 ) , is the input - output operator formalism commonly used for linear quantum - optical networks , either in the heisenberg or in the schrdinger pictures ( see , for instance , @xcite ) . a second approach , suited when the classical problem in eq.(1 ) is formulated as a propagative ( rather than as an initial - value ) problem , is to adopt a quantization procedure for the classical field @xmath6 as an evolution in space ( rather than in time ) . in the schrdinger picture , this leads to an evolution in space of a many - photon probability amplitude . such a phenomenological approach , which will be adopted in the following analysis , has received a growing use and appreciation in quantum theories of optical solitons @xcite ; its consistency with standard canonical quantization procedure has been discussed in ref.@xcite . similar procedures have been also developed to study , in the heisenberg picture , paraxial propagation of nonclassical light and applied to problems of quantum imaging ( see , for instance , @xcite ) . the quantization procedure consists in writing the classical paraxial wave equation ( 1 ) in hamiltonian form assuming the paraxial spatial coordinate @xmath1 as an independent variable @xcite . introducing the new field @xmath80 and the hamiltonian @xmath81 with density @xmath82 it readily follows that the hamilton equations @xmath83 , @xmath84 yield eq.(1 ) and its complex conjugate , so that @xmath85 is canonically conjugated to @xmath6 . quantization is then accomplished by replacing the classical fields @xmath6 and @xmath85 with the operators @xmath86 and @xmath87 satisfying the commutation relations @xmath88=\delta(\rho-\rho ' ) \delta(t - t')$ ] and @xmath89=[\hat{\psi^{\dag}}(\rho , t),\hat{\psi^\dag}(\rho',t')]=0 $ ] , where we have set @xmath90 . by introducing the spectral decomposition @xmath91 , the second - quantized hamiltonian operator reads @xmath92 \hat{\phi}^\dag \hat{\phi } \right\}.\ ] ] note that in the spectral domain the following commutation relations hold for the operators @xmath93 and @xmath94 @xmath95 = \delta(\rho-\rho ' ) \delta(\omega-\omega ' ) , \nonumber \\ \left [ \hat{\phi}(\rho,\omega ) , \hat{\phi}(\rho',\omega ' ) \right ] = \left [ \hat{\phi^\dag } ( \rho,\omega),\hat{\phi ^\dag}(\rho',\omega ' ) \right]=0.\end{aligned}\ ] ] note also that the field energy @xmath96 [ eq.(2 ) ] corresponds to the operator @xmath97 . in the schrdinger picture , the quantum field is described by a vector state @xmath98 which evolves according to @xmath99 do not evolve with @xmath1 @xcite . the state @xmath100 can be expanded in fock space as @xmath101 , where the @xmath102-photon number state @xmath103 is defined by ( see , for instance , @xcite ) @xmath104 and where we have set @xmath105 , @xmath106 . the normalization conditions @xmath107 and @xmath108 are also assumed , which ensure that @xmath109 . note that @xmath110 , i.e. the fock state @xmath103 is obtained from the vacuum state @xmath111 by creating @xmath102 photons with space - frequency weighting function @xmath112 . the evolution equation for the weighting function @xmath112 is obtained by substituting eqs.(18 ) and ( 21 ) into the scrdinger equation ( 20 ) and using the commutation relations of field operators [ eqs.(19 ) ] . one then obtains @xmath113 f^{(n)}.\ ] ] owing to the bosonic nature of photons , solely symmetric functions @xmath112 should be considered . let us consider first the propagation of monochromatic fields , so that in eqs.(18 ) , ( 19 ) , ( 21 ) and ( 22 ) we may disregard integration over different spectral components @xmath51 and use a single renormalized bosonic creation operator @xmath114 at frequency @xmath52 satisfying the commutation relations @xcite @xmath115=\delta(\rho-\rho')$ ] and @xmath116= [ \hat{\phi}^\dag ( \rho),\hat{\phi}^\dag(\rho')]=0 $ ] , which replace eq.(19 ) . the simplest @xmath102-photon number state , denoted by @xmath117 , is obtained by assuming in eq.(22 ) @xmath118 , where the function @xmath119 satisfies the classical wave optics equation @xmath120 with the normalization @xmath121 . in this case one has @xmath122 physically , this state describes the excitation of the optical system with an @xmath102-photon number state input beam with a spatial profile @xmath123 at the entrance plane @xmath17 . the classic wave optics description of light propagation , discussed in sec.ii , is attained by considering a superposition of photon number states @xmath124 with a poissonian distribution with c - number @xmath125 , i.e. the coherent state @xmath126 defined by @xmath127 one can readily show that the coherent state @xmath128 is an eigenstate of the field annihilation operator @xmath129 with eigenvalue @xmath130 , i.e. @xmath131 . more generally , for a nonclassical state @xmath132 obtained by an arbitrary superposition of photon number states @xmath117 with amplitudes @xmath133 , one can readily show that the expectation value of @xmath134 yields the classic wave optics intensity distribution , namely @xmath135 , where @xmath136 is the mean photon number of the input beam . the quantum aspects of nonclassical light for single beam excitation may be revealed when the statistics of photons trapped in waveguides w@xmath3 and w@xmath4 are considered . for example , let us consider excitation of waveguide w@xmath3 in its fundamental mode at the input plane @xmath17 , so that @xmath137 , and let us compare the statistics of photons that remain in waveguide w@xmath3 when the input beam is a photon number state ( nonclassical light ) or a coherent state ( classical light ) . according to the analysis of sec.ii.b , the wave amplitude @xmath138 evolves according to [ see eq.(15 ) ] @xmath139 where @xmath140 and @xmath56 defines the normalized spatial profile of the field tunnelled into the slab waveguide . if we introduce the operators @xmath141 the commutation relations @xmath142=\delta_{i , k}$ ] and @xmath143=[\hat { a}_{i},\hat { a}_{k}]=0 $ ] ( @xmath144 ) hold . assuming that the vector state @xmath132 is given by a superposition of photon number states @xmath117 with amplitudes @xmath133 , one can write @xmath145 the joint photon distribution @xmath146 to find @xmath147 photons in waveguide w@xmath3 , @xmath148 photons in waveguide w@xmath4 and @xmath149 photons in the slab waveguide s is given by @xmath150 where we have set @xmath151 the explicit expression of @xmath152 can be obtained by a double binomial expansion of the operator @xmath153 entering in eq.(30 ) the marginal photon distribution @xmath154 to find @xmath147 photons in waveguide w@xmath3 is then obtained as @xmath155 , and reads explicitly ( see , for instance , @xcite ) @xmath156 where @xmath157 . similar expressions are obtained for the marginal photon distributions @xmath158 and @xmath159 for waveguides w@xmath4 and @xmath160 after setting @xmath161 and @xmath162 , respectively . let us now suppose that the input beam is a coherent state with mean photon number @xmath163 and poissonian distribution @xmath164 from eq.(33 ) it follows that the marginal photon distribution @xmath165 remains poissonian with mean photon number @xmath166 that decays along the propagation distance @xmath1 according to the classical decay law given by eq.(12 ) . conversely , if the input beam is a photon number state , i.e. @xmath167 , from eq.(33 ) it follows that the marginal photon distribution @xmath165 is given by the binomial distribution @xmath168 [ @xmath169 for @xmath170 with photon mean @xmath171 and variance @xmath172n_0 $ ] . the binomial photon distribution highlights the particle - like behavior of photons undergoing the decay from waveguide w@xmath3 and it is analogous to that created by a beam splitter when excited by a photon number state in one port , and the vacuum state in the other one ( see , for instance , @xcite ) . the photons in the initially excited waveguide behave like independent classical particles and tunnel into the other waveguides is ruled by a bernoulli trial ( a coin toss ) with a cumulative tunneling probability given by @xmath173 . + when the two waveguides w@xmath3 and w@xmath4 are simultaneously excited by two nonclassical independent beams , quantum signatures of light propagation resulting from quantum interference can be detected by photon coincidence measurements . to describe propagation of independent beams , let us notice that for a given set of normalized and orthogonal solutions @xmath174 , @xmath175 , ... to the classic wave equation ( 23 ) , one can construct the @xmath102-photon number state @xmath176 which describes excitation of the optical system with a set of independent beams with spatial profiles @xmath177 , @xmath178 , ... carrying @xmath147 , @xmath148 , ... photons ( @xmath179 ) . in particular , let us assume that at the input plane the waveguides w@xmath3 and w@xmath4 are excited in their fundamental modes by single photon number states , i.e. @xmath180 , @xmath181 and @xmath182 where the operators @xmath183 and @xmath184 are defined by eqs.(27 ) and ( 28 ) . according to the classical analysis of sec.ii.b , the waves @xmath177 and @xmath178 evolve according to @xmath185 with @xmath186 for symmetry reasons @xcite , @xmath187 , @xmath188 [ see eqs.(12 - 14 ) ] , and @xmath189 for power conservation . from eqs.(36 ) , ( 38 ) and ( 39 ) it follows that the state vector of the system at the generic propagation distance @xmath1 is given by @xmath190 where @xmath191 is defined in eq.(29 ) . it can be readily shown that the expectation value of the field intensity for the two - photon state ( 40 ) is given by the incoherent superposition latexmath:[\[\langle \mathcal{q}|\hat{\phi}^{\dag}(\rho ) \hat{\phi}(\rho ) interference being due to the lack of a definite phase relationship between the two photons ( see , for instance , @xcite ) . the two independent beams which excite the two waveguides w@xmath3 and w@xmath4 behave , therefore , as two incoherent classical fields , and therefore according to the analysis of sec.ii.b half of the light power tunnels , on average , into the slab waveguide s for propagation distances @xmath193 . as the operators @xmath194 , @xmath195 and @xmath196 create photons in waveguides w@xmath3 , w@xmath4 and w@xmath197 , respectively [ see eqs.(27 - 29 ) ] , from eq.(40 ) the joint photon distribution @xmath152 can be readily calculated , and its nonvanishing terms are explicitly given by @xmath198 ^ 2 \\ p(1,1,0;z ) & = & |s_{11}s_{22}+s_{12}s_{21}|^2= \frac{1}{4 } \left[1+\exp(-4 \sigma z ) \right]^2 \\ p(1,0,1;z ) & = & p(0,1,1;z)=|s_{11}s_{23}+s_{13}s_{21}|^2= \frac{1}{2 } \exp(-4 \sigma z ) \left[1-\exp(-4 \sigma z ) \right ] \\ p(0,0,2;z ) & = & 2 |s_{13}|^2|s_{23}|^2= \frac{1}{2 } \left[1-\exp(-4 \sigma z ) \right]^2.\end{aligned}\ ] ] an important result is that , for propagation distances @xmath1 larger than the characteristic decay length @xmath199 , the joint probability @xmath200 to find one photon in waveguide w@xmath3 and one in the slab waveguide s vanishes , and similarly for @xmath201 [ see eq.(44 ) ] . such a result indicates that , if one of the two initially injected photons tunnels into the slab waveguide , the other photon does the same , i.e. photon pairs bunch when decaying into the continuum . this is obviously a nonclassical effect similar to the two - photon hong - ou - mandel quantum interference in a 50@xmath202 beam splitter @xcite . in our case , the vanishing of @xmath200 [ and similarly of @xmath201 ] is related to a destructive interference between the probability amplitudes @xmath204 and @xmath205 entering in eq.(44 ) which describe two possible paths for the photon pair . + in the previous subsection , we have considered propagation of nonclassical light in the monochromatic limit , however in practice nonclassical light such as that generated by spontaneous parametric down conversion in a nonlinear crystal is always polychromatic to some extent . moreover , in experimental settings quantum interference such as the two - photon hong - ou - mandel interference is typically revealed as a dip in intensity correlation ( photon coincidence ) measurements when the time delay between the two incoming wave packets is varied @xcite . it is therefore useful to extend the analysis of sec.iii.b to the case of polychromatic wave packets . + for the sake of definiteness , let us assume that waveguides w@xmath3 and w@xmath4 are excited in their fundamental spatial modes by two spectrally - narrow wave packets generated by spontaneous parametric down conversion in type - i nonlinear crystal . in this case , the vector state @xmath132 at the input plane of the waveguiding system is a generalization of eq.(37 ) and given by a superposition of two - photon states with a spectral function @xmath206 ( see , for instance , @xcite ) @xmath207 where the operators @xmath208 and @xmath209 are defined by @xmath210 the evolution of vector state along the propagation distance @xmath1 can be obtained by a straightforward extension of the analysis of sec.iii.b and reads explicitly @xmath211 \left [ s_{11}(z ) \hat{a}_{1}^{\dag}(\omega_1)+ s_{12}(z ) \hat{a}_{2}^{\dag}(\omega_1 ) + s_{13}(z ) \hat{a}_{3}^{\dag}(\omega_1 ) \right ] \times \nonumber \\ & \times & \left [ s_{21}(z ) \hat{a}_{1}^{\dag}(\omega_2)+ s_{22}(z ) \hat{a}_{2}^{\dag}(\omega_2 ) + s_{23}(z ) \hat{a}_{3}^{\dag}(\omega_2 ) \right ] |0\rangle\end{aligned}\ ] ] where @xmath212 to study quantum interference effects with wave packets , and in particular the vanishing of the joint photon probability @xmath213 for @xmath193 found for monochromatic beams [ eq.(44 ) ] , let us introduce the integrated intensity correlation function at times @xmath214 and @xmath215 in waveguides w@xmath3 and s defined as @xmath216 where @xmath217 and @xmath218 are two areas in the transverse @xmath219 plane surrounding waveguides w@xmath3 and s , respectively . the correlation function @xmath220 is proportional to the joint probability of detecting one photon in waveguide w@xmath3 at time @xmath214 , and one photon in waveguide s at time @xmath215 , after a propagation distance @xmath1 from the input plane . in fact , @xmath221 is proportional to the joint probability of detecting one photon at point @xmath222 and time @xmath214 , and one photon at point @xmath223 and time @xmath215 at the same propagation distance @xmath1 . the integral over the areas @xmath217 and @xmath218 thus gives the joint probability of detecting one photon in waveguide w@xmath3 at time @xmath214 , and one photon in waveguide s at time @xmath215 . for photons generated by spontaneous parametric down conversion in type - i nonlinear crystal using a monochromatic pump beam at frequency @xmath224 , the two - photon spectrum @xmath206 of a pair of signal and idler photons can be expressed as @xcite @xmath225\ ] ] where @xmath226 is the phase matching function . the last exponential term on the right hand side in eq.(51 ) has been introduced to account for a possible time delay @xmath72 between signal and idler wave packets introduced by different optical paths from the crystal to waveguides w@xmath3 and w@xmath4 . the phase matching function @xmath226 is assumed to be a real - valued and symmetric function [ i.e. @xmath227 , peaked at around @xmath228 , with e.g. a gaussian profile @xcite . taking into account that @xmath229 , substitution of eqs.(48 ) and ( 51 ) into eq.(50 ) , using the commutaion relations @xmath230=u_{1,2}(\rho ) \delta(\omega-\omega')$ ] , @xmath231=\theta(\rho , z ) \delta(\omega-\omega')$ ] and the relations @xmath232 , @xmath233 , after some lengthy but straightforward calculations one obtains @xmath234 where @xmath235 and where we introduced the real - valued correlation function @xmath236 defined by @xmath237 in practice , coincidence measurements correspond to an integration of @xmath238 with respect to the time difference @xmath235 over the resolving coincidence time , which is typically much longer than the correlation time @xmath77 of @xmath239 . integrating eq.(52 ) with respect to @xmath240 from @xmath241 to @xmath242 and taking into account that @xmath243 and @xmath244 , the following expression for the correlation function @xmath245 versus time delay @xmath72 is finally obtained @xmath246 \left [ |s_{11}(z)|^2 + |s_{21}(z)|^{2 } + \right . \\ + \left . 2 { \rm re } \left [ s_{11}(z)s_{21}^*(z ) \right ] \frac{\int_{-\infty}^{\infty } d \tau r(\tau-\delta)r(\tau+\delta)}{\int_{-\infty}^{\infty } d \tau r^2(\tau ) } \right]\end{aligned}\ ] ] where @xmath247 and the expression of the coefficients @xmath248 and @xmath249 are given by eqs.(12 ) and ( 13 ) . the behavior of @xmath250 versus @xmath72 shows a characteristic dip at @xmath76 of width @xmath251 , which is analogous to the hong - ou - mandel dip observed in two - photon interference from a beam splitter @xcite . far from the dip , @xmath252 reaches a constant value @xmath253 . for @xmath1 larger than the characteristic decay length @xmath254 , the correlation @xmath250 vanishes at the dip @xmath76 , i.e. when signal and idler wave packets are temporally overlapped , according to the analysis of sec.iii.b . in this work we have theoretically investigated propagation of classical and nonclassical light in a waveguide - based photonic structure that provides an optical analogue of population trapping in the continuum encountered in atomic physics . for classical light waves , coupled - mode equation analysis , previously studied in ref.@xcite , shows that fano interference between different light leakage channels is responsible for the appearance of a trapped state embedded in the continuum . to study propagation of nonclassical light , a second quantization model for the scalar wave equation , in the paraxial and quasi - monochromatic approximations , has been adopted . as for input beam excitation in a coherent state the classical picture of light propagation is retrieved , quantum interference effects with no classical counterpart have been highlighted for photon number state excitation of the waveguide structure . in particular , the tendency of photon pairs to bunch when decaying into the continuum has been predicted . such an effect , which is similar to the two - photon hong - ou - mandel interference in a beam splitter @xcite , may be observed as a dip in photon coincidence measurements . our results indicate that photonic structures originally designed to mimic with optical waves the classical analogues of quantum - mechanical phenomena encountered in atomic , molecular or condensed - matter physics @xcite , may exhibit themselves a strictly quantum behavior when single photon level is reached . a.m. kenis , i. vorobeichik , m. orenstein , and n. moiseyev , ieee j. quant . * 37 * , 1321 ( 2001 ) ; e. paspalakis , opt . * 258 * , 31 ( 2006 ) ; s. longhi , phys . rev . e * 73 * , 026607 ( 2006 ) ; s. longhi , phys . lett . a * 359 * , 166 ( 2006 ) . s. longhi , g. della valle , m. ornigotti , and p. laporta , phys . b * 76 * , 201101(r ) ( 2007 ) ; g. della valle , m. ornigotti , t. toney fernandez , p. laporta , s. longhi , a. coppa , and v. foglietti , appl . . lett . * 92 * , 011106 ( 2008 ) ; y. lahini , f. pozzi , m. sorel , r. morandotti , d.n . christodoulides , and y. silberberg , phys . * 101 * , 193901 ( 2008 ) . smith , h. chang , k.a . fuller , a.t . rosenberger , and r.w . boyd , phys . a * 69 * , 063804 ( 2004 ) ; a. naweed , g. farca , s.i . shopova , and a.t . rosenberger , phys . a * 71 * , 043804 ( 2005 ) ; q. xu , s. sandhu , m. l. povinelli , j. shakya , s. fan , and m. lipson , phys . lett . * 96 * , 123901 ( 2006 ) ; p. ginzburg and m. orenstein , opt . express * 14 * , 11312 ( 2006 ) . coleman and p.l . knight , j. phys . b * 15 * , l235 ( 1982 ) ; p.e . coleman , p.l . knight , and k. burnett , opt . commun . * 42 * , 171 ( 1982 ) ; b.n . dai and p. lambropoulos , phys . a * 36 * , 5205 ( 1987 ) ; s. cavalieri , f.s . pavone , and m. matera , phys . lett . * 67 * , 3673 ( 1991 ) ; t. nakajima and p. lambropoulos , opt . commun . * 118 * , 40 ( 1995 ) ; t. halfmann , l.p . yatsenko , m. shapiro , b.w . shore , and k. bergmann , phys . a * 58 * , r46 ( 1998 ) ; e. paspalakis , m. protopapas , and p.l . knight , j. phys . b * 31 * , 775 ( 1998 ) . s. fan , p.r . villeneuve , j.d . joannopoulos , and h.a . haus , phys . lett . * 80 * , 960 ( 1998 ) ; s. fan , p.r . villeneuve , j.d . joannopoulos , m.j . khan , c. manolatou , and h.a . haus , phys . b * 59 * , 15882 ( 1999 ) ; y. xu , y. li , r.k . lee , and a. yariv , phys . e * 62 * , 7389 ( 2000 ) ; s. fan and j. d. joannopoulos , phys . b * 65 * , 235112 ( 2002 ) ; p. chak , s. pereira , and j.e . sipe , phys . b * 73 * , 035105 ( 2006 ) . a.e . miroshnichenko , s.f . mingaleev , s. flach , and yu.s . kivshar , phys . e * 71 * , 036626 ( 2005 ) ; a.e . miroshnichenko and y.s . kivshar , phys . rev . e * 72 * , 056611 ( 2005 ) ; m.i . tribelsky , s. flach , a.e . miroshnichenko , a.v . gorbach , and yu.s . kivshar , phys . * 100 * , 043903 ( 2008 ) . j. janszky , c. sibilia , and m. bertolotti , j. mod . opt . * 35 * , 1757 ( 1988 ) ; a. bandyopadhyay and j. rai , opt . commun . * 140 * , 41 ( 1997 ) ; m.s . kim , w. son , v. buek , and p.l . knight , phys . a * 65 * , 032323 ( 2002 ) ; a. rai , g.s . agarwal , and j.h.h . perk , phys . a * 78 * , 042304 ( 2008 ) . b. yurke and m. j. potasek , j. opt . b * 6 * , 1227 ( 1989 ) ; c. sibilia , v. schiavone , m. bertolotti , r. horak , and j. perina , j. opt . b * 11 * , 2175 ( 1994 ) ; b crosignani , p di porto and a treppiedi , quantum semiclass * 7 * , 73 ( 1995 ) ; j.m . fini , p.l . hagelstein , and h. a. haus , phys . a * 60 * , 2442 ( 1999 ) ; d. rand , k. steiglitz , and p.r . prucnal , phys . a * 71 * , 053805 ( 2005 ) . yuen , and j.h . shapiro , ieee trans . theory * it-24 * , 657 ( 1978 ) ; m.i . kolobov , rev . mod . phys . * 71 * , 1539 ( 1999 ) ; m. bache , e. brambilla , a. gatti , and l.a . lugiato , phys . rev . a * 70 * , 023823 ( 2004 ) ; a. aiello and j.p . woerdman , phys . a * 72 * , 060101(r ) ( 2005 ) ; m. tsang and d. psaltis , phys . a * 73 * , 013822 ( 2006 ) . in the heisenberg picture , the state vector of the system would be constant whereas the operator @xmath255 evolve according to @xmath256 $ ] . one can easily check that , with the hamiltonian operator given by eq.(18 ) , the evolution equation of the operator @xmath255 is precisely eq.(3 ) , where the c - field @xmath257 is replaced by the operator @xmath255 . more precisely , the monochromatic limit is attained by assuming in eqs.(21 ) and ( 22 ) @xmath258 , where @xmath259 is a spectrally narrow function at around @xmath52 normalized such that @xmath260 , and @xmath261 satisfies eq.(22 ) with @xmath262 . the operator @xmath263 is then formally defined as @xmath264 . the @xmath102-photon number state @xmath265 , given by eq.(21 ) , takes then the simplified form @xmath266 . as the waveguides w@xmath3 and w@xmath4 are symmetrically placed at opposite sides from the slab waveguide s , if @xmath267 is a solution to eqs.(5 - 7 ) with initial condition @xmath268 , @xmath269 and @xmath270 , then @xmath271 is the solution to eqs.(5 - 7 ) with reversed initial condition @xmath272 , @xmath273 and @xmath270 . light tunnelled into the slab waveguide s is thus given by the same superposition of continuous modes ( @xmath274 ) for the two different initial conditions . this means that the last two terms on the right hand sides of eqs.(38 ) and ( 39 ) are equal each other . ( blue curve ) and w@xmath4 ( green curve ) versus propagation distance in a @xmath275-cm - long structure and corresponding transverse light intensity distributions at the input ( @xmath17 ) and output ( @xmath276 cm ) planes , as obtained by numerical simulations of the wave equation ( 1 ) for two different excitation conditions . in ( a ) waveguide w@xmath3 is excited in its fundamental mode , leading to fractional decay . in ( b ) the trapped state is excited , corresponding to full suppression of light leakage into the slab s. parameter values used in the simulations are : @xmath277 nm , @xmath278 , @xmath279 , @xmath280 , @xmath281 m , @xmath282 m , and @xmath283 m . ]

a quantum theory of light propagation in two optical channel waveguides tunnelling - coupled to a common continuum of modes ( such as those of a slab waveguide ) is presented , and classical and quantum interference effects are investigated . for classical light , the photonic system realizes an optical analogue of coherent population trapping in the continuum encountered in atomic physics , where destructive interference between different light leakage channels leads to the appearance of a trapped state embedded in the continuum . for nonclassical light , two - photon interference effects are predicted , such as the tendency of photon pairs to bunch when decaying into the continuum .

SECTION 1. SHORT TITLE. This Act may be cited as the ``United States Naval Station Guantanamo Bay Preservation Act''. SEC. 2. FINDINGS. Congress makes the following findings: (1) United States Naval Station, Guantanamo Bay, Cuba, has been a strategic military asset critical to the defense of the United States and the maintenance of regional security for more than a century. (2) The United States continues to exercise control over the area of United States Naval Station, Guantanamo Bay, Cuba, pursuant to the Guantanamo Lease Agreements, which were initiated and concluded pursuant to an Act of Congress. (3) Senior United States military leaders have consistently voiced strong support for maintaining United States Naval Station, Guantanamo Bay, Cuba, noting its strategic value for military basing and logistics, disaster relief, humanitarian work, terrorist detention, and counter-narcotics purposes. (4) On February 29, 2016, Secretary of Defense Ashton B. Carter, discussing United States Naval Station, Guantanamo Bay, Cuba, stated that ``it's a strategic location, we've had it for a long time, it's important to us and we intend to hold onto it''. (5) On March 12, 2015, Commander of United States Southern Command, General John Kelly, testified that the United States facilities at Naval Station Guantanamo Bay ``are indispensable to the Departments of Defense, Homeland Security, and State's operational and contingency plans. . . . As the only permanent U.S. military base in Latin America and the Caribbean, its location provides persistent U.S. presence and immediate access to the region, as well as supporting a layered defense to secure the air and maritime approaches to the United States''. (6) In testimony before Congress in 2012, then-Commander of United States Southern Command, General Douglas Fraser, stated that ``the strategic capability provided by U.S. Naval Station Guantanamo Bay remains essential for executing national priorities throughout the Caribbean, Latin America, and South America''. (7) Following a 1991 coup in Haiti that prompted a mass exodus of people by boat, United States Naval Station, Guantanamo Bay, Cuba, provided a location for temporary housing and the orderly adjudication of asylum claims outside of the continental United States. (8) In 2010, United States Naval Station, Guantanamo Bay, Cuba, was a critical hub for the provision of humanitarian disaster relief following the devastating earthquakes in Haiti. (9) The United States presence at United States Naval Station, Guantanamo Bay, Cuba, has its origins in Acts of Congress undertaken pursuant to the powers of Congress expressly enumerated in the Constitution of the United States. (10) By joint resolution approved on April 20, 1898, Congress ``directed and empowered'' the President ``to use the entire land and naval forces of the United States'' as necessary to ensure that the Government of Spain ``relinquish its authority and government in the island of Cuba, and withdraw its land and naval forces from Cuba and Cuban waters''. (11) Congress declared war against Spain on April 25, 1898, which lasted until December 10, 1898, when the United States and Spain signed the Treaty of Paris, in which Spain relinquished all claims of sovereignty over Cuba, and United States governance of Cuba was established. (12) Nearly three years later, in the Act of March 2, 1901 (Chapter 803; 31 Stat. 898), Congress granted the President the authority to return ``the government and control of the island of Cuba to its people'' subject to several express conditions including, in article VII of the Act of March 2, 1901, the sale or lease by Cuba to the United States of lands necessary for naval stations. (13) Pursuant to the authority granted by article VII of the Act of March 2, 1901, the United States negotiated the Guantanamo Lease Agreements, which specified the area of, and United States jurisdiction and control over, what became United States Naval Station, Guantanamo Bay, Cuba. (14) On October 2, 1903, when approving the Lease to the United States by the Government of Cuba of Certain Areas of Land and Water for Naval or Coaling Stations, signed in Havana on July 2, 1903, President Theodore Roosevelt cited the Act of March 2, 1901, as providing his authority to do so: ``I, Theodore Roosevelt, President of the United States of America, having seen and considered the foregoing lease, do hereby approve the same, by virtue of the authority conferred by the seventh of the provisions defining the relations which are to exist between the United States and Cuba, contained in the Act of Congress approved March 2, 1901, entitled `An Act making appropriation for the support of the Army for the fiscal year ending June 30, 1902.'''. (15) Obtaining United States naval station rights in Cuba was an express condition of the authority that Congress gave the President to return control and governance of Cuba to the people of Cuba. In exercising that authority and concluding the Guantanamo Lease Agreements, President Theodore Roosevelt recognized the source of that authority as the Act of March 2, 1901. (16) The Treaty of Relations between the United States of America and the Republic of Cuba, signed at Washington, May 29, 1934, did not supersede, abrogate, or modify the Guantanamo Lease Agreements, but noted that the stipulations of those agreements ``shall continue in effect'' until the United States and Cuba agree to modify them. (17) The Constitution of the United States expressly grants to Congress the power to provide for the common defense of the United States, the power to provide and maintain a Navy, and the power ``to dispose of and make all needful Rules and Regulations respecting the Territory or other Property belonging to the United States''. SEC. 3. PROHIBITION ON MODIFICATION, ABROGATION, OR OTHER RELATED ACTIONS WITH RESPECT TO UNITED STATES JURISDICTION AND CONTROL OVER UNITED STATES NAVAL STATION, GUANTANAMO BAY, CUBA, WITHOUT CONGRESSIONAL ACTION. No action may be taken to modify, abrogate, or replace the stipulations, agreements, and commitments contained in the Guantanamo Lease Agreements, or to impair or abandon the jurisdiction and control of the United States over United States Naval Station, Guantanamo Bay, Cuba, unless specifically authorized or otherwise provided by-- (1) a statute that is enacted on or after the date of the enactment of this Act; (2) a treaty that is ratified with the advice and consent of the Senate on or after the date of the enactment of this Act; or (3) a modification of the Treaty Between the United States of America and Cuba signed at Washington, DC, on May 29, 1934, that is ratified with the advice and consent of the Senate on or after the date of the enactment of this Act. SEC. 4. GUANTANAMO LEASE AGREEMENTS DEFINED. In this Act, the term ``Guantanamo Lease Agreements'' means-- (1) the Agreement Between the United States of America and the Republic of Cuba for the Lease to the United States of Lands in Cuba for coaling and naval stations, signed by the President of the United States on February 23, 1903; and (2) the Lease to the United States by the Government of Cuba of Certain Areas of Land and Water for Naval or Coaling Stations, signed by the President of the United States on October 2, 1903.

. United States Naval Station Guantanamo Bay Preservation Act (Sec. 3) This bill prohibits any action to modify, abrogate, or replace the stipulations, agreements, and commitments contained in the Guantanamo Lease Agreements, or to impair or abandon the jurisdiction and control of the United States over United States Naval Station, Guantanamo Bay, Cuba, unless specifically authorized or otherwise provided by: a statute enacted on or after the enactment of this Act; a treaty ratified with the advice and consent of the Senate on or after enactment of this Act; or a modification of the Treaty Between the United States of America and Cuba signed at Washington, DC, on May 29, 1934, that is ratified with the advice and consent of the Senate on or after enactment of this Act. (Sec. 4) &quot;Guantanamo Lease Agreements&quot; means: the Agreement Between the United States of America and the Republic of Cuba for the Lease to the United States of Lands in Cuba for coaling and naval stations, signed by the President of the United States on February 23, 1903; and the Lease to the United States by the Government of Cuba of Certain Areas of Land and Water for Naval or Coaling Stations, signed by the President of the United States on October 2, 1903.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Generating Real Opportunities for Workers and Transitional Help Act'' or the ``GROWTH Act''. SEC. 2. EXTENSION OF MODIFIED FIRST-TIER EMERGENCY UNEMPLOYMENT COMPENSATION. (a) Extension.-- (1) In general.--Section 4007 of the Supplemental Appropriations Act, 2008 (Public Law 110-252; 26 U.S.C. 3304 note) is amended by adding at the end the following: ``(c) Special Rule for First-Tier Emergency Unemployment Compensation.--Nothing in this section shall prevent the commencement or continued payment of emergency unemployment compensation under this title to the extent that such compensation-- ``(1) represents amounts established in an account under section 4002(b); and ``(2) is payable for a week ending on or before January 1, 2015.''. (2) Modification.--Section 4002(b) of the Supplemental Appropriations Act, 2008 (Public Law 110-252; 26 U.S.C. 3304 note) is amended by inserting after paragraph (3) the following: ``(4) Special rule relating to amounts payable for a week ending after january 1, 2014.--Notwithstanding any provision of paragraph (1) or (2), for purposes of determining whether an amount is payable, out of amounts established in an account under this subsection, for a week ending after January 1, 2014-- ``(A) paragraph (1)(A) shall be applied by substituting `54 percent' for `80 percent'; ``(B) paragraph (1)(B) shall be applied by substituting `14 weeks' for `20 weeks'; and ``(C) any amount established in an account under paragraph (1) or (2), which becomes nonpayable by reason of this paragraph, shall be treated in the same way as if it had never been established in such account.''. (b) Funding.--Section 4004(e)(1) of the Supplemental Appropriations Act, 2008 (Public Law 110-252; 26 U.S.C. 3304 note) is amended-- (1) in subparagraph (I), by striking ``and'' at the end; (2) in subparagraph (J), by inserting ``and'' at the end; and (3) by inserting after subparagraph (J) the following: ``(K) the amendment made by section 2(a) of the Generating Real Opportunities for Workers and Transitional Help Act;''. (c) Effective Date.--The amendments made by this section shall take effect as if included in the enactment of the American Taxpayer Relief Act of 2012 (Public Law 112-240). SEC. 3. FLEXIBILITY FOR UNEMPLOYMENT PROGRAM AGREEMENTS. (a) Flexibility.-- (1) In general.--Subsection (g) of section 4001 of the Supplemental Appropriations Act, 2008 (Public Law 110-252; 26 U.S.C. 3304 note) shall not apply with respect to a State that has enacted a law before December 1, 2013, that, upon taking effect, would violate such subsection. (2) Effective date.--Paragraph (1) is effective with respect to weeks of unemployment beginning on or after December 29, 2013. (b) Permitting a Subsequent Agreement.--Nothing in title IV of such Act shall preclude a State whose agreement under such title was terminated from entering into a subsequent agreement under such title on or after the date of the enactment of this Act if the State, taking into account the application of subsection (a), would otherwise meet the requirements for an agreement under such title. SEC. 4. AUTHORITY TO USE ANY DISCRETIONARY APPROPRIATIONS AVAILABLE TO THE SECRETARY OF LABOR TO CONDUCT IN-PERSON REEMPLOYMENT AND UNEMPLOYMENT INSURANCE ELIGIBILITY ASSESSMENTS FOR UNEMPLOYMENT INSURANCE BENEFICIARIES. (a) Authority.--Notwithstanding any other provision of law, the Secretary of Labor may, for fiscal years 2014 through 2023, use any discretionary appropriations available to the Secretary to conduct in- person reemployment and unemployment insurance eligibility assessments for unemployment insurance beneficiaries. (b) Limitation.--Amounts used in a fiscal year pursuant to the authority under subsection (a) may not exceed the following: (1) $20,000,000 for fiscal year 2014. (2) $25,000,000 for fiscal year 2015. (3) $30,000,000 for fiscal year 2016. (4) $35,000,000 for fiscal year 2017. (5) $36,000,000 for fiscal year 2018. (6) $37,000,000 for fiscal year 2019. (7) $38,000,000 for fiscal year 2020. (8) $39,000,000 for fiscal year 2021. (9) $40,000,000 for fiscal year 2022. (10) $41,000,000 for fiscal year 2023. SEC. 5. REPEAL OF MEDICAL DEVICE EXCISE TAX. (a) In General.--Chapter 32 of the Internal Revenue Code of 1986 is amended by striking subchapter E. (b) Conforming Amendments.-- (1) Subsection (a) of section 4221 of such Code is amended by striking the last sentence. (2) Paragraph (2) of section 6416(b) of such Code is amended by striking the last sentence. (3) The table of subchapters for chapter 32 of such Code is amended by striking the item relating to subchapter E. (c) Effective Date.--The amendments made by this section shall apply to sales after the date of the enactment of this Act. SEC. 6. KEYSTONE XL PERMIT APPROVAL. Notwithstanding Executive Order No. 13337 (3 U.S.C. 301 note), Executive Order No. 11423 (3 U.S.C. 301 note), section 301 of title 3, United States Code, and any other Executive order or provision of law, no Presidential permit shall be required for the pipeline described in the application filed on May 4, 2012, by TransCanada Keystone Pipeline, L.P., to the Department of State for the Keystone XL pipeline, as supplemented to include the Nebraska reroute evaluated in the Final Evaluation Report issued by the Nebraska Department of Environmental Quality in January 2013 and approved by the Nebraska governor. The final environmental impact statement issued by the Secretary of State on August 26, 2011, coupled with the Final Evaluation Report described in the previous sentence, shall be considered to satisfy all requirements of the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.) and of the National Historic Preservation Act (16 U.S.C. 470 et seq.). SEC. 7. REPEAL OF 30-HOUR THRESHOLD FOR CLASSIFICATION AS FULL-TIME EMPLOYEE FOR PURPOSES OF THE EMPLOYER MANDATE IN THE PATIENT PROTECTION AND AFFORDABLE CARE ACT AND REPLACEMENT WITH 40 HOURS. (a) Full-Time Equivalents.--Paragraph (2) of section 4980H(c) of the Internal Revenue Code of 1986 is amended-- (1) by repealing subparagraph (E), and (2) by inserting after subparagraph (D) the following new subparagraph: ``(E) Full-time equivalents treated as full-time employees.--Solely for purposes of determining whether an employer is an applicable large employer under this paragraph, an employer shall, in addition to the number of full-time employees for any month otherwise determined, include for such month a number of full- time employees determined by dividing the aggregate number of hours of service of employees who are not full-time employees for the month by 174.''. (b) Full-Time Employees.--Paragraph (4) of section 4980H(c) of the Internal Revenue Code of 1986 is amended-- (1) by repealing subparagraph (A), and (2) by inserting before subparagraph (B) the following new subparagraph: ``(A) In general.--The term `full-time employee' means, with respect to any month, an employee who is employed on average at least 40 hours of service per week.''. (c) Effective Date.--The amendments made by this section shall take effect as if included in the amendments made by section 1513 of the Patient Protection and Affordable Care Act. SEC. 8. DISQUALIFICATION ON RECEIPT OF DISABILITY INSURANCE BENEFITS IN A MONTH FOR WHICH UNEMPLOYMENT COMPENSATION IS RECEIVED. (a) In General.--Section 223(d)(4) of the Social Security Act (42 U.S.C. 423(d)(4)) is amended by adding at the end the following: ``(C)(i) If for any month an individual is entitled to unemployment compensation, such individual shall be deemed to have engaged in substantial gainful activity for such month. ``(ii) For purposes of clause (i), the term `unemployment compensation' means-- ``(I) `regular compensation', `extended compensation', and `additional compensation' (as such terms are defined by section 205 of the Federal-State Extended Unemployment Compensation Act (26 U.S.C. 3304 note)); and ``(II) trade adjustment assistance under title II of the Trade Act of 1974 (19 U.S.C. 2251 et seq.).''. (b) Trial Work Period.--Section 222(c) of the Social Security Act (42 U.S.C. 422(c)) is amended by adding at the end the following: ``(6)(A) For purposes of this subsection, an individual shall be deemed to have rendered services in a month if the individual is entitled to unemployment compensation for such month. ``(B) For purposes of subparagraph (A), the term `unemployment compensation' means-- ``(i) `regular compensation', `extended compensation', and `additional compensation' (as such terms are defined by section 205 of the Federal-State Extended Unemployment Compensation Act (26 U.S.C. 3304 note)); and ``(ii) trade adjustment assistance under title II of the Trade Act of 1974 (19 U.S.C. 2251 et seq.).''. (c) Data Matching.--The Commissioner of Social Security shall implement the amendments made by this section using appropriate electronic data. (d) Effective Date.--The amendments made by this section shall apply with respect to months beginning after the date of the enactment of this Act. SEC. 9. SOCIAL SECURITY NUMBER REQUIRED TO CLAIM THE REFUNDABLE PORTION OF THE CHILD TAX CREDIT. (a) In General.--Subsection (d) of section 24 of the Internal Revenue Code of 1986 is amended by adding at the end the following: ``(5) Identification requirement with respect to taxpayer.-- ``(A) In general.--Paragraph (1) shall not apply to any taxpayer for any taxable year unless the taxpayer includes the taxpayer's Social Security number on the return of tax for such taxable year. ``(B) Joint returns.--In the case of a joint return, the requirement of subparagraph (A) shall be treated as met if the Social Security number of either spouse is included on such return.''. (b) Omission Treated as Mathematical or Clerical Error.-- Subparagraph (I) of section 6213(g)(2) of the Internal Revenue Code of 1986 is amended to read as follows: ``(I) an omission of a correct Social Security number required under section 24(d)(5) (relating to refundable portion of child tax credit), or a correct TIN under section 24(e) (relating to child tax credit), to be included on a return,''. (c) Conforming Amendment.--Subsection (e) of section 24 of the Internal Revenue Code of 1986 is amended by inserting ``With Respect to Qualifying Children'' after ``Identification Requirement'' in the heading thereof. (d) Effective Date.--The amendments made by this section shall apply to taxable years beginning after the date of the enactment of this Act.

Generating Real Opportunities for Workers and Transitional Help Act or GROWTH Act - Amends the Supplemental Appropriations Act, 2008 to declare that nothing in the Act shall prevent the commencement or continued payment of first-tier emergency unemployment compensation (EUC) to the extent that it: represents amounts established in an applicant's EUC account (EUCA); and is payable for a week ending on or before January 1, 2015. (Thus provides for a 12-month extension of EUC.) Revises the formula for crediting Tier-1 amounts to an applicant's EUCA to include a week ending after January 1, 2014. Decreases the percentages in the formula (the lesser of which shall be the amount credited): (1) from 80% to 54% of the total amount of regular compensation (including dependents' allowances) payable to the individual during the benefit year, and (2) from 20 to 14 times the individual's average weekly benefit amount for the benefit year. Directs the Secretary of the Treasury to transfer necessary amounts from the Treasury general fund to the EUC account to make payments to states for this extension of EUC. Makes a change in application of a certain requirement (nonreduction rule) to a state that has entered a federal-state EUC agreement, under which the federal government would reimburse the state's unemployment compensation agency making EUC payments to individuals who have exhausted all rights to regular unemployment compensation under state or federal law and meet specified other criteria. (Under the nonreduction rule such an agreement does not apply with respect to a state whose method for computing regular unemployment compensation under state law has been modified to make the average weekly unemployment compensation benefit paid on or after June 2, 2010, less than what would have been paid before June 2, 2010.) Declares that the nonreduction rule shall not apply to a state which has enacted a law before December 1, 2013, that, upon taking effect, would violate the nonreduction rule. Allows a state whose agreement was terminated, however, to enter into a subsequent federal-state EUC agreement on or after enactment of this Act if, taking into account this inapplicability of the nonreduction rule, it would otherwise meet the requirements for an EUC agreement. (Thus allows such a subsequent EUC agreement to permit payment of less than the average weekly unemployment compensation benefit paid on or after June 2, 2010.) Authorizes the Secretary of Labor, for FY2014-FY2023, to use any available discretionary appropriations to conduct in-person reemployment and unemployment insurance eligibility assessments for unemployment insurance beneficiaries. Specifies limits in such amount for each fiscal year. Amends the Internal Revenue Code (IRC) to repeal the excise tax on medical devices. Declares that no presidential permit shall be required for a specified application filed on May 4, 2012, by TransCanada Keystone XL pipeline, L.P., to the Department of State for the Keystone XL pipeline, as supplemented to include the Nebraska reroute featured in the Final Evaluation Report issued by the Nebraska Department of Environmental Quality in January 2013 and approved by the Nebraska governor. Considers the final environmental impact statement regarding the pipeline issued by the Secretary of State on August 26, 2011, coupled with the Final Evaluation Report, to satisfy all requirements of the National Environmental Policy Act of 1969. Amends the IRC, as amended by the Patient Protection and Affordable Care Act, to redefine "full-time employee," for purposes of the mandate requiring employers to provide health care coverage for their employees, as an employee who is employed on average at least 40 hours of service a week (currently, at least 30 hours of service a week). Amends title II (Old Age, Survivors and Disability Insurance) (OASDI) of the Social Security Act to declare that for any month that an individual is entitled to unemployment compensation (UC) he or she shall be deemed to have engaged in substantial gainful activity and so be disqualified from receiving Social Security disability benefits after a certain period has elapsed. States that, for purposes of determining services rendered by an individual during a period of trial work which will not disqualify the individual for disability benefits, the individual shall be deemed to have rendered services in a month if he or she is entitled to UC or trade adjustment assistance for that month. Amends the IRC to require taxpayers who are claiming the refundable portion of the child tax credit to include their Social Security numbers on their tax returns..

the studies of the quantum systems of three particles of different nature , which are performed within various theoretical approaches , remain to be actual for a long period ( see survey @xcite ) . this is related to both the presence of nontrivial effects , which appear in this simplest many - particle system , such as the famous efimov effect @xcite , and the importance of the theoretical consideration of real three - particle and three - cluster systems of different nature , e.g. , nuclei with three nucleons or with three clusters , hypothetical systems of the type of trineutrons , molecular trimers , etc . important and insufficiently studied are the fine near - threshold effects in the systems of three particles . the present work is devoted to the analysis of the general properties of these effects and the thresholds of stability for three - particle systems . the study of properties of the three - particle thresholds is executed qualitatively on the basis of the analysis of the asymptotic estimates , and also using the high - precision variational calculations with the use of optimized gaussian bases . this approach allows us to investigate , with a high controlled accuracy , even such fine effects as the efimov effect , as well as the structure functions of these near - threshold levels @xcite that are characterized by a very small energy . in the present work , we consider a system of three particles , among which two particles are identical ( we set their masses @xmath0 without loss of generality ) , and the third one can differ from them by the mass and the pairwise interaction potential . we write the hamiltonian of such a system in the case of pairwise interactions in the form ( in the system of units with @xmath1 ) @xmath2 let the intensities of two - particle interaction potentials be defined by the dimensionless interaction constants @xmath3 ( for the pair of identical particles @xmath4 ) and @xmath5 ( for the pairs of particles @xmath6 and @xmath7 ) on the given form of the interaction , where @xmath8 and @xmath9 . we consider the potential functions @xmath10 and @xmath11 mainly with positive values . negative values of @xmath3 and @xmath5 correspond to the attraction , and positive ones to the repulsion . we will study the properties of the energy thresholds of stability for three - particle systems , i.e. the regions of such values of the constants @xmath3 and @xmath5 , at which the _ n_-th energy level of the three - particle system appears below the two - particle thresholds or below zero if the two - particle subsystems are not bound , @xmath12 @xmath13 we will study the energy thresholds of stability for three - particle systems with the zero total angular momentum , @xmath14 , for various ratios of the masses of particles , the form of pairwise interaction potentials , and the symmetry of the wave function relative to the permutations of identical particles ( for the symmetric @xmath15 and antisymmetric @xmath16 states ) . on the plane ( @xmath17 ) , we will present the results of studies in the form of the diagrams of the thresholds of energy levels , namely the thresholds of stability of the energy levels of three particles with the zero angular momentum ( fig.[fig1 ] ) . the systematization of the significant amount of calculations and the qualitative analysis allow us to represent the thresholds of stability in the universal form of the diagrams of thresholds . in fig.[fig1 ] , we give , for the sake of specificity , the example of the diagrams of stability corresponding mainly to potentials @xmath10 and @xmath18 which have the same gaussian form and correspond to almost equal masses . we emphasize that the characteristic properties of a diagram are preserved for nonsingular short - range potentials of more general forms . in fig.[fig1 ] , we show the main peculiarities of such diagrams schematically without holding the scale , but with the preservation of all main regularities . each line of the threshold of the @xmath19-th level ( for the states @xmath20 symmetric relative to the permutation of the identical first and second particles , and for the antisymmetric states @xmath21 ) separates the region of the existence of a bound state ( the region of stability ) with the corresponding @xmath19-th level of three particles from the region , where this level does not exist ( this side of the curve is shaded ) . because the bound states of three particles can appear only under the attraction between different particles ( the potential @xmath22 with the negative constant @xmath23 while the interaction between identical particles ( the potential @xmath24 ) can be both attractive ( @xmath25 ) and repulsive ( @xmath26 ) , the three - particle thresholds are positioned to the left from the axis of ordinates . on the axes , we marked the points where two - particle ground bound states appear : the @xmath27-state with the orbital moment @xmath28 ( @xmath29 , @xmath30 ) and the @xmath31-state with the orbital moment @xmath32 ( @xmath33 , @xmath34 ) . we also show the corresponding two - particle thresholds on the axes by lines with different thicknesses . the inclined dashed lines separate the regions , where the lowest threshold from two two - particle ones is the threshold for two identical particles ( due to the potential @xmath35 , below the dashed line ) or for two different particles ( due to the potential @xmath36 , above the dashed line ) . the three - particle levels exist below the lowest two - particle threshold . the dash - dotted vertical lines in the lower part of fig.[fig1 ] are the asymptotes of three - particle thresholds as @xmath37 . in this case , the lower part of the figure is correlated with the rest parts so as it follows from direct calculations . in the diagram of the thresholds of stability , the bound states of the system of three particles exist , by starting from the lines of thresholds , as a rule , towards the increase in the intensities of the attraction ( i.e. to the left and down on the diagram ) . on the energy diagrams of stability , we can distinguish eight different regions by characteristic peculiarities of the ground and excited three - particle levels : region i the asymptotic region , where @xmath38 , region ii the asymptotes of thresholds as @xmath39 , @xmath40 , region iii the region of the infinite series of efimov levels near the values of the two - particle interaction constants critical as for the appearance of the bound @xmath27 states @xmath41 , @xmath42 ; on the diagram of thresholds , the nonmonotonous and closed curves correspond to the efimov states ( they are marked by the words `` efimov s effect '' ) , region iv the axis @xmath5 in the case of the absence of the interaction between identical particles @xmath43 , when @xmath44 and the conditions of the thomas theorem are satisfied , region v the region where the effect of a `` tube '' is manifested for @xmath45 and arbitrary positive @xmath3 , region vi we indicate the characteristic behavior of thresholds for the symmetric three - particle states in the region @xmath46 with the appearance of an acute `` wedge '' on the line of equality of the threshold binding energies of different pairs of particles , @xmath47 , region vii the region of a `` rearrangement '' of the thresholds of energy levels , region viii the region of the nonmonotonicity of the curves for the thresholds of antisymmetric levels . the characteristic peculiarities of the behavior of the energy thresholds of stability of the three - particle system in different regions on the plane @xmath48 , the general established phenomenon of the nonmonotonicity of thresholds , and the effect of `` traps '' are studied analytically and with the use of numerical calculations within the galerkin variation method with a gaussian basis and various high - precision optimization schemes . consider region i for the ground and excited symmetric states on the diagram of thresholds , where @xmath49 and simultaneously @xmath50 ( the left upper part of the diagram of thresholds in fig.[fig1 ] ) . we rewrite hamiltonian ( [ e1 ] ) in the center - of - mass system as @xmath51 where @xmath52 , @xmath53 jacobi relative coordinates . let a short - range repulsive potential @xmath35 have a maximum at zero and monotonically decrease , and let the potential @xmath36 have a minimum value @xmath54 ( @xmath55 the attraction , and this occurs not obligatorily at @xmath56 ) . in the limit of strong coupling , the main contribution to the ground - state energy is determined by the minimum of the full three - particle potential well , which is positioned at @xmath57 and at some @xmath58 , minimizing the effective total potential energy @xmath59 . for nonsingular short - range potentials @xmath60 and @xmath61 , the threshold line is determined by the formula @xmath62 which determines the value of @xmath58 , where the minimum of the effective attractive potential energy of three particles @xmath63 is attained , and establishes the connection between the constants @xmath3 and @xmath64 in the considered region of the diagram of thresholds . in the simple case of the interaction potentials @xmath60 and @xmath61 in the gaussian form with unit radii , which is thoroughly studied numerically , the condition for the threshold has the form @xmath65 from the condition of the minimum of the left - hand side of ( [ e5 ] ) , we get @xmath66 and , with regard for ( [ e5 ] ) , @xmath67 then , in the limit @xmath68 , the asymptotic formula with regard for the next correction for the lines of the thresholds of the ground and excited levels has finally the following form : @xmath69 here , @xmath70 we note that the quantum numbers @xmath71 in ( [ e8 ] ) and ( [ e9 ] ) correspond to the ground state . the series of states in @xmath31 is due to one - dimensional small oscillations along the coordinate @xmath72 , whereas the series of states in @xmath73 corresponds to three - dimensional oscillations along the coordinate @xmath74 near the minimum of the potential well in the three - particle system . indeed , if we expand the potential energy ( in the case of the gaussian potentials @xmath60 and @xmath61 ) in hamiltonian ( [ e3 ] ) averaged over angles near the minimum in @xmath75 and in the squared deviation @xmath76 , we get , instead of ( [ e3 ] ) , the approximate oscillatory hamiltonian as a function of both coordinates @xmath77 the energy states of the oscillatory hamiltonian ( [ e10 ] ) generate the lines of thresholds ( [ e8 ] ) and ( [ e9 ] ) . the motion of the system of three particles in symmetric states in approximation ( [ e10 ] ) is oscillations relative to the following configuration . at the center of the system , a particle with mass @xmath78 is located . on the same diameter with it , particles 1 and 2 ( @xmath79 ) are positioned , but the wave function is spherically symmetric in angles ( the sphere diameter @xmath80 ) . the distance between particles 1 and 2 does not depend in the main approximation on the mass of the third particle . that is , such a configuration of the system ( the third particle is at the center between the two identical particles ) occurs even in the case where the mass @xmath78 of the third particle is small . the more detailed consideration of the threshold in region i shows that asymptote ( [ e8 ] ) for the ground state is defined as @xmath81 and the coefficient @xmath82 is positive at very small masses . moreover , @xmath83 as @xmath84 , is negative at greater masses and reaches a minimum value at @xmath85 ( @xmath86 ) . at @xmath87 , it approaches the constant , @xmath88 . thus , the linear asymptote of the threshold for the ground state in region i of the threshold diagram in fig.[fig1 ] is reached from the top for very small masses ( @xmath89 ) and is reached from the bottom for the greater mass of the third particle . we also note that , in region i of the diagram of thresholds , the result which is asymptotic in the coupling constant , @xmath90 , is easily generalized to other potentials . in particular , let the interaction potential @xmath61 between different particles be chosen in the gaussian form with another interaction radius @xmath91 . then we get the same configuration of three particles ( the third particle is located between two identical ones ) . moreover , instead of ( [ e7 ] ) , we obtain ( for @xmath92 , when @xmath93 ) @xmath94 in the main approximation , we get @xmath95 where @xmath96 the least value of the coefficient , @xmath97 , is reached in ( [ e14 ] ) at @xmath98 , when @xmath99 and all three particles approach one another at small distances . as @xmath100 , the coefficient @xmath101 grows indefinitely . for @xmath102 , all three particles are , all the more , at small distances , where the small oscillations of the particles relative to the equilibrium position occur . the asymptotics of a threshold remains invariable : @xmath103 . hence , in the region of the diagram of thresholds where @xmath104 and @xmath105 , the three - particle system can possess different configurations even in the case of the simplest interactions . qualitatively , analogous results are obtained for a wider class of the pairs of potentials @xmath60 and @xmath61 . for example , for potentials in the form of exponentials , @xmath106 and @xmath107 , we have , for @xmath108 , @xmath109 in this case , the least value of the coefficient @xmath110 is also attained at @xmath111 , when @xmath112 , and both @xmath58 and @xmath113 grow with increase in @xmath114 . moreover , for an arbitrary pair of the monotonous repulsive potential @xmath24 between the identical particles and the attractive potential @xmath22 between different particles in region i , a linear dependence between the intensities of the potentials takes place , which separates the region of stability of three particles from the region , where the coupling is absent . if the repulsive potential @xmath60 is nonmonotonous and has a sufficient decrease at zero , and if the attractive potential @xmath61 has a minimum at finite distances @xmath115 , a two - cluster configuration of the system of three particles is also possible : in this case , the identical particles are positioned near each other , and the third one is located at a distance @xmath116 from them . all the main qualitative and analytic results concerning the asymptotics of the thresholds of stability in region i are confirmed by the high - precision systematic calculations with two - particle potentials of the gaussian form for a great variety of masses within the variational approach with the use of gaussian bases . the separate calculations were executed for other potentials , and they also support the general schematic fig . [ fig1 ] . we now consider the asymptotic limit of the strong coupling between the identical first and second particles ( region ii , where @xmath117 in the lower part of the diagram of thresholds ( fig.[fig1 ] ) ) . in this limit , the size of subsystem @xmath4 tends to zero , and the variables in ( [ e1 ] ) are separated in the cluster approach . then the three - particle wave functions for hamiltonian ( [ e3 ] ) can be chosen as @xmath118 where @xmath119 is the ground state oscillatory wave function of the relative coordinate @xmath120 of pair @xmath4 , and the wave function of the third particle , being in the effective field of two other particles , depends on the coordinate @xmath121 and is the eigenfunction of the effective hamiltonian reckoned from the two - particle threshold , @xmath122 with the reduced mass @xmath123 and the effective averaged potential @xmath124 consider the motion of the third particle relative to the pair of particles @xmath4 in potential ( [ e19 ] ) which looks , in particular for the gaussian form , as @xmath125 then , for the critical constants @xmath126 , at which the @xmath19-th three - particle near - threshold level in the three - particle system appears , we get the asymptotics as @xmath127 : @xmath128 here , @xmath129 are the critical constants of the appearance of the @xmath19-th level in the system of two particles with the zero orbital moment @xmath28 ( for the gaussian potential with unit radius in the case of the unit masses of particles , the critical constants of the @xmath27-states are as follows : @xmath130 ; @xmath131 ; @xmath132 ; @xmath133 , etc . ) . the expressions analogous to ( [ e21 ] ) can be also obtained in the case where the subsystem of two particles in the state with the wave function ( [ e17 ] ) has a nonzero orbital moment . it follows from ( [ e21 ] ) that the threshold of each three - particle level ( in the states symmetric in the permutations of the pair of particles @xmath4 ) is positioned always to the left from the corresponding vertical asymptote for @xmath134 ( they are marked by dash - dotted vertical lines in the lower part of fig.[fig1 ] ) . we can show analogously that , for the states antisymmetric relative to the permutations of the pair of particles @xmath43 , the thresholds approach , on the contrary , the corresponding vertical asymptotes from the right side . the high - precision calculations for different masses and potentials in the form of a superposition of gaussian functions confirm completely the above - presented conclusions about the asymptotics of thresholds for different levels as @xmath127 . consider region iii in the vicinity of the critical constants of the appearance of the two - particle ground bound @xmath27-states : @xmath135 and @xmath136 in fig.[fig1 ] . this is the region where the efimov effect @xcite is manifested , and the infinite series of efimov weakly bound levels for the system of three ( generally saying , different ) particles is observed . in the diagram of thresholds , it is seen as the infinite collection of closed self - similar ( with the universal scale for highly excited states ) convex curves are accumulated at the critical point ( @xmath137 ) for three pairs of particles interacting in a resonance way . the lines of thresholds for the series of efimov energy levels are considerably stretched along the dashed inclined line ( which starts from the region of the efimov effect ) , where the two - particle thresholds of different pairs of particles in the @xmath27-state coincide , and are somewhat elongated vertically upward along the @xmath3 axis , when only two pairs of particles interact in a resonance way . the fundamental efimov effect is described in detail by v. efimov himself and many other researchers . here , we should like to emphasize only separate points . firstly , the infinite series of symmetric three - particle efimov levels with the zero angular momentum is realized only in the limit @xmath138 , @xmath139 , i.e. in the case where all three pairs of particles in singlet states are at a resonance . outside this region , the number of levels is always bounded , though these levels have the certain specific properties of properly efimov levels especially in the case of two resonating pairs of particles @xmath6 and @xmath7 ( @xmath140 ) even under a sufficiently large decrease in the attraction between the particles of the third pair , @xmath4 . secondly , by the example of the series of efimov levels , we have the ideal demonstration of the energy `` traps '' ( see section 5 for more details ) , when the strengthening of the attraction on the diagram of thresholds leads to a nonmonotonous variation of the number of energy levels : the three - particle levels at first separate from the two - particle threshold and then disappear on it . the efimov levels exist only in a certain interval of the coupling constants of all three pairs of particles interacting in a resonance way . thirdly , for three - particle states antisymmetric in the pair of the identical particles @xmath4 , the singlet point ( @xmath141 ) is nonsingular ( see fig.[fig1 ] , region viii ) . at the same time , the limiting region near the point ( @xmath142 ) , where one pair @xmath4 of the identical particles resonates in the state with the angular momentum @xmath143 , is , as if , `` attractive '' for the corresponding states . in this region of fig.[fig1 ] , there exists a certain anomaly : the curves for the thresholds of antisymmetric states are significantly stretched towards small coupling constants along the line where the two - particle thresholds of two different pairs of particles in the singlet and triplet states coincide . finally , we note that we do not discuss the three - particle antisymmetric states with nonzero angular momentum , where there exists the possibility for a collapse to arise @xcite , which requires a separate consideration . consider the case where the interaction of one pair of particles , @xmath4 is absent ( when @xmath44 ) . this corresponds to region iv on the @xmath64 axis in fig.[fig1 ] , where the conditions of the thomas theorem @xcite are satisfied . then , there always exists the bound ground state of three particles in a wider region of coupling constants @xmath64 of two pairs of particles as compared with an isolated pair of two particles . this means that the three - particle threshold of the ground state for @xmath144 is always positioned to the right from the two - particle critical point in the constant @xmath64 . first of all , we note that the important common point for the thomas and efimov effects is the presence of pairs of particles interacting in a resonance way . moreover , the regions of these effects are positioned near each other in the diagram of thresholds ( fig . [ fig1 ] ) . at the same time , the thomas effect is referred only to the ground state of three particles , whereas the efimov effect concerns the infinite series of near - threshold weakly bound states . secondly , the universality of the thomas theorem consists in that it holds for hamiltonian ( [ e3 ] ) with @xmath44 for an arbitrary attractive potential @xmath36 between two pairs of particles and an arbitrary finite mass @xmath78 of the third particle . moreover , the less the mass @xmath78 , the wider is the region of the manifestation of the thomas effect relative to the interaction constant . we note that , for small masses , the number of three - particle levels becomes great , when the two - particle subsystems are not bound yet . thirdly , there occurs the effect of a `` trap '' for the first excited state at @xmath44 for particles with close masses ( under certain conditions , this concerns higher excited states too ) , as distinct from the ground state . in this case , the existence of an excited level depends nonmonotonically on strengthening the attraction by variation of @xmath145 . in addition , the intersection points of the lines of the thresholds of excited levels with the abscissa axis ( fig.[fig1 ] ) from the side of great values of @xmath145 are located to the right from the corresponding two - particle critical values of the coupling constants , where the binding energies of two particles are equal to zero . we emphasize once more that the schematic figure 1 represents all main regularities so as they follow from the asymptotic estimates and the high - precision calculations . a special attention should be paid to the effect of a `` tube '' for symmetric states at the diagram of thresholds ( region v in the upper part of fig.[fig1 ] ) , where the bounded region near @xmath146 contains at least one bound state of three particles even under the unlimited increase of the repulsion between the pair of identical particles ( @xmath3 is arbitrary ) . the effect of a `` tube '' is seen more clearly in fig.[fig2 ] , where , on the real scale , we show the results of high - precision calculations for the threshold of the ground state and the isolines of the energy of three particles , which is reckoned from the two - particle threshold , for the gaussian potentials with unit interaction radii for the mass @xmath147 . the form of the energy surface in the region @xmath148 and near @xmath149 , indeed , reminds of a `` tube '' positioned vertically . it is seen that the isoenergetic lines @xmath150 for the ground state of three particles with small values of @xmath151 are pulled into the `` tube '' in the upper part of the figure for @xmath152 and great repulsive constants @xmath3 . the isolines do not form a `` tube '' already at @xmath153 and greater values , but reveal the clear asymptotic behavior characteristic of the isolines with great values of @xmath154 , showing a sharp change of the modes near the abscissa axis ( on the given scale ) . it is important that , on the increase of the attraction between particles @xmath6 and @xmath7 ( the motion along the horizontal axis in fig.[fig2 ] ) under a significant repulsion between the pair of particles @xmath4 , the nonmonotonicity in the number of bound states is always observed ( we call this as the effect of a `` trap '' related to the presence of the `` tube '' ) . the phenomenon of a `` tube '' can be explained on a qualitative level . we will show firstly that the number of levels in a `` tube '' is always bounded , but it grows infinitely as @xmath84 . we use the fact @xcite that the pair correlation functions @xmath155 in efimov states @xmath156 for @xmath157 for the adjacent levels satisfy the relation @xmath158 where @xmath159 is the ratio of the energies of adjacent efimov levels in the limit @xmath160 ( @xmath161 in the case of three identical particles , and the danilov minlos faddeev efimov constant @xmath162 determines the index of singularity of the limiting equation of skornyakov ter - martirosyan in the case of the zero interaction radius ) . relation ( [ e22 ] ) takes place due to the fact that , as @xmath160 , the spatial region , where the pair correlation function behaves itself as @xmath163 @xcite , is spreading . it is true from distances of the order of the radius of forces to distances of the order of the size of the system @xmath164 ( here , @xmath165 is the characteristic size of the system in the ground state , @xmath19 is the level number , and @xmath166 is the ratio of sizes of the system for adjacent efimov levels ) . therefore , the pair correlation function for sufficiently great @xmath19 has the following normalizing factor of @xmath167 : @xmath168 at small distances , the pair correlation function is of the same order as that at @xmath169 , therefore we obtain relation ( [ e22 ] ) . in order to approach the region of the `` tube '' from the region , where the efimov effect manifests itself , we consider some additional short - range repulsion @xmath170 between the pair of particles @xmath4 which is taken as a perturbation of the zero hamiltonian , for which the efimov effect is observed . the greater the number of a level , the greater is the size of the three - particle system , which reminds of a spherical concentric `` halo '' @xcite with the ratio of the radii of the adjacent spheres @xmath171 . the greater the size of a system of particles with short - range interaction , the better are satisfied the conditions for the `` gas '' approach @xcite taking into account a contribution of the short - range repulsion @xmath172 to the energy . in the principal approximation in the `` gas '' parameter , a shift of the @xmath19-th level is determined by the two - particle @xmath173-matrix : @xmath174 here , @xmath175 is the two - particle @xmath173-matrix defined for the potential @xmath170 , @xmath176 is the scattering length by the potential @xmath170 ( for the repulsive potentials , @xmath177 ) . these quantities are finite for short - range repulsive potentials of the given form in the limit of the infinitely great repulsion , @xmath104 . in this case , the effective radius and other low - energy parameters which are present in the next terms of the expansion of the energy in the `` gas '' parameter are also finite . these conclusions allow us to consider the most wide region in the constant @xmath3 in the diagram of thresholds from the region of the efimov effect to the region of the `` tube '' with @xmath104 , if the summary potential @xmath178 is replaced by @xmath179 . hence , if the intensity of the repulsive potential increases , @xmath104 , the energy shift @xmath180 obtained due to the repulsion has a finite limit . moreover , the greater the number @xmath19 of an excited level , the more exact is the relation @xmath181 . let @xmath182 be the quantity of the order of the binding energy of the ground state of three particles for the critical two - particle constant . with regard for the energy @xmath183 of the @xmath19-th level of the `` zero '' hamiltonian near the critical constants ( near the efimov region ) , the total energy of the @xmath19-th level in the region of the `` tube '' looks as @xmath184 and @xmath185 . since @xmath186 ( for @xmath187 , the energy @xmath188 becomes positive with increase in @xmath19 for an arbitrary small repulsion which is characterized by the scattering length @xmath176 . this clarifies the above - mentioned conclusion about the finiteness of the number of levels under a deviation from the accumulation point of efimov levels by the constant @xmath3 . that is , for the infinite number of levels to exist , it is necessary that the interaction of all three pairs of particles be resonant , @xmath189 and @xmath190 simultaneously . all the more , the number of levels becomes finite , when the repulsion @xmath191 reaches a significant intensity ( in this case , the @xmath173-matrix is bounded , and the length @xmath176 tends to a finite limit of the order of the radius of forces ) . at the same time , the arbitrariness of the repulsion intensity for the pair @xmath4 , the finiteness of the @xmath192-matrix , and the conditions for the resonance and hence the appearance of the effective long - range interaction for two pairs of particles do not contradict the possibility for the bound states of three particles to exist . the presence of at least one bound state of three particles in the region under study is confirmed by the numerical calculations for different forms of potentials and for different masses . we note that the `` tube '' ( see figs.[fig1 ] and [ fig2 ] ) is asymmetrically positioned relative to the vertical asymptote @xmath193 ( the resonance region for two pairs of particles ) . to a great degree , it is positioned to the left from the asymptote , where the attractive constant @xmath64 is greater by modulus . but , with the further increase in the attractive constant @xmath194 by modulus , we come away from the resonance region . and at sufficiently large repulsive constants @xmath3 , the three - particle level can disappear , arising again only in the limit of a strong coupling ( see figs . [ fig1 ] and [ fig2 ] ) . we emphasize once more that all main qualitative conclusions of this section are confirmed by the numerical calculations . the interesting universal phenomenon of a `` wedge '' ( region vi in fig.[fig1 ] and , respectively , in figs . [ fig3 ] and [ fig4 ] ) is observed on the line where the binding energies of two different pairs of particles are equal , @xmath195 ( on the dashed inclined lines ) . for the sake of specificity , we consider fig.[fig3 ] . as above , we have correctly preserved all the regularities , which are obtained in the calculations , though the scale of the figure is rather arbitrary . the effect of a `` wedge '' consists in the following . if we move along the dashed line ( from the left to the right ) from the region of a strong coupling , @xmath196 , to the side where the attraction decreases , then the threshold line of the @xmath19-th symmetric state of three particles ( in fig.[fig3 ] , they are the lines of the 6-th and 5-th excited states ) is finished by a sharp cusp in the form of a `` wedge '' oriented from the left to the right . the lines of thresholds approach the dashed inclined line from the top and from the bottom with different slopes , and the derivative of the threshold line undergoes a break here . the `` wedge '' arises not due to the nonanalyticity , but as a consequence of the competition of thresholds . on the further motion to the right ( within fig.[fig3 ] ) , firstly the 6-th excited state and then the 5-th one stop to exist . but with the decrease of the attraction along the dashed inclined line , where the energies of the two - particle thresholds are equal , the 5-th excited state appears again , while we approach the efimov region . its threshold line has the form of a `` wedge '' oriented from the right to the left . for higher excited states , the effect of a `` wedge '' holds analogously . inside the closed region of the thresholds of efimov states , the bulbous curves of thresholds have a cusp in the form of a `` wedge '' on the dashed inclined line . we note that , for antisymmetric states , no similar regularities are observed . firstly , we consider the case of great values of the mass @xmath78 of the third particle . if the mass is infinite ( the three - particle model passes into a model with two particles in the short - range field of a fixed center ) , then it is obvious from ( [ e1 ] ) that , in the absence of the potential @xmath197 , the problem of three particles is equivalent to that of two independent particles in the field of the attractive center @xmath198 . the ground state of such a system arises under the same conditions as those for each of the particles in the field of a center : @xmath199 in the general case of arbitrary masses , @xmath200 ) , and , for the gaussian potential with unit radius , we get @xmath201 . we emphasize that , for the infinite mass of the third particle in the case where @xmath44 , the thomas theorem becomes trivial , and the three - particle state exists , by beginning exactly from the two - particle critical constant . for the excited states in the case of the infinite mass @xmath202 , the couplings for three and two particles also appear at the same points on the @xmath64 axis . in addition , the energies monotonically increase with @xmath203 . generally , for @xmath202 , the thresholds of stability are transformed only slightly on the whole plane @xmath48 as compared with the case where @xmath204 , though , in the region of the `` tube '' , there remains only the ground state which differs cardinally from the excited states for this reason . as @xmath202 , the whole `` tube '' is positioned to the left from the asymptote @xmath205 . moreover , the right edge of the threshold of a three - particle state crosses the abscissa axis at the resonance point of two pairs of particles @xmath206 and rises sharply ( almost vertically ) upward . in the resonance region of all three pairs of particles ( @xmath207 ) , the conditions for the appearance of the infinite efimov spectrum , which possesses the universal properties by beginning already from the second excited level , are realized in the standard way . in other regions in the diagram of the thresholds of stability in the case @xmath202 , the general peculiarities seen in fig.[fig1 ] are preserved as well . we now consider the other limiting case of very small mass @xmath208 ( a two - center model of three particles ) . in the region where @xmath209 , heavy particles @xmath4 are not coupled in the absence of the third light particle , and @xmath210 , as well as in the case where there exists the coupling in the pair of heavy and light particles ( pair @xmath6 or @xmath7 ) , we can adiabatically separate the variables . if we make averaging over the fast movement of the light particle ( in the state @xmath211 ) , then we get the equation for the wave function of the coordinate of the relative motion of particles @xmath4 @xmath212 ( in the case of the gaussian potentials with unit radii ) with the additional potential @xmath213 @xmath214 where @xmath215 , and all quantities of the dimension of energy are multiplied by @xmath78 . then , as @xmath84 and for small deviations from the position of equilibrium , we have the oscillatory potential ( @xmath216 ) . since the oscillatory frequency @xmath217 , the spectrum becomes denser for smaller masses . hence , for constants @xmath218 and small masses ( @xmath84 ) , we have the growing number of bound levels of the equidistant spectrum . respectively , the thresholds for small masses will represent the equidistant spectrum in this region . in the diagrams of the thresholds of stability ( see fig.[fig3 ] ) , the indicated regularities are manifested , as @xmath219 , in the enlargement of `` islands '' ( `` traps '' ) of the infinite series of efimov levels , the separation ( due to the merging with the earlier isolated thresholds in the places of a `` wedge '' ) of the increasing number of the new lines of thresholds from the islands , the `` pulling '' of them into the region of the `` tube '' , and the gradual filling of the whole region @xmath220 , @xmath221 . it is easy to trace the change of the general pattern in fig.[fig3 ] with decrease in the mass of the third particle or , conversely , an increase in this mass . we can qualitatively explain the growth of the number of thresholds in the `` tube '' by the following reasoning . because @xmath159 depends on the mass of particles @xcite and tends to 1 with decrease in the mass of the third particle , energy ( [ e24 ] ) depends more and more weaker on the level number @xmath19 . therefore , the number of levels , for which energy ( [ e24 ] ) remains negative , increases . that is , the less the mass , the greater is the number of thresholds which correspond to excited levels and can be `` pulled '' into the `` tube '' . this is completely confirmed by the high - precision calculations for small masses . in particular , the first excited level begins to move into the `` tube '' on the transition from great masses to @xmath222 ( fig.[fig1 ] ) . in the limit @xmath84 , the number of levels in the `` tube '' tends to infinity , but , for any finite mass , the number of levels is finite ( fig.[fig3 ] ) . in the general aspect , the less the mass of the third particle , the more the symmetric states become similar to the first excited one ( for @xmath223 ) . this implies that , in a certain sense , the effects of efimov and thomas and the effect of a `` tube '' have many common features . on the contrary , we may expect that , in the case of the model of two particles in the field of a fixed center and under a variation of the forms of interaction potentials , all three effects can be significantly impoverished , so that they will have few common features . the nonmonotonous change of the number of levels of the three - particle system with increase in the interaction constants in the region of attraction , where the levels appear and then disappear on a two - particle threshold with increase in the attraction ( the effect of a `` trap '' ) is characteristic ( see the diagrams of thresholds in figs.[fig1 ] and [ fig3 ] ) of a wide region of the interaction constants which can be positioned even sufficiently far from the efimov region of the resonance interaction . if the general constant of attraction in the three - particle system grows so that @xmath3 and @xmath5 are linearly related to each other , we can easily reveal a nonmonotonous character of the behavior ( appearance and disappearance ) of levels . that is , the effect of a `` trap '' has a sufficiently universal character . in fig.[fig4 ] , the lines with arrows show some directions of the coordinated increase in the intensities of the interaction potentials , where the three - particle levels appear and then disappear with increase in the interaction constants ( the continuous and dotted lines correspond , respectively , to the absence and presence of the given bound state ) . in this figure , we present ( schematically ) the results of high - precision calculations with the gaussian potentials of unit radii and @xmath224 ( but , for the convenience of a perception , we choose the scale to be arbitrary ) . the figure demonstrates the presence of a `` trap '' even in a very narrow interval of the constant @xmath64 near a critical value of the resonance interaction constant @xmath225 , though this region is small . for the sake of convenience , we schematically present ( to the right in fig.[fig4 ] ) the dependence of the binding energies on the coupling constants with strengthening the attraction along the mentioned directions . in this case , we see the appearance of `` traps '' for the energy levels in both the ground and excited states near two - particle thresholds . in the general aspect , the effect of a `` trap '' for three - particle levels , which demonstrates the essentially different mode of the dependence of the ground - state energy of two particles and that of the three - particle levels on the interaction constants , is a consequence of the two - particle structure of the full interaction potential in the three - particle system . quite nontrivial is the possibility to vary the modes of behavior of the thresholds ( and of the energy levels ) with the help of the interaction potentials which involve at least two modes of attraction with essentially different radii . in this case , we can nontrivially realize a certain generalization of the well - known zeldovich two - particle effect of a `` rearrangement '' of the energy spectra in the system of three particles . for the pairwise interaction potentials with the components of different radii , for example , of the type @xmath226 ( where @xmath227 and @xmath228 ) , one observes a `` rearrangement '' ( fig.[fig5 ] ) of the energy spectrum in the three - particle system ( a three - particle analog of the zeldovich effect ) . due to a great value of the ratio of the interaction radii of the two - component attractive potential ( @xmath229 ) , the spectrum of three particles is close to the superposition of the spectra of two problems involving three particles with the separately taken components of the interaction potential , and the quasidegeneration of the levels occurs . but , at the points of the expected intersection of levels of these two spectra , we observe the effects related to the `` rearrangement '' of levels . for example , the first excited level replaces the ground - state level with increase in the total attraction ( with increase in @xmath3 ) . in its turn , the ground - state level sharply changes the mode of the dependence on the interaction constant . in fig.[fig5 ] , on the real scale , we present the results of calculations of a three - particle completely symmetric energy spectrum ( the binding energies ) as a function of the interaction constant @xmath3 for a specific example of potential ( [ e28 ] ) ( @xmath230 @xmath231 @xmath232 ) . at the same interaction constant @xmath233 , the `` rearrangement '' of the spectrum of four levels occurs successively : @xmath19-th level replaces @xmath234-th level . the ground state level is the only one which , after the `` rearrangement '' , corresponds to the binding energy with a quite different mode of the dependence on @xmath3 . the effect of a `` rearrangement '' of the three - particle spectrum is much more pronounced than that for the two - particle threshold and occurs for a less attraction . by changing the class of the corresponding interaction potentials and their parameters , we can vary the number of levels in the region of a `` rearrangement '' and can also create a `` trap '' for other levels ( see results in @xcite for nonlocal separable potentials ) . the close conditions for a realization of the effects of `` rearrangement '' and `` traps '' for the energy states are known in solid state physics for a long time in the case where , for example , the conditions for a `` quasidegeneration '' of the phonon and optical branches of oscillations are realized , or the crystals with admixtures are considered . even for simple potentials in the gaussian form , the performed high - precision studies of the energy thresholds for three particles reveal one more effect of a sharp change of the modes in the diagrams of the thresholds of stability which can be also named the effect of a `` rearrangement '' . this effect has no analog on the two - particle level . there exist the regions of parameters ( in the @xmath64 axis , these are the regions close to the vertical asymptotes in fig.[fig3 ] ) , where the `` rearrangement '' of the adjacent energy thresholds occurs in the digram of thresholds . that is , on the monotonous change of the interaction intensities , the threshold of the @xmath235-th level sharply approaches that of the @xmath19-th one and occupies its place . this effect is especially clearly manifested in the case of small masses of the third particle ( see fig.[fig6 ] , where the lower part of the diagram of the thresholds of three first excited levels calculated for the mass @xmath147 is shown ) . we note that , in fig.[fig3 ] , this effect of the rearrangement of thresholds is not marked in order to avoid the complication of a perception of the general scheme of three - particle thresholds . the presence of the effect of a `` rearrangement '' is probably related to the following . in addition to the considerable short - range attractive interaction between particles @xmath4 present in hamiltonian ( [ e1 ] ) , there appears an additional effective oscillatory interaction having a great radius at small masses of the third particle . this additional interaction between particles @xmath43 is generated by the motion of the third light particle . then , as @xmath84 , the radius of the oscillatory well grows . as known@xcite , in the presence of two potentials with essentially different radii , there occurs the `` rearrangement '' of the energy spectrum on increasing the intensities of the potentials . in our case where the intensity of the short - range attraction becomes close to the critical constant of the appearance of the @xmath19-th level in this well , the lowest level of the other well falls into the well with less radius . on its previous place , the next level falls , etc . in this case , the spectrum for the well with a greater radius is practically renewed and is preserved , until the increase of the intensity of the short - range attraction induces the appearance of a new , @xmath236-th level , and the `` rearrangement '' repeats . as seen from fig.[fig6 ] , this region of the rearrangement of thresholds contains also `` traps '' , because the lines of thresholds depending on @xmath3 are not monotonous . finally , we note that , for the three - particle problem , the nonmonotonicity of the thresholds of stability is a general regularity , which is rather a rule than the exception . one can assume that the nonmonotonicity of thresholds in a three - particle system is a consequence of the difference of the modes of dependence of the ground - state energy of two particles and three - particle energies for the chosen , even simple , interaction potentials . indeed , for simple attractive potentials in a two - particle system , one mode is always realized ; we will say that this is one configuration . at the same time , for the system of three particles with pairwise interaction potentials and greater number of coordinates , various spatial configurations of three particles can be realized . this can induce a change of the modes of the dependence of three - particle energies and thresholds and , therefore , the nonmonotonous behavior of the number of levels of three particles in various regions of parameters of the interaction potentials . we may expect a more complicated behavior of the thresholds of stability in the problems with four and greater number of particles with pairwise interaction potentials . in conclusion , we emphasize that we have systematically studied the energy thresholds of stability for the general quantum problem of three particles interacting by short - range potentials . analytically and by the high - precision calculations of the energy spectra of three particles , we have established the general nonmonotonic dependence of the thresholds of stability on the strengthening ( or the weakening ) of the attraction between particles . as a result , we have revealed a number of new nontrivial universal effects in the behavior of the three - particle thresholds of stability . in the first turn , we mark the effect of a `` trap '' , when the number of three - particle bound states nonmonotonically depends on the strengthening of the interaction between particles . secondly , we have discovered the effect of a `` rearrangement '' of the energy levels and the thresholds of stability , which has no analog in the two - particle systems . at the same time , we have constructed a three - particle generalization of the zeldovich effect of a `` rearrangement '' of the energy levels for the attractive interaction potentials with the modes of attraction which essentially differ by their interaction radii . thirdly , we have revealed both the effect of a `` tube '' for the energy states in the region of a significant repulsion between a pair of identical particles and the effect of a `` wedge '' on the boundary , where the binding energies of two different pairs of particles coincide . we have made a sufficiently full and clear analysis of the dependences of the thresholds of stability on the masses of particles and the form of a short - range interaction , and have also considered different symmetries of states . the revealed regularities are important for the comprehension of the general properties of three - particle systems of different nature . in addition , the possibilities to describe the characteristic peculiarities of thresholds in three - particle systems with the coulomb interaction , as well as those of the states with nonzero angular momenta , are open . these problems will be analyzed in further publications . challenging is also the necessity to study the thresholds of stability for one- and two - dimensional systems , where one can expect significant differences in properties from those in three - dimensional problems . e. nielsen , d.v . fedorov , a.s . jensen , e. garrido , phys . rep . * 347 * , n 5 , 373459 ( 2001 ) . efimov , yad . fiz . * 12 * , iss . 5 , 10801091 ( 1970 ) . grinyuk , m.v . kuzmenko , i.v . simenog , ukr . zh . * 48 * , n 10 , 10141023 ( 2003 ) , lanl e - print nucl - th/0308003 . shermatov , teor . mat . * 136 * , n 2 , 257270 ( 2003 ) . thomas , phys . rev . * 47 * , n 12 , 903909 ( 1935 ) . grinyuk , i.v . simenog , in : _ physics of multiparticle systems _ ( naukova dumka , kyiv , 1985 ( in russian ) ) , iss . 8 , 6695 . simenog , a.i . sitnichenko , ukr . * 28 * , n 1 , 16 ( 1983 ) . symmetric , @xmath21 antisymmetric states relative to the permutations of particles @xmath4 . the asterisks indicate the intersections of the lines of the thresholds of states with different symmetries , the vertical dash - dotted lines in the lower part of the figure are the asymptotes for the lines of thresholds , and the dashed inclined lines correspond to the equality of the binding energies @xmath237 of different pairs of particles.,width=480 ] . to the right , the dependence of the energies of three particles on the strengthening of the attraction is shown : @xmath238 corresponds to the dependence of the ground state energy on the constant @xmath5 ( at @xmath239 ) with the available `` trap '' in the resonance region , @xmath240 corresponds to the dependence of the energies of the ground and first excited levels on the constant @xmath241 ( at @xmath242 ) with the available `` trap '' for the excited state , @xmath243 demonstrates the presence of a `` trap '' for the ground state ( at @xmath244 ) . ]

we have studied the general properties of the energy thresholds of stability for a three - particle system with short - range interaction . a wide region of the interaction constants and various ratios of the masses of particles are considered . the specific effects characteristic of the near - threshold stationary energy levels of three particles are revealed . the asymptotic estimates are obtained for the thresholds at some limiting cases , and the high - precision variational calculations of the thresholds for various values of the interaction constants and the masses of particles are carried out .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Internet Tax Moratorium and Equity Act''. SEC. 2. FINDINGS. The Congress makes the following findings: (1) The moratorium of the Internet Tax Freedom Act on new taxes on Internet access and on multiple and discriminatory taxes on electronic commerce should be extended. (2) States should be encouraged to simplify their sales and use tax systems. (3) As a matter of economic policy and basic fairness, similar sales transactions should be treated equally, without regard to the manner in which sales are transacted, whether in person, through the mails, over the telephone, on the Internet, or by other means. (4) Congress may facilitate such equal taxation consistent with the United States Supreme Court's decision in Quill Corp. v. North Dakota. (5) States that adequately simplify their tax systems should be authorized to correct the present inequities in taxation through requiring sellers to collect taxes on sales of goods or services delivered in-state, without regard to the location of the seller. (6) The States have experience, expertise, and a vital interest in the collection of sales and use taxes, and thus should take the lead in developing and implementing sales and use tax collection systems that are fair, efficient, and non- discriminatory in their application and that will simplify the process for both sellers and buyers. (7) Online consumer privacy is of paramount importance to the growth of electronic commerce and must be protected. SEC. 3. EXTENSION OF INTERNET TAX FREEDOM ACT MORATORIUM THROUGH 2005. Section 1101(a) of the Internet Tax Freedom Act (47 U.S.C. 151 note) is amended by striking ``3 years after the date of the enactment of this Act--'' and inserting ``on December 31, 2005:''. SEC. 4. STREAMLINED SALES AND USE TAX SYSTEM. (a) Development of Streamlined System.--It is the sense of the Congress that States and localities should work together, with the advice of the National Conference of Commissioners on Uniform State Laws, to develop a streamlined sales and use tax system that addresses the following in the context of remote sales: (1) A centralized, one-stop, multi-state registration system for sellers. (2) Uniform definitions for goods or services, whose sale may, by State action, be included in the tax base. (3) Uniform rules for attributing transactions to particular taxing jurisdictions. (4) Uniform procedures for-- (A) the designation and identification of purchasers exempt from sales and use taxes; and (B) immunization from liability for sellers that rely on such State procedures. (5) Uniform procedures for the certification of software that sellers rely on to determine sales and use tax rates and taxability. (6) Uniform bad debt rules. (7) A uniform format for tax returns and remittance forms. (8) Consistent electronic filing and remittance methods. (9) State administration of all State and local sales and use taxes. (10) Uniform audit procedures, including a provision giving a seller the option to be subject to no more than a single audit per year using those procedures; provided that if the seller does not comply with the procedures to elect a single audit, any States can conduct an audit using those procedures. (11) Reasonable compensation for tax collection by sellers. (12) Exemption from use tax collection requirements for remote sellers falling below a de minimis threshold of $5,000,000 in gross annual sales. (13) Appropriate protections for consumer privacy. (14) Such other features that the States deem warranted to promote simplicity, uniformity, neutrality, efficiency, and fairness. (b) No Undue Burden.--The Congress finds that, if adopted, the system described in subsection (a) will not place an undue burden on interstate commerce or burden the growth of electronic commerce and related technologies in any material way. SEC. 5. INTERSTATE SALES AND USE TAX COMPACT. (a) Authorization and Consent.--In general, the States are authorized to enter into an Interstate Sales and Use Tax Compact. Subject to subsection (c), the Congress consents to their entry into that Compact. The Compact shall describe a uniform, streamlined sales and use tax system consistent with section 4(a), and shall provide that States joining the Compact must adopt that system. (b) Expiration.--The authorization and consent in subsection (a) shall expire if the Compact has not been formed before January 1, 2006. (c) Congressional Consent Withdrawn if Compact Disapproved.-- (1) Adopting states to transmit.--Upon the 20th State becoming a signatory to the Compact, the adopting States shall transmit a copy of the Compact to Congress. (2) Congressional action.--The consent of the Congress to the Compact is withdrawn if the Congress, by law, disapproves the Compact within 120 days (computed in accordance with section 154 of the Trade Act of 1974 (19 U.S.C. 2194)) after the adopting States transmit it to the Congress. SEC. 6. AUTHORIZATION TO SIMPLIFY STATE USE-TAX RATES THROUGH AVERAGING. (a) In General.--A State that levies a use tax shall impose a single, uniform State-wide use-tax rate on all remote sales on which it assesses a use tax for any calendar year for which the State meets the requirements of subsection (b). (b) Averaging Requirement.--A State meets the requirements of this subsection for any calendar year in which the single, uniform State- wide use-tax rate is in effect if such rate is no greater than the weighted average of the sales tax rates actually imposed by a State and its local jurisdictions during the second calendar year prior to such calendar year. (c) Computation of Rate No Greater Than Weighted Average.--For purposes of subsection (b), a State-wide use tax rate is no greater than the weighted average of the sales tax rates imposed in a prior calendar year only if, had such rate been assessed during such prior calendar year on all sales on which a sales tax was actually assessed by such State and its local jurisdictions, such rate would not have yielded a greater total assessment of taxes than the total taxes actually assessed on such sales during such year. (d) Annual Option To Collect Actual Tax.--Notwithstanding subsection (a), a remote seller has the annual option of collecting applicable State and local use taxes throughout a State. SEC. 7. AUTHORIZATION TO REQUIRE COLLECTION OF USE TAXES. (a) Grant of Authority.-- (1) States that adopt the system may require collection.-- Any State that has adopted the system described in the Compact is authorized, notwithstanding any other provision of law, to require all sellers not qualifying for the de minimis exception to collect and remit sales and use taxes on remote sales to purchasers located in such State after the expiration of the 120 day period described by section 5(c)(2) unless the Compact is disapproved under section 5(c). (2) States that do not adopt the system may not require collection.--Paragraph (1) does not extend to any State that does not adopt the system described in the Compact. (b) No Effect on Nexus, Etc.--No obligation imposed by virtue of authority granted by subsection (a)(1) or denied by subsection (a)(2) shall be considered in determining whether a seller has a nexus with any State for any other tax purpose. Except as provided in subsection (a), nothing in this Act permits or prohibits a State-- (1) to license or regulate any person; (2) to require any person to qualify to transact intrastate business; or (3) to subject any person to State taxes not related to the sale of goods or services. SEC. 8. LIMITATION. In general, nothing in this Act shall be construed as subjecting sellers to franchise taxes, income taxes, or licensing requirements of a State or political subdivision thereof, nor shall anything in this Act be construed as affecting the application of such taxes or requirements or enlarging or reducing the authority of any State or political subdivision to impose such taxes or requirements. SEC. 9. DEFINITIONS. In this Act: (1) State.--The term ``State'' means any State of the United States of America and includes the District of Columbia. (2) Goods or services.--The term ``goods or services'' includes tangible and intangible personal property and services. (3) Remote sale.--The term ``remote sale'' means a sale in interstate commerce of goods or services attributed, under the rules established pursuant to section 4(a)(3) of this Act, to a particular taxing jurisdiction that could not, except for the authority granted by this Act, require that the seller of such goods or services collect and remit sales or use taxes on such sale. (4) Locus of remote sale.--The term ``particular taxing jurisdiction'', when used with respect to the location of a remote sale means a remote sale of goods or services attributed, under the rules established pursuant to section 4(a)(3) of this Act, to a particular taxing jurisdiction.

Expresses the sense of the Congress that States and localities should work together, with the advice of the National Conference of Commissioners on Uniform State Laws, to develop a uniform streamlined sales and use tax system that addresses remote sales. Authorizes States to enter into an Interstate Sales and Use Tax Compact which shall describe a uniform, streamlined sales and use tax system consistent with such system.

the startling properties of one - dimensional ( 1d ) interacting electrons , commonly referred to as ( non - chiral ) tomonaga - luttinger liquid ( tll ) behavior,@xcite see refs . for reviews , have recently moved into the focus of attention of the mesoscopic physics community . this was in particular prompted by the successful demonstration of electrical transport experiments for a variety of 1d materials , such as semiconductor quantum wires,@xcite fractional quantum hall edge states,@xcite and single - wall carbon nanotubes ( swnts).@xcite in this paper , we mainly focus on electrical transport in swnts to keep the discussion concrete . nevertheless , our results apply also to other systems . shortly after the theoretical proposal of tll behavior in individual metallic swnts,@xcite the first experimental evidence for this peculiar many - body state was reported.@xcite the expected tll power - law scaling in the energy - dependent tunneling density of states @xcite in swnts has been verified experimentally . in later experiments , @xcite transport through an intrinsic quantum dot formed by a double barrier within the swnt has been probed , allowing one to study the well - known resonant or sequential tunneling including coulomb blockade phenomena,@xcite but now for the case of leads formed by strongly correlated electrons . when varying an externally applied gate voltage , the linear conductance then typically displays a sequence of peaks , which can be interpreted as coulomb oscillations or resonant tunneling peaks , depending on the parameter regime . the peak spacing is governed by the charging energy @xmath0 and the plasmon level spacing @xmath1 on the dot ( the latter coincides with the single - particle level spacing @xmath2 for the case of noninteracting electrons ) . we mention in passing that a similar double - barrier experiment has been performed for semiconductor quantum wires , where in fact a tll power - law temperature dependence of the peak conductance was reported.@xcite in the nanotube experiments,@xcite two intramolecular barriers have been created within an individual metallic swnt , and a power - law temperature dependence of the conductance maximum has been reported.@xcite however , the exponent turned out to be inconsistent with expectations based on the sequential tunneling theory for a tll ; see below . the experiments clearly indicate that a detailed theoretical understanding of transport through a double barrier in a tll is required . since the initial theoretical work on this topic,@xcite the double - barrier problem in a tll has attracted a significant amount of attention among theorists.@xcite those works show that the electron - electron interactions present in 1d leads imply significant deviations from the conventional theory for fermi liquid leads.@xcite this is most easily seen through the change of the temperature dependence of the linear conductance peak height , which now exhibits a typical tll power law @xmath3 , where @xmath4 depends on the interaction strength . as is discussed in detail below , for a tll , the exponent @xmath4 reveals the particular tunneling mechanism ruling transport through the dot . swnts possess an additional flavor degeneracy,@xcite which ( together with the spin degree of freedom ) can be captured by an effective four - channel tll model . for an analysis of the linear conductance on resonance , which is the focus of our work , however , a spinless single - channel tll turns out to be sufficient.@xcite within the standard bosonization method,@xcite the tll is then characterized by a boson field @xmath5 with conjugate momentum @xmath6 . including a symmetric double barrier , composed of short - range scattering centers at @xmath7 of strength @xmath8 , the basic hamiltonian is@xcite @xmath9 where @xmath10 is the fermi velocity , @xmath11 , \ ] ] and we put @xmath12 throughout this paper . asymmetric barriers can also be studied using our approach below , but to keep the discussion as simple as possible , we restrict ourselves to the symmetric case alone . the electron - electron interaction strength in the leads is measured in terms of the standard dimensionless tll parameter @xmath13 , where @xmath14 for a fermi gas and @xmath15 for repulsive interactions.@xcite we then have an intrinsic quantum dot within the tll , with a plasmon level spacing @xmath16 , where @xmath17 is the single - particle level spacing , and a charging energy @xmath18 . ( note that our convention for @xmath0 differs from the standard one.@xcite ) finally , the coupling to an applied bias voltage @xmath19 and to an external gate voltage @xmath20 , acting onto the dot s electrons via a capacitance @xmath21 , is encoded in@xcite @xmath22 where @xmath23 with the island capacitance @xmath24 . in eq . ( [ driving ] ) , we used the notation @xmath25 , \nonumber\\ n&= & \frac{1}{\sqrt{\pi}}\left[\vartheta \left(\frac{x_0}{2}\right)-\vartheta \left(-\frac{x_0}{2}\right)\right]+n_0 , \end{aligned}\ ] ] where @xmath26 gives the charge difference between the left and right leads , @xmath27 is the total electronic charge occupying the dot , and @xmath28 describes a possible offset charge . note that with our conventions , @xmath29 decreases ( increases ) when electrons are transferred towards the right ( left ) lead . likewise , @xmath30 increases ( decreases ) for tunneling onto ( out ) of the dot . the hamiltonian ( [ hamg1 ] ) has been studied in most of the previous works on the subject and also forms the basis of our work . the linear conductance through the dot is periodic in @xmath31 , and we can restrict ourselves to one period , @xmath32 , where @xmath33 has a resonance peak at @xmath34 . one can compute @xmath33 analytically for the non - interacting limit , @xmath14 , by refermionizing this model,@xcite @xmath35 ) + w^2 } \ , , \ ] ] with @xmath36 and @xmath37 $ ] , where @xmath38 for the bandwidth @xmath39 , which provides a high - energy cut - off . for strong barriers , eq . ( [ cond1 ] ) leads to the standard breit - wigner resonant tunneling line shape with linewidth @xmath40 . ( for @xmath14 , the infinite - barrier limit is reached already for @xmath41 , where the associated phase shift is in the unitary limit . ) unfortunately , as the model ( [ hamg1 ] ) is not integrable for @xmath15 , exact solutions covering a wide parameter range of interest for this transport problem are out of reach . analytical progress then generally has to rely on approximations . initial work @xcite pursued perturbative approaches , using the renormalization group , instanton methods or cumulant expansions , both for strong and weak barriers . furusaki @xcite presented a detailed study of the _ uncorrelated sequential tunneling _ ( ust ) regime , including also cotunneling contributions important away from the resonance peak . this regime allows for a _ master equation approach _ , whose validity requires that the barriers are sufficiently strong and that the temperature @xmath42 is sufficiently high . for @xmath42 well above @xmath1 but still below @xmath0 , the discrete nature of the plasmon modes on the dot is not relevant while coulomb blockade still exists . then the corresponding results of ref . apply . in particular , one obtains power - law scaling for the peak conductance with @xmath43 , implying that in this case the double barrier effectively acts as a single impurity . in what follows , we only discuss the case @xmath44 . keeping only rates to lowest order in @xmath45 from the tll leads onto the island ( dot ) , which is equivalent to taking the standard ust mechanism , the conductance is given by@xcite @xmath46 where @xmath47 denotes the gamma function , and @xmath48 measures the distance from the resonance peak . the hybridization @xmath49 can be expressed in terms of the 1d density of states , @xmath50 , and the hopping amplitude @xmath51 onto the dot,@xcite @xmath52 the line shape ( [ seq ] ) is rather close to the fermi - liquid form ( [ cond1 ] ) for large barrier heights and evidently characterized by a linear @xmath42 dependence of the linewidth . in the tails of a peak , the conductance ( [ seq ] ) vanishes exponentially , but then also ( elastic ) cotunneling has to be included.@xcite note that the ust peak conductance in eq . ( [ seq ] ) scales as @xmath53 , so that the power - law exponent is @xmath54 . finally , at low temperatures , instead of sequential tunneling , _ coherent resonant tunneling _ is possible , characterized by non - lorentzian universal line shapes,@xcite where the linewidth scales as @xmath55 . in this paper , we only address the incoherent regime by employing a markovian master equation approach . moreover , we focus on the temperature dependence of the peak conductance , for which cotunneling is always a subleading process.@xcite therefore we neglect cotunneling throughout this work . this is not a fundamental restriction to our approach , but implies some technical simplifications . on resonance , the basically only restriction for the validity of our master equation approach is then given by the condition @xmath56.@xcite remarkably , the available experimental data obtained in swnts@xcite seem incompatible with eq . ( [ seq ] ) , since the observed temperature dependence of the conductance peak height @xmath57 does not follow the ust scaling but rather suggests a @xmath58 power law . the exponent @xmath59 has been proposed to arise from a `` correlated sequential tunneling '' ( cst ) mechanism.@xcite cst processes are sequential tunneling processes that can not be subdivided into two uncorrelated steps , yet still can be captured in a master equation framework . such processes have been studied previously in the chemical physics community , e.g. , in the context of electron transfer reactions through an intermediate bridge state . in particular , hu and mukamel@xcite have treated the sequential tunneling regime for this problem using a very similar master equation theory . here we compute the sequential tunneling current through a double barrier in a tll , see eq . ( [ hamg1 ] ) , beyond the lowest order in @xmath45 , implying modifications to eq . ( [ seq ] ) . we analyze to what extent such processes could indeed cause power - law scaling in @xmath60 with the cst exponent @xmath61 . the remainder of the paper is structured as follows . in sec . [ sec2 ] we introduce the general master equation approach , and apply it to the regime of linear transport . the transition rates entering the master equation are evaluated in sec . [ sec3 ] , and in sec . [ sec4 ] explicit results for the temperature dependence of the conductance peak , @xmath60 , are presented . we conclude by discussing our results and their relation to other ( experimental as well as theoretical ) work in sec . [ sec5 ] . technical details concerning sec . [ sec3 ] can been found in the appendix . let us start with the case of large tunneling barriers @xmath8 , which can be described within a dual version of eq . ( [ hamg1 ] ) , see refs . . in this regime , the dynamics is dominated by tunneling events connecting minima of the periodic potential @xmath62 in the @xmath63-plane.@xcite such tunneling events induce a change @xmath64 for tunneling onto / out of the dot , and @xmath65 for tunneling towards the right / left . hence transfer of one unit of charge across the complete double barrier structure requires @xmath66 . the current through the double barrier is then given by @xmath67 where the expectation value stands for a quantum - statistical average with hamiltonian ( [ hamg1 ] ) , and eq . ( [ currentr ] ) has to be evaluated in the stationary long - time limit . the discrete dynamics underlying eq . ( [ currentr ] ) can be described by a master equation@xcite for the probability @xmath68 of being in state @xmath63 at time @xmath69 . master equations have previously been employed for the non interacting case,@xcite and for the tll case to lowest order in @xmath45.@xcite the rates entering the master equation can be extracted as irreducible diagrams for the self - energy,@xcite which to lowest order are simple golden rule rates . these first - order ust contributions to the transition rates imply @xmath70 jumps . below we will systematically take into account transition rates up to second order in @xmath45 . it turns out that the second - order contributions to those rates are plagued by nontrivial divergences , which require a resummation of higher - order diagrams . this resummation is done below by employing the weisskopf - wigner approximation.@xcite on the one hand , this procedure yields a direct cst process , @xmath71 . on the other hand , additional ( indirect ) cst contributions to the transition rates for @xmath70 arise . apart from the need of a regularization scheme , the same situation is encountered in the theory of bridged electron transfer reactions.@xcite the master equation for @xmath68 then has the general structure@xcite @xmath72 where @xmath73 denotes the forward / backward rate for a transition over the left / right barrier , having _ started_with @xmath30 electrons on the dot . in addition , @xmath74 denotes the forward / backward rate for a direct cst transition @xmath66 . moreover , we use @xmath75 which is related to the linewidth of the state @xmath63 . it is useful to also introduce the probability @xmath76 for the dot being occupied with @xmath30 electrons at time @xmath69 . in order to calculate the current @xmath77 , we insert eq . ( [ mastereq ] ) into eq . ( [ currentr ] ) , which yields after some algebra @xmath78 p(n , t\to \infty ) . \label{current3}\end{aligned}\ ] ] summing both sides of eq . ( [ mastereq ] ) over @xmath29 , we obtain a master equation for @xmath79 directly , @xmath80 p(n+1,t ) \nonumber \\ \nonumber & + & \left [ \gamma_l^f(n-1 ) + \gamma_r^b(n-1 ) \right ] p(n-1,t ) .\end{aligned}\ ] ] the stationary solution @xmath81 follows by requiring @xmath82 , which yields the detailed balance relation @xmath83 taking into account conservation of probability , @xmath84 , this relation can be solved recursively . we note that the direct cst rates @xmath74 do not appear in eq . ( [ mesmall ] ) , since they do not alter the net population of the dot . however , they do appear in the current ( [ current3 ] ) . let us now focus on the linear transport regime and sufficiently low temperatures , @xmath85 , where at most two charge states @xmath30 are allowed on the dot due to charging effects.@xcite without loss of generality , we may choose @xmath86 and @xmath87 to label those states . in the linear transport regime , we can disregard the rates @xmath88 , and @xmath89 , since they involve energetically forbidden states with dot occupation numbers @xmath90 or @xmath91 . the recursive solution of the detailed balance relation ( [ detbal ] ) then yields @xmath92 combining eqs . ( [ probs ] ) and ( [ current3 ] ) , we obtain @xmath93 , with the standard contribution@xcite @xmath94 and an additional term caused by direct cst rates , @xmath95 \left [ \gamma_l^f(-1)+\gamma_r^b(-1 ) \right ] + \left [ \gamma_{cst}^f(-1 ) - \gamma_{cst}^b(-1 ) \right ] \left [ \gamma_l^b(0)+\gamma_r^f(0 ) \right ] } { \gamma_r^f(0)+ \gamma_l^f(-1)+\gamma_r^b(-1 ) + \gamma_l^b(0 ) } .\ ] ] so far we have discussed a general procedure to determine the current in the linear regime . to make progress , the transition rates entering the above equations must be computed for the hamiltonian in eq . ( [ hamg1 ] ) . we now systematically compute all rates entering eqs . ( [ currentx1 ] ) and ( [ currentx2 ] ) . rates of order higher than @xmath96 will be included approximately within the weisskopf - wigner scheme . for consistency , besides the direct cst rates , it is also mandatory to include all indirect cst contributions to the rates @xmath97 with @xmath98 and @xmath99 . all these transition rates can be extracted as the irreducible components of an exact perturbation series expression for the probability distribution @xmath68 . the latter corresponds to the diagonal element of the reduced density matrix ( rdm ) , which in turn allows for a path - integral representation.@xcite tracing out the gaussian tll modes away from the barriers at @xmath100 , one obtains an effective action which is equivalent to the action of a quantum brownian particle hopping in the @xmath63-plane.@xcite then a path can be visualized in the @xmath101-plane of the rdm , see fig . [ fig.plan ] , with a corresponding dynamics in the @xmath102-plane . alternatively , the rate expressions given below can also be derived using the projection operator formalism.@xcite the rates @xmath97 for a transition @xmath70 then have contributions of first and at least second order in @xmath45 , @xmath103 where we keep only the @xmath104 states . the first - order contribution is well - known,@xcite and schematically depicted in fig . [ fig.ust](a ) . there are two independent ( uncorrelated ) steps , one from the left tll `` lead '' onto the island , and another to the right tll `` lead '' . using the hopping matrix element @xmath51 in eq . ( [ gamma0 ] ) , these steps individually correspond to irreducible golden rule rates , @xmath105 , \ ] ] where @xmath106 , with the correlation functions@xcite @xmath107 \\ \nonumber & & \times\coth(\omega/2 t ) + i\sin(\omega t)\}.\end{aligned}\ ] ] the spectral densities follow as @xmath108,\ ] ] where @xmath109 , @xmath110 , and @xmath111 is the plasmon level spacing on the dot . the @xmath112-peaks are a result of the finite level spacing on the dot , while the first part in eq . ( [ spectral ] ) yields a standard ohmic spectral density . the bandwidth @xmath39 is taken as smooth ( exponential ) ultraviolet cutoff for the model ( [ hamg1 ] ) . these correlation functions arise in the process of integrating out the tll modes away from the barrier , see ref . for a detailed review of this procedure . finally , the energies @xmath113 appearing in eq . ( [ lowestorder ] ) are defined as @xmath114 with the electrochemical potential @xmath115 the correlation function @xmath116 can be decomposed into two different parts,@xcite namely an ohmic part @xmath117 and an oscillatory part @xmath118 . here the first contribution comes from the smooth part in @xmath119 , and takes the standard form @xmath120 + i(\pi / g ) { \rm sgn } ( t)\\ & = & s_{\rm ohm}(t ) + i r_{\rm ohm}(t ) . \label{ohmic}\end{aligned}\ ] ] at low temperatures , @xmath121 , the dot correlation function is given by its @xmath122 limiting form @xmath123 up to exponentially small corrections in @xmath124 . this function arises due to the finite level spacing , and is periodic in @xmath69 with period @xmath125 . it can therefore be expanded in a fourier series,@xcite leading to @xmath126 the fourier coefficients @xmath127 can be found in the appendix , and from eq . ( [ ohmic ] ) , one gets@xcite @xmath128 which in turn directly leads to eq . ( [ seq ] ) . we note that the first - order forward / backward rates ( [ lowestorder ] ) fulfill a detailed balance relation @xmath129 which formally follows from the reflection property @xmath130 of the above correlation functions . .all transition processes of order @xmath131 contributing to the master equation . the off - diagonal states @xmath132 and @xmath133 are specified in fig . [ fig.plan ] . [ tab.paths ] [ cols="^,<",options="header " , ] we mention in passing that in contrast to the first - order contributions in sec . [ sec31 ] , the above indirect cst contributions do not obey detailed balance . this is true although the correlation functions entering these rates in table [ tab.diag ] still have the reflection property . the violation of the detailed balance relation follows directly by inspection of the triple integrals in table [ tab.diag ] , i.e. , forward and backward rates are not linked by a relation of the form ( [ detbalance ] ) . of course , the total rates and populations of the states are still linked by detailed balance , but there is no reason why individual rates should obey eq . ( [ detbalance ] ) . a simple example for this fact is given by superexchange rates in electron transfer theory,@xcite see also ref . for related observations . the direct cst rates @xmath134 for a transition @xmath135 have only contributions of at least order @xmath96 . there are two possible transition processes cst1 and cst2 , see table [ tab.paths ] and figs . [ fig.plan ] and [ fig.cst](b ) . the corresponding transition rates are simply @xmath136 these relations hold not only on resonance but in general . since cst transitions do not alter the stationary population @xmath137 , they do not enter the linewidth ( [ linewidth ] ) . the rates @xmath134 _ per se _ are also not subject to a detailed balance relation ( [ detbalance ] ) . note that the cotunneling diagram in fig . [ fig.ust](b ) is subleading on resonance and therefore not taken into account here . on resonance , @xmath138 , and hence forward and backward rates are equal , @xmath139 neglecting the @xmath140-term as explained above , the self - consistency equation for @xmath141 can then be written as @xmath142 this quadratic equation has two real solutions , as long as the dimensionless parameter @xmath143 , where @xmath144 if indeed @xmath143 , these solutions are given by @xmath145 \frac{1 \pm \sqrt{1-\xi}}{2 } .\ ] ] for @xmath146 , we thus have @xmath147 and @xmath148 . for @xmath149 , the two solutions are complex valued , and @xmath141 acquires an imaginary part . if this happens , the description in terms of the master equation in combination with the weisskopf - wigner approximation is questionable and not used below . we identify the linewidth with the solution @xmath150 , since we recover the well - known result@xcite @xmath151 when second - order rates are neglected , while then @xmath152 . the requirement @xmath143 typically results in a temperature @xmath153 determined by @xmath154 below which our weisskopf - wigner theory becomes problematic . this equation yields @xmath153 provided @xmath155 and @xmath156 ( assumed independent of temperature ) are known . however , since no reliable low-@xmath42 estimates for @xmath157 are available , see table [ tab.acg ] , it is often difficult to provide good estimates for @xmath153 . of course , the validity of the master equation in addition always requires @xmath158 . in what follows , the parameter @xmath156 is assumed to be temperature independent and given by its value at @xmath159 in fig . [ fig.acg ] . although we expect @xmath160 to be constant ( see above ) , we can not rule out that this is approximative . the linewidth @xmath161 now consists of two contributions . the first term in eq . ( [ lingam ] ) is @xmath162 , while the second term is constant due to the @xmath42 independence of @xmath156 . this implies a crossover from power - law scaling of @xmath161 to a basically constant @xmath141 as the temperature is lowered . this crossover depends in an essential way on the tunneling amplitude @xmath51 . results for @xmath161 from eq . ( [ lingam ] ) are shown in fig . [ fig.linewdel60](a ) , taking @xmath163 and @xmath164 . figure [ fig.linewdel60](b ) shows ( for several @xmath42 ) that the validity condition @xmath143 , with @xmath165 defined in eq . ( [ xi ] ) , is indeed fulfilled . this choice for @xmath51 reflects rather transparent barriers , where cst effects are clearly pronounced . obviously , at low @xmath42 , fig . [ fig.linewdel60 ] suggests that @xmath141 is essentially independent of temperature . this behavior is most pronounced for strong interactions ( small @xmath13 ) . going towards less transparent barriers , @xmath161 is shown in fig . [ fig.linewdel30 ] for @xmath166 . in sec . [ sec5 ] , we argue that the hopping amplitudes @xmath51 appropriate for the experiment in ref . and for the numerical simulations in ref . are comparable to this value . now a crossover from the ust power law at high temperatures to an approximately @xmath42-independent behavior at low @xmath42 becomes apparent . for @xmath167 , we now find @xmath149 , implying that our approach breaks down for such interactions . finally , for very high barriers , @xmath168 , the linewidth is _ always _ dominated by the ust term , in accordance with standard reasoning.@xcite this is illustrated in fig . [ fig.linewdel01 ] , where results for @xmath141 at @xmath169 are depicted . in this regime , higher - order corrections are obviously negligible . remarkably , for weak interactions , the linewidth @xmath141 is always dominated by the ust result over the _ entire _ range of temperatures where the master equation approach is valid ( @xmath170 ) . cst effects then apparently do not have a finite domain of observability in the limit of weak interactions . we can therefore rationalize that previous calculations that essentially expand around the noninteracting case @xcite do not observe a clear cst power - law scaling . the fate of cst effects near the noninteracting limit @xmath14 will be further discussed at the end of sec . we conclude that _ for cst effects to be observable , it is essential to allow for rather transparent barriers , a finite level spacing , and intermediate - to - strong interactions . _ the parameter regime where cst plays a role is therefore rather narrow . the linear conductance @xmath33 follows directly from eqs . ( [ currentx1 ] ) and ( [ currentx2 ] ) by performing the derivative with respect to the transport voltage @xmath19 . moreover , since we are interested in the conductance maximum at resonance , we can put @xmath171 . for the first - order rates , the detailed balance relation ( [ detbalance ] ) can be exploited . for the second - order rates , we find the relation @xmath172 . finally setting @xmath173 , we obtain @xmath174 where @xmath175 here the prime denotes the derivative @xmath176 , taken at @xmath173 , and we omit the arguments of the rates , since on resonance they are all equal . the dominant term is the first term in @xmath177 . in order to show that the second term @xmath178 is always negligible against @xmath177 , it is instructive to evaluate the second class of diagrams ( @xmath179 ) in table [ tab.diag ] within a simple approximation . since at long times the ohmic part in @xmath180 cancels out in the square - bracketed terms of the corresponding rate expressions in table [ tab.diag ] , one may replace @xmath181 by @xmath182 in those square brackets . after this replacement , the fourier expansion method discussed in the appendix applies to all eight diagrams , with fourier sums including terms like @xmath183 . these sums can easily be calculated numerically . for all cases that are described below ( and many more not shown here ) , we find that @xmath178 is numerically zero . although it looks like the direct cst rates @xmath184 have effectively no influence in the end , this is not true since they exactly cancel certain contributions to the conductance coming from the indirect rate @xmath185 . in that sense , the direct cst diagram , jumping by two steps along the diagonal of the reduced density matrix via an intermediate diagonal state , see fig . [ fig.plan ] , but without cutting the diagram in the intermediate state , is crucial for cst effects in the conductance maximum @xmath57 . such diagrams are known to cause important effects in other systems,@xcite but were previously not taken into account since the main focus was on the limit @xmath168 . hence we find for the conductance maximum @xmath186 judging from our numerical results for @xmath187 , the @xmath188 should in fact be replaced by an exact equality , although we have no analytical proof for this statement . for @xmath189 , we find @xmath190 , leading to the ust result ( [ seq ] ) . however , for @xmath191 , @xmath161 stays approximately constant , and hence an approximate power - law behavior follows , @xmath192 with the cst exponent @xmath59 . we stress that eq . ( [ gcst ] ) is not meant in the sense of universal power - law scaling behavior . the crossover between ust and cst - dominated regimes occurs around a temperature @xmath193 discussed below . the effective doubling in the exponent reflects the physics of this correlated transport process . for @xmath194 , plasmon modes excited on the island will correlate electrons in both leads . since each lead has a end - tunneling density of states @xmath195 , correlated transport leads to an effective doubling in the exponent due to the presence of two leads.@xcite results for @xmath196 at @xmath197 are shown in fig . [ fig.conddel30 ] and follow eq . ( [ gcst ] ) at low @xmath42 . for @xmath198 , the master equation breaks down ( @xmath57 exceeds @xmath199 ) , while for @xmath200 , the validity condition @xmath143 is violated . nevertheless , there is a well - defined region of applicability , where cst effects are important and observable . finally , for @xmath201 , the expected ust scaling is recovered , see the inset of fig . [ fig.conddel30 ] . the crossover between the ust and cst regimes is characterized by a temperature @xmath202 , which in turn follows from the condition that both contributions to @xmath141 in eq . ( [ lingam ] ) be equal , @xmath203 . although @xmath204 contains the sum over all fourier modes , see eq . ( [ ustrate ] ) , the zero mode @xmath205 dominates on resonance , implying the condition @xmath206 . this leads to the crossover temperature @xmath207 where we use the abbreviation @xmath208 in fig . [ fig.tcg ] , results for the crossover temperature @xmath193 are shown as a function of @xmath209 for the tll parameters @xmath210 and @xmath211 , always respecting the validity conditions @xmath212 and @xmath213 . generally , @xmath193 increases when increasing @xmath51 and/or decreasing @xmath13 , i.e. , for more transparent barriers and/or stronger interactions . apparently , for weak interactions , @xmath214 , the @xmath51 dependence of @xmath193 becomes very steep , restricting the cst regime to extremely low temperatures for reasonable @xmath51 . in practice , at such low temperatures coherent resonant tunneling processes dominate , rendering cst effects unobservable . for stronger interactions , however , cst effects can be pronounced even for moderately transparent barriers at low temperatures . by using a master equation approach , linear transport in a tll with two tunneling barriers forming a quantum dot has been studied . we find an approximate power - law temperature dependence of the peak conductance in the linear transport regime , with a characteristic @xmath13-dependent exponent , where @xmath13 is the tll parameter . by including second - order contributions to the tunneling rates in combination with a self - consistent weisskopf - wigner regularization , a comprehensive picture has been obtained . for temperatures below the plasmon level spacing @xmath215 for dot size @xmath216 , the dominant transport mechanism depends on the transparency @xmath51 of the barriers . for sufficiently transparent barriers , @xmath217 , we find that correlated sequential tunneling ( cst ) is important , leading to an approximate power law with exponent @xmath59 , while for very high barriers ( @xmath218 ) , the uncorrelated sequential tunneling ( ust ) exponent @xmath54 is recovered . note that despite the large @xmath51 necessary to reach the cst regime , the master equation should still apply as the peak conductance remains small . we have determined the crossover temperature @xmath193 separating both regimes . as a function of the physical parameters ( @xmath219 , it is given by eq . ( [ tcc ] ) , where the dimensionless number @xmath156 can be read off from fig . [ fig.acg ] . for @xmath220 , the cst mechanism is effective , while for @xmath189 , the ust picture is recovered . the peak conductance in the cst regime has been derived and is given by eq . ( [ condmax ] ) , with the well - known first - order rates @xmath204 specified in eq . ( [ ustrate ] ) . the linewidth parameter @xmath141 as a function of the physical parameters is given in eq . ( [ lingam ] ) . these relations allow for a comparison to existing work and provide estimates for the parameter regime where such effects should be of importance . notice that the modification of the standard picture of sequential tunneling here arises due to a renormalization of @xmath141 by higher - order processes , and we have given a physical explanation for this mechanism above . our findings regarding approximate cst power laws in @xmath60 are consistent with recent numerically exact real - time quantum monte carlo simulations @xcite and also with experimental observations . let us first discuss the experimental work on swnts,@xcite where the conductance through the dot followed the cst power law ( [ gcst ] ) . from the exponent , the interaction strength was deduced to be @xmath221 , corresponding to a tll parameter @xmath222 for the charged sector of the effective four - channel tll theory of swnts.@xcite the quantum dot was formed by two nearby buckles acting as tunneling barriers . since cst effects are predicted only for quite transparent barriers , it is instructive to estimate @xmath51 . this is simpler for a single buckle used in earlier experiments,@xcite where also a power - law linear conductance @xmath223 was observed . the single - barrier case is analytically solvable,@xcite and for a high barrier , @xmath224 the measurements@xcite for @xmath225 yield together with @xmath221 a barrier transparency @xmath226 mev , taking a bandwidth of @xmath227 ev ; see ref . . assuming that the buckles have similar features when two are designed in a row , we can now establish a connection to the double - barrier case . in ref . , @xmath228 mev was measured , yielding @xmath229 , consistent with our conclusions above . for cst to be operative , one needs finite level spacing , low ( but not too low ) temperatures , and not too high barriers . these conditions apparently were met in the swnt experiments in ref . . let us then comment on the monte carlo results of ref . , where also the cst power law ( [ gcst ] ) has been found . for a direct comparison , we determine @xmath51 for the potential strength @xmath8 used in fig . 4 of ref . . using eq . ( [ gamma0 ] ) , for the simulation parameters @xmath230 , and @xmath231 , we find @xmath232 , again consistent with our conclusions . we note in passing that eq . ( [ gcst ] ) has been obtained in ref . starting from finite - range interactions among the electrons . the divergence has been regularized by summing up a selection of higher - order terms . however , this selection was too strict,@xcite leading to the incorrect conclusion that finite - range interactions would be a prerequisite for cst to occur . as shown here , also zero - range interactions suffice , as long as the tunneling barriers are not too high . we emphasize that for fermi liquid leads ( @xmath14 ) and @xmath121 , one finds @xmath233 both within a ust and a cst analysis . several researchers recently approached the double - barrier tll problem by considering weak interactions , @xmath13 close to 1 , without evidence for cst scaling.@xcite as we have discussed in sec . [ sec4 ] , in this weak - interaction limit , the crossover temperature @xmath193 very quickly goes to zero when decreasing @xmath51 , excluding cst effects for weak interactions even for finite level spacing . put differently , for @xmath13 close to 1 , the master equation approach for large @xmath51 will always break down ( @xmath165 becomes larger than 1 ) upon lowering @xmath42 _ before _ cst sets in . therefore our results are in fact consistent with previous results.@xcite furthermore , the functional renormalization group calculation of ref . @xcite reported traces of an `` apparent '' power law ( as opposed to true scaling ) that could be linked to the cst mechanism . finally , komnik and gogolin@xcite presented an exact solution of a related model at the point @xmath234 . in their model , however , there is _ no sequential tunneling regime at all _ , and therefore we believe that this represents a non generic situation that has nothing to say about the issues at stake here . this point has also been clarified in other recent publications.@xcite unfortunately , this also excludes the possibility of an independent analytical check of our results . to conclude , we hope that these novel features of interacting one - dimensional electrons will stimulate other theoretical work as well as further experimental checks of the cst versus ust picture put forward here . we thank a.o . gogolin , v. may , yu . nazarov , u. weiss , and especially j. stockburger for discussions . this work has been supported by the eu network dienow , the sfb tr/12 , and the gerhard - hess program of the dfg . to evaluate the rate expressions in sec . [ sec3 ] , we often need the quantities @xmath235 and @xmath236 . exploiting the periodicity of these correlation functions with period @xmath125 , it is convenient to perform a fourier expansion , @xmath237 we note that eqs . ( [ wdot ] ) and ( [ wdelta ] ) imply that these fourier coefficients are real . for low temperatures @xmath42 , but keeping leading corrections in @xmath124 , one finds , with the heaviside function @xmath238 : @xmath239 note that @xmath240 . the fourier coefficients are shown in figs . [ fig.fourierdc ] and [ fig.fouriervw ] for @xmath210 and @xmath194 . in that case , the @xmath122 form of the correlation functions ( [ wdot ] ) and ( [ wdelta ] ) can be taken . since the number of non zero fourier coefficients is not exceedingly large , a quick , very accurate , and reliable numerical scheme can be implemented for the evaluation of diagrams of the first class . next , as mentioned in sec . [ sec32 ] , we show in detail how diagrams of the first class ( @xmath241 ) in table [ tab.diag ] have been handled , taking @xmath242 as concrete example . we consider the expressions on resonance and for low temperature @xmath121 . after inserting the above fourier expansions , the integration over @xmath243 can be performed directly . since @xmath244 , the ` @xmath245 ' in the square bracket expression in @xmath246 , see table [ tab.diag ] , is exactly canceled by the corresponding fourier term . we find where we have introduced the notation @xmath248 , and analogously for @xmath249 . the prime in @xmath250 indicates that the term with @xmath251 is excluded from the sum . next , we define the dimensionless kernels [ cf . ( [ ohmic ] ) and ( [ ohmicrate ] ) ] @xmath252 \nonumber \\ & = & \frac{2 \varepsilon}{\delta^2 } \gamma_{\rm ohm } ( e ) , \\ k_{\rm i } ( e ) & = & \varepsilon \int_0^{\infty } d\tau e^{-s_{\rm ohm}(\tau ) } \sin \left [ e \tau - r_{\rm ohm}(\tau)\right ] , \nonumber \label{kernk}\end{aligned}\ ] ] such that for completeness , we finally summarize the corresponding results for the remaining diagrams of this type , @xmath259 . the final result for each diagram will be of the form ( [ funcdep ] ) , with @xmath260 and finally , we explain why we expect @xmath160 to be @xmath42 independent , focusing on diagrams of the first class ( @xmath262 . using eqs . ( [ abc1 ] ) and ( [ abc2 ] ) , the only @xmath42-dependent terms are the @xmath263 defined above . although @xmath264 has a power - law @xmath42 dependence with @xmath265 , for finite energies @xmath266 , and hence for @xmath121 , the @xmath42 dependence is exponentially suppressed since the finite level spacing acts as an effective energy bias , see eqs . ( [ kernk ] ) and ( [ ohmicrate ] ) . similar arguments apply to @xmath267 , which can be evaluated numerically in a straightforward manner . although no closed analytical expression can be given , the overall @xmath42 dependence follows directly from these considerations .

the problem of resonant tunneling through a quantum dot weakly coupled to spinless tomonaga - luttinger liquids has been studied . we compute the linear conductance due to sequential tunneling processes upon employing a master equation approach . besides the previously used lowest - order golden rule rates describing uncorrelated sequential tunneling ( ust ) processes , we systematically include higher - order correlated sequential tunneling ( cst ) diagrams within the standard weisskopf - wigner approximation . we provide estimates for the parameter regions where cst effects can be important . focusing mainly on the temperature dependence of the peak conductance , we discuss the relation of these findings to previous theoretical and experimental results .

the liver plays an important role in the regulation of whole body lipid and carbohydrate homeostasis during fluctuations in nutrient intake . during fasting , hepatocyte glucose output is facilitated by an altered metabolic state wherein fatty acids are preferentially oxidized as an energy source to prevent the catabolism of glucose . in contrast , food intake triggers a rapid switch in hepatocyte metabolism that promotes the oxidation and metabolism of excess carbohydrates to glycogen and fat . with feeding , the acetyl - coa carboxylase ( acc ) enzymes acc1 and acc2 are important regulators of these metabolic transitions through their product malonyl - coa . acc1 is localized in the cytosol and generates malonyl - coa for de novo lipogenesis , while acc2 is bound to the mitochondrial outer membrane and produces malonyl - coa that can be used both as a substrate for lipogenesis and as a negative modulator of mitochondrial fat oxidation by inhibiting carnitine palmitoyltransferase 1a ( cpt1a ) . thus , acc - dependent malonyl - coa production is considered to be a central control point for metabolic flexibility . both acc isotypes are susceptible to dysregulation and are commonly over - expressed or over - activated in disease states associated with fatty liver [ 79 ] . simple hepatosteatosis alone is thought to have a benign course , but up to 25% of patients progress to advanced diseases . fatty liver disease is a risk factor for insulin resistance , diabetes , and hepatocellular cancer . thus , there is considerable interest in developing small molecule drugs that inhibit acc enzymes . recently , it was shown that chronic activation of acc enzymes in mice is sufficient to increase hepatic fat accumulation ; however , it remains unclear how the complete and chronic inhibition of acc activity will impact liver lipid content , whole body metabolic physiology , or the metabolic fate of cytosolic acetyl - coa in hepatocytes . to investigate these questions ozgene australia ( murdoch , australia ) was contracted to generate acc1 and acc2 floxed mice described previously . acc1 and acc2 floxed mice were bred with c57bl/6 flpe mice to delete the neomycin selection cassettes . to generate liver - specific deletions , female acc1/acc2 mice were bred with male acc1/acc2 mice expressing liver - specific albumin - cre . offspring from this cross produced a 1:1 ratio of ldko ( liver - specific double acc knockout ) to flox control offspring . dark cycle and fed normal chow ad libitum ( 7912 teklad lm-485 from harlan laboratories ; 25 kcal% protein , 17 kcal% fat and 58 kcal% carbohydrates ) . all animal experiments were performed according to standard operating procedures approved by the institutional animal care and use committee at university of virginia . oxygen consumption rate ( vo2 ) and respiratory control ratio ( rcr ) were measured under consistent environmental temperature ( 2022 c ) using an indirect calorimetry system ( oxymax series , columbus instruments , columbus , oh ) , as described . studies were commenced after acclimation to the metabolic chamber with airflow of 0.5 l / min . gas samples were measured at 16-min intervals over a 24 h period with food and water provided ad libitum unless indicated otherwise . primary hepatocytes from control and ldko mice were isolated based on established protocol , seeded in dulbecco 's modified eagle 's medium ( dmem ) supplemented with 4.5 g / l glucose , 10% fetal bovine serum , 1 m dexamethasone and 0.1 m insulin for 4 h , and cultured overnight prior to experiment in serum - free dmem with 4.5 g / l glucose , 0.2% bovine serum albumin , 100 nm dexamethasone and 1 nm insulin . for protein acetylation experiments , primary hepatocytes were treated with nicotinamide ( nam ) at 5 mm for 24 h. for insulin stimulation experiments , hepatocytes were cultured in serum - free dmem with 1 g / l glucose , 0.2% bovine serum albumin , 100 nm dexamethasone and no insulin for 3 h prior to addition of insulin for 10 min . substrate competition assays were performed on monolayered hepatocytes ( 20,000 cells / cm ) in krebs - ringer phosphate buffer ( 1.2 m nacl , 6 mm na2hpo4 , 60 mm kcl , 4 mm nah2po4 , 12 mm mgso4 , 125 mm hepes ph7.4 , 10 mm cacl2 ) supplemented with non - labeled substrates : 50 m acetate , 5 mm glucose , 0.5 mm glutamine , 125 m palmitate and 1 mm carnitine , and one of the following radioactive labeled substrates : 10 ci / ml c - acetate ( de novo lipogenesis ) , 10 ci / ml h - glucose ( glycolysis ) or 2 ci / ml c - palmitate ( fatty acid oxidation ) . cells were incubated in sealed wells at 37 c for 1.5 h. lipids were extracted by the folch method and analyzed by scintillation counting or thin - layer chromatography to measure de novo lipogenesis . palmitate oxidation was determined by acidifying each well with 2 m perchloric acid and trapping carbon dioxide in 2 m naoh in a small tube placed in the well . acid soluble c - labeled metabolites were extracted by centrifugation to determine incomplete palmitate oxidation . glycolysis was measured by scintillation counting h - glucose that was converted to h - h2o using the diffusion equilibrium method . measurements of the activity of oxidative enzymes involved in metabolism and mitochondrial function were performed as described previously . acetyl - coa levels were measured by mass spectrometry using methods described in refs . . for quantification in mouse liver , tissue pieces ( 40 mg ) were homogenized in 500 l ice - cold isolation media ( 250 mm sucrose , 10 mm tris hcl and 1 mm egta ) , and centrifuged at 800 g for 5 min at 4 c to pellet cell debris and nuclei . cleared cell lysate was centrifuged at 10,000 g for 10 min at 4 c to obtain a pellet enriched in mitochondria . pellets were resuspended in 1 ml of 6% perchloric acid , and the supernatant ( cytoplasm and microsome ) fraction was mixed with an equal volume of 12% perchloric acid . c-3-malonyl - coa ( 0.5 m final ) was added as a recovery standard . after centrifugation and ultracentrifugation of extract , supernatant was applied to a solid - phase extraction column ( oasis hlb 1 cc30 mg , waters ) preconditioned with acetonitrile then milliq water . bound acyl - coas were washed with milliq water , eluted with acetonitrile , dried under nitrogen gas at 37 c , and resuspended in 120 l of solvent a ( 2% acn , 10 mm ammonium acetate , 5 mm acetic acid , 10 mm dipea ) and analyzed by hplc ms . analyses were performed using a triple quadrupole mass spectrometer ( ab - sciex 4000 q - trap ) coupled to a shimadzu lc-20ad lc system equipped with a supelco discovery c18 column ( 50 mm 2.1 mm 5 m bead size ) integrated with a precolumn ( 4 4 mm ) . a binary solvent system ( total flow 0.25 ml / min ) was used that consisted of the following solvents , a : 98.6% h2o , 2% acetonitrile , 5 mm acetic acid , 10 mm n , n - diisopropylethylamine , 10 mm ammonium acetate ; b : 75% acetonitrile , 25% solvent a. chromatographic runs started at 100% a for 1 min , a linear gradient to reach 100% at 3.5 min , then 100% b for 2 min , and finally 100% solvent a for 2.5 min ( 8 min total ) . column temperature was set to 30 c and the flow rate was 0.5 ml / min . measurements were carried out in positive mode using previously published transitions for acetyl - coa ( m / z 857.2 m / z 350.2 ) and c - malonyl - coa ( m / z 810.4 m / z 303.2 ) using the following settings ( dp , ep , ce , cxp , in volts : 91 , 10 , 43 , 8 ; 106 , 10 , 41 , 10 ; 116 , 10 , 43 , 10 ) . quantification was carried out by measuring peak areas using the software analyst 1.5.1 that were corrected for recovery using c - malonyl - coa as an internal standard . liver tissue was dounce homogenized in 9 m urea with addition of complete edta - free protease inhibitor cocktail ( roche ) , 10 mm nicotinamide , and 50 mm butyric acid . after sonication on ice for 30 seconds , lysates were centrifuged at 10,000 g and assayed for protein content using the bca method . protein extracts were reduced with 5 mm dtt and alkylated with 15 mm iodoacetamide . a 2.5 mg aliquot of protein from each sample was diluted 5-fold with 50 mm tris ph 8.2 and digested overnight with trypsin ( promega ) at 37 c . the resulting peptides were acidified to ph 2 with trifluoroacetic acid ( tfa ) and desalted ( but not eluted ) using a tc18 seppak cartridge ( waters ) prior to on - column isotopic labeling of primary amines by reductive dimethylation . after desalting , 5 ml of labeling reagent ( light : 0.4% ch2o , 60 mm nacnbh3 in 0.5 m mes ph 5.5 , heavy : 0.4% cd2o , 60 mm nacnbd3 in 0.5 m mes ph 5.5 ) was passed through the column at approximately 0.5 ml / min . the reaction was quenched by 15 column volumes of 1% tfa , washed with 0.5% acetic acid . labeled peptides were eluted and mixed in a 1:1 ratio for further analysis . immediately after mixing heavy ( + 34.0689 da ) and light ( + 28.0313 da ) peptides , a 100 g aliquot peptides were resuspended in 0.1% nh4oh and fractionated in step - wise format with increasing concentrations of acetonitrile on microfilters constructed in - house using ph - resistant sdb - xc reverse phase chromatography material ( 3 m empore ) . eluates were dried by vacuum centrifugation and stored at 20 c prior to further analysis . labeled peptides containing acetylated lysines were enriched after mixing by immunoaffinity purification . briefly , 4.9 mg of dried peptides were resuspended in 50 mm mops - naoh ph 7.2 , 10 mm na2hpo4 , 50 mm nacl and incubated overnight at 4 c with pre - conjugated acetyl - lysine antibody ( immunechem ) . acetylated peptides were desalted and fractionated in a step - wise format with increasing concentrations of nh4hco3 using microfilters constructed in - house using scx material ( 3 m empore ) . eluates were desalted , dried , and stored at 20 c prior to further analysis . samples were subjected to reverse phase liquid chromatography on an easy nlc ( thermo ) equipped with a 40 cm 75 m column packed in - house with 1.9 m reprosil c18 particles ( dr . maisch ) and online analyzed by tandem mass spectrometry in a q - exactive ( for unmodified peptides , 90 min gradients ) or an ltq orbitrap velos ( for acetylated peptides , 120 min gradients ) . mass spectra were acquired using a data dependent acquisition method ( twenty most intense precursors selected for fragmentation ) with dynamic exclusion ( 30 seconds ) . raw spectra were converted to mzxml open data format and searched using sequest against a concatenated forward and reverse version of the uniprot mouse protein sequence database ( v11/29/2012 ) , digested with trypsin and allowing for up to two missed cleavages . fragment ion tolerance was 0.36 for ltq - orbitrap - velos data and 0.01 for q - exactive data . carbamidomethylated cysteine ( + 57.021464 ) , dimethylated lysine ( + 28.0313 ) , and dimethylated peptide n - terminus ( + 28.0313 ) were searched as fixed modifications . oxidized methionine ( + 15.994915 ) , heavy dimethylated lysine ( + 6.03766 ) , and heavy dimethylated peptide n - terminus ( + 6.03766 ) were searched as variable modifications in all cases . for acetyl - lysine enriched samples , an additional variable lysine modification was used : + 13.97926 , which corresponds to the difference between an acetyl group ( + 42.0105 ) and the fixed dimethyl group ( + 28.0313 ) . this accounts for the fact that a lysine can be acetylated or dimethylated , but not both . identified peptides were filtered to a false discovery rate of < 1% and allowing only peptides that were correctly labeled and a minimum of 7 amino acids in length . for protein analysis , peptides were additionally filtered to a protein level fdr of < 1% . in general , because acetylation events cause missed cleavages to occur yielding only one possible lysine candidate , site localization was not an issue . nevertheless , localization scores and site refinement were performed using an in - house implementation of the ascore algorithm where an ascore > 13 equates to p < 0.05 . maximum peak intensities and heavy - to - light ( h / l ) ratios for identified peptides were calculated using an in - house peptide quantification algorithm . to be considered for quantitation , we required a peptide signal to noise ratio > 5 . for most peptides ( > 90% ) , both light and heavy isotope intensities were measured . if only one isotope was measured , a ratio was calculated between peptide intensity and local noise . when more than one peptide was measured , the average h / l ratio was computed . for protein quantitation , h / similarly , for acetylation site quantitation , h / l ratios for peptides mapping to the same site were averaged . both the acetylation site data and protein data were normalized to the median protein ratio . finally , acetylation site quantifications were individually corrected for changes in its respective protein by subtracting the log2 ratio of the parent protein from the acetylation site ratio . protein identifications were mapped to gene ontology cellular component terms using gene sets from the molecular signatures database msigdb . for mitochondrial protein analysis , the mouse mitocarta database was converted to uniprot identifiers and used to assign high confidence mitochondrial proteins to the datasets . metabolic pathways and proteins were manually curated from iubmb - nicholson metabolic pathway diagrams ( http://www.iubmb-nicholson.org ) , and plotted according to log2 fold change using cytoscape v2.8.3 . acetylated proteins were queried for enrichment against a background containing all proteins found in the proteome dataset . to measure hepatic triglyceride production rate , female mice ( 12 wks of age ) / kg body weight poloxamer 407 and serum triglyceride levels were measured over 24 h. mice were fasted from 9 am1 pm , and tail vein whole blood was sampled prior to injection then at 1 , 2 , 6 , and 24 h after injection . to determine oral triglyceride tolerance , mice were fasted for 4 h ( 8 am12 pm ) prior to receiving safflower oil by oral gavage ( 10 l / g body weight ) . tail vein blood was sampled prior to gavage then hourly for 6 h. serum was isolated and stored at 20 c until triglyceride assay ( pointe scientific ) . submandibular whole blood was sampled from 16-week - old mice at fed ( 9 pm ) then 12 h fasted states . serum was isolated by centrifugation at 2,000 g for 15 min at 4 c . metabolites were determined according to manufacturers ' protocols : triglyceride assay ( pointe scientific ) ; cholesterol assay ( infinity cholesterol liquid reagent , thermo scientific ) ; free fatty acid assay ( biovision ) ; insulin elisa ( crystal chem inc ) ; ketone assay ( cayman ) ; nad assay ( bioassay system ) . liver samples were fixed in 10% neutral buffered formalin and paraffin - embedded for microtome sectioning ( 5 m thick ) and hematoxylin eosin staining . frozen - sections from oct - embedded liver samples were used for oil - red - o staining as previous described . glucose , insulin and pyruvate tolerance tests were performed 6 h after the removal of food ( 8 am2 pm ) . glucose ( 1.5 g / kg ) , insulin ( 1 u / kg ) or pyruvate ( 2 g / kg ) tolerance tests were performed via i.p . for acetyl - lysine immunoblotting , liver tissue or cells were lysed in ripa buffer ( 50 mm tris ph 8.0 , 100 mm nacl , 2 m egta ph 7.0 , 0.4% v / v triton x-100 , 10 mm nicotinamide ) , with protease inhibitors cocktail ( roche ) and phosphatase inhibitors ( 2 mm sodium orthovanadate , 1 mm sodium pyrophosphate , 10 mm sodium fluoride , 250 nm microcystin lr ) , and immunoblotted with an anti - acetyl - lysine antibody ( cell signaling 9441 ) . other antibodies used in this study : phospho - akt ( s473 ) ( 587f11 ; cell signaling 4051 ) , pan akt ( c67e7 , cell signaling 4691 ) , pan 14 - 3 - 3 ( h-8 , santa cruz , sc-1657 ) , mitomix rodent oxphos cocktail ( mitosciences ms604 ) , cpt1 ( h-40 , santa cruz , sc-98834 ) and alpha - tubulin ( h-300 , santa cruz , sc-5546 ) . line scan analysis was performed using image j. liver ( 2 g , trizol ) or cells ( 1 g , direct - zol ) total rna was semi - quantitated by standard two - step rt - pcr ( high capacity cdna synthesis kit , roche ; sensifast sybr green mix , bioline ) using gene - specific primers ( integrated dna technologies ) . acaca - sense , 5-catcaccatcagcctggttaca-3 , acaca - antisense 5-actgtgtacgctcttcggcat-3 ; acacb - sense , 5-gtttgggcactgcttctcct-3 , acacb - antisense , 5-cacacaccaccccaagcat-3 ; acadm - sense 5-gcaggtttcaagatcgcaatg-3 , acadm - antisense 5-tgaaactccttggtgctccact-3 ; ppargc1b - sense 5-gacgagctttcactgctacaga-3 , ppargc1b - antisense , 5-tgccatccaccttgacaca-3 ; esrrg - sense , 5-gaggacgattcaaggtaacatagag-3 , esrrg - antisense , 5-gacggaccccttctttcagc-3. other genes of interest were performed using primer pairs established in previous publications : ppara , fgf21 , and pdk4 ; acox1 and hmgcs2 ; cpt1a ; pck1 and g6pc ; ppargc1a and esrra ; ppifa ( housekeeping gene ) . data are expressed as means standard error of the mean ( sem ) . whitney test or one - way anova with fisher 's plsd post - hoc test , unless otherwise stated . other groups have reported single gene knockout of either acc1 or acc2 individually in mice . however , no studies have genetically knocked out both acc enzymes specifically in mouse liver . in this study we generated liver - specific acc1 and acc2 double knockout ( ldko ) mice , as follows . acc1 and acc2 floxed mice were bred with mice expressing cre under the control of a liver - specific albumin promoter . knockout was confirmed at the mrna and protein levels in liver tissue ( figures 1a and b ) . to verify that acc enzymatic activity was deficient in the liver , we isolated primary hepatocytes from ldko and flox control mice and tested their capacity to utilize c - acetate ( a cell - permeable precursor to cytosolic acetyl - coa ) for lipogenesis . hepatocytes from ldko mice were completely deficient in lipogenic conversion of acetate into lipid , but were fully capable of synthesizing sterols from this substrate ( figure 1c ) . the utilization of c - acetate for sterol synthesis was expected because this process does not require acc activity . compared to flox controls , ldko mice had similar body weight and adiposity ( supplemental figure s1 ) , and had normal energy expenditure and respiratory quotient in both fed and fasted states ( supplemental figures s2 and s3 ) . the ldko mice also demonstrated normal responses to metabolic challenges with a bolus injection of glucose , pyruvate , or insulin ( figure 1d f ) . ldko mice had similar serum glucose , insulin , free fatty acid , and triglyceride levels to flox controls in both the fed and fasted states , but had 22% less ( p < 0.05 ) serum cholesterol in the fasted state ( table 1 ) . hepatocytes and liver tissue demonstrated normal insulin - stimulation of akt ( supplemental figure s4 ) . together , these data demonstrate that loss of acc activity in the liver does not adversely affect whole body nutrient handling or insulin sensitivity . however , we did find that ldko liver mass was increased ( figure 1 g ) concomitant with increased triglyceride content ( figure 1h ) . histological analysis of liver tissue by oil - red - o and h&e staining revealed that ldko hepatocytes accumulated microvesicular fat ( figure 1i ) , a phenotype normally associated with a defect in fat oxidation . acc enzymes normally function to promote fat storage ; therefore , the finding that acc deletion increases basal liver fat accumulation was unexpected . hepatic fat accumulation can be caused by numerous mechanisms including defective lipid export , increased lipid intake , increased lipid synthesis , or decreased fat oxidation . lipid synthesis can be ruled out ( figure 1c ) ; therefore , we measured triglyceride export from the liver , the clearance of triglyceride after a bolus oral gavage of safflower oil , and the oxidation of the saturated fatty acid palmitate ( figure 2a c ) . the rate of lipid efflux from the liver was measured by treating ldko and flox mice with the lipoprotein lipase inhibitor , poloxamer 407 , and monitoring serum triglyceride accumulation over time ( figure 2a ) . ldko mice had greater rates of triglyceride export from the liver compared to flox control mice ( figure 2a ) , thus indicating the increase in hepatic fat in ldko mice was not due to impaired lipid efflux from the liver . we next challenged ldko and flox mice with an oral bolus of safflower oil and measured triglyceride appearance and clearance from the serum . this experiment showed that ldko mice had normal uptake and clearance of lipid ( figure 2b ) . finally , we measured fatty acid oxidation in ldko and flox primary hepatocytes using c - palmitate . this experiment revealed that ldko hepatocytes had a significant decrease in fatty acid oxidation compared to flox controls ( 48% decrease , p < 10 , figure 2c ) . the mechanism(s ) of reduced fat oxidation were investigated in more detail by assaying the activity of key enzymes in the mitochondrial and peroxisomal fatty acid oxidation pathways in liver lysates . compared to flox control tissue , ldko liver lysates had decreased activity of mitochondrial 3-hydroxyacyl - coa dehydrogenase ( -had , p = 0.002 ) , mitochondrial medium - chain acyl - coa dehydrogenase ( mcad , p = 0.07 ) , and peroxisomal acyl - coa oxidase ( acox , p = 0.002 ) ( figure 2d f ) . the ldko liver tissue also had lower mrna and protein expression of cpt1a ; the rate - limiting enzyme in mitochondrial fat oxidation ( figure 2 g and h ) . furthermore , ldko mice showed a trend of impaired fasting - induced ketone production ; an indirect marker of hepatic fat oxidation in vivo ( figure 2i ) . to determine whether the decrease in fat oxidation was compensated by altered glucose utilization , as predicted by the randle cycle , we measured the rate of glycolysis in isolated primary hepatocytes from ldko and flox mice . these data revealed a 40% increase in glycolysis in ldko hepatocytes compared to flox controls ( figure 2j ) . collectively , these data identify that inhibition of acc enzymes leads to reprogramming of hepatic glucose and fatty acid metabolism that resembles the chronic fed state . peroxisomal proliferator - activation receptor alpha ( ppar ) regulates the expression of several hepatic genes involved in fat oxidation , including cpt1a . therefore , we investigated transcriptional changes in pathways involved in nutrient metabolism including 5 other ppar-regulated genes : pdk4 , fgf21 , acox1 , hmgcs2 and ppara . in contrast to cpt1a , no other ppar-regulated genes were down regulated and both pdk4 and hmgcs2 were upregulated in liver tissue from ldko mice compared to controls ( figure 3a ) . furthermore , there were no statistically significant transcriptional changes in other glucose or fatty acid metabolic genes regulated by srebp1c , pgc-1 or pgc-1 ( figure 3b d ) . these data also show that the decreases in acox and mcad activity in ldko liver tissue ( figure 2d f ) was not due to alterations in transcription of their respective genes , acox1 and acadm ( figure 3a and d ) . acetyl - coa is a versatile cellular metabolite utilized for atp production , cholesterol and lipid biosynthesis , and protein acetylation . given the high flux of acetyl - coa through acc enzymes for lipogenesis , we investigated whether the perturbation of acc activity could impact acetyl - coa utilization for protein acetylation . primary hepatocytes and liver tissue from ldko and flox control mice were immunoblotted with an antibody that recognizes acetylated lysine residues ( figure 4a and b ) . compared to flox controls , the ldko tissues and cells had increased immunoblotting signals across a broad range of molecular weights ( figure 4a and b ) . since deacetylase enzymes may also regulate protein acetylation , we measured nad levels and compared the acetylation pattern of acc - deficient cells with the pattern caused by the nad - dependent deacetylase inhibitor , nicotinamide . nad levels were similar in flox and ldko liver lysates ( figure s5a ) , and nam treatment induced a different pattern of protein acetylation than was observed with acc inhibition ( figure 4a ) . these data reveal that acc inhibition promotes global protein acetylation , and indicate that nad - dependent deacetylase inhibition can not account for the changes in lysine acetylation . it was recently shown in saccharomyces cerevisiae that acc1 inhibition increases nuclear histone acetylation ; however , the western blots demonstrated lysine hyper - acetylation across a broad range of protein molecular weights that are not indicative of histones . to identify the proteins that were hyper - acetylated , we enriched for acetyl - peptides by an anti - acetyl - lysine antibody pulldown and quantified them by proteomics ( figure 4c ) . this approach resulted in the quantification of 26,843 acetylated peptides corresponding to 3586 unique acetylation sites on 1151 proteins ( supplementary dataset s1 ) . after normalization to protein abundance ( supplementary dataset s2 ) , the distribution of acetylation site relative abundances were positively biased ( mean log2(ldko / flox ) = 0.30 ) , signifying global hyper - acetylation in the ldko liver . specifically , 788 acetylation sites were increased by greater than 2-fold ( 22% of the unique sites identified ) ( figure 4d ) . curiously however , 274 acetylation sites ( 8% of the unique sites identified ) were decreased by more than 2-fold compared to floxed controls . since acc enzymes only have access to cytoplasmic acetyl - coa , we investigated whether subcellular protein distribution correlated with lysine acetylation . these analyses identified a significant enrichment in the acetylation of proteins in the extra - mitochondrial space and hypo - acetylation of proteins located in mitochondria ( figures 4e and 5a ) . we next evaluated whether altered protein acetylation patterns caused by acc inhibition were biased toward particular biological or metabolic pathways . functional enrichment analysis identified that proteins involved in intermediary nutrient metabolism were highly acetylated in the liver tissue of ldko mice compared to flox controls ( eight out of the ten most acetylated pathways , figure 5b ) . in livers from ldko mice , glycolytic and peroxisomal fatty acid metabolic enzymes were generally hyper - acetylated , while mitochondrial proteins involved in fat oxidation and the tricarboxylic acid cycle ( tca ) were generally unaffected or hypo - acetylated compared to floxed controls ( figures 5c and 6 ) . to determine whether protein acetylation corresponded with acetyl - coa levels , we measured acetyl - coa in mitochondrial and cytoplasmic fractions of flox control and ldko liver tissues . curiously , both mitochondrial and cytoplasmic acetyl - coa levels were similar between flox and ldko liver tissues ( supplementary figure s5b ) . these data suggest that alterations in metabolic substrate flux or increased protein acetylation balance cellular acetyl - coa levels independently of functional acc enzymes . since mitochondria were generally hypo - acetylated , we investigated the activity and acetylation status of complexes i , ii and iv of the electron transport chain ( etc ) and citrate synthase of the tricarboxylic acid cycle ( tca ) . the expression of all etc complexes was similar between flox and ldko livers as determined by western blot using antibodies against complex i subunit ndufb8 , complex ii subunit of 30 kda , complex iii core protein 2 , complex iv subunit i and complex v alpha subunit ( figure 7a ) . however , proteomics analysis of acetylated etc components revealed variable differences in the expression and acetylation of other individual components of the etc ( figure 7b ) . to determine whether these changes affected complex activity , we measured their activity ( figure 7c ) . ldko liver lysates had increased activity of etc complex i , lower activity of complex ii , and similar activity of complex iv compared to control ( figure 7c ) . in addition , citrate synthase enzyme activity was increased in ldko tissue lysates ( figure 7c ) . acc enzymes are attractive drug targets for fatty liver diseases because inhibition of their activity is predicted to decrease lipogenesis , increase fat oxidation , and thereby reduce fat storage . our observation that the deletion of acc activity in the liver promotes excess fat accumulation is entirely unexpected based on previous work in this area . the only study to genetically target both acc enzymes in vivo utilized an antisense oligonucleotide ( aso ) in rats . the aso markedly decreased acc expression in both adipose tissue and liver , and resulted in a decrease in hepatic fat and improved insulin sensitivity when rats were fed a high - fat diet . the phenotype of the ldko mouse and aso treatment are not directly comparable for many reasons including differences in the species of rodent , the diet , the duration of inhibition , and the different tissues targeted . regardless of these discrepancies , the ldko mouse described herein has allowed us to evaluate the consequences of hepatic acc inhibition on liver fat metabolism and whole animal physiology . importantly , the increase in liver fat storage in ldko mice reveals a gap in knowledge concerning the role of acc enzymes in liver fat metabolism . the increase in liver fat in ldko hepatocytes is likely caused by reduced fatty acid oxidation , as supported by our findings demonstrating decreased cpt1a expression ; decreased fasting ketone production ; accumulation of microvesicular fat ; and reduced activities of peroxisomal acyl - coa oxidase , mitochondrial had and mitochondrial mcad enzymes in the ldko liver compared to floxed controls . furthermore , since complex ii is involved in fadh2 oxidation that is driven by fatty acid catabolism , the reduced activity of this complex may also contribute to impaired fatty acid oxidation in ldko hepatocytes . however , our data indicate that liver - derived lipogenesis is not required for ppar-mediated gene transcription since only cpt1a was decreased in lkdo liver tissue compared to flox controls , while five other ppar regulated genes were unaltered or upregulated ( pdk4 and hmgcs2 ) . furthermore , we did not observe significant effects on other metabolic genes regulated by srebp1c , pgc-1 or pgc-1 in ldko mice . these data reveal the existence of a very precise , but unknown , mechanism whereby acc inhibition specifically targets cpt1a at the mrna level to decrease fatty acid oxidation without disrupting other closely regulated genes involved in carbohydrate and mitochondrial metabolism . in organelles such as the nucleus , the regulation of protein acetylation is fairly well - characterized with respect to the roles of histone acetyltransferases and deacetylases . by contrast , the regulation of protein acetylation in the cytoplasm is insufficiently understood . in recent years , several reports have demonstrated that protein acetylation , particularly in cytoplasmic proteins , plays an important role in liver metabolism . in ldko liver , protein hyper - acetylation was observed in all organelles except mitochondria , indicating an important regulatory role for acc enzymes in the control of protein acetylation in the extra - mitochondrial space . it is likely that the metabolic phenotype of reduced fat oxidation and increased glycolysis observed in lkdo liver is related to the alterations in protein acetylation . the mechanisms that underlie the compartment - specific changes in acetylation caused by acc inhibition require further investigation , and several scenarios are possible . first , the loss of acc activity in the extra - mitochondrial space may increase the availability of acetyl - coa for protein acetyltransferases . several acetyltransferases are known to localize in the cytoplasmic compartment including gcn5 and pcaf [ 4850 ] ; however , it remains unclear whether these acetyltransferases have the broad substrate specificity or subcellular distribution necessary to mediate the hyper - acetylation observed in ldko liver tissue . another possibility is that the increase in protein hyper - acetylation occurs non - enzymatically , as has been demonstrated previously [ 5153 ] . studies in yeast demonstrate that acc gene inhibition is sufficient to promote histone acetylation due to increased availability of acetyl - coa . similarly , inhibition of ampk in yeast activated acc and led to reduced histone acetylation . therefore , a similar regulation of protein acetylation by acc enzymes may also exist in the mammalian hepatocyte on non - histone proteins . although we were unable to detect an increase in acetyl - coa levels in ldko liver , it remains possible that certain nutritional or hormone - activated states are required to observe acetyl - coa accumulation . it is less likely that decreased nad - dependent deacetylase activity drives global protein acetylation since nad levels were unchanged in ldko tissue and nicotinamide did not increase protein acetylation with a similar pattern . finally , it was recently shown that decreased activity of mitochondrial etc complex i is associated with increased mitochondrial protein acetylation . the ldko liver had significantly higher complex i activity concomitant with a decrease in protein acetylation in mitochondria , thus it is possible that mitochondrial hypo - acetylation may be secondary to increased complex i activity . in summary , we observe that complete inhibition of hepatocyte acc enzymes triggers the activation of a compensatory pathway that preserves fat storage in the liver . we hypothesize that the mechanism linking the loss of acc activity to increased fat storage is due to increased acetylation of key metabolic enzymes and transcriptional regulatory sensors . these sensors interpret hyper - acetylation as a nutrient replete state and coordinate the feeding response to decrease fatty acid oxidation ; an appropriate response to nutrient excess . future mutational studies are required to test this hypothesis and to define how specific acetyl - lysine sites identified in this study affect protein function . collectively , this new information advances our understanding of the role of acc enzymes in hepatic nutrient metabolism and protein acetylation , and also reveals the existence of a therapeutic window for drug discovery efforts targeting acc . one possibility is that an ideal acc inhibitor would impair lipogenesis but maintain enough residual activity in specific subcellular compartments to prevent protein hyper - acetylation and avoid the compensatory inhibition of fat oxidation . these data also implicate acetyl - coa , like malonyl - coa , as a potent regulator of hepatic metabolic flexibility .

lipid deposition in the liver is associated with metabolic disorders including fatty liver disease , type ii diabetes , and hepatocellular cancer . the enzymes acetyl - coa carboxylase 1 ( acc1 ) and acc2 are powerful regulators of hepatic fat storage ; therefore , their inhibition is expected to prevent the development of fatty liver . in this study we generated liver - specific acc1 and acc2 double knockout ( ldko ) mice to determine how the loss of acc activity affects liver fat metabolism and whole - body physiology . characterization of ldko mice revealed unexpected phenotypes of increased hepatic triglyceride and decreased fat oxidation . we also observed that chronic acc inhibition led to hyper - acetylation of proteins in the extra - mitochondrial space . in sum , these data reveal the existence of a compensatory pathway that protects hepatic fat stores when acc enzymes are inhibited . furthermore , we identified an important role for acc enzymes in the regulation of protein acetylation in the extra - mitochondrial space .

the standard model ( sm ) of particle physics has been extremely successful in explaining all microscopic phenomena observed down to distances of order @xmath9 . however , the model has two notable under - explored corners : the neutrino and higgs sectors . having discovered the higgs boson the next major goal of the large hadron collider ( lhc ) is to scrutinize the properties of the higgs boson and search for deviations from the sm predictions . a particularly interesting question is whether cp is a good symmetry of the higgs sector . since all higgs boson couplings are predicted to be cp even in the sm , any observation of a cp - odd or cp - violating component will constitute unambiguous evidence of physics beyond the sm . cp - violating higgs interactions may be motivated by the fact that baryogenesis requires the existence of a new source of cp violation and the possibility that such a primordial source of new cp violation may leave traces in the couplings of the higgs boson . recently , a novel variable @xmath1 for measuring the cp phase in the @xmath10-@xmath5-@xmath5 coupling was proposed in ref . the distribution of @xmath1 was shown to have the simple form @xmath11 , where @xmath12 is the phase of the @xmath10-@xmath5-@xmath5 yukawa coupling , with @xmath13 and @xmath14 corresponding to the cp - even and -odd limits , respectively , while @xmath15 and @xmath16 are independent of @xmath12 and @xmath1 . what distinguishes the @xmath10-@xmath5-@xmath5 yukawa coupling from other couplings is that its _ phase _ ( i.e. the cp angle @xmath12 ) is currently completely unconstrained by data @xcite , even though its _ magnitude _ ( i.e. the rate of @xmath17-@xmath18 production ) is roughly consistent with the sm prediction @xcite . field theoretically , as discussed in ref . @xcite , an @xmath19 @xmath12 in the @xmath10-@xmath5-@xmath5 coupling can easily coexist with other higgs boson couplings whose cp phases are known to be small , such as @xmath10-@xmath20-@xmath21 and @xmath10-@xmath22-@xmath23 ( @xmath24 and @xmath25 , respectively @xcite ) , and @xmath10-@xmath26-@xmath26 ( for which @xmath27 is disfavored @xcite ) . in ref . @xcite using parton - level analyses it is estimated that the @xmath10-@xmath5-@xmath5 cp phase , @xmath12 , may be measured from the @xmath1 distribution to an accuracy of @xmath28 at the 14-tev lhc with @xmath29 of data , or the @xmath7 and @xmath8 cases may be distinguished at @xmath30 level with @xmath31 . however , these conclusions are for an ideal detector . in this paper , we examine the impact of realistic detector effects on the measurement of @xmath12 via @xmath1 . there are various ways that detector effects can affect those estimates . most importantly , the reconstruction of the @xmath1 variable requires resolving the charged and neutral pions in the @xmath32 decay mode , but these @xmath33 are highly boosted as they come from higgs decays . one therefore expects the two photons from each @xmath4 decay to hit the same tower of the electromagnetic calorimeter ( ecal ) , thereby making the standard identification of a @xmath4 using photons useless . moreover , one expects the same ecal tower to be hit by the @xmath3 , raising the question of how much of the ecal tower s activity should be attributed to the @xmath4 . another obvious issue is the reconstruction of the neutrinos . in ref . @xcite , the so - called collinear approximation @xcite is adopted , where the neutrino from each @xmath5 decay is taken to be exactly collinear with its parent @xmath5 . as shown in ref . @xcite , the collinear approximation results in a 6070% reduction of the amplitude of the @xmath34 curve . so , one might expect that here lies a significant opportunity for improvement . in this paper , however , we present a theoretical calculation that strongly suggests that it is extremely difficult , if not impossible , to outperform the collinear approximation for the purpose of @xmath1 reconstruction . adopting the collinear approximation , we then focus on the aforementioned issues of pion identifications in the presence of realistic detector effects , and propose a realistic algorithm to identify `` @xmath5 candidates '' specifically suited for constructing @xmath1 . surprisingly , we find that the amplitude of the @xmath34 curve of the signal is virtually unchanged by the finite angular resolution of the lhc detectors . instead , we find that the measurement of @xmath12 through the @xmath1 distribution is significantly hampered by the contamination by the @xmath35 background . this degradation arises due to resolution effects in reconstructing the @xmath36 invariant mass as a consequence of large uncertainties in the measurement of the missing transverse energy . fortunately , this is an area where future improvement can be hoped for , unlike the angular resolution . we leave the important question of pileup effects for future work . while we focus on the measurement of @xmath12 through the @xmath1 variable , similar but different acoplanarity angles have been studied both for @xmath37 colliders @xcite as well as for the lhc @xcite . for the @xmath2 decay mode , which is the most dominant decay mode of the @xmath5 , the acoplanarity angles used in those studies are not as effective as the @xmath1 variable at @xmath37 colliders in which the neutrino momenta can be reconstructed up to a two - fold ambiguity @xcite . an advantage of the lhc studies mentioned above is that they can be applied to all 1-prong @xmath5 decays including leptonic decays . however , realistic detector effects are not considered in those studies . @xcite performs a realistic study for the lhc but assuming universal cp violation for all sm fermions , unlike our study in which we assume @xmath12 is non - zero only for the @xmath5 . finally , the use of the @xmath5 impact parameter associated with a displaced @xmath5 vertex was studied in ref . @xcite in the @xmath37 context . our @xmath1 variable does not depend on the measurement of the @xmath5 impact parameter . the paper is organized as follows . in section [ s.theory ] , we review the @xmath1 variable and rewrite it in a simple form by expanding it in terms of a small parameter @xmath38 that characterizes the degree of collinearity of the decay products of the taus , with @xmath39 in the exactly collinear limit . we use this expansion to argue that the collinear approximation appears the best we can do for the purpose of reconstructing @xmath1 . section [ s.parton ] describes the parton level simulation of the signal and background processes . section [ s.simulation ] describes the detector simulation and selection of the parametrized detector quantities corresponding to the higgs boson decay products . section [ s.results ] evaluates the results of the simulation and sensitivity as a function of integrated luminosity , and we conclude in section [ s.conc ] . following ref . @xcite , we define the cp phase @xmath12 by @xmath40 where the scalar field @xmath10 and dirac spinor @xmath5 describe the higgs boson and @xmath5 lepton , respectively . in order to maintain the sm decay rate for @xmath41 , we fix the @xmath10-@xmath5-@xmath5 yukawa coupling , @xmath42 , to its sm value @xmath43 with @xmath44 , but keep the cp phase @xmath12 as a free parameter to be measured . the sm prediction is @xmath45 . gauge - invariant form of the interaction ( [ e.yukawa ] ) as well as an example of renormalizable realizations of it , see ref . ] we are interested in the decay chain @xmath46 as calculated in ref . @xcite , the squared matrix element for this decay has the form @xmath47 where @xmath15 and @xmath16 are both positive and depend neither on @xmath1 nor @xmath12 . the angular variable @xmath1 is defined through @xmath48 with a common proportionality factor . the subscripts @xmath49 and @xmath50 refer to the @xmath17 and @xmath18 branches of the decay , respectively ( e.g. , @xmath51 and @xmath52 ) . the 4-momenta @xmath53 ( @xmath54 , @xmath50 ) are defined by @xmath55 with @xmath56 and @xmath57 the fact that the taus from higgs boson decay are highly boosted can be exploited to obtain an even simpler expression for @xmath1 . we define two lightlike 4-vectors @xmath58 and @xmath59 whose spatial components , @xmath60 and @xmath61 , are unit vectors taken along the 3-momenta of the @xmath62 from the @xmath5 decays : @xmath63 we also define @xmath64 then , an arbitrary 4-momentum @xmath65 can be expanded in terms of @xmath66 and @xmath67 as @xmath68 where @xmath69 by definition satisfies @xmath70 . alternatively , @xmath65 can be expanded in a similar manner in terms of @xmath71 and @xmath72 . to avoid notational clutter , we do not make explicit whether @xmath73 and @xmath69 are defined in the @xmath66-@xmath67 basis or the @xmath71-@xmath72 basis , but it should be clear that the momenta of all particles originating from the @xmath17 will be expanded in the @xmath66-@xmath67 basis , while those from @xmath18 will be in @xmath71-@xmath72 . next , we introduce a small expansion parameter @xmath74 to quantify the degree of collinearity between the @xmath33 and the respective @xmath62 . first , by construction , `` collinear '' means that @xmath75 is dominated by the @xmath76 component , @xmath77 , while the remaining components @xmath78 and @xmath79 are small . therefore , by definition , we assign the @xmath38 scaling law @xmath80 to the @xmath81 component . this implies that numerically we have @xmath82 . then , in the ultra - relativistic limit , we have @xmath83 , so we see that @xmath84 . to summarize , we characterize the collinearity of @xmath85 as @xmath86 since neutrinos are invisible at the lhc , we must devise a method to assign momenta to the neutrinos from the @xmath33 decays . however , the choice of method is a delicate issue for the reconstruction of the @xmath1 variable . performing the @xmath38 expansion in the expressions ( [ e.theta ] ) , we see that all @xmath87 and @xmath88 terms exactly cancel , so we are left with @xmath89 therefore , for the purpose of reconstructing @xmath1 , values must be carefully assigned to the invisible neutrino momenta so as not to disturb these delicate cancellations . in particular , the @xmath38 scaling law ( [ e.lambda_scaling ] ) must be respected . a simple method with this property is provided by the _ collinear approximation _ @xcite , where we set @xmath90 for each @xmath91 . in other words , the collinear approximation applies the @xmath39 limit to the @xmath5 and @xmath92 momenta . then , to @xmath93 , the expressions ( [ e.theta ] ) become @xmath94 again with a common proportionality factor . finally , noticing that the definitions of @xmath53 in ( [ e.k ] ) give @xmath95 in the collinear approximation , we arrive at the following very simple expressions that determine @xmath1 : @xmath96 with a common proportionality factor . the 4-vectors @xmath97 , @xmath58 and @xmath59 are defined in ( [ e.q ] ) and ( [ e.n1_and_n2 ] ) , respectively . in the rest of the paper , we use the expressions ( [ e.theta:coll_approx ] ) to compute @xmath1 unless noted otherwise . one might think we should be able to do better than the collinear approximation by using statistical correlations of the neutrino momenta with other , visible , momenta in the process . however , the delicate cancellation shown in ( [ e.cancellations ] ) implies that the correlations must get the neutrino momenta correctly at the level of @xmath98 in order to outperform the collinear approximation . although we could not prove that this is impossible , it certainly suggests that it is extremely difficult . in this section , we outline our generation of the parton level samples used in the detector simulation . we generated tree level event samples with a combination of madgraph5 @xcite and mcfm as explained below for the background ( @xmath99 ) and the signal ( @xmath100 ) with @xmath101 gev for the jet . the associated jet facilitates triggering and provides sufficient @xmath102 transverse momentum for the collinear approximation to hold . other associated production modes could be used , notably @xmath103 and @xmath104 , but they have lower cross sections than @xmath100 , though potentially better signal to noise that could be exploited in a further study . multijet events are a potential background ; however , this background is found to be small once tau selection criteria are imposed . therefore , consideration of @xmath99 alone is sufficient for our purposes . the jet-@xmath105 cut was imposed at the generator level in anticipation of the high-@xmath105 jet requirement we impose in our analysis to ensure that the event will pass the trigger as well as to avoid kinematic configurations where the @xmath102 is produced back - to - back in the transverse plane and the collinear approximation for the neutrino momenta fails . the model files were generated using feynrules package @xcite by modifying the sm template provided by feynrules to include the cp violating coupling in the @xmath10-@xmath5-@xmath5 vertex as well as the effective vertices for the decay of @xmath106 and @xmath107 given by @xmath108 where @xmath109 is the projection operator onto left - handed chirality . we implement the higgs boson production from @xmath110 fusion using the effective field theory ( eft ) ( in which the top quark is integrated out ) available from the feynrules repository . in principle , such an effective vertex is applicable only when the energy scale of the process lies well below the mass of the top quark . however , using the mcfm program @xcite , we have verified that the higgs boson @xmath105 distribution from the eft in the region of interest ( @xmath111 gev ) agrees at the percent level with the full 1-loop qcd calculation . finally , note that all the coupling constants in eq . ( [ e.leff ] ) are set to unity . to get the physical cross section , we use the cross sections from mcfm re - weighted by @xmath112 and @xmath113 branching fractions . the cteq6l1 pdf set was used throughout . parton showering and hadronization effects are included by processing the madgraph5 samples using the pythia8 program @xcite . in principle , higher order corrections can be implemented by including events with higher jet multiplicity from tree level matrix elements and performing the corresponding jet merging with pythia s parton showering . however , we have verified that the inclusion of these corrections do not affect the higgs boson @xmath105 distribution and they differ at most by a few percent in the region of interest . in order to incorporate detector effects into the measurement of the @xmath1 angle , we use the snowmass detector model @xcite , implemented in delphes 3 @xcite . in delphes , energy from particles deposited within the calorimeter is partitioned between the electromagnetic and hadronic sections according to a fixed ratio . this ratio is unity for the fraction of energy from a charged pion deposited in the hadronic calorimeter , which fails to account for energy depositions from hadronic showers that begin before the hadronic calorimeter . we account for this effect , including potential systematic effects due to overlap between the energy deposition of the neutral pion and the charged pion , by distributing the energy of charged pions in both calorimeter sections according to a probability distribution that models the one given in ref . @xcite for 30gev pions . 85% percent of the time the particle is presumed to deposit energy via ionization only , and the energy is entirely deposited within the hadronic calorimeter . for the remaining 15% of events , the fraction of the particle energy deposited in the electromagnetic calorimeter is drawn from a gaussian distribution of mean 0.4 and width 0.3 ( selecting only physical values ) . the rest of the energy is assigned to the hadronic calorimeter . the gaussian models the probability with which the pion interacts early , in which case a significant fraction of its energy will be deposited in the ecal . tau identification in delphes is abstracted to an efficiency , which is insufficient for our purposes . therefore , we develop an algorithm to identify taus explicitly that assigns the charged pion and the neutral pion to a track and a calorimeter tower , respectively . we select jets reconstructed with the anti-@xmath114 algorithm @xcite with a distance parameter of 0.5 , which are reconstructed in delphes using fastjet @xcite . at least three jets are required in each event with @xmath115gev within @xmath116 ( the tracking limit of the detector ) , of which the lead jet must have @xmath117gev ( well above the parton level requirement of 70gev ) . all jets with @xmath11830gev are examined as potential @xmath5-candidates . the lead track within @xmath119 of the jet axis is selected , and the sum of the transverse momenta of the remaining tracks , within @xmath120 , is required to be less than 7gev in order to exclude jets that are unlikely to be taus . these selection requirements emulate the more sophisticated selection of taus in the lhc experiments , and are treated as equivalent to the delphes efficiency of 65% . we make further selections on the individual elements within the tau candidate in order to ensure that the decay products have been measured with sufficient precision for the calculation of @xmath1 . the lead track is required to have @xmath121gev , or this candidate is rejected . we then proceed to examine calorimeter towers within @xmath119 of the jet axis . we select the tower with the largest transverse energy in the electromagnetic portion of the tower . the tower in question must also have an electromagnetic fraction ( emf ) of 0.9 , that is , at least 90% of its total energy within the ecal . if this tower has @xmath122gev , is within @xmath123 of the selected track , and the sum of the selected tower transverse energy and the track momentum is greater than 20gev , then this jet becomes a @xmath5-candidate suitable for @xmath1 reconstruction , and the charged pion is assumed to be the selected track with the neutral pion the selected tower . finally , the electromagnetic portion of the actual atlas and cms detectors have finer granularity than a single tower , which is not properly accounted for by the snowmass detector . to approximate a position resolution of one detector element of the lhc detectors , we introduce the resolution for the position in @xmath124-@xmath125 of the neutral pion as a gaussian smearing with standard deviation @xmath126 . a resolution no better than a tower ( as in the default snowmass detector ) was found to degrade significantly the sensitivity to the modulation in the @xmath1 distribution . finally , events are required to have at least two @xmath5-candidates with opposite charges . should there be more than two @xmath5-candidates , the highest @xmath105 pair with opposite charge is selected . we now come to the critical question of whether the signal modulation survives detector effects . in order to answer that question , consider the analysis cut - flow shown in table [ t.cutflow ] . .[t.cutflow]cut - flows for z@xmath127 and @xmath128 . the generator and reconstruction level cuts on the jet are @xmath129gev , and 100gev , respectively . see text for more details . [ cols="<,^,^",options="header " , ] comparison of parton level @xmath1 distribution ( monte carlo truth ) with the distribution after the delphes simulation and event reconstruction for @xmath130 . ] comparison of parton level @xmath1 distribution ( monte carlo truth ) with the distribution after the delphes simulation and event reconstruction for @xmath131 . ] now , we address the crucial question : how well can we distinguish the @xmath1 distribution with @xmath132 from that with @xmath133 ? given @xmath134 events , each yielding a measurement of @xmath135 , we construct a test statistic @xmath20 designed to distinguish between the sm hypothesis @xmath45 and the alternatives @xmath136 . a standard choice for @xmath20 is @xmath137 where @xmath138 is the likelihood function , while @xmath139 is the @xmath1 distribution for a given value of @xmath12 . in order to enhance the signal to background ratio ( @xmath140 ) , we use a boosted decision tree ( bdt ) , trained using the invariant mass of the reconstructed @xmath33 system , the kinematic variables ( @xmath141 ) of the final state visible particles , and the missing transverse energy . therefore , each event can be characterized by the measurement of @xmath135 and the value of the bdt discriminant @xmath142 , which yields the modified likelihood function , @xmath143 where the probability density function of the data @xmath144 is modelled as follows , @xmath145 \ , , \end{split}\ ] ] where @xmath146 and @xmath147 are , respectively , the signal and background bdt distributions for the discriminant parameter @xmath148 , while @xmath149 and @xmath150 are , respectively , the total expected background and signal counts given by @xmath151 here , @xmath152 and @xmath153 are the associated cross section times branching fractions , the @xmath154 s are the signal and background efficiencies discussed above and @xmath155 is the integrated luminosity . in order to quantify how well one might be expected to distinguish a @xmath136 hypothesis from the sm hypothesis @xmath45 , we generate three samples of @xmath1 and @xmath148 values with @xmath45 , @xmath156 , and @xmath157 . for each sample , we calculate the values of @xmath20 as defined in eq . ( [ e.t ] ) , which yield the @xmath20 distributions as illustrated in fig . [ f.tdist ] for the @xmath45 and @xmath156 samples . to quantify the discrimination between the two hypothesis , the @xmath85-value of the sm @xmath20 distribution is computed using the median of the non - sm @xmath20 distribution . as proxies for systematic uncertainties in the @xmath150 and @xmath158 parameters , the @xmath85-values are varied in the 10% neighborhood of their nominal values . in fig . [ f.reach ] we present the reach as a function of the integrated luminosity for @xmath159 and @xmath157 . because we have chosen the observed " value of @xmath20 to be the median of the non - sm hypothesis , the reach in this context is interpreted as follows : if the non - sm hypothesis is true , then there is a 50% chance to reject the sm hypothesis @xmath45 at the @xmath26-sigma level , where @xmath160 with @xmath85 being the @xmath85-value shown in fig . [ f.tdist ] . distributions of the @xmath20 statistic for the sm hypothesis ( @xmath45 ) and a non - sm hypothesis ( @xmath161 ) . the observed " value of the statistic is taken to be the median of the @xmath20 distribution of the non - sm hypothesis . ] the reach , quantified on the @xmath26-sigma scale of the normal distribution , versus the integrated luminosity . the uppermost plot shows the effect of reducing the background by a factor of two , while keeping every else fixed . ] it is clear from fig . [ f.reach ] that the optimistic conclusion obtained for an ideal detector does not survive the smearing effects of a realistic detector and our reconstruction algorithms . at best , at @xmath162 fb@xmath163 , there is a 50:50 chance of rejecting the @xmath45 hypothesis at 95% confidence level . it is important to note where the poor performance stems from . as mentioned earlier , the reduction of the modulation amplitude @xmath158 of the signal due to the angular resolution is negligible . rather , we find that the discrimination power of the bdt dominantly comes from the invariant mass of the reconstructed @xmath17-@xmath18 system , and consequently the @xmath140 ratio is sensitive to the mass resolution , which in turn is sensitive to the resolution of the missing transverse energy ( met ) . therefore , our analysis shows that the current met resolution of the lhc detectors is too low to achieve a sufficient reduction of the total background count @xmath149 . to illustrate the effects of improved missing transverse energy resolution , we show in the uppermost plot in fig . [ f.reach ] the effect of increasing @xmath140 by a factor of two by decreasing @xmath149 by a factor two , while keeping everything else the same . increasing the @xmath140 by increasing @xmath150 by a factor two ( while keeping @xmath158 unchanged ) has a similar but more pronounced effect . we have examined a recent proposal @xcite for measuring a potentially non - zero cp phase @xmath12 in higgs to @xmath102 decays using an angular variable @xmath1 that can be reconstructed from the decay chains @xmath164 . a non - zero phase of the @xmath10-@xmath5-@xmath5 yukawa coupling would be unambiguous evidence of physics beyond the sm . contrary to previous expectations @xcite , with @xmath6 we find that the standard model cp phase , @xmath7 , can be distinguished from the @xmath8 hypothesis at no more than 95% confidence level . we have addressed two obvious effects that are expected to degrade our ability to measure @xmath12 from the @xmath1 distribution . first , we examined the issue of neutrino momentum reconstruction , for which the original proposal @xcite employed the collinear approximation . we have presented a theoretical argument that strongly suggests that this can not be improved further . second , we have closely studied how finite resolutions of a realistic detector affects our ability to distinguish between the sm signal and its deviations induced by a non - zero cp violating phase @xmath12 , using the snowmass detector model implemented in the delphes detector simulation program . contrary to the naive expectation that a finite angular resolution should hamper the reconstruction of @xmath1 as it requires resolving the charged and neutral pions from the @xmath5 decays , we have found that the finite angular resolution of the lhc detectors reduces the modulation amplitude of the signal @xmath1 distribution by only @xmath165% , compared to that of an ideal detector . instead , we have found that the experimental ability to distinguish the hypotheses @xmath132 from @xmath133 is strongly limited by the missing transverse energy resolution . the finite energy resolution significantly degrades the use of the @xmath166 invariant mass distribution as the principal discriminant between the @xmath167 signal and the @xmath35 background . in contrast , the reconstruction of @xmath1 itself is nearly unaffected by the finite energy resolution , as the @xmath1 variable is basically determined by the angular topology of the higgs boson decay products . fortunately , the resolution of missing transverse energy is an area in which improvements can be hoped for , e.g. , by using multivariate methods @xcite . this work was supported in part by the us department of energy under grant de - fg02 - 13er41942 . the work of n. s. was partially supported by the us department of energy contract no . de - ac05 - 06or23177 , under which jefferson science associates , llc operates jefferson lab .

the search for a new source of cp violation is one of the most important endeavors in particle physics . a particularly interesting way to perform this search is to probe the cp phase in the @xmath0 coupling , as the phase is currently completely unconstrained by all existing data . recently , a novel variable @xmath1 was proposed for measuring the cp phase in the @xmath0 coupling through the @xmath2 decay mode . we examine two crucial questions that the real lhc detectors must face , namely , the issue of neutrino reconstruction and the effects of finite detector resolution . for the former , we find strong evidence that the collinear approximation is the best for the @xmath1 variable . for the latter , we find that the angular resolution is actually not an issue even though the reconstruction of @xmath1 requires resolving the highly collimated @xmath3 s and @xmath4 s from the @xmath5 decays . instead , we find that it is the missing transverse energy resolution that significantly limits the lhc reach for measuring the cp phase via @xmath1 . with the current missing energy resolution , we find that with @xmath6 the cp phase hypotheses @xmath7 ( the standard model value ) and @xmath8 can be distinguished , at most , at the 95% confidence level .

vibrationally resolved electronic spectra ( _ e.g. _ one - photon absorption and emission spectra ) are within the born - oppenheimer framework usually interpreted in terms of franck - condon ( fc ) factors ( fcfs ) @xcite . accordingly , one can try to obtain the shape of the spectral profile for a fc - allowed transition from computed fcfs in frequency domain . however , the evaluation of fcfs for large molecular systems is challenging even within the harmonic approximation if one has to take duschinsky mode mixing ( rotation ) @xcite into account . this is because multi - variate hermite polynomials have then to be evaluated for each fc integral , rather than only uni - variate hermite polynomials as is the case for the comparatively simple parallel harmonic oscillator model . the computational task becomes more difficult as the molecular size and temperature increases because the number of fc integrals grows vastly . to describe fc - forbidden or weakly allowed transitions , one has to go beyond the condon approximation and employ for instance a herzberg - teller ( ht ) expansion @xcite of the electronic transition moment with respect to the normal coordinates . as a result , the calculation of the vibronic spectrum for a non - condon process is even more difficult than for a fc - allowed transition because one has to evaluate many matrix elements of the non - condon operators which require for each ht integral in general the calculation of combinations of several fc integrals . the number of fc integrals and matrix elements of non - condon operators to be evaluated in a sum - over - states approach can be significantly reduced with the help of rigorous integral prescreening strategies @xcite . however , this time - independent ( ti ) calculation of the spectral profile in frequency domain is still considerably more expensive than an alternative time - dependent ( td ) approach that exploits time - correlation functions ( tcfs ) ( see _ e.g. _ ref . @xcite ) , but offers the ability to directly assign individual peaks in the spectrum . as we have outlined earlier @xcite , a unified coherent state - based generating function ( csgf ) approach @xcite can be used both for rigorous integral prescreening strategies and tcf calculations which combine the strengths of both approaches and complement each other favourably . even in the less demanding td approach , however , one usually has to invest significant computational time for often unnecessary spectral details . cumulants ( or moments ) of a distribution ( see _ e.g. _ refs . @xcite ) can deliver highly useful information . from this one can either attempt to reconstruct the spectral shape or try to estimate the relevant spectral profile , which can be exploited in subsequent ti and td approaches @xcite . cumulants of the vibronic spectrum can be obtained from the csgf directly without computing the total spectrum in frequency domain . this method was exploited already in ref . @xcite for fc - allowed transitions , and we report herein an extension of this method to incorporate non - condon transitions . as application , we present the profile of the @xmath1 transition of benzene , which is in the electric dipole approximation franck - condon forbidden , at various temperatures within the linear ht approximation and compare the cumulant expansion result with the tcf approach . the spectral profile ( @xmath2 ) can be expressed via the fourier transform ( ft ) of the tcf ( @xmath3 ) that depends on the time @xmath4 and temperature @xmath5 , namely @xmath6 where @xmath7 is the transition energy and @xmath8 the @xmath9 transition energy . the corresponding occupancy representation for the tcf can be obtained from fermi s golden rule , _ i.e. _ @xmath10 where we have assumed an electric dipole transition with the electronic transition dipole moment ( @xmath11 ) , which is a function of normal coordinates of the initial electronic state . the @xmath12-dimensional harmonic oscillator eigenstates of the initial and final electronic state are denoted by @xmath13 and @xmath14 with the corresponding harmonic energy vectors @xmath15 and @xmath16 , respectively . the vibrational hamiltonians of the the initial and final electronic states are @xmath17 and @xmath18 , respectively . @xmath19 is the boltzmann constant . @xmath20 is the vibronic transition energy with respect to the @xmath9 transition energy . the time - dependent part with the vibronic transition energy corresponds to a dirac delta distribution in frequency domain and accordingly this expression is usually evaluated in frequency domain , which is straightforward . the spatial representation of the tcf in closed form can be found by evaluating the following quantum mechanical traces @xmath21 the traces can be evaluated with any complete basis . in our work coherent states were used ( see _ e.g. _ refs . @xcite ) with the duschinsky relation between initial and final state normal coordinates ( @xmath22 where @xmath23 and @xmath24 are the duschinsky rotation matrix and displacement vector , respectively and @xmath25 are the normal coordinates of the final state ) and the ht expansion of the electronic transition dipole moment ( @xmath26 where @xmath27 is the first derivative of @xmath28 with respect to @xmath29 . ) . the vibronic spectral density function can be related to a probability density function ( pdf ) because the vibronic transition process follows a certain pdf . if all cumulants or moments of a pdf are defined and available , the pdf can be reconstructed as follows @xmath30 where @xmath31 is the @xmath32-th order cumulant at temperature @xmath5 . the cumulants of the spectral density function are normalised to give the total intensity @xmath33 . moments ( cumulants and moments are inter - convertible ) can be obtained by partial derivatives of @xmath34 with respect to time , @xmath35 thus , cumulants can be evaluated analytically or numerically by evaluating partial derivatives of @xmath34 in eq . with respect to the time variable at @xmath36 . analytic evaluation of the cumulants to arbitrary order within the linear ht approximation can be performed along the lines of the development in refs . @xcite for the cumulants of fc profiles to arbitrary order . for numerical evaluation of low - order cumulants one needs to compute @xmath34 only at the first few time steps . to obtain the corresponding moments numerically , @xmath37 and @xmath38 are used for the calculation of even and odd moments , respectively , because @xmath39 in eq . ( see _ e.g. _ ref . @xcite ) . the closed form of @xmath40 within the linear ht approximation can be found in ref . therein , additional flexibility was introduced to the gf by distinguishing individual vibrational modes to allow for rigorous prescreening strategies and detailed control of the dynamics . this can be done by assigning different time and temperature variables to each vibrational degrees of freedom . the corresponding gf in an occupancy representation reads as follows @xmath41 \mathrm{e}^{-({\underline{v}}^{\mathrm{t}}{\mathbf{b}}{\underline{\epsilon } } + { \underline{v}}'^{\mathrm{t}}{\mathbf{b}}'{\underline{\epsilon } } ' ) } \ , , \label{eq : occfg}\end{aligned}\ ] ] where the general operators @xmath42 and @xmath43 , which can be products of momentum and position operators , are given instead of @xmath44 . the time variables are assigned to the matrices @xmath45 = @xmath46 and @xmath47 = @xmath48 for initial and final vibrational modes , respectively . different temperatures can be given to the initial and final vibrational degrees of freedom via @xmath49 = @xmath50 and @xmath51 = @xmath52 , respectively . @xmath53 is the corresponding normalising factor . the electronic @xmath0 transition of benzene is fc - forbidden in the electric dipole approximation ( @xmath54 ) such that only the ht terms contribute to the spectral density function . the corresponding tcf is given as follows , here with same time and temperature ( @xmath4,@xmath5 ) for all vibrational degrees of freedom , @xmath55 a time increment of 0.51 fs and a grid with 2@xmath56 grid points are used for the corresponding fft calculations . the experimental uv absorption spectrum of fischer @xcite is additionally shown in read . right part of the figure : the dashed lines are drawn for the tcf - fft approach with a gaussian line shape function of with fwhm of 500 @xmath57 . a time increment of 0.10 fs and a grid with 2@xmath58 grid points are used for the corresponding fft calculations . solid lines are drawn for the curve obtained by edgeworth expansion using up to 4-th order cumulants and , for 1000 k by edgeworth expansion using up to 8-th order cumulants . , scaledwidth=45.0% ] the vibronic profiles for benzene s @xmath0 transition at zero kelvin and finite temperatures are calculated with two methods , namely tcf and time - independent cumulant expansion ( ce ) . we use herein the term time - independent ce , which was employed in ref . @xcite , to distinguish this ce from the conventional ( time - dependent ) ce ( see _ e.g. _ refs . @xcite ) which involves time integration for the cumulant calculation . the spectra obtained are displayed in fig . [ fig : benzenespectrum ] . to compute the vibronic spectra via the tcf method , the fftw library @xcite is used for fast fourier transform ( fft ) . the approximate curves are generated for the ce with edgeworth expansion @xcite using the computed low - order cumulants . some of the problems related to this type of expansion for the description of fc profiles are discussed in ref . @xcite . the moments ( eq . [ eq : moments ] ) are calculated both analytically and numerically , the latter by taking partial derivatives of @xmath34 in eq . [ eq : closedform ] with respect to time . analytical and numerical results are compared in table [ table : moments ] . required input data from electronic structure calculations for benzene , _ i.e. _ molecular equilibrium structures and corresponding harmonic force fields for each electronic state ( @xmath59 and @xmath60 ) as well as first derivatives of the electronic transition dipole moments are taken from ref . @xcite ( casscf / dzv ) . these data have recently been compared to results obtained via analytical derivatives techniques for electronic transition dipole moments within a time - dependent density functional theory framework @xcite . the vibronic structure methods employed in the present work are implemented in a development version of our vibronic structure program package hotfcht @xcite . the left hand side in fig . [ fig : benzenespectrum ] shows vibronic profiles from tcf - fft which are convoluted by a lorentzian line shape function with full width at half maximum ( fwhm ) of 50 @xmath57 at temperatures elevating from 0 k to 1000 k. this fc - forbidden vibronic transition is mediated by the non - totally symmetric vibrational modes in the irreducible representation e@xmath61 . the main feature of the vibronic spectrum is from progressions in the totally symmetric c - c stretching mode ( 963 @xmath57 ) building on the so - called false origin from a single excitation of a non - totally symmetric ( e@xmath61 ) in - plane bending mode ( 575 @xmath57 ) as indicated in the spectrum at zero kelvin . the calculated spectrum at 300 k is compared with the experimental data of fischer @xcite . the two spectra agree fairly well in the low energy region but the computed peaks at higher energies are slightly shifted to larger wavenumbers due to the harmonic approximation . as temperature increases the vibrational structure becomes very congested and washed out . at 1000 k ( only employed for testing the method ) one can not see a resolved vibrational structure any longer , only the corresponding envelope . on the right hand side of fig . [ fig : benzenespectrum ] the two methods ( tcf - fft and ce - edgeworth ) are compared for increasing temperatures . the spectra are convoluted in the tcf - fft curves ( dashed lines ) with a gaussian line shape function of 500 @xmath57 for fwhm . the second moments ( 4.51@xmath6210@xmath63 @xmath64 ) of the gaussian line shape function is added to the second moments of the vibronic spectrum to take the line shape function into account ( see ref . @xcite for the rationalisation and details ) . the relatively broad line shape function is used for the tcf - fft curves to have vibrationally relatively structureless spectra for comparison . at 0 , 300 and 500 k , the tcf - fft curves still show vibrational structure and the ce - edgeworth curves ( solid lines ) look like nonlinear regression curves of the corresponding tcf - fft spectra . when the vibrational structures are also essentially smoothed out in the tcf - fft curves at 1000 k , the two approaches agree with each other extremely well . up to the 4-th order cumulants are used for 0 , 300 , 500 k and up to 8-th order cumulants are computed for 1000 k. in table [ table : moments ] the moments computed numerically ( via derivatives ) and analytical are compared . at low orders and all temperatures the two methods agree well and for higher orders still the agreement is satisfactory . one of the advantages of the numerical method is that one only needs to compute the tcf for the first few time steps . the analytical method usually meets a combinatorial problem in high order cumulant calculations due to the analytic derivatives of the inverse matrix . the second advantage is that it is easy to include linear and nonlinear non - condon effects . the third advantage is that one can incorporate general line shape functions which would not have well defined cumulants ( see the discussion on page 415 of ref . @xcite ) . mean excitation wavenumbers are computed for the ht active @xmath65 symmetric vibrational modes of the final state . the mean excitation energy can serve as a parameter for the individual vibrational degrees of freedom as an effective reorganisation energy or a huang ( when normalised by its harmonic energy ) , which can be characterised as a function of structural deformation , frequency change , duschinsky mode coupling and temperature both in the condon and non - condon approximation . one might naively expect a larger mean excitation energy as the temperature increases but the mean values of high frequency modes ( 1665 and 3389 @xmath57 ) in some intermediate temperature rages are smaller than at zero kelvin . this can be rationalised as follows : because the duschinsky mode mixing between low and high frequency modes is small in the present case , the high frequency modes can not obtain thermal energy from the low frequency modes efficiently . thus the high frequency modes are almost thermally inactive , whereas the total intensity ( @xmath66 ) increases as temperature increases . in the mean energy calculation of the high frequency modes at finite temperatures the denominator ( total intensity ) increases because low frequency modes accept thermal energy while the numerator ( excitation of high frequency modes ) stays constant . therefore the mean excitation energies of high frequency modes are reduced at finite temperatures . if duschinsky rotation couples the low and high frequency modes significantly ( see _ e.g. _ ref . @xcite ) , however , thermal energy can be transfered to the high frequency modes via the low frequency modes in the initial state , accordingly the mean excitation energies of high frequency modes can increase as temperature increases . we have discussed a cumulant expansion method for describing non - condon transitions and applied it to the prototypical one - photon electric dipole @xmath0 transition of benzene , which is fc forbidden but ht allowed in the linear ht approximation . the method is particularly powerful when one does not require all the details of the vibronic structures , but rather only quantities such as peak maximum , mean and variance of the spectral shape . this method is computationally much cheaper than the sum - over - states and time - correlation function approach . moreover , the information ( _ e.g. _ relevant energy window ) from the cumulant expansion method can be used in the calculation within the other two methods . herein we compared a numerical approach for the calculation of cumulants with the results from an analytical scheme . the results obtained numerically are still fairly good . with this method , one can incorporate easily nonlinear non - condon terms and various line shape functions . in the time - correlation function calculation the real part and imaginary part at each time step provide automatically the even and odd moments , respectively . in the first few time steps we already have the first few moments available and the probability distribution function ( information ) becomes complete as time progresses . financial support by the beilstein - institut , frankfurt / main , and computer time provided by the center for scientific computing ( csc ) frankfurt are gratefully acknowledged . we are indebted to jason stuber for discussions . 26ifxundefined [ 1 ] ifx#1 ifnum [ 1 ] # 1firstoftwo secondoftwo ifx [ 1 ] # 1firstoftwo secondoftwo `` `` # 1''''@noop [ 0]secondoftwosanitize@url [ 0 ] + 12$12 & 12#1212_12%12@startlink[1]@endlink[0]@bib@innerbibempty @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop ( ) @noop ( ) @noop * * , ( ) @noop ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop _ _ ( , , ) @noop * * , ( ) @noop _ _ ( , , ) @noop * * , ( ) @noop ( ) @noop * * ( ) @noop _ _ ( , , ) @noop * * , ( ) , @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * ( ) @noop ( )

when existing , cumulants can provide valuable information about a given distribution and can in principle be used to either fully reconstruct or approximate the parent distribution function . a previously reported cumulant expansion approach for franck - condon profiles [ faraday discuss . , 150 , 363 ( 2011 ) ] is extended to describe also the profiles of vibronic transitions that are weakly allowed or forbidden in the franck - condon approximation ( non - condon profiles ) . in the harmonic approximation the cumulants of the vibronic spectral profile can be evaluated analytically and numerically with a coherent state - based generating function that accounts for the duschinsky effect . as illustration , the one - photon @xmath0 uv absorption spectrum of benzene in the electric dipole and ( linear ) herzberg - teller approximation is presented herein for zero kelvin and finite temperatures .

the behaviour and dependence of the structure functions on the bjorken @xmath0 is among the most actively discussed subjects in the unpolarized and polarized deep - inelastic scattering . the particular role here belongs to the small @xmath0 region where asymptotical properties of the strong interactions can be studied . the characteristic property of the low-@xmath0 region is an essential contribution of nonperturbative effects @xcite and one of the possible ways to treat this region is the construction and application of models . of course , the shortcomings of any model approach to the study of this nonperturbative region is evident . however , one could hope to gain from these models an information which can not be obtained by perturbative methods ( cf . @xcite ) . among possible extensions in these studies are the considerations of the geometrical features of the structure functions , i.e. the dependence of the structure functions on the transverse coordinates or the impact parameter . this subject is not new . the importance of the parton distributions in the transverse plane was stressed in @xcite and , e.g. a brief model discussion was recently given in @xcite . this work is a revised and extended version of the latter one . as it has been demonstrated @xcite the @xmath1-dependent parton distribution can be related to the fourier transform of the off - forward matrix elements of parton correlation functions in the limiting case of zero skewedness . impact parameter dependence would allow one to gain an information on the spatial distribution of the partons inside the parent hadron and the spin properties of the nonperturbative intrinsic hadron structure . the geometrical properties of structure functions play an important role under analysis of the lepton nuclei deep inelastic scattering and in the hard production in the heavy ion collisions . we suppose that the deep inelastic scattering is determined by the aligned - jet mechanism @xcite and consider the @xmath1dependence of the structure functions along the lines used in @xcite . the aligned - jet mechanism is an essentially nonperturbative and allows one to relate structure functions with the discontinuities of the amplitudes of quark hadron elastic scattering . these relations are the following @xcite @xmath2|_{t=0},\quad \delta q(x ) = \frac{1}{2}\mbox{im}[f_3(s , t)-f_1(s , t)]|_{t=0 } , \quad \delta q(x ) = \frac{1}{2}\mbox{im } f_2(s , t)|_{t=0}.\ ] ] the functions @xmath3 are helicity amplitudes for the elastic quark - hadron scattering in the standard notations for the nucleon nucleon scattering . we consider high energy limit or the region of small @xmath0 . the structure functions obtained according to the above formulas should be multiplied by the factor @xmath4 probability that such aligned jet configuration occurs @xcite . the amplitudes @xmath5 are the corresponding fourier - bessel transforms of the functions @xmath6 . the relations eqs . ( [ def1 ] ) will be used as a starting point under definition of the structure functions which depend on impact parameter . according to these relations it is natural to give the following operational definition : @xmath7,\quad \delta q(x , b ) \equiv \frac{1}{2}\mbox{im}[f_3(x , b)-f_1(x , b)],\quad \delta q(x , b ) \equiv \frac{1}{2}\mbox{im}f_2(x , b),\ ] ] and @xmath8 , @xmath9 and @xmath10 are the integrals over @xmath1 of the corresponding @xmath1-dependent distributions , i.e. @xmath11 the functions @xmath12 , @xmath13 and @xmath14 depend also on the variable @xmath15 and have simple interpretations , e.g. the function @xmath16 represent probability to find in the hadron a quark @xmath17 with fraction of its longitudinal momenta @xmath0 at the transverse distance @xmath18 from the hadron geometrical center . interpretation of the spin distributions directly follows from their definitions : they are the differences of the probabilities to find quarks in the two spin states with longitudinal or transverse directions of the quark and hadron spins . it should be noted that the unitarity plays crucial role in the direct probabilistic interpretation of the function @xmath12 . indeed due to unitarity @xmath19 . the integral @xmath8 is a quark number density which is not limited by unity and can have arbitrary non negative value . thus , the given definition of the @xmath1dependent structure functions is self - consistent . of course , spin distributions @xmath13 and @xmath14 are not positively defined . the unitarity can be fulfilled through the @xmath20matrix representation for the helicity amplitudes of elastic quark hadron scattering . in the impact parameter representation the expressions for the helicity amplitudes are the following @xmath21},\quad f_2(x , b ) = { u_2(x , b)}/{[1-iu_1(x , b)]^2}\label{fu}\ ] ] unitarity requires im@xmath22 . the @xmath20matrix form of unitary representation contrary to the eikonal one does not generate itself essential singularity in the complex @xmath0 plane at @xmath23 and implementation of unitarity can be performed easily . the model which provides explicit form of helicity functions @xmath24 has been described elsewhere @xcite . a hadron consists of the constituent quarks aligned in the longitudinal direction and embedded into the nonperturbative vacuum ( condensate ) . the constituent quark appears as a quasiparticle , i.e. as current valence quark surrounded by the cloud of quark - antiquark pairs of different flavors . we refer to effective qcd approach and use the njl model @xcite as a basis . the lagrangian in addition to the four fermion interaction @xmath25 of the original njl model includes the six fermion @xmath26breaking term @xmath27 @xcite . transition to partonic picture is described by the introduction of a momentum cutoff @xmath28 gev , which corresponds to the scale of chiral symmetry spontaneous breaking @xcite . this picture for a hadron structure implies that overlapping and interaction of peripheral condensates in hadron collision occurs at the first stage . in the overlapping region the condensates interact and as a result virtual massive quark pairs appear . being released a part of hadron energy carried by the peripheral condensates goes to generation of massive quarks . in another words nonlinear field couplings transform kinetic energy into internal energy of dressed quarks . of course , number of such quarks fluctuates . the average number of quarks in the cosidered case is proportional to convolution of the condensate distributions @xmath29 of the colliding constituent quark and hadron : @xmath30 where the function @xmath31 is determined by a transformation thermodynamics of kinetic energy of interacting condenstates to the internal energy of massive quarks . to estimate the @xmath31 it is feasible to assume that it is proportional to the maximal possible energy dependence @xmath32 where @xmath33 is the average fraction of energy carried by the constituent quarks , @xmath34 is the mass scale of constituent quarks . in the model each of the constituent valence quarks located in the central part of the hadron is supposed to scatter in a quasi - independent way by the produced virtual quark pairs at given impact parameter and by the other valence quarks . when smeared over longitudinal momenta the scattering amplitude of constituent valence quark @xmath35 may be represented in the form @xmath36\langle v_q(b ) \rangle,\label{sme}\ ] ] where @xmath37 is the total number of quarks in the system of the colliding constituent quark and hadron and @xmath38 is the smeared amplitude of single quark - quark scattering . in this approach the elastic scattering amplitude satisfies the unitarity since it is constructed as a solution of the following equation @xmath39 which is presented here in operator form . the function @xmath40 ( generalized reaction matrix ) the basic dynamical quantity of this approach is then chosen as a product of the averaged quark amplitudes @xmath41 in accordance with assumed quasi - independent nature of valence quark scattering . the strong interaction radius of the constituent quark @xmath35 is determined by its compton wavelength and the @xmath1dependence of the function @xmath42 related to the quark formfactor @xmath43 has a simple form @xmath44 . the helicity flip transition , i.e. @xmath45 occurs when the valence quark knocks out a quark with the opposite helicity and the same flavor @xcite . the explicit expressions for the helicity functions @xmath24 at small @xmath0 have been obtained from the functions @xmath46 @xcite by the substitute @xmath47 and at small values of @xmath0 they are the following : @xmath48,\quad u_2(x , b)=g_f^2(q^2)\frac{m_q^2x}{q^2}\exp[-2(\alpha -1)m_qb/\xi]u_0(x , b ) , \label{uis}\ ] ] where @xmath49^{n}\exp[-mb/\xi].\ ] ] @xmath50 , @xmath51 , @xmath52 , @xmath53 and @xmath54 are the model parameters , some of them in this particular case of quark - hadron scattering depend on the virtuality @xmath15 . the meaning of these parameters is not crucial here ; note only that @xmath55 is the average mass of constituent quarks in the quark - hadron system of @xmath37 quarks and @xmath56 is their total mass , i.e. @xmath57 . we consider here for simplicity pure imaginary case . we need to keep the subleading terms in the expressions for @xmath58 and @xmath59 since the @xmath13 is determined by their difference . for @xmath60 one can keep only leading term . then using eqs . ( [ fu ] ) we obtain at small @xmath0 : @xmath61 ^ 2},\ ] ] @xmath62 \frac{\tilde u_0(x , b)}{[1+\tilde u_0(x , b)]^2},\ ] ] where @xmath63 . from the above expressions it follows that @xmath12 has a central @xmath1dependence , while @xmath13 and @xmath14 have peripheral profiles . their qualitative dependence on the impact parameter @xmath1 is depicted in fig . 1 . the function @xmath13 has a maximum located at @xmath64.\ ] ] = 80 mm . from eqs.([qxb],[dqxb ] ) it follows that factorization of @xmath0 and @xmath1 dependencies is not allowed by unitarity and this provides constraints for the model parameterizations of structure functions which depend on @xmath0 and @xmath1 variables . indeed , it is clear from eqs.([qxb],[dqxb ] ) that factorized form of the input `` amplitude '' @xmath65 can not survive after unitarization due to the presence of the denominators . it is to be noted here that from the relation of impact parameter distributions with the off - forward parton distributions @xcite it follows that the same conclusion on the absence of factorization is also valid for the off - forward parton distributions with zero skewedness . the following relation between the structure functions @xmath13 and @xmath14 can also be inferred from the above model - based formulas @xmath66 thus , the function @xmath14 which describes transverse spin distribution is suppressed by the factors @xmath67 and @xmath68 , i.e. it has a more central profile . this suppression also reduces double - spin transverse asymmetries in the central region in the drell - yan production compared to the corresponding longitudinal asymmetries . the strange quark structure functions have also a more central @xmath1dependence than in the case of @xmath69 and @xmath70 quarks . the radius of the corresponding quark matter distribution follows from eq . ( [ dqxb ] ) and is the following @xmath71 while the ratio of the strange quark distributions to the light quark distributions radii is given by the corresponding constituent quark masses , i.e. for the nucleon this ratio would be @xmath72 where @xmath73 . time reversal invariance of strong interactions allows one to write down relations similar to eqs.([def1 ] ) for the fragmentation functions also and obtain expressions for the fragmentation functions @xmath74 , @xmath75 , @xmath76 which have just the same dependence on the impact parameter @xmath1 as the corresponding structure functions . the fragmentation function @xmath77 is the probability for fragmentation of quark @xmath17 at transverse distance @xmath78 ( @xmath79 ) into a hadron @xmath80 which carry the fraction @xmath81 of the quark momentum . in this case @xmath1 is a transverse distance between quark @xmath17 and the center of the hadron @xmath80 . it is positively defined and due to unitarity obey to the inequality @xmath82 . the physical interpretations of spin dependent fragmentation functions @xmath83 and @xmath84 is similar to that of corresponding spin structure function . it is interesting to note that the spin structure functions have a peripheral dependence on the impact parameter contrary to central profile of the unpolarized structure function . it could be related to the orbital angular momentum of quarks inside the constituent quark . the important point what the origin of this orbital angular momenta is . it was proposed @xcite to use an analogy with an anisotropic extension of the theory of superconductivity which seems to match well with the picture for a constituent quark . the studies @xcite of that theory show that the presence of anisotropy leads to axial symmetry of pairing correlations around the anisotropy direction @xmath85 and to the particle currents induced by the pairing correlations . in another words it means that a particle of the condensed fluid is surrounded by a cloud of correlated particles which rotate around it with the axis of rotation @xmath86 . calculation of the orbital momentum shows that it is proportional to the density of the correlated particles . thus , it is clear that there is a direct analogy between this picture and that describing the constituent quark . an axis of anisotropy @xmath86 can be associated with the polarization vector of current valence quark located at the origin of the constituent quark . the orbital angular momentum @xmath87 lies along @xmath86 . spin of constituent quark , e.g. @xmath20-quark , in the model used is given by the sum : @xmath88 in principle , @xmath89 and @xmath90 can include contribution of gluon angular momentum , however , since we consider effective lagrangian approach where gluon degrees of freedom are overintegrated , we do not concern problems of the separation and mixing of the quark angular momentum and gluon effects in qcd ( cf . @xcite ) . in the njl model @xcite the six - quark fermion operator simulates the effect of gluon operator @xmath91 , where @xmath92 is the gluon field tensor in qcd . it is worth to note here that in general large gluon orbital angular momentum is expected to be almost canceled by gluon spin contribution @xcite . the value of the orbital momentum contribution into the spin of constituent quark can be estimated according to the relation between contributions of current quarks into a proton spin and corresponding contributions of current quarks into a spin of the constituent quarks and that of the constituent quarks into proton spin @xcite : @xmath93 where @xmath94 . the value of @xmath95 was measured in the deep inelastic scattering . thus , on the grounds of the experimental data for polarized dis we arrive to conclusion that the significant part of the spin of constituent quark in the model should be associated with the orbital angular momentum of the current quarks inside the constituent one @xcite . then the peripherality of the spin structure functions can be correlated with the large contribution of the orbital angular momentum , i.e. with the quarks coherent rotation . indeed , there is a compensation between the total spin of the quark - antiquark cloud and its orbital angular momenta , i.e. @xmath96 and therefore this correlation follows if the above compensation has a local nature and valid for a fixed impact parameter . the important role of orbital angular momentum was known long before emc discovery @xcite and reappeared after as one of the transparent explanations of the polarized deep - inelastic scattering data @xcite . lattice qcd calculations in the quenched approximation also indicate significant quark orbital angular momentum contribution to spin of a nucleon @xcite . it is interesting to find out possible experimental signatures of the peripheral geometrical profiles of the spin structure functions and the significant role of the orbital angular momentum . one of such indications could be an observation of the different spatial distributions of charge and magnetization at jefferson lab @xcite . it would also be important to have a precise data for the strange formfactor . + * acknowledgements : this work was supported in part by the russian foundation for basic research under grant no . 99 - 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we consider impact parameter dependence of the polarized and unpolarized structure functions . unitarity does not allow factorization of the structure functions over the bjorken @xmath0 and the impact parameter @xmath1 variables . on the basis of the particular geometrical model approach we conclude that spin of constituent quark may have a significant orbital angular momentum component which can manifest itself through the peripherality of the spin dependent structure functions . + pacs numbers : 13.60.hb ; 13.88.+e

SECTION 1. SHORT TITLE; AMENDMENT OF 1986 CODE. (a) Short Title.--This Act may be cited as the ``Higher Education Savings Credit Act of 1997''. (b) Amendment of 1986 Code.--Except as otherwise expressly provided, whenever in this Act an amendment or repeal is expressed in terms of an amendment to, or repeal of, a section or other provision, the reference shall be considered to be made to a section or other provision of the Internal Revenue Code of 1986. SEC. 2. CREDIT FOR CONTRIBUTIONS TO EDUCATION INVESTMENT ACCOUNTS. (a) In General.--Subpart A of part IV of subchapter A of chapter 1 (relating to nonrefundable personal credits) is amended by inserting after section 23 the following new section: ``SEC. 24. CONTRIBUTIONS TO EDUCATION INVESTMENT ACCOUNTS. ``(a) Allowance of Credit.-- ``(1) In general.--In the case of an individual, there shall be allowed as a credit against the tax imposed by this chapter for the taxable year an amount equal to the applicable percentage of the contributions made by the taxpayer for the taxable year to an education investment account of an account holder who is an individual with respect to whom the taxpayer is allowed a deduction under section 151(c) for such taxable year. ``(2) Applicable percentage.--For purposes of paragraph (1), the applicable percentage is the percentage determined in accordance with the following table with respect to the age of the account holder as of the close of the taxable year: ``If the account The applicable holder's age is: percentage is: Not over 6................................. 50 Over 6 but not over 9...................... 40 Over 9 but not over 12..................... 30 Over 12 but not over 15.................... 20 Over 15 but not over 18.................... 10 ``(b) Limitation on Amount of Contributions Taken Into Account in Determining Credit.--The amount of contributions which may be taken into account under subsection (a) with respect to each account holder shall not exceed $500. ``(c) Definitions and Special Rules.--For purposes of this section-- ``(1) Education investment account.--The term `education investment account' means a trust created or organized in the United States exclusively for the purpose of paying the qualified higher education expenses of the account holder, but only if the written governing instrument creating the trust meets the following requirements: ``(A) No contribution will be accepted-- ``(i) unless it is in cash, ``(ii) except in the case of rollover contributions from another education investment account, in excess of $1,500 for any calendar year, and ``(iii) after the date on which the account holder attains age 18. ``(B) The trustee is a bank (as defined in section 408(n)) or another person who demonstrates to the satisfaction of the Secretary that the manner in which that person will administer the trust will be consistent with the requirements of this section. ``(C) No part of the trust assets will be invested in life insurance contracts. ``(D) The assets of the trust shall not be commingled with other property except in a common trust fund or common investment fund. ``(E) Any balance in the education investment account on the day after the date on which the account holder attains age 30 (or, if earlier, the date on which such holder dies) shall be distributed within 30 days of such date to the account holder (or in the case of death, the beneficiary). ``(2) Qualified higher education expenses.-- ``(A) In general.--The term `qualified higher education expenses' means the cost of attendance (within the meaning of section 472 of the Higher Education Act of 1965 (20 U.S.C. 1087ll), as in effect on the date of the enactment of the Higher Education Access and Affordability Act of 1997) of the account holder at an eligible educational institution, except that such expenses shall be reduced by-- ``(i) the amount excluded from gross income under section 135 by reason of such expenses, and ``(ii) the amount of the reduction described in section 135(d)(1) (other than subparagraph (E)). ``(B) State tuition plans.--Such term shall include amounts paid or incurred to purchase tuition credits or certificates, or to make contributions to an account, under a qualified State tuition program (as defined in section 529(b)). ``(3) Eligible educational institution.--The term `eligible educational institution' has the meaning given such term by section 135(c)(3). ``(4) Account holder.--The term `account holder' means the individual for whose benefit the education investment account is established. ``(5) Time when contributions deemed made.--A taxpayer shall be deemed to have made a contribution on the last day of the preceding taxable year if the contribution is made on account of such taxable year and is made not later than the time prescribed by law for filing the return for such taxable year (not including extensions thereof). ``(6) Account may not be established for benefit of more than 1 individual.--An education investment account may not be established for the benefit of more than 1 individual. ``(7) Special rule where more than 1 account.--If, at any time during a calendar year, 2 or more education investment accounts are maintained for the benefit of an individual, only the account first established shall be treated as an education investment account for purposes of this section. This paragraph shall not apply to the extent more than 1 account exists solely by reason of a rollover contribution. ``(d) Tax Treatment of Account.-- ``(1) In general.--An education investment account shall be exempt from taxation under this subtitle. Notwithstanding the preceding sentence, the education investment account shall be subject to the taxes imposed by section 511 (relating to imposition of tax on unrelated business income of charitable organizations). ``(2) Special rules.--Rules similar to the rules of paragraphs (2) and (4) of section 408(e) shall apply to any education investment account, and any amount treated as distributed under such rules shall be treated as not used to pay qualified higher education expenses. ``(e) Tax Treatment of Distributions.-- ``(1) In general.--Except as otherwise provided in this subsection, any amount paid or distributed out of an education investment account shall be included in gross income of the payee or distributee for the taxable year in the manner prescribed by section 72. For purposes of the preceding sentence, rules similar to the rules of section 408(d)(2) shall apply. ``(2) Distribution used to pay educational expenses.-- Paragraph (1) shall not apply to any payment or distribution out of an education investment account to the extent such payment or distribution is used exclusively to pay the qualified higher education expenses of the account holder. ``(3) Special rule for applying section 2503.--If any payment or distribution from an education investment account is used exclusively for the payment to an eligible educational institution of the qualified higher education expenses of the account holder, such payment shall be treated as a qualified transfer for purposes of section 2503(e). ``(4) Additional tax and credit recapture for distributions not used for educational expenses.-- ``(A) In general.-- ``(i) Additional tax.--The tax imposed by this chapter for any taxable year on any taxpayer who receives a payment or distribution from an education investment account which is includible in gross income under paragraph (1) shall be increased by 10 percent of the amount which is so includible. ``(ii) Credit recapture.--If any payment or distribution out of an education investment account is not used exclusively to pay the qualified higher education expenses of the account holder, the account holder's tax imposed by this chapter for the taxable year in which such payment or distribution is made shall be increased by the lesser of the amount of the payment or distribution or the excess (if any) of-- ``(I) the aggregate credit allowed under this section for contributions to such account, over ``(II) the aggregate increase in tax under this clause for all prior taxable years with respect to payments and distributions out of such account. ``(B) Exception for disability, death, or scholarship.--Subparagraph (A) shall not apply if the payment or distribution is-- ``(i) made on account of the death or disability of the account holder, or ``(ii) made on account of a scholarship (or allowance or payment described in section 135(d)(1) (B) or (C)) received by the account holder to the extent the amount of the payment or distribution does not exceed the amount of the scholarship, allowance, or payment. ``(C) Excess contributions returned before due date of return.--Subparagraph (A) shall not apply to the distribution to a contributor of any contribution paid during a taxable year to an education investment account to the extent that such contribution, when added to previous contributions to the account during the taxable year, exceeds $1,500 if-- ``(i) such distribution is received on or before the day prescribed by law (including extensions of time) for filing such contributor's return for such taxable year, and ``(ii) such distribution is accompanied by the amount of net income attributable to such excess contribution. Any net income described in clause (ii) shall be included in the gross income of the contributor for the taxable year in which such excess contribution was made. ``(5) Rollover contributions.--Paragraph (1) shall not apply to any amount paid or distributed from an education investment account to the extent that the amount received is paid into another education investment account for the benefit of the account holder not later than the 60th day after the day on which the holder receives the payment or distribution. The preceding sentence shall not apply to any payment or distribution if it applied to any prior payment or distribution during the 12-month period ending on the date of the payment or distribution. ``(6) Special rules for death and divorce.--Rules similar to the rules of section 220(f) (7) and (8) shall apply. ``(f) Community Property Laws.--This section shall be applied without regard to any community property laws. ``(g) Custodial Accounts.--For purposes of this section, a custodial account shall be treated as a trust if the assets of such account are held by a bank (as defined in section 408(n)) or another person who demonstrates, to the satisfaction of the Secretary, that the manner in which he will administer the account will be consistent with the requirements of this section, and if the custodial account would, except for the fact that it is not a trust, constitute an account described in subsection (b)(1). For purposes of this title, in the case of a custodial account treated as a trust by reason of the preceding sentence, the custodian of such account shall be treated as the trustee thereof. ``(h) Reports.--The trustee of an education investment account shall make such reports regarding such account to the Secretary and to the account holder with respect to contributions, distributions, and such other matters as the Secretary may require under regulations. The reports required by this subsection shall be filed at such time and in such manner and furnished to such individuals at such time and in such manner as may be required by those regulations.'' (b) Tax on Prohibited Transactions.--Section 4975 (relating to prohibited transactions) is amended-- (1) by adding at the end of subsection (c) the following new paragraph: ``(5) Special rule for education investment accounts.--An individual for whose benefit an education investment account is established and any contributor to such account shall be exempt from the tax imposed by this section with respect to any transaction concerning such account (which would otherwise be taxable under this section) if, with respect to such transaction, the account ceases to be an education investment account by reason of the application of section 24 to such account.''; and (2) in subsection (e)(1), by striking ``or'' at the end of subparagraph (D), by redesignating subparagraph (E) as subparagraph (F), and by inserting after subparagraph (D) the following new subparagraph: ``(E) a education investment account described in section 24(c), or''. (c) Failure To Provide Reports on Education Investment Accounts.-- Section 6693 (relating to failure to provide reports on individual retirement accounts or annuities) is amended-- (1) by striking ``individual retirement'' and inserting ``certain tax-favored'' in the heading of such section, and (2) in subsection (a)(2), by striking ``and'' at the end of subparagraph (A), by striking the period at the end of subparagraph (B) and inserting ``, and'', and by adding at the end the following new subparagraph: ``(C) section 24(h) (relating to education investment accounts).'' (d) Coordination With Savings Bond Exclusion.--Section 135(d)(1) is amended by striking ``or'' at the end of subparagraph (C), by striking the period at the end of subparagraph (D) and inserting ``, or'' , and by adding at the end the following new subparagraph: ``(E) a payment or distribution from an education investment account (as defined in section 24(c)).'' (e) Clerical Amendments.-- (1) The table of sections for subpart A of part IV of subchapter A of chapter 1 is amended by inserting after the item relating to section 23 the following new item: ``Sec. 24. Contributions to education investment accounts.'' (2) The item relating to section 6693 in the table of sections for subchapter B of chapter 68 is amended by striking ``individual retirement'' and inserting ``certain tax- favored''. (f) Effective Date.--The amendments made by this section shall apply to taxable years beginning after December 31, 1997.

Higher Education Savings Credit Act of 1997 - Amends the Internal Revenue Code to establish a credit for contributions made by a taxpayer to a qualifying higher education investment account for a dependent not over 18 years old. Determines such credit upon a maximum annual contribution of $500 per account holder and an age-based percentage. Excludes account distributions from gross income if used to pay the holder's qualified higher education expenses, and provides for an additional tax and credit recapture (with exceptions) if used otherwise. Sets forth related reporting requirements.

`` stochastic resonance '' ( sr ) is a recently observed cooperative phenomena in nonlinear systems , where the ambient noise helps in amplifying a sub threshold signal ( which would have been otherwise undetected ) when the signal frequency is close to a critical value @xcite ( see @xcite for a recent review ) . a simple scenario for observing such a phenomena is a heavily damped bistable dynamical system ( e.g. , a potential well with two minima ) subjected to an external periodic signal . as a result , each of the minima are alternately raised and lowered in the course of one complete cycle . if the amplitude of the forcing is less than the barrier height between the wells , the system can not switch between the two states . however , the introduction of noise can give rise to such switching . as the noise level is gradually increased , the stochastic switchings will approach a degree of synchronization with the periodic signal until the noise is so high that the bistable structure is destroyed , thereby overwhelming the signal . so , sr can be said to occur because of noise - induced hopping between multiple stable states of a system , locking on to an externally imposed periodic signal . the characteristic signature of sr is the non - monotonic nature of the _ signal - to - noise ratio _ ( snr ) as a function of the external noise intensity . a theoretical understanding of this phenomena in bistable systems , subject to both periodic and random forcing , has been obtained based on the rate equation approach @xcite . as the output of a chaotic process is indistinguishable from that of a noisy system , the question of whether a similar process occurs in the former case has long been debated . in fact , benzi _ et al _ @xcite indicated that the lorenz system of equations , a well - known paradigm of chaotic behavior might be showing sr . later studies @xcite in both discrete- and continuous - time systems seemed to support this view . however , it is difficult to guarantee that the response behavior is due to `` resonance '' and not due to `` forcing '' . in the latter case , the periodic perturbation is of so large an amplitude , that the system is forced to follow the driving frequency of the periodic forcing . the ambiguity is partly because the snr is a monotonically decreasing function of the forcing frequency and can not be used to distinguish between resonance and forcing . signature of sr can also be observed in the _ residence time distribution_. in the presence of a periodic modulation , the distribution shows a number of peaks superposed on an exponential background . however , this is observed both in the case of resonance as well as forcing . the ambiguity is , therefore , present in theoretical @xcite and experimental @xcite studies of noise - free sr , where regular and chaotic phases take the role of the two stable states in conventional sr . although the distribution of the lengths of the chaotic interval shows a multi - peaked structure , this by itself is not sufficient to ensure that the enhanced response is not due to `` forcing '' . in the present work this problem is avoided by measuring the response of the system in terms of the peaks in the normalized distribution of residence times @xcite . for sr , the strength of the peaks shows non - monotonicity with the variation of both noise intensity and signal frequency . in this paper we present two simple models for studying stochastic resonance where the role of noise is played by the chaos generated through the inherent dynamics of the system . in section 2 , the first model for studying deterministic sr is introduced . it is a 1-dimensional piecewise linear map with uniform slope throughout . the numerical observation of resonance in computer simulations for parametric perturbation is described and a theoretical analysis of these observations is given . additive perturbations also give rise to similar resonance behavior . in section 3 , we consider the second model , an excitatory - inhibitory neural pair . it is additively perturbed with a very low amplitude signal and the system response is observed , for which numerical and theoretical results are given . we conclude with a discussion on the implication of such resonance phenomena for biological systems . recently , sr has been studied in 1-d maps with two well - defined states ( but not necessarily stable ) with switching between them aided by either additive or multiplicative external noise @xcite . however , dynamical contact of two chaotic 1-d maps can also induce rhythmic hopping between the two domains of the system @xcite . we now show how the chaotic dynamics of a system can itself be used for resonant switching between two states , without introducing any external noise . the model chosen here is a piecewise linear anti - symmetric map , henceforth referred to as the discontinuous anti - symmetric tent ( dat ) map @xcite , defined in the interval [ @xmath0 : @xmath1 the map has a discontinuity at @xmath2 . the behavior of the system is controlled by the parameter @xmath3 @xmath4 . the map has a symmetrical pair of fixed points @xmath5 which are stable for @xmath6 and unstable for @xmath7 . another pair of unstable fixed points , @xmath8 come into existence for @xmath9 . onset of chaos occurs at @xmath10 . the chaos is symmetry - broken , i.e. , the trajectory is restricted to either of the two sub - intervals r:(@xmath11 and l:[@xmath12 ) , depending on initial condition . symmetry is restored at @xmath13 . it is to be noted that as @xmath14 from above , @xmath15 both collide at @xmath16 causing an interior crisis , which leads to symmetry - breaking of the chaotic attractor . the lyapunov exponent of the map is a simple monotonic function of the parameter @xmath3 . to observe sr , the value of @xmath3 was kept close to 2 , and then modulated sinusoidally with amplitude @xmath17 and frequency @xmath18 , i.e. , @xmath19 we refer to this henceforth as multiplicative or parametric perturbation , to distinguish it from additive perturbation ( discussed later ) . the system immediately offers an analogy to the classical bistable well scenario of sr . the sub intervals l and r correspond to the two wells between which the system hops to and fro , aided by the inherent noise ( chaos ) and the external periodic forcing . the response of the system is measured in terms of the normalized distribution of residence times , @xmath20 @xcite . this distribution shows a series of peaks centered at @xmath21 , i.e. , odd - integral multiples of the forcing period , @xmath22 . the strength of the @xmath23-th peak @xmath24 is obtained at different values of @xmath18 , keeping @xmath25 fixed for @xmath23=1,2 and 3 . to maximize sensitivity , @xmath26 was taken to be @xmath27 . for @xmath28 and @xmath29 , the response of the system showed a non - monotonic behavior as @xmath18 was varied , with @xmath30 peaking at @xmath31 , a value dependent upon @xmath25 @xmath32 a clear signature of sr - type phenomenon . @xmath33 and @xmath34 also showed non - monotonic behavior , peaking roughly at odd - integral multiples of @xmath35 ( fig . [ fig204 ] ( a ) ) . similar observations of @xmath36 were also done by varying @xmath25 , keeping @xmath18 fixed . [ fig204 ] ( b ) shows the results of simulations for @xmath37 and @xmath29 . here also a non - monotonicity was observed for @xmath30,@xmath33 and @xmath34 . the broadness of the response curve and the magnitude of the peak - strengths are a function of the perturbation magnitude , @xmath17 . analytical calculations were done to obtain the average residence - time at any one of the sub intervals . this gives the dominant time - scale of the intrinsic dynamics . mapping the system dynamics to an approximately first - order markov process , the mean residence time is obtained as @xcite @xmath38 where , @xmath39 . so , for @xmath28 , @xmath40 . this predicts that a peak in the response should be observed at a frequency @xmath41 , which agrees with the simulation results . the mean time spent by the trajectory in any one of the sub - intervals ( l or r ) can also be calculated exactly for piecewise linear maps @xcite . from the geometry of the dat map , the total fraction of r which escapes to l after @xmath42 iterations is found to be @xmath43 @xcite . this is just the probability that the trajectory spends a period of @xmath42 iterations in r before escaping to l ( @xmath44 ) . so the average lifetime of a trajectory in r is @xmath45 note that , as @xmath46 , eqn . ( [ avgeq ] ) becomes identical to the above expression . for @xmath25 = 2.01 , @xmath47 = 200 , in good agreement with the result obtained using the approximate markov partitioning ( which ensures the validity of the approximation ) . by symmetry of the map , identical results will be obtained if we consider the trajectory switching from l to r. similar study was also conducted with additive perturbation for the above map . in this case the dynamical system is defined as @xmath48 . the simulation results showed non - monotonic behavior for the response , as either @xmath18 or @xmath49 was varied , keeping the other constant , but this was less marked than in the case of multiplicative perturbation . the resonance phenomenon is also observed in an excitatory - inhibitory neural pair , with anti - symmetric , piecewise linear activation function . this type of activation function has been chosen for ease of theoretical analysis . however , sigmoidal activation functions also show similar resonance behavior . [ exinpair ] shows a pair of coupled excitatory and inhibitory neurons . the discrete - time dynamics of such simple neural networks are found to exhibit a rich variety of behavior , including chaos @xcite . if @xmath50 and @xmath51 ( @xmath52 $ ] ) be the state of the excitatory and inhibitory elements at the @xmath42-th iteration , respectively , then the discrete time - evolution equation of the system is given by @xmath53 @xmath54 where @xmath55 is the connection weight from neuron @xmath23 to neuron @xmath56 , and @xmath57 is an external input . the activation function is of anti - symmetric , piecewise linear nature , viz . , @xmath58 , @xmath59 , and @xmath60 under the restriction @xmath61 , the 2-dimensional dynamics reduces to a simple 1-dimensional form . the relevant variable is now the effective neural potential @xmath62 ( @xmath63 $ ] ) , whose dynamics is governed by the map @xmath64 where @xmath65 are the suitably scaled transfer function parameters . the design of the network ensures that the phase space [ @xmath66 is divided into two well - defined and segregated sub - intervals l:[@xmath67 and r:[@xmath68 . the critical points of the map are at @xmath69 . note that , if @xmath70 , the chaos is asymmetric , the trajectory being confined to any one of the subintervals . again , if @xmath71 , the trajectory will eventually converge to a superstable periodic cycle . therefore , for symmetric chaos , the following inequalities must be satisfied : @xmath72 from the first inequality , we have @xmath73 , and solving for @xmath74 in the limiting case of an equality , the @xmath74-value at which the symmetry is just restored is obtained as @xmath75 . note that , real roots exist only for @xmath76 . therefore , for @xmath77 , there is no dynamical connection between the two sub - intervals and the trajectory , while chaotically wandering over one of the sub intervals , can not enter the other sub interval . for @xmath78 , in a certain range of @xmath79 values the system shows both symmetry - broken and symmetric chaos , when the trajectory visits both sub intervals in turn . the curves in @xmath80-parameter space forming a boundary between the symmetric and symmetry - broken chaotic domains are given by @xmath81 . the second inequality of ( [ ineq ] ) gives , in the limiting case of an equality , @xmath82 , which forms the boundary between the regions showing symmetric chaos and superstable periodic cycles , in the ( @xmath83 ) parameter plane . the parameter space diagram in fig . [ fig204iii ] shows the various dynamical regimes occurring for different values of @xmath74 and @xmath84 , at @xmath85 . for the simulations reported here , @xmath85 and @xmath86 , for which the system shows symmetric chaos over a range of values of @xmath74 . the chaotic switching between the two sub - intervals occurs at random . however the average time spent in any of the sub - intervals before a switching event can be exactly calculated for the present model as @xmath87 as a complete cycle would involve the system switching from one sub - interval to the other and then switching back , the `` characteristic frequency '' of the chaotic process is @xmath88 . e.g. , for the system to have a `` characteristic frequency '' of @xmath37 ( say ) , the above relation provides the value of @xmath89 for @xmath90 . the system being symmetric , there is no net drift between l and r. however , in the presence of an external signal of amplitude @xmath17 , the symmetry is broken . the net drift rate , which measures the net fraction of phase space of one sub - interval mapped to the other after one iteration , is given by @xmath91 and @xmath92 otherwise . the _ critical signal strength _ , @xmath93 is a limit above which the net drift rate no longer varies in phase with the external signal . for the aforementioned system parameters @xmath94 , @xmath95 . if the input to the system is a sinusoidal signal of amplitude @xmath96 and frequency @xmath97 , we can expect the response to the signal to be enhanced , as is borne out by numerical simulations . the effect of a periodic input , @xmath98 , is to translate the map describing the dynamics of the neural pair , to the left and right , periodically . [ fig204iv ] shows the unperturbed map ( solid lines ) along with the maximum displacement to the left and right ( dotted lines ) for @xmath29 . the resultant intermittent switching between the two sub intervals , l and r , is shown in fig . [ figtime ] for @xmath37 and @xmath99 . as in the previous section , we verify the presence of resonance by looking at the peaks of the residence time distribution , where the strength of the @xmath23th peak is given by eqn . ( [ eq303 ] ) . for maximum sensitivity , @xmath26 is set as 0.25 . as seen in fig . [ fig205 ] , the dependence of @xmath100 on external signal frequency , @xmath18 , exhibits a characteristic non - monotonic profile , indicating the occurrence of resonance at @xmath101 . for the system parameters used in the simulation , @xmath102 . the results clearly establish that the switching between states is dominated by the sub - threshold periodic signal close to the resonant frequency . . [ fig205a ] the variation of @xmath30 with @xmath18 for different values of signal amplitude , @xmath17 , was also studied . for @xmath103 , the variation in the drift rate no longer matches the signal , and the maximum response is found to shift to higher frequency values ( fig . [ fig205a ] ) : e.g. , at @xmath104 , the maximum response in @xmath30 occurs at @xmath105 . for @xmath106 , the magnitude of @xmath30 at the resonance frequency , @xmath107 , has a non - monotonic nature ( fig . [ fig205a ] , inset ) . for the system parameters mentioned here , the maximum response occurs at @xmath108 . these results assume significance in light of the work done on detecting sr in the biological world . in neuronal systems , a non - zero snr is found even when the external noise is set to zero @xcite . this is believed to be due to the existence of internal noise " . this phenomenon has been examined through neural network modeling , e.g. , in @xcite , where the main source of such noise " is the effect of activities of adjacent neurons . the total synaptic input to a neuron , due to its excitatory and inhibitory interactions with other neurons , turns out to be aperiodic and noise - like . the neural network model employed in the present work is , however , the simplest system to date , which uses its aperiodic activity to show sr - like behavior . there is also a possible connection of such ` resonance ' to the occurrence of epilepsy , whose principal feature is the synchronization of activity in neurons . low - dimensional discrete - time dynamical systems are amenable to several analytical techniques and hence can be well - understood compared to other systems . the examination of resonance phenomena in this scenario was for ease of numerical and theoretical analysis . however , it is reasonable to assume that similar behavior occurs in higher - dimensional chaotic system , described by both maps and differential equations . in fact , sr has been reported for spatially extended systems ( spatiotemporal sr ) @xcite , e.g. , in coupled map lattices @xcite . a possible area of future work is the demonstration of phenomena analogous to spatiotemporal sr with a network of coupled excitatory - inhibitory neural pairs . the above results indicate that deterministic chaos can play a constructive role in the processing of sub - threshold signals . it has been proposed that the sensory apparatus of several creatures use sr to enhance their sensitivity to weak external stimulus , e.g. , the approach of a predator . experimental study involving crayfish mechanoreceptor cells have provided evidence of sr in the presence of external noise and periodic stimuli @xcite . the above study indicates that external noise is not necessary for such amplification as chaos in neural networks can enhance weak signals . the evidence of chaotic activity in neural processes of the crayfish @xcite suggests that nonlinear resonance ( as reported here ) due to inherent chaos might be playing an active role in such systems . as chaotic behavior is extremely common in a recurrent network of excitatory and inhibitory neurons , such a scenario is not entirely unlikely to have occurred in the biological world . this can however be confirmed only by further biological studies and detailed modeling of the phenomena . r. benzi , a. sutera , and a. vulpiani , j. phys . a 14 ( 1981 ) l453 . l. gammaitoni , p. hnggi , p. jung , and f. marchesoni , rev . 70 ( 1998 ) 223 . b. mcnamara and k. wiesenfeld , phys a 39 ( 1989 ) 4854 . g. nicolis , c. nicolis , and d. mckernan , j. stat . 70 ( 1993 ) 125 ; v. s. anishchenko , a. b. neiman , and m. a. safanova , j. stat . 70 ( 1993 ) 183 . a. crisanti , m. falcioni , g. paladin , and a. vulpiani , j. phys . a 27 ( 1994 ) l597 . e. reibold , w. just , j. becker , and h. benner , phys . 78 ( 1997 ) 3101 . l. gammaitoni , f. marchesoni , and s. santucci , phys . 74 ( 1995 ) 1052 . m. gade , r. rai , and h. singh , phys . e 56 ( 1997 ) 2518 . c. seko and k. takatsuka , phys . e 54 ( 1996 ) 956 . s. sinha and b. k. chakrabarti , phys . rev . e 58 ( 1998 ) 8009 . r. m. everson , phys . lett . a 122 ( 1987 ) 471 . s. sinha , fundamenta informaticae ( in press , 1999 ) ; s. sinha , ph.d . thesis , indian statistical institute , calcutta , 1998 . k. wiesenfeld and f. moss , nature 373 ( 1995 ) 33 . w. wang and z. d. wang , phys . e 55 ( 1997 ) 7379 . j. f. lindner , b. k. meadows , w. l. ditto , m. e. inchiosa , and a. r. bulsara , phys . lett . 75 ( 1995 ) 3 . j. k. douglass , l. wilkens , e. pantazelou , and f. moss , nature 365 ( 1993 ) 337 . x. pei and f. moss , nature 379 ( 1996 ) 618 .

the phenomenon of stochastic resonance ( sr ) is reported in a completely noise - free situation , with the role of thermal noise being taken by low - dimensional chaos . a one - dimensional , piecewise linear map and a pair of coupled excitatory - inhibitory neurons are the systems used for the investigation . both systems show a transition from symmetry - broken to symmetric chaos on varying a system parameter . in the latter state , the systems switch between the formerly disjoint attractors due to the inherent chaotic dynamics . this switching rate is found to `` resonate '' with the frequency of an externally applied periodic perturbation ( either parametric or additive ) . the existence of a resonance in the response of the system is characterized in terms of the residence - time distributions . the results are an unambiguous indicator of the presence of sr - like behavior in these systems . analytical investigations supporting the observations are also presented . the results have implications in the area of information processing in biological systems . pacs nos . : 05.40.+j , 05.45.+b

SECTION 1. LIQUIDATION OR RELIQUIDATION OF CERTAIN TOMATO SAUCE PREPARATION ENTERED IN MAY 9, 1992 THROUGH SEPTEMBER 18, 1993. (a) In General.--Notwithstanding section 514 of the Tariff Act of 1930 (19 U.S.C. 1514) or any other provision of law and subject to the provisions of subsection (b), the United States Customs Service shall, not later than 180 days after the receipt of the request described in subsection (b), liquidate or reliquidate each entry described in subsection (d) containing any merchandise which, at the time of the original liquidation, was classified under subheading 2002.10.00 of the Harmonized Tariff Schedule of the United States (relating to tomatoes, prepared or preserved) at the rate of duty that would have been applicable to such merchandise if the merchandise had been liquidated or reliquidated under subheading 2103.90.60 of the Harmonized Tariff Schedule of the United States (relating to tomato sauce preparation) on the date of entry. (b) Requests.--Reliquidation may be made under subsection (a) with respect to an entry described in subsection (d) only if a request therefor is filed with the Customs Service within 90 days after the date of enactment of this Act and the request contains sufficient information to enable the Customs Service to locate the entry or reconstruct the entry if it cannot be located and to confirm that the entry consists of tomato sauce preparations properly classifiable under subheading 2103.90.60 of the Harmonized Tariff Schedule of the United States. (c) Payment of Amounts Owed.--Any amounts owed by the United States pursuant to the liquidation or reliquidation of an entry under subsection (a) shall be paid not later than 180 days after the date of such liquidation or reliquidation. (d) Affected Entries.--The entries referred to in subsection (a) are as follows: Entry number Date of entry 084-0532527-8 05-09-92 084-0532938-7 06-13-92 084-0532939-5 06-13-92 084-0533381-9 07-29-92 084-0533382-7 07-29-92 084-0533383-5 07-29-92 084-0533384-3 07-29-92 084-0533732-3 09-01-92 084-0533823-0 09-01-92 084-0533824-8 09-01-92 084-0534010-3 09-19-92 084-0534052-5 09-26-92 084-0534199-4 10-06-92 084-0534205-9 10-14-92 084-0534206-7 10-14-92 084-0534207-5 10-14-92 084-0534669-6 11-18-92 084-0534670-4 11-18-92 084-0534930-2 11-28-92 084-0535157-1 12-23-92 084-0535311-4 01-09-93 084-0535312-2 01-02-93 084-0535441-9 01-09-93 084-0535578-8 01-27-93 084-0535694-3 02-07-93 084-0535695-0 02-07-93 084-0535854-3 02-24-93 084-0535855-0 02-24-93 084-0535857-6 02-24-93 084-0535858-4 02-24-93 084-0535859-2 02-24-93 084-0536160-4 03-28-93 084-0536291-7 04-07-93 084-0536292-5 04-07-93 084-0536357-6 04-11-93 084-0536361-8 04-11-93 084-0536362-6 04-11-93 084-0536424-4 05-02-93 084-0536518-3 05-02-93 084-0536519-1 05-02-93 084-0536727-0 05-23-93 084-0536839-3 05-29-93 084-0536840-1 05-29-93 084-0536841-9 05-29-93 084-0536842-7 05-29-93 084-0537443-3 07-31-93 084-0537444-1 07-31-93 084-0538038-0 09-18-93 084-0538039-8 09-18-93 084-0538040-6 09-18-93

Directs the Customs Service, upon request, to liquidate or reliquidate certain entries of tomato sauce preparation.

asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness , variable airflow limitation , and symptoms such as dyspnea , wheezing , and cough , which improve spontaneously or with treatment . the primary goals of asthma treatment include complete symptom control , optimal management of limitations in activities of daily living , and reducing future risks . 1 2 most asthma patients have mild to moderate asthma , which is easily controlled with the use of inhaled corticosteroids ( ics ) alone or in association with a long - acting 2 agonist ( laba ) . 3 however , among patients with severe asthma , there is a small subset of patients who remain symptomatic despite good adherence to treatment , correct use of inhalers , appropriate management of comorbidities , and use of high - dose ics in association with labas , oral corticosteroids , omalizumab , or any combination of the three . 4 5 such patients are considered to have uncontrolled severe asthma ( ucsa ) , which , according to current asthma guidelines , should be treated at specialized centers . 4 5 patients with ucsa require high - dose ics alone or in association with oral corticosteroids , the adverse effects of which include decreased protein synthesis and increased protein degradation and contribute to muscle atrophy . 6 in addition , increased airway resistance and lung hyperinflation also contribute to reducing inspiratory muscle efficiency , resulting in increased muscle work and energy expenditure to overcome airflow limitation . 7 the aforementioned factors have yet to be well studied in patients with ucsa . the six - minute walk test ( 6mwt ) is a submaximal exercise test that evaluates the overall and integrated responses of all body systems involved in physical exercise , including the pulmonary system , the cardiovascular system , peripheral and systemic circulation , blood , neuromuscular units , and muscle metabolism . 8 9 respiratory muscle strength can be estimated from airway pressures generated by respiratory muscle contraction . maximal static respiratory pressures are usually measured at the mouth during inhalation and exhalation , the former being designated mip and the latter being designated mep . 10 the role of the 6mwt in the evaluation and follow - up of patients with copd , interstitial lung disease , pulmonary arterial hypertension , and heart failure is well established . 8 however , the only study evaluating the impact of severe asthma on the six - minute walk distance ( 6mwd ) in adults was a study conducted by canuto et al . , 11 who found that the 6mwd was significantly shorter in patients with difficult - to - control asthma ( dca ) using oral corticosteroids than in healthy controls . in addition , although respiratory muscle strength ( particularly mip ) has been reported to be reduced in several studies involving asthma patients , it has yet to be evaluated in patients with ucsa . 12 the primary objective of the present study was to evaluate respiratory muscle strength and 6mwt variables in patients with ucsa . secondary objectives were to evaluate the impact of oral corticosteroid use on respiratory muscle strength and to determine the correlation of the level of physical activity with the 6mwd and the level of asthma control in such patients . this was a cross - sectional study of ucsa patients over 18 years of age treated at the difficult - to - control asthma outpatient clinic of the federal university of minas gerais hospital das clnicas , in the city of belo horizonte , brazil , between september and december of 2012 . the research project was approved by the research ethics committee of the federal university of minas gerais ( etic ruling no . the diagnosis of severe asthma was based on the american thoracic society / european respiratory society ( ats / ers ) criteria , 13 as follows : major criteria - use of oral corticosteroids for at least six months per year and continuous use of high - dose ics ( 1,600 g of budesonide or equivalent ) in association with labasminor criteria - fev1 of < 80% ; pef variability > 20% ; daily use of short - acting 2 agonists ; use of more than three courses of oral corticosteroids per year ; history of near - fatal asthma ; one or more emergency room visits in the previous year ; and rapid decline in lung function after a decrease in the dose of corticosteroid therapy major criteria - use of oral corticosteroids for at least six months per year and continuous use of high - dose ics ( 1,600 g of budesonide or equivalent ) in association with labas minor criteria - fev1 of < 80% ; pef variability > 20% ; daily use of short - acting 2 agonists ; use of more than three courses of oral corticosteroids per year ; history of near - fatal asthma ; one or more emergency room visits in the previous year ; and rapid decline in lung function after a decrease in the dose of corticosteroid therapy the patients who were included in the present study received outpatient treatment for at least six months in order to control environmental factors and comorbidities , as well as to improve inhaler technique and treatment adherence . in addition , we included only patients assigned to global initiative for asthma ( gina ) and brazilian thoracic association ( bta ) asthma treatment step 4 or 5 ( labas / high - dose ics plus oral corticosteroids , anti - ige treatment , or both ) 1 2 and meeting two major ats / ers criteria or one major and two minor ats / ers criteria . 13 we excluded patients with severe heart disease ; current smokers ; former smokers who had a smoking history 10 pack - years or who had quit smoking less than one year prior ; and patients who had had exacerbations requiring emergency room treatment / hospitalization , use of prednisone or equivalent at doses above 20 mg , use of antibiotics , or any combination of the three in the last four weeks . the 6mwt was performed in a 25.6-m corridor with the use of a portable oximeter ( nonin medical , inc . , plymouth , mn , usa ) , in accordance with the recommendations of the ats . 14 each of the participants underwent two 6mwts , at least 30 min apart . we evaluated the following parameters : spo2 , as measured by pulse oximetry ; hr ; rr ; and patient perception of dyspnea and leg fatigue , as assessed by borg scale scores at the beginning and end of each test . in addition , we determined the percentage of the predicted maximal hr ( % hrmax ) for adults , hr recovery at one minute after completion of the 6mwt ( hrr1 ) , and the 6mwd . values of desaturation 4% , 8 14 % hrmax > 85% of predicted , 8 14 and hrr1 > 12 bpm were considered significant . 15 17 the 6mwt during which the longest 6mwd was covered was considered valid ; absolute and percent predicted 6mwd values were calculated by the reference equation for the 6mwd in the brazilian population . 18 spirometry was performed with a koko spirometer ( pds instrumentation inc . , louisville , co , usa ) . the tests were performed and the results were interpreted in accordance with the bta guidelines . 10 all post - bronchodilator test results were reported as absolute values and as percentages of predicted values , in accordance with pereira et al . 19 respiratory muscle strength was evaluated in accordance with the bta guidelines , 10 with a digital manometer ( warren e collins inc . , braintree , ma , usa ) , the signals being read and recorded through individual ducts . a 2-mm hole in the circuit prevented false measurements as a result of involuntary contractions of the cheeks . 20 the level of asthma control was assessed with the asthma control test ( act ) , previously validated for use in brazil , 21 23 a score of 25 points indicating clinical remission of symptoms or totally controlled asthma , a score of 20 - 24 points indicating adequately controlled asthma , and a score of < 20 points indicating uncontrolled asthma . the level of physical activity was measured with the short version of the international physical activity questionnaire ( ipaq ) , previously validated for use in brazil . 24 25 the instrument consists of seven questions regarding the frequency ( in number of days per week ) and duration ( in number of minutes per day ) of vigorous physical activity , moderate physical activity , and walking activity . on the basis of their ipaq scores , individuals are classified as very active , active , irregularly active , or sedentary . in the present study , we divided the participants into two major groups : the group of very active / active individuals and the group of irregularly active / sedentary individuals . 24 25 all study participants underwent chest hrct for the differential diagnosis of other diseases , such as copd , bronchiectasis , and allergic bronchopulmonary aspergillosis . data analysis was performed with the statistical package for the social sciences , version 18 ( spss inc . , chicago , il , usa ) , and minitab software , version 16 ( minitab inc . the shapiro - wilk test was used in order to evaluate the distribution of the data . categorical variables were expressed as absolute and relative frequencies , and continuous variables were expressed as mean and standard deviation ( parametric distribution ) or as median and range ( nonparametric distribution ) . the mann - whitney test was used in order to evaluate the difference between the 6mwd recorded for the patients with ucsa and that predicted for healthy individuals , as well as to evaluate the association of physical activity levels ( ipaq scores ) with the 6mwd , act scores , % hrmax , and hrr1 . spearman 's correlation test and the kruskal - wallis test were used in order to evaluate the association of oral corticosteroid use with mip and mep . values of p < 0.05 were considered statistically significant . on the basis of the longest 6mwd found in the literature ( with a standard deviation of 90.44 m ) and using a level of significance of 0.05 and an unpaired two - tailed student 's t - test , we estimated that a sample size of 26 was needed in order to detect a difference of 50 m between the 6mwd found in the present study and that found in the literature . three patients were excluded because of a probable overlap between asthma and copd , and another one was excluded because of asthma exacerbation during the month of data collection . the final sample consisted of 25 asthma patients ( 18 females and 7 males ) , their mean age being 49 years and their mean body mass index being 28.9 7.9 kg / m ( table 1 ) . all patients had act scores of < 15 points , 14 ( 56% ) were classified as being irregularly active / sedentary , and 20 ( 80% ) had exercise limitation in the period between asthma attacks . ten patients ( 40% ) had a history of exacerbations requiring icu admission , and 7 ( 28% ) had a history of exacerbations requiring mechanical ventilation . table 1.baseline characteristics of the uncontrolled severe asthma patients studied.acharacteristicn = 25age , years 49.8 12.6female gender18 ( 72)bmi , kg / m 28.9 7.9former smokers 4 ( 16)activity limitations in the period between attacksno limitations0 ( 0)limitations in exercise performance20 ( 80)limitations in activities of daily living3 ( 12)limitations in self - care2 ( 8)limitations at rest0 ( 0)attacks in the previous year 5 ( 0 - 23)systemic corticosteroid use during attacks ( 4 courses / year)9 ( 36)continuous oral corticosteroid use6 ( 24)total number of hospitalizations 15 ( 0 - 100)icu admissions10 ( 40)need for mechanical ventilation7 ( 28)history of cpa1 ( 4)comorbidities21 ( 84)chronic rhinosinusitis22 ( 88)nasal polyposis2 ( 8)gerd13 ( 52)obesity11 ( 44)sah2 ( 8)diabetes mellitus4 ( 16)psychiatric disorder4 ( 16)copd2 ( 8)sequelae of tuberculosis1 ( 4)abpa1 ( 4)act 14.0 3.9physical activities - ipaq score active or very active11 ( 44)irregularly active or sedentary14 ( 56)bmi : body mass index ; cpa : cardiopulmonary arrest ; gerd : gastroesophageal reflux disease ; sah : systemic arterial hypertension ; abpa : allergic bronchopulmonary aspergillosis ; act : asthma control test ; and ipaq : international physical activity questionnaire . avalues expressed as n ( % ) , except where otherwise indicated . cindividuals who had a smoking history of = 10 packyears at the time of smoking cessation or those who had quit smoking at least one year prior . bmi : body mass index ; cpa : cardiopulmonary arrest ; gerd : gastroesophageal reflux disease ; sah : systemic arterial hypertension ; abpa : allergic bronchopulmonary aspergillosis ; act : asthma control test ; and ipaq : international physical activity questionnaire . cindividuals who had a smoking history of = 10 packyears at the time of smoking cessation or those who had quit smoking at least one year prior . all patients were receiving treatment with labas and high - dose ics ( 1,600 g of budesonide or equivalent ) , 6 ( 24% ) had been using at least 10 mg / day of prednisone for more than one year , and 3 ( 12% ) were using omalizumab . the most common ct findings were bronchiectasis that was minimal / moderate and predominantly central , in 3 patients ; small areas of centrilobular emphysema , in 11 ; mild right upper lobe fibrosis / atelectasis , in 1 ; and air trapping , in 1 . there was a predominance of obstructive lung disease ( mean fev1 , 58.8 21.8% of predicted ) , and 17 patients ( 68% ) had positive bronchodilator test results . although mean mip and mep were normal , 7 ( 28% ) and 11 ( 44% ) of the 25 patients studied had reduced mip and mep ( of < 65% of predicted ) , respectively ( table 2 ) . of the 7 patients who had reduced mip , only 2 had spirometric signs of lung hyperinflation . table 2.spirometry results and maximal respiratory pressures in the uncontrolled severe asthma patients studied ( n = 25).avariableresultpre - bdpost - bdfev1,% of predicted58.8 21.8 66 22.4fev1 , l1.61 0.63 1.81 0.62fvc , % of predicted83.4 20.7 91.0 19.1fvc , l2.79 0.71 3.05 0.65fev1/fvc56.3 12.0mip , cmh2o87.2 21.0mip , % of predicted72.9 15.2mep , cmh2o108.3 42.9mep , % of predicted67.6 22.2bd : bronchodilator . avalues expressed as mean sd . there was no significant difference ( p = 0.14 ) between the median 6mwd recorded for the ucsa patients in the present study-512 m ( range , 307.2 - 597.3 m)-and that predicted for healthy individuals-534 m ( range , 382.6 - 621.3 m)-(figure 1 ) . figure 1.distribution of the six - minute walk distance ( 6mwd ) in 25 patients with uncontrolled severe asthma ( 6mwd - ucsa ) in comparison with the 6mwd predicted for healthy adults in brazil ( 6mwd - ha).(18)a * outliers . none of the patients required supplemental oxygen and there was no significant decrease in mean spo2 during the 6mwt ; however , 5 patients experienced desaturation during the test . of those , 2 experienced bronchospasm , which was reversed with the use of a short - acting 2 agonist , 2 had comorbidities ( allergic bronchopulmonary aspergillosis and sequelae of pulmonary tuberculosis ) , and 1 had evidence of emphysema and air trapping on chest ct scans . at the end of the 6mwt , table 3.six-minute walk test in the uncontrolled severe asthma patients studied ( n = 25).avariablebefore the 6mwtafter the 6mwtspo2 , % 96.1 1.193.7 3.5hr , bpm81.8 16.7117.8 20.3rr , breaths / min18.5 2.630.4 5.5borg scale score ( leg fatigue)0.1 0.42.9 2.6borg scale score ( dyspnea)0.9 1.24.7 1.96mwd , m-512 4.2hrr1 , bpm-21.7 8.3hrmax , % -71 116mwt : six - minute walk test ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the 6mwt ; and hrmax : predicted maximal hr . 6mwt : six - minute walk test ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the 6mwt ; and hrmax : predicted maximal hr . when we compared the subset of patients treated with continuous oral corticosteroids or four or more courses of oral corticosteroids per year ( n = 15 ) with that of those treated with three or fewer ( n = 10 ) , in order to investigate the association between the frequency of oral corticosteroid use and respiratory muscle strength , we found no statistically significant differences in median mip-74.5% ( range , 59.0 - 104.0% ) and 72.5% ( range , 43.0 - 104.0% ; p = 0.15 ) , respectively - or mep-67.5% ( range , 29.0 - 121.0% ) and 63.5% ( range , 34.0 - 121.0% ; p = 0.45 ) , respectively . the 11 most physically active patients and the 14 least physically active patients were found to be similar in terms of their act scores , 6mwd , hrr1 , and % hrmax during the 6mwt ( table 4 ) . table 4.association of the level of physical activity with the level of asthma control and six - minute walk test variables in the uncontrolled severe asthma patients studied ( n = 25).avariablelevel of physical activity ( ipaq score)pvery active or activeirregularly active or sedentary(n = 11)(n = 14)6mwd , m537.6 ( 320.0 - 597.3)490.0 ( 307.2 - 588.6)0.308hrr1 , bpm19.0 ( 11.0 - 37.0)19.5 ( 10.0 - 36.0)0.935hrmax , % 72 ( 53 - 89)73 ( 50 - 84)0.621act score15 ( 7 - 17)13 ( 6 - 24)0.144ipaq : international physical activity questionnaire ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the six - minute walk test ; hrmax : predicted maximal hr ; and act : asthma control test . ipaq : international physical activity questionnaire ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the six - minute walk test ; hrmax : predicted maximal hr ; and act : asthma control test . patients who do not achieve asthma control at gina asthma treatment step 4 or 5 have historically been classified as having dca . 1 however , debate over the most appropriate terminology has been ongoing for more than two decades because of the different criteria used in order to define severe asthma , dca , refractory asthma , therapy - resistant asthma , and , more recently , ucsa . in 2000 , the ats proposed criteria for defining dca , and those criteria contributed to resolving part of the controversy . 13 however , it was only after the publication of the 2013 ats / ers task force guidelines - ratified and cited in the 2014 gina guidelines - that the classification of severe asthma became clearer . 4 5 according to the aforementioned guidelines , the term " difficult - to - treat asthma " should be reserved for asthma in patients who are able to achieve better disease control after improving environmental hygiene , inhaler technique , treatment adherence , or comorbidity management . however , the same guidelines defined patients with " severe asthma " as those who , despite the aforementioned measures , required drugs assigned to gina asthma treatment steps 4 and 5 in the last 12 months or systemic corticosteroids for at least 6 months in the last 12 months in order to maintain asthma control or those in whom the disease remained inadequately controlled despite treatment . 4 5 patients defined as having ucsa are those who , in addition to having poorly controlled asthma , meet at least one of the following criteria 4 5 : an act score of < 20 points or an equivalent score on any other validated instrument for assessing asthma control ; two or more exacerbations requiring systemic corticosteroid use in the last year ; severe exacerbation requiring hospitalization in the last year ; and persistent airflow limitation despite gina asthma treatment step 4 or 5 . 4 5 therefore , it is increasingly important to characterize ucsa patients and identify outcomes that can aid in evaluating the impact of interventions on such patients . among such outcomes the 6mwd recorded for the patients with ucsa was similar to that predicted for healthy brazilians . 18 in addition , the patients with ucsa had normal post-6mwt spo2 , hrr1 , and respiratory muscle strength . it is known that the 6mwt provides indicators of functional capacity ( the 6mwd ) , pulmonary gas exchange ( spo2 ) , cardiovascular stress ( hr ) , cardiac automaticity ( hrr1 ) , and sensory stress ( dyspnea scores ) . 8 although our patients were irregularly active or sedentary and had moderate obstructive lung disease and uncontrolled asthma , their mean 6mwd was 512 72 m. in addition , mean desaturation was less than significant during the test ( spo2 having decreased < 4% from baseline ) . we found that % hrmax was achieved in approximately 71% of the study participants , a finding that indicates efficient gas exchange and adequate cardiovascular stress . mean hrr1 ( 21.7 8.3 bpm ) was significant , suggesting normal cardiac automaticity , although perceived leg fatigue and perceived dyspnea after completion of the 6mwt were moderate and somewhat strong , respectively . after reviewing the literature , we found only one study evaluating adults with severe asthma during the 6mwt . 11 in that study , the 6mwd was significantly shorter in the group of patients with dca than in the controls . 11 however , the mean 6mwd in the group of patients with dca was 435 m , 11 which is approximately 112 m shorter than the 6mwd recorded for our sample of patients with ucsa . it is of note that the patients in that study were older than those in the present study ( 52.3 8.3 years vs. 49.8 14.4 years ) , had more severe obstruction , as shown by percent predicted fev1 ( 44.0 15.9% vs. 58.8 21.8% ) , and used drugs that were more potent , such as oral corticosteroids ( 64% vs. 24% ) and omalizumab ( 47% vs. 12% ) . at the end of the 6mwt , there was a decrease in spo2 in 5 of the 25 ucsa patients investigated in the present study . in 2 , this was attributed to bronchospasm , which was rapidly reversed by rest and by using short - acting 2 agonists . the remaining 3 had comorbidities ( bronchiectasis due to sequelae of tuberculosis , allergic bronchopulmonary aspergillosis , and pulmonary emphysema with air trapping , respectively ) . these results suggest that , in the absence of bronchospasm , the presence of desaturation during the 6mwt in patients with ucsa should raise the suspicion of comorbidities . according to one group of authors , 27 the reasons for exercise limitation in patients with ucsa should be investigated and include asthma itself , alveolar hyperventilation , exercise - induced bronchoconstriction , physical deconditioning , submaximal test , and cardiac ischemia . the authors noted that , after the reasons for exercise limitation have been identified , treatment can be revised , particularly the use of high - dose corticosteroids in patients without pulmonary limitation . 27 respiratory muscle strength measurements ( mean mip and mep ) in the ucsa patients investigated in the present study were no different from those in healthy individuals . an increase in functional residual capacity ( caused by lung hyperinflation ) flattens the diaphragm and alters respiratory mechanics , resulting in a mechanical disadvantage , which can be inferred by a reduction in respiratory muscle strength . 7 28 however , asthma patients with mild or moderate obstructive lung disease might not have significant lung hyperinflation resulting in changes in diaphragm position . 29 30 the fact that the patients in the present study had moderate airway obstruction might explain why their mips and meps were similar to those in healthy individuals . we found no significant differences in mean mip and mep between the asthma patients who often used oral corticosteroids and those who did not ( i.e. , those who were treated with three or fewer courses of oral corticosteroids per year ) . one group of authors found that inspiratory muscle strength was lower in oral corticosteroid - dependent asthma patients than in asthma patients using high - dose ics , the level of lung hyperinflation being similar between the two groups of patients . 28 it should be noted that mip and mep were found to be reduced in 28% and 48% of the patients , respectively . a reduction in respiratory muscle strength can occur , particularly in obese females , as a result of respiratory muscle dysfunction . respiratory muscle activity can also be negatively affected by increased elastic resistance caused by the presence of excess adipose tissue in the rib cage and abdomen , which results in a mechanical disadvantage to the muscles . 31 32 in our study , 72% of the patients were female , their mean body mass index being 28 kg / m . although the results of the present study should be interpreted with caution , particularly because of the lack of a control group , the small sample size , the cross - sectional study design , and the single - center nature of the study , they are relevant because of the lack of studies examining exercise capacity in patients with severe asthma and because of the difficulties in investigating exercise capacity in such patients . in addition , the present study is relevant because it examined a sample of patients treated at a referral center in a university hospital and because of its high statistical power ( of 81% ) . in conclusion , the 6mwd recorded for the ucsa patients in the present study was found to be similar to that predicted for healthy brazilians . the fact that there was a decrease in spo2 in 5 of the 25 patients studied can be explained by the presence of bronchospasm and comorbidities . respiratory muscle strength measurements ( mean mip and mep ) were found to be above the predicted lower limit , regardless of the use of oral corticosteroids . further studies , involving a larger number of patients and including a control group , are needed in order to gain a better understanding of exercise capacity in patients with severe asthma and determine its role in the management of the disease . avaliar a fora muscular respiratria e variveis obtidas no teste de caminhada de seis minutos ( tc6 ) em pacientes com asma grave no controlada ( agnc ) . os pacientes foram submetidos a tc6 , espirometria e medidas da fora muscular respiratria e responderam o asthma control test ( act , teste de controle da asma ) . o teste de mann - whitney foi utilizado na anlise das variveis do tc6 , e o teste de kruskal - wallis foi utilizado na verificao de uma possvel associao do uso de corticoide oral com a fora muscular respiratria . foram includos 25 pacientes , com mdias de vef1 de 58,8 21,8% do previsto e escore do act de 14,0 3,9 pontos . no houve diferena significativa entre a mediana da distncia percorrida no tc6 dos pacientes com agnc e aquela prevista para brasileiros saudveis ( 512 m e 534 m , respectivamente ; p = 0,14 ) . durante o tc6 , no houve queda significativa da spo2 . as mdias de pimx e pemx foram normais ( 72,9 15,2% e 67,6 22,2% , respectivamente ) . no houve diferenas significativas nas medidas de pimx ( p = 0,15 ) e pemx ( p = 0,45 ) entre os pacientes que usavam ao menos quatro ciclos de corticoide oral por ano e os que o usavam por trs ou menos ciclos por ano . nossos achados sugerem que os pacientes com agnc so semelhantes a indivduos normais em termos das variveis do tc6 e da fora muscular respiratria . a asma uma doena inflamatria crnica das vias areas , caracterizada por hiper - reatividade brnquica , limitao varivel do fluxo areo e sintomas , como dispneia , chiado e tosse , que melhoram espontaneamente ou com tratamento . os objetivos bsicos do manejo da asma so o controle total dos sintomas e das limitaes das atividades dirias e a reduo dos riscos futuros . 1 2 a maioria dos pacientes tem asma leve ou moderada , facilmente controladas com o uso de corticoides por via inalatria ( ci ) de forma isolada ou associados com long - acting 2 agonist ( laba , 2-agonista de longa durao ) . 3 entretanto , entre os asmticos graves , h um pequeno subgrupo de pacientes que permanecem sintomticos apesar de boa adeso ao tratamento , uso correto dos dispositivos , manejo adequado de comorbidades e uso de altas dosagens de ci associados com laba e / ou corticoide oral e / ou omalizumabe . 4 5 esta condio particular denominada asma grave no controlada ( agnc ) , a qual , segundo as diretrizes atuais de asma , deve ser tratada em servios especializados . 4 5 pacientes com agnc necessitam de altas doses de ci associados ou no a corticoides orais , os quais tm , entre seus efeitos adversos , a reduo da sntese de protenas e o aumento de sua degradao , efeitos esses que contribuem para a atrofia muscular . 6 adicionalmente , o aumento da resistncia das vias areas e da hiperinsuflao pulmonar tambm contribuem para a reduo da eficincia de msculos inspiratrios , resultando em maior trabalho muscular e maior gasto energtico para vencer a limitao ao fluxo areo . 7 esses fatores ainda no foram bem estudados na agnc . o teste de caminhada de seis minutos ( tc6 ) um teste submximo que prov uma avaliao da resposta global e integrada de todos os aspectos corporais envolvidos na realizao do exerccio ( sistema pulmonar , sistema cardiovascular , circulao sistmica e perifrica , sangue , unidade neuromuscular e metabolismo muscular ) . 8 9 j a fora muscular respiratria pode ser estimada a partir das presses geradas nas vias areas pela contrao dos msculos respiratrios . as presses respiratrias estticas mximas so habitualmente medidas ao nvel da boca na inspirao ( pimx ) e na expirao ( pemx ) . 10 o papel do tc6 na avaliao e no acompanhamento de pacientes com dpoc , doena intersticial pulmonar , hipertenso arterial pulmonar e insuficincia cardaca est bem estabelecido . 8 no entanto , em adultos , o impacto do comprometimento na asma grave foi avaliado apenas em um estudo de canuto et al . , 11 que verificaram uma distncia percorrida no tc6 ( dtc6 ) significativamente menor nos pacientes com asma de difcil controle ( adc ) , em uso de corticoide oral , quando comparados com indivduos saudveis do grupo controle . por outro lado , embora a reduo da fora muscular , principalmente da pimx , tenha sido descrita em vrios estudos com pacientes asmticos , a mesma ainda no foi avaliada no grupo de pacientes com agnc . 12 o objetivo principal do presente estudo foi investigar o comportamento das variveis do tc6 , assim como pimx e pemx , em pacientes com agnc . de forma secundria , objetivamos investigar o impacto do uso de corticoide oral na fora muscular respiratria e a correlao do nvel de atividade fsica dos pacientes com a dtc6 e o nvel de controle da asma . trata - se de estudo transversal que incluiu pacientes maiores de 18 anos com asma grave acompanhados no ambulatrio de asma de difcil controle do hospital das clnicas da universidade federal de minas gerais ( ufmg ) , em belo horizonte ( mg ) , no perodo entre setembro e dezembro de 2012 . o projeto foi aprovado pelo comit de tica em pesquisa da ufmg ( parecer etic n 156.403/2012 ) . todos os participantes assinaram o termo de consentimento livre e esclarecido . o diagnstico de asma grave baseou - se nos critrios da american thoracic society / european respiratory society ( ats / ers ) , 13 assim definidos : como critrios maiores , uso de corticoide oral por no mnimo seis meses no ano e uso contnuo de ci em doses elevadas ( 1.600 g de budesonida ou equivalente ) associado a laba ; como critrios menores , vef1 < 80% ; variabilidade do pfe > 20% ; uso dirio de 2-agonista de curta durao ; uso de mais de trs cursos de corticoide oral no ano ; histria de episdio de asma quase fatal ; uma ou mais consultas em servios de urgncia no ano anterior ; e deteriorao rpida da funo pulmonar ao diminuir a dose do tratamento com corticoide . os pacientes includos tiveram acompanhamento ambulatorial por , no mnimo , seis meses , visando o controle de fatores ambientais e de comorbidades , a melhora da tcnica de uso dos dispositivos inalatrios e o aumento da adeso ao tratamento . alm disso , foram includos apenas os pacientes nas etapas 4 e 5 de tratamento da asma ( laba / ci em dose elevada mais corticoide oral e / ou anti - ige ) segundo as diretrizes da global initiative for asthma ( gina ) 1 e da sociedade brasileira de pneumologia e tisiologia ( sbpt ) , 2 e com dois critrios maiores ou um critrio maior e dois menores dos critrios da ats / ers . 13 foram excludos os pacientes com cardiopatia grave ; fumantes ativos ; ex - fumantes com carga tabgica 10 maos - ano ou que cessaram tabagismo h menos de um ano ; e pacientes que tiveram exacerbao necessitando de atendimento em pronto - socorro / internao , uso de prednisona ou equivalente acima de 20 mg e / ou de antibiticos nas ltimas quatro semanas . o tc6 foi realizado em um corredor de 25,6 m utilizando um oxmetro porttil ( nonin medical , inc . , plymouth , mn , eua ) , seguindo as recomendaes da ats . 14 todos os pacientes fizeram dois tc6 , com um intervalo mnimo de 30 min entre eles . foram avaliados os seguintes parmetros : spo2 medida por oximetria de pulso , fc , fr , e percepo da intensidade de dispneia e de fadiga nos membros inferiores pela escala de borg ao incio e ao final dos testes . foram verificados tambm o valor percentual da fc em relao fc mxima prevista para adultos ( % fcmx ) , a fc de recuperao no primeiro minuto aps o trmino do teste ( fcr1 ) e a dtc6 . foram considerados significativos valores de dessaturao 4% , % fcmx > 85% do previsto 8 14 e fcr1 > 12 bpm . 15 17 considerou - se vlido o tc6 com o maior valor para dtc6 ; os valores absolutos e percentuais do previsto para a dtc6 foram calculados atravs da equao de referncia para tc6 da populao brasileira . 18 a espirometria foi realizada utilizando um espirmetro da marca koko ( pds instrumentation inc . , louisville , co , eua ) . 10 os valores encontrados no teste ps - broncodilatador foram relatados como valores absolutos e percentuais em relao aos valores previstos de acordo com pereira et al . 19 a fora dos msculos respiratrios foi avaliada atravs de um manovacumetro digital ( warren e collins inc . , braintree , ma , eua ) seguindo as diretrizes nacionais da sbpt , 10 com leitura e armazenamento dos sinais atravs de ductos individuais . um orifcio de 2 mm no circuito impedia falsas medidas por contrao involuntria das bochechas . a pimx foi mensurada ao nvel do vr , e a pemx foi mensurada ao nvel da cpt . os resultados foram expressos em cmh2o . 20 o nvel de controle da asma foi avaliado atravs do asthma control test ( act , teste de controle da asma ) , no qual 25 pontos representam remisso clnica dos sintomas ou controle total da asma ; de 20 a 24 pontos , controle adequado da doena ; e abaixo de 20 pontos , asma no controlada ; foi utilizada a verso validada para uso no brasil . 21 23 o nvel de atividade fsica foi medido de acordo com international physical activity questionnaire ( ipaq , questionrio internacional de atividade fsica ) , verso curta , validado para uso no brasil . 24 25 o instrumento contm sete questes relacionadas frequncia , em dias por semana , e durao , em minutos por dia , das atividades fsicas vigorosas , moderadas e de caminhada . o escore classifica os indivduos em muito ativo , ativo , irregularmente ativo e sedentrio . agrupamos as classificaes em dois grupos : muito ativo ou ativo e irregularmente ativo ou sedentrio . 24 25 todos os pacientes do estudo realizaram tcar de trax para o diagnstico diferencial de outras doenas associadas , como dpoc , bronquiectasias e aspergilose broncopulmonar alrgica . a anlise dos dados foi realizada no statistical package for the social sciences , verso 18 ( spss inc . , chicago , il , eua ) e minitab , verso 16 ( minitab inc . , state college , ma , eua ) . o teste de shapiro - wilk foi utilizado para avaliar a distribuio dos dados . as variveis categricas foram apresentadas em frequncia e proporo , e as variveis contnuas foram expressas como mdia e desvio - padro ( distribuio paramtrica ) ou como mediana e variao ( distribuio no paramtrica ) . para avaliar a diferena entre a dtc6 nos pacientes com agnc e o valor previsto da dtc6 em indivduos normais , assim como para verificar a associao da prtica de atividade fsica ( ipaq ) com as variveis dtc6 , escore do act , % fcmx e fcr1 , foi utilizado o teste de mann - whitney . a possvel associao entre o uso de corticoide oral com pimx e pemx foi avaliada atravs do teste de correlao de spearman e teste de kruskal - wallis . com base na maior dtc6 encontrada na literatura , considerando - se um desvio - padro de 90,44 m , nvel de significncia de 0,05 , usando - se o teste t de student bicaudal para uma amostra nica , o tamanho da amostra foi estimado em 26 pacientes para se verificar uma diferena de trs indivduos foram excludos por se tratarem de pacientes com provvel sndrome de sobreposio asma / dpoc , e outro foi excludo devido a exacerbao da asma durante o ms da coleta dos dados . participaram 25 pacientes asmticos ( 18 do sexo feminino e 7 do sexo masculino ) , com mdia de idade de 49 anos e mdia de ndice de massa corprea de 28,9 7,9 todos os pacientes apresentaram escores do act < 15 pontos , 14 pacientes ( 56% ) eram irregularmente ativos / sedentrios , e 20 ( 80% ) tinham limitaes para exerccios no perodo intercrise . dez pacientes ( 40% ) tinham histria de exacerbao com internao em terapia intensiva , e 7 ( 28% ) , com necessidade de ventilao mecnica . tabela 1.caractersticas basais dos pacientes com asma grave no controlada.acaractersticasn = 25idade , anos 49,8 12,6sexo feminino18 ( 72)imc , kg / m 28,9 7,9ex - fumantes 4 ( 16)limitaes das atividades na intercrisesem limitaes0 ( 0)no exerccio20 ( 80)nas atividades dirias3 ( 12)nos cuidados pessoais2 ( 8)em repouso0 ( 0)presena de crises no ltimo ano 5 ( 0 - 23)uso de ct sistmico nas crises ( 4 ciclos / ano)9 ( 36)uso de ct oral contnuo6 ( 24)total de internaes 15 ( 0 - 100)internaes em uti10 ( 40)necessidade de ventilao mecnica7 ( 28)histria de pcr1 ( 4)comorbidades21 ( 84)rinossinusite crnica22 ( 88)polipose nasal2 ( 8)drge13 ( 52)obesidade11 ( 44)has2 ( 8)diabetes mellitus4 ( 16)distrbio psiquitrico4 ( 16)dpoc2 ( 8)sequela de tuberculose1 ( 4)abpa1 ( 4)act 14,0 3,9atividades fsicas - ipaq ativo ou muito ativo11 ( 44)irregularmente ativo ou sedentrio14 ( 56)mc : ndice de massa corprea ; ct : corticosteroide ; pcr : parada cardiorrespiratria ; drge : doena do refluxo gastroesofgico ; has : hipertenso arterial sistmica ; abpa : aspergilose broncopulmonar alrgica ; act : asthma control test ; e ipaq : international physical activity questionnaire . . cconsiderado como o indivduo que cessou o tabagismo com carga tabgica = 10 anosmao ou que cessou o tabagismo h pelo menos um ano . mc : ndice de massa corprea ; ct : corticosteroide ; pcr : parada cardiorrespiratria ; drge : doena do refluxo gastroesofgico ; has : hipertenso arterial sistmica ; abpa : aspergilose broncopulmonar alrgica ; act : asthma control test ; e ipaq : international physical activity questionnaire . cconsiderado como o indivduo que cessou o tabagismo com carga tabgica = 10 anosmao ou que cessou o tabagismo h pelo menos um ano . todos os pacientes estavam em uso de laba e dose alta de ci ( 1.600 g de budesonida ou equivalente ) , 6 ( 24% ) usavam pelo menos 10 mg / dia de prednisona h mais de um ano , e 3 ( 12% ) utilizavam omalizumabe . as principais alteraes tomogrficas foram bronquiectasias mnimas / moderadas com predomnio central , em 3 pacientes ; pequenas reas de enfisema centrolobular , em 11 ; fibroatelectasia discreta do lobo superior direito , em 1 ; e aprisionamento areo , em 1 . houve predomnio de distrbio ventilatrio obstrutivo com mdia de vef1 de 58,8 21,8% do previsto , e 17 pacientes ( 68% ) tiveram prova broncodilatadora positiva . as mdias da pimx e pemx foram normais ; entretanto , 7 ( 28% ) e 11 ( 44% ) dos pacientes apresentaram pimx e pemx reduzidas ( < 65% do previsto ) , respectivamente ( tabela 2 ) . dos 7 pacientes que tinham pimx reduzidas , somente 2 apresentaram sinais espiromtricos de hiperinsuflao pulmonar . tabela 2.resultados de espirometria e presses respiratrias mximas nos pacientes com asma grave no controlada ( n = 25).avariveisresultadospr - bdps - bdvef1,% predito58,8 21,8 66 22,4vef1 , l1,61 0,63 1,81 0,62cvf , % predito83,4 20,7 91,0 19,1cvf , l2,79 0,71 3,05 0,65vef1/cvf56,3 12,0pimx , cmh2o87,2 21,0pimx , % predito72,9 15,2pemx , cmh2o108,3 no houve diferena significativa ( p = 0,14 ) entre os valores medianos da dtc6 - 512 m ( variao : 307,2 - 597,3 m ) - e da dtc6 prevista para indivduos normais - 534 m ( variao : 382,6 - 621,3 m ) - ( figura 1 ) . figura 1.distribuio da distncia percorrida no teste de caminhada de seis minutos no grupo de pacientes ( n = 25 ) com asma grave no controlada ( dtc6-agnc ) em comparao com a mesma distncia prevista para adultos brasileiros saudveis ( dtc6-as).(18)a * valores discrepantes . nenhum paciente utilizou oxignio suplementar e no houve queda da spo2 mdia durante o tc6 ; porm , 5 pacientes apresentaram dessaturao durante o mesmo . dentre esses , 2 apresentaram broncoespasmo , que foi revertido com a utilizao de 2-agonista de curta durao , 2 tinham comorbidades ( aspergilose broncopulmonar alrgica e sequela de tuberculose pulmonar ) , e 1 apresentara enfisema e aprisionamento areo na tc de trax . ao final do tc6 , a intensidade da percepo da fadiga de membros inferiores foi leve e a de dispneia foi de leve a moderada . tabela 3.teste de caminhada de seis minutos nos pacientes com asma grave no controlada ( n = 25).avariveis antes do tc6aps o tc6spo2 , % 96,1 1,193,7 3,5fc , bpm81,8 16,7117,8 20,3fr , ciclos / min18,5 2,630,4 5,5escala de borg ( fadiga membros inferiores)0,1 0,42,9 2,6escala de borg ( dispneia)0,9 1,24,7 1,9dtc6 , m-512 4,2fcr1 , bpm-21,7 8,3fcmx , % -71 11tc6 : teste de caminhada de seis minutos ; dtc6 : distncia percorrida no tc6 ; fcr1 : queda da fc no primeiro minuto aps o trmino do tc6 ; e fcmx : fc mxima prevista . tc6 : teste de caminhada de seis minutos ; dtc6 : distncia percorrida no tc6 ; fcr1 : queda da fc no primeiro minuto aps o trmino do tc6 ; e fcmx : fc mxima prevista . ao compararmos o subgrupo de pacientes em uso continuo de corticoide oral ou com quatro ou mais ciclos por ano ( n = 15 ) com o subgrupo de pacientes com trs ou menos ciclos por ano ( n = 10 ) a fim de investigar a associao entre a frequncia de uso de corticoide oral e a fora muscular respiratria , no encontramos diferenas estatisticamente significativas entre os valores medianos de pimx - 74,5% ( variao : 59,0 - 104,0% ) e 72,5% ( variao : 43,0 - 104,0% ; p = 0,15 ) , respectivamente - e pemx - 67,5% ( variao : 29,0 - 121,0% ) e 63,5% ( variao : 34,0 - 121,0% ; p = 0,45 ) , respectivamente . os 11 pacientes mais ativos fisicamente e os 14 menos ativos apresentaram resultados semelhantes em relao a act , dtc6 , fcr1 e % fcmx no tc6 ( tabela 4 ) . tabela 4.associao do nvel de atividade fsica dos pacientes com asma grave no controlada ( n = 25 ) com o nvel de controle de asma e variveis do teste de caminhada de seis minutos.avariveisnvel de atividade fsica ( ipaq)pmuito ativo ou ativoirregularmente ativo ou sedentrio(n = 11)(n = 14)dtc6 , m537,6 ( 320,0 - 597,3)490,0 ( 307,2 - 588,6)0,308fcr1 , bpm19,0 ( 11,0 - 37,0)19,5 ( 10,0 - 36,0)0,935fcmx , % 72 ( 53 - 89)73 ( 50 - 84)0,621escore act15 ( 7 - 17)13 ( 6 - 24)0,144ipaq : international physical activity questionnaire ; dtc6 : distncia percorrida no teste de caminhada de seis minutos ; fcr1 : queda da fc no primeiro minuto aps o trmino do teste de caminhada de seis minutos ; fcmx : fc mxima prevista ; e act : asthma control test . ipaq : international physical activity questionnaire ; dtc6 : distncia percorrida no teste de caminhada de seis minutos ; fcr1 : queda da fc no primeiro minuto aps o trmino do teste de caminhada de seis minutos ; fcmx : fc mxima prevista ; e act : asthma control test . historicamente , os pacientes que no atingem o controle da asma , apesar do tratamento nas etapas 4 ou 5 segundo o gina , so classificados como portadores de adc . 1 entretanto , h mais de duas dcadas persistem muitas discusses sobre a terminologia mais apropriada devido aos diferentes critrios de definio utilizados para asma grave , adc , asma refratria ou resistente ao tratamento e , mais recentemente , agnc . em 2000 , uma publicao da ats sugeriu critrios de definio de adc , que ajudaram a reduzir parte dessas controvrsias . 13 no entanto , somente aps a publicao da fora tarefa da ats / ers em 2013 , ratificada e citada na diretriz gina de 2014 , que essa classificao tornou - se mais clara . 4 5 de acordo com aquelas publicaes , o termo " asma difcil de tratar " deve ser reservado para os pacientes que melhoram o controle da asma aps medidas de higiene ambiental , melhora da tcnica de uso dos dispositivos , melhora da adeso ao tratamento ou manejo adequado de comorbidades . por outro lado , as mesmas publicaes definiram " asma grave " como o grupo de pacientes que , apesar das medidas citadas anteriormente , necessitaram de medicamentos nas etapas 4 e 5 segundo gina nos ltimos 12 meses ou de corticoides sistmicos por , no mnimo , 6 meses nos ltimos 12 meses para manter o controle da asma ou que permaneceram sem um controle adequado apesar do tratamento . 4 5 cabe destacar ainda que os pacientes definidos como agnc seriam aqueles que mantiveram pelo menos um dos critrios alm do baixo controle de sintomas 4 5 : act < 20 pontos ou resultados equivalentes em outro escore validado para a verificao do controle da asma ; duas ou mais exacerbaes , necessitando de corticoide sistmico no ltimo ano ; exacerbao grave com necessidade de internao no ltimo ano ; e persistncia de limitao do fluxo areo apesar do tratamento nas etapas 4 ou 5 segundo gina . 4 5 portanto , torna - se cada vez mais importante a caracterizao de pacientes com agnc , bem como a identificao de desfechos que auxiliem na avaliao do impacto de intervenes nesses pacientes . nesse contexto , inclui - se a capacidade de exerccio e a fora muscular respiratria . no nosso estudo , os pacientes com agnc percorreram uma dtc6 semelhante quela prevista para a populao brasileira . alm disso , eles apresentaram comportamento normal da spo2 mdia ao final do teste , reduo adequada da fc um minuto aps o trmino do tc6 e fora muscular respiratria normal . como se sabe , o tc6 fornece indicadores da capacidade funcional , por meio da dtc6 , da integridade da troca gasosa intrapulmonar pela spo2 , do estresse cardiovascular pela fc , da automao cardaca pela fcr1 e do estresse sensorial pelos escores de dispneia . 8 em nosso estudo , os pacientes percorreram , em mdia , 512 72 m no tc6 , apesar de apresentarem padro obstrutivo moderado , serem irregularmente ativos ou sedentrios e apresentarem asma no controlada . adicionalmente , no se observou dessaturao mdia significativa durante o teste ( queda da spo2 < 4% em relao aos valores basais ) . aproximadamente 71% dos participantes atingiram a % fcmx , denotando uma troca gasosa eficiente e estresse cardiovascular satisfatrio . a mdia de fcr1 ( 21,7 8,3 bpm ) foi significativa , sugerindo automao cardaca normal , o se que contrape com o achado de percepo da fadiga moderada e de dispneia ( um pouco forte ) ao final do teste . aps revisarmos a literatura , encontramos apenas um estudo em adultos sobre o comportamento de pacientes com asma grave durante o tc6 . 11 naquele estudo , a dtc6 nos pacientes com adc foi significativamente menor em relao aos seus controles . 11 entretanto , a mdia da dtc6 no grupo com adc foi de 435 m , 11 aproximadamente 112 m inferior dtc6 em nossa amostra . cabe ressaltar que os pacientes daquele estudo eram mais velhos que os do presente estudo ( 52,3 8,3 anos vs. 49,8 14,4 anos ) , com maior grau de obstruo , indicado pelo vef1 em % do previsto ( 44,0 15,9% vs. 58,8 21,8% ) e faziam uso de mais medicamentos potentes , como corticoide oral ( 64% vs. 24% ) e omalizumabe ( 47% vs. 12% ) . em 2 pacientes essa queda foi atribuda a broncoespasmo , revertido rapidamente com repouso e uso de 2-agonistas de curta durao . os outros 3 pacientes tinham comorbidades ( bronquiectasias devido a sequela de tuberculose , aspergilose broncopulmonar alrgica e enfisema pulmonar com aprisionamento areo , respectivamente ) . esses resultados sugerem que , na ausncia de broncoespasmo , a presena de dessaturao durante o tc6 em pacientes com agnc deve alertar para a possibilidade de presena de comorbidades . para um grupo de autores , 27 a limitao ao exerccio em pacientes com agnc deve ser investigada quanto aos possveis fatores , como a prpria asma , hiperventilao alveolar , broncoconstrio induzida pelo exerccio , descondicionamento fsico , teste submximo e isquemia cardaca . os autores observaram que , ao se identificarem os fatores limitantes , pode - se rever o tratamento , em especial o uso de altas doses de corticoide naqueles pacientes nos quais no foi encontrada limitao pulmonar . 27 a medida da fora muscular respiratria ( pimx e pemx ) dos pacientes no presente estudo , em mdia , no foi diferente da observada em indivduos normais . o aumento na capacidade residual funcional , causado pela hiperinsuflao pulmonar , retifica o diafragma e altera a mecnica respiratria , resultando em desvantagem mecnica , que pode ser inferida pela reduo da fora dos msculos respiratrios . 7 28 entretanto , os asmticos com distrbio ventilatrio obstrutivo leve ou moderado podem no apresentar hiperinsuflao pulmonar significativa que altere a posio do diafragma . 29 30 como os pacientes da presente casustica apresentavam obstruo moderada das vias areas , possvel que esse fato justifique a similaridade de seus valores de pimx e pemx com a de indivduos normais . no encontramos diferenas significativas entre as mdias de pimx e pemx dos asmticos com uso frequente de corticoide oral com aqueles com uso infrequente ( trs ou menos ciclos por ano ) . um grupo de autores relatou reduo da fora muscular inspiratria em asmticos dependentes de corticoides orais quando comparados com pacientes em uso de ci em altas doses e com graus semelhantes de hiperinsuflao pulmonar . 28 deve - se ressaltar que 28% e 48% dos pacientes tiveram pimx e pemx reduzidas , respectivamente . a fora muscular respiratria pode estar reduzida principalmente em mulheres obesas em consequncia de uma disfuno muscular respiratria . a atividade muscular ventilatria pode ser tambm comprometida pelo aumento da resistncia elstica causada pelo excesso de tecido adiposo na caixa torcica e no abdome , o qual acarreta desvantagem mecnica aos msculos . 31 32 em nosso estudo , 72% das pacientes eram do sexo feminino , com mdia de ndice de massa corprea de 28 kg / m . embora os resultados do presente estudo devam ser avaliados com cautela , principalmente devido falta de um grupo controle , pequena casustica , ao delineamento transversal e por ter sido conduzido em um nico centro , os mesmos so relevantes devido escassez e s dificuldades de pesquisa da capacidade de exerccio em pacientes com asma grave , assim como por representar uma amostra de um centro de referncia de um hospital universitrio e pelo alto poder estatstico observado ( poder do teste de 81% ) . em concluso , de acordo com a presente casustica , a dtc6 nos pacientes com agnc foi semelhante aos valores previstos para a dtc6 em indivduos normais no brasil . a queda da spo2 em 5 pacientes pode ser explicada pela presena de broncoespasmo e de comorbidades . a mdia das foras musculares respiratrias foi acima do limite inferior previsto , independente do uso de corticoide oral . so necessrios novos estudos envolvendo um maior nmero de pacientes e com a incluso de um grupo controle para um maior entendimento do comportamento da capacidade de esforo em pacientes com asma grave e para a definio do seu valor no manejo dessa doena .

objective : to evaluate respiratory muscle strength and six - minute walk test ( 6mwt ) variables in patients with uncontrolled severe asthma ( ucsa ) . methods : this was a cross - sectional study involving ucsa patients followed at a university hospital . the patients underwent 6mwt , spirometry , and measurements of respiratory muscle strength , as well as completing the asthma control test ( act ) . the mann - whitney test was used in order to analyze 6mwt variables , whereas the kruskal - wallis test was used to determine whether there was an association between the use of oral corticosteroids and respiratory muscle strength . results : we included 25 patients . mean fev1 was 58.8 21.8% of predicted , and mean act score was 14.0 3.9 points . no significant difference was found between the median six - minute walk distance recorded for the ucsa patients and that predicted for healthy brazilians ( 512 m and 534 m , respectively ; p = 0.14 ) . during the 6mwt , there was no significant drop in spo2 . mean mip and mep were normal ( 72.9 15.2% and 67.6 22.2% , respectively ) . comparing the patients treated with at least four courses of oral corticosteroids per year and those treated with three or fewer , we found no significant differences in mip ( p = 0.15 ) or mep ( p = 0.45 ) . conclusions : our findings suggest that ucsa patients are similar to normal subjects in terms of 6mwt variables and respiratory muscle strength . the use of oral corticosteroids has no apparent impact on respiratory muscle strength .

annually more than 12 million neonates are born prematurely that include 10 - 12 percent of births worldwide . some of these neonates undergo mechanical ventilation including endotracheal tube suctioning ( ets ) that is one of the basic steps in caring and maintaining air way . even though ets is performed to maintain upper air way permeability , it is not a safe procedure and may lead to short and long term detrimental effects . ets is one of the most frequent interventions in nursing and in fact it is the most important responsibility of nurses in intensive care units . however , studies have shown that performance of nurses in this procedure is weak and in most wards there is no manual based on evidence about ets to guide nurses performance . studies on adults have revealed that ets caused moderate to severe pain . what is painful for adults is painful for neonates as well , even if the neonate does n't show the physiologic and behavioral symptoms . today , there is sufficient evidence that pain , especially due to repeated routine painful procedures like ets is traumatic in neonates , increasing the likelihood of short and long term complications . pain increases demands on cardio - respiratory system and elevates intracranial pressure , theoretically increasing the risk of intraventricular hemorrhage . other studies have shown that there is a relationship between long term repeated pain during neonatal period and changes in pain sensitivity and pain processing later in life . neonates , especially premature ones , are subjected to diagnostic and therapeutic procedures which are essential for their survival . one of the most routine procedures done in nicu is nasal , pharyngeal and endotracheal tube suctioning . simons and his colleagues in 2003 showed that 63.6% of the procedures done on neonates are suctioning but often no releasing intervention was done for this repeated painful procedure . lago et al showed that only 25% of nicus in italy had policies for acute pain control and 50% for chronic pain and health care providers took measures for pain control only in 14% of ets procedures . studies showed that administering analgesic drug before ets and non - pharmacological intervention after that could not decrease the pain of ets . therefore , given that the underlying factors , such as nurses skills in performing procedures , affect the pain , we made an attempt to improve the performance of the nurses by evidence based education and assessed the pain in neonates . a quasi - experimental study carried out in august 2009 in nicu ( level 3 ) in zeinab ( pbuh ) hospital of shiraz . this ward was equipped with 8 beds with mechanical ventilation , pulse oximetry and central monitoring . the equipment were controlled before the study and all of them were calibrated and scot free . there was no protocol for pain control in this ward and nothing was done to control the pain of neonates during ets . inclusion criteria for nurses were consent form and working in nicu . first , one of the researchers observed the performance of 25 nurses during ets with a checklist including 43 items with maximum score of 43 which were developed by literature review and validated by expert panel . its content validity was confirmed by a team of 7 nursing specialists and its inter - observer reliability was 93% . the neonates had a gestational age of less than 37 weeks , were intubated ( at least for 8 hours and up to 24 hours ) and did not get any analgesics . the exclusion criteria were suffering from ivh grade 3 and 4 , having chest tube and being complicated due to ets such as hemorrhage and pneuomothorax . pain was assessed using premature infant pain profile ( pipp ) one minute before , during and 5 minutes after ets . it has two physiologic indicators ( heart rate and oxygen saturation ) , three facial indicators ( brow bulge , eye squeeze and nasolabial furrow ) , and two contextual factors ( gestational age and behavioral state ) . pain scores 6 indicate minimum pain or no pain , 7 - 12 indicate mild to moderate pain and scores > 2 indicate moderate to severe pain . this tool was translated into persian and back translated to english by a professional translator ( content validity ) . intra - reliability coefficients analysis was equally high at 0.94 - 0.98 . in a 6 hour workshop , the standard principle of ets in neonates one day following the education , the performance of the nurses in ets was observed and pain score of the neonates was assessed using pipp . data were gathered only in the morning for controlling confounding variables such as light , noise , crowding , etc , before and after education . this study was approved by the research and ethics committee of shiraz university of medical sciences and consent forms were gathered from nursing staff . ets is a routine procedure in nicu and the researchers did not interfere in it , so obtaining consent form from the parents was not necessary . chi square and t - test were used for controlling confounding variables before and after education . wilcoxon test was used for comparison of performance scores of nurses before and after education . friedman tests were used for comparing pain before , during and after ets and mann - whitney tests were used for comparing pain of neonates before and after education . all the nurses were female with a mean age of 30.16.8 years and mean experience of 6.95.6 years . wilcoxon test showed statistically significant differences between the mean score of nurses performance in ets before ( 20.63.12 ) and after ( 39.143.06 ) education ( p=0.001 ) . before education , 4% of the nurses and after that 72% of them assessed the neonatal need for ets , showing significant differences with mcnemar test ( p=0.001 ) . demographic variables such as sex , gestational age , and weight , and intubation period of neonates were not significantly different ( table 1 ) . demographic characteristics of premature neonates in different groups result of friedman nonparametric test showed that pipp1 , pipp2 and pipp3 were significantly different before and after education and wilcoxon test affirmed that the differences were significant between all pairs except pipp1-pipp3 after education ( p=0.61 ) ( table 2 ) . mann - whitney test showed no significant differences between pipp1 before and after education ( p=0.25 ) but pipp2 and pipp3 were significantly different before and after education ( p0.01 ) ( fig . 1 ) . comparison of pain score before and after education comparisons of pain scores in different times of endotracheal tube suctioning pipp : premature infant pain profile ets procedure was performed in each neonatal ward differently , even every nurse uses her own methods and the standard instructions were not used . in this study before education , nurses performance in ets was poor and theoretical and practical education improved the performance . they showed that the performance of nurses were poor in ets and in addition to theoretical education , practical education , administrative and prevocational support are also required to improve the performance and decrease ets complications . painful procedures in nicu may be inevitable , so it is necessary that nurses balance the painful , but medically necessary care and employ painful procedures based on neonatal needs . an outstanding result of this study is that before education , a small number of nurses ( 4% ) assessed neonatal need for ets while after the education the majority of nurses ( 72% ) did this assessment . it can be inferred that education can improve nursing performance and prevent pain due to unnecessary painful procedures . wood in her study showed that assessing patients need for ets reduced the number of procedures and decreased its complications . this study showed that pain scores were different before , during and after ets before education . neonates had no pain before ets or they had minimum pain , but they experienced moderate to severe pain during and mild pain after ets . arroyo - novoa and colleagues ( 2007 ) showed that in 169 hospitals of canada , australia , england and usa , the severity of pain just before , after and ten minutes after ets were different and pain severity just after ets was more . in addition 64% of patients reported moderate to severe pain related to ets . in our study after education , neonates experienced pain during ets but this pain was mild , in addition pain severity after ets was similar to that before ets . these results revealed that education had effect on reducing pain severity during and after ets . saarenmaa et al ( 2001 ) in a clinical trial administered ketamine for relieving pain of ets in the neonatal intensive care unit but the result showed that ketamine could not relieve pain and it had even no effect on the heart rate and blood pressure changes due to ets procedure . also , cignacco et al ( 2008 ) used morphine before and multisensorial stimulation after ets procedure but none of them had an effect on the pain of ets , concluding that due to concerns about potential complications of narcotics especially in premature neonates , non - pharmacological interventions should be considered and performed . according to the results of this research and other studies , various interventions and preferably a combination of different strategies are recommended to stimulate various senses and relieve pain . our data support the assumption that education on principals of ets could relieve pain in neonates during and after this procedure . the finding that education could decrease complications is consistent with the results of mohamadi et al ( 1391 ) indicating that education could control the changes in the heart rate and oxygen saturation due to ets and decrease its complications . therefore , it can be concluded that education on ets principles could decrease pain in premature neonates . it is recommended that such education become a part of in - service education programs in nicu , and manuals and policies must be prepared in these wards . the main limitations of the present study were lack of a suitable control group and a sample size that did not permit the meaningful evaluation of the large number of variables that can influence pain score ets caused moderate to severe pain in premature neonates but performing a standard procedure based on neonatal need and improving nursing performance could decrease this pain . despite these interventions , neonates will still experience mild pain . there is a need for more research to illuminate optimal pain management and strategies to relieve pain in neonates . further studies can compare two groups of neonates with administration of analgesics and other groups with skillful nurses in suctioning practices .

objectiveendotracheal tube suctioning ( ets ) is a painful and invasive procedure . studies have shown that the performance of nurses in this procedure is weak , so we conducted a study to evaluate the effect of ets education for nurses on neonates pain in neonatal intensive care units ( nicus).methodsin a quasi - experimental study , performance of 25 nurses working in nicu was assessed before and after ets education by a checklist . in addition pain score of 50 neonates was measured using pain assessment tool ( pipp ) one minute before , during and 5 minutes after ets . the neonates had a gestational age of less than 37 weeks and were intubated ( at least for 8 hours and up to 24 hours ) . a p. value of less than 0.05 was considered as statistically significant.findingsmean scores of nurses performance were significantly different before and after education ( p0.001 ) by wilcoxon test . friedman test revealed that pipps before , during and after ets were significantly different before and after education ( p0.05 ) . mann - whitney test showed no significant differences between pipps before ets , before and after education ( p=0.2 ) , but pipps during and after ets were significantly different ( p0.01).conclusionets causes moderate to severe pain in neonates . education improved performance of nurses and decreased pain in neonates during and after ets . despite education , neonates will experience mild pain during ets , so other interventions need to be considerate .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Promotion of Commerce On-Line in the Digital Era (Pro-CODE) Act of 1996''. SEC. 2. FINDINGS; PURPOSE. (a) Findings.--The Congress finds the following: (1) The ability to digitize information makes carrying out tremendous amounts of commerce and personal communication electronically possible. (2) Miniaturization, distributed computing, and reduced transmission costs make communication via electronic networks a reality. (3) The explosive growth in the Internet and other computer networks reflects the potential growth of electronic commerce and personal communication. (4) The Internet and the global information infrastructure have the potential to revolutionize the way individuals and businesses conduct business. (5) The full potential of the Internet for the conduct of business cannot be realized as long as it is an insecure medium in which confidential business information and sensitive personal information remain at risk of unauthorized viewing, alteration, and use. (6) Encryption of information enables businesses and individuals to protect themselves against the unauthorized viewing, alteration, and use of information by employing widely understood and readily available science and technology to ensure the confidentiality, authenticity, and integrity of information. (7) In order to promote economic growth and meet the needs of businesses and individuals in the United States, a variety of encryption products and programs should be available to promote strong, flexible, and commercially acceptable encryption capabilities. (8) United States computer, computer software and hardware, communications, and electronics businesses are leading the world technology revolution, as those businesses have developed and are prepared to offer immediately to computer users worldwide a variety of communications and computer hardware and computer software that provide strong, robust, and easy-to-use encryption. (9) United States businesses seek to market the products described in paragraph (8) in competition with scores of foreign businesses in many countries that offer similar, and frequently stronger, encryption products and programs. (10) United States businesses have been discouraged from further developing and marketing products with encryption capabilities because of regulatory efforts by the Secretary of Commerce, acting through the National Institute of Standards and Technology, and other entities to promulgate standards and guidelines in support of government-designed solutions to encryption problems that-- (A) were not developed in the private sector; and (B) have not received widespread commercial support. (11) Because of outdated Federal controls, United States businesses have been prohibited from exporting strong encryption products and programs. (12) The Secretary of Commerce, acting through the National Institute of Standards and Technology, has attempted to leverage the desire of United States businesses to sell commercial products to the United States Government, and sell a single product worldwide, to force the businesses to include features in products sold by the businesses in the United States and in foreign countries that will allow the Federal Government easy access to the plain text of all electronic information and communications. (13) Specifically, the Secretary of Commerce, acting through the National Institute of Standards and Technology, has proposed that United States businesses be allowed to sell products and programs offering strong encryption to the United States Government and in foreign countries only if the products and programs include a feature guaranteeing the Federal Government access to a key that decrypts information (hereafter in this section referred to as ``key escrow encryption''). (14) The key escrow encryption approach to regulating encryption is reflected in the approval in 1994 by the National Institute of Standards and Technology of a Federal information processing standard for a standard of escrowed encryption, known as the ``clipper chip'', that was flawed and controversial. (15) The Federal Government-- (A) has designed key escrow encryption to solve a perceived problem; and (B) has ignored the fact that-- (i) there is no demonstrated commercial demand for features which give governments easy access to information; and (ii) numerous nonkey escrow encryption alternatives are available commercially from foreign suppliers and free of charge from the Internet. (16) In order to promote electronic commerce in the twenty- first century and to realize the full potential of the Internet and other computer networks-- (A) United States businesses should be encouraged to develop and market products and programs offering encryption capabilities; and (B) the Federal Government should be prohibited from promulgating regulations and adopting policies that discourage the use and sale of encryption. (b) Purpose.--The purpose of this Act is to promote electronic commerce through the use of strong encryption by-- (1) recognizing that businesses in the United States that offer computer hardware and computer software made in the United States that incorporate encryption technology are ready and immediately able, with respect to electronic information that will be essential to conducting business in the twenty- first century to provide products that are designed to-- (A) protect the confidentiality of that information; and (B) ensure the authenticity and integrity of that information; (2) restricting the Department of Commerce with respect to the promulgation or enforcement of regulations, or the application of policies, that impose government-designed encryption standards; and (3) promoting the ability of United States businesses to sell to computer users worldwide computer software and computer hardware that provide the strong encryption demanded by such users by-- (A) restricting Federal or State regulation of the sale of such products and programs in interstate commerce; (B) prohibiting mandatory key escrow encryption systems; and (C) establishing conditions for the sale of encryption products and programs in foreign commerce. SEC. 3. DEFINITIONS. For purposes of this Act, the following definitions shall apply: (1) As is.--The term ``as is'' means, in the case of computer software (including computer software with encryption capabilities), a computer software program that is not designed, developed, or tailored by a producer of computer software for specific users or purchasers, except that such term may include computer software that-- (A) is produced for users or purchasers that supply certain installation parameters needed by the computer software program to function properly with the computer system of the user or purchaser; or (B) is customized by the user or purchaser by selecting from among options contained in the computer software program. (2) Computing device.--The term ``computing device'' means a device that incorporates one or more microprocessor-based central processing units that are capable of accepting, storing, processing, or providing output of data. (3) Computer hardware.--The term ``computer hardware'' includes computer systems, equipment, application-specific assemblies, modules, and integrated circuits. (4) Decryption.--The term ``decryption'' means the unscrambling of wire or electronic communications or information using mathematical formulas, codes, or algorithms. (5) Decryption key.--The term ``decryption key'' means the variable information used in a mathematical formula, code, or algorithm, or any component thereof, used to decrypt wire or electronic communications or information that has been encrypted. (6) Designed for installation by the user or purchaser.-- The term ``designed for installation by the user or purchaser'' means, in the case of computer software (including computer software with encryption capabilities) computer software-- (A) with respect to which the producer of that computer software-- (i) intends for the user or purchaser (including any licensee or transferee), to install the computer software program on a computing device; and (ii) has supplied the necessary instructions to do so, except that the producer or distributor of the computer software program (or any agent of such producer or distributor) may also provide telephone help-line or onsite services for computer software installation, electronic transmission, or basic operations; and (B) that is designed for installation by the user or purchaser without further substantial support by the supplier. (7) Encryption.--The term ``encryption'' means the scrambling of wire or electronic communications or information using mathematical formulas, codes, or algorithms in order to preserve the confidentiality, integrity, or authenticity of such communications or information and prevent unauthorized recipients from accessing or altering such communications or information. (8) General license.--The term ``general license'' means a general authorization that is applicable to a type of export that does not require an exporter of that type of export to, as a condition to exporting-- (A) submit a written application to the Secretary; or (B) receive prior written authorization by the Secretary. (9) Generally available.--The term ``generally available'' means, in the case of computer software (including software with encryption capabilities), computer software that-- (A) is distributed via the Internet or that is widely offered for sale, license, or transfer (without regard to whether it is offered for consideration), including over-the-counter retail sales, mail order transactions, telephone order transactions, electronic distribution, or sale on approval; or (B) preloaded on computer hardware that is widely available. (10) Internet.--The term ``Internet'' means the international computer network of both Federal and non-Federal interconnected packet-switched data networks. (11) Secretary.--The term ``Secretary'' means the Secretary of Commerce. (12) State.--The term ``State'' means each of the several States of the United States, the District of Columbia, the Commonwealth of Puerto Rico, and any territory or possession of the United States. SEC. 4. RESTRICTION OF DEPARTMENT OF COMMERCE ENCRYPTION ACTIVITIES IMPOSING GOVERNMENT ENCRYPTION SYSTEMS. (a) Limitation on Regulatory Authority Concerning Encryption Standards.--The Secretary may not (acting through the National Institute of Standards and Technology or otherwise) promulgate, or enforce regulations, or otherwise adopt standards or carry out policies that result in encryption standards intended for use by businesses or entities other than Federal computer systems. (b) Limitation on Authority Concerning Exports of Computer Hardware and Computer Software With Encryption Capabilities.--The Secretary may not promulgate or enforce regulations, or adopt or carry out policies in a manner inconsistent with this Act, or that have the effect of imposing government-designed encryption standards on the private sector by restricting the export of computer hardware and computer software with encryption capabilities. SEC. 5. PROMOTION OF COMMERCIAL ENCRYPTION PRODUCTS. (a) Prohibition on Restrictions on Sale or Distribution in Interstate Commerce.-- (1) In general.--Notwithstanding any other provision of law, neither the Federal Government nor any State may restrict or regulate the sale in interstate commerce, by any person of any product or program with encryption capabilities. Nothing in this paragraph may be construed to preempt any provision of Federal or State law applicable to contraband or regulated substances. (2) Applicability.--Paragraph (1) shall apply without regard to the encryption algorithm selected, encryption key length chosen, or implementation technique or medium used for a product or program with encryption capabilities. (b) Prohibition on Mandatory Key Escrow.--Neither the Federal Government nor any State may require, as a condition of sale in interstate commerce, that a decryption key be given to any other person (including a Federal agency or an entity in the private sector that may be certified or approved by the Federal Government or a State). (c) Control of Exports by Secretary.-- (1) General rule.--Notwithstanding any other provision of law and subject to paragraphs (2), (3), and (4), the Secretary shall have exclusive authority to control exports of all computer hardware, computer software, and technology with encryption capabilities, except computer hardware, computer software, and technology that is specifically designed or modified for military use, including command, control, and intelligence applications. (2) Items that do not require validated licenses.--Only a general license may be required, except as otherwise provided under the Trading With The Enemy Act (50 U.S.C. App. 1 et seq.) or the International Emergency Economic Powers Act (50 U.S.C. 1701 et seq.) (but only to the extent that the authority of the International Emergency Economic Powers Act is not exercised to extend controls imposed under the Export Administration Act of 1979), for the export or reexport of-- (A) any computer software, including computer software with encryption capabilities, that is-- (i) generally available, as is, and designed for installation by the user or purchaser; or (ii) in the public domain (including on the Internet) or publicly available because it is generally accessible to the interested public in any form; or (B) any computing device or computer hardware solely because it incorporates or employs in any form computer software (including computer software with encryption capabilities) that is described in subparagraph (A). (3) Computer software and computer hardware with encryption capabilities.-- (A) In general.--Except as provided in subparagraph (B), the Secretary shall authorize the export or reexport of computer software and computer hardware with encryption capabilities under a general license for nonmilitary end-uses in any foreign country to which those exports of computer software and computer hardware of similar capability are permitted for use by financial institutions that the Secretary determines not to be controlled in fact by United States persons. (B) Exception.--The Secretary shall prohibit the export or reexport of computer software and computer hardware described in subparagraph (A) to a foreign country if the Secretary determines that there is substantial evidence that such software and computer hardware will be-- (i) diverted to a military end-use or an end-use supporting international terrorism; (ii) modified for military or terrorist end-use; or (iii) reexported without the authorization required under Federal law. (d) Statutory Construction.--Nothing in this Act may be construed to affect any law in effect on the day before the date of enactment of this Act designed to prevent the distribution of descramblers and any other equipment for illegal interceptions cable and satellite television signals.

Promotion of Commerce On-Line in the Digital Era (Pro-CODE) Act of 1996 - Prohibits the Secretary of Commerce (acting through the National Institute of Standards and Technology or otherwise) from promulgating or enforcing regulations, or otherwise adopting standards or carrying out policies: (1) that result in encryption standards intended for use by businesses or entities other than Federal computer systems; or (2) in a manner inconsistent with this Act, or that have the effect of imposing Government-designed encryption standards on the private sector by restricting the export of computer hardware and computer software with encryption capabilities. (Sec. 5) Prohibits the Federal and State governments from: (1) restricting or regulating the interstate sale by any person of any product with encryption capabilities; or (2) requiring, as a condition of such a sale, that a decryption key be given to any other person (including a Federal agency or a private entity certified or approved by the Federal or a State government). Grants the Secretary exclusive authority to control exports of all computer hardware, software, and technology with encryption capabilities, except that which is specifically designed or modified for military use, including command, control, and intelligence applications. Prohibits requiring any validated license (with limited exceptions) for the export or reexport of any: (1) computer software, including that with encryption capabilities, that is generally available, as is, and designed for installation by the purchaser, or that is in the public domain (including on the Internet) or publicly available because it is generally accessible to the public in any form; or (2) computing device or computer hardware solely because it incorporates or employs in any form such computer software (including that with encryption capabilities). Directs the Secretary to authorize the export or reexport of computer software with encryption capabilities under a general license for nonmilitary end-uses in any country to which exports of software or hardware of similar capability are permitted for use by financial institutions not controlled in fact by U.S. persons, unless there is substantial evidence that such software and hardware will be diverted to a military end-use or an end-use supporting international terrorism, modified for military or terrorist end-use, or reexported without requisite Federal authorization. Declares that nothing in this Act may be construed to affect any law in effect before this Act's enactment designed to prevent the distribution of descramblers and any other equipment for illegal interceptions of cable and satellite television signals.

Jennifer Hudson and fiancé David Otunga have ended their relationship after 10 years. “They have been in the process of ending their relationship for a number of months,” Hudson’s rep tells PEOPLE exclusively in a statement. “Today, Jennifer requested and received a protective order against her ex-fiancé. Jennifer’s actions are solely taken in the best interest of their son,” the statement concluded. Hudson, 36, and Otunga, 37, are parents to 8-year-old David Daniel Otunga Jr. Otunga’s attorney, Tracy M. Rizzo, released a statement to PEOPLE on behalf of the former pro wrestler following the split news. Kevin Mazur/WireImage “Mr. Otunga has never abused or harassed Ms. Hudson or their son, and it is unfortunate, especially in today’s climate, that she would feel the need to make these false allegations against him. Mr. Otunga looks forward to his day in court and in being awarded the residential care of the parties’ only child,” a part of the statement read. Former pro wrestler Otunga proposed to Hudson in September 2008 after less than a year of dating. The couple welcomed their only child nearly a year later in August 2009. About a month after becoming engaged, Hudson’s mother, Darnell Donerson, and her brother, Jason Hudson, were found fatally shot in a Chicago home. Her 7-year-old nephew, Julian King, was found dead in the backseat of a car. Hudson’s former brother-in-law William Balfour was convicted of the murders in 2012. ||||| Jennifer Hudson Cops Throw David Otunga out of Family Home After She Gets Order of Protection Jennifer Hudson Gets Order of Protection Claiming David Otunga is Threat to Her and Child EXCLUSIVE Jennifer Hudson had the cops come to her Chicago-area home Thursday night and throw baby daddy David Otunga out ... TMZ has learned. Sources familiar with the case tell TMZ, Hudson went to court Thursday without telling Otunga and got an order of protection, claiming he is a risk to both her and their 8-year-old son, David Jr. The police came, allowed Otunga to pack a bag and ordered him out. Sources tell TMZ the catalyst for the order of protection is turf and custody war. Our sources say the couple has been broken up for several months ... after David allegedly found out Hudson was dating someone else. David stayed in the family home -- which is owned by Jennifer -- partly because he's been the primary caregiver since she's on the road a lot. We're told the couple has been negotiating a custody arrangement for the last few weeks, but the negotiations broke down after both David and Jennifer dug in ... each wanting primary physical custody of their son. Our sources say Jennifer demanded that David leave the home, and when it became apparent he wasn't going to comply she went to court for the order of protection. She's also filed a petition for full physical custody. ||||| Jennifer Hudson may not have her fairytale ending with David Otunga after all. The couple have broken up and ended their relationship after 10 years, E! News confirms. "[They] have been in the process of ending their relationship for a number of months," Jennifer's rep tells E! News. "Today, Jennifer requested and received a protective order against her ex-fiancé. Jennifer's actions are solely taken in the best interest of their son. Please respect her privacy at this time." David's attorney would also release a separate statement to E! News. "David Otunga has been trying to negotiate the terms of an amicable parenting agreement with Ms. Hudson for several weeks now. However, when it became apparent to Ms. Hudson that Mr. Otunga would be the parent granted residential care of the child, as a result of Mr. Otunga being the child's primary caregiver while Ms. Hudson pursues her career all over the world, Ms. Hudson decided to file a meritless Petition for Order of Protection in an effort to gain an unfair advantage in the custody dispute," Tracy Rizzo explained. "As a result of Mr. Otunga's career in the WWE, Ms. Hudson felt that she could give an award winning performance in court to portray herself as the victim. Mr. Otunga has never abused or harassed Ms. Hudson or their son, and it is unfortunate, especially in today's climate, that she would feel the need to make these false allegations against him. Mr. Otunga looks forward to his day in court and in being awarded the residential care of the parties' only child."

– Jennifer Hudson has split from the fiance she once said "saved her life" after her mother, brother, and nephew were murdered—and she also got a protective order against him. Hudson, 36, and former pro wrestler David Otunga, 37, have been together a decade, got engaged in 2008, and had a son together in 2009. "They have been in the process of ending their relationship for a number of months," Hudson's rep tells People. "Today, Jennifer requested and received a protective order against her ex-fiancé. Jennifer’s actions are solely taken in the best interest of their son." Per TMZ, police ordered Otunga to leave the couple's Chicago-area home, which Hudson owns, Thursday night. But a rep for Otunga says the couple had been attempting to work out a custody arrangement for weeks, and only when it became apparent that Otunga would be granted residential care of their son because he is "the child’s primary caregiver while Ms. Hudson pursues her career all over the world," per a statement given to E!, did Hudson file for a protective order. "Mr. Otunga has never abused or harassed Ms. Hudson or their son, and it is unfortunate, especially in today’s climate, that she would feel the need to make these false allegations against him," the statement continues. As for what was behind the initial split, TMZ's sources say Hudson started dating someone else.

a general review on small @xmath1 physics and ccfm evolution can be found in @xcite . the original ccfm splitting function is given by : @xmath2 with @xmath3 and with the non - sudakov form factor @xmath4 defined as : @xmath5 here only the singular terms @xmath6 and @xmath7 were included and for simplicity the scale in the running @xmath8 was not treated in the same way for the small and large @xmath9 part . due to the angular ordering a kind of random walk in the propagator gluon can be performed . for values of @xmath10 the non - perturbative region is entered , which is avoided in a strictly -ordered evolution ( dglap ) . the region of small is characterized by @xmath8 and the parton density being large , and collective phenomena , like gluon recombination or saturation might play a role . at such small the total cross section is expected to rise only weakly with energy , equivalently to a constant @xmath11 for small @xmath1 and @xmath12 . a practical treatment is therefore to fix @xmath13 to @xmath14 for @xmath15 . until @xmath16 is reached , no gluon emissions are allowed , but energy - momentum conservation is properly treated . in the * js * unintegrated gluon density @xcite , the soft region was defined by @xmath17 gev . in the new sets presented here , @xmath18 was chosen , with @xmath19 being the collinear cut for the real emissions ( the scale for resolvable branchings ) . following the arguments in @xcite , it was investigated in @xcite to change the scale in @xmath8 to @xmath20 everywhere , in @xmath6 part of the splitting function as well as in the non - sudakov form factor . from eq.([non_sudakov_int ] ) it is obvious , that a special treatment of the soft region ( and the lower integration limit ) is needed , because @xmath21 can become very small and even @xmath22 at small values of @xmath23 . the problematic region in the non - sudakov form factor in eq.([non_sudakov_int ] ) is avoided by fixing @xmath13 for @xmath24 gev @xcite : @xmath25 with @xmath26 and @xmath27 being the number of active flavours . the integration limits are defined by @xmath28 , @xmath29 gev and @xmath30 . however in practical application we observe only a small effect from changing the scale of the small @xmath9 part from to . at very high energies , the @xmath6 term in @xmath31 will certainly be dominant . however , at present colliders the non - singular terms , as suggested in @xcite should also be included : @xmath32 as already mentioned before , the change of the scale in @xmath8 from to does not produce significant differences . for simplicity , is still taken as the scale for the small @xmath9 part in the non - sudakov form factor . the ccfm evolution equations have been solved numerically @xcite using a monte carlo method . three new sets ( * j2003 set 1 - 3 * , details are given in tab . [ pdfsets ] ) of unintegrated gluon densities were determined and compared to the previous one * js * @xcite . the input parameters were fitted to describe the structure function @xmath0 in the range @xmath33 and @xmath34 gev@xmath35 as measured at h1 @xcite and zeus @xcite . set * js * @xcite was fitted only to @xmath0 of ref . @xcite . .the different settings of the ccfm unintegrated gluon densities . in * j2003 set 2 * and * j2003 set 3 * the lower integration limit in the non - sudakov form factor is changed from eq.([non_sudakov_int ] ) to @xmath36 . in the last column , the @xmath37 to hera @xmath38 data @xcite is given ( for @xmath39 and @xmath40 gev@xmath35 ) . [ cols="^,^,^,^,^",options="header " , ] a comparison of the different sets of ccfm unintegrated gluon densities is shown in fig . [ ccfm - new ] . it is clearly seen , that the treatment of the soft region , defined by @xmath10 influences the behavior at small @xmath1 and small . it is interesting to note , that the change of the scale form to in * j2003 set 2 * is visible only in the small region , whereas at larger * j2003 set 1 * and * j2003 set 3 * agree reasonably well . in tab . [ pdfsets ] the parameters of the ccfm unintegrated gluon densities are summarized and also the @xmath41 of the fits are shown . we use the same parameter settings as given in tab . [ pdfsets ] , to calculate the ccfm unintegrated gluon density of the real photon . for the input gluon density at the scale @xmath19 we chose grv set @xcite , which also determined the normalization . the set corresponding to * j2003 set 2 * is used in 1.2 @xcite to calculate heavy quark production in @xmath42 reactions and are compared with the measurements at lep ( fig . [ bbar_lep ] ) . charm production is reasonably well described , whereas bottom production falls below the measurement . the prediction obtained in -factorization is only slightly larger than that obtained in the collinear approach at nlo . we are grateful to the organizers of the dis2003 workshop for the stimulating atmosphere and the good organization .

new fits of the unintegrated gluon density obtained from ccfm evolution to hera @xmath0 data are presented . also predictions of the unintegrated gluon density of the real photon are presented .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Removing Barriers to Adoption and Supporting Families Act of 2013''. SEC. 2. REAUTHORIZATION OF ADOPTION INCENTIVE PAYMENTS. (a) In General.--Section 473A of the Social Security Act (42 U.S.C. 673b) is amended-- (1) in subsection (b)(5), by striking ``2008 through 2012'' and inserting ``2013 through 2017''; and (2) in subsection (h)-- (A) in paragraph (1)(D), by striking ``2013'' and inserting ``2018''; and (B) in paragraph (2), by striking ``2013'' and inserting ``2018''. SEC. 3. ENCOURAGEMENT OF INTERSTATE ADOPTIONS. (a) Additional Incentive Payment for Sending and Receiving States of an Interstate Adoption.-- (1) In general.--Section 473A(d) of the Social Security Act (42 U.S.C. 673b(d)) is amended-- (A) in paragraph (1)-- (i) in the matter preceding subparagraph (A), by striking ``and (3)'' and inserting ``(3), and (4)''; (ii) in subparagraph (B), by striking ``and'' after the semicolon; (iii) in subparagraph (C), by inserting ``or'' after the semicolon; and (iv) by adding at the end the following: ``(D) subject to paragraph (4), $8,000 multiplied by the amount (if any) by which the number of interstate adoptions in the State during the fiscal year exceeds the base number of interstate adoptions for the State for the fiscal year.''; and (B) by adding at the end the following: ``(4) Sending and receiving states sharing of interstate adoption incentive payment.--The Secretary shall pay each State that was a receiving State for an interstate adoptive placement for a fiscal year, a pro rata share of the portion of the adoption incentive payment paid to the sending State for the fiscal year under this section that is attributable to the amount determined under paragraph (1)(D).''. (2) Conforming amendments.--Section 473A of such Act (42 U.S.C. 673b) is amended-- (A) in subsection (b)(2)-- (i) in subparagraph (B), by striking ``or'' after the semicolon; (ii) in subparagraph (C), by inserting ``or'' after the semicolon; and (iii) by adding at the end the following: ``(D) the number of interstate adoptions in the State during the fiscal year exceeds the base number of interstate adoptions for the State in the fiscal year;''; and (B) in subsection (g), by adding at the end the following: ``(9) Base number of interstate adoptions.--The term `base number of interstate adoptions for a State' means, with respect to any fiscal year, the number of interstate child adoptions in the State in fiscal year 2012. ``(10) Interstate adoptions.--The term `interstate adoptions' means the final adoption of a child who, at the time of adoptive placement out-of-State, was in foster care under the supervision of the State or for whom an adoption assistance agreement was in effect under section 473 with respect to the child. ``(11) Receiving state.--The term `receiving State' means the State in which the adoptive parents reside at the time of final adoption of a child from another State. ``(12) Sending state.--The term `sending State' means the State in which the child resided before being placed for an adoption in another State.''. (b) Requirement To Report Data on Interstate Adoptions.--Section 473A(c) of such Act (42 U.S.C. 673b(c)) is amended by adding at the end the following: ``(4) Determination of numbers of interstate adoptions based on state reporting of data.-- ``(A) In general.--A State is in compliance with this subsection for a fiscal year if the State has provided to the Secretary the following data with respect to the preceding fiscal year: ``(i) The total number of interstate adoptions completed by the State with respect to children in foster care under the responsibility of the State, and with respect to each such adoption the identity of the other State involved. ``(ii) The total number of adoptions completed by the State with respect to children who were in foster care under the responsibility of other States, and with respect to each such adoption, the identity of the other State involved. ``(iii) Such other information as the Secretary may require in order to determine whether the State is eligible for an adoption incentive payment under subsection (d)(1)(D) for the fiscal year. ``(B) Verification of data.--The Secretary shall verify the data submitted by a State under subparagraph (A).''. SEC. 4. NATIONAL STANDARDS FOR STATE HOME STUDIES. (a) National Standards for State Home Studies.--Section 476 of the Social Security Act (42 U.S.C. 676) is amended by adding at the end the following: ``(d) National Standards for State Home Studies.-- ``(1) In general.--Not later than 12 months after the date of enactment of this subsection, the Secretary shall develop national standards for home studies for use in evaluating potential foster and adoptive parents. In developing these standards, the Secretary shall consult with a working group composed of representatives of the adoption and foster care community, experts in the field of social work, State child welfare leaders and other qualified individuals. ``(2) Periodic review and updating.--The Secretary shall periodically review and update, as appropriate, the standards developed under this subsection.''. (b) Enhanced Matching Rate for States Adopting Home Study in Compliance With National Standards.--Section 474 of the Social Security Act (42 U.S.C. 674) is amended-- (1) in each of paragraphs (1) and (2) of subsection (a), by inserting ``subject to subsection (h),'' before ``an amount equal to the Federal''; and (2) by adding at the end the following: ``(h) The percentage applicable under paragraphs (1) and (2) of subsection (a) for amounts expended during a quarter by a State or the District of Columbia, or, in the case of an Indian tribe, tribal organization, or tribal consortium that has elected to operate a program under this part in accordance with section 479B, the tribal FMAP, referred to in such paragraphs, shall be increased by 5 percentage points for each quarter that begins on or after the effective date of an election by the State, District of Columbia, or Indian tribe, tribal organization, or tribal consortium operating a program under this part in accordance with section 479B, to use the home study standards developed under section 476(d).''. SEC. 5. LIMITING ANOTHER PLANNED PERMANENT LIVING ARRANGEMENT AS A PERMANENCY OPTION. (a) Elimination of Option for Children Under Age 17.--Section 475(5)(C) of the Social Security Act (42 U.S.C. 675(5)(C)) is amended by inserting ``only if the child has attained age 17'' before ``(in cases where the State agency has documented''. (b) GAO Report on Use of Another Planned Permanent Living Arrangement Placements.--The Comptroller General of the United States shall conduct a study and submit a report to Congress regarding-- (1) the number of children in each State (as defined for purposes of parts B and E of title IV of the Social Security Act (42 U.S.C. 621 et seq., 670 et seq.)) that are assigned a permanency goal of another planned permanent living arrangement for the most recent fiscal year for which data are available; (2) with respect to such fiscal years and on a State-by- State basis, the ages, gender, race, and special needs of children whose permanency goal is another planned permanent living arrangement; (3) a review and analysis of court practices for determining that another planned permanent living arrangement is the appropriate placement for a child; (4) information with respect to foster youths' involvement in deciding to enter into a permanency goal of another planned permanent living arrangement, including, but not limited to, how another planned permanent living arrangement is presented as an option to foster youth, how involved foster youth are in selecting the option, and what alternative options are offered instead of another planned permanent living arrangement; and (5) a summary of the reasons that reunification, adoption, kinship care, or guardianship were not found to be in the best interests of the child. SEC. 6. INCREASED FUNDING SUPPORT FOR POST-ADOPTION AND POST-PERMANENCY SERVICES. (a) Dedicated Use of Portion of Savings From Adoption Assistance De-Linkage for Post-Adoption and Post-Permanency Services.--Section 473(a)(8) of the Social Security Act (42 U.S.C. 673(a)(8)) is amended-- (1) by inserting ``(A)'' after ``(8)''; (2) by striking ``(including post-adoption services)''; (3) by striking ``, including on post-adoption services.'' and inserting ``. A State shall spend an amount equal to 20 percent of the amount of such savings to provide post-adoption and post-permanency services to children or families and shall document how such amounts are spent.''; and (4) by adding at the end the following: ``(B) The Secretary shall establish a formula for States to use to calculate the amount of savings in State expenditures under this part resulting from the application of paragraph (2)(A)(ii) to all applicable children for a fiscal year based on the State and Federal shares of expenditures for adoption assistance payments under this section as of fiscal year 2009.''. (b) Dedicated Uses of Promoting Safe and Stable Families Funds Including for Post-Adoption and Post-Permanency Services.--Section 432(a)(4) of the Social Security Act (42 U.S.C. 629b(a)(4)) is amended to read as follows: ``(4) contains assurances that not more than 10 percent of the expenditures under the plan for any fiscal year with respect to which the State is eligible for payment under section 434 for the fiscal year shall be for administrative costs, and 20 percent of remaining expenditures shall be for programs of family preservation services, 20 percent for community based family support services, 20 percent for time- limited family reunification services, 10 percent for adoption promotion, and 10 percent for post-adoption and post-permanency services;''. (c) Post-Adoption and Post-Permanency Services Defined.--Section 431(a) of the Social Security Act (42 U.S.C. 629a(a)) is amended by adding at the end the following: ``(10) Post-adoption and post-permanency services.--The term `post-adoption and post-permanency services' means services for children placed in adoptive, kinship, or guardianship placements and their families, and may include any or all of the following: ``(A) Individual counseling. ``(B) Group counseling. ``(C) Family counseling. ``(D) Case management. ``(E) Respite care. ``(F) Training of public adoption personnel, personnel of private child welfare and adoption agencies licensed by the State to provide adoption services, mental health services professionals, and other support personnel to provide services under this part and part E. ``(G) Assistance to adoptive parent organizations. ``(H) Assistance to support groups for adoptive parents, adopted children, and siblings of adopted children. ``(I) Rigorous evaluations of post-adoption and post-permanency services.''. SEC. 7. ENCOURAGING DEVELOPMENT OF ROBUST, COMPREHENSIVE PRACTICE MODELS OF ADOPTIONS FROM FOSTER CARE. (a) State Plan Amendment.--Section 471(a) of the Social Security Act (42 U.S.C. 671(a)) is amended-- (1) in paragraph (32), by striking ``and'' after the semicolon; (2) in paragraph (33), by striking the period at the end and inserting ``; and''; and (3) by adding at the end the following: ``(34) provides that the State will engage in public- private partnerships to promote evidence-based child-focused recruitment practices that focus measurable attention on the adoption of children out of foster care with an emphasis on those children most at risk of aging out of care .''. (b) Technical Assistance.--The Secretary of Health and Human Services shall provide guidance and technical assistance to State child welfare agencies on the use of Federal funds available under section 474 (a)(3)(B) of the Social Security Act (42 U.S.C. 674(a)(3)(B)) for training for the implementation of intensive recruitment and child- focused strategies that have been shown to increase permanent placements for older youth in foster care. SEC. 8. ENCOURAGING PLACEMENT OF CHILDREN WITH SIBLINGS. (a) State Plan Amendment.--Section 471(a)(29) of the Social Security Act (42 U.S.C. 671(a)(29)) is amended by striking ``all adult grandparents'' and inserting ``notice to the following relatives: all adult grandparents, all parents of the child's siblings, where such parent has legal custody of such sibling,''. (b) Definition of Siblings.--Section 475 of the Social Security Act (42 U.S.C. 675) is amended by adding at the end the following: ``(9) The term `siblings' means individuals who satisfy at least one of the following conditions: ``(A) The individuals are considered by State law to be siblings. ``(B) The individuals would have been considered siblings under State law but for termination of parental rights or other disruption of parental rights, such as the death of a parent.''. SEC. 9. EFFECTIVE DATE. (a) In General.--Except as provided in subsection (b), the amendments made this Act shall take effect on October 1, 2013. (b) Delay Permitted if State Legislation Required.--In the case of a State plan approved under part B or E of title IV of the Social Security Act which the Secretary of Health and Human Services determines requires State legislation (other than legislation appropriating funds) in order for the plan to meet the additional requirements imposed by this Act, the State plan shall not be regarded as failing to comply with the requirements of such part solely on the basis of the failure of the plan to meet such additional requirements before the 1st day of the 1st calendar quarter beginning after the close of the 1st regular session of the State legislature that ends after the 1-year period beginning with the date of the enactment of this Act. For purposes of the preceding sentence, in the case of a State that has a 2-year legislative session, each year of the session is deemed to be a separate regular session of the State legislature. SEC. 10. DETERMINATION OF BUDGETARY EFFECTS. The budgetary effects of this Act, for the purpose of complying with the Statutory Pay-As-You-Go Act of 2010, shall be determined by reference to the latest statement titled ``Budgetary Effects of PAYGO Legislation'' for this Act, submitted for printing in the Congressional Record by the Chairman of the Senate Budget Committee, provided that such statement has been submitted prior to the vote on passage.

Removing Barriers to Adoption and Supporting Families Act of 2013 - Amends part E (Foster Care and Adoption Assistance) of title IV of the Social Security Act (SSA) to reauthorize the adoption incentive payment program through FY2018. Adds a new adoption incentive payment for states involved in sending and receiving interstate adoptions. Directs the Secretary of Health and Human Services (HHS) to pay each state that was a receiving state for an interstate adoptive placement for a fiscal year a pro rata share of the portion of the adoption incentive payment paid to the sending state. Requires a state to report to the Secretary data on interstate adoptions. Directs the Secretary to develop national standards for home studies for use in evaluating potential foster and adoptive parents. Establishes a matching rate for states adopting home study in compliance with national standards. Limits planned permanent living arrangements to children who have attained age 17. Directs the Comptroller General to study: (1) the number of children in each state that are assigned a permanency goal of another planned permanent living arrangement for the most recent fiscal year for which data are available; (2) the ages, gender, race, and special needs of children whose permanency goal is another planned permanent living arrangement; (3) a review and analysis of court practices for determining that another planned permanent living arrangement is the appropriate placement for a child; (4) information with respect to foster youths' involvement in deciding to enter into a permanency goal of another planned permanent living arrangement; and (5) a summary of the reasons that reunification, adoption, kinship care, or guardianship were not found to be in the best interests of the child. Requires a state to spend an amount equal to 20% of the amount of savings from adoption assistance de-linkage to provide post-adoption and post-permanency services to children and families. Requires the state foster care and adoption assistance plan to: (1) commit the state to engage in public-private partnerships to promote evidence-based child-focused recruitment practices that focus measurable attention on the adoption of children out of foster care with an emphasis on those children most at risk of aging out of care, and (2) encourage placement of children with siblings.

in this section technical details of magnetization - induced optical second harmonic generation ( mshg ) in the eu@xmath0gd@xmath1o system are given . this includes a discussion of the coupling effects and the electronic states involved in the mshg process . furthermore , details on the experiment confirming that the shg process probes the spin dynamics and is not influenced by other carrier - related nonequilibrium effects are provided . the photo - absorption and -emission constituting the shg process can be parametrized by a multipole expansion of the coupling of the light field to the system . in the leading order of this expansion , we get electric dipole ( ed ) transitions and , hence , shg is described by the relation @xcite , @xmath59 here , @xmath60 represents the electric - field components of the incident light wave at @xmath25 whereas @xmath61 represents the nonlinear electric polarization induced at @xmath62 which acts as source of a light wave of intensity @xmath63 . the nonlinear susceptibility @xmath64 incorporates the crystal structure , the electronic states , and the symmetry of the nonlinear material . shg according to eq . ( [ eq : ed - shg ] ) is only allowed in non - centrosymmetric media . in centrosymmetric compounds like euo , shg becomes allowed only in higher orders of the multipole expansion , that is , to leading order , when one magnetic dipole ( md ) is taken into account . in addition , ed - shg as in eq . ( [ eq : ed - shg ] ) may also originate at the surface where space inversion symmetry is always broken . for centrosymmetric euo , bulk - generated md - shg according to @xmath65 was identified in refs . @xcite and @xcite . here , @xmath66 and @xmath67 denote contributions with linear coupling to , respectively , the paramagnetic crystal or the magnetic order @xcite . in the ( 001)-oriented euo films investigated by us , the non - magnetic shg contributions according to @xmath66 can not be excited @xcite . with the normal - incidence transmission setup sketched in the inset of fig . [ fig2 ] , the aforementioned surface ( non - magnetic ) ed - shg contributions can not be excited either , since in this geometry the shg process only involves in - plane components of the light field , which are not sensitive to the inversion symmetry breaking by the surface . thus , in our experiments , shg should provide a background - free probe of the magnetic order . this is confirmed by the emergence of the shg signal at @xmath16 . likewise , the linear dependence of the shg intensity on the thickness of the euo films corroborates that shg couples to the bulk of the euo films @xcite . microscopically , mshg in eu@xmath0gd@xmath1o is based on a two - photon transition from the @xmath17 ground state to the @xmath8 conduction band @xcite . the band state at @xmath68 ev is resonantly excited and there may be further resonance enhancement by the @xmath11 exciton state near @xmath69 ev . this is reminiscent of the doubly resonant md - shg process observed in nio @xcite . in eu@xmath0gd@xmath1o we identify experimentally a linear dependence of the shg amplitude on the value of the effective exchange interaction @xmath15 ; see main text . this is a clear indication that the two - photon absorption in eu@xmath0gd@xmath70o is assisted by an interaction process between the local spin magnetic moments . as an explanation for the linear @xmath15-dependence , we thus speculate that this _ local _ interaction process provides momentum transfer to the photoexcited carriers and thus facilitates the resonant @xmath9-@xmath10 transition . in principle such a coupling can be expressed by expanding in powers of @xmath15 , and according to our experiment the leading , first - order contribution is dominant . ( a detailed analysis of the two - photon excitation processes is currently in progress . ) measurements , as in fig . [ fig1](c ) , clearly demonstrate that the shg process in eu@xmath0gd@xmath1o couples linearly to the magnetic order of the sample . this might , however , no longer be the case when the magnetic state of a sample is investigated in the non - equilibrium state acquired after intense photoexcitation . the redistribution of the charge carriers by the pump pulse and the ensuing relaxation dynamics may also influence the mshg signal . in order to scrutinize this issue we performed time - resolved linear transmission measurements on the eu@xmath0gd@xmath1o system . the transmittance ( or reflectance ) is an established probe for studying charge - carrier dynamics because it directly reproduces the population of the electronic states affected by the pump pulse @xcite . the linear transmittance at the photon energies of the fundamental and the frequency - doubled light expresses a highly complex dynamics that remains to be understood ( experimental and theoretical investigations are in progress ) . but even without having achieved such understanding yet none of the dynamics seen in the transmittance transients is reproduced in the mshg scan and vice versa . we can therefore conclude that the mshg process truly probes the magnetic order whereas , within our resolution , it is insensitive to the charge carrier dynamics . with respect to the effective coupling @xmath15 this means that the mshg transient includes contributions by the virtual ( undoped ground state ) or the real ( gd- or photo - generated ) occupation of the @xmath10 orbitals . another carrier - related contribution to the shg signal that might be suspected is related to the absorption of the pump light . it leads to an exponential decrease of the pump - light intensity and , hence , of the density of photoexcited carriers across the thickness of the eu@xmath0gd@xmath1o films . the carrier density gradient breaks the inversion symmetry and might lead to additional shg tensor components . the presence of such contributions in the mshg signal can , however , be excluded for three reasons . first , its temporal evolution would reflect that of the transmittance at @xmath25 . yet , such shg contributions were not detected . second , the absorption of the pump light is so moderate that the related carrier density changes by a factor of less than two across the films investigated by us . third , carrier gradient contributions to shg would occur below and above the magnetic ordering temperature . above @xmath16 the shg signal in the photoexcited samples is , however , zero at all delays . after photoexcitation of the non - equilibrium @xmath9-@xmath10 exciton population , it will take a certain time @xmath41 for the magnetic rkky correlations in the @xmath8 conduction band and , hence , for the @xmath15 enhancement to be established . as stated in the main text , @xmath41 can be estimated from the time it takes the electronic correlation to spread through the system . the relevant distance is the rkky wavelength , and the propagation velocity is the group velocity of the magnetic exciton , which is effectively reduced with respect to the conduction electron group velocity by the ratio @xmath71 of the effective masses of the @xmath8 conduction electrons ( @xmath72 ) and of the heavy holes in the @xmath9 band ( @xmath73 ) , which together form the magnetic exciton . this effective mass ratio was taken to be equal to the inverse ratio of the respective band widths and was extracted from literature data @xcite to be in the order of @xmath74 . in addition , we assume a parabolic conduction bands ( appropriate for our low excitation energy within the conduction band of @xmath75 ev ) . with @xmath76 we thus obtain a buildup time @xmath41 of about 10 ps which is in good agreement with the measured value of @xmath403 ps in fig . the rkky - like magnetic coupling and , hence , the photoinduced enhancement of @xmath15 are proportional to the density of photoexcited non - thermalized conduction electrons which , in turn , is proportional to the conduction electron density of states , @xmath77 , at the final - state energy of the photoexcited electrons , @xmath78 . as earlier calculations have shown @xcite , this density of states is sensitively affected by the gd - doping concentration @xmath20 . increasing @xmath20 leads to a downward shift of spectral weight and an enhancement of @xmath77 for the photon energy @xmath79 ev used in our experiments . we have calculated the rkky coupling produced by the photoinduced , non - equilibrium electron population in the conduction band , where the latter is renormalized by the presence of the gd impurities as described above @xcite . for @xmath20 in the order of 1% , this coupling is ferromagnetic and increasing with @xmath20 , whereas for growing @xmath20 it acquires increasingly antiferromagnetic contributions . in order to extract the effective exchange coupling as a single number that can be compared with the experiment , first the curie temperature @xmath16 was calculated for the long - range rkky coupling using mean - field theory . the effective exchange coupling @xmath80 as shown in fig . [ fig4](b ) was then determined as the effective nearest - neighbor coupling within a heisenberg model displaying the same value of @xmath81 . the interplay of the @xmath20-dependent increase of density of states and of the increasingly antiferromagnetic rkky contributions leads to the non - monotonous behavior of @xmath82 depicted in fig . [ fig4](b ) . thermalization processes becoming more effective for larger @xmath20 may lead to an additional reduction of @xmath80 at @xmath83% . note that the theoretical curve of fig . [ fig4](b ) contains only a _ single _ freely adjustable parameter . this is the unknown overlap integral of the conduction electron wave functions with the local @xmath9 wave functions . this parameter determines the overall size of @xmath82 , i.e. , the scale on the vertical axis of fig . [ fig4](b ) . the only other parameter of the model calculation is the ratio of the effective masses of the @xmath8 conduction electrons and of the heavy holes in the @xmath9 band , which was calculated in appendix b and is thus not a fit parameter . b. kaminski , m. lafrentz , r. v. pisarev , d. r. yakovlev , v. v. pavlov , v. a. lukoshkin , a. b. henriques , g. springholz , g. bauer , e. abramof , p. h. o. rappl , and m. bayer , phys . lett . * 103 * , 057203 ( 2009 ) .

ultrafast strengthening or quenching of the ferromagnetic order of semiconducting eu@xmath0gd@xmath1o was achieved by resonant photoexcitation . the modification of the magnetic order is established within 3 ps as revealed by optical second harmonic generation . a theoretical analysis shows that the response is determined by the interplay of chemically and optically generated carriers in a nonequilibrium scenario _ beyond _ the three - temperature model . general criteria for the design of spintronics materials with tunable ultrafast spin dynamics are given . the demand for an ever - increasing density and speed of manipulation in magnetic information storage triggered an intense search for ways to control the magnetic moment by means other than magnetic fields . following the pioneering demonstration of light - induced magnetization change on the sub - ps time scale @xcite , the manipulation and control of magnetic order by ultrashort laser pulses has developed into an exciting research topic @xcite . most of the time - resolved investigations are focused on ultrafast _ demagnetization _ @xcite . this involves quenching of magnetic order and is often described by a three - temperature model ( 3tm ) , where the coupled electron , spin , and lattice subsystems are each assumed to be in equilibrium at their respective temperatures @xcite . in special cases , however , the photoexcitation leads to the nonthermal _ generation _ and/or _ enhancement _ of magnetic order by photo - controlling the exchange interaction . enhancement is possible if the photoexcited carriers connect neighboring magnetic sites more efficiently . for example , the ultrafast generation of ferromagnetic order in a strongly correlated manganite is based on photo - activated `` double - exchange '' interaction between mn@xmath2 and mn@xmath3 ions @xcite . transient enhancement of ferromagnetism in a diluted magnetic semiconductor is mediated by photoexcited mobile carriers connecting magnetic ions ( `` @xmath4-@xmath5 exchange '' ) @xcite . these observations arouse the question if criteria can be identified that allow us to _ enhance or attenuate _ the magnetic order of a system at will . in this letter we show that , depending on the carrier density , ultrafast strengthening or quenching of the ferromagnetic order in eu@xmath0gd@xmath1o can be achieved via resonant photoexcitation . the change of the magnetic order is established within 3 ps and detected via magnetization - induced optical second harmonic generation ( mshg ) . the spin dynamics can not be explained by a 3tm , but is a consequence of the photoinduced non - equilibrium carrier distribution , as the theoretical analysis shows . in contrast to systems with a high carrier concentration like transition - metal , rare - earth , or certain diluted - magnetic - semiconductor ferromagnets , the sub - ps carrier dynamics in low - doped eu@xmath0gd@xmath1o is far from equilibrium due to a substantially longer electron thermalization time . the resulting spin dynamics is explained by the interplay of chemically and optically generated carriers and the dynamic renormalization of the rkky - like exchange coupling . the change from ultrafast enhancement to quenching of ferromagnetism is marked by the crossover from the predominantly semiconducting to the predominantly metallic doping range of eu@xmath0gd@xmath1o . aside from the generalized insight into ultrafast spin as well as charge dynamics , a key requirement for spintronics technology , our investigation provides a guide for the selection and design of materials for ultrafast optical control of magnetic order . ( solid triangles ) @xcite and of the square root of the static mshg intensity @xmath6 ( open squares ) on the carrier density @xmath7 at 4.2 k in eu@xmath0gd@xmath1o . the inset shows the relation of the gd concentration to @xmath7 @xcite . ( b ) spin - dependent electronic structure of undoped ferromagnetic euo . the eu @xmath8 conduction band is split by the @xmath9-@xmath10 exchange interaction . the mshg process probes the magnetic order via a two - photon transition to the @xmath8 conduction band . a more detailed figure showing the splitting of the @xmath11 sub - states can be found in ref . @xcite . ( c ) temperature dependence of @xmath6 for undoped and 2.65% gd - doped euo.,width=302 ] gd - doped euo was chosen as a candidate material because of the multitude of extreme magnetism - related properties ( full spin polarization , simultaneous ferromagnetic and insulator - metal transition , colossal magnetoresistance , giant magneto - optical effects , etc . @xcite ) . undoped euo is a prototype heisenberg ferromagnet . the magnetic moment of 7 @xmath12 arises from the strongly localized , half - filled @xmath9 shell of the eu@xmath13 ions on a cubic rock salt structure . due to the strong localization of the @xmath9 orbitals , however , the direct @xmath9-@xmath9 exchange coupling with the nearest eu@xmath13 neighbors is too weak to explain a curie temperature as high as @xmath14 k. instead , the ferromagnetic order is driven by a virtual exchange mechanism @xcite : a virtual magnetic exciton is created by a localized @xmath9 electron fluctuating into the empty eu @xmath10 state so that the magnetic exchange coupling @xmath15 can be mediated via the spatially more extended @xmath10 orbitals . in eu@xmath0gd@xmath1o , @xmath15 and @xmath16 are further enhanced by _ truly populating _ the @xmath10 orbitals with the extra electron introduced by replacing eu@xmath13 by the otherwise magnetically equivalent gd@xmath2 @xcite , as shown in fig . [ fig1](a ) . note that these dopant electrons do not form excitons , but rather occupy the gd @xmath10 impurity orbitals , which in the metallic phase below @xmath16 merge with the eu @xmath8 conduction band @xcite to produce a long - range rkky contribution to @xmath15 . this mechanism suggests that , alternatively , an ultrafast enhancement of @xmath15 may be driven by resonant optical pumping of electrons from the eu @xmath17 ground state to the @xmath11 magnetic exciton state [ fig . [ fig1](b ) ] , since this turns the virtual magnetic exciton into a real one , promoting the magnetic order . in order to study the ultrafast spin dynamics , epitaxial eu@xmath0gd@xmath1o ( 001 ) films ( @xmath18% ) with a thickness of 35 nm were grown under adsorption - controlled conditions on two - side - polished yalo@xmath19 ( 110 ) single - crystal substrates by molecular beam epitaxy @xcite . the films were protected against air by an amorphous silicon capping layer 10 - 20 nm in thickness and found to be free of oxygen vacancies within the resolution limit of x - ray absorption spectroscopy ( xas ) @xcite . uniform growth without secondary phases was confirmed by x - ray diffraction , and the gd concentration @xmath20 was determined by prompt - gamma activation analysis and xas @xcite . all eu@xmath0gd@xmath1o films possess an in - plane magnetic easy axis . their physical properties were reported in ref . . 380 @xmath21j/@xmath22 . the insets show the schematic of the time - resolved mshg spectroscopy and a magnified view of the ultrafast increase of the mshg signal . solid lines are guides to the eye . ] the experimental pump - probe setup is shown as inset in fig . [ fig2 ] . the output of a ti : sapphire regenerative amplifier system at 800 nm ( @xmath23 ev ) with a pulse width of 130 fs and a repetition rate of 1 khz was divided into two beams . one was used for resonant pumping of the @xmath24 transition at 1.55 ev . the other was converted into a frequency - tunable beam by an optical parametric amplifier . this light was used for probing the time - evolution of the ferromagnetic order by mshg . a light wave of frequency @xmath25 is incident onto the sample where it generates a polarization @xmath26 in a two - photon transition to the @xmath8 conduction band [ fig . [ fig1](b ) ] . the coupling to the magnetic order occurs with high symmetry selectivity and is background - free @xcite . the mshg yield @xmath27 was measured in a normal - incidence transmission geometry under an in - plane magnetic field of 50 mt which was applied to sustain a magnetic single - domain state . the sizes of the linearly polarized probe and pump pulses were about 0.4 and 1 mm , respectively . in appendix a we describe additional technical aspects of the mshg measurement . in particular , we show that the mshg signal does not display a sensitivity to the redistribution of the charge carriers by the pump pulse . we also confirmed that it originates in the bulk of the eu@xmath0gd@xmath1o film and not at its surface or interface . mshg thus is an ideal probe for the dynamics of the magnetic order . we begin by clarifying the coupling of the shg signal to the magnetic state . ( i ) in fig . [ fig1](a ) we compare the dependence of @xmath16 and of @xmath6 at 10 k where @xmath28 is saturated , on the gd - related carrier density @xmath29 . the two curves show the same qualitative dependence on @xmath7 and even quantitatively the relative difference never exceeds 25% . according to mean - field theory , @xmath16 is proportional to @xmath15 @xcite . with good qualitative and reasonable quantitative accuracy one may approximate the relation between @xmath6 and @xmath15 ( resp . @xmath16 ) as linear . ( ii ) the temperature dependence of @xmath6 shown in fig . [ fig1](c ) is well reproduced by that of the spontaneous magnetization @xmath28 @xcite . this includes the double - dome - like dependence in the gd - doped samples , which is related to the complementary eu- and gd - driven ferromagnetic ordering processes @xcite supplemented by magnetic polaron formation @xcite . thus , ( i ) and ( ii ) lead us to the phenomenological relation @xmath30 note that , as mentioned above , the mshg signal is insensitive to the redistribution of the charge carriers by the pump pulse . moreover , previous experiments revealed @xcite that at @xmath31 ev the interference by temperature - dependent linear absorption effects is avoided . we therefore chose it for the mshg probe energy . figure [ fig2 ] shows a typical time evolution of the photoinduced change of the mshg intensity , normalized by the value before optical excitation , @xmath32 . the data were taken at 77 k on euo doped with 2.65% gd . following the photoexcitation at @xmath33 we observe a continuous _ increase _ of the mshg intensity up to @xmath34% at @xmath35 ps . this is followed by a continuous _ decrease _ passing zero at @xmath36 ps and @xmath37% at @xmath35 ns . we conclude that the photoexcitation populates the @xmath10 orbital , resulting in an enhancement of the effective @xmath9-@xmath10 exchange @xmath15 and , by aligning the thermally fluctuating @xmath9 spins , of the magnetization @xmath28 . the intra - atomic @xmath9-@xmath10 exchange energy of @xmath38 ev @xcite corresponds to a time of @xmath39 fs so that an instantaneous mshg increase after photoexcitation might be expected in contrast to the strikingly different time of @xmath403 ps . however , we have to take into account that the magnetic exchange coupling is mediated via the rkky interaction . the time @xmath41 required to coherently establish its enhancement in the photoexcited region can be estimated from the time it takes the electronic correlation to spread through the crystal . the relevant distance is the rkky wavelength , and the propagation velocity is the group velocity of the magnetic exciton ( see appendix b for numbers ) . the calculated buildup time @xmath41 of @xmath4010 ps is in surprisingly good agreement with the measured value of 3 ps . the ensuing decrease of mshg intensity on the ns time scale is associated with the demagnetization by the heating of the spin system through the transfer of the optical excitation energy from the electron system to the lattice and subsequent spin - lattice relaxation . the observed slow relaxation is consistent with the empirical thermal demagnetization time @xcite inferred from the magnetocrystalline anisotropy constant in euo @xcite , and the decrease of the mshg intensity is consistent with the laser - pulse heating calculated from the absorption coefficient and the heat capacity of euo @xcite . gd@xmath1o as a function of time delay and gd concentration . the excitation density of the pump pulse is @xmath40130 @xmath21j/@xmath22 for all traces . the inset shows the magnified view of the ultrafast change of the mshg intensity for @xmath42% and 9.63% . ] as the central part of the present work , we investigated the relation between the magnetic coupling dynamics and the carrier density @xmath7 in eu@xmath0gd@xmath1o . in order to simplify this investigation , the corresponding dynamics were measured at 10 k , where the magnetic moment is saturated . hence , according to eq . ( [ eq : imshg ] ) , all the non - thermal changes of the mshg intensity can then be associated with changes of @xmath15 . figure [ fig3 ] shows the temporal evolution of the normalized change of mshg intensity induced by optical pumping for gd concentrations between 0 and 19.5% . a common behavior of all samples is the decreasing mshg yield on a ns time scale . as mentioned above , this is caused by the thermal destabilization of the magnetic order mediated by the spin - lattice relaxation . in contrast , the mshg response on the ps time scale depends strongly on the gd concentration . at the lowest doping an ultrafast _ increase _ of the mshg signal is observed . it strikingly confirms that our magneto - optical probe process reflects a variation of @xmath15 rather than of the already saturated magnetization @xmath28 , in contrast to the results of earlier time - resolved magneto - optical rotation measurements on undoped euo @xcite . by increasing the gd concentration , the magnitude of this initial increase becomes progressively more pronounced and reaches a maximum near 0.25% . further gd doping reduces its magnitude , and at @xmath43 5% an ultrafast _ decrease _ of the mshg signal is observed . in fig . [ fig4](a ) we summarize the pump - induced change of the mshg yield as a function of @xmath7 at the fixed delay @xmath44 ps . here , @xmath7 has been derived for each gd concentration @xmath20 from the relation displayed in the inset of fig . [ fig1](a ) . the growth of the mshg response @xmath45 with increasing gd concentration occurring on the ps time scale is striking . according to the widely used 3tm @xcite , the optical pump pulse would , in addition to exciting the localized @xmath9 electrons and creating the @xmath11 magnetic excitons , lead to the excitation of the chemically doped carriers in the @xmath8 conduction band and to their thermalization at the elevated temperature corresponding to the deposited energy . this would invariably _ reduce _ @xmath15 since the magnetic coupling with electrons in the energetically higher band states becomes increasingly antiferromagnetic because of their increased wave number . ( this was checked by explicitly calculating the rkky interaction for the corresponding electron distribution in the conduction band : see appendix c. ) thermalization effects would further contribute to the demagnetization . the key to understanding the initial _ increase _ of @xmath45 with @xmath7 [ fig . [ fig4](a ) ] is that in the low - doped eu@xmath0gd@xmath1o the carrier thermalization time @xmath46 is enhanced over the one in dense itinerant ferromagnets , like ni or gd . this is because charge thermalization occurs by electron - electron scattering whose rate is proportional to the carrier concentration . taking the carrier thermalization time in pure gd as @xmath47 fs @xcite , the @xmath29 ratio of @xmath48 lets us estimate @xmath46 in low - doped eu@xmath0gd@xmath1o to be @xmath49 ps . this means that the dynamics for the first few ps is dominated by a _ non - equilibrium _ charge carrier distribution , i.e. , the 3tm is not applicable . more importantly , since electron - electron interactions are scarce in this time range , photoexcitation of the chemically doped carriers within the @xmath8 band into higher band states is kinematically forbidden . because of the large energy and the small momentum transferred by the photon , energy and momentum conservation can not simultaneously be fulfilled in this two - body process . in contrast , resonant pumping of the @xmath24 transition can occur because it satisfies energy and momentum conservation [ fig [ fig4](c ) ] . hence , for the first few ps after the photoexcitation , the carrier distribution is comprised of chemically doped carriers in the @xmath8 conduction band , which remain nearly unaffected by the pump pulse , and of the fraction of the @xmath9 electron population which is photo - excited into the state with @xmath10 electron character . all the mobile carriers contribute to a stronger magnetic coupling between the eu @xmath9 spins . as an additional effect , the increase in the carrier density in the conduction band strengthens its interaction with the gd impurity band . as shown in ref . @xcite , this entails an energetic downshift of the conduction band toward the gd impurity band and , hence , a reduction of the @xmath9-@xmath8 gap energy @xmath50 . this also affects the @xmath9-@xmath9 exchange as detailed in the discussion of fig . [ fig4 ] below . and the photoinduced change of the mshg intensity at @xmath35 ps and at 10 k extracted from fig . [ fig3 ] . the line is a guide to the eye . ( b ) calculated change of @xmath15 due to the modification of the rkky interaction by the photoinduced nonequilibrium population of the @xmath8 conduction band . ( c ) sketch of the photoexcitation dynamics beyond the 3tm in low - doped eu@xmath0gd@xmath1o . the photoinduced long - lived nonequilibrium carrier dynamics modifies the rkky interaction , and thus @xmath15 . the crossed out arrow refers to photon absorption within the @xmath8 conduction band which is kinematically forbidden . for clarity , only the majority ( spin - up ) carriers are shown . ] using the many - body renormalization theory introduced in ref . @xcite , we have calculated the rkky - like coupling for the non - equilibrium electron distribution described above ( see appendix c for technical details ) . the result is shown in fig . [ fig4](b ) . considering the crudeness of the theoretical model , the semi - quantitative , numerical agreement with the experimental result in fig . [ fig4](a ) is compelling . note that even without reference to the technical aspects of the calculation , the non - monotonous behavior in figs . [ fig4](a ) and [ fig4](b ) can be understood as follows . the density of photoexcited carriers is proportional to the spectral density at the energy @xmath51 addressed by the photoexcitation . hence , as @xmath50 is reduced with increasing @xmath7 ( see above ) , more states can be populated with photoexcited carriers ; see fig . [ fig4](c ) . this contributes to the increase of @xmath52 with @xmath7 for @xmath53 @xmath54 . for @xmath55 @xmath54 , @xmath52 and @xmath56 get quenched to negative values for two reasons : ( i ) with further downward shift of the conduction band the energy mismatch @xmath51 , and with it the wave number of the photoexcited carriers , increases further , so that @xmath15 acquires increasingly _ antiferromagnetic _ rkky - like contributions . ( ii ) with the increasing metallic nature the electron - electron scattering time gets reduced , leading to ultrafast thermalization and concomitant magnetization quenching , i.e. , conventional demagnetization according to the 3tm begins to dominate . this is nicely reflected by the change of the buildup time from @xmath403 ps ( manifestation of rkky interaction ) to @xmath40100 fs ( thermalization according to the 3tm ) in the inset of fig . [ fig3 ] . in summary , we have demonstrated that the ultrafast magnetic coupling dynamics can be tuned from photoinduced _ enhancement _ to photoinduced _ quenching _ of ferromagnetic order in eu@xmath0gd@xmath1o by controlling the carrier density . the largest enhancement of the ferromagnetic order and the crossover to quenching were observed around @xmath57 and @xmath58 @xmath54 , respectively . this behavior is explained by a nonequilibrium theory going beyond the established 3tm . our experimental results and their theoretical modelling not only demonstrate how to control the stability of a ferromagnetic state at the ultrafast time scale , but also give a guide to the material selection and design for the dynamical optical control of magnetic order : systems with a _ low density of conduction band carriers _ ( which is tuneable ) but with a _ high density of magnetic moments _ ( unlike e.g. in diluted magnetic semiconductors ) are in general favorable candidates . we thank t. stollenwerk for fruitful discussions . this work was supported by the alexander von humboldt foundation , by the eth , by the trr 80 of the deutsche forschungsgemeinschaft , and by the afosr ( grant no . fa9550 - 10 - 1 - 0123 ) .

the most luminous known agn with an ionized absorber is the radio - loud lobe - dominated quasar 3c351 ( l@xmath5 erg s@xmath6 , z=0.371 , fiore et al . , 1993 ) . ionized absorbers are common in low redshift , low luminosity seyfert 1 galaxies ( reynolds , 1997 ) , but rare in higher redshift , higher luminosity quasars . high luminosity agns are very likely physically larger and so may exhibit slower time variability and have different physical conditions . 3c 351 has a very high uv to x - ray ratio ( @xmath7 , tanambaun et al . , 1989 ) and its ir to uv spectrum does not show any evidence of reddening , in contrast to several low redshift seyfert 1 galaxies thought to host dusty / warm absorbers . only two other radio - loud quasars , 3c 212 ( mathur et al . , 1994 ) and 3c 273 ( grandi et al , 1997 ) , have candidate ionized absorbers . the main absorption feature in the rosat pspc x - ray spectrum of 3c 351 is a deep edge at @xmath1 kev ( quasar frame ) , which is likely to be due to ovii - oviii . mathur et al . ( 1994 ) built a simple one - zone model of this absorber that also explained the ovi , civ and ly@xmath8 uv absorption lines seen in a nearly simultaneous hst fos spectrum . such simple models , although elegant , have come under criticism . ionized absorbers in some seyfert galaxies show different variability behavior in different absorption features , some of which are not as predicted for gas in photoionization equilibrium . multiple absorbing zones have been introduced to explain these effects ( e.g. reynolds 1997 ) . in another paper ( nicastro et al . , 1998 ) we instead explore additional physics ( non - equilibrium photonionization models and collisional models ) while retaining a single zone of absorbing gas . 3c 351 is a relatively slowly varying source , compared to the rapidly variable seyfert with warm absorbers . this persistent variability on timescales that span possible ionization and recombination times makes it hard to define an initial equilibrium state . in contrast 3c 351 presents a simplified situation in which to study changes in the ionization state in response to luminosity changes . here we show that in 3c 351 at least the simplest photoionization equilibrium , single zone model continues to be sufficient . 3c351 was observed twice by rosat , on 1991 october and 1993 august . the first observation was reported by fiore et al . the second observation was then proposed in order to search for time variability that could test photoionization models . fortunately a factor 1.7 decrease in the pspc count rate was seen , providing just such a test . here we present the second data set and compare the results with predictions . we considered the two pspc observations of 3c351 taken roughly two years apart , in 1991 october and 1993 august . table 1 gives , for each observation , the observation date , its duration , the net exposure time , the net source counts , the count rate , and the signal to noise ratio . the data reduction and the timing analysis were performed using xselect . we reduced the second pspc observation of 3c351 following the procedures used in fiore et al . ( 1993 ) for the first observation . for the first observation we used the spectrum and light curve obtained by fiore et al . the source intensity was consistent with a constant value during both pspc observations , with no more than 20% change in the @xmath9 day and @xmath10 day spans of the two observations . 3c 351 thus appears more stable than the lower luminosity seyferts with ionized absorber ( reynolds , 1997 ) . since 3c 351 has a flat x - ray spectrum and broad optical emission lines it is consistent with the trend exhibited by the three similar but radio - quiet , pg quasars of the fiore et al . ( 1998 ) sample . those quasars show little or no variability on timescales as short as 10 days ( compared to the narrow line objects of that sample which are rapidly variable and have steep x - ray spectra ) . however the mean count rate dropped by a factor @xmath11 during the 22 months between the observations ( see table 1 ) , again consistently with the fiore et al . ( 1998 ) discovery . hereinafter we shall call these the high and low states , respectively . [ cols="^,^,^,^,^,^,^,^ " , ] @xmath12 in @xmath13 ph s@xmath6 @xmath14 kev@xmath6 ( at 1 kev ) . = 4.5 in = 3.in collisional ionization models can fit the data equally well , as they should at low column densities ( nicastro et al . , 1997 ) . to do so however they require arbitrary changes , by a factor 1.5 in temperature or a factor 2 in n@xmath15 . instead photoionization equilibrium models predict the observed correlation with the ionizing continuum . to the authors this is a strong argument in favor of a photoionization model . the behavior of the main physical properties of the absorber can be seen in a color - color diagram . in fig . 3 we plot the hardness ratios hr = h / m against the softness ratio sr = s / m from the count rates in three bands ( s=0.15 - 0.58 kev , m=0.88 - 1.47 kev , and h=1.69 - 3.40 kev , at z=0.371 ) for theoretical curves ( for log(@xmath16)=21 , 21.5 , 22 and 22.14 ) obtained by folding the equilibrium photoionization models ( for log(u ) in the range -0.3 - 1.5 , and galactic @xmath16 ) with the response matrix of the pspc . = 4.0 in = 4.0 in the position of a point in this diagram readily gives the dominant ion in the gas . the rapid change of sr as u increase from 0.5 to 5.5 ( on the curve corresponding to log(@xmath16)=22.14 ) corresponds to large increases of the transparency of the gas at e@xmath17 kev as h and he becomes rapidly fully ionized . as u further increases from 5.5 to 16.5 the sr color changes more slowly , and inverts its trend at u@xmath18 , with hr now changing more rapidly than sr . the inversion point indicates the switch from an ionization state dominated by ovii to that dominated by oix . in the last part of the curve as u increases , sr and hr decrease until all the ions in the gas are fully stripped and the gas is completely transparent to radiation of any energy . the two data points show the two 3c 351 observations . the best fit u in the high observation is marked on the log(@xmath16)=22.14 curve along with the value obtained by scaling by the intensity ratio between the two observations ( a factor 1.7 ) . the two points are consistent with the position of the observed colors of 3c351 in the two observations , so the predictions of the simple equilibrium photoionization model is consistent with the data . the as predicted change of the ionization parameter in the 3c 351 absorber to a change in the ionizing continuum is strong evidence that photoionization is the dominant ionization mechanism . we also see that the absorber comes to ionization equilibrium within 22 months , and can use this to constrain the physical properties of the absorber . the time @xmath19 measures the time the gas needs to reach equilibrium with the instantaneous ionizing flux ( nicastro et al , 1997 ) . this time depends on the particular ionic species considered . the ionic abundances of oxygen in the absorber in 3c 351 are distributed mainly between only two ionic species : ovii and oviii . in this simple case a useful analytical approximation for @xmath19 is : @xmath20_{t+\delta t}}}\nonumber \normalsize\end{aligned}\ ] ] where _ eq _ indicates the equilibrium quantities . by requiring that @xmath19 for ovii and oviii species is shorter than the @xmath21 s ( quasar frame ) elapsed between the two observations , we can find a lower limit to the electron density of the absorber : @xmath22 @xmath3 . since we know the values of u and @xmath23 , this density limit translates into a limit on the distance of the ionized gas from the central source , r@xmath24 pc . these limits are consistent with the upper limit of @xmath25 @xmath3 , and r@xmath26 pc , found by mathur et al . ( 1994 ) using a lower limit for the distance of the cloud from the central source , based on the absorber being outside the broad emission line region . the relative closeness of these two limits ( factor @xmath0100 ) implies that a variation in shorter times ( @xmath27 month ) , would be likely to show non - equilibrium effects ( nicastro et al , 1997 ) . if a factor 2 flux change in @xmath28 week showed no such effects the simplest photoionization model would have to be abandoned . we have tested ionization models for the ionized absorber in 3c 351 . in particular , we tested a simple one zone photoionization equilibrium model on two pspc spectra of 3c 351 that show a factor @xmath29 decrease in flux . the model correctly predicts the sense and amplitude of the observed change in the ionization state of the absorber , correlated with the ionizing continuum flux . given that photoionization equilibrium applies we can derive a lower limit to the electron density of the absorber : @xmath30 @xmath3 . this is consistent with the upper limit of @xmath31 @xmath3 found by mathur et al . the distance of the ionized gas from the central source is then 0.3 pc @xmath4 r @xmath4 50 pc . the closeness of these two limits creates a strong test of photoionization models : factor 2 variations in 3c 351 on timescales of order a week _ must _ show non - equilibrium effects .

we present two rosat pspc observations of the radio - loud , lobe - dominated quasar 3c 351 , which shows an ` ionized absorber ' in its x - ray spectrum . the factor 1.7 change in flux in the @xmath02 years between the observations allows a test of models for this ionized absorber . the absorption feature at @xmath1 kev ( quasar frame ) is present in both spectra but with a lower optical depth when the source intensity - and hence the ionizing flux at the absorber - is higher , in accordance with a simple , single - zone , equilibrium photoionization model . detailed modeling confirms this agrement quantitatively . the maximum response time of 2 years allows us to limit the gas density : @xmath2 @xmath3 ; and the distance of the ionized gas from the central source r @xmath4 19 pc . this produces a strong test for a photoionized absorber in 3c 351 : a factor 2 flux change in @xmath01 week in this source _ must _ show non - equilibrium effects in the ionized absorber .

the transforming growth factor pathway plays a central role in cellular proliferation , recognition , differentiation , apoptosis and specification of developmental fate , during embryogenesis as well as in mature tissues . nearly thirty members have been described in human , many orthologs are known in other vertebrates . one subfamily contains of the bone morphogenetic proteins ( bmp ) plus the growth and differentiaion factors ( gdf ) . the second family consists of the transforming growth factor and activin and nodal proteins . the tgf protein is released as an inactive ' latent ' complex , comprising a tgf dimer in a non - covalent complex with two prosegments , to which one of several ' latent tgf-binding proteins ' is often linked . this latent complex represents an important safeguard against ' inadvertent ' activation , and may stabilize and target latent tgf to the extracellular matrix , where it is sequestered . the matrix thus acts as a reservoir from which tgf can readily be recruited without the need for new synthesis . the secretion of tgf as a latent complex necessitates the existence of a regulated activation process , which is most probably mediated through the activities of proteases that preferentially degrade the tgf prosegments and thereby release the highly stable , active tgf dimer . because plasmin activates latent tgf and plasminogen is converted into plasmin at sites of cell migration and invasion ; it is assumed that endothelial and tumor cells are exposed to active tgf. tgf signaling is mediated by a heterotetrameric complex of two trans - membrane receptor serine / threonine kinases , containing a type ii ligand binding receptor ( tgf-rii ) and a type i signaling receptor ( tgf-ri ) . smads 2 and 3 are direct substrates of tgf-ri and , together with the common mediator , smad4 , play key roles as cytoplasmic signaling mediators . although the smad pathway has received much attention in the past years , it is now appreciated that the activated receptor complex can also signal through other pathways , such as those involving the mitogen - activated protein kinases ( mapks ) , phosphoinositol-3 kinase ( pi3k ) , and pp2a / p70s6k , though the molecular details of this coupling are still obscure . the relative importance and interplay of these various pathways in the changing responses of cells to tgf are just beginning to be probed . in mammal cells , there are three tgfs , tgf1 , tgf2 and tgf3 , which are encoded by different genes and which all function through the same receptor system . of these , tgf1 is most frequently upregulated in tumor cells and is the focus of most studies on the role of tgf in tumorigenesis . the integrin family of cell adhesion molecules mediates cellular contacts to the extracellular matrix ( ecm ) or cell counter receptors , thereby regulating development , cell motility , cell polarity , cell growth and survival . ligand binding to integrins leads to integrin clustering and recruitment of actin filaments and signaling proteins to the cytoplasmic domain of integrins , referred to as focal complexes when they are still nascent and in the process of forming , or focal adhesions ( fas ) when they have matured into larger complexes . the formation of cell adhesion complexes assures substrate adhesion as well as targeted location of actin filaments and signaling components . cell adhesion complexes are also essential for establishing cell polarity , directed cell migration , and maintaining cell growth and survival . the integrin - actin cytoskeleton connection is highly dynamic and is differentially regulated in different locations of the cell . at the leading edge of migrating cells , integrins bind the ecm , recruit the actin cytoskeleton and initiate local reorganization of the actin network , promoting different types of membrane protrusion . at the rear of the cell , integrins detach from the ecm , dissolve the link to the cytoskeleton and are , at least partially , recycled to the front of the cell . signaling pathways , which depend on localized integrin activation have also been reported ; this is essential for the reorientation of the microtubular network and the directed movement of cells . integrin - linked actin binding proteins attach to signaling molecules and function as platforms , bringing kinases and substrates together . integrin - bound signaling molecules , on the other hand , bind to actin binding proteins , enforcing the integrin - cytoskeleton connection . as it turns out for integrin - linked kinase ( ilk ) , such adapter function might be even more important in vivo than the kinase function demonstrated in vitro . the integrin v6 is expressed principally on epithelial cells where it has been shown to be a receptor for rgd and non - rgd sites in ligands . it is demonstrated that the mature form of tgf1 binds to and activates of v6 integrin . among others , binding of mature tgf1 to v6 integrin resulted in an enhanced immobilization and phosphorylation of proteins , which are associated with focal adhesions . surprisingly , stimulation with mature tgf1 leads to upregulation of c - jun in tgf1 sensitive cells . we therefore sought to determine if mature tgf1 activates c - jun via mekk1/p38 and if this activation may influence cytoskeletal reorganization . here , we show that binding of mature tgf1 recruits the mitogen - activated protein kinase kinase kinase 1 ( mekk1 ) , a mediator of c - jun activation , and the extracellular signaling - regulated kinase-1 ( erk1 ) to focal adhesions . in addition , the p21-activated kinase 1 ( pak1 ) is associated with focal adhesions and differentially phosphorylated upon stimulation with mature tgf1 . we conclude that tgf1 activates c - jun via the mekk1/p38 map kinase pathway and influences cytoskeletal organization . crosstalk between integrins and growth factor receptors are an important signaling mechanism to provide specificity during normal development and pathological processes in vascular biology . evidence from several model systems demonstrates the physiological importance of the coordination of signals from growth factors and the extracellular matrix to support cell proliferation , migration , and invasion in vivo [ 12 - 14 ] . several examples of crosstalk between these two important classes of receptors indicate that integrin ligation is required for growth factor - induced biological processes . furthermore , integrins can directly associate with growth factor receptors , thereby regulating the capacity of integrin / growth factor receptor complexes to propagate downstream signaling . we have demonstrated that mature tgf1 colocalizes with v6 integrin in panc-1 cells . to further support our initial findings , we assayed for colocalization between tgf1 , v6 integrin and the f - actin filaments of the cytoskeleton in sw48 , dld1 , hela cells as well as keratinocytes . after preparation of the cytoskeletal fraction by triton - x100 extraction , slides were stained using alexa fluor 680 goat anti - mouse igg ( molecular probes , eugene , or ) for actin , alexa fluor 488 donkey anti - rabbit igg ( molecular probes ) for v6 integrin , and alexa fluor 350 donkey anti - rabbit igg ( molecular probes ) for tgf1 labeling . as shown in figure 1 , in tgf1 , v6 integrin and the f - actin filaments of the cytoskeleton colocalize after stimulation with mature tgf1 in all cell lines used . these results further support our initial findings that mature tgf1 is a ligand for v6 integrin . 10,000 cells(sw48 , dld1 , hela , keratinocytes ) were cultured on glass coverslips in dmem supplemented with 17% of heat inactivated fetal bovine serum and stimulated with 10 nm of mature tgf1 ( from r&d systems ) for ten minutes . after preparation of the cytoskeletal fraction by triton - x100 extraction , slides were stained using alexa fluor 680 goat anti - mouse igg ( molecular probes , eugene , or ) for actin ( sc-8432 , santa cruz ) , alexa fluor 488 donkey anti - rabbit igg ( molecular probes ) for v6 integrin ( sc-6617 and sc-6632 ) , and alexa fluor 350 donkey anti - rabbit igg ( molecular probes ) for tgf1 ( sc-146 ) labeling and viewed using a zeiss lsm-510 confocal microscope . magnification 1000 . adhesion to the extracellular matrix is an important process that controls cell shape change , migration , proliferation , survival , and differentiation . upon adhesion , integrins and a selective group of cytoskeletal and signaling proteins are recruited to cell matrix contact sites where they link the actin cytoskeleton to the ecm and mediate signal transduction between the intracellular and extracellular compartments . we demonstrated that mature tgf1 induces an enhanced immobilization and phosphorylation of proteins , which are associated with focal adhesions , in tgf1 sensitive cells . in order to provide further evidence for the specificity of this interaction , we preincubated cells with antibodies against v8 , v6 , v5 , v3 , and v1 integrins prior to stimulation with mature tgf1 . consistent with our initial report , preincubation with v6 antibodies abolished the tgf1-induced tyrosine phosphorylation of proteins , which are associated with focal adhesions ( figure 2 ) . in sum , we could confirm our initial findings that mature tgf1 is a ligand for v6 integrin and that this association results in immobilization and tyrosine phosphorylation of proteins , which are associated with focal adhesions , in tgf1 sensitive cells . cytoskeletally anchored v6 was immunoprecipitated after tgf1 stimulation ( 10 nm for 10 minutes ) followed by western analysis with antibodies against tyrosine - phosphorylated proteins or v integrin . in part the cells were preincubated with v- and 8- , 6- , 5- , 3- , and 1-antibodies ( 1:100 each for 30 min , all from santa cruz ) or with a tgf1 antibody ( 15 g / ml for 30 min , from santa cruz ) . paxillin is a multi - domain protein that localizes in cultured cells primarily to sites of cell adhesion to the extracellular matrix ( ecm ) called focal adhesions . focal adhesion proteins including paxillin also serve as a point of convergence for signals resulting from stimulation of various classes of growth factor receptors . it binds to many proteins that are involved in effecting changes in the organization of the actin cytoskeleton , which are necessary for cell motility events associated with embryonic development , wound repair and tumor metastasis . these range from structural proteins such as vinculin and actopaxin , that bind actin directly to regulators of actin cytoskeletal dynamics , such as the arf gap , pkl , the exchange factor pix and the p21-activated kinase , pak . these proteins serve as modulators / effectors of the arf and rho gtpase families . in our assays , paxillin was found to be phosphorylated at yafter stimulation and associated with focal adhesions after stimulation of bxpc-3 cells with mature tgf1 ( figure 3 ) . this phosphorylation was dependent on an intact cytoskeleton as well as free intracellular calcium ( figure 3 ) . bxpc-3 cells were stimulated with 10 nm of mature tgf1 for ten minutes followed by preparation of the triton - x100 nonsoluble fraction and precipitation with v6 integrin antibodies . the precipitate was then re - precipitated with anti - fak antibodies ( sc-1688 ) and analyzed with antibodies against p - paxillin(2541 , cell signaling ) and p - c - jun(9621 , cell signaling ) . in part , the cells were preincubated with a tgf-rii antibody ( santa cruz ) , bapta - am and cytochalasin d , respectively . both paxillin and focal adhesion kinase ( fak ) undergo phosphorylation during integrin - mediated cell adhesion and during stimulation by a variety of mitogens and growth factors . there is growing evidence that integrins function as mechanotransducers and that the regulation of cellular responses to mechanical stimuli is coordinated by the complex of cytoskeletal proteins that associate with the cytoplasmic domains of integrin molecules . in cultured cells , fak and paxillin undergo tyrosine phosphorylation in response to periods of repetitive mechanical strain . in a number of cultured cell types , including endothelial cells and airway smooth muscle cells , cyclic mechanical strain has been shown to induce the alignment of actin filaments along the axis perpendicular to the force vector . paxillin and fak were identified as integration points in signaling proximal to integrins and growth - factor receptors . we speculate that the conversion of growth - factor and adhesion signaling occurs on the actin filaments . the cytoplasmic domains of integrins and receptors for growth factors and cytokines are closely associated with the ends of the cytoskeleton ; reorganization of microfilaments may influence the environment of these integrins and receptors , thereby facilitating the triggering of a signaling pathway . activation of paxillin / fak by integrins and growth factors is important for efficient signal propagation by pathways including paxillin that lead to the regulation growth and differentiation . a similar role for fak was described in the control of growth factor- and integrin - mediated cell migration in fibroblasts . this suggests that paxillin / fak have a general role in linking integrins / growth - factor receptors with the regulation of cytoskeletal changes that controls various biological processes in different cells . paxillin and fak have been proposed to play an integral role in these strain - induced morphological changes . reorganization of the cytoarchitecture regulates signaling pathways including the mobilization of intracellular calcium , activation of tyrosine kinases , ras , extracellular signal - regulated kinase ( erk ) , and c - jun nh2-terminal kinase ( jnk ) . consistent with the activation of signaling pathways , specific transcription factors are activated by cytoskeletal restructuring . we stimulated bxpc-3 cells with 10 nm of mature tgf1 , prepared the triton - x100 nonsuluble fraction , precipitated with v6 integrin antibodies followed by re - precipitation with fak antibodies . our assays revealed that mekk1 and c - jun are phosphorylated and associated with focal adhesions after stimulation of bxpc-3 cells with mature tgf1 ( figures 3 and 4 ) . our findings are in part supported by verrecchia et al showing that tgf induces c - jun and junb . in addition , our finding that mekk1 associates with focal adhesions finds support in the report from cuevas et al . cuevas et al show evidence that mekk1 colocalizes with focal adhesions in adhering mekk1fibroblasts reconstituted with egfp - mekk1 . however , this is the first report that c - jun is associated with the cytoskeleton , whilst phosphorylated . bxpc-3 cells were stimulated with 10 nm of mature tgf1 for ten minutes followed by preparation of the triton - x100 nonsoluble fraction and precipitation with v6 integrin antibodies . the precipitate was then re - precipitated with anti - fak antibodies ( sc-1688 ) and analyzed with a mekk1 antibody ( sc-448 ) . in part mekk1 is absolutely required for cellular responses , which alter the integrity of the microtubule cytoskeleton and cell shape ; mekk1 is the mapk kinase kinase regulating the jnk pathway . we also detected erk1 associated with focal adhesions in bxpc-3 cells , stimulated with 10 nm of mature tgf1 ( figure 5 ) . bxpc-3 cells were stimulated with 10 nm of mature tgf1 for ten minutes followed by preparation of the triton - x100 nonsoluble fraction and precipitation with v6 integrin antibodies . the precipitate was then re - precipitated with anti - fak antibodies ( sc-1688 ) and analyzed with an erk1 antibody ( sc-93 ) . in part the mitogen - activated protein kinase , referred to as map kinase or extracellular signal - regulated kinase ( erk ) , is a serine / threonine protein kinase whose activity is rapidly stimulated by a number of external stimuli through mechanisms mediated by tyrosine kinase - encoded receptors , non - receptor type tyrosine kinases , and g protein - coupled receptors . map kinase is activated by phosphorylation on its threonine and tyrosine residues , a process , which is carried out by a dual - specificity protein kinase , map kinase kinase . map kinases have been shown to phosphorylate and thereby activate many well studied regulatory proteins located in diverse cellular compartments , including nuclear transcriptional factors . a function of map kinases may therefore be to provide a link between transmembrane signaling and the nucleus . there is much evidence that map kinases may be involved in cell growth and differentiation by phosphorylating and thereby activating nuclear transcriptional factors . meanwhile , there are many compelling examples of gene expression induced by adhesive interactions with ecm [ 28 - 30 ] . thus , map kinase may play a pivotal role in adhesion - dependent gene activation through the integrin - mediated signaling pathways . the fact that map kinase is activated by both , growth factor- and integrin - mediated signals , suggests that these two signaling pathways converge at this or upstream points . however , resolving the nature and degree of interactions between integrin- and growth factor - mediated signaling pathways , and their relative contributions , must await more complete definition and understanding of integrin - mediated growth - factor - induced signal transduction pathways . tau hyperphosphorylation by abnormaly active erk is demonstrated in neuroblastoma cells , suggesting that abnormak erk activity function as apoptosis inducing kinase . additional factors may compensate this effect , leading to resistance to apoptosis , multidrug resistance , or metastatic behavior of cancers . support for this speculation comes from another report showing that the family of p21 activated kinases ( pak ) is involved in actin cytoskeleton organization . the p21-activated kinases ( paks ) are serine / threonine protein kinases that bind to and , in some cases , are stimulated by activated forms of the small gtpases , cdc42 and rac . the pak family of kinases has been implicated in control of actin filaments and in cell motility . targets for pak are likely to be involved in migration , including myosin light chain kinase ( mlck ) and lim kinase . mlck phosphorylates mlc , and this phosphorylation has been shown to be important in regulating actin cytoskeletal dynamics . in addition , pak phosphorylates and activates limk , which in turn phosphorylates and inhibits the actin severing protein cofilin , thus promoting filament assembly . the pak interacting guanine nucleotide exchange factor pix , the arf gtpase activating protein pkl , and the adaptor protein nck , are also mediators of rho gtpase signaling ; they form a complex with pak to regulate the actin cytoskeleton and stimulate focal complex formation through paxillin interactions . g protein coupled receptor kinase interacting protein ( git1 ) links pak to fak and results in focal contact turnover , while another protein , p95 app 1 , of the git family , has been implicated in membrane recycling during locomotion , suggesting a role of git family members in cell motility . thus , pak plays an important role in rac - driven cell motility through several different signaling cascades . the erk - map kinase , including pak , pi3k , and mekk1 , have been linked to motility . rac activates pi3k and akt independent of jnk , and activates the mekk - jnk cascade independent of pak . in addition to the rac - mekk - jnk and the erk cascades , pi3k - akt has also been shown to promote cell migration . we found that pak1 is associated with focal adhesions upon stimulation of bxpc-3 cells with 10 nm of mature tgf1 ( figure 6 ) . the src family kinase inhibitor 4-amino-5-(4-chloro - phenyl)-7-(t - butyl)pyrazolo- [ 3,4-d]-pyrimidine ( pp2 ) significantly reduced the phosphorylation level of pak1 compared with the mek1 inhibitor pd98059 . the effect of the mek1 inhibitor on the pak1 phosphorylation is striking because pak1 is considered upstream of mek1/erk . blocking of pak activity is considered a so called " signal therapy for ras - induced cancers " . bxpc-3 cells were stimulated with 10 nm of mature tgf1 for ten minutes followed by preparation of the triton - x100 nonsoluble fraction and precipitation with v6 integrin antibodies . the precipitate was then reprecipitated with anti - fak antibodies ( sc-1688 ) , followed by re - precipitation with anti - phospho(ab9334 , abcam ) , anti - phospho(ab2286 ) , and analyzed with a pak1 antibody ( 71 - 9300 , zymed ) . in part , the cells were preincubated with 50 m pp2 ( calbiochem ) , and 50 m pd98059 ( calbiochem ) , respectively . as is clear from this study , there is a lot that remains to be understood about the integrin - mediated signal transduction elicited by mature tgf1 . further studies will provide us with answers in the near future that will shed light on many of the remaining mysteries of the tgf puzzle . cs acknowledges support from the german research foundation and is indebted to martin paul kracklauer and jonathan a.f .

transforming growth factor ( tgf ) plays an important role in animal development and many cellular processes . a variety of cellular functions that are required for tumor metastasis are controlled by integrins , a family of cell adhesion receptors . overexpression of v6 integrin is associated with lymph node metastasis of gastric carcinomas . it has been demonstrated that a full tgf1 signal requires both v6 integrin and smad pathway . tgf1 binds to v6 via the dlxxl motif , a freely accessible amino acid sequence in the mature form of tgf1 . binding of mature tgf1 to v6 leads to immobilization and tyrosine phosphorylation of proteins , which are associated with focal adhesions , a hallmark of integrin - mediated signal transduction . here , we show that binding of mature tgf1 recruits the mitogen - activated protein kinase kinase kinase 1 ( mekk1 ) , a mediator of c - jun activation , and the extracellular signaling - regulated kinase-1 ( erk1 ) to focal adhesions . in addition , the p21-activated kinase 1 ( pak1 ) is associated with focal adhesions and differentially phosphorylated upon tgf1 stimulation . we conclude that tgf1 activates c - jun via the mekk1/p38 map kinase pathway and influences cytoskeletal organization . these finding may provide a link between tgf1 and the metastatic behavior of cancers .

the epoch of galaxy formation has been the subject of much recent controversy . initially , observational evidence for a late epoch of galaxy formation appeared to come from analysis of the canada - france redshift survey and the hubble deep field where the universal star - formation rate ( sfr ) appeared to peak at @xmath4 ( lilly et al . 1995 , madau et al . 1996 ) . however , it was also suggested that the cfrs / hdf data could still be consistent with models ( bruzual & charlot 1993 ) with a constant space density of galaxies whose sfr rises exponentially to redshifts @xmath5 ( metcalfe et al . 1996 , shanks et al . 1998 ) . indeed , if these ` pure luminosity evolution ' models are modified by assuming a small amount of dust internal to spirals and a dwarf - dominated imf for early - type galaxies , then they appeared to give very good fits to galaxy number count data from the uv to the near - infrared , at least in the case of low @xmath6 ( metcalfe et al . the recent detection of high redshift galaxies as sub - mm sources ( smail et al . 1997 , hughes et al . 1998 , barger et al . 1998 ) also appears to support the idea that the sfr may rise to much higher redshifts . the ` pure luminosity evolution ' models with internal spiral dust absorption have also been shown to be capable of producing fits to the sub - mm galaxy counts and the optical / near - ir galaxy counts simultaneously ( busswell & shanks 2000 ) . details of further constraints from the uv colours of galaxies on the dust extinction law and its evolution with redshift are given by metcalfe et al . ( 2000 ) . in the einstein - de sitter universe , with its smaller volume , it has been known for some time that such simple models only fit the optical counts to b@xmath725mag ( yoshii & takahara 1988 , guiderdoni & rocca - volmerange 1990 , koo et al . 1993 ) before underestimating the counts at fainter magnitudes . in this case , a new population of faint galaxies must be postulated ; these extra galaxies could be the result of a process of dynamical merging at high redshift ( kauffmann & charlot 1998 ) . alternatively , as we assume here , they could be due to a population of ` disappearing dwarfs ' , denoted ` de ' , that are luminous at high redshift but then dim dramatically to be virtually undetectable at low redshift ( babul & rees 1992 , metcalfe et al . 1996 , 2000 ) we now test how well these models fit new ultra - deep optical and ir count data from hdf - n ( williams et al . 1996 , thompson et al . 1999 ) , hdf - s ( gardner et al . 2000 , williams et al . 2000 ) and the william herschel deep field ( whdf ) . full details of our analyses of the hubble and herschel deep fields are given elsewhere ( metcalfe et al . 1995 , 1996 , 2000 ) . the new optical ( @xmath8 ) counts from hst stis observations in the hdf - s are shown in the lower part of fig . the stis passband is centred at 5850 and has a width of @xmath94000 . the field - of - view is 50@xmath1050 arcsec@xmath11 . the exposure time was 43hrs and these are the deepest optical galaxy counts , reaching beyond r@xmath12=30 . also shown are the hdf - n ,- s wfpc-2 r counts . above these in fig . 1 are the new h - band counts from nicmos observations in hdf - n ,- s . the field - of - view was @xmath950@xmath1050 arcsec@xmath11 . the exposure time was 36.5hrs for hdf - n and 48.3hrs for hdf - s and these are the deepest galaxy counts in the near - ir so far produced . 1 also shows the whdf h counts from calar alto 3.5-m observations plus h counts from other authors . the models shown are those of metcalfe et al . ( 1996 , 2000 ) applied to both passbands . the no - evolution models generally underestimate the optical data . the q@xmath13=0.05 and @xmath14=0.7 evolutionary models give excellent fits to the faintest limit of the hst stis r counts . the q@xmath13=0.5 @xmath15 de dwarfs model includes the ` disappearing dwarf ' galaxy population previously invoked to improve the galaxy count fit of the q@xmath13=0.5 evolutionary model ( metcalfe et al . 1996 ) and this model also remains consistent with the new , fainter data . this model slightly overestimates the faintest counts at @xmath16 and @xmath17 , possibly indicating a slightly smaller contribution from the de population than assumed here ( metcalfe et al . , 1996 ) . nevertheless , we also regard this model as remaining in reasonable agreement with the ultra - deep galaxy counts data . at h , where the non - evolving models lie closer to the data than in the optical , all the evolving models except the q@xmath13=0.5 models without the de component , provide a reasonable fit to the counts to the faintest @xmath18 limit of the hst nicmos data . we conclude that the predictions for the evolutionary models continue to agree with the data to these new , very deep completeness limits of @xmath8=30 and @xmath19 . beyond @xmath20 and @xmath21 we are looking down the luminosity function of galaxies and seeing intrinsically faint galaxies(m@xmath22 - 12 ) , which on consideration of their colours are mostly at @xmath23 ( metcalfe et al . 1996 , 2000 ) . thus intrinsically faint galaxies at relatively low redshifts dominate the galaxy number counts at the faintest limits . in the low q@xmath13 case , the excellent fit of the evolutionary models suggests that the slope of the faint galaxy luminosity function at @xmath242 may be consistent with that measured locally . the need for the extra dwarf population to fit the optical counts in the @xmath25=0.5 case suggests that here the luminosity function slope must steepen by @xmath23 to match the faint count data . finally , we compare the model predictions for the @xmath0 colour - colour diagrams with the data from the whdf . fig . 2 shows how the predictions show a distinctive plume of early - type galaxies which first rise from @xmath26 to redder @xmath27 colours before turning bluewards again , as the increasing sfr at high redshift begins to affect the redshifted uv light . in the case of the spirals a horseshoe - shaped curve is predicted reaching out to @xmath1 at its faint limit . the agreement between models and data in both cases is quite remarkable , suggesting that for all their simplicity these models share the essential qualities required by the data ; for example , the faint galaxies seem to divide into just two evolutionary classes corresponding to early and late types as we assume . and the parameter differentiating the evolution in each class appears to be the star - formation rate , with an exponential e - folding time of @xmath28gyr for early - types and @xmath29gyr for spirals . we now use these models to predict the number counts of galaxies detected by the lyman break technique ( steidel et al . 1999 ) at @xmath30 . we first consider the @xmath1 range , where the data comes from detecting the lyman break galaxies via the uv dropout technique in ground - based data ( steidel et al . 1999 , metcalfe et al . 2000 ) and at fainter limits from the hubble deep fields n , s ( madau et al . 1996 , metcalfe et al . 2000 ) . in fig . 3a , we then simply compare the observed ground - based number counts of the @xmath1 galaxies with the model predictions , with the same comparison for the hst - based data being shown in fig . we see that in both cases at @xmath1 there is excellent agreement between the three basic evolutionary models and the data . thus models which were last adjusted to fit the keck b@xmath3124 n(z ) at @xmath4 are now found to give a strikingly good fit to what is effectively the galaxy luminosity function at @xmath1 . since it is the spirals which dominate the bright part of the model luminosity functions at z=3 , this means that the lyman break galaxies might be identified with the bright end of the evolved spiral luminosity function . this result is consistent with the flat sfr : z relation between @xmath32 found by steidel et al . ( 1999 ) and the slightly rising sfr : z relation predicted by the models in this range ( metcalfe et al . 2000 ) ; the models predict only a small amount of evolutionary brightening in the range @xmath32 and the constant space density of spiral galaxies then ensures the sfr : z relation remains fairly flat . in the fainter , hst - based data in fig . 3b , the models continue to fit well . however , it should be noted that the q@xmath13=0.5 model relies on the contribution of the ` disappearing dwarfs ' to maintain agreement with the faint count data ; it can be seen that , without this de contribution , the q@xmath13=0.5 model would start to underestimate the counts . in fig . 4a we now compare the number count of @xmath2 lyman break galaxies detected by b dropout to the same models . at bright magnitudes , where the data comes mainly from steidel et al . ( 1999 ) , the models appear to fit the data well , suggesting that the bright spirals may have been in place even as early as @xmath2 . however , at fainter magnitudes where the data comes from the hdf - n ,- s and the whdf , the simple pure luminosity evolution models at last appear to be breaking down , with the models generally overestimating the @xmath2 faint galaxy luminosity function . the observed faint ( @xmath33 ) galaxy count falls below our predictions by a factor of @xmath345 , indicating that while bright l@xmath35 galaxies may have been in place at @xmath2 , the faint galaxy population may have formed in the range @xmath36 . steidel et al . ( 1999 ) also noted that the galaxy luminosity function at @xmath2 appeared flatter than at @xmath1 but speculated that this may be due to the hdf - n being an unrepresentative field . the fact that the same result is seen in the whdf and hdf - s argues that this result may be real . the result also explains why the sfr density of steidel et al . ( 1999 ) appears to be constant between @xmath36 when measured from bright ground - based data , but appears to fall at @xmath2 when measured from the fainter hdf data . in fig . 4b we extend this approach , now comparing the number counts of @xmath3 lyman break galaxies detected by r dropout in the hdf and whdf to the same models . we have taken galaxies with @xmath37 and @xmath38 in the whdf and ( f606-f814)@xmath392.44 in the hdf - n ,- s to define consistently the redshift range 5.3@[email protected] or @xmath3 as suggested by the models . again we see that the observed number density of bright whdf galaxies is well fitted by the models . the fainter galaxies from the hdf remain a factor of @xmath345 lower than predicted . since the hdf data probes less deeply into the galaxy luminosity function than at @xmath2 , this is consistent with a further decrease in the number of faint galaxies relative to the local density . the crosses in fig . 4b show the number counts we have compiled from 6 galaxies with keck or hst spectroscopy ( dey et al . 1998 , weymann et al . 1998 , spinrad et al . 1998 , chen et al . 1998 ) . it can be seen that although there is reasonable agreement at the faint end with our unconfirmed hdf - n ,- s r dropout candidates , at the bright end there are somewhat fewer galaxies detected . this disagreement may be partly due to the difficulty of detecting ly @xmath40 emission against an increasingly bright sky at these longer wavelengths and partly due to contamination of our whdf candidates by lower redshift early - type galaxies . however , the fact that a population of spectroscopically confirmed @xmath3 galaxies have already been identified and that even larger numbers of r dropout candidates exist , again suggests that significant numbers of bright galaxies had formed by @xmath3 , pushing the epoch of formation of giant galaxies back to even higher redshifts . thus the picture of galaxy formation which is suggested is that bright galaxies form first at @xmath41 and then faint galaxies form later at @xmath42 . this is similar to the ` downsizing ' scenario suggested in other data at @xmath4 ( cowie et al . 1997 ) and may possibly be connected to claims of evolving , faint luminosity function slopes at even lower redshifts ( brinchmann et al . this scenario is unexpected in hierarchical galaxy formation theories where dwarf galaxies are expected to form _ earlier _ than giant galaxies . in a cdm model with feedback , this order may be reversed with supernovae winds blowing gas out of dwarf galaxies preferentially because of their shallower gravitational potentials . however , suppression of star formation at @xmath43 is usually required in such models to produce the observed luminosity function at the present day ( brinchmann et al . 1998 ) ; it thus remains to be seen how well a cdm model will deal with the large numbers of luminous galaxies detected between @xmath44 . new observations of the galaxy luminosity function at even higher redshifts are now required to determine the redshift of formation of the brightest galaxies . we gratefully acknowledge g. bruzual and s. charlot for use of their isochrone synthesis code . we also acknowledge the use of the hubble space telescope deep field data . we further acknowledge use of the calar alto 3.5-m telescope and the @xmath45 camera . the wht is operated on the island of la palma by the isaac newton group at the spanish observatorio del roque de los muchachos of the instituto de astrofisica de canarias . mccracken and n. metcalfe acknowledge pparc funding . shanks , t. , metcalfe , n. , fong , r. , mccracken , h.j . , campos , a. & gardner , j.p . , 1998 . in ` the young universe : galaxy formation and evolution at intermediate and high redshift ' , eds . dodorico , s. , fontana , a. and giallongo , e. , asp conference series vol . 146 , san francisco : asp , pp . 102 - 109 .

metcalfe et al . ( 1995 , 1996 ) have shown that galaxy counts from the uv to the near - ir are well - fitted by simple evolutionary models where the space density of galaxies remains constant with look - back time while the star - formation rate rises exponentially . we now extend these results , first by using data from the herschel deep field to show that these same models give detailed fits to the faint galaxy @xmath0 colour - colour diagram . we then use these models to predict the number counts of high redshift galaxies detected by the lyman break technique . at @xmath1 there is almost exact agreement between our prediction and the data , suggesting that the space density of galaxies at @xmath1 may be close to its local value . at @xmath2 the space density of bright galaxies remains unchanged ; however , the space density of dwarf galaxies is significantly lower than it is locally , suggesting that we have detected an epoch of dwarf galaxy formation at @xmath2 . finally , significant numbers of lyman - break galaxy candidates are also detected at @xmath3 in the hubble and herschel deep fields ; taking this observation together with a number of recent detections of spectroscopically confirmed @xmath3 galaxies suggests that the space density of bright galaxies at @xmath3 remains comparable to the local space density and thus that the epoch of formation of bright galaxies may lie at yet higher redshift . # 1_#1 _ # 1_#1 _ = # 1 1.25 in .125 in .25 in

Update, September 6, 2016: According to TMZ, Dani Mathers' body shaming victim has come forward to the police. TMZ's sources say the LA Fitness goer, who is in her seventies, wants the Playboy Playmate to face charges for dissemination of private images, which entails a maximum punishment of six months in jail. Advertisement - Continue Reading Below Mathers' attorney Tom Mesereau, best known for defending Michael Jackson in his 2005 molestation case, responded to the unconfirmed rumors, telling NY Daily News that he hoped "the rumor is not correct." He added, "Dani Mathers never tried to hurt anyone at any time, and certainly never tried to break any law." Regardless of her supposed intentions, TMZ's sources say the Los Angeles City Attorney is reviewing Mathers' case and "will make a decision soon." Update, July 15, 2016: As of Friday, Dani Mathers has been suspended indefinitely from Heidi and Frank, the radio show she has regularly appeared on for several years. On top of being fired, the gym in which the incident took place, LA Fitness, has banned Mathers for life. An LA Fitness spokesperson told TMZ that Mathers "is not permitted back at any club, ever" due to her violation of the club's privacy policy. The spokesperson also stated that the incident has been reported to the police. Original, July 14, 2016: For some people, the gym is a frightening place. Not only can the equipment be intimidating, but the gym-goers themselves can make you feel insecure or uncomfortable — are they judging you? Making fun of you? Worse, are they taking photos of you so other people can make fun of you? Unfortunately, that last hypothetical became the reality for one woman when model Dani Mathers snuck a photo of her to post online. But that's not the worst part: She took the pic while the woman was changing in the locker room. Yes, really. Mathers, a 29-year-old model from Los Angeles who was crowned Playboy's Playmate of the Year in 2015, was sitting in the sauna when she decided to snap some pictures of the naked woman changing in the locker room and post them to Snapchat. Here are screenshots (the woman has been concealed for her privacy): Advertisement - Continue Reading Below Snapchat/Dani Mathers The caption makes it even worse: "If I can't unsee this then you can't either." Message being that if you don't fit into Mathers' ideal of beauty, your body is disgusting and shouldn't be seen by people. And not only did Mathers insult the woman's body for no apparent reason other than because she thought it was funny, she also violated her privacy. The woman has a reasonable expectation of privacy within a locker room setting. The response was swift, with people on Twitter, Instagram and Facebook quickly rushing to condemn Mathers' choice to post the photos. I haven't tweeted in over a year probably. But @danimathers made me SO disturbed to the core, I had to say something. Should be prosecuted. — Julie Fitzgerald (@Julie4417) July 14, 2016 Shame on you. Now we know who you really are. Can't unsee that either. — Greg Mann (@gmann72) July 14, 2016 Advertisement - Continue Reading Below Advertisement - Continue Reading Below In a brief series of videos posted to her Snapchat, Mathers had this to say regarding the response to her reprehensible behavior: "I just wanted to acknowledge a photo that I accidentally posted on Snapchat earlier today and let you guys know that that was absolutely wrong, and not what I meant to do. I have chosen to do what I do for a living because I love the female body and I know that body shaming is wrong and that's not what I'm about, that's not the type of person that I am. That photo was taken to be a personal conversation with a girlfriend, and because I am new to Snapchat, I didn't realize that I had posted it and that was a huge mistake." This apology not only lacks remote understanding of what was wrong here, but also leaves me with more questions than I started with. So, she knows body shaming is wrong, but was going to do it anyway — just privately? She loves the female body, just not the ones that don't look like her own? She's body shaming someone, yet that person is literally at the gym. And which was the huge mistake, posting it for everyone to see or taking the photo in the first place? Oh, so she's just upset she got caught and called out. Cool. This is literally many folks' worst fear about walking into a gym. By the way, she posted two photos to her Snapchat story, which is a feed that allows people who follow you to see the photos you post publicly. If you have a rudimentary understanding of how Snapchat works, it's extremely easy to distinguish between sending not one, but two photos to your Snapchat story rather than directly to another user. This writer finds it highly doubtful that this was an accident; rather, this seems like a case of "whoops, I didn't realize people would be offended." Advertisement - Continue Reading Below All negativity aside, I hope this woman doesn't stop going to the gym simply because Dani Mathers decided to be a bully that day — but more than anything, that she has no idea this was ever posted in the first place. Follow Sam on Instagram and Twitter. ||||| Image Source: Getty / Paul Archuleta Model and Playboy Playmate Dani Mathers, 29, is facing backlash after sharing a photo to Snapchat that ridicules a fellow gym-goer's body. While at LA Fitness in Los Angeles, Mathers took an unsolicited photo of a woman changing in the locker room. She captioned the photo with, "If I can't unsee this then you can't either." Moments later, Mathers shared a selfie reacting to the photo with her hand placed on her mouth, presumably in shock or disgust. The egregious photo has since been shared by The Daily Mail and various other sources and has thus sparked a pretty enraged conversation. First of all, taken without the woman's knowledge, the photo is absolutely unacceptable and — quite frankly — illegal. On an ideological level, however, it also discourages people from going to the gym, working out, and just living their lives out of fear that an onlooker should mock them. It is body shaming at its worst. ADVERTISEMENT After receiving criticism on social media, Mathers deleted the snaps and issued a public apology . . . also on Snapchat. In the video available on The Daily Mail, she simultaneously apologized while also claiming that her intentions were not to publicly share the photo. So, she still meant to body shame the woman, but she only meant to send it to her friend? She said, "I just wanted to acknowledge a photo that I accidentally posted on Snapchat earlier today and let you guys know that that was absolutely wrong, and not what I meant to do. I have chosen to do what I do for a living because I love the female body and I know that body shaming is wrong and that's not what I'm about, that's not the type of person that I am. That photo was taken to be a personal conversation with a girlfriend, and because I am new to Snapchat, I didn't realize that I had posted it and that was a huge mistake." Since the whole incident, Mathers has deleted all of her social media accounts apart from her Facebook page. According to TMZ, LA Fitness has filed a police report against Mathers for violating the gym-goer's privacy. A spokesperson for the gym told TMZ, "Her behavior is appalling and puts every member's privacy at risk. We have handled this internally and also notified the police." ||||| Playboy model Dani Mathers has said sorry after making fun of a naked woman at her gym. She posted the photo on Snapchat, which showed her laughing at an unsuspecting woman in the showers. The caption said: "If I can't unsee this then you can't either." But she was then hit with a wave of criticism, with people accusing her of body shaming. She's now apologised and deleted the image. This is the picture that sparked it off... Unsurprisingly, people weren't that impressed, especially from a woman who's famous for her body. She was crowned Playmate of the Year in 2015. The model then went into serious damage limitation mode, with the well-used "I didn't meant it" excuse. After deleting the picture, she went on Twitter. "There is no excuse," she said. "I understand fully the magnitude of this post that I have hurt a lot of people, women. Body shaming is not okay...and not something to joke about." She then said it was a private conversation that "should never have happened." The model added she was "deeply sorry" for "hurting and offending you all." She also filmed an apology too. Third party content may contain ads But the apology didn't wash with everyone. And others used her own words against her. The 29-year-old model from Los Angeles ended her apology by saying "I need to take some time to myself now to reflect on why I did this horrible thing." Find us on Instagram at BBCNewsbeat and follow us on Snapchat, search for bbc_newsbeat

– Dani Mathers says she became a Playboy model because she loves the female body. She had a funny way of showing it Thursday when she posted a photo to Snapchat of a nude woman in a locker room at an LA Fitness in Los Angeles, with the caption, "If I can't unsee this then you can't either." The 29-year-old, named Playboy's 2015 Playmate of the Year, then shared a selfie of herself covering her mouth, as though to hide a laugh. The backlash was hard and swift. The photo is "body shaming at its worst" and "maybe illegal," Kelsey Garcia writes at POPSUGAR. Twitter users, some of whom called on LA Fitness to ban Mathers, were equally outraged. "Shame on you," wrote one user. "Now we know who you really are. Can't unsee that either." In a series of Snapchat videos, Mathers later said she was "deeply sorry" and had only meant to share the photo with a friend, per the BBC. "I love the female body and I know that body shaming is wrong and that's not what I'm about," she added. In other words, "she knows body shaming is wrong, but was going to do it anyway—just privately," writes Sam Escobar at Good Housekeeping. Escobar also casts doubt on her claims of a posting oops, noting it's "extremely easy" to tell the difference between posting direct to a user versus to one's Snapchat story. Mathers has since deleted all of her social media accounts except for Facebook and says she will "take some time to myself now to reflect on why I did this horrible thing." LA Fitness tells TMZ that Mathers' "behavior is appalling and puts every member's privacy at risk. We have handled this internally and also notified the police." (Snapchat just got sued by a teen over sexually explicit content.)

the lattice - boltzmann method ( lbm ) provides an alternative to the orthodox approach to computational fluid dynamics , in which the starting point is always a discretization of the navier stokes equations . the method , which is fundamentally based on boltzmann s kinetic transport equation , instead describes a fluid by a number of interacting populations of particles moving and colliding on a fixed lattice . with the advent of the introduction of a diagonal collision integral with single - time relaxation to local equilibrium , the method becomes tantalisingly simple and efficient . in recent years , the lbm has enjoyed much applied success modelling various flows of genuine engineering interest ( see e.g. , @xcite and the references therein ) . however , when populations are far from equilibrium , such as is the case in the vicinity of shocks , the lbm exhibits numerical instability . often , numerical instability in the lbm is attributed to the absence of a positivity constraint on the populations . recent development of the entropic lbm ( elbm ) @xcite are attempts to improve stability properties through compliance with a discrete entropy @xmath0-theorem . although such techniques should , conceivably , reduce the magnitude of spurious oscillations , one should perhaps not be disappointed to find that such numerical instabilities are not removed entirely . in this paper we suggest an alternative and versatile approach . the idea is simply stated : we propose a lbm in which the difference between microscopic and macroscopic entropy is monitored in the simulation , and populations are returned to their equilibrium states if a threshold value is exceeded . this technique is appealing because dissipation is introduced in a controlled , targeted and illiberal manner . furthermore , we stress that equilibration itself will leave macroscopic entropy completely unchanged . we coin the name _ ehrenfests steps _ for this procedure because we feel that the technique is most clearly understood if introduced using the ehrenfests coarse - graining idea @xcite . this report is organised as follows . in section [ sec2 ] the lbm is recalled . in section [ sec3 ] we recall the basic theory required to discuss the ehrenfests coarse - graining and introduce ehrenfests steps . the reader is directed to @xcite for a more comprehensive review of coarse - graining . finally , we present the results of a shock tube numerical experiment which compares various lbms . the boltzmann kinetic transport equation is the following time evolution equation for one - particle distribution functions @xmath1 : @xmath2 the _ collision integral _ , @xmath3 , describes the interactions of the populations @xmath4 . the lattice - boltzmann approach drastically simplifies this model by stipulating that populations can only move with a finite number of velocities @xmath5 : @xmath6 where @xmath7 is the one - particle distribution function associated with motion in the @xmath8th direction . for example , in one - dimension , one might consider three velocities @xmath9 , for some @xmath10 . the model is further simplified by specifying the collision integral as the bhatnager krook ( bgk ) operator @xcite : @xmath11 . we make this assumption for the remainder of the paper . now , describes free - flight dynamics together with relaxation to local equilibria , @xmath12 , in time proportional to @xmath13 . the discrete velocities and local equilibrium states can all be mindfully chosen so that the navier stokes equations are recovered by the lattice - boltzmann equation , subject to ceratin conservation laws , in the large time - scale , @xmath14 , limit via a chapman enskog procedure @xcite . here , the macroscopic fluid density @xmath15 and momentum @xmath16 are the zeroth- and first - order hydrodynamic moments of the populations respectively . the rate of dissipation introduced by the model is proportional to @xmath13 . the local equilibrium states can be found by maximising a local entropy functional subject to the constraints of conservation of mass and momentum . there are numerous ways to discretize and obtain a numerical method . we prefer the following , second - order accurate in time , lattice - based lbgk scheme @xcite : @xmath17 with @xmath18 . here , the discrete velocities are associated with an underlying spatial lattice @xmath19 and @xmath20 . populations live on this lattice , propagate to neighbouring lattice sites with their corresponding discrete velocities and are updated via . the parameter @xmath21 $ ] controls the viscosity in the model , with @xmath22 corresponding to the zero - viscosity limit . to introduce the ehrenfests coarse - graining idea @xcite we use a formal kinetic equation @xmath23 together with a strictly concave entropy functional @xmath24 . we tacitly assume that entropy does not decrease with time : @xmath25 . for our purposes , we are always interested in the example of the lattice - boltzmann equation with associated entropy functional which defines the local equilibrium states . the ehrenfests idea was to supplement the mechanical motion from with periodic averaging in cells to produce piecewise constant , or _ coarse - grained _ , densities . this operation necessitates entropy production . we wish to allow a generalisation of the ehrenfests coarse - graining whereby averaging in cells is replaced with some other partial equilibration procedure . specifically , we assume we have some linear operator @xmath26 which transforms a microscopic description of the system @xmath4 into a macroscopic description @xmath27 . for our example , the macroscopic description is that provided by the usual hydrodynamic moments . now , given a macroscopic description , @xmath28 , we consider the solution @xmath29 of the optimisation problem @xmath30 averaging in cells is a particular example of this entropy maximisation problem for the boltzmann gibbs shannon ( bgs ) entropy functional @xmath31 , where the integration is taken over the whole of phase space . we will refer to @xmath29 as the quasi - equilibrium distribution . the quasi - equilibrium manifold @xmath3 is the set of quasi - equilibrium distributions parameterised by the macroscopic variables @xmath28 . entropy maximisation leads naturally to an evolution equation for the macroscopic description . the so - called _ quasi - equilibrium approximation _ to is an equation for the evolution of @xmath28 : @xmath32 for our example , the quasi - equilibrium distributions are precisely the local equilibria @xmath33 and coincides with the compressible euler equations @xcite . now , one can envisage constructing various _ coarse - graining chains _ which provide stepwise approximation to the macroscopic equations . let @xmath34 be the phase flow for the kinetic equation . let @xmath13 be a fixed _ coarse - graining time _ and suppose we have an initial quasi - equilibrium distribution @xmath35 . the ehrenfests chain is the sequence of quasi - equilibrium distributions @xmath36 , where @xmath37 . entropy increases in the ehrenfests chain . the entropy gain in a link in the chain is made up from two parts : the entropy gain from the mechanical motion ( from @xmath7 to @xmath38 ) and the gain from the equilibration ( from @xmath38 to @xmath39 ) . consequently , conservative systems become dissipative and dissipative systems more so . the gain in macroscopic entropy in a particular link is given by the expression @xmath40 . note that there is zero gain in macroscopic entropy from the equilibration part . the ehrenfests chain provides a stepwise approximation to a solution of some coarse - grained macroscopic equations via @xmath41 , @xmath42 . for our example , these equations are the compressible navier stokes equations @xcite . however , this chain is computationally prohibitive because the rate of introduced dissipation is proportional to @xmath13 . the ehrenfests chain corresponds to the following lbm : @xmath43 which we recognise as a forward euler discretization of . another possibility is to construct a chain as follows . as already noted , the dissipative term introduced by the ehrenfests chain depends linearly on @xmath13 . therefore , there is symmetry between forward and backward motion in time starting from any quasi - equilibrium initial condition . it is precisely this principle that enables one to construct chains with zero macroscopic entropy production . each subsequent link in the chain is constructed using entropic involution . to make such a chain useful , the user is at liberty to add a required amount of dissipation by shifting the involuted point in the direction of the quasi - equilibrium state , with some entropy increase . of course , this shift leaves macroscopic entropy unchanged . this chain corresponds to the elbm that we have eluded to in the introduction : @xmath44 with @xmath45 . the number @xmath46 is chosen so that a constant entropy condition is satisfied . this , in itself , provides a positivity constraint on the populations . if the entropic involution operator is partially linearised so that subsequent links are constructed with the use of reflections in the quasi - equilibrium manifold , rather than inversions , then the corresponding lbm is precisely lbgk . we can now state the main idea of the paper . we propose to create a new chain . this chain begins and proceeds , for the bulk of time , as the either the entropic involution chain or its linearised version , as described in the previous subsection . however , the difference between microscopic and macroscopic entropy is monitored throughout the simulation , by which we mean the quantities @xmath47 a threshold value is set and an alarm is triggered if exceeded . the alarm simply signals that a link from the ehrenfests chain an ehrenfests step be used in place of a regular link of the primary chain at this point . links in the chain which are intolerably far from their quasi - equilibrium states are merely returned to their equilibrium . the result is a chain which provides additional dissipation only where it is anticipated to be required . coupling the entropic involution chain with ehrenfests steps will , in general , no longer constitute a chain with zero macroscopic entropy production . indeed , in a chain of length @xmath48 the total macroscopic entropy gain is given by the expression @xmath49 $ ] , where @xmath50 is the set of indices corresponding to the ehrenfests steps . to conclude this report , we perform a one - dimensional numerical experiment to demonstrate the performance of the proposed lbm corresponding to a chain with ehrenfests steps . the implementation is as follows . if @xmath51 , for some given tolerance @xmath52 then we accept an ehrenfests step . the resulting lbm is as follows : @xmath53 we have selected lbgk as the primary chain and we will henceforth refer to this lbm as lbgk - es . the method lbgk - es , as described , is a second - order accurate in time scheme with first - order degradation in regions where ehrenfests steps are employed . however , as is often found , when the thickness of such regions is of the order of the lattice spacing , the method remains second - order everywhere . for contrast we are interested in comparing lbgk - es with lbgk and elbm ( as described in @xcite ) . in all of our simulations we select the three - velocity model mentioned in the introduction and a uniformly spaced lattice . further , we always choose @xmath54 and @xmath55 . the coefficient @xmath56 , which controls the viscosity in the model , is fixed at @xmath57 , which is close to the zero viscosity limit . in each case the entropy is @xmath58 , with @xmath59 @xcite , where @xmath60 , @xmath61 and @xmath62 denote the static , left - moving and right - moving populations respectively . for this entropy , the local equilibria are available analytically for the three - velocity model . they are given by the expressions @xmath63 for lbgk - es we fix the tolerance , @xmath64 , to either @xmath65 or @xmath66 . as already mentioned , for elbm , there is a parameter , @xmath67 , which is chosen to satisfy a constant entropy condition . this involves finding the nontrivial root of the equation @xmath68 inaccuracy in the solution of this equation can introduce artificial viscosity . to solve numerically we employ a robust routine based on bisection . the root is solved to an accuracy of @xmath69 . furthermore , we always ensure that the returned value of @xmath67 does not lead to an entropy decrease . so that our results can be faithfully reproduced , we stipulate that we will consider two possibilities if no nontrivial root of exists . we either elect to select @xmath70 or we select the positivity bound @xmath71 , with @xmath72 . for fairness , since both of these procedures introduce diffusivity into elbm , we consider analogous procedures for lbgk too , i.e. , we elect to select either @xmath70 or @xmath73 if a populations is predicted to become negative . shock tube simulation after @xmath74 time steps using ( a ) lbgk ; ( b ) elbm ; ( c ) lbgk - es with @xmath75 ; ( d ) lbgk - es with @xmath76 . in this example , lbgk does not produce a negative population so the aforementioned regularisation procedures are redundant . similarly , for elbm in this example , the entropy estimate equation always has a nontrivial root . sites where ehrenfests steps are employed are indicated by crosses . [ shocktube],height=529 ] the one - dimensional shock tube for a compressible isothermal fluid is a standard benchmark test for hydrodynamic codes . our computational domain will be the interval @xmath77 $ ] and we discretize this interval with @xmath78 uniformly spaced lattice sites . we choose the initial density ratio as @xmath79 . initially , for @xmath80 we set @xmath81 else we set @xmath82 . we observe that , of all the lbms considered in the experiment , only the method which includes ehrenfests steps is capable of suppressing spurious post - shock oscillations ( fig . [ shocktube ] ) . the code used to produce the simulations in this section is freely available by making contact with the corresponding author . ehrenfests steps introduce additional dissipation _ locally _ , on the base of _ point - wise analysis of non - equilibrium entropy_. they admit a huge variety of generalisations : incomplete ehrenfests steps , partial involution , etc . @xcite . in order to preserve the second - order of lbm accuracy it is worthwhile to perform ehrenfests steps on only a small share of sites ( the number of sites should be @xmath83 , where @xmath84 is the number of sites , @xmath85 is the macroscopic characteristic length and @xmath86 is the lattice step ) with highest @xmath51 . numerical experiments show that even small shares of such steps drastically improve stability . more tests are presented in @xcite .

the lattice - boltzmann method ( lbm ) and its variants have emerged as promising , computationally efficient and increasingly popular numerical methods for modelling complex fluid flow . however , it is acknowledged that the method can demonstrate numerical instabilities , e.g. , in the vicinity of shocks . we propose a simple and novel technique to stabilise the lattice - boltzmann method by monitoring the difference between microscopic and macroscopic entropy . populations are returned to their equilibrium states if a threshold value is exceeded . we coin the name _ ehrenfests steps _ for this procedure in homage to the vehicle that we use to introduce the procedure , namely , the ehrenfests idea of coarse - graining .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Digital Coast Act''. SEC. 2. FINDINGS. Congress makes the following findings: (1) The Digital Coast is a model approach for effective Federal partnerships with State and local government, nongovernmental organizations, and the private sector. (2) Access to current, accurate, uniform, and standards- based geospatial information, tools, and training to characterize the United States coastal region is critical for public safety and for the environment, infrastructure, and economy of the United States. (3) More than half of all people of the United States (153,000,000) currently live on or near a coast and an additional 12,000,000 are expected in the next decade. (4) Coastal counties in the United States average 300 persons per square mile, compared with the national average of 98. (5) On a typical day, more than 1,540 permits for construction of single-family homes are issued in coastal counties, combined with other commercial, retail, and institutional construction to support this population. (6) Over half of the economic productivity of the United States is located within coastal regions. (7) Highly accurate, high-resolution remote sensing and other geospatial data play an increasingly important role in decision making and management of the coastal zone and economy, including for-- (A) flood and coastal storm surge prediction; (B) hazard risk and vulnerability assessment; (C) emergency response and recovery planning; (D) community resilience to longer range coastal change; (E) local planning and permitting; (F) habitat and ecosystem health assessments; and (G) landscape change detection. SEC. 3. DEFINITIONS. In this Act: (1) Coastal region.--The term ``coastal region'' means the area of United States waters extending inland from the shoreline to include coastal watersheds and seaward to the territorial sea. (2) Coastal state.--The term ``coastal State'' has the meaning given the term ``coastal state'' in section 304 of the Coastal Zone Management Act of 1972 (16 U.S.C. 1453). (3) Federal geographic data committee.--The term ``Federal Geographic Data Committee'' means the interagency committee that promotes the coordinated development, use, sharing, and dissemination of geospatial data on a national basis. (4) Remote sensing and other geospatial.--The term ``remote sensing and other geospatial'' means collecting, storing, retrieving, or disseminating graphical or digital data depicting natural or manmade physical features, phenomena, or boundaries of the Earth and any information related thereto, including surveys, maps, charts, satellite and airborne remote sensing data, images, LiDAR, and services performed by professionals such as surveyors, photogrammetrists, hydrographers, geodesists, cartographers, and other such services. (5) Secretary.--The term ``Secretary'' means the Secretary of Commerce, acting through the Administrator of the National Oceanic and Atmospheric Administration. SEC. 4. ESTABLISHMENT OF THE DIGITAL COAST. (a) Establishment.-- (1) In general.--The Secretary shall establish a program for the provision of an enabling platform that integrates geospatial data, decision-support tools, training, and best practices to address coastal management issues and needs. Under the program, the Secretary shall strive to enhance resilient communities, ecosystem values, and coastal economic growth and development by helping communities address their issues, needs, and challenges through cost-effective and participatory solutions. (2) Designation.--The program established under paragraph (1) shall be known as the ``Digital Coast'' (in this section referred to as the ``program''). (b) Program Requirements.--In carrying out the program, the Secretary shall ensure that the program provides data integration, tool development, training, documentation, dissemination, and archive by-- (1) making data and resulting integrated products developed under this section readily accessible via the Digital Coast Internet website of the National Oceanic and Atmospheric Administration, the GeoPlatform.gov and data.gov Internet websites, and such other information distribution technologies as the Secretary considers appropriate; (2) developing decision-support tools that use and display resulting integrated data and provide training on use of such tools; (3) documenting such data to Federal Geographic Data Committee standards; and (4) archiving all raw data acquired under this Act at the appropriate National Oceanic and Atmospheric Administration data center or such other Federal data center as the Secretary considers appropriate. (c) Coordination.--The Secretary shall coordinate the activities carried out under the program to optimize data collection, sharing and integration, and to minimize duplication by-- (1) consulting with coastal managers and decision makers concerning coastal issues, and sharing information and best practices, as the Secretary considers appropriate, with-- (A) coastal States; (B) local governments; and (C) representatives of academia, the private sector, and nongovernmental organizations; (2) consulting with other Federal agencies, including interagency committees, on relevant Federal activities, including activities carried out under the Ocean and Coastal Mapping Integration Act (33 U.S.C. 3501 et seq.), the Coastal Zone Management Act of 1972 (16 U.S.C. 1451 et seq.), the Integrated Coastal and Ocean Observation System Act of 2009 (33 U.S.C. 3601 et seq.), and the Hydrographic Services Improvement Act of 1998 (33 U.S.C. 892 et seq.); (3) participating, pursuant to section 216 of the E- Government Act of 2002 (Public Law 107-347; 44 U.S.C. 3501 note), in the establishment of such standards and common protocols as the Secretary considers necessary to assure the interoperability of remote sensing and other geospatial data with all users of such information within-- (A) the National Oceanic and Atmospheric Administration; (B) other Federal agencies; (C) State and local government; and (D) the private sector; (4) coordinating with, seeking assistance and cooperation of, and providing liaison to the Federal Geographic Data Committee pursuant to Office of Management and Budget Circular A-16 and Executive Order 12906 of April 11, 1994 (59 Fed. Reg. 17671), as amended by Executive Order 13286 of February 28, 2003 (68 Fed. Reg. 10619); and (5) developing and maintaining a best practices document that sets out the best practices used by the Secretary in carrying out the program and providing such document to the United States Geological Survey, the Corps of Engineers, and other relevant Federal agencies. (d) Filling Needs and Gaps.--In carrying out the program, the Secretary shall-- (1) maximize the use of remote sensing and other geospatial data collection activities conducted for other purposes and under other authorities; (2) focus on filling data needs and gaps for coastal management issues, including with respect to areas that, as of the date of the enactment of this Act, were underserved by coastal data and the areas of the Arctic that are under the jurisdiction of the United States; (3) pursuant to the Ocean and Coastal Mapping Integration Act (33 U.S.C. 3501 et seq.), support continue improvement in existing efforts to coordinate the acquisition and integration of key data sets needed for coastal management and other purposes, including-- (A) coastal elevation data; (B) land use and land cover data; (C) socioeconomic and human use data; (D) critical infrastructure data; (E) structures data; (F) living resources and habitat data; (G) cadastral data; and (H) aerial imagery; and (4) integrate the priority supporting data set forth under paragraph (3) with other available data for the benefit of the broadest measure of coastal resource management constituents and applications. (e) Financial Agreements and Contracts.-- (1) In general.--In carrying out the program, the Secretary-- (A) may enter into financial agreements to carry out the program, including-- (i) support to non-Federal entities that participate in implementing the program; and (ii) grants, cooperative agreements, interagency agreements, contracts, or any other agreement on a reimbursable or non-reimbursable basis, with other Federal, tribal, State, and local governmental and nongovernmental entities; and (B) may, to the maximum extent practicable, enter into such contracts with private sector entities for such products and services as the Secretary determines may be necessary to collect, process, and provide remote sensing and other geospatial data and products for purposes of the program. (2) Fees.-- (A) Assessment and collection.--The Secretary may assess and collect fees for the conduct of any training, workshop, or conference that advances the purposes of the program. (B) Amounts.--The amount of a fee under this paragraph may not exceed the sum of costs incurred, or expected to be incurred, by the Secretary as a direct result of the conduct of the training, workshop, or conference, including for subsistence expenses incidental to the training, workshop, or conference, as applicable. (C) Use of fees.--Amounts collected by the Secretary in the form of fees under this paragraph may be used to pay for-- (i) the costs incurred for conducting an activity described in subparagraph (A); or (ii) the expenses described in subparagraph (B). (3) Survey and mapping.--Contracts entered into under paragraph (1)(B) shall be considered ``surveying and mapping'' services as such term is used in and as such contracts are awarded by the Secretary in accordance with the selection procedures in chapter 11 of title 40, United States Code. (f) Ocean Economy.--The Secretary may establish publically available tools that track ocean and Great Lakes economy data for each coastal State. (g) Authorization of Appropriations.--There is authorized to be appropriated to the Secretary $4,000,000 for each fiscal year 2018 through 2022 to carry out the program. Passed the Senate May 25, 2017. Attest: Secretary. 115th CONGRESS 1st Session S. 110 _______________________________________________________________________ AN ACT To require the Secretary of Commerce, acting through the Administrator of the National Oceanic and Atmospheric Administration, to establish a constituent-driven program to provide a digital information platform capable of efficiently integrating coastal data with decision-support tools, training, and best practices and to support collection of priority coastal geospatial data to inform and improve local, State, regional, and Federal capacities to manage the coastal region, and for other purposes.

. The expanded summary of the Senate reported version is repeated here.) Digital Coast Act (Sec.4)This bill requires the National Oceanic and Atmospheric Administration (NOAA) to establish a constituent-driven Digital Coast program. (This program currently exists under NOAA to provide data, tools, and training that communities use to manage their coastal resources.) The program must: (1) provide an online resource that integrates geospatial data, decision-support tools, training, and best practices to address coastal management issues and needs, and to enhance resilient communities, ecosystem values, and coastal economic growth and development; and (2) provide for the documentation, dissemination, and archiving of the data. NOAA must focus on filling data needs and gaps for critical coastal management issues and support continued improvement in existing efforts to coordinate the acquisition and integration of key data sets needed for coastal management, and other purposes. NOAA may: (1) enter into financial agreements and collect fees to carry out the program; (2) enter into contracts with private sector entities as may be necessary to collect, process, and provide remote sensing and other geospatial data and products. Additionally, NOAA may establish publicly available tools that track ocean and Great Lakes economy data for each coastal state.

clinical presentation of sporadic inclusion body myositis ( sibm ) is variable , but most frequently characterized by painless weakness of the hand , fingers and hip flexors . absence of symptoms and signs but mild hyper - ck - emia as the sole manifestation of sibm has not been reported . for assessment of the muscle biopsy routine stainings on frozen sections ( hematoxylin and eosin , gomori - trichrome , pas , oil - red - o ) , enzymehistochemistry ( cox / sdh , nadh , atpase ph 4,2 ) , immunohistochemistry ( slow and fast myosin , utrophin - nt , dystrophin and associated proteins , ncam , vimentin , desmin ) , a panel of so - called nonsense proteins and neurofilament ( smi-31 ) , and inflammatory markers were performed . we examined in sum nine semithin sections and two were selected for electron microscopy using a zeiss em 109 turbo / dps ( carl zeiss inc . , thornwood , ny , usa ) . the patient is a 73-year - old caucasian male , with a previous history of left bundle - branchblock since age 64 years , recurrent hyper - ck - emia since a border - zone stroke at age 64 ranging between 200 and 1324 u / l ( n<171 u / l ) , hyperlipidemia since age 64 years requiring statin therapy after detection of hyper - ck - emia , ischemic left posterior borderzone stroke at age 72 , a 60% stenosis of the left internal carotid artery , and arterial hypertension since age 72 . nerve conduction studies and needle electromyography of the right brachial biceps and right gastrocnemius muscles were non - informative . muscle biopsy from the right lateral vastus muscle was strongly indicative of ibm ( figure 1 ) . the most obvious muscle pathological alterations were the caliber changes with atrophic fibers ( figure 1a ) and many rimmed vacuoles together with endomysial inflammatory infiltrates ( figure 1b and c ) . in addition , cox negative - fibers ( figure 1d ) and a single ragged - red fiber ( rrf ) and rimmed - vacuoles ( figure 1e and f ) were noted in the gomoritrichrome staining . the inflammatory infiltrates consisted mainly of cd3-positive t - cells , including cd8-positive cytotoxic t - cells with invasion of intact muscle fibers ( figure 1 g , h ) . there were only single b - cells and only a few cd68-immunoreactive monocyte / macrophages . hla - class i antigen was only focally and weakly upregulated and there was no evidence for the deposition of terminal complement complex ( c5b9 ) in capillaries . smi-31 ( neurofilament ) and p62 ( figure 1i ) showed immunoreactivity in the vacuoles . dystrophin and associated proteins ( table 1 ) did not show alterations and there was a lack of accumulation of desmin ( figure 1j ) . we noted signs of a neurogenic muscle lesion with groups of atrophic fibers , upregulation of ncam ( figure 1k ) without corresponding vimentin immunoreactivity , and decreased central activity of nadh without typical targets ( figure 1l ) . ultrastructural examination revealed fibers with autophagic vacuoles with sequestered cytoplasmic organelles and degradation products ( figure 1m - o ) . typical tubulofilamentous inclusions were not detected . in summary , according to the presence of i ) invasion of non - necrotic fibers by mononuclear cells , ii ) vacuolated muscle fibers , iii ) smi-31 and p62/ubiquitin immunoreactivity of inclusions and vacuoles , ibm was diagnosed . since there is no established therapy available for sporadic ibm and since symptoms and signs were absent , the presented patient is interesting for hyper - ck - emia as the sole manifestation of ibm , a poorly understood progressive muscle disease of middle or late life . contrary to the classical clinical presentation with weakness of the proximal leg and distal arm muscles in an asymmetric distribution , our patient presented only with hyper - ck - emia but had not developed muscle weakness so far . in the majority of the cases , sibm manifests already at onset with muscle weakness of the proximal and distal arm and leg muscles . causes of asymptomatic hyper - ck - emia other than sibm include calpainopathy , dysferlinopathy , central core disease , multicore disease , mcardle s disease , metabolic myopathy , polymyositis , sarcoid myopathy , endocrine myopathy , statin myopathy , and rhabdomyolysis . these differentials were excluded in the presented patient by musclce biopsy and other blood chemical values . weakness in sibm predominantly affects the finger flexors , the wrist flexors , or the quadriceps muscle . sibm has a dual pathology of autoimmunity and unexplained myofiber degeneration or loss of myofibers . the diagnosis is established by muscle biopsy showing the typical features of invasion of non - necrotic fibers by mononuclear cells , vacuolated muscle fibers , and either intracellular amyloid deposits or tubulofilaments 15 - 18 nm in diameter on electron microscopy . contrary to sibm hereditary inclusion body myopathy ( hibm ) may initially affect the quadriceps muscle and may follow an autosomal dominant trait of inheritance , may spare the quadriceps muscle but may follow an autosomal dominant transmission , may manifest as distal myopathy nonaka , may be associated with paget s disease and fronto - temporal dementia , or may be linked to the myosin - heavy chain - ii locus . patients with hibm are usually younger than patients with sibm , are virtually always symptomatic , and there is no inflammation in their biopsies . the reason why sibm in the presented patient manifested only with hyper - ck - emia remains speculative but could be explained by a new mutation in one of the genes associated with hibm . recently it has been shown that ageing may have an influence on the development of sibm . this case shows that sibm may be asymptomatic and may manifest with hyper - ck - emia exclusively . sibm has to be included in the differential diagnoses of asymptomatic hyper - ck - emia .

sporadic inclusion body myositis ( sibm ) usually manifests with painless weakness of the hand , finger and hip flexors . absence of symptoms or signs , but mild hyper - ck - emia as the sole manifestation of ibm , has not been reported . we report the case of a 73-year - old male who presented with asymptomatic recurrent hyper - ck - emia ranging from 200 to 1324u / l ( n<171u / l ) , since 10 years . clinical neurologic investigation , nerve conduction studies and emg were non - informative . muscle biopsy surprisingly revealed sibm . sibm may be asymptomatic and may manifest with hyper - ck - emia exclusively . so , it has to be included in the differential diagnoses of asymptomatic hyper - ck - emia .

since more than a century normal diffusion , characterized by a linear increase in time of the mean square displacement ( msd ) of an ensemble of moving particles , provides a paradigmatic example of a stochastic process . here the msd can be expressed by the ensemble average @xmath0 with an exponent @xmath1 , where @xmath2 holds for the position of a particle on the real line at time @xmath3 . however , exponents @xmath4 are also possible yielding two important examples of anomalous diffusion : superdiffusion with @xmath5 and subdiffusion with @xmath6 . more recently , the importance of anomalous diffusive regimes was realized not only in physics but also in chemistry , biology and economics . these regimes were found in theoretical models and experiments related , among others , to turbulence , amorphous semiconductors , porous media , surface diffusion , glasses , granular matter , reaction - diffusion processes , plasmas and biological cell motility , see refs . @xcite for reviews . parallel to this development low dimensional deterministic maps attracted much attention as simple models of anomalous dynamics which can be understood analytically @xcite . a characteristic feature of the stochastic processes generated by these maps is provided by the probability density functions ( pdfs ) of the dynamical variables . in case of normal diffusion these pdfs exhibit gaussian forms , whereas for subdiffusion they yield tails with stretched exponential decay and for superdiffusion lvy power laws @xcite . several theoretical approaches have been worked out over the past few decades in order to explain anomalous diffusion . perhaps the most famous one is continuous time random walk ( ctrw ) theory , pioneered by the work of montroll , weiss and scher @xcite . their stochastic approach was later on adapted to sub- and superdiffusive deterministic maps @xcite . related maps were originally proposed by pomeau and manneville as simple models of intermittency @xcite . a classification of their dynamics was provided particularly by gaspard and wang combining stochastic with dynamical systems theory @xcite . exploiting the deterministic properties of these maps , anomalous diffusion was further studied in the framework of the thermodynamic formalism @xcite , by means of periodic orbit theory @xcite and by spectral decomposition techniques @xcite . currently aging phenomena @xcite , non - ergodic behavior @xcite and infinite invariant measures @xcite are in the focus of investigations demonstrating that these simple models provide ongoing inspiration for important new research . however , all of the above studies focused on specific values of control parameters only for which these maps are to a large extent analytically tractable . that generally the dynamics is more intricate was shown by calculating the parameter - dependent diffusion coefficient of a piecewise linear one - dimensional map , which turned out to be fractal @xcite . similar behavior was detected in more complicated models like the climbing sine map @xcite , in experimentally accessible systems like particles bouncing on corrugated surfaces @xcite and in models of josephson junctions @xcite . these findings can be explained by the existence of deterministic dynamical correlations that are topologically unstable under parameter variation @xcite ; for a review see part 1 of ref . @xcite . in this paper we show that a fractal parameter dependence of physical quantities is not only typical for low - dimensional periodic deterministic dynamical systems exhibiting normal transport laws but also for anomalous dynamics . as an example we study parameter - dependent subdiffusion in a simple deterministic map , however , our main arguments hold for a broad class of anomalously diffusive systems . a specific feature of our analysis is that it employs a blending of techniques from stochastic theory and the theory of dynamical systems . that way we wish to contribute to the microscopic foundations of a general theory of anomalous deterministic transport , which does not yet seem to be fully developed . our paper is organized as follows : the model is introduced in section [ model ] . as a rate of diffusivity we choose a generalized diffusion coefficient ( gdc ) , which generalizes the diffusion constant known from normal diffusion . in section [ numres ] we present results from computer simulations showing that the gdc has a nonmonotonic , irregular dependence on control parameters of the map . we give a qualitative explanation of this phenomenon by arguing that the gdc is a self similar - like , fractal function . the gdc is furthermore conjectured to be everywhere discontinuous . in section [ theory ] we briefly review ctrw theory . in section [ mod_theory ] we show that an amended version of it correctly describes the coarse functional form of the gdc . apart from fractal parameter dependencies , the map under consideration exhibits an interesting dynamical transition , which is studied in detail in section [ sup ] . in section [ ffp ] we compute the pdf of this map from simulations and analyze it by means of a time fractional diffusion equation . section [ ff ] finally outlines a deterministic approach for analyzing the fractal gdc , which is based on a taylor - green - kubo ( tgk ) formula for anomalous diffusion . this theory enables us to relate anomalous diffusion processes to fractal de rham - type functions . section [ con ] summarizes our results . for an outline of this work we refer to ref . we focus on a subdiffusive map which , restricted onto the unit interval , was introduced by pomeau and manneville to describe intermittency @xcite , @xmath7 where the parameter @xmath8 holds for the degree of nonlinearity and @xmath9 is a second control parameter . in the following we will omit these two indices for convenience , @xmath10 . the variable @xmath11 denotes the position of a point particle at discrete time @xmath12 . translation symmetry , @xmath13 , and reflection symmetry , @xmath14 , complete the definition of the map on the real line . the iterated dynamics of this model is illustrated in fig . [ figmap ] for particular values of the two control parameters : given some initial condition @xmath15 , the equations of motion eq . ( [ map_eq ] ) produce the next value @xmath16 , @xmath16 determines @xmath17 , and so on . a typical trajectory of the system , displayed in fig . [ figmap ] in a cobweb plot , is therefore represented in form of jumps @xmath18 on the real line . ( [ map_eq ] ) for parameters @xmath19 with a typical trajectory generated by the map ( cobweb plot with dashed horizontal and vertical lines ) starting at initial condition @xmath15 . bottom : the demonstration of intermittency in a time series plot of a typical trajectory . note the long laminar periods in the trajectory , which are interrupted by chaotic ` bursts ' . here and in the following figures all quantities are without units.,title="fig:",scaledwidth=40.0% ] + , eq . ( [ k ] ) , for the map eq . ( [ map_eq ] ) as a function of the map s nonlinearity @xmath20 for different values of the prefactor @xmath21 in the anomalous diffusive region @xmath22 . the semi - logarithmic scale is chosen in order to magnify the irregular fine structure . the values for @xmath21 from bottom to top are @xmath23 . the curves consist of @xmath24 points , respectively.,title="fig:",scaledwidth=48.0% ] + for @xmath25 the diffusion process generated by this map is normal , whereas for @xmath26 it is anomalous @xcite . this anomaly is due to the existence of marginally stable fixed points located at all integer values of @xmath27 around which a particle gets ` trapped ' for a long time @xcite . however , in regions with larger local derivative , where the particle can jump to different unit intervals , the dynamics becomes more irregular , see fig . [ figmap ] . thus , a typical trajectory of the spatially continued map eq . ( [ map_eq ] ) consists of long laminar pieces interrupted by short chaotic bursts . such a behavior is the hallmark of what is called intermittency @xcite . an example of a typical intermittent trajectory generated by this map is shown at the bottom of fig . [ figmap ] . in the groundbreaking works of thomae , geisel @xcite , zumofen and klafter @xcite , main attention was paid to the time dependence of the msd for specific fixed values of the parameter @xmath21 . in contrast , our aim is to study how a suitably defined gdc behaves under variation of the two control parameters @xmath21 and @xmath20 . in refs . @xcite an anomalous diffusion coefficient was introduced by @xmath28 where @xmath29 is the gamma function and @xmath30 is some constant that will be specified in the following . for convenience we define the gdc by @xmath31 for numerical simulations of the spatially extended map eq . ( [ map_eq ] ) we have typically used an ensemble of @xmath32 particles , where the initial conditions are uniformly distributed on the unit interval @xmath33 . if not said otherwise , each trajectory was calculated up to @xmath34 time steps . for different values of @xmath21 we have confirmed that the numerically computed power law dependence of the msd is in full agreement with the ctrw solution @xcite @xmath35 we remark that at the transition point between normal and anomalous diffusion a logarithmically corrected dependence of the msd is obtained , @xmath36 which again is in complete agreement with ctrw theory . hence , for the rest of this paper @xmath30 is defined by the theoretically correctly predicted values eq . ( [ alfa ] ) . we first fix the parameter @xmath21 and study the dependence of @xmath37 as a function of the degree of nonlinearity @xmath20 . numerical results are presented in figs . [ k_z_a ] and [ k_z ] . @xmath37 as a function of @xmath20 appears to be highly irregular exhibiting a lot of structure on fine scales . particularly fig . [ k_z_a ] shows how the fine structure as a function of @xmath20 evolves under variation of @xmath21 . in fig . [ k_z ] the calculations were performed both for the normal and for the anomalous diffusive regime . ( [ supp ] ) suggests that at @xmath38 the gdc exhibits a local minimum in form of a total suppression of the strength of anomalous diffusion , that is , @xmath39 for all values of @xmath21 . interestingly , this transition from normal to anomalous diffusion appears to be approached continuously by @xmath37 as a function of @xmath20 . the reason is that for @xmath40 logarithmic terms are still present in the dynamics , but they contribute for transient times only . this peculiar behavior does not only diminish the gdc but also significantly slows down the convergence of the simulation results . the inset of fig . [ k_z ] shows several representative values of @xmath37 in the transition region , where different symbols correspond to different computation times and different numbers of trajectories for fixed @xmath21 . due to the slow convergence , even for the largest computation times the results for @xmath37 are quantitatively still apart from the ctrw prediction , which holds in the limit of time to infinity . however , qualitatively there is a tendency towards zero at @xmath38 . this specific problem will be analyzed in full detail in section [ mod_theory ] . as a function of @xmath20 for different values of @xmath21 . the parameter values from bottom to top ( at @xmath38 ) are @xmath41 . the curves consist of @xmath42 points , respectively . the inset shows several representative values of @xmath37 around @xmath38 for @xmath43 . lines are guides for the eyes only . different symbols from top to bottom correspond to simulations with @xmath32 trajectories and the different computation times @xmath44 ( circles ) , @xmath45 ( squares ) , @xmath34 ( rhombuses ) , @xmath46 ( triangles ) indicating ultra - slow convergence of @xmath37 towards zero at @xmath38 . also the curve calculated with @xmath47 trajectories , each of the length of @xmath34 time steps , is shown . in the inset it coincides with the curve calculated with @xmath32 trajectories , each of the length of @xmath34 time steps.,title="fig:",scaledwidth=48.0% ] + from normal diffusive maps it is known that iterations of the critical points of a map , which here are the points of discontinuity at @xmath48 , play a crucial role in order to understand the complicated parameter dependence of a diffusion process @xcite . accordingly , variations of the height of the map @xmath49 strongly affect the parameter - dependent gdc , as we will discuss in detail below . such variations are achieved both by changing @xmath20 and @xmath21 . in order to more clearly represent the impact of variations of @xmath20 only on the gdc , we study @xmath37 as a function of @xmath20 for fixed height @xmath50 . we emphasize that the topology of the orbit of the critical point is still affected by variations of @xmath20 only , however , it is less sensitive to @xmath20 than to varying @xmath50 . respective simulation results are shown in fig . as expected , @xmath51 for fixed @xmath50 is considerably smoother compared to figs . [ k_z_a ] and [ k_z ] . indeed , the local minimum in the transition from normal to anomalous diffusion is now less obscured by a non - trivial fine structure . however , note that very small irregularities forming a self similar - like pattern are still present , as is suggested by fig . [ k_h ] and the inset , which depicts a magnification of a small characteristic region . the figure also shows the convergence of the data with respect to simulation time and number of trajectories from which the formation of the irregularities is clearly seen . as a function of @xmath20 for the fixed height of the map @xmath52 as defined in the text . different curves correspond to simulations with @xmath32 trajectories and different computation times , from bottom to top on the right hand side of the figure @xmath53 . note the inverse order of the curves at the point @xmath38 marked by the vertical dashed line . curves consist of @xmath54 points , respectively . several values of @xmath37 for @xmath55 are also shown ( circles ) . the data indicate clear convergence in time and the formation of irregularities . additionally , several representative values of @xmath37 calculated for @xmath47 trajectories , each of the length of @xmath34 time steps , are shown ( squares ) . they coincide with corresponding values of @xmath37 calculated with @xmath32 trajectories , each of the length of @xmath34 time steps . the inset shows a magnified region of the curve calculated for @xmath44 . the dashed box marks a region that appears to be self - similar to the whole region shown in the inset indicating the existence of an underlying fractal pattern . the curve was calculated for @xmath56 trajectories and consists of @xmath57 points.,title="fig:",scaledwidth=50.0% ] + now we focus on the dependence of @xmath37 on the parameter @xmath50 with the parameter of nonlinearity @xmath20 kept fixed . in fig . [ k_s ] the behavior of the gdc as a function of @xmath50 is shown for different values of @xmath20 which , as expected , is more non - monotonous than that of @xmath58 . the structure of @xmath59 for different @xmath20 looks somewhat similar , however , we could not detect a simple scaling . for @xmath60 the map eq . ( [ map_eq ] ) reduces to a piecewise linear map for which it was shown analytically and numerically that diffusion is normal and that the diffusion coefficient is a fractal function of the slope @xmath21 @xcite , see the upper curve in fig . [ k_s ] . for @xmath61 and over a larger range of @xmath21 , @xmath62 as obtained from simulations is presented in fig . [ z3 ] ( a ) . magnifications of the initial region , see fig . [ z3 ] ( b ) and ( c ) , show a self similar - like behavior of @xmath37 on finer and finer scales indicating a fractal structure . as a function of parameter @xmath50 for different values of @xmath20 . from top to bottom it is @xmath63 . for clarity the curves are shifted vertically by @xmath64 , respectively.,title="fig:",scaledwidth=48.0% ] + over a large range of the parameter @xmath21 at @xmath61 . note that @xmath65 for @xmath66 . the dashed line represents the ctrw approximation eq . ( [ ctrw_geisel ] ) . the dashed - dotted line is the modified ctrw eqs . ( [ jump_length ] ) , ( [ mod_gdc_ctrw ] ) . ( b ) and ( c ) show magnifications of the initial region of ( a ) demonstrating the existence of irregularities on finer scales . the dashed line in ( b ) shows the modified ctrw eqs . ( [ int_jump_length ] ) , ( [ mod_gdc_ctrw ] ) . the sets of symbols included in ( a ) to ( c ) correspond to specific turnstile parameter values ( see section [ numres ] for explanations ) . the inset in ( a ) depicts the development of a discontinuity in the gdc around @xmath67 . the different lines correspond to different iteration times , from bottom to top at left @xmath68 ( circles ) , @xmath34 ( squares ) , @xmath46 ( rhombuses ) , @xmath32 ( triangles ) , thus yielding a higher numerical precision . the curve with @xmath47 trajectories and @xmath34 time steps , which coincides with the one calculated with @xmath32 trajectories and @xmath34 time steps , shows that we gain convergence with respect to the number of trajectories . the data in ( a ) consists of @xmath69 points.,title="fig:",scaledwidth=49.0% ] + a qualitative explanation for the fractality of all these curves can be given in terms of _ turnstile dynamics _ , which has successfully been applied in order to understand the fractality of the normal diffusion coefficient in piecewise linear maps . here we outline the basic idea of this approach only , for technical details we refer to refs . @xcite . the key ingredient of this method is the orbit generated by iterations of the critical point @xmath70 of the map @xmath71 restricted onto the unit interval , @xmath72 . if this orbit is periodic it defines a _ markov partition _ with certain partition parts representing coupling regions ( _ turnstiles _ ) where , in the associated periodically continued map , particles can jump from one unit interval to another one . specific parameter values define markov partitions with specific turnstile couplings which , in more physical terms , generate specific sequences of forward- and backward scattering of particles that start nearby the critical point . it turns out that these markov partitions are topologically highly unstable under parameter variation , in the present case both for varying @xmath20 and @xmath21 . in fig . [ z3 ] ( a ) three parameter values are identified representing markov partitions that correspond to two local minima and a local maximum of @xmath62 thus highlighting a specific fine structure in the whole curve . higher - order markov partitions can now be constructed ( generated by higher - order iterations of the critical point ) which are of the same type as the initial three identified in fig . [ z3 ] ( a ) , however , yielding new sets of parameter values . such higher - order parameter triples are shown in fig . [ z3 ] ( b ) , ( c ) . they identify the same type of fine structure on finer and finer scales . a similar analysis can be performed for other local peaks of @xmath62 qualitatively explaining the fractal structure of the gdc . more quantitatively , one may wish to calculate some fractal dimension for these curves . however , this is a hard task even if analytical formulas for a diffusion coefficient are available @xcite and is left for further studies . we conclude this section with an unexpected detail of the gdc . for the piecewise linear map at @xmath60 the diffusion coefficient as a function of slope of the map is continuous @xcite . for @xmath61 , however , numerical results suggest that the dependence of @xmath37 on @xmath21 is discontinuous . in the inset of fig . [ z3 ] we have magnified a small region of @xmath37 around @xmath67 ( analogous behavior is found around @xmath73 ) . note that for @xmath74 particles can jump for the first time from the first unit interval to the fourth one . increasing the numerical precision by increasing the computation time , @xmath62 near @xmath67 gradually approaches a step function , which suggests that a discontinuity develops . similar discontinuities have already been reported for lyapunov exponents as functions of a bias in piecewise linear maps @xcite . more complicated ones are known to exist for diffusion coefficients of nonlinear maps exhibiting bifurcation scenarios @xcite and have recently been highlighted in research on transport in polygonal billiard channels @xcite . an explanation why for our model the gdc is discontinuous for @xmath61 while it is continuous for @xmath60 may be sought in the completely different character of the pdf of the map for @xmath61 , which develops non - integrable singularities at all marginally stable fixed points . details of this peculiar behavior will be discussed later , see fig . [ pdf ] and the analysis after eq . ( [ msd2 ] ) . note that at suspected points of discontinuity of the gdc like @xmath67 the critical point is getting mapped right onto these singular regions of the pdf at the very first iteration . simultaneously , the orbit of the critical point exhibits a transition from forward to backward scattering under variation of @xmath21 , which leads to a local maximum of the gdc in terms of turnstile dynamics . for @xmath61 this change in the microscopic scattering process is drastically amplified by the singular behavior of the pdf probably leading to a discontinuity in the gdc . in contrast , for @xmath60 the pdf is not singular but a non - differentiable step function @xcite , thus the gdc is locally maximal but still continuous . it would be valuable to have a mathematical proof of this conjectured discontinuity phenomenon . the discontinuity at @xmath67 is furthermore a boundary point of the specific fine structure identified in fig . [ z3 ] , which was previously discussed in terms of turnstile dynamics . as we have just emphasized , this parameter value is determined by a specific periodic orbit of the critical point of the map . however , as was outlined before , one can now construct infinitely many higher - order iterates of the same type of periodic orbits yielding new sets of parameter values . these parameter values are related to the same type of structure and , hence , identify the same type of discontinuity on finer and finer scales . furthermore , such parameter values are typically densely distributed on the parameter axis @xcite . this leads us to conjecture that @xmath62 shown in fig . [ z3 ] is discontinuous on a dense set of parameter values ( probably being of measure zero ) . note that the argument carries over to @xmath58 in fig . [ k_h ] , where a careful study of the largest point of irregularity at @xmath75 reveals the same type of discontinuity . so far we have focused on the fine structure of the gdc only . the next section proceeds with an understanding of its coarse functional form . as far as we know there is only one analytical result in the literature trying to predict the whole parameter dependence of the gdc of this map @xcite . however , as we will show the respective calculation needs to be modified in order to match to computer simulation results . this necessitates to briefly review the whole approach by explaining our corrections . the ctrw theory of montroll , weiss and scher @xcite has become a standard tool to model diffusion in intermittent maps like eq . ( [ map_eq ] ) @xcite . this approach assumes that diffusion can be decomposed into two stochastic processes characterized by waiting times and jumps . thus one has two sequences of independent identically distributed random variables , namely a sequence of positive random waiting times @xmath76 with pdf @xmath77 , @xmath78 , and a sequence of random jumps @xmath79 with a pdf @xmath80 , @xmath81 . for example , if a particle starts at point @xmath82 at time @xmath83 and makes a jump of length @xmath84 at time @xmath85 , its position is @xmath82 for @xmath86 and @xmath87 for @xmath88 . the probability that at least one jump is performed within the time interval @xmath89 is then @xmath90 while the probability for no jump during this time interval reads @xmath91 . the master equation for the pdf @xmath92 to find a particle at position @xmath2 and time @xmath93 is then @xmath94 it has the following probabilistic meaning : the pdf to find a particle at position @xmath2 at time @xmath93 is equal to the pdf to find it at point @xmath95 at some previous time @xmath96 multiplied with the transition probability to get from @xmath97 to @xmath98 integrated over all possible values of @xmath95 and @xmath96 . the second term accounts for the probability to remain at the initial position @xmath99 . it is easy to check that this equation yields a normalized pdf @xmath92 . the most convenient representation of this equation is obtained in terms of the fourier - laplace transform of the pdf , @xmath100 where the hat stands for the fourier transform and the tilde for the laplace transform . respectively , this function obeys the fourier - laplace transform of eq . ( [ master_eq ] ) , which is called the montroll - weiss equation @xcite , @xmath101 the laplace transform of the msd can be readily obtained by differentiating the fourier - laplace transform of the pdf , @xmath102 in order to calculate the msd within this theory , it thus suffices to know @xmath80 and @xmath77 generating the stochastic process . for one - dimensional maps of the type of eq . ( [ map_eq ] ) , using the symmetry of the map the waiting time distribution can be calculated from the approximation @xmath103 where we have introduced the continuous time @xmath104 . solving this equation for initial condition @xmath15 yields @xmath105^{-\frac{1}{z-1}}\quad .\ ] ] we now define that a particle makes a jump when it leaves the unit interval . note that this definition is different from the one of ref . @xcite , which used the interval @xmath106 $ ] . that the unit interval is the right choice for calculating the parameter - dependent random walk diffusion coefficient was shown for @xmath60 in refs . @xcite . from eq . ( [ cont_time_map_sol ] ) one can then obtain the time @xmath93 that a particle spends on the unit interval before making a jump according to the condition @xmath107 . the waiting time thus becomes a function of the injection point @xmath15 , @xmath108 accordingly , the waiting time pdf @xmath77 is related to the yet unknown pdf of injection points , @xmath109 making the assumption that the pdf of injection points is uniform , @xmath110 , the waiting time pdf is calculated to @xmath111^{- \frac{z}{z-1}}\ ] ] for long enough times @xmath93 , where normalization is used to obtain the prefactor . if jumps between neighboring cells _ only _ are taken into account , the jump pdf and its fourier transform may be assumed as @xcite @xmath112 combining eq . ( [ laplace_msd ] ) with eq . ( [ jump_pdf ] ) leads to the laplace transform @xcite @xmath113 for the following calculations it is useful to define @xmath114 note that for @xmath115 , @xmath116 is identical with @xmath30 defined in eq . ( [ alfa ] ) . for @xmath117 the laplace transform of eq . ( [ times_pdf2 ] ) reads @xmath118 with @xmath119 and the incomplete gamma function @xmath120 . for @xmath121 the laplace transform of the waiting time distribution is @xmath122 where @xmath123 is the exponential integral , @xmath124 . here we are only interested in the long time behavior of the msd , which corresponds to taking the limit @xmath125 in eqs . ( [ laplace_times_pdf ] ) , ( [ laplace_times_pdf_g1 ] ) with @xmath116 being constant . for @xmath126 , taking the lowest order of the expansion we get @xmath127 and @xmath128 eq . ( [ laplace_msd2 ] ) then yields @xmath129 and its inverse laplace transform is @xmath130 similarly , for the normal diffusive case @xmath131 we get from eq . ( [ laplace_times_pdf ] ) as the small @xmath132-asymptotics of the waiting time distribution @xmath133 using eq . ( [ laplace_msd2 ] ) and the inverse laplace transform yields @xmath134 in the remaining case @xmath121 , the expansion of the exponential integral is @xmath135 , where @xmath136 is euler s constant . for small @xmath132 eq . ( [ laplace_times_pdf_g1 ] ) reads @xmath137 and eq . ( [ laplace_msd2 ] ) gives @xmath138 the inverse laplace transform of the first term can be obtained by applying karamata s tauberian theorem @xcite , which relates the laplace transform of a function given in the form @xmath139 for @xmath125 and @xmath140 to the inverse @xmath141 for @xmath142 . the function @xmath143 must meet the requirement of being slowly varying , @xmath144 for @xmath145 as @xmath146 . in our case we have @xmath121 , @xmath147 and the function @xmath148 satisfies the above condition . for the msd we thus get @xmath149 in summary , we obtain for the gdc @xmath150 with @xmath151 . for @xmath152 we get @xmath153 because of the logarithmic term in eq . ( [ x2g1 ] ) . now we compare this result with our numerical simulations . as an example , @xmath37 as a function of @xmath21 determined by eq . ( [ ctrw_geisel ] ) is shown in fig . [ z3 ] ( a ) , where @xmath61 . for @xmath22 , the difference to the result of ref . @xcite is by a factor of two . this yields approximately the right slope for small @xmath21 , however , it does not reproduce the trivial value of @xmath154 when particles can not escape from the unit interval anymore . hence , further modifications are necessary . the easiest way to modify standard ctrw theory is by varying either the waiting time or the jump pdf . however , the waiting time distribution is straightforwardly determined by the model as a power law for all intermittent values of @xmath20 . this suggests to change the jump pdf eq . ( [ jump_pdf ] ) only , which in a first attempt one may write as @xmath155 here the second term reflects the fact that the particle can stay on the unit interval with probability @xmath156 . by assuming that the density of particles is uniform on the unit interval , @xmath157 is determined by the size of the escape region , @xmath158 with @xmath159 , where @xmath160 is the solution of the equation @xmath161 . for normal diffusion it is well - known that @xmath162 provides a random walk approximation for the diffusion coefficient which is asymptotically correct in case of nearest neighbor jumps , @xmath163 @xcite . for farther than nearest neighbor jumps this approximation is straightforwardly generalized by weighting the integer jump distance squared with the respective probability , based on the escape region , to perform such a jump @xcite . assuming that one knows about the power law time dependence of the msd eq . ( [ gdc_def ] ) for this map , one can apply the same approximation to anomalous diffusion . in fig.[k_z_ctrw ] the result is shown for @xmath58 at @xmath43 . as one can see , this simple argument indeed roughly reproduces the coarse functional form of @xmath58 and yields the exact value at @xmath60 . as a function of @xmath20 for @xmath164 . the bold black line depicts again the computer simulation results from fig . the thin line that is on top at @xmath38 represents the simple random walk approximation eq . ( [ eq : dknorm ] ) for @xmath165 . the dashed line corresponds to the modified ctrw approximation eqs . ( [ int_jump_length ] ) , ( [ mod_gdc_ctrw ] ) . the thin line that is in the middle at @xmath38 displays the first term of the tgk formula eq . ( [ gdc_gk ] ) . the inset reveals the existence of logarithmic corrections in the msd by plotting @xmath166 with respect to @xmath167 for @xmath168 and different @xmath20 close to the transition point at @xmath38 . the dashed lines correspond to @xmath169 from bottom to top , the dashed - dotted lines to @xmath170 from top to bottom . the thick solid line represents @xmath38 , the thin solid line is proportional to @xmath167 as a guide for the eye.,title="fig:",scaledwidth=48.0% ] + accordingly , the modification of standard ctrw theory eq . ( [ real_jump_pdf1 ] ) works for nearest neighbor jumps only . we thus further amend the jump pdf eq . ( [ real_jump_pdf1 ] ) by introducing a typical jump length @xmath171 , @xmath172 with fourier transform @xmath173 . this jump length we define either by the actual mean displacement @xmath174 or , under the simplifying assumption of integer jumps , by the coarse - grained displacement @xmath175 | \right\ } \quad , \ ] ] where the square brackets hold for the largest integer less than the argument . here the averages , denoted by curly brackets , are performed starting from a uniform initial ensemble of walkers with respect to the conditional probability density that particles leave the unit interval . the latter ensemble averages are then averaged over time . repeating the calculations from the previous section with eq . ( [ real_jump_pdf ] ) , we obtain the msd @xmath176 @xmath177 , where the typical jump length @xmath178 is given by eqs . ( [ jump_length ] ) , ( [ int_jump_length ] ) . hence , our final ctrw expression for the gdc reads @xcite @xmath179 fig . [ z3 ] ( a ) shows the ctrw approximation eq . ( [ mod_gdc_ctrw ] ) with jump length @xmath180 , eq . ( [ jump_length ] ) , which describes the coarse dependence of the gdc very well over a large range of parameters . the ctrw result with integer jump length @xmath181 , eq . ( [ int_jump_length ] ) with eq . ( [ mod_gdc_ctrw ] ) , is shown in fig . [ z3 ] ( b ) . it gives an asymptotically exact approximation of the gdc for small values of @xmath21 , however , it also holds well for larger parameters . a quantitative comparison moreover indicates ( within numerical accuracy ) that this combination yields results which exactly correspond to our numerical findings for @xmath37 at all integer values of @xmath182 , which for @xmath61 are equivalent to @xmath183 . this generalizes results obtained previously for the normal diffusion coefficient at @xmath60 @xcite . we now focus on @xmath37 as a function of @xmath20 . [ k_z_ctrw ] shows the modified ctrw approximation eqs . ( [ int_jump_length ] ) , ( [ mod_gdc_ctrw ] ) in comparison with simulation results . in the strongly anomalous regime of large @xmath20 the approximation reproduces the gdc from simulations very well , however , for smaller values of @xmath20 there are obvious deviations . let us first explain the problem for @xmath184 , the region around @xmath38 will be discussed in the following section . let us recall that according to eqs . ( [ gdc_def]),([alfa ] ) , for @xmath185 the map exhibits normal diffusion in the long - time limit . one can further split this regime into @xmath186 , where the msd shows transient anomalous diffusion which becomes normal for long times while for @xmath187 it represents purely normal dynamics @xcite . however , in the latter case it is well - known that the waiting time distribution is exponential @xcite , @xmath188 where @xmath136 is the escape rate , and not a power law such as the ctrw approximation eq . ( [ times_pdf2 ] ) . in fact , in the limit of @xmath189 eq . ( [ mod_gdc_ctrw ] ) leads to @xmath190 , whereas the correct random walk result for normal diffusion reads @xcite @xmath191 note that for @xmath189 and by assuming a uniform density on the unit interval , in case of @xmath192 this equation yields @xmath193 , whereas for @xmath194 we get @xmath195 thus recovering the two simple random walk results mentioned earlier . ( [ eq : dknorm ] ) is indeed straightforwardly obtained from ctrw theory if one repeats the calculations with the exponential waiting time distribution eq . ( [ eq : wtexp ] ) and @xmath196 , i.e. , by assuming that on average a particle leaves the unit cell after one time - discrete jump . we thus conclude that the ctrw result eq . ( [ mod_gdc_ctrw ] ) gives only a reliable approximation for the gdc if @xmath197 , whereas for @xmath198 the simple random walk result for normal diffusion eq . ( [ eq : dknorm ] ) should be used . this is in line with fig . [ k_z_ctrw ] . let us now understand the behavior of @xmath58 around @xmath38 , where the map exhibits a dynamical transition @xcite from normal to anomalous diffusion , see eqs . ( [ gdc_def]),([alfa ] ) . interestingly , this transition is clearly visible in the strength of the gdc , which to our knowledge has not been reported before . we now explain this phenomenon in detail . as mentioned in section [ numres ] , around the transition point there are significant deviations between ctrw theory and the simulation results . these differences are displayed in fig . [ k_z_ctrw ] . at @xmath38 the ctrw approximation forms a non - differentiable little wedge with @xmath199 at the minimum , whereas the simulations yield @xmath200 . we recall that by increasing the computation time there is some slow convergence of the simulation data towards the ctrw solution , see the inset of fig . [ k_z ] , but that we were not able to achieve quantitative agreement with the ctrw prediction of @xmath199 . this very slow convergence of the simulation results as well as the logarithmic term in the msd at @xmath38 , see eq . ( [ mod_x2 ] ) , suggest that the deviations between simulations and ctrw theory are due to logarithmic corrections in the msd for parameter values around @xmath38 . curiously , such terms are not present in eq . ( [ mod_x2 ] ) for @xmath201 ( @xmath202 ) . by refining our ctrw analysis , we will now show that such logarithmic terms indeed exist . however , for @xmath40 they hold for large but finite times only , whereas for @xmath38 they persist in the limit of infinite time . as is obvious from eqs . ( [ mod_x2 ] ) , ( [ mod_gdc_ctrw ] ) , for @xmath38 the surviving logarithmic term leads to a full suppression of the gdc , whereas close to the transition point finite - time logarithmic corrections yield a gradual suppression of the strength of diffusion . we start again from the exact expression for the laplace transform of the waiting time pdf @xmath203 , eq . ( [ laplace_times_pdf ] ) . combining this equation with the jump pdf eq . ( [ real_jump_pdf ] ) and eqs . ( [ montroll_weiss ] ) , ( [ laplace_msd ] ) we obtain the laplace transform of the msd @xmath204 we immediately drop the second term , since its inverse laplace transform is simply constant . let us focus now on the limits @xmath205 and @xmath206 . in case of @xmath207 the @xmath29 function in eq . ( [ sup_laplace_msd2 ] ) can be expanded to @xmath208 from this equation it follows that as @xmath116 approaches @xmath209 from below one may consider not only the first term as in eq . ( [ wait ] ) but also the second one , since both terms are divergent for @xmath210 . all other terms are nonsingular and can be safely neglected . we further expand the second term of eq . ( [ s1 ] ) to @xmath211 note that here we have obtained a series of logarithmic terms which , as we shall see , provides the logarithmic corrections we are looking for . by imposing the condition that @xmath212 , we may keep only the first two terms of eq . ( [ s2 ] ) , @xmath213 finally , we expand the first term of eq . ( [ s1 ] ) to @xmath214 where @xmath136 is again euler s constant . because we are interested in the small @xmath116 limit , we keep only the first term of this expansion . in summary , we obtain for the laplace transform of the msd eq . ( [ sup_laplace_msd2 ] ) in the limits of @xmath212 and @xmath210 @xmath215 inversion of the laplace transform yields as the final result @xmath216 with @xmath217 . for @xmath218 and @xmath219 one can drop the second term in the @xmath29 function expansion eq.([s1 ] ) , and the asymptotic ctrw result eq . ( [ mod_x2 ] ) is recovered . interestingly , @xmath220 diverges when @xmath221 , and at @xmath121 one thus arrives at the asymptotic @xmath222 dependence of eq . ( [ mod_x2 ] ) . analogous corrections are obtained for @xmath223 near the dynamical transition point , @xmath224 . by applying the same arguments as above we get @xmath225 where @xmath226 . in the long time limit we again recover the ctrw asymptotics eq . ( [ mod_x2 ] ) @xcite . these analytical findings are in agreement with results from computer simulations . in the inset of fig . [ k_z_ctrw ] , @xmath227 is shown as a function of @xmath167 close to the transition point at @xmath38 for different values of @xmath20 and @xmath168 . the logarithmic corrections are less obvious if @xmath20 is sufficiently different from @xmath228 , where @xmath166 quickly converges to @xmath229 . however , the logarithmic corrections are getting significant when @xmath20 approaches the dynamical transition value . we have thus identified the precise dynamical origin of the suppression of the gdc at @xmath38 . dynamical transitions are quite ubiquitous in intermittent maps and have been widely discussed in the literature in terms of the time dependence of the msd . however , it appears that so far no attention has been paid to a possible critical behavior of the associated gdc . our results lead us to conjecture that suppression and enhancement of the gdc are typical for dynamical transitions in anomalous dynamics altogether @xcite . the great success of the ctrw approach is related to the fact that it not only predicts the power @xmath230 but also the form of the coarse grained pdf @xmath92 of displacements @xcite . correspondingly the anomalous diffusion process generated by our model is not described by an ordinary diffusion equation but by a fractional generalization of it . starting from the montroll - weiss equation and making use of the expressions for the jump and waiting time pdfs eqs . ( [ times_pdf2 ] ) , ( [ jump_pdf ] ) , we rewrite eq . ( [ montroll_weiss ] ) in the long - time and -space asymptotic form @xmath231 with @xmath232 and @xmath233 . for the initial condition @xmath234 of the pdf we have @xmath235 . it is now helpful to recall the definition of the caputo fractional derivative of a function @xmath236 @xmath237 and its laplace transform @xcite , @xmath238 noticing that the left part of eq . ( [ montroll - weiss_2 ] ) precisely coincides with the laplace transform of the caputo derivative of the pdf and turning back to real space , we arrive at the time - fractional diffusion equation @xmath239 with @xmath240 given by the modified ctrw theory eqs . ( [ k ] ) , ( [ mod_gdc_ctrw ] ) . time - fractional diffusion equations of such a form have already been extensively studied by mathematicians @xcite . note that in application to our model another version of such an equation was proposed in ref . @xcite , which uses a riemann - liouville fractional derivative . it can be easily shown that both forms of time - fractional diffusion equations are equivalent under rather weak assumptions @xcite . yet two other forms of subdiffusive fractional equations ( however , not with applications to maps ) were proposed in refs . @xcite and @xcite . again , after some recasting these equations yield eq . ( [ frac_dif_eq ] ) @xcite . the solution of eq . ( [ frac_dif_eq ] ) is expressed in terms of an m - function of wright type @xcite , @xmath241 with @xmath242 , where we use the representation of the m - function @xmath243 this solution gives exactly the same asymptotics that was obtained in ref . @xcite for small and large values of @xmath244 , @xmath245 ) for @xmath246 and @xmath247 . the simulated pdf was computed from an ensemble of @xmath47 trajectories after @xmath248 iterations . the crosses ( x ) represent the simulated pdf coarse - grained over unit intervals . the continuous line in the middle yields the analytical solution of the fractional diffusion equation eq . ( [ sol ] ) with the same @xmath20 while @xmath240 is taken from simulations . the upper and the lower curves correspond to fits with an m - function form , calculated with the same @xmath20 but for different @xmath240 , and a gaussian form , respectively . more explanations are provided in the text , see sec.[ffp ] below . the inset depicts schematically the simulated pdf for the map eq . ( [ map_eq ] ) modulo @xmath209.,title="fig:",scaledwidth=48.0% ] + where @xmath249 are some constants that are given explicitly in ref . @xcite . similar to the modified ctrw approximation of the parameter - dependent gdc we now find that the analytical pdf eq . ( [ sol ] ) describes only the coarse scale of the pdf obtained from simulations but not its fine structure . this mismatch can be understood related to the fact that our model consists of a periodic lattice defined by specific elementary cells . any elementary cell develops a characteristic `` microscopic '' pdf , characterized by the map eq . ( [ map_eq ] ) restricted onto the unit interval , which exhibits singularities at the marginally stable fixed points . the inset of fig . [ pdf ] schematically depicts such a pdf of an elementary cell after a large number of iterations . precisely this functional form yields the building block for the pdf of the periodically continued map , see the main part of fig . if one eliminates the fine structure by averaging over whole unit intervals , one obtains a coarse - grained pdf that is in excellent agreement with the analytical solution of the fractional diffusion equation eq . ( [ frac_dif_eq ] ) , see fig . [ pdf ] . such an interplay between the `` microscopic '' pdf of a single scatterer and the `` macroscopic '' pdf of the spatially extended system was already reported for the normal diffusive model at @xmath60 @xcite and was recently also studied in billiards @xcite . however , in case of anomalous diffusion the pdf exhibits a further remarkable property : fig . [ pdf ] shows that the oscillatory structure of the whole pdf is bounded by two different functions . the upper curve is of m - function type and connects all local maxima of the microscopic pdf . these maxima are situated in regions of the map where the dynamics is regular , due to the marginally stable fixed points . the lower curve , on the other hand , is gaussian and is determined by all local minima of the microscopic pdf . these minima are generated in regions of the map being far away from the marginally stable fixed points , where the dynamics is locally most strongly chaotic @xcite . [ pdf ] thus nicely exemplifies the microscopic origin of anomalous diffusion in terms of intermittency . we now turn back to the parameter dependence of the gdc . in section [ mod_theory ] we have shown that an amended ctrw theory correctly describes the coarse dependence of the model s gdc , whereas the fractal fine structure is not captured by this approach . this reflects the fact that ctrw theory is a purely _ stochastic _ approach involving a randomness assumption between jumps , see the approximations involved as outlined in section [ theory ] and [ mod_theory ] , whereas the origin of the fractality of the gdc lies in the existence of long - range _ deterministic _ dynamical correlations , see the analysis in section [ numres ] . this motivates us to propose an alternative approach for analyzing the gdc , which is based on the taylor - green - kubo ( tgk ) formula @xcite for diffusion in maps . this theory has successfully been applied to the fractal diffusion coefficient of the normal diffusive map at @xmath60 , where it could partly be worked out analytically @xcite , to a nonlinear map with a complicated bifurcation scenario @xcite and to normal diffusion in billiards @xcite . an advantage of this analysis is that it systematically incorporates dynamical correlations . a disadvantage is that , in contrast to ctrw theory , for the map under consideration we could implement it only numerically . the basic idea is to generalize the tgk formula for maps to anomalous diffusion . following the usual derivation @xcite , the first step is to transform the msd in eq . ( [ gdc_def ] ) into sums over increments , or velocities , @xmath250 , @xmath251 for normal diffusion the second step requires to define the ensemble average expressed by the angular brackets in terms of the invariant pdf obtained for the map restricted onto the unit interval . in case of the map eq . ( [ map_eq ] ) this still works for @xmath185 , where the dynamics of the spatially extended map is normal diffusive . however , for @xmath252 it is well - known that the map of the elementary cell does not possess a non - trivial invariant pdf anymore . mathematical analysis @xcite shows that in this case there exist two physically relevant invariant measures , one which is concentrated on the marginally stable fixed points and one that lies in - between on the interval @xmath33 . the first measure has still nice , so - called srb properties and yields a pdf in form of a @xmath253-distribution on the marginally stable fixed points . the second one , however , is not normalizable anymore and hence is called an infinite invariant measure . in other words , if one starts a computer simulation from an ensemble of points uniformly distributed on the unit interval , the underlying stochastic process is not stationary and the pdf of an elementary cell , computed by a histogram method , does not converge in time to a well - defined invariant pdf @xcite . consequently , in contrast to normal diffusion eq . ( [ msd2 ] ) can not further be simplified by using time - translational invariance , and for the gdc eq . ( [ k ] ) we have to stop at @xmath254 \ : . \label{gdc_gk}\ ] ] in numerical simulations we find that the first term alone is already proportional to @xmath255 . if the system is ergodic , as for @xmath185 in our model , this term boils down to @xmath256 , and by neglecting any higher - order terms in eq . ( [ gdc_gk ] ) we recover the random walk result for normal diffusion @xcite . for @xmath257 the situation is again more complicated . here only generalized ergodic theorems may hold @xcite , which is intimately related to the existence of infinite invariant measures as outlined above . whether in this case a ctrw result such as eq . ( [ mod_gdc_ctrw ] ) can be extracted from the first term is a non - trivial open question . however , considering the first term only as an approximation of @xmath37 for all @xmath20 , the numerical results are depicted in fig . the comparison of this approximation with the previous simulation results shows that this term provides a first little step beyond a modified ctrw approach , since it reproduces the major irregularities of @xmath37 as a function of @xmath21 and even follows the suspected discontinuities discussed in section [ numres ] . however , our numerical precision is not sufficient to conclude whether it yields exact values for @xmath37 at integer heights . ( [ gdc_gk ] ) thus provides a suitable starting point for a systematic evaluation of the fractal structure of the gdc . since the series expansion in eq . ( [ gdc_gk ] ) is exact , working out further terms one should recover more and more structure in the gdc on fine scales @xcite . interestingly , the second term in eq . ( [ gdc_gk ] ) can be understood as a velocity autocorrelation function that , in contrast normal diffusion , depends on two time scales . the existence of a second time scale points to the phenomenon of _ aging _ in dynamical systems @xcite . in our case this can be understood as a consequence of infinite invariant measures . here we do not further pursue these questions but focus instead onto a direct link between the gdc and fractal functions as provided by the tgk formula , see refs . @xcite for normal diffusion . as was shown in ref . @xcite , eq . ( [ gdc_gk ] ) also holds if the velocities @xmath258 are replaced by the integer velocities @xmath259 - [ x_k]$ ] . it is now useful to start from @xmath37 expressed again by eq . ( [ msd2 ] ) , trivially rewritten as ) ( lower line ) with the computer simulation results from fig . [ z3 ] ( a).,title="fig:",scaledwidth=48.0% ] + @xmath260 the two sums suggest to define the jump function @xmath261 which satisfies the recursion relation @xcite @xmath262 the jump function gives the integer value of the displacement of a particle after @xmath263 time steps , which started at some initial position @xmath264 . it thus contains essential information about the microscopic scattering process of a particle by showing how sensitively the displacement depends on initial conditions . ( [ gdc_gk2 ] ) , ( [ j ] ) imply @xmath265 fig . [ jump_func ] displays the product of jump functions @xmath266 , which governs the anomalous diffusion process , for a representative parameter value . clearly , as time evolves the structure of this function is getting more complicated . the gdc , in turn , is determined by the cumulative function @xmath267 where we fix the integration constants by the condition that @xmath268 and by requiring that the whole function is continuous . integration of eq . ( [ j_recursion ] ) would yield a recursive functional equation for @xmath269 , which is of the same type as the one derived in ref . the solutions of such equations are generalized de rham- , respectively generalized takagi functions @xcite . however , at present such generalized de rham - equations can not be solved analytically , hence we do not work out the details but instead compute @xmath269 directly from simulations , according to the definition eqs . ( [ j ] ) , ( [ t ] ) . results for the first four iterations of @xmath269 are shown in fig . [ anom_takag ] . with respect to the construction of @xmath269 , it may not come too much as a surprise that in the limit of @xmath270 this function exhibits a fractal structure . interestingly , the gdc is obtained by integrating over this structure . if one starts from a uniform ensemble of initial conditions the result reads defined by eq . ( [ j ] ) for @xmath61 , @xmath271 , @xmath272 based on a uniform ensemble of @xmath273 initial conditions . note that there emerges a complicated fine structure.,title="fig:",scaledwidth=48.0% ] + @xmath274 this equation relates the gdc to a fractal function representing the microscopic scattering process of our model . the numerical result for the gdc eq . ( [ kt ] ) is in good agreement with the one employing the msd . in the light of fig . [ anom_takag ] and eq . ( [ kt ] ) , it may not be too surprising anymore that under parameter variation a highly non - trivial gdc is obtained from this model . as defined by eq . ( [ t ] ) , which is obtained by numerically integrating @xmath266 depicted in fig . [ jump_func ] . the parameter values are the same as in fig . [ jump_func ] . note that there emerges a fractal structure.,title="fig:",scaledwidth=48.0% ] + in this paper we have studied subdiffusion generated by a paradigmatic one - dimensional intermittent map . in contrast to previous works here we focused onto the parameter dependence of the gdc , which is an anomalously diffusive generalization of the diffusion coefficient known for normal diffusion . computer simulations suggested that this gdc is a fractal function of control parameters . this finding was corroborated by a qualitative explanation of the fractal structure in terms of complicated sequences of forward- and backward scattering ( turnstile dynamics ) , which are topologically unstable under parameter variation . our analysis furthermore led us to conjecture that the gdc is a discontinuous function of control parameters . in trying to understand the coarse functional form of the gdc , we applied standard ctrw theory to our model . by suitably amending previous calculations , we arrived at analytical approximations that enabled us to reproduce the whole coarse functional form of the gdc yielding asymptotically exact results in the limit of large and small parameter values . however , there are clear deviations between this theory and simulations around a dynamical transition from normal to anomalous diffusion . by refining our amended theory , we were able to explain these deviations in terms of logarithmic corrections leading to ultra - slow convergence of our simulation results and eventually yielding a full suppression of the gdc right at the transition point . these findings were confirmed by simulations of the msd . we then studied in detail the pdf of our model . we first derived a time - fractional subdiffusion equation from ctrw theory . the coarse - grained pdf of our model turned out to be in excellent agreement with the non - gaussian solution of our fractional diffusion equation . on a fine scale , however , the simulation results yielded an oscillatory structure reflecting the microscopic details of the intermittent scattering process . this structure was generated by the invariant density of the single scatterers hence revealing an interesting interplay between microscopic scattering and macroscopic diffusion . a more detailed understanding of the gdc was finally provided in terms of an anomalous tgk formula , which again is a generalization of the tgk formula for normal diffusion . the structure of this formula points at intimate relations to infinite invariant measures , aging , and generalized de rham - type fractal functions . all these terms define very active topics of research . we thus hope that , along these lines , in future work more detailed relations between mathematical infinite ergodic theory and the physics of anomalous diffusive processes can be established . in the present paper we have only studied a one - dimensional subdiffusive map , however , we expect these findings to be typical for spatially extended , low - dimensional , anomalous deterministic dynamical systems altogether . further studies may also focus on the relation between the anomalous tgk formula and ctrw theory , on a spectral analysis of the frobenius - perron operator of this model , and on analyzing a superdiffusive map by similar methods . the authors gratefully acknowledge helpful discussions with j. drger , r. gorenflo , j. klafter , r. metzler and a. pikovsky . they thank the mpipks dresden for hospitality and financial support . avc acknowledges financial support from the dfg . r. artuso , g. casati , r. lombardi , phys . rep . * 71 * , 62 ( 1993 ) ; r. artuso , phys . rep . * 290 * , 37 ( 1997 ) ; p. cvitanovi , r. artuso , r. mainieri , g. tanner , g. vattay , _ classical and quantum chaos _ , www.nbi.dk/chaosbook/ , niels bohr institute ( copenhagen , 2005 ) . h. hu , l .- s . young , erg . . syst . * 15 * , 67 ( 1995 ) ; r. zweimller , nonlinearity * 11 * , 1263 ( 1998 ) ; j. aaronson , _ an introduction to infinite ergodic theory . _ ( mathematical surveys and monographs vol . * 50 * , american mathematical society , providence , 1997 ) ; m. thaler , erg . . sys . * 22 * , 1289 ( 2002 ) . we remark that for @xmath207 it is possible to _ first _ invert eq . ( [ sup_laplace_msd2 ] ) by karamata s tauberian theorem and _ then _ to expand the result in terms of the physical time @xmath93 . this immediately yields the msd for all times in terms of the logarithmic corrections eq . ( [ s2 ] ) in physical time @xmath93 . unfortunately , this procedure does not work for @xmath275 , since here the gamma function is not slowly varying anymore . f. mainardi , fractional calculus : some basic problems in continuum and statistical mechanics . in : a. carpinteri and f. mainardi ( eds . ) _ fractals and fractional calculus in continuum mechanics _ , p.291 - 348 ( springer , new york , 1997 ) .

an intermittent nonlinear map generating subdiffusion is investigated . computer simulations show that the generalized diffusion coefficient of this map has a fractal , discontinuous dependence on control parameters . an amended continuous time random walk theory well approximates the coarse behavior of this quantity in terms of a continuous function . this theory also reproduces a full suppression of the strength of diffusion , which occurs at the dynamical transition from normal to anomalous diffusion . similarly , the probability density function of this map exhibits a nontrivial fine structure while its coarse functional form is governed by a time fractional diffusion equation . a more detailed understanding of the irregular structure of the generalized diffusion coefficient is provided by an anomalous taylor - green - kubo formula establishing a relation to de rham - type fractal functions .

the element lithium has provided many clues concerning stellar evolution and nucleosynthesis , as well as cosmology . however , its origin is still far from clear . nowadays there is an increasing belief that this element has a multi - source nature : primordial nucleosynthesis ( see the review by wallerstein et al . 1997 ) , galactic cosmic ray spallation in the interstellar medium and/or in the neighbourhood of supernova remnants ( meneguzzi et al . 1971 ; feltzing & gustafsson 1994 ) , late type stars and novae ( abia et al . 1993a ; hernanz et al . 1996 ) , supernovae explosions ( woosley & weaver 1995 ) and even spallation reactions around compact objects ( guessoum & kazanas 1998 ) . however , except perhaps for the li production during the big bang there is no consensus about the contribution of these sources to the present cosmic abundance , log @xmath2(li)@xmath3(x)@xmath4log(n(x)/n(h ) ) where n(x)/n(h ) is the abundance by number of the element x. ] the discovery of an unusually strong li line at @xmath1 by mckellar ( 1940 ) in the carbon star ( c - star ) wz cas strongly suggested that agb stars might be an important source of li in the galaxy . the work of mckellar was followed by similar discoveries in other agb stars : the c - stars wx cyg and iy hya ( sanford 1950 ; abia et al . 1991 ) , the s - stars t ara and t sgr ( feast 1974 ; boesgaard 1970 ) and the sc - stars henize 166 and vx aql ( catchpole & feast 1971 ; warner & dean 1970 ) . the same figure has also been reported in agb stars of the magellanic clouds ( plez et al . 1993 ; smith et al . the pioneering analysis by cohen ( 1974 ) showed that the measured equivalent width of the @xmath1 li i line ( w@xmath5 ) in these stars is mainly the consequence of a strong enhancement of the lithium abundance in the atmosphere . quantitative determinations by spectral synthesis ( denn et al . 1991 ; abia et al . 1993b ; plez et al . 1993 ; smith et al . 1995 ) have shown that the abundance of li in these stars is 1 - 2 orders of magnitude higher than the present cosmic li abundance . therefore , these stars have been named super lithium - rich ( slir ) stars and might well constitute the main source of li in the galaxy . the production of li in agb stars has received special attention in recent years ( e.g. sackmann & boothroyd 1992 ) . basically , li is produced by the reaction @xmath6 , followed by @xmath7 in a hot convective region that brings the @xmath8 or @xmath9 to cooler regions before the @xmath10li is destroyed by @xmath11 . this is the so - called @xmath10be - transport mechanism ( cameron & fowler 1971 ) . results of these theoretical studies quantitatively agree with the li abundances derived in agb stars of the galaxy and the magellanic clouds , although there are still many open questions related to the li production in these stars . among others we find questions about the minimum initial stellar mass which can eventually become a slir star during the agb phase , the duration of the slir phase or the actual li yield into the interstellar medium . our purpose in this work is related to the reality of the li abundances in slir stars and its consequences on the li yield . at present , the uncertainty in the derivation of the li abundances in agb stars is not lower than 0.4 - 0.5 dex ( see references above ) , mainly due to uncertainties in the stellar parameters and the fit to the observed spectra . note , that in many situations no single set of stellar parameters is found to fit the observations . however , there are also systematic errors that are not usually taken into account that might dramatically change the li abundance derived : uncertainties in the atmosphere models , the existence of velocity stratifications ( most slir stars are actually variable ) , sphericity and nlte effects are not currently considered as possible systematic sources of error . of course , the consequences of each of these phenomena on li abundance merit individual study and are beyond the scope of this work ( see , however , scholtz 1992 ; jrgensen et al . here , we will focus our attention on the effects of departures from lte in the formation of the li lines in c - stars . the study of nlte effects in the formation of lithium lines in stellar atmospheres was begun by the work of mller et al . they performed nlte analysis of the very weak lithium resonance line @xmath12 in the spectrum of the sun . later , luck ( 1977 ) investigated the statistical balance of lithium in the atmospheres of g - k giants for a 4-level atom model of li . a similar atom model was used by de la reza & querci ( 1978 ) and de la reza et al . historically , these papers considered for the first time the impact of a stellar chromosphere on the lithium lines . a new stage of research was begun with the work of steenbock & holweger ( 1984 ) , who used the technique of complete linearization for an 8-level atom model . they studied nlte effects in lithium lines in atmospheres of dwarfs and giants . pavlenko ( 1991 ) considered in detail the effects of deviation from lte in the atmosphere of red giants . later , magazz et al . ( 1992 ) , martin et al . ( 1994 ) and pavlenko ( 1994 ) , continued the nlte studies in t - tau stars , g - k giants , subgiants and dwarfs . the main results of these studies were confirmed by the independent work of carlsson et al . ( 1994 ) , who made a similar investigation using atmosphere models with various effective temperatures , luminosities and metallicities . finally , houdebine et al . ( 1995 ) , pavlenko et al . ( 1995 ) , pavlenko & magazz ( 1996 ) and martin et al . ( 1997 ) have continued the studies of different aspects of nlte formation of lithium lines in stellar atmospheres . as far as we know , the sole study on this subject for agb stars is that by de la reza & querci ( 1978 ) who performed kinetic equilibrium calculations of neutral lithium lines in c - stars and determined the influence of the possible chromospheric radiation into the photosphere . in the present work we revise this study using up to date atomic data , collisional and radiative rates , an extended li atom model and more reliable model atmospheres for c - stars in a wider range of effective temperatures ( t@xmath13 k ) and c / o ratios ( 1.0 - 1.35 ) ( see below ) . we explicitly apply our results deriving li abundances from synthetic spectra , both in lte and nlte , in three well known slir stars ( wx cyg , wz cas and iy hya ) from four accessible li i lines : the resonance line at @xmath1 and the subordinate transitions at @xmath14 , @xmath15 and @xmath16 , respectively , benefiting from the high signal - to - noise ratio and high resolution spectra of these stars . the consequences on the real li abundances in agb stars and on their net li yield into the interstellar medium is then reexamined . the observations were made during 1997 and 1998 in two different observatories . we used the 4.2 m wht at the observatory of el roque de los muchachos with the utrecht echelle spectrograph as the main instrument and a 2048@xmath172048 ccd with 24 @xmath18 m pixel size . we used the 79.0 lines / mm grating which provides less wavelength coverage , but more space between orders ( 20 - 30 arcsec ) . the projected size of the slit on the chip was around two pixels which gave a resolving power of 50000 , the effective resolution ranging between 0.05 - 0.19 from the blue orders to the red ones . the total number of orders on the chip were 30 covering the wavelength range 0.4 - 1.0 @xmath18 m with some gaps between orders . wz cas and wx cyg were also observed by the 2.2 m telescope at the calar alto observatory . for this observational run a fibre optics cassegrain echelle spectrograph ( foces ) ( pfeiffer et al . 1998 ) was used . this time the chip was a 1024@xmath171024 tektronik ccd with 24 @xmath18 m pixel size . the foces image covers the visible spectral region from 0.38 to 0.96 @xmath18 m in about 80 orders with full spectral coverage . spectral orders are separated by 20 pixels in the blue and 10 in the red . the maximum resolving power is 40000 with a two pixel resolution element . ! the reduction of the spectra was made following the standard procedures using the echelle task of the iraf software package : bias subtraction , division by flat - field images , removal of the scattered - light , extraction of the orders and wavelength calibration with th - ar lamps . typically the rms in the residuals of the calibrations were better than 10 m . finally , the spectra were divided by the spectrum of a hot rapidly rotating star to remove telluric absorptions , although they are only important in the @xmath16 range . the signal - to - noise ratio of the spectra vary along the wavelength , from s / n@xmath19 in the bluest orders to s / n@xmath20 around @xmath21 . since our stars are relatively bright objects ( v@xmath22 ) , this strong variation in the s / n ratio achieved is mainly due to the very low emissivity of the stars below @xmath23 . this is particularly evident in iy hya , which is an extremely red object . for this reason , its spectrum in the @xmath14 range is of too low quality ( s / n@xmath24 ) and has not been considered . the line list described in lbre et al . ( 1999 ) completed with c@xmath25 lines has been used for the analysis of the @xmath1 region . lines from the @xmath26c@xmath25 , @xmath26c@xmath27c and @xmath27c@xmath25 swan system ( kurucz 1998 ) were considered and from the phillips red system were predicted as in de laverny & gustafsson ( 1998 ) . the line lists for the @xmath28 and @xmath16 spectral domains were built in a similar way for the c@xmath25 and cn molecules , and atomic line data were found in vald ( piskunov et al . the broadening by radiation and van der waals damping were calculated as in de laverny & gustafsson ( 1998 ) . line data were adjusted as described in lbre et al . ( 1998 ) by comparison with the solar spectrum using the holweger & mller ( 1974 ) model atmosphere for the sun with element abundances from anders & grevesse ( 1989 ) . a good fit to the solar spectrum was obtained in the @xmath1 and @xmath16 spectral domains in @xmath29 around the corresponding li line . the fit , however , was not as good in the other two spectral ranges . indeed , in the @xmath14 and @xmath15 regions there are a number of unidentified features in the solar spectrum with a modest absorption ( @xmath30 m ) . most of these features could be atomic in nature because no such intense molecular absorptions are expected in the sun in these spectral ranges . however , we did not find any atomic lines in the data base of vald or of kurucz ( 1998 ) at the wavelengths of the missing features . nevertheless , we were able to obtain a good fit to the solar spectrum in at least 10 around the @xmath14 and @xmath15 li i features . thus , we do not believe this problem will introduce an additional source of error into the abundance of li derived from these two spectral domains . stellar parameters for the stars studied were taken from the literature when available . for wx cyg the effective temperature derived by ohnaka & tsuji ( 1996 ) from the infrared flux method ( irfm ) was adopted . for wz cas , effective temperature derived from the irfm and angular radii measurements ( dyck et al . 1996 ) agree quite well ( @xmath31 k ) . however , the value derived from these two methods ( 3150 k ) contrasts with that derived from infrared photometry ( @xmath32 k ; see noguchi et al . 1981 ; frogel et al . 1972 ) . we adopted here the value obtained by dyck et al . ( 1996 ) . for iy hya there is no estimate of its effective temperature nor its photometry is available in the literature . we estimated the effective temperature by comparing its spectrum with the temperature sequence spectral atlas for c - stars created by barnbaum et al . ( 1996 ) . from that comparison we believe that iy hya is a cool n - star and consequently , we adopted the lower effective temperature in our grid of atmosphere models i.e. : t@xmath33 k. the uncertainty in t@xmath34 is , however , no less than @xmath35 k ; it might well be larger for iy hya . note also that these stars are variable and we suspect variations as large as @xmath36 k during their cycle ( see richichi et al . the consideration of an unique effective temperature for these stars is therefore a strong assumption . a solar metallicity ( [ fe / h]=0.0 ) was considered for the three stars . most galactic c - stars are of population i with near solar metallicity although typically they show strong enhancements of heavy elements ( zr , ba , la etc ... )(utsumi 1985 ; dominy 1985 ) . we checked that there is no intense heavy element line close enough to the four li absorptions in our line lists that may affect the li abundance derivation . a study of the heavy element enhancements in the slir stars and other normal c - stars will be presented in a separate work . a gravity of log g@xmath37 and a microturbulence parameter of @xmath38 kms@xmath39 were adopted . these are typical values for c - stars ( see lambert et al . 1986 ) . concerning gravity , note that studies by pavlenko ( 1990 ) and magazz et al . ( 1992 ) on o - rich dwarfs , subgiants and giant stars showed no important sensitivity in the ratio of lte / nlte li abundances caused by changes in the gravity of @xmath40log g@xmath41 , especially in the case of strong lines . thus , uncertainties in gravity play a minor role in the formation of the lithium lines in c - rich atmospheres . radiative damping ( which does not depend on log g ) plays the main role in the formation of the wings of the saturated lithium lines . more serious seem to be the consequences of changes in the temperature structure of the atmosphere with decreasing gravity due to the increase in the effectiveness of sphericity effects . however , analysis of these effects lies beyond the scope of this paper . finally , a model atmosphere was interpolated in t@xmath34 and the c / o ratio for each star from an unpublished grid of models for c - stars ( eriksson et al . , private communication ) . these models are constructed under the basic hypotheses of hydrostatic equilibrium and plane - parallel approximation . the models include more complete opacity data of hcn and c@xmath25h@xmath25 ( in addition to diatomic molecules ) with the sampling treated by an opacity distribution function ( see eriksson et al . 1984 , for details ) . the final c / o ratio of the model atmosphere used in the spectral synthesis was obtained by an iterative procedure comparing synthetic and observed spectra until a good fit was obtained . li lines were not included in this procedure . however , the same c / o ratio was not found to give the best fit in the four spectral domains for a given star , although differences in the c / o ratio never exceeded a few hundredths . for instance , in the @xmath14 and @xmath15 regions we systematically derived a lower c / o ratio by @xmath42 hundredths . table 1 shows the log of the observations and the final stellar parameters used in the analysis . the quoted cno abundances are the mean values of those obtained from the best fit for each spectral domain ( n abundance plays a minor role ) . lithium abundances were derived by synthetic spectra * generated by using a modified version of code written at the uppsala astronomical observatory . the theoretical spectra were * convolved with the corresponding fwmh to match the instrumental profile in the four spectral domains following the procedure used in abia et al . ( 1993b ) . the carbon isotopic ratios ( @xmath26c/@xmath27c ) derived in abia & isern ( 1997 ) from spectral synthesis to the @xmath26cn and @xmath27cn lines in the @xmath43 spectral region were adopted ( see also abia & isern ( 1996 ) and de laverny & gustafsson ( 1998 ) , for details on the analysis and the choice of the cn parameters , respectively ) . table 1 shows the carbon isotopic ratio adopted in the stars . they are in fair agreement with those derived by ohnaka & tsuji ( 1996 ) and lambert et al . ( 1986 ) in wx cyg and wz cas . the total error due to stellar atmosphere parameter uncertainties , continuum placement and the fit itself amount to @xmath44 dex for li ( lte ) abundances and @xmath45 for the @xmath26c/@xmath27c ratio ( see references above ) . figures 1 and 2 ( solid lines ) show the behaviour with t@xmath34 and the c / o ratio of curves of growth calculated in lte for the four li absorptions . as can be clearly seen , subordinate lines are saturated for high li abundances ( log @xmath2(li)@xmath46 ) . for the resonance line , however , the li absorption increases more steeply with increasing li abundance . for very high li abundances ( log @xmath2(li)@xmath47 ) , the subordinate lines are not very sensitive to the effective temperature , the c / o ratio or gravity ( as mentioned before ) . this is a consequence of their saturated behaviour . the opposite occurs with the resonance line . this might lead us to consider the resonance line the better tool for abundance determinations in c - stars . however , the resonance line forms in the outermost layers ( see below ) where the atmosphere structure is quite uncertain in c - stars and the microturbulence may even become supersonic . we will also see that nlte effects are much larger for this transition . figures 3 to 6 show synthetic fits in lte to the different spectral domains in wz cas . synthetic spectra agree quite well with the observations for the @xmath1 and @xmath16 regions but this is not the case for the @xmath14 and @xmath15 ones . some of the discrepancy is certainly due to the missing features in our line lists as mentioned in 3.1 . moroever , in the @xmath14 and @xmath15 regions we obtain systematically larger residual fluxes than observed . this , by the way , means that the li abundances derived from the @xmath14 and @xmath15 li lines are systematically lower ( see table 3 ) than those derived from the red li lines . the same figure was found by de la reza & da silva ( 1995 ) studying the formation of li lines in k - giant stars . the reason for this is unknown . bad gf - values for c@xmath25 lines , which are numerous in these bluest spectral regions , might partially explain this problem . note that in these two spectral domains most of the c@xmath25 lines were taken from the data compilation by kurucz ( 1998 ) , which is probably not very accurate . note also that we were not able to check their gf values with the solar spectrum as mentioned above . the discrepancy between theoretical and observed fluxes is particularly evident in the @xmath04603 region . we confirmed that most of the strong absorptions in this spectral range are due to atomic lines while molecular lines contribute most to the background absorption . however , no reasonable reduction of the metallic abundances in the star can solve this discrepancy . therefore , we are led to believe that an incorrect figure for continuous opacity might be the main cause of this . the problem of the missing opacity in the blue has been widely discussed in the literature . recently there have been some new results in this sense . yakovina & pavlenko ( 1998 ) showed that to fit the head of the strong nh band @xmath48 at @xmath0336 nm in the spectrum of the sun , one should increase the continuum absorption coefficient in the region by a factor @xmath49 . recently , bell & balachandran ( 1998 ) increased @xmath50 to fit be ii lines at @xmath0313.0 nm in the solar spectrum . we tried to artificially simulate this missing opacity by increasing the h@xmath51 opacity by a free factor ( namely , increasing the electronic pressure by a factor @xmath52 ) . indeed , in this case theoretical residual fluxes are lower ( except for the very strong ( saturated ) lines ) and the agreement between observed and theoretical spectra improve . we preferred , nevertheless , to be coherent in our analysis in the four spectral domains and did not artificially change our set of conventional opacity sources . thus , we used the same model atmosphere for all the spectral ranges and decided , for that reason , not to consider li abundances derived from the @xmath04603 range . we will have to wait for the next generation of atmosphere models for c - stars to study this problem better ( plez et al . note that in principle sphericity effects should be more pronounced in the blue part of the spectrum because here the sensitivity to the temperature structure is higher even for strong spectroscopic features formed in the outer atmosphere . on the other hand , this discrepancy may be caused ( at least partially ) by the impact of dust opacity on the star s spectrum . indeed , the formation of dust in the atmosphere of agb stars and their envelopes has been known for a long time ( see references in wallerstein & knapp 1998 ) . dust particles can contribute to total opacity via scattering processes , i.e. with cross - sections @xmath53 . in that case the contribution of the dust opacity would increase to the blue . li - rich k - giants also show an red excess , probably caused by a dusty envelope ( although of a different nature ; de la reza & da silva 1995 ) . one may propose other explanations to explain this effect . for instance , the procedure used to place the continuum level in the observed spectrum still seems very subjective . to provide more balanced conclusions regarding this problem we suggest that a more detailed study of these regions should be carried out in several slir stars . ! to carry out the nlte analysis for a 20-level li atom model , we followed the procedure described in pavlenko ( 1994 ) and pavlenko & magazz ( 1996 ) . a few specific items were taken into account here : * ionization - dissociation equilibria were computed for the carbon - rich case , i.e. considering c - contained molecules formation : co , ch , cn , c@xmath25 , cs , hcn , h@xmath25c , h@xmath54c , h@xmath55c , hc@xmath25 , h@xmath25c@xmath25 and hc@xmath54 . * in the frequencies of bound - free transitions of li i the opacity of diatomic molecules was computed in the framework of just - overlapping - line approximation ( jola , see table 2 ) . * in the frequencies of bound - bound linearized transitions of li i the atomic absorption was included . furthermore , in the frequencies of the four li lines we considered the absorption of cn and c@xmath25 for a given @xmath26c/@xmath27c ratio ( see table 1 ) . the work most relevant to the present study was done by de la reza & querci ( 1978 ; thereafter rq ) . using a divergence flux method these authors carried out an extensive modelling of nlte effects of lithium lines in c - stars . they used a 4 level lithium atom model , atmosphere models by querci et al . ( 1974 ) and johnson ( 1974 ) with effective temperatures of 3800 , 3600 and 3500 k ( warmer than the t@xmath56 values usually derived in c - n stars ) , gravity log g@xmath57 , c / o@xmath58 and modelled three li i lines , namely the @xmath15 , @xmath1 and @xmath16 lines . they also tried to model the impact of a chromosphere on the formation of lithium lines using the approach of _ radiative temperature _ ( t@xmath59 ) on the bound - free transitions of lithium . several aspects in their nlte calculation differ from the present study : 1 . _ the atom model_. we used a 20-level atom model , which allowed us to consider the interlocking of lithium lines ( transitions ) more appropriately . the ionization equilibrium of lithium is formed by the whole system of the bound - free transitions . hovewer , as noted by rq ( see also pavlenko 1991 ) , transitions from / on the second level play the main role . 2 . _ bound - free transitions . _ the radiation field in bound - free transition computations is very important in the modelling of lithium lines without lte . indeed , the effectiveness of the overionization of lithium depends directly on the mean intensities of the radiation field in the blue part of the spectrum ( pavlenko 1991 ) . the approximation @xmath60 ( _ electronic temperature _ ) used by rq does not produce any overionization of lithium . only in the case of @xmath61 does the ionization of lithium increase with respect to the lte case . note that @xmath61 was considered by rq only when a chromospheric radiation field was included . as noted by these authors , this approximation seems to be rather crude for the radiation field . _ bound - bound transitions_. lithium lines were treated by rq as singlets . basically , radiation transfer in the frequencies of several multiplet lines should differ from the case one single ( strongest ) line . moreover , we include molecular line absorption in the continuous ( background ) opacity . in principle , this should reduce the probability of photon losses from the atmosphere , i.e. it directly affects the processes of radiative transfer . on the other hand , the radiative transfer in the continuum differs substantially from the case of continuum+lines in an atmosphere with chromosphere , as here the impact of the hot chromospheric layers on the photosphere might be weaker . * nlte computations were performed by using a modified version of the code wita2 ( pavlenko et al . 1995 ) described in pavlenko ( 1999 ) * dex ) . * ] . the dependence of the departure coefficients @xmath62 , where @xmath63 and n@xmath64 are the nlte and lte populations of the @xmath65 level , upon the depth in a typical c - star atmosphere is shown in fig . the behaviour of the departure coefficients of lower and upper lithium levels differ substantially . the populations of the lower levels are reduced by the overionization processes . on the contrary , upper levels are overpopulated relative to the lte case because they are more closely linked with the continuum ( see also pavlenko 1994 , carlsson et al . 1994 , pavlenko & magazzu 1996 ) . indeed , for log @xmath2(li)@xmath66 4.0 the departure coefficients of the first level become very low in the outermost layers ( @xmath67 at p@xmath68 ) , where the nlte core of the li resonance line forms . on the other hand , the depth of formation of lithium resonance and subordinate lines is quite different . for large lithium abundances ( log @xmath2(li)@xmath69 ) the formation region for the resonance line shifts toward the outermost layers , where the temperature drops below 1000 k. in fact , we have to extrapolate the model atmosphere structure to log p@xmath70 to take the line formation consistently into account . this produces additional problems in the computation of collisional and radiative rates . here we are approaching the interstellar medium regime , where our approximations for collisional and radiative rates may not be valid . moroever , in this regime the splitting of li terms into sublevels may also become inportant although , since we are dealing with saturated lines , we believe that this effect is not critical . lithium subordinate lines are formed in deeper layers . for instance , even for log @xmath2(li)@xmath71 the core of the @xmath15 doublet forms in a region with temperature @xmath72 k. as a consequence , the nlte formation regime of this li line changes dramatically : the interlocking processes of radiative transitions ( see magazz et al . 1992 ; carlsson et al . 1994 ) become more important than overionization . in this situation , line profiles depend on the behaviour of the source function which is affected by the whole set of radiative transitions . in brief , considering the formation of lines in the outermost layers we note : i ) the opacity here drops sharply due to the low molecular and h@xmath73 density , ii ) the electron density is low and its effect on collision rates is small and iii ) the electron temperature is also low , so that the effectiveness of the overionization @xmath74 would be high . figures 1 and 2 ( dashed lines ) also show theoretical nlte curves of growth for the four li lines . departures from lte are very important for the resonance @xmath1 line . nlte corrections for this line can amount to 0.6 dex ! however , nlte effects for the subordinate lines are weak ( @xmath75 dex ) and even decrease for strong li absorptions ( high li abundances , log @xmath2(li)@xmath76 ) . we also see from these figures that nlte effects decrease for decreasing and increasing c / o ratio in the model atmosphere . when drops the opacity of the carbon - contained molecules increases so that the difference between t@xmath59 ( of the radiation field in the bound - free frequencies of li ) and t@xmath77 decreases . the same holds when the c / o ratio increases in the atmosphere . it is interesting to note that lte / nlte abundances converge for high li abundances for the subordinate lines whatever the and/or the c / o ratio in the atmosphere . this gives us a chance to use subordinate lines as a tool for deriving li abundances in li - rich agb stars even in the lte approach , despite their saturated nature . figures 3 to 6 show synthetic fits in nlte ( only for li lines ; i.e. dashed lines ) in our stars . the difference between the lte / nlte fits to the resonance line is remarkable . for the subordinate lines , lte and nlte fits differ only slightly . table 3 shows the final nlte li abundances derived in our stars . nlte corrections are always positive , ranging from 0.1 to 0.5 dex . as was shown by magazz et al . ( 1992 ) for the case of g - m stars with solar abundances , the significance of nlte effects depends upon the line strength . li lines of moderate intensity ( w@xmath78 ) form in a region where s@xmath79 . the nlte cores of the resonance doublet become stronger than the lte ones and , as a result , nlte abundance corrections @xmath40log @xmath2(li)@xmath80log @xmath2(li)@xmath81log @xmath2(li)@xmath82 are negative . however , in the case of the strongest ( saturated ) li resonance doublets the difference between lte and nlte cores can not be large ( because both approach to zero ) then , nlte corrections again become positive as in the case of weak lines . note that there is a region in the atmosphere where @xmath83 holds for all except the @xmath14 line ( fig . 8) in the case of intermediate strong lines ( log @xmath2(li)@xmath84 ) . in these regions the interlocking processes of li radiative transitions play the main role . we now compare our lte / nlte results with the literature . abia et al . ( 1991 ) derived li abundances in the same stars using the @xmath1 li line . the abundances obtained here are considerably lower . in wz cas and wx cyg the differences can be ascribed to the different choice of and the c / o ratio in the model atmosphere but also to the more complete molecular line list used in this work , which makes the background absorption more intense in the @xmath1 region . note that abia et al . ( 1991 ) did not include the c@xmath25 molecule ( in any isotopic form ) or the @xmath27cn molecule in their line list . in iy hya , moroever , the spectrum now analyzed in the @xmath1 range shows a much less intense li line than that from which the li abundance was derived by these authors : w@xmath85 here against 7.5 in abia et al . a similar variation in time might be present in the spectrum of wx cyg analyzed here ( 4.5 vs. 6.5 ) . whether this variation is an effect of a varying along the pulsational phase or just evidence of the time scale for li formation / depletion in agb stars is a question which merits further studies . note that asplund et al . ( 1999 ) found the same figure in a post - agb star and they concluded that they were observing the characteristic time scale of the mechanism responsible for the lithium production . qualitatively our nlte results agree with rq but quantitatively some discrepancies are found . * for instance , inspection to their fig . 7 shows a nlte correction by @xmath86 dex at log @xmath2(li)@xmath87 for the @xmath88 line . however , our computations give a correction of @xmath89 dex ( see fig . 2)*. this can be easily explained by differences in the nlte procedure , model atmospheres etc . * namely * , in this paper we fully computed the opacities in the bound - free and bound - bound lithium transitions . this allowed us to establish the dependence of nlte in lithium lines on c / o and the @xmath26c/@xmath27c isotopic ratio . moreover , the analysis of rq was based on the comparison between the lte and nlte curves of growths . our lte / nlte spectral synthesis approach to determine li abundances in the atmosphere of li - rich agb stars seems to be better . only in this way is the lithium abundance determination possible , since the conventional definition of the equivalent width becomes meaningless due to the severe blending of li lines . in this sense our results for subordinate li lines are of great interest . since we underestimate the opacity of the bound - free and bound - bound transitions of lithium we get an upper limit to the nlte effects in these lines , but comparatively , we obtain low nlte corrections on li abundances . using a more complete opacity source list , nlte effects should be even less pronounced . that would comprise a good chance to obtain accurate abundance determinations based on the subordinate li lines in the frame of the lte approach , which is simpler and therefore more useful . * on the other hand , we can only qualitatively compare our nlte results with those by pavlenko & magazz ( 1996 ) in m ( o - rich ) stars due to the obvious differences in opacities , model atmospheres etc , although in both cases , strong li resonance lines are formed in the outermost layers of the atmosphere . their curves of growth ( see their fig . 5 ) show a similar behaviour than ours ( figs . 1 - 2 ) : for the @xmath88 line w@xmath90 w@xmath91 for log @xmath2(li)@xmath92 ; i.e. , in the case of strong lines formed high enough in the atmosphere nlte effects reduce the equivalent width due to the dominant role of the overionization . for the @xmath93 li line they found w@xmath94w@xmath91 for log @xmath2(li)@xmath95 ( see their fig . however , we obtain the contrary . this can be explained since in our case ( c - rich atmospheres ) the overionization should increase in the line - forming regions due to the drop of the density and pressure . * abia et al . ( 1993a ) computed an empirical li yield from a homogeneous sample of galactic c - stars . they derived li abundances from the @xmath1 line in @xmath96 c - stars and by considering the mass - loss rate estimates for the stars in their study , obtained a li yield into the interstellar medium of @xmath97 m@xmath98pc@xmath99gyr@xmath39 . these authors showed that this yield is extremely dependent on the stellar mass - loss rate assumed and on the real li abundance in the star . since approximately 90% of this value is determined by the actual yield from the slir c - stars , it is straightforward to revise this figure on the basis of the more accurate li abundances obtained in this work . now , considering the nlte abundances obtained from the @xmath16 li line as the best estimate of the lithium abundance , we obtain the revised yield of @xmath100 m@xmath98pc@xmath99gyr@xmath39 , a factor @xmath84 lower than the previous value . this is mainly because the revised li abundances in wx cyg and iy hya are considerably lower . as in abia ( 1993a ) , we can roughly estimate the contribution of c - stars to the galactic li . assume that the above production rate has been constant during the lifetime of the galaxy ( @xmath101 gyr ) and that the surface density of c - stars has been uniform and also constant during this time within a galactocentric radius of @xmath102 kpc ( @xmath29 c - stars kpc@xmath99 , see claussen et al . 1987 ) . in this case , the total contribution to galactic li abundance by c - stars is m@xmath103 m@xmath98 , i.e. @xmath104 of the total li in the galaxy . this contribution might be higher if evolutionary effects are taken into account , since the star formation rate was certainly higher in the past . correspondingly , the number of c - stars that eventually became a slir c - star at a given time was also higher ( see abia et al 1993a for details ) . \1 . the formation of the lithium resonance line in c - stars is severely affected by nlte effects . nlte li abundances are higher and can differ from the lte ones up to 0.6 dex . the core of this strong li line is formed in the outermost layers where we approach the interstellar medium regime . furthermore , these layers are affected by different phenomena such as the stellar chromosphere , inhomogeneities , dusty shells , outflow / infall velocities etc . our computations also show that lithium is severely overionized . therefore , the use of this saturated lithium line for abundance determinations in agb stars seems quite impossible . in that sense , we confirm the results of rq . \2 . subordinate lithium lines are formed in the inner parts of the atmosphere . we have shown that nlte effects are rather weak even for strong lines ( 0.1 - 0.3 dex ) . thus , they may be used for lithium abundance determinations in agb stars even in the framework of the lte approach . of the three subordinate lines , the @xmath16 li i line is probably the best one for li abundance determinations because it is less blended , because nlte effects are weak , because the molecular and atomic line list appears to be complete and because continuous opacity seems rather well reproduced in this spectral domain . nlte effects in the lithium lines show a complicated dependence on the input parameters and the c / o ratio . we found that nlte effects increase with increasing and a decreasing c / o ratio . for a given , nlte effects decrease with increasing li abundance for the subordinate lines but increase for the resonance line . furthermore , for high li abundances ( log @xmath2(li)@xmath47 ) lte / nlte abundances from the subordinate lines are not very sensitive to or the c / o ratio . for the resonance line , however , the opposite happens . the possibility of using the lithium subordinate doublet at @xmath04603 was considered . theoretical spectra , however , show a bad agreement with the observations , probably due to a wrong estimate of the continuous opacity in this spectral range and to an incomplete line list in this region . furthermore , this lithium line forms a strong blend with iron lines . due to the very weak nlte corrections found for it , the use of this li doublet would be promising in the case of metal deficient stars if using very high resolution spectra . since we are confident of the atomic and molecular line list used beyond @xmath105 , we suggest that the c@xmath25 lines of the swan system observed in the blue part of the spectrum are the largest source of error . more accurate line lists for these transitions are therefore needed . such an improvement , together with better atmosphere modelling , solving the problem of the missing continuous opacity in the blue part of the spectrum , should improve the agreement between observed and synthetic spectra in the future . we have used observational data of high quality to determine lithium abundances in three c - stars : wx cyg , wz cas and iy hya . we have shown , that they are indeed slir stars with li abundances in the range log @xmath2(li)@xmath106 to 5 . however , up to now we have still failed to accurately determine li abundances in agb stars , mainly due to uncertainties in modelling their atmosphere . this leads to an important uncertainty concerning the estimate of the li yield by agb stars . these stars might account for up to 30@xmath107 of the currently observed li or merely be a secondary source of li in the galaxy . patrick de laverny acknowledges support from the _ socit de secours des amis des sciences_. data from the vald data base at vienna , austria , were used for the preparation of this paper . k. eriksson and the stellar atmosphere group of the uppsala observatory are thanked for providing the grid of model atmospheres . the 4.2 m wht is operated on the island of la palma by the rgo in the spanish observatorio del roque de los muchachos of the instituto de astrofsica de canarias . based in part on observations collected at the german - 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the formation of lithium lines in the atmosphere of c - rich giants is discussed . lte and nlte approximations are used to model lithium lines in the spectra of super li - rich agb stars . the system of equations of the statistical balance of neutral li in plane - parallel model atmospheres is solved for a 20-level atom model . jola and line - by - line models of molecular absorption are used to compute synthetic spectra as well as the opacity in the frequencies of bound - bound and bound - free transitions of the lithium lines . curves of growth and synthetic spectra are computed in lte and nlte for several model atmospheres of different and c / o ratios for four lithium absorptions , namely : the @xmath04603 , @xmath06104 , @xmath06708 and @xmath08126 li i lines . the sensitivity of nlte effects on and the c / o ratio is discussed . we found that nlte mainly affects the resonance line doublet ( @xmath1 ) while the impact of nlte effects on the lithium subordinate lines , formed in the inner regions of c - rich giant atmospheres , is rather weak . therefore the use of these lines is recommended for li determination in agb stars . however , in no case can we properly account for the formation of li lines in agb stars until sphericity , velocity stratifications , dust , chromospheres and other related phenomena , which are in fact present in agb star atmospheres , are considered . our results are used to derive li abundances in three super - li rich c - stars taking into account nlte effects . finally , the net li yield from this class of stars into the interstellar medium is reconsidered .

one of the most essential components of the evaluation programs on children 's health status is investigation of their developmental skills . nowadays , social changes , advancements in medical sciences , burdensome economic condition , and disabling changes in the families have resulted in occurrence of behavioral , social , and educational problems in children , which can have a negative effect on their development and lead to challenges in their childhood and adolescence period . there is no accurate estimation about the prevalence of developmental disorders in the general population of iranian children . but few studies conducted in this context show a relatively high prevalence of these disorders among the children . one of the most appropriate childhood periods to investigate developmental skills is between 36 and 60 months of age . during this period , the child has a rapid pace of development in physical , motor , cognitive , verbal , and socio - psychological skills . absence of such an important information resource for determination of children developmental status results in a defective assessment . numerous studies have recently shown that parents can yield accurate information about their children 's developmental status , regardless of their different socio - economic status , geographical location of residence , or even their level of education . a study conducted in boston in 2009 showed that routine use of parents information in assessment of children 's developmental status can facilitate early diagnosis of their developmental disorders , as the afore - mentioned study led to detection of 61.6% of these children with developmental disorders . parents participation in these assessments also yields valuable information about their children 's development and , therefore , helps them have relevant and logical expectations from their children . in addition , with regard to the high costs of children 's developmental status assessments conducted by the specialists , completion of the developmental skills questionnaire to assess large groups of children in the initial stages of assessment is more cost effective . the american academy of pediatrics recommends assessment of developmental skills in health care centers from the first week of life and at ages of 2 weeks , 2 , 4 , 6 , 9 , 12 , 15 , and 18 months , 2 , 2.5 , and 3 years , and once a year until the age of 6 years , and every 2 years between 6 years of age and adolescence period for all children . in iran , assessment of growth and development is conducted in health care centers by health aids in rural areas and by technicians or bachelors of health in urban areas . in the series of assessments that continue until the age of 8 years , the children are routinely assessed concerning their weight gain and height , but are less assessed with regard to their developmental trend . therefore , a delayed development in children is diagnosed at higher ages ( entrance to primary school ) in iran compared to other countries . the researcher has witnessed inadequate attention paid to children 's developmental skills during her attendance in health care houses , health care centers , and daycare centers in isfahan . therefore , with regard to irrecoverable complications of delayed assessment of children 's developmental skills at different ages , this study aimed to determine the developmental skills of 36 - 60-month - old children in isfahan daycare centers . firstly , the list of all daycare centers in 14 districts in isfahan ( based on municipal categorization ) was obtained from the isfahan province welfare office , and a daycare center was selected through convenient random sampling from each district . the name list of children aged 36 - 60 months was extracted from the selected daycare center , and 14 children were selected from the extracted list as the subjects in each daycare center . inclusion criteria were children with iranian nationality , born and residing in isfahan , living with their biological parents , no chronic diseases in children or parents , and the parents who voluntarily accepted for their children 's participation in the study . the number of the subjects was calculated as 196 children by the following formula and with a confidence interval of 1.96 , power of 0.84 , and d = 0.25 : finally , from each municipal district , one daycare center was selected , and from each daycare center , 14 children meeting the inclusion criteria were selected . one of the researchers attended the daycare center , introduced herself to the manager , and then met the parents and gave them enough explanations about the research goals during an orientation session . the researcher ensured the parents about the confidentiality of their children 's data , and after the parents signed a written consent form , they were explained how to complete the questionnaires and were asked to return the completed questionnaires to the daycare manager within 2 - 3 days . the data collection tools were a demographic information questionnaire and the third version of ages and stages questionnaire . this ( each ) questionnaire has been prepared for developmental skills assessment at a specific age rank , so insufficient knowledge of parents about the normal pattern of child development could not leads to their miss judgment . therefore , most of the researches who intend to investigate children 's developmental skills through their parents reports use this questionnaire . this test includes 19 questionnaires for 19 different age groups ( 4 , 6 , 8 , 10 , 12 , 14 , 16 , 18 , 20 , 22 , 24 , 27 , 30 , 33 , 36 , 42 , 48 , 54 , and 60 months ) and is completed by the parents . in the present study , the questionnaires specific for the age groups of 36 , 42 , 48 , 54 , and 60 months were used . for instance , the questionnaire for the age of 36 months can be used for children aged 35 - 37 months . each questionnaire contains 30 questions in five domains : communications , gross motor , fine motor , problem solving , and personal - social ( each domain contains six questions ) . yes indicates the child can thoroughly do the activity , not yet indicates the child has not done the activity yet , and the response yes is scored 10 points , sometimes is scored 5 points , and the response no is scored zero . the total score is separately calculated for each domain and is compared with the cut - off point related to that domain and in the same age group ( scores in each domain range 0 - 60 points ) . if the score of each developmental domain is less than or equal to the related cut - off point , it shows that the child probably has delayed development and needs to refer for more evaluation and follow - up . the questionnaire has been designed in a way that the people with even primary school education can understand the items well . the questionnaire of ages and stages is an internationally valid tool with a sensitivity of 82 - 89% and specificity of 77 - 92% . in iran , translation , equalization , and standardization of the questionnaire were conducted in 2002 and 2008 under the supervision of ministry of health , treatment and medical education , unisef , exceptional child education and training organization , population and family health office , and exceptional child research center . its validity , reliability , and power of test for diagnosis of developmental disorder were reported to be 0.84 , 0.94 , and over 96% , respectively . in addition , a study was conducted in tehran in 2006 with the goal of standardization and validation of ages and stages questionnaire and the cronbach 's alpha was calculated to be 0.79 , showing its scientific reliability . after collection of the completed questionnaires , the related score for each child was calculated by one of the researchers . data were analyzed by descriptive statistical methods . cut - off points for each developmental domain based on age groups scientific and ethical considerations of this study has been approved by isfahan university of medical sciences . scientific and ethical considerations of this study has been approved by isfahan university of medical sciences . in this study , 103 male ( 52.6% ) and 93 female ( 47.4% ) children ( out of total number of 196 subjects ) participated . 29.6% of the children were in the age group 59 - 61 months , 24.5% in the age group 53 - 55 months , 18.9% in the age group 47 - 49 months , 16.3% in the age group 41 - 43 months , and 10.7% were in the age group 35 - 37 months . mean age of entering a daycare center was 38.06 ( sd = 11.85 ) months and mean hours of attendance in the daycare center was 4.4 ( sd = 1.3 ) h / day . 58.6% and 50.5% of the subjects fathers and mothers had a university educational degree , respectively . most of the subjects ( 91.2% ) had normal birth weight ( 2500 - 4000 g ) . the obtained results showed that in making communication , gross motor , fine motor , problem solving , and personal social domains , 1.5% , 3.1% , 7.7% , 7.7% , and 2% of the children scored below or equal to the cut - off point . the highest frequency was for delays in development in the domains of fine motor and problem solving [ table 2 ] . distribution of subjects scores based on cut - off points in different developmental domains mean and statistical indices of subjects different developmental domains scores the obtained results showed that some of the subjects had obtained scores lower than or equal to the cut - off points in all developmental domains and needed a follow - up . this was more frequent in fine motor and problem - solving domains , compared to others . in the study of kerstjens et al . on 544 dutch children aged 46 months , the subjects needed a follow - up in all domains , especially in gross motor . in the study of nelson et al . on 1171 children aged 36 - 60 months among the general population and in the study of troude et al . on 179 children aged 36 months among the general population , some of the subjects obtained scores less than or equal to the cut - off point and needed a follow - up , especially in fine motor domain . the frequency distribution of children with developmental delay in the present study was different from the above - mentioned studies in gross motor , fine motor , and personal - social domains ( either higher or lesser ) . cultural differences including methods of child breeding , parental style , families socio - economic status , etc . meanwhile , in the domain of making communication , the number of the studied children in isfahan who needed follow - up was less than that in all the afore - mentioned countries , and in the domain of problem solving , it was more . different sample sizes and subjects characteristics in the above - mentioned studies and in the present study may have played a role in the observed difference . dorre et al . , in a study on 114 children aged 4 - 60 months with a history of hospitalization in neonatal intensive care unit ( nicu ) in arak , iran , used ages and stages questionnaire and showed that making communication was the most frequent developmental disorder among subjects . a lower percentage of children needed follow - up in all developmental domains in the present study compared to dorre et al . ali akbari et al . , in an investigation on the correlation between high - risk pregnancy with developmental retardation in 356 children of age 4 - 60 months in isfahan , showed that the subjects had major problems in fine motor and gross motor domains . but in the present study , the subjects needed a follow - up in fine motor and gross motor domains . comparison of the present study with the other studies conducted in iran also showed a different prevalence in developmental retardation among the children . comparison of the mean developmental scores of the subjects in the present study with those of kerstjens et al . 's study shows that the mean scores in the domains of communication , gross motor , and fine motor were higher in the present study compared to their study , although they were lower in problem - solving domain and equal in personal - social domain . a reason for this difference can be the different characteristics of the subjects , as in kerstjens et al . 's study , 72.9% of the subjects ( 1510 out of 2072 ) had a history of being pre - term , but in the present study , mothers were unaware of their children 's history of being pre - term and 6% ( n = 13 ) of the subjects had birth weight lower than 2500 g. as the history of prematurity and low birth weight can negatively affect the trend of development , it can be the reason for lower score of children 's development obtained in kerstjens et al . 's study , compared to the present study . on the other hand , in the present study , 58.6% of the mothers had university education , whereas 28.5% of the mothers had university education in kerstjens et al . as the mothers level of education can affect their understanding of the questionnaire items or their accountability in giving responses to the questions , it can be a reason for the different results obtained in these two studies , although cultural differences and their effects should not be ignored . the obtained results showed that the children needed developmental follow - up mostly in fine motor , problem - solving , and gross motor domains . therefore , the health care centers staff should pay a close attention to this issue and teach families the related developmental skills , especially in these domains . the developmental status of the children in different age groups should be regularly monitored , as timely diagnosis of developmental problems and initiation of proper treatment can prevent many of the disabilities occurring to these children in future .

background : assessment of developmental skills is one of the most essential components of children 's health evaluation . since several pubertal disorders are caused by parental negligence in diagnosis , prevention , and treatment of childhood problems , failure to make a timely diagnosis of these problems could have adverse effects on the health of children in future . this study was conducted to determine the developmental skills of 36 - 60-month - old children in isfahan.materials and methods : in this cross - sectional study , 196 children , aged 36 - 60 months , were recruited through random cluster sampling . ages and stages questionnaire was filled for each subject by their parents ( father , mother , or both ) , and the frequency of developmental delay was determined based on cut - off points . the data were analyzed by descriptive statistics using spss 20.0.results:about 52.6% of the children were male . mean age of the children was 50.71 ( sd = 8.16 ) months . the abnormal findings were in the five domains of communication ( 1.5% ) , gross motor ( 3.1% ) , fine motor ( 7.7% ) , problem solving ( 7.7% ) and personal - social ( 2%).conclusions : the results suggest that some of the children had scores below or equal to the cut - off points and needed more evaluation by a professional person . the domains in which the children had problems were fine motor , problem solving , and gross motor . therefore , health staff should pay more attention to assessment of these domains and parents should be trained to develop their children 's skills in these domains .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Family Notification of Death in Custody or Life-Threatening Emergency Act of 2017'' or the ``Wakiesha's Law''. SEC. 2. PURPOSE. To encourage State, local and tribal jurisdictions to implement and enforce appropriate and time-sensitive procedures to notify the next- of-kin or designated person upon the death or life-threatening emergency of an individual who is in the custody of law enforcement. SEC. 3. COMPLIANCE AND INELIGIBILITY. (a) Compliance.-- (1) Federal law enforcement agencies.--Each Federal law enforcement agency shall take such actions as may be necessary to ensure compliance with the requirements of sections 4 and 5. (2) States and localities.--For purposes of this section, a State or unit of local government is a noncompliant jurisdiction if that State or unit of local government does not establish, implement, or enforce a law, policy, or procedure to ensure compliance with the requirements of sections 4 and 5. (b) Reduction of Grant Funds.--For each fiscal year beginning after the date of enactment of this Act, a State shall be subject to a 10- percent reduction of the funds that would otherwise be allocated for the fiscal year to the State under subpart 1 of part E of title I of the Omnibus Crime Control and Safe Streets Act of 1968 (42 U.S.C. 3750 et seq.), whether characterized as the Edward Byrne Memorial State and Local Law Enforcement Assistance Programs, the Local Government Law Enforcement Block Grants Program, the Edward Byrne Memorial Justice Assistance Grant Program, or otherwise, if during the prior fiscal year-- (1) the State was a noncompliant jurisdiction; or (2) a unit of local government was a noncompliant jurisdiction. (c) Reallocation of Funds.--Amounts not allocated accordingly to a State for failure to fully comply with this Act shall be reallocated under that program to States that have complied with this Act. SEC. 4. INFORMATION REQUIRED UPON ARREST OR DETENTION. (a) In General.--In the case of an individual taken into the custody of a law enforcement agency, the agency shall, at the time of taking custody, including during an arrest, during or prior to booking or intake screening as a new commitment, in transfer from another institution, as a court return, as a return from a writ, or as a holdover, obtain basic identification information for the individual, including his or her name, date of birth, and last known address, as well as ensuring that the information is accurate and complete. The individual may not be placed into any correctional institution prior to the acquisition and confirmation of such information. (b) Emergency Notification Information.--The receiving institution or agency shall also obtain the name, relationship, and contact information, including mailing address and one or more phone numbers, of at least one person or next-of-kin to be notified in case of death or emergency. In all instances where counsel has entered appearance on the record as a representative for the individual, the attorney listed shall by default be listed as the designated emergency contact. The attorney contact shall be provided in addition to the contact or contacts provided by the individual. (c) No Use in Proceedings.--Under no circumstances may any information obtained for the purpose of identifying a next-of-kin or designated emergency contact be used in any criminal, civil or investigative proceeding against the individual. SEC. 5. NOTIFICATION BY LAW ENFORCEMENT OF FAMILY WITH REGARD TO DEATH OR LIFE-THREATENING EMERGENCY OCCURRING TO INDIVIDUAL IN CUSTODY. (a) Death Notification Minimum Standards.--In the case of an individual who dies while in the custody of a law enforcement agency: (1) Written notification plan.--A law enforcement agency shall have a written notification plan in place identifying all designated staff members who are authorized, trained and prepared to deliver notification of death to the next-of-kin or designated contact in a professional and compassionate manner. (2) Timeframe for notification.--In the event an individual dies while in the custody of law enforcement, such notification shall be delivered not later than 3 hours after the declaration of death. (3) Manner of notification.--To minimize confusion and trauma suffered by the family or designated contact of the deceased, reasonable efforts may be taken when practical to ensure that notification is provided in-person and in a private setting. (4) Information required.--Such notification shall include the official time of death, the cause of death (if determined) and all pertinent circumstances surrounding the death, including whether the individual's death is under investigation and the reason for opening an investigation. (5) Documentation of attempts.--All notification attempts shall be documented and maintained within the custodial record, including-- (A) the staff name and corresponding agency or department contact information for all those responsible for carrying out the notification; (B) the date and time of successful and unsuccessful contacts; (C) the names and contacts to which attempts were made, and any reason for failed or unsuccessful contact; and (D) any incidents of unclaimed or rejected claims for the body or property of the deceased, including a detailed description of where any unclaimed bodies and property have been disposed of. (b) Autopsy Notifications.--In the case of an individual who dies while in the custody of a law enforcement agency, if an autopsy of that individual is required: (1) Notification.--The next-of-kin or designated contacts shall be informed immediately upon any determination that an autopsy shall be performed, and such notification shall include the reason that the autopsy is being performed. (2) Results reported.--A copy of the autopsy report and results shall be made available to the next-of-kin or designated contact immediately upon completion. (3) Independent autopsy.--The State and the next of kin shall have the opportunity to perform a separate autopsy. (c) Life-Threatening Emergency Notification Minimum Standards.--In the case of any life-threatening event occurring to an individual in the custody of a law enforcement agency: (1) Written notification plan.--A law enforcement agency shall have a written notification plan in place identifying all designated staff members who are authorized, trained and prepared to deliver notification of a life-threatening event to the next-of-kin or designated contact in a professional and compassionate manner. (2) Timeframe for notification.--Notice to the designated emergency contact shall be made as soon as practicable after the life-threatening event occurs, and, where practicable without delaying treatment, prior to any required medical procedure, but in any event, not later than any medical discharge or clearance. (3) Manner of notification.--To minimize confusion and trauma suffered by the family or designated contact of the individual who has suffered a life-threatening event, reasonable efforts may be taken when practical to ensure that notification is made in-person and in a private setting. (4) Information required.--Such notification shall include details of the life-threatening event, including-- (A) whether the individual is incapacitated, unconscious, or unable to speak; (B) the cause and nature of the life-threatening event; (C) whether any medical procedures or life-saving measures were performed in response to the life- threatening event; and (D) whether any medical followup is recommended and the nature of the recommended followup. (5) Documentation of attempts.--All notification attempts shall be documented and maintained within the custodial record, including-- (A) the staff name and corresponding agency or department contact information for all those responsible for carrying out the notification; (B) the date and time of successful and unsuccessful contacts; and (C) the names and contacts to which attempts were made, and any reason for failed or unsuccessful contact. SEC. 6. REPORT TO ATTORNEY GENERAL. Section 2(b) of the Death in Custody Reporting Act of 2013 (42 U.S.C. 13727(b)) is amended-- (1) in paragraph (3), by striking ``and'' at the end; (2) in paragraph (4), by striking the period at the end and inserting a semicolon; and (3) by inserting after paragraph (4) the following: ``(5) the date and time notification of death was provided to the next of kin or designated contact; ``(6) the date and time of each unsuccessful notification attempt was made; and ``(7) a detailed description of where any unclaimed bodies and property have been disposed of, including the amount of time lapsed prior to taking such action.''. SEC. 7. DEFINITIONS. In this Act: (1) In custody of a law enforcement agency.--The term ``in the custody of a law enforcement agency'' means, with regard to an individual, that the individual is detained, under arrest, or is in the process of being arrested, is en route to be incarcerated, or is incarcerated at a municipal or county jail, State prison, State-run boot camp prison, boot camp prison that is contracted out by the State, any State or local contract facility, or other local, tribal or State correctional facility, including a juvenile facility or a medical or mental health facility. (2) Custodial record.--The term ``custodial record'' means the central file of an individual in custody. (3) Juvenile facility.--The term ``juvenile facility'' includes juvenile or youth detention center, placement facility, group home or other State, private or contracted unit maintaining the custody of a youth under court order or law enforcement action. (4) Life-threatening.--The term ``life-threatening event'' means a medical event, episode, condition, or accident-- (A) where, without immediate treatment for the condition, death is eminent; (B) where hospitalization is required because of a serious, life-threatening medical or surgical condition that requires immediate treatment; or (C) where an individual is unconscious or incapacitated such that they are incapable of providing consent for medical treatment.

Family Notification of Death in Custody or Life-Threatening Emergency Act of 2017 or Wakiesha's Law This bill requires federal, state, and local law enforcement agencies to obtain identifying information about an individual in custody and contact information for the individual's next of kin or designated emergency contact. It establishes minimum standards with respect to notifying the next of kin or designated emergency contact following an individual's death or life-threatening emergency while in custody. The Department of Justice must reduce by 10% the allocation of funds under the Edward Byrne Memorial Justice Assistance Grant program for a state or local government that fails to comply. The bill also amends the Death in Custody Reporting Act of 2013 to require a state or federal law enforcement agency to include, in its quarterly report on deaths in custody, additional information such as the date and time that death notification was provided and the date and time of each unsuccessful notification attempt.

periodontitis is a common , multi - factorial disease , primarily caused by microbial plaque . in the presence of periodontal disease , bleeding on probing indicates bacterial plaque , which in turn , causes inflammation and ulceration in the epithelial lining wall of the pocket . based on epidemiological findings , chronic periodontitis is the most prevalent form of periodontal disease which , if left untreated , will cause irreversible bone loss . periodontal pockets are chronic inflammatory lesions , which constantly undergo repair and destruction . thorough healing can not be completed due to the remained bacterial plaque and persistent inflammatory response as well as subsequent degeneration . the final outcome is brought about as a result of the interplay between destruction and construction . what tips the balance in favor of the latter includes infection eradication , inflammation relief and wound healing . a relatively new agent for accelerating wound healing , phenytoin ( pht ) has already been used as an anticonvulsant drug since 1938.[5 - 6 ] a common side - effect , gingival hyperplasia , reported in as many as 50% of patients on long - term phenytoin therapy.[6 - 11 ] deeply inspired , shapiro initially assessed the potential effects of oral phenytoin on periodontal wound healing in 1958 with favorable outcomes.[5 - 7,12 - 15]this also motivated other research investigating potential effects in burns , trauma , leprosy,[15 - 17 ] aphthous stomatitis , diabetes , and lichen planus . pht supposedly contributes to healing via modulating cellular immunity as well as hindering white blood cells ( wbc ) migration . it may also indirectly stimulate proliferation and migration of fibroblasts through the expression of growth factor genes , namely platelet - derived growth factor ( pdgf ) from macrophages and monocytes . the drug is also claimed to trigger collagen fibers maturation , promote collagen deposition and enhance angiogenesis.[6,9,20 - 21 ] other desired effects regard edema reduction22 by decreasing both exudate and transudate.8,16,20 the antibacterial feature is still subject to controversy , yet the drug s potential effect in curtailing infection seems to be owing to enhanced blood flow as a result of the stimulus the pharmaceutical agent creates for angiogenesis . it is also claimed that pht stabilizes neural fiber membranes , thus contributes in topical pain relief . there has also been research on the role of phenytoin in improving periodontal parameters as well as healing process in the extraction socket . the previous investigators almost all applied topical phenytoin but in different forms : mouthwash , suspension , gel and mucoadhesive paste . in this study , we primarily intended to investigate the effect of topical phenytoin use on periodontal indices . this was a double - blind , randomized , split - mouth controlled clinical study , conducted on 40 dental sites of twenty patients , five men and fifteen women , with a mean age of ( 36.212.2 ) years , diagnosed with moderate to severe chronic periodontitis . patients had all been referred to the department of periodontology , shahid sadoughi university of medical sciences , yazd , iran , from may to september 2014 . the irct ( iranian registry of clinical trials ) code for this study was 201408171883 4n1 . patients were included if they were nonsmokers , without any history of traumatic occlusion and systemic conditions namely diabetes and heart diseases . as for their drug history , they should not take antihyperte - nsive , immune suppressants and anticonvulsants , which would have affected their periodontium . they all had at least two contra - lateral teeth with similar conditions ( number of roots , without furcation involvement and similar pocket depth ) on posterior sextants , with no decay and restorations . all patients signed the informed consent form when an internist was consulted for medical assessment and possible drug interactions . demographic data was provided via having patients filled a questionnaire whereas the rest was collected throughout oral examinations . periodontal pocket depth ( ppd ) , the distance from the gingival margin to the base of the probable crevice , was measured along six areas for each tooth ( mesiobuccal , midbuccal , distobuccal , distolingual , midlingual and mesiolingual ) using a william s periodontal probe . bleeding on probing ( bop ) , sites which bled 30 to 60 seconds after probing in percentage terms , as well as modified gingival index ( mgi ) were also recorded . one clinician was assigned to carry out clinical measurements as described , both prior to applying the mucoadhesive paste , which was randomly ( using toss of coin ) chosen to be either pht or placebo . all patients underwent thorough scaling , root - planning , and oral hygiene instructions such as bass brushing technique and flossing , conducted by a trained periodontology resident who was also blind to the study polishing were done of course if needed . following the first round of data collection , muco - adhesive pastes preserved in two different containers with different colors . one containing pht 1% and the other placebo ( figure 1 ) were applied to randomly selected sextants by a second periodontist who was blind to the study . containers in different colors we also preferred to keep our patients incognizant to prevent any possible bias and/or incompliance , though they were given detailed instructions about their oral hygiene . gingival facial surfaces in two posterior sextants , with at least two teeth with similar conditions , were randomly selected as described before . one surface received a pea - sized amount of phenytoin paste ( approximately 2 grams ) as prepared , and the other side had placebo as control ( figure 2 ) . application of mucoadhesive paste on facial surface of gingivae and cervical one third of teeth the periodontist in charge of drug application used her index finger to rub this size of paste on the exposed gingival surface so as to cover cervical one third of the teeth . they were often kept busy in the waiting room so as to make sure they did as instructed . any patient who had failed to comply with paste application ( 7 patients ) or refer for follow - up ( 10 cases ) were excluded from the study , out of a total of 37-patients registry . since buccal phenytoin dosage is not commercially available , the common local skin dosage ( 1% ) phenytoin powder and carbopol 934 were purchased from alhavi pharmaceutical corporation ( iran ) and lubrizol ( usa ) respectively . methyl cellulose ( hydroxypropyl ) , nominal viscosity 2% in water : 2600 - 5600 cp and liquid paraffin was prepared from sigma aldrich , germany . one percent phenytoin mucoadhesive paste was prepared in yazd school of pharmacy , extemporaneously . to prepare this paste , one gram of phenytoin powder was mixed with 50 grams of mucoadhesive polymers including carbomer 934 and methyl cellulose ( 1:1 w / w ) . subsequently , the mixed powders were gradually levigated with 50 grams of liquid paraffin using mortar and pestle to obtain a uniform consistency ( figure 3 ) . preparation of mucoadhesive paste the mixing was continued until the preparation of a homogenous paste without existence of separate particles . thumb test was used for qualitative determination of peel adhesive strength of the paste . the paste was then inserted into 100 mg containers ( yellow and pink ) ( figure 3).as for the placebo , the composition and preparation method was almost the same except for the fact that it was pht - free . we used t - test and paired t - test for comparative analysis by using spss 21 software . since buccal phenytoin dosage is not commercially available , the common local skin dosage ( 1% ) was mixed with a mucoadhesive paste formulation which is routinely used in orabase . phenytoin powder and carbopol 934 were purchased from alhavi pharmaceutical corporation ( iran ) and lubrizol ( usa ) respectively . methyl cellulose ( hydroxypropyl ) , nominal viscosity 2% in water : 2600 - 5600 cp and liquid paraffin was prepared from sigma aldrich , germany . one percent phenytoin mucoadhesive paste was prepared in yazd school of pharmacy , extemporaneously . to prepare this paste , one gram of phenytoin powder was mixed with 50 grams of mucoadhesive polymers including carbomer 934 and methyl cellulose ( 1:1 w / w ) . subsequently , the mixed powders were gradually levigated with 50 grams of liquid paraffin using mortar and pestle to obtain a uniform consistency ( figure 3 ) . preparation of mucoadhesive paste the mixing was continued until the preparation of a homogenous paste without existence of separate particles . thumb test was used for qualitative determination of peel adhesive strength of the paste . the paste was then inserted into 100 mg containers ( yellow and pink ) ( figure 3).as for the placebo , the composition and preparation method was almost the same except for the fact that it was pht - free . we used t - test and paired t - test for comparative analysis by using spss 21 software . there were statistically significant differences in indices ( ppd , bop and mgi ) following three weeks after phenytoin application in test group . there could be seen a decline of 0.930.57 mm in ppd on the phenytoin - applied sites , as opposed to placebo - applied locus ( 0.560.49 mm ) . paired t - test revealed a significant difference in this respect ( p < 0.05 ) ( figure 4 ) . the average ppd changes in case and control groups ( error bars 1 sd ) as can be seen in table 1 , bop and mgi were also significantly declining in the phenytoin group . thus as expected anti - inflammatory effects of pht were highlighted based on changes in the latter inflammation indices ( bop , mgi ) . also it should be noted that in this trial study , any adverse events or side effects were not reported by patients . it has been stated that pht would accelerate healing rate in surgical wounds following the oral application of the drug . this encouraged the topical applications for skin breaches due to ulcers , burns , skin infections namely impetigo , infected dermatitis and boils , with somewhat mixed results , especially in experimental models . we decided to use mucoadhesive paste 1% considering its longevity in the oral cavity and the relative immunity against potential interventional parameters namely saliva washout and tongue poking . this also enabled us to suffice to the application of the drug twice per day , which , in turn , made it possible to rule out incompliance as patients , from the walking and driving distances , managed to come and receive medication under our supervision . to the best of our knowledge , mucoadhesive paste of phenytoin has not been assessed in human except in one study designed by baharvand et al . the majority of earlier researches were animal studies or some of them have evaluated the effects of other forms of this drug such as cream or gel on human skin wounds . for example , abrishami et al . , , though having applied phenytoin gel instead of paste , were shown consistent in their findings as their planned therapy led to the reduction of the pocket depth while promoting connective tissue strength . ghapanchi et al . also used phenytoin mouthwash in cases of chemotherapy - related mucositis . a 2-week treatment including drug use three and/or four times per day yielded favorable results . applied the 1% mucoadhesive paste onto small biopsy - induced lesions , which had healed more quickly as a result . all the above findings were confirmatory of our findings about healing effect and reduce inflammation of topical use of phenytoin . other studies reported accelerated healing in melanocytic mole removal scars29 as well as stomatitis - related lesions . the drug was used on the surface of the de - epithelialized gingiva twice per day for two months , yielding no significant change in the height and width of the recession , without any plausible explanation . topical phenytoin was also shown to have alleviated pain , possibly owing to sodium channel blockage . used pht suspension 1% to soothe pain and induce healing in palatal graft donor sites . pht was proven superior in these lesions for their being superficial and thus extensive exposure to the solution . our study was different , as periodontal pocket wall is less exposed to drug , requiring a longer span of time for healing ( 3 - 4 weeks ) even under normal circumstances . meanwhile , it would promote pharmacological efficacy , yet more research is warranted to explore the mechanism of action as well as monitoring the healing process in detail . in a microarray analysis investigating the role of phenytoin in wound healing , swamy et al . the most striking finding of theirs was that pht accelerated the autocrine as well as the paracrine activities pertaining to growth factors through up - regulating the related receptors . thus , though not with a certain degree of certainty , the somewhat similar mechanism can be imagined to explain our positive findings . yet , it still remains unknown as to why pht fails to stop creeping attachment in gingival graft cases . with the drug inducing some growth factors such as transforming growth factor ( tgf- ) and pdgf , and also up - regulating various matrix remodeling genes and receptors at the messenger rna ( mrna ) level , it sounds that further research is warranted regarding the possible differences between wound / ulcerative lesions and creeping attachment . we were restricted in our choice of patients as we aimed to ensure that compliance was thoroughly fulfilled . we intended to apply the drug ourselves to rule out any possible negligence and/or misapplication . we did not also investigate the possible mechanism of action as this was beyond the scope of our research . it is shown that the application of pht mucoadhesive paste following conventional therapy for periodontitis contributes to improve clinical parameters . given the low cost , relative safety and above all , user - friendly application , the drug seems to be a promising choice of adjunct therapy in cases of chronic periodontitis .

statement of the problem : phenytoin ( pht ) has been known to promote wound healing in some medical conditions owing to its proliferative as well as anti - inflammatory effects . yet , its application in oral lesions was less investigated . purpose : the aim of this study was to evaluate changes in periodontal indices following the topical use of phenytoin in chronic periodontitis . materials and method : in this doubled - blind , randomized , split - mouth controlled clinical study , 20 patients with moderate to severe chronic periodontitis referred to periodontology department of shahid sadoughi medical university of yazd in 2014 were selected consecutively . after initial therapy ( scaling and root planning and oral hygiene instructions ) , periodontal indices including bleeding on probing ( bop ) , periodontal pocket depth ( ppd ) and modified gingival index ( mgi ) were recorded . gingival facial surface of two posterior sextants with at least two teeth with similar conditions , were selected randomly . then one surface received pht paste whereas the other side had placebo as control . patients were received the mucoadhesive pastes under strict control by an examiner , twice a day for a week . periodontal indices were measured 3 weeks after treatment . data was analyzed with t - test and paired t - test by using spss 21 software . results : it was observed that periodontal pocket depth was significantly more decreased in phenytoin side in comparison with placebo one ( p < 0.05 ) . in addition , inflammatory indices including bleeding on probing and modified gingival index declined more in the phenytoin group ( p= 0.001 and p < 0.05 respectively ) . conclusion : these encouraging results support the use of 1% phenytoin mucoadhesive paste as an adjunctive in periodontal treatment .

it is caused by a defect in the decidua basalis resulting in an abnormally invasive placental implantation . this disruption is often related to previous uterine scars , including caesarean sections and prior uterine curettage . other risk factors associated with placenta accreta are multiparity ( > 6 pregnancies ) ; placenta previa ; prior intrauterine infections ; elevated maternal serum alpha - fetoprotein ; and maternal age over 35 years [ 24 ] . histologically , placenta accreta is identified by trophoblastic invasion of the myometrium in the absence of intervening decidua . the spectrum includes invasion of the superficial myometrium ( accreta ) , invasion into deeper myometrial layers ( increta ) , and invasion through the serosa and/or adjacent pelvic organs ( percreta ) . ideally , the diagnosis might be evaluated antenatally in high - risk pregnancies and suspected using ultrasound . unfortunately , most cases are identified only at the time of delivery when forcible attempts at manual removal of the placenta are unsuccessful . severe postpartum hemorrhage may result and may lead to complications such as massive transfusion of blood products ; dic ; acute renal failure ; infectious morbidities ; ards ; loss of fertility . traditionally , caesarean hysterectomy at the time of delivery has been the preferred management strategy for placenta accreta . not only does this approach preclude future fertility , but it is also a procedure synonymous with significant perioperative risks . for women who wish to conserve their reproductive function , other treatment options have been described . in some settings , uterine conservation ( with the placenta left in situ ) adjuvant therapy with methotrexate has also been used to expedite resorption of placental tissue [ 68 ] . a 32-year - old multiparous woman ( gravida 7 , para 6 ) presented to a nursing station in arviat , nunavut at 34 weeks gestational age in preterm labour . her obstetrical history was significant for six previous vaginal deliveries and two neonatal deaths secondary to an autosomal recessive metabolic disorder . she had been transferred to a tertiary centre in winnipeg twice during her current pregnancy for episodes of antepartum hemorrhage . at 19 weeks , she was admitted to hospital for observation and was discharged home after 24 hours . at 32 weeks g / l . a subsequent fetal assessment confirmed an unremarkable right anterolateral placenta that was clear of the internal os and an active fetus with a biophysical profile score of 8/8 . the patient was transferred to a community hospital in northern manitoba for manual removal . upon arrival , she was hemodynamically stable without significant vaginal bleeding . the patient was taken to the operating room to undergo manual removal of the retained placenta . the surgeon was only able to remove small fragments of tissue as the remainder of the placenta was densely adherent to the myometrium . intraoperative vaginal bleeding occurred and was managed with a combination of vigorous fundal massage , uterine packing , oxytocin , and carboprost . the bleeding settled over the following 18 hours , at which point the packing was removed . a large 12 cm soft tissue mass was visualized at the uterine fundus that was felt to be invading the myometrium . on postpartum day 3 , only mild vaginal bleeding had occurred , and the patient was transferred to a tertiary centre in winnipeg with a presumed diagnosis of placenta accreta . upon arrival , the following day , she received a single dose of 75 mg of methotrexate intramuscularly and was started on a course of prophylactic cephalexin . management then continued as an outpatient with twice - weekly visits to clinic to monitor for infection and bleeding . by postpartum day 16 , her serum hcg had decreased to 1447 that day , she described ongoing mild - to - moderate vaginal bleeding and was found to have an isolated temperature of 38.5c . blood cultures were taken , two units of packed red blood cells were transfused , and oral cephalexin was continued . an abdominal ultrasound ( figure 1(a ) ) revealed persistent retained placental tissue . over the next week , the patient was again followed in an outpatient setting ( figure 1(b ) ) . a repeat hcg was 479 ui / l . on postpartum day 26 , she reported a five - day history of nausea , vomiting , reduced oral intake , abdominal pain with eating , and failure to pass stool or flatus . she was afebrile with a heart rate of 100 beats per minute and blood pressure of 96/58 . she had evidence of leukocytosis ( white blood cells 21.7 10/l ) , thrombocytosis ( platelets 560 10/l ) , and pre - renal failure ( creatinine 140 mol / l , urea 12.6 mmol / l ) . an abdominal plain film demonstrated dilated loops of bowel and multiple air - fluid levels consistent with a small bowel obstruction . at this time , blood cultures from the previous admission had grown prevotella corporis . the patient was admitted for hydration , bowel rest , pain management , and intravenous antibiotics . intravenous cefoxitin 1 g every eight hours was chosen based on the blood culture sensitivities . a ct abdomen confirmed a mechanical small bowel obstruction with a possible adhesion noted between the uterine fundus and small bowel ( figure 2 ) . in consultation with the general surgery service , the obstruction was to be managed conservatively . a consultation was also requested with a senior gynecologist regarding management of the retained placental tissue . the prevailing consensus was that an endomyometritis had occurred secondary to the placenta accreta and had progressed to bacteremia , peritonitis , and intestinal ileus . the patient was consented for an elective dilatation and curettage to be carried out within the next few days . she was received informed consent with respect to possible complications , including laparotomy and hysterectomy . on postpartum day 29 , the patient was taken to the operating room for a dilatation and curettage . during the procedure , a uterine perforation identified as bowel was pulled through the cervix with forceps . surgical management of the findings included a total hysterectomy , in addition to an intraoperative consultation with a general surgeon for a small bowel resection with primary reanastomosis . she received volume resuscitation with crystalloid , colloid , and packed red blood cells . the patient returned to the operating room for an emergency exploratory laparotomy . upon entry , she received further bowel rest with total parenteral nutrition until she was consistently passing flatus and able to tolerate oral intake . a mild wound infection developed on postoperative day 4 , and antibiotic therapy was changed to oral amoxicillin / clavulin based on culture sensitivities to cover prevotella ( blood ) , e. coli ( wound ) , and non - hemolytic streptococcus ( wound ) . pathology confirmed the presence of necrotic and infarcted villous tissue at the uterine fundus consistent with placenta accreta . the incidence of placenta accreta approximates 1 in 1000 deliveries and has been increasing largely due to the global increase in caesarean deliveries . patients at risk for abnormal placentation should be assessed antenally by ultrasonography , with or without adjunct magnetic resonance imaging if indicated . the women at the highest risk are those with placenta previa in the current pregnancy and a history of prior caesarean delivery . traditionally , primary hysterectomy at the time of caesarean section has been the mainstay of therapy particularly in cases where the diagnosis has been discovered antenatally . this procedure has been associated with significant maternal morbidity and mortality . in a recent systematic review , emergency postpartum hysterectomy was found to be associated with maternal morbidity in 56% of cases and with a mortality rate of 3% . in addition to obvious loss of fertility , complications include injury to the gastrointestinal or urinary tracts , infection , as well as massive obstetrical hemorrhage and its sequelae [ 6 , 11 ] . furthermore , it has been recognized that planned caesarean hysterectomy is associated with fewer perioperative complications compared to emergent procedures . when an extirpative approach is utilized to excise the placenta from the uterus , severe bleeding necessitating urgent hysterectomy this scenario is encountered when placenta accreta is diagnosed peripartum following failed removal of a retained placenta . several reports have described the use of more conservative strategies aimed at preserving the uterus and maintaining future fertility [ 59 ] . this approach involves leaving the placental tissue in situ providing that the patient remains hemodynamic stable , without life - threatening hemorrhage , and with a desire for ongoing fertility . presuming the diagnosis at placenta accreta can be anticipated , efforts to minimize blood loss may be utilized . these might include having blood products and uterotonic agents available for delivery ; blood cell saver technology ; compression sutures ; uterine packing ; selective arterial embolization and/or balloon occlusion ; and uterine and/or hypopgastric artery ligation . although prenatal imaging may be useful , ultrasound findings suggestive of placenta accreta may not always be appreciated . in one review , methotrexate has also been described an as adjuvant therapy for the conservative management of placenta accreta [ 1 , 69 ] . it has been hypothesized that methotrexate acts by inducing placental necrosis and expediting a more rapid involution of the placenta . this contradicts the belief that methotrexate acts only on rapidly dividing cells , given that trophoblast proliferation is not felt to occur at term . thus , there is controversy as to the effectiveness of methotrexate as an adjuvant treatment . also , there is a lack of consensus regarding optimal dosing , frequency , or route of administration . in this particular case , a single dose of 50 mg per m of body surface area was used , similar to the protocol used in the management of ectopic pregnancy at our centre . in a recent review , the failure rate was 22% and hysterectomy , either primary or delayed , was required mostly for severe hemorrhage . severe maternal morbidity , including one maternal death , occurred in 6% of cases . the death was attributed to aplasia and nephrotoxicity secondary to intraumbilical administration of methotrexate . this case highlights the adverse effects that may occur following even a single dose of adjuvant methotrexate . another retrospective review of 60 cases of placenta accreta found similar outcomes among women managed conservatively with the placenta in situ whether or not adjuvant treatments were used . of the twenty - six women managed without the use of additional therapies , 22 ( 85% ) had a favourable outcome . in the remaining 4 cases , conservative management failed , and a hysterectomy was required either due to severe hemorrhage or infection . treatment failed in 5 patients ; thus , hysterectomy was avoided in 77% of cases . in the first time period , a policy of removing all placenta tissue was employed ( 13 cases ) . in the second , the standard of care changed to leaving the placenta in situ ( 20 cases ) . the hysterectomy rates in the first and second time periods were 85% and 15% , respectively . most cases occurred in women where the diagnosis was recognized at the time of delivery and were subsequent to severe hemorrhage or infection . although conservative management of placenta accreta appears to be successful at preventing hysterectomy in most cases , there is still potential for morbidity . sentilhes et al . reported a median period to delayed hysterectomy of 22 weeks . most cases are secondary to endomyometritis or florid sepsis ; however , fever may also represent an inflammatory response to tissue necrosis in the absence of an infectious source . prophylactic broad - spectrum antibiotic therapy may reduce the incidence of infectious morbidity [ 68 ] . in our case , prevotella species are anaerobic gram - negative bacilli that can be implicated in puerperal infections . therapy must be adjusted based on culture sensitivities as up to one third of strains may be resistant to -lactam antimicrobials . vaginal bleeding may also complicate management for several months following delivery . in timmermans ' review , fever and vaginal bleeding each occurred in 35% of patients and were the inciting factors leading to hysterectomy in all but one ( 92% ) of the patients with treatment failure . similarly , sentilhes et al . reported delayed vaginal bleeding as the reason for hysterectomy in 8 of the 36 treatment failures ( 22% ) , while sepsis was implicated in 7 cases . describe a significantly lower occurrence of disseminated intravascular coagulopathy , presumably secondary to severe hemorrhage , in women managed with the placenta in situ ( 5% ) compared to cases where the placental tissue was removed ( 39% ) . another controversy surrounding the use of methotrexate in the management of placenta accreta has been the utility of monitoring serum hcg . the prognostic implications of decreasing hcg levels following administration of methotrexate are better described in the setting of ectopic pregnancy . for placenta accrete , it is not clear whether decreasing levels correlate with the rate of involution of placental tissue . in one study , the serum hcg levels decreased with a half - life of 5.2 days in women managed by leaving the placenta in situ and did not vary with the volume of remaining tissue . another report described a half - life of serum hcg of 5.8 days in cases of retained placenta managed with methotrexate . we report a case of placenta accreta in a multiparous patient that was conservatively managed with the placenta in situ and adjuvant methotrexate . although initially the patient did well , she developed severe endomyometritis at the placental site that spread to involve the small bowel , a rare complication not previously reported by other authors . the conservative approach failed as a subsequent hysterectomy , and bowel resection were required . furthermore , despite the significant decrease in the serum hcg levels , a large placental mass persisted as evidenced by repeat ultrasound examinations during her management . this case depicts a common complication associated with this approach to treatment of placenta accreta as well as the need for intensive monitoring . despite the use of prophylactic antibiotics , our patient developed endomyometritis and bacteremia . nonetheless , experience in the literature suggests that conservative management of placenta accreta may be valid in select patients with favourable outcomes .

placenta accreta refers to any abnormally invasive placental implantation . diagnosis is suspected postpartum with failed delivery of a retained placenta . massive obstetrical hemorrhage is a known complication , often requiring peripartum hysterectomy . we report a case of presumed placenta accreta in a patient following failed manual removal of a retained placenta . we describe an attempt at conservative management with methotrexate in a stable patient desiring future fertility . treatment was unsuccessful and led to the development of a disseminated intrauterine infection complicated by a bowel obstruction , requiring both a hysterectomy and small bowel resection . in hemodynamically stable patients , conservative management of placenta accreta may involve leaving placental tissue in situ with subsequent administration of methotrexate . however , ongoing close observation is required to identify complications .

antiretroviral drugs are medication for treatment of infection by retroviruses , primarily human immunodeficiency virus ( hiv ) . when several such drugs , typically three or four , are taken in combination , the approach is known as highly active antiretroviral therapy , or haart . the american national institute of health and other organizations recommend offering antiretroviral treatment to all patients with aids . because of the complexity of selecting and following a regimen , the severity of the side effects and the importance of compliance to prevent viral resistance , such organizations emphasize the importance of involving patients in therapy choices and recommend analyzing the risks and the potential benefits to patients with low viral loads . there is no doubt that haart has been the most important progress in the therapy of hiv - infected patients in the last decade . a growing number of observations suggest that the beneficial effects of haart also include improvement of hiv - related haematological complications . current guidelines for treatment of human immune - deficiency virus ( hiv ) infection recommend the combination of three antiretroviral agents , two reverse transcriptase inhibitors ( rtis ) plus one protease inhibitor , or the association of three rtis [ 1 , 3 ] . these regimens of haart have dramatically reduced the morbidity and mortality of hiv infection . the values of haematologic parameters are affected by a number of factors even in apparently healthy populations . these factors include age , sex , ethnic background , body build , and social , nutritional , and environmental factors , especially altitude [ 46 ] . it has also been shown in several studies that some of the heamatological parameters exhibit considerable variations at different periods of life and disease conditions [ 79 ] . although haart has dramatically improved survival in hiv - infected patients , precautions still need to be taken to prevent haart - related haematotoxicity and other life - threatening side - effects . due to the fact that there are no available preclinical safety data on the treatment with the combinations of lamivudine , zidovudine , and nevirapine in animals , the aim of the present study was to examine the potential haematotoxicity of combinations of lamivudine , zidovudine , and nevirapine in albino wistar rats . the three ( 3 ) fixed - dose antiretroviral combination drugs used for the study were obtained from one of the accredited united states presidential emergency plan for aids relief ( pepfar ) centers in enugu , enugu state , nigeria . the haart considered in the study was a fixed - dose combinations ( fdcs ) of lamividine ( 150 mg ) , zidovudine ( 300 mg ) , and nevarapine ( 200 mg ) per tablet . 313 , bachupally village , quthubullapur mandal , ranga reddy district ( a.p ) india . this was according to the guidelines issued by world health organization ( who ) , geneva , switzerland and the indian national science academy ( insa ) , new delhi , india on the care and use of laboratory animals . the albino wistar rats which were three ( 3 ) months old and weighing 200250 g were selected from the colony maintained under the controlled conditions of temperature ( 33 2c ) , humidity , and light ( 12 hours of light and dark ) in the animal house of university of nigeria , enugu campus ( unec ) , enugu , enugu state , nigeria . the animals had free access to food ( standard pellet diet , starter feed ) and clean tap water . the animals were housed in standard environmental conditions in wire - mesh - bottomed stainless steel cages . fifty ( 50 ) three ( 3 ) months old male albino wistar rats weighing between 200250 g were randomly assigned to five ( 5 ) groups ( a , b , c , d , and e ) according to similar body weight with ten ( 10 ) animals per group . groups b , c , d , and e received graded doses ( 3 , 6 , 12 , and 24 mg / kg body weight , resp . ) two ( 2 mls ) of venous blood was aseptically collected on days 5 , 10 , 15 , 20 , and 25 of treatment after overnight fasting from each animal into tripotassium ethylene diamine tetra acetic acid ( k3edta ) anticoagulant bottle . this was immediately mixed by gentle inversion and used in the determination of the haematological profile using a haematology auto analyser ( sysmex kx-2 in ) following the manufacturer 's guidelines . two ( 2 ) animals were bled painlessly under chloroform anesthesia by ocular puncture through the retro - bulber plexus of the medial canthus . data were analysed using students ' t-test and one - way analysis of variance ( anova ) to determine significant differences between means . red blood cells ( rbcs ) count mean value recorded statistically significant increase ( p < 0.05 ) in groups b ( 3 mg / kg body weight ) and group c ( 6 mg / kg body weight ) when compared with the control group . however , total white blood cell ( wbc ) count showed statistically significant decrease ( p < 0.01 ) in group b when compared with the control group . rbc and mean cell haemoglobin ( mch ) mean values revealed dose dependent statistically significant decrease ( p < 0.001 and p < 0.05 ) , respectively , in the one - way analysis of variance ( anova ) when groups b , c , d , and e were compared on day 5 ( table 1 ) . however , rbc , haemoglobin ( hb ) , and packed cell volume ( pcv ) recorded statistically significant decrease ( p < 0.05 ) in group e ( 24 mg / kg body weight ) when compared with the control group . also , mean cell volume ( mcv ) and mchc revealed statistically significant decrease ( p < 0.001 and p < 0.05 ) when compared with the control group . neutrophil count showed a statistically significant increase ( p < 0.05 ) in group b when compared with the control group , while lymphocyte count recorded statistically significant decrease ( p < 0.05 ) when compared with the control group . mcv revealed a dose - dependent statistically significant increase ( p < 0.05 ) in the one way anova when groups b , c , d , and e were compared on day 10 ( table 2 ) . only platelet count mean value recorded a dose - dependent statistically significant increase ( p < 0.05 ) when all the test groups were compared on day 15 ( table 3 ) . in addition , there was no statistically significant difference ( p > 0.05 ) in all the parameters evaluated when the test groups was compared with the control group on day 20 ( table 4 ) . however , only total wbc showed a statistically significant decrease ( p < 0.05 ) in groups d ( 12 mg / kg body weight ) and e when compared with the control group on day 25 ( table 5 ) . furthermore , in group c , rbc , and hb mean values demonstrated a time - dependent statistically significant increase ( p < 0.05 ) . similarly , platelet and lymphocyte count showed a statistically significant increase ( p < 0.01 and p < 0.001 ) , respectively . however , mchc and neutrophil mean values showed a time - dependent statistically significant decrease ( p < 0.01 and p < 0.001 , resp . ) in all the test groups ( table 6 ) . although haart has dramatically improved survival in hiv patients , precautions still need to be taken to prevent haart - related haematotoxicity and other life threatening side effects . in this study , red blood cell ( rbc ) mean value recorded statistical significant increase ( p < 0.05 ) in groups b and c when compared with the control group on day 5 . this could most likely be due to the stimulatory effect of haart on haemopoiesis since the total white blood cell ( wbc ) count showed a statistical significant decrease in the same group b. however , one may be tempted to suggest that the drug had an inhibitory effect on haemopoiesis in general and erythropoiesis in particular as shown by a statistically significant decrease ( p < 0.05 ) in rbc , haemoglobin concentration ( hb ) , packed cell volume ( pcv ) , and some red cell indices on day 10 . this was in line with an earlier report by ejele et al . and umar et al . though the drugs were administered singly and at variance with high pcv and leucocytes mean value reported by odunukwe et al . . there was no statistically significant difference ( p > 0.05 ) in all the parameters evaluated when the test group were compared with the control on day 25 . the most probable explanation may be that in the test groups , the animals must have adapted or adjusted to its normal body physiology through a negative feedback mechanism , hence , must have compensated for the reduction in some blood parameters at the start of drug administration . however , this was disproved by a statistically significant decrease ( p < 0.05 ) in the total wbc on day 25 in groups c and e indicating that the drug may possess both dose- and time - dependent leucopenic inhibitory effects on the progenitor cells in the bone - marrow as earlier reported by umar et al . or directly on the matured cells in the peripheral system . there was a time - related statistically significant increase ( p < 0.05 ) in the two major blood cells rbc and platelet count suggesting that administration of fixed - dose combination of haart stimulated both erythropoietic and thrombopoietic activities by indirectly stimulating erythropoietin and thrombopoietin in the kidney or directly stimulating the pluripotential stem cells in the bone marrow . it could also be contested that the pancytopenia observed in hiv / aids patients may probably be due to either the virus infection or other latent malignancies not as a result of haart administration . hence , from the result of this present study , it can be concluded that haart when administered in fixed - dose combinations have no subacute haematotoxic effects . its use in the treatment of hiv and other viral related infection should be encouraged and haematological parameters should be monitored .

highly active antiretroviral therapy ( haart ) is considered toxic and has other life - threatening side effects . our aim was to evaluate the haematotoxic effects of lamivudine , zidovudine , and nevirapine fixed - dose combinations in albino wistar rats . fifty ( 50 ) three ( 3 ) months old male albino wistar rats weighing between 200 and 250 g were randomly assigned to five ( 5 ) groups ( a , b , c , d , and e ) . group a served as control . two ( 2 mls ) of venous blood was aseptically collected on days 5 , 10 , 15 , 20 , and 25 of treatment . red blood cell ( rbc ) mean value recorded statistically significant increase ( p < 0.05 ) in groups b and c when compared with the control group on day 5 . however , there was a statistically significant decrease ( p < 0.05 ) in rbc , haemoglobin concentration ( hb ) , packed cell volume ( pcv ) , and some red cell indices on day 10 . in addition there was no statistically significant difference ( p > 0.05 ) in all the parameters evaluated when the test group was compared with the control on day 25 . furthermore , there was a time - related statistically significant increase ( p < 0.05 ) in the two major blood cells rbc and platelet counts . from the result of this present study , it can be concluded that haart when administered in fixed - dose combinations have no subacute haematotoxic effects .

The 30-year-old had a heart attack while in surgery and the trauma of the attack caused her to quietly pass. According to Kidspot.au, after his wife's death Jonathan had thought that it was time to close her account and end this chapter of their lives. But in the end, decided against it. Instead, he has been steadily giving updates on their son, Alvaro, who Jonathan explained is becoming stronger every day. "Alvaro is recovering little by little. Many thanks to all with all my heart, I had not imagined that a farewell message in honor of my wife would have caused such an avalanche of support, you have helped me as much as I hope she helped you," he said in a post on September. "I want you to know that I will continue on this dream of helping more couples on the hard road of being parents and I will be there for everything you need," he added. ||||| Her IVF journey inspired thousands. “So here begins our story, our story with a happy ending,'' Vanessa wrote. A popular Spanish blogger who inspired people by documenting her IVF journey has died in childbirth, Spanish news outlet El Mundo reports. Vanessa Fernandez Arango, 30, shared her and husband Jonathan Garcia, Arango's, 32, IVF journey on Instagram. The couple shared pictures of ultrasounds and baby clothes as well as their past struggles with infertility. “The beginning of the end. The beginning of feeling life and the end of suffering,” Vanessa wrote with a picture showing a positive pregnancy test back in May. “So here begins our story, our story with a happy ending.” But tragically, it wasn't to be the happy ending they were hoping for. At 38 weeks the mum-to-be fainted while eating breakfast and was rushed to hospital. Doctors performed an emergency cesarean but Vanessa died after going into cardiac arrest. This morning she was in pain while having breakfast and fainted,” Jonathan, 32, wrote in a post on September 2 after his wife was taken to hospital. “They have taken us by ambulance to the hospital and there they had to do an emergency c-section. The baby is in very serious condition in the ICU and my wife has suffered a cardiac arrest that she could not overcome.” Her posted a heartbreaking message on her Twitter account. "This is Vanessa's husband. They have carried out an emergency Cesarean. The baby is in intensive care. Vanessa has died. You will understand that this account will now close. Thank you all for making her laugh," he wrote. Their baby boy is now doing well and Jonathan has been keeping Instagram followers up to date with his progress as a single dad. “I can finally get something positive. Alvaro is recovering little by little, he still has many tests and will continue for a while in intensive care, but it’s a little step,” he wrote. “I never imagined a goodbye message in her honor would have led to such an avalanche of support… I want you to know I will continue with her dream of helping other couples.”

– A Spanish blogger whose fertility journey was followed by thousands on Instagram died giving birth to her son via emergency C-section, Cafe Mom and Kidspot report. Vanessa Fernandez Arango started her Instagram in May with a photo of a positive pregnancy test, explaining that after two ectopic pregnancies damaged her fallopian tubes, she was five months pregnant thanks to assisted reproductive technology. "The beginning of the end. The beginning of feeling life and the end of suffering," she wrote. "So here begins our story, our story with a happy ending." But at 38 weeks pregnant, Arango, in pain, passed out at the breakfast table, her husband Jonathan Garcia posted on her Instagram account Sept. 2. Doctors decided she needed to deliver the baby via emergency C-section. The couple's son survived the birth, but Arango had a heart attack during the surgery and did not recover. Garcia posted a photo of baby Alvaro Sept. 6, noting that he had received "an avalanche of messages of support" from his wife's followers—and that while he initially planned to close his wife's account, he decided to continue on with her mission of helping others trying to become parents. He has since posted more updates on Alvaro's progress, noting in one that the baby had been receiving breast milk donations. On Saturday, he posted a photo of himself, Alvaro, and their dog, announcing the baby had been allowed to leave the hospital and come home. "Here you have our first family photo, missing the fourth member of the group that watches us from the sky and helps us get up at 3," he wrote, ending the post with his gratitude for the clinic that helped him and his wife get pregnant.

SECTION. 1. PAYMENTS TO MEDICARE MANAGED CARE PLANS. (a) In General.--Section 1876(a) of the Social Security Act (42 U.S.C. 1395mm(a)) is amended to read as follows: ``(a)(1)(A) The Secretary shall annually determine, and shall announce (in a manner intended to provide notice to interested parties) not later than August 1 before the calendar year concerned-- ``(i) a per capita rate of payment for individuals who are enrolled under this section with an eligible organization which has entered into a risk-sharing contract and who are entitled to benefits under part A and enrolled under part B, and ``(ii) a per capita rate of payment for individuals who are so enrolled with such an organization and who are enrolled under part B only. For purposes of this section, the term ``risk-sharing contract'' means a contract entered into under subsection (g) and the term ``reasonable cost reimbursement contract'' means a contract entered into under subsection (h). ``(B) The annual per capita rate of payment for each Medicare payment area (as defined in paragraph (5)) shall be equal to the adjusted capitation rate (as defined in paragraph (4)), adjusted by the Secretary for-- ``(i) individuals who are enrolled under this section with an eligible organization which has entered into a risk-sharing contract and who are enrolled under part B only; and ``(ii) such risk factors as age, disability status, gender, institutional status, and such other factors as the Secretary determines to be appropriate so as to ensure actuarial equivalence. The Secretary may add to, modify, or substitute for such factors, if such changes will improve the determination of actuarial equivalence. ``(C) In the case of an eligible organization with a risk-sharing contract, the Secretary shall make monthly payments in advance and in accordance with the rate determined under subparagraph (B) and except as provided in subsection (g)(2), to the organization for each individual enrolled with the organization under this section. ``(D) The Secretary shall establish a separate rate of payment to an eligible organization with respect to any individual determined to have end-stage renal disease and enrolled with the organization. Such rate of payment shall be actuarially equivalent to rates paid to other enrollees in the payment area (or such other area as specified by the Secretary). ``(E)(i) The amount of payment under this paragraph may be retroactively adjusted to take into account any difference between the actual number of individuals enrolled in the plan under this section and the number of such individuals estimated to be so enrolled in determining the amount of the advance payment. ``(ii)(I) Subject to subclause (II), the Secretary may make retroactive adjustments under clause (i) to take into account individuals enrolled during the period beginning on the date on which the individual enrolls with an eligible organization (which has a risk- sharing contract under this section) under a health benefit plan operated, sponsored, or contributed to by the individual's employer or former employer (or the employer or former employer of the individual's spouse) and ending on the date on which the individual is enrolled in the plan under this section, except that for purposes of making such retroactive adjustments under this clause, such period may not exceed 90 days. ``(II) No adjustment may be made under subclause (I) with respect to any individual who does not certify that the organization provided the individual with the explanation described in subsection (c)(3)(E) at the time the individual enrolled with the organization. ``(F)(i) At least 45 days before making the announcement under subparagraph (A) for a year, the Secretary shall provide for notice to eligible organizations of proposed changes to be made in the methodology or benefit coverage assumptions from the methodology and assumptions used in the previous announcement and shall provide such organizations an opportunity to comment on such proposed changes. ``(ii) In each announcement made under subparagraph (A) for a year, the Secretary shall include an explanation of the assumptions (including any benefit coverage assumptions) and changes in methodology used in the announcement in sufficient detail so that eligible organizations can compute per capita rates of payment for individuals located in each county (or equivalent medicare payment area) which is in whole or in part within the service area of such an organization. ``(2) With respect to any eligible organization which has entered into a reasonable cost reimbursement contract, payments shall be made to such plan in accordance with subsection (h)(2) rather than paragraph (1). ``(3) Subject to subsections (c)(2)(B)(ii) and (c)(7), payments under a contract to an eligible organization under paragraph (1) or (2) shall be instead of the amounts which (in the absence of the contract) would be otherwise payable, pursuant to sections 1814(b) and 1833(a), for services furnished by or through the organization to individuals enrolled with the organization under this section. ``(4)(A) For purposes of this section, the `adjusted capitation rate' for a medicare payment area (as defined in paragraph (5)) is equal to the greatest of the following: ``(i) The sum of-- ``(I) the area-specific percentage for the year (as specified under subparagraph (B) for the year) of the area-specific adjusted capitation rate for the year for the medicare payment area, as determined under subparagraph (C), and ``(II) the national percentage (as specified under subparagraph (B) for the year) of the input-price- adjusted national adjusted capitation rate for the year, as determined under subparagraph (D), multiplied by a budget neutrality adjustment factor determined under subparagraph (E). ``(ii) An amount equal to-- ``(I) in the case of 1998, 80 percent of the input- price-adjusted national adjusted capitation rate for the year, as determined under subparagraph (D); and ``(II) in the case of a succeeding year, the amount specified in this clause for the preceding year increased by the national average per capita growth percentage specified under subparagraph (F) for that succeeding year. ``(iii) An amount equal to-- ``(I) in the case of 1998, 102 percent of the annual per capita rate of payment for 1997 for the medicare payment area (determined under this subsection), as in effect on the day before the date of enactment of this subclause; and ``(II) in the case of a subsequent year, 102 percent of the adjusted capitation rate under this subsection for the area for the previous year. ``(B) For purposes of subparagraph (A)(i)-- ``(i) for 1998, the `area-specific percentage' is 90 percent and the `national percentage' is 10 percent, ``(ii) for 1999, the `area-specific percentage' is 85 percent and the `national percentage' is 15 percent, ``(iii) for 2000, the `area-specific percentage' is 80 percent and the `national percentage' is 20 percent, ``(iv) for 2001, the `area-specific percentage' is 75 percent and the `national percentage' is 25 percent, and ``(v) for a year after 2001, the `area-specific percentage' is 70 percent and the `national percentage' is 30 percent. ``(C) For purposes of subparagraph (A)(i), the area-specific adjusted capitation rate for a medicare payment area-- ``(i) for 1998, is the average of the annual per capita rates of payment for the area for 1994 through 1997, after adjusting the 1994 and 1995 rates of payment to 1997 dollars, increased by the national average per capita growth percentage for 1997 (as defined in subparagraph (F)); or ``(ii) for a subsequent year, is the area-specific adjusted capitation rate for the previous year determined under this subparagraph for the area, increased by the national average per capita growth percentage for such subsequent year. ``(D)(i) For purposes of subparagraph (A)(i) and subparagraph (A)(ii), the input-price-adjusted national adjusted capitation rate for a medicare payment area for a year is equal to the sum, for all the types of medicare services (as classified by the Secretary), of the product (for each such type of service) of-- ``(I) the national standardized adjusted capitation rate (determined under clause (ii)) for the year, ``(II) the proportion of such rate for the year which is attributable to such type of services, and ``(III) an index that reflects (for that year and that type of services) the relative input price of such services in the area compared to the national average input price of such services. In applying subclause (III), the Secretary shall, subject to clause (iii), apply those indices under this title that are used in applying (or updating) national payment rates for specific areas and localities. ``(ii) In clause (i)(I), the `national standardized adjusted capitation rate' for a year is equal to-- ``(I) the sum (for all medicare payment areas) of the product of (aa) the area-specific adjusted capitation rate for that year for the area under subparagraph (C), and (bb) the average number of standardized medicare beneficiaries residing in that area in the year; divided by ``(II) the total average number of standardized medicare beneficiaries residing in all the medicare payment areas for that year. ``(iii) In applying this subparagraph for 1998-- ``(I) medicare services shall be divided into 2 types of services: part A services and part B services; ``(II) the proportions described in clause (i)(II) for such types of services shall be-- ``(aa) for part A services, the ratio (expressed as a percentage) of the national average annual per capita rate of payment for part A for 1997 to the total average annual per capita rate of payment for parts A and B for 1997, and ``(bb) for part B services, 100 percent minus the ratio described in item (aa); ``(III) for part A services, 70 percent of payments attributable to such services shall be adjusted by the index used under section 1886(d)(3)(E) to adjust payment rates for relative hospital wage levels for hospitals located in the payment area involved; and ``(IV) for part B services-- ``(aa) 66 percent of payments attributable to such services shall be adjusted by the index of the geographic area factors under section 1848(e) used to adjust payment rates for physicians' services furnished in the payment area, and ``(bb) of the remaining 34 percent of the amount of such payments, 70 percent shall be adjusted by the index described in subclause (III). The Secretary may continue to apply the rules described in this clause (or similar rules) for 1999. ``(E) For each year, the Secretary shall compute a budget neutrality adjustment factor so that the aggregate of the payments under this section shall be equal to the aggregate payments that would have been made under this section if the area-specific percentage for the year had been 100 percent and the national percentage had been 0 percent. ``(F) In this section, the `national average per capita growth percentage' is equal to the percentage growth in medicare fee-for- service per capita expenditures, which the Secretary shall project for each year. ``(5)(A) In this section, except as provided in subparagraph (C), the term `medicare payment area' means a county, or equivalent area specified by the Secretary. ``(B) In the case of individuals who are determined to have end stage renal disease, the medicare payment area shall be specified by the Secretary. ``(C)(i) Upon written request of the Chief Executive Officer of a State for a contract year (beginning after 1997) made at least 7 months before the beginning of the year, the Secretary shall adjust the system under which medicare payment areas in the State are otherwise determined under subparagraph (A) to a system which-- ``(I) has a single statewide medicare payment area, ``(II) is a metropolitan based system described in clause (iii), or ``(III) which consolidates into a single medicare payment area noncontiguous counties (or equivalent areas described in subparagraph (A)) within a State. Such adjustment shall be effective for payments for months beginning with January of the year following the year in which the request is received. ``(ii) In the case of a State requesting an adjustment under this subparagraph, the Secretary shall adjust the payment rates otherwise established under this section for medicare payment areas in the State in a manner so that the aggregate of the payments under this section in the State shall be equal to the aggregate payments that would have been made under this section for medicare payment areas in the State in the absence of the adjustment under this subparagraph. ``(iii) The metropolitan based system described in this clause is one in which-- ``(I) all the portions of each metropolitan statistical area in the State or in the case of a consolidated metropolitan statistical area, all of the portions of each primary metropolitan statistical area within the consolidated area within the State, are treated as a single medicare payment area, and ``(II) all areas in the State that do not fall within a metropolitan statistical area are treated as a single medicare payment area. ``(iv) In clause (iii), the terms `metropolitan statistical area', `consolidated metropolitan statistical area', and `primary metropolitan statistical area' mean any area designated as such by the Secretary of Commerce. ``(6) Subject to subsections (c)(2)(B)(ii) and (c)(7), if an individual is enrolled under this section with an eligible organization having a risk-sharing contract, only the eligible organization shall be entitled to receive payments from the Secretary under this title for services furnished to the individual.''. (b) Effective Date.--The amendment made by subsection (a) shall take effect on October 1, 1997.

Amends title XVIII (Medicare) of the Social Security Act to revise the formulae for payments to health maintenance organizations and competitive medical plans. Provides for a metropolitan based system under which: (1) all portions of each metropolitan statistical area in a State are treated as a single Medicare payment area; and (2) all areas in that State that do not fall within a metropolitan statistical area are treated as a single Medicare payment area. Requires the Secretary of Health and Human Services to determine the annual per capita rate of payment for each Medicare payment area by adjusting the adjusted capitation rate for: (1) individuals (not, as currently, a class of individuals) who are enrolled with an eligible organization which has entered into a risk-sharing contract and who are enrolled under Medicare part B (Supplementary Medical Insurance) only; and (2) such risk factors as age, disability status, gender, institutional status, and other appropriate factors so as to ensure actuarial equivalence. Requires the Secretary to establish a separate rate of payment to an eligible organization with respect to any individual determined to have end-stage renal disease and enrolled with the organization. Prescribes a general formula for the adjusted capitation rate of a Medicare payment area based on an area-specific adjusted capitation rate and an input-price-adjusted national adjusted capitation rate. Specifies area-specific and national percentages for contract years 1998 through 2001 and after. Requires the Secretary, upon written request of the Chief Executive Officer of a State for a contract year, to adjust the system under which Medicare payment areas in the State are otherwise determined to a system which: (1) has a single Statewide Medicare payment area; (2) is a metropolitan based system; or (3) consolidates into a single Medicare payment area noncontiguous counties (or equivalent areas) within the State.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Early Childhood Education Professional Improvement Act of 2013''. SEC. 2. PURPOSE. The purpose of this Act is to provide assistance to States to improve the knowledge, credentials, compensation, and professional development of early childhood educators working with children in early childhood education programs. SEC. 3. DEFINITIONS. In this Act: (1) The term ``early childhood education program'' means a Head Start Program carried out under the Head Start Act (42 U.S.C. 9831 et seq.), a State-funded prekindergarten program, a licensed child care serving prekindergarten children, and special education preschool. (2) The term ``institution of higher education'' has the meaning given the term in section 101(a) of the Higher Education Act of 1965 (20 U.S.C. 1001(a)). SEC. 4. PROGRAM AUTHORIZED. The Secretary of Education, in consultation with the Secretary of Health and Human Services, is authorized to award grants to States to implement and administer the activities described in section 6. SEC. 5. APPLICATIONS. (a) In General.--Each State desiring a grant under this Act shall submit an application to the Secretary of Education at such time, in such manner, and accompanied by such information as the Secretary may reasonably require. (b) Contents.--Each application submitted under subsection (a) shall include a description of the State's comprehensive early childhood professional development system, including the following: (1) A description of how the State's system was developed in collaboration with the State Advisory Council on Early Childhood Education and Care designated or established under section 642B of the Head Start Act, the State agency responsible for administering childcare, the State Head Start collaboration director, the State educational agency, institutions of higher education, organizations that represent early childhood educators, and credible early childhood education professional organizations. (2) A designation of a State agency to administer the grant program. (3) A description of how the State's system provides-- (A) an oversight structure for the system; (B) professional standards and competencies; (C) a career lattice; (D) coordination with State higher education agencies, higher education accrediting bodies, and accredited two- and four-year institutions of higher education; (E) encouragement of articulation agreements between two- and four-year institutions of higher education and credit-bearing opportunities and articulation agreements that recognize prior learning and expertise; (F) more accessible higher education for working learners through offering of college courses at accessible time and locations, with particular attention to rural areas; (G) support to adult learners who are dual language learners, or come from low-income or minority communities; (H) use of workforce data to assess the State's workforce needs; and (I) its financing over time. SEC. 6. STATE USE OF FUNDS. A State that receives a grant under this Act shall ensure that grant funds are used to carry out the following: (1) To provide scholarships to cover the costs of tuition, fees, materials, transportation, paid substitutes, and release time for preschool teachers employed in an early childhood education program to pursue a bachelor's degree in early childhood education or a closely related field. (2) To support preschool teachers employed in an early childhood education program, and who have obtained a bachelor's degree in a field other than early childhood education or a closely related field, to attain a credential, licensure, or endorsement that demonstrates competence in early childhood education. (3) To increase compensation for teachers who are enrolled and making progress toward a degree in early childhood education and to provide parity of compensation upon completion of such degree and retention in the early childhood education program. (4) To provide ongoing professional development opportunities to preschool teachers and teacher assistants employed in an early childhood education program that address-- (A) all areas of child development and learning (cognitive, social, emotional, and physical); (B) teacher-child interaction; (C) family engagement; and (D) cultural competence for working with a diversity of children (including children with special needs and dual language learners) and families. SEC. 7. SUPPLEMENT NOT SUPPLANT. Grant funds provided under this Act shall supplement, and not supplant, other Federal, State, and local funds that are available for early childhood educator preparation and professional development. SEC. 8. MAINTENANCE OF EFFORT. A State that receives funds under this Act for a fiscal year shall maintain the fiscal effort provided by the State for the activities supported by the funds under this Act at a level equal to or greater than the level of such fiscal effort for the preceding fiscal year. SEC. 9. AUTHORIZATION OF APPROPRIATIONS. There are authorized to be appropriated to carry out this Act such sums as may be necessary for fiscal years 2014 through 2019.

Early Childhood Education Professional Improvement Act of 2013 - Authorizes the Secretary of Education to award grants to states to: provide scholarships that enable preschool teachers employed in an early childhood education program to pursue a bachelor's degree in early childhood education or a closely related field; support preschool teachers employed in an early childhood education program to attain a credential, licensure, or endorsement that demonstrates competence in early childhood education if their bachelor's degree is not in that or a closely related field; increase the compensation of teachers who are making progress toward a degree in early childhood education or who have attained that degree; and provide ongoing professional development opportunities to preschool teachers and teacher assistants employed in an early childhood education program. Requires each state that desires a grant to include a description of its comprehensive early childhood professional development system in its application. Requires grant recipients to maintain their fiscal effort for the activities supported by the grant funds for a fiscal year at levels equal to or greater than their fiscal effort for such activities during the preceding fiscal year.

the interest in the cosmic history of supernovae stems from several sources . first , core - collapse supernovae ( types ii and ib / c ) directly follow the star formation history and some of them may be related to gamma - ray bursts . secondly , type ia supernovae ( sne ia ) are being used as the primary standard candle sources for the determination of the cosmological parameters @xmath0 and @xmath1 ( e.g. perlmutter et al . 1999 ; riess et al . thirdly , a comparison of sne ia rates ( for the different models of their progenitors ) with observations may shed light on both the star formation history and on the nature of the progenitors ( e.g. yungelson & livio 1998 ; madau 1998a ) . finally , the counts of distant sne could be used to constrain cosmological parameters ( e.g. ruiz - lapuente & canal 1998 ) . as a consequence of the above , studies of cosmological sne are among the primary targets for the next generation space telescope ( ngst ) , which presumably will be able to detect , with proper filters , virtually all the sne up to a redshift @xmath2 ( see e.g. http://ngst.gsfc.nasa.gov/images/sn.gif ) . in the present study we combine data on the precursors of sne ia in our galaxy with data on the cosmic star formation rate in an attempt to analyse the frequency of events as a function of redshift . in view of the uncertainties that still exist concerning the cosmic star formation history , we use two types of inputs to characterize the star formation rate ( sfr ) . in the first , we use profiles inferred from deep observations ( e.g. madau , panagia & della valle 1998 ) . in the second , we use a step - wise sfr which includes a burst of star formation and a subsequent stage of a lower sfr . in the latter case the star formation history is parameterized by the duration of the star burst phase and by the fraction of the total mass of the stellar population that is formed in the burst . the different scenarios for sne ia are briefly discussed in 2 . the basic assumptions and model computations are presented in 3 and 4 , and a discussion and conclusions follow . the observed sne ia do represent somewhat of a mixture of events , with a majority of `` normal '' ones and a small minority of `` peculiar '' ones ( see e.g. branch 1998 , and references therein ) . a more moderate diversity is present even among the `` normals . '' there exist certain relations between the absolute magnitudes and light curve decline rates and the morphological types of the host galaxies ( e.g. branch , romanishin , & baron 1996 ; hamuy et al . this may suggest a possible diversity among the progenitors of sne ia ( see e.g. review by livio 1999 ) . on the theoretical side , sne ia are very probably thermonuclear disruptions of accreting white dwarfs . two classes of explosive events are generally considered in the literature . the first involves central ignition of carbon when the accreting white dwarf reaches the chandrasekhar mass @xmath3 in the second , the ignition of the accreted helium layer on top of the white dwarf induces a compression of the core which leads to the ignition of carbon at sub - chandrasekhar masses ( these are known as edge - lit detonations or elds ) . parameterized models for the events in the former class are able to reproduce most of the typical features of sne ia , while eld models encounter a few serious problems when confronted with observations ( see e.g. hflich & khokhlov 1996 ; nugent et al . 1997 ; branch 1998 ; livio 1999 for a discussion and references ) . on the other hand , binary evolution theory clearly predicts situations in which helium may accumulate on top of white dwarfs ( see e.g. branch et al . 1995 ; yungelson & tutukov 1997 ) . it is presently not entirely clear whether elds indeed do not occur in nature , or whether they are responsible for a subset of the events ( e.g. the subluminous ones ) . however , both the existing diversity in the observed properties of sne ia and the uncertainties still involved in theoretical models , suggest that it is worthwhile to explore all the possible options . the occurence rate of sne ia inferred for our galaxy is @xmath4 ( cappellaro et al . there are three evolutionary channels in which according to population synthesis calculations the realization frequency of potentially explosive configurations in the disk of the milky way is at least at the level of @xmath5 these are : * a*. mergers of double degenerates resulting in the formation of a @xmath6 object and central c ignition . the channel involves the accretion of carbon - oxygen . * b*. accretion of helium from a nondegenerate helium - rich companion at a rate of @xmath7 , resulting in the accumulation of a he layer of @xmath8 and an eld . * c*. accretion of hydrogen from a ( semidetached ) main - sequence or evolved companion . the burning of h may result either in the accumulation of and central c ignition or in the accumulation of a critical layer of he for an eld . the positive aspects and draw - backs of these channels were discussed in detail elsewhere and also by other authors ( e.g. tutukov , iben , & yungelson 1992 ; branch et al . 1995 ; iben 1997 ; ruiz - lapuente et al . 1997 ; yungelson & livio 1998 ; hachisu , kato & nomoto 1999 ; livio 1999 ) . here we present for `` pedagogical '' purposes a simplified flow - chart which illustrates some of the evolutionary scenarios which may result in sne ia ( fig . 1 ) . other channels may definitely contribute to the total sne ia rate but they are either less productive or they involve large uncertainties ( see also 5 ) . in a typical scenario , one starts with a main - sequence binary in which the mass of the primary component is in the range @xmath9 . the initial system has to be wide enough to allow the primary to become an asymptotic giant branch ( agb ) star with a degenerate co core . after the agb star overfills its roche lobe a common envelope forms . if the components do not merge inside the common envelope , the core of the former primary becomes a co white dwarf . the subsequent evolution depends on the separation of the components and on the mass of the secondary . if the latter is higher than @xmath10 and the secondary fills its roche lobe in the agb stage , then following a second common envelope phase , a pair of co white dwarfs forms . the two white dwarfs may merge due to systemic angular momentum losses via gravitational wave radiation . as a result , a chandrasekhar mass may be accumulated , leading potentially to a sn ia ( scenario * a * ) . if the mass of the secondary is above @xmath11 and it fills its roche lobe before core he ignition it becomes a compact he star . if inside the common envelope the components get sufficiently close , the he star may fill its roche lobe in the core he burning stage and transfer matter at a rate of @xmath12 . the accumulation of he on top of the white dwarf may result in an eld ( scenario * b * ) . finally , if the mass of the companion to the white dwarf is below @xmath13 , the companion may fill its roche lobe on the main - sequence or in the subgiant phase . such a star could stably transfer matter at a rate which allows for the accumulation of , or of a critical - mass he layer ( scenario * c * ) . below we refer to all the potentially explosive situations listed above as `` sne ia , '' in spite of the fact that it is not entirely clear whether most of these configurations actually result in a sn ( see e.g. livio 1999 ) . we should note that while the above quoted masses are only approximate , the uncertainties are not such that they can change the expected rates significantly . a special remark has to be made concerning the exclusion of symbiotic stars . yungelson et al . ( 1995 ) have shown that the accumulation of in these systems occurs at a low rate : @xmath14 ( see however discussion in 5 ) . the accumulation of 0.15 of he via h burning occurs at a rate of @xmath15 , but the accretion rate is typically high , and hence , one would normally not expect an eld to ensue . rather , weak helium flashes may occur . a cautionary note has also to be made concerning elds which under certain sets of parameters have an occurence rate of @xmath4 in semidetached systems ( scenario * c * , yungelson & livio 1998 ) . we assumed that elds occur even if the accretion rate of hydrogen was initially high but then dropped to below @xmath16 . by this , we neglected the possible influence of hydrogen flashes on the helium layer . the response of the helium layer and the underlying white dwarf to the varying accretion rate ( from several times @xmath17 to @xmath18 ) was never treated in detail to the best of our knowledge . one may expect a competition between cooling ( due to the expansion of the hydrogen layer ) and the inward heat propagation ( due to nuclear burning ) . cassisi , iben , & tornamb ( 1998 ) for example , claim that heating by hydrogen flashes keeps the temperature of the he layer high and may even prevent the explosive ignition of he . rather , they conclude , quiescent burning may be expected ( for accretion rates @xmath19 @xmath20 m@xmath21 yr@xmath22 ) during which the white dwarf expands to giant dimensions and its envelope may be removed by interaction with the companion . if an explosion nevertheless happens , it may produce a powerful nova - type event ( a `` super nova '' ) . as a result of all of these uncertainties ( and others ) the issue of elds via a channel of hydrogen accretion is not definitively settled ( see livio 1999 ) . one of the cornerstones of channel * c * is the assumption of negligible mass loss in the form of a wind during helium flashes ( e.g. kato , saio , & hachisu 1989 ) , which allows for the accumulation of despite the flashes . the expansion of the helium layers found by cassisi et al . and the accompanying mass loss may ( in some cases at least ) prevent the accumulation of . thus , the realization frequency of both scenarios for sne ia ( explosion at or at a sub mass ) via channel * c * is a matter of considerable uncertainty . nevertheless , we include channel * c * in our consideration ( although see discussion in 5 ) . the basic difference between the possible progenitor scenarios of sne ia is in the `` evolutionary clock''the time interval between the formation of the binary system and the sn explosion . figure 2 shows the dependence of the supernova rate on time after an instantaneous star formation burst , for the four mechanisms listed above , as computed in the present study . the curves shown were computed for a common envelope efficiency parameter @xmath23 ; the dependence on this parameter within reasonable limits on between 0.5 and 2 is not too strong . for semidetached systems , we considered the case of mass exchange stabilized by the presence of a thick stellar wind ( hachisu , kato , & nomoto 1996 , henceforth , hkn ) as modified by yungelson and livio ( 1998 ) . further suggested modifications to the standard evolution will be discussed in 5 . the differences in the timespan between the formation of a binary and the sn ia event , and in the rate of decay of the sne rates in the different channels , manifests itself in the redshift dependence of the sne ia rates . our calculations are based on the assumption that the imf , and the mechanisms of sne ia are the same throughout the hubble time . this assumption may not be valid , for example because of metallicity effects . stars with lower @xmath24 develop larger helium and carbon - oxygen cores for the same main - sequence mass ( e.g. umeda et al . 1998 ) , and hence , form more massive white dwarfs . at the same time , the upper mass limit of stars which form co white dwarfs decreases towards a lower metallicity . however , assuming a power - law imf both of these effects result in an increased number of potential pre - sne ia white dwarfs . on the other hand , a low metallicity can inhibit strong optically thick stellar winds which are essential for the hkn model of sne ia ( kobayashi et al . assuming for the moment that several channels may contribute ( see however livio 1999 ) , the net effect may be an enhanced rate of sne ia from the channels of double - degenerates and elds from systems with nondegenerate he donors , and a reduction in the rate from the channel of hydrogen - donor systems . the rest - frame frequency of sne of a certain type at any time @xmath25 , @xmath26 , may be derived by convolving the star formation rate @xmath27 with the function @xmath28 giving the rate of sne after an instantaneous burst of star formation : @xmath29 two approaches for the evaluation of @xmath28 are encountered in the literature . the first is not to consider any specific mechanisms of sne ( which are still a matter of some debate ) , but rather to parameterize @xmath30 by the fraction of exploding stars in the binary star population ( the `` explosion efficiency '' ) and the delay between formation and explosion , or the `` evolutionary clock '' ( e.g. madau et al . 1998 ; dahln & fransson 1998 ; sadat et al . 1998 ) . for core - collapse supernovae ( sn ii and sn ib / c ) it is natural to assume that the shape of @xmath30 follows the sfr and the delay between the formation of the star and the sn event is negligible , since the lifetime of stars more massive than 10 is @xmath31myr . for sne ia madau et al . considered a parameterized @xmath28 with timescales of 0.3 , 1 , and 3 gyr between the formation of the wd and the explosion . these authors reproduce the ratio of @xmath32 in the local universe , if the explosion efficiency is 5% to 10% . a similar parameterization was adopted by dahln & fransson ( 1998 ) , who estimated the number of core - collapses and type ia sne which may be detected by ngst in different filters for different limiting stellar magnitudes . sadat et al . ( 1998 ) considered a power - law @xmath33 , and explored a range of @xmath34 from 1.4 to 1.8 . another parameter of sadat et al . is the rise time of the sne ia rate from 0 to a maximum which was fixed at 0.75 gyr . the ranges of @xmath34 and rise times were derived from models of the chemical evolution of fe in elliptical galaxies and in clusters of galaxies . concerning the explosion efficiency , sadat et al . actually do not exploit this parameter since they additionally normalize their rates , in order to reproduce the local rate of sne ia by the adopted sfr . a different approach to the determination of @xmath30 relies on population synthesis calculations . using this method , jrgensen et al . ( 1997 ) derived the rates of core - collapse supernovae ( sne ii and sni b ) , mergers of binary wds with a total mass exceeding , and collapses of chandrasekhar mass white dwarfs in semidetached systems ( in the standard model , without the thick wind of hkn ) . ruiz - lapuente & canal ( 1998 ; see also ruiz - lapuente , canal , & burkert 1995 ; canal , ruiz - lapuente , & burkert 1996 ) considered as sne ia progenitors merging double degenerates and cataclysmic binaries . for the latter channel , @xmath26 was estimated in two cases . first , the `` standard '' case which allows only thermally stable mass exchange for @xmath35 second , the case of the `` wind '' solution of hkn , which allows for mass exchange at rates of up to @xmath36 for systems with @xmath37 ruiz - lapuente & canal find a distinct difference between the behavior of the predicted sn ia rates _ vs_. limiting red stellar magnitude for different families of progenitors . namely , the @xmath38 relation for descendants of cataclysmic variables is much steeper than that for merging double degenerates . however , the computations of dahln & fransson ( 1998 ) do not show any significant difference in the behavior of the sne ia counts for different delays in the 0.33 gyr range ( the main difference between double degenerates and cataclysmic variable like systems is in the delay time ) . the star formation rate which is used as an ingredient in calculations of the evolution of the cosmic sne rate is usually derived from studies which model the observed evolution of the galaxy luminosity density with cosmic time . for example , madau , pozetti , & dickinson ( 1998 ) and madau , della valle , & panagia ( 1998 , hereafter mdvp98 ) have shown that the observational data can be fitted if one assumes , as an ingredient of the model , a time - dependent star formation rate . however , there exist uncertainties in this model , due to the uncertain amount of dust extinction at early epochs . for example , mdvp98 have shown that the same observational data may be fitted if one assumes a constant @xmath39 or a @xmath40-dependent dust extinction which rises rapidly with redshift , @xmath41 . the latter authors provide convenient fitting formulae for the star formation rates for these two cases . model 1 ( `` little dust extinction '' ) has @xmath42 where @xmath43 is the time in gyr , @xmath44 . model 2 ( `` @xmath40-dependent dust opacity '' ) has @xmath45 note that eqs . ( 2 ) and ( 3 ) give slightly different current sfr and the integrated values are also different by about 10% . both sfr models predict a similar , rather steep rise , by a factor @xmath46 , at @xmath47 . the difference between the two rates is in the behavior at @xmath48 . while in the `` little dust extinction '' case the rate drops almost linearly by a factor of about 10 to @xmath49 , in the `` @xmath40-dependent dust opacity '' case it continuously grows to @xmath50 , by a factor of @xmath11 . formally , the star formation process switches on discontinuously at @xmath50 . we should note that model 2 may be a more realistic representation of the global star formation history , since there is growing evidence of a significant effect of dust absorption at high @xmath40 ( e.g. pettini et al . 1998 ; calzetti & heckman 1998 ; huges et al . 1998 ; steidel et al . 1998 ; blain et al . also , selection effects due to the low surface brightness of galaxies ( e.g. ferguson 1998 ) or the shift of typical spectral features to the red ( e.g. hu , cowie , & mcmahon 1998 ) may result in an underestimate of the sfr at high redshifts . equation ( 2 ) gives a star formation history which is consistent with expectations from hierarchical clustering cosmologies , while eq . ( 3 ) gives the model prediction for sfr typical for a monolitic collapse scenario ( e.g. madau 1998b ) . ruiz - lapuente & canal ( 1998 ) used in their computations the star formation rate given by madau ( 1997 ) , without corrections for dust extinction . the effect of extinction was considered by dahln & fransson ( 1998 ) and by sadat et al . ( 1998 ) . in the latter case , the sfr at @xmath51 was taken to be several times higher than in the `` low - dust '' case . jrgensen et al . ( 1997 ) considered two modes of star formation : a `` burst '' lasting for 500 myr , and a continuous sfr for a hubble time , and computed models for a range of relative contributions of both star formation modes . the population synthesis code used for the computations of the sne rates was previously applied by the authors to a number of problems related to the population of galactic binary stars and , in particular , to sne . within the range of observational uncertainties , the code reproduces correctly the rates of sne inferred for our galaxy ( tutukov , yungelson , & iben 1992 ; yungelson & livio 1998 and references therein ) . throughout this paper we assume a cosmology with @xmath52 , @xmath53 . these values of the cosmological parameters are assumed only for convenience . our qualitative results and conclusions do not depend on this choice . star formation is assumed to start at @xmath54 . the hubble time in this model was taken to be 13 gyr . for the different sne ia scenarios listed in 2 and for different star formation histories , we first calculated the rest - frame rates of events @xmath55 . we then computed differential functions for the number of events observed at redshift @xmath40 and cumulative functions @xmath56 . we use eq . [ 3.3.25 ] from zeldovich & novikov ( 1983 ) for the number of events observed from a layer between redshifts @xmath40 and @xmath57 in an expanding , curved universe , taking into account time dilation : @xmath58 where , for the particular case of @xmath52 @xmath59 ^ 2 } { z^2(1+z)^{5/2}}~~.\ ] ] notice , that @xmath60 . time @xmath25 is related to @xmath40 as @xmath61 we operate with the _ number of events per yr _ instead of expressing the sne rates in the more conventional supernovae units ( snu ) , since both the computation of blue luminosities and their observational determination involve additional parameters ( expressing the rates in snu may result in loss of information on both the sne rates and on the sfr ) . our simulations give the rates of sne as a function of @xmath40 . clearly , the number of observable events depends on other factors such as the limiting stellar magnitude of the sample , etc . nevertheless , our results provide the basis for theoretical expectations , which need subsequently to be convolved with observational selection effects . in principle , ngst observations can approach the theoretical limits . figure 3 compares the values of @xmath62 for the different channels of sne and the different assumptions about the sfr given by eqs . ( 2 ) and ( 3 ) . figure 4 shows the behavior with redshift of the cumulative numbers of sne . the behavior of @xmath62 can be understood as follows . in model 1 ( low dust ) as one progresses from @xmath63 to @xmath50 , the sfr reaches a maximum at @xmath64 the maxima of the rest - frame sne rates happen at a slightly lower @xmath40 in order of decreasing delay times : elds in systems with subgiant companions , accumulations in the latter , mergers of double degenerates , elds in systems with nondegenerate he donors , core - collapse sne ( fig . 2 ) . the behavior of the @xmath62 counts depends also on the geometrical @xmath40-dependent factors given by eqs . ( 4 ) and ( 5 ) . in particular , the derivative of the product @xmath65 changes sign from positive to negative at @xmath66 . this factor shifts the maximum in the counts to a lower @xmath40 . the steep rise of @xmath62 at low @xmath40 is entirely due to the expanding horizon . similarly , in model 2 ( @xmath40-dependent dust opacity ) , the behavior of @xmath62 at low @xmath40 is dominated by the expansion of the comoving volume and the rates suggested by the two models are almost indistinguishable . however , already at @xmath67 , the increase in the rates in model 2 becomes somewhat less steep , reflecting the more moderate growth of the sfr . the rate of core - collapse sne starts to decrease at @xmath68 despite the continuous growth of the sfr . this is a consequence of the negative @xmath69 . the rates of sne ia start to decline at a higher @xmath40 , as a consequence of the longer delay times . the difference in the time delays between sne ii and the different hypothetical sne ia manifests itself in an increase in the sn ia / sn ii ratio at low @xmath40 and its subsequent decline ( fig . this feature was already noticed by yungelson & livio ( 1998 ) for sne ia from double degenerates , but in the present study we find that ( i ) this effect is less pronounced due to the different approximation to the sfr and ( ii ) the redshift of the maximum of the ratio is different for different sne ia scenarios . the difference in the rate of decline of @xmath62 at @xmath70 is clearly distinct in models 1 and 2 and may provide important information about the star formation behavior . the most pronounced feature of @xmath62 for both types of dust models is the disappearance of sne ia at @xmath71 for the channels of progenitors with relatively long delays . thus , in principle , a determination of sne ia rates at @xmath72 with ngst can unambiguously distinguish between different progenitor models . long delay times are typical for both modes ( chandrasekhar or sub - chandrasekhar explosions ) of sne ia resulting from systems with subgiant donors . the relative role of different channels for sne ia changes with @xmath40 . in both models 1 and 2 ( for the dust ) mergers of double degenerates dominate over elds in systems with he nondegenerate donors up to @xmath73 . in model 1 , elds in systems with subgiants dominate over he - eld at @xmath74 and over dd - ch at @xmath75 . in model 2 these limits are at about @xmath76 and @xmath77 . if it were the case that all three channels really contribute to sne ia but have somewhat different characteristics , one would expect to find variations in the statistical properties of sne ia with redshift . we will return to this point in the discussion . as expected , the cumulative numbers of sne grow faster in the `` low dust '' case than in the model with dust . only the cumulative counts of sne ii and sne ia from the dd - ch and he - eld channels grow continuously to high redshifts , while those for sne involving subgiants saturate at @xmath78 . to summarize this section : observations of sne beyond @xmath79 can provide valuable information on the star formation rate ( see also 5 ) . the counts of sne ia at @xmath80 will indicate the timescale of the delay between births of binaries and sn events and will then provide information on the nature of the progenitors . the main uncertainty in the global sfr is due to the effects of dust obscuration in star - forming galaxies ( see e.g. calzetti & heckman 1998 ; pettini et al . 1998 ; for a discussion of the fraction of light absorbed by dust ) . therefore , it is worthwhile to investigate the cosmic history of sne for several parameterized sfr . we consider four parameterized modes of galactic star formation ( intended to bracket and cover a range of possibilities ) : model 3constant star formation rate from @xmath81 to @xmath63 ; model 4a star formation burst which begins at @xmath50 and has a constant sfr for 1 gyr ; model 5a star formation burst which begins at @xmath50 and has a constant sfr for 4 gyr ; model 6an initial star formation burst which lasts for 4 gyr with a constant sfr and converts 50% of the total mass into stars , followed by another stage of a lower constant sfr which produces the remaining 50% of the stars ( `` step - wise sfr '' ) . for all the cases we normalize the sfr in such a way that the total amount of matter converted into stars is equal to the integral over time of eq . the overall normalization is of no real significance however , since we are interested in the qualitative behavior of sne counts . the computations provide us with information on the behavior of sne rates with redshift , for different star formation histories . the results provide insights into the understanding the sne histories in galaxies of different morphological types , which show a wide variety of star formation patterns both along the hubble sequence and within particular classes ( e.g. sandage 1986 ; hodge 1989 ; kennicutt , tamblyn , & congdon 1994 ; kennicutt 1998 ) . even among the local group dwarf galaxies one encounters very different star formation histories , including early bursts , almost constant sfr , and step - wise ones ( e.g. mateo 1998 ) . figures 5 and 6 present the number counts of sne ia per unit @xmath82 and the cumulative rates of events @xmath83 for the above models . the results can be summarized as follows . models 3 and 4 , with initial starbursts of different durations @xmath84 , clearly predict an abrupt decline in the sne ii rate when moving from @xmath85 to lower redshifts , reflecting the cessation of star formation . the redshift of this sharp decline in the rate indicates ( for given cosmological parameters ) the value of @xmath84 . it also depends of course on @xmath85 . the behavior of sne ia from elds in systems with he donors ( he - eld ) and chandrasekhar mass sne in systems with subgiant donors ( sg - ch ) shows a similar decline , but shifted to a lower @xmath40 and less abrupt . for stellar populations with strong initial star formation bursts this means that , if he - eld and sg - ch sne ia were the only mechanisms for sne ia , then as one advances to higher redshifts , first the rate of sne ia and then the rate of sne ii would rapidly rise . in the case of sg - ch sne ia the rate would rapidly decline at @xmath86 . such a behavior of the rates of sne ia in e - s0 galaxies would provide evidence supporting the sg - ch mechanism for sne ia . strong initial peaks in the sfr followed by a variation of the sfr on a short timescale manifest themselves in changes in @xmath87 for sne ia . these changes are delayed ( to lower redshifts ) compared to the decrease in the sne ii rates . sne ia from the mergers of double degenerates ( dd - ch ) are the only types of events which may show up close to @xmath85 and which continue to @xmath63 irrespective of the star formation mode . although sne ia from elds in subgiant systems ( sg - eld ) start to explode only at @xmath88 , in the constant sfr and step - wise sfr models , at @xmath89 the distribution of their number counts _ vs_. @xmath40 becomes very similar to the one from double degenerates ( dd - ch ) both in morphology and in amplitude . these sne , however , follow the variations in the sfr slightly slower . these two types of sne ia are the only events which may be present at low @xmath40 even if the star formation process ceased long ago ( see however 5 ) . sne ia from collapses of chandrasekhar mass white dwarfs in subgiant systems may be observed only if the star formation still continues or ceased less than @xmath90 gyr ago ( see however 5 ) . the same is true for sne from elds in systems with nondegenerate donors . a fast decline of the sne ia rate shortly after ( at lower @xmath40 ) the decline of the sne ii rate would indicate that either he - eld or sg - ch occur . \6 . in the case of a sfr which was almost constant during the past several gyr there is no decline in the sne ia / sne ii ratio between @xmath63 and 1 . the difference between the behavior of @xmath62 for a constant - rate and for step - wise sfr models is not significant . this means that only a very significant increase in the sfr towards high @xmath40 ( like in model 2 ) may be reflected in the behavior of the differential sne counts . on the other hand , a rapid decline in the sfr beyond a certain redshift ( like in model 2 ) can be detected easily . the counts of @xmath62 in the redshift range @xmath910.4 can hardly provide any information about the sfr since they are dominated by the increase of the comoving volume . since observations of sne ia are now being used as one of the main methods for the determination of cosmological parameters , the importance of identifying the progenitors of sne ia can not be overemphasized . we have shown that different progenitor models result in different sne ia rates ( or different ratios of frequencies of sne ia to those resulting from massive stars ) as a function of redshift . one key difference , for example , is in the fact that in all the models that involve relatively long delays between the formation of the system and the sn event ( e.g. models with subgiant donors ) , the ratio @xmath92 decreases essentially to zero at @xmath72 ( fig . thus , future observations with ngst will in principle be able to determine the viability of such progenitor models on the basis of the frequencies of sne ia at high redshifts . probably the most important question that needs to be answered is the following : assuming that two ( or more ) different classes of progenitors may produce sne ia , is it possible that the rate of sne ia is entirely dominated by one class at low redshifts ( @xmath93 ) and by another at higher redshifts ( @xmath94 ) ? clearly , if this were the case , then the suggestion of a cosmological constant would have to be re - examined ( sne ia at the higher @xmath40 only need to be systematically dimmer by @xmath95 mag to mimic the existence of a cosmological constant ) . an examination of the qualitative behavior of the rates in fig . 7 reveals that _ in principle _ , the rate at low redshifts could be dominated by elds , while the rate at higher redshifts by coalescing double - degenerates . however , if elds produce sne ia at all , these are probably of the underluminous variety ( like sn 1991bg ; e.g. nugent et al . 1997 ; livio 1999 ; ruiz - lapuente et al . therefore , a division of this type would produce exactly the opposite effect to the one required to explain away the need for a cosmological constant ( the high redshift ones would be brighter ) . a second possibility is that the rate of sne ia resulting from the accumulation of in systems with giant or subgiant components ( sg - ch ) has been underestimated . this is in fact a very likely possibility . a number of potential ways have been suggested to increase the frequency of sne ia of this class ( e.g. hachisu , kato & nomoto 1999 ) . these ways include : ( i ) mass stripping from the ( sub-)giant companion by the strong wind from the white dwarf ( this has the effect of increasing the range of mass ratios which result in stable mass transfer ) . ( ii ) an efficient angular momentum removal by the stellar wind in wide systems ( where the wind velocity and orbital velocity are comparable ; this increases the range of binary separations with result in interaction ) . while large uncertainties plague both of these suggestions ( see livio 1999 for a discussion ) , it is definitely possible that some physical processes which have not yet been properly included in the population synthesis calculations , will result in a significant increase in the rates from the channel with giant or subgiant companions . this means that in principle , the curve describing the sg - ch channel ( subgiant donor ) in fig . 7 ( with the @xmath40-dependent dust opacity ) , may have to be shifted upwards ( essentially parallel to itself , because of the involved delays ) . the curve could be shifted just enough for double - degenerates to dominate at redshifts @xmath96 , while sg - ch dominate at @xmath97 . the question is now , could such a dominance shift be responsible for the apparent need for a cosmological constant ? the answer is that this is definitely possible _ in principle_. in particular , it has recently been suggested that the fiducial risetime of nearby sne ia is @xmath98 days longer than that of high - redshift sne ia ( riess et al . 1999a , b ) . it is far from clear though , whether such a change in the risetime ( if real ) could be attributed to different progenitor classes or to other evolutionary effects . one possibility could be that because sne ia resulting from double - degenerates ( if they indeed occur ; livio 1999 ) may have different surface compositions from those resulting from subgiant donors , this could affect the risetime . we would like to note , however , that we find the possibility of one progenitor class dominating at low redshifts and another at high redshifts rather _ unlikely _ ( see also livio 1999 ) . the reason is very simple . as fig . 7 shows , even if the sg curve were to be shifted upwards , the result would be that the local ( low @xmath40 ) sample would have to contain a significant fraction of the sne resulting from the sg channel . therefore , unless sne ia from the sg channel conspire to look identical to those from double - degenerates at low @xmath40 , but different at high @xmath40 , this would result in a _ much less homogeneous _ local sample than the observed one ( which has 8090% of all sne ia being nearly identical `` branch normals '' ; e.g. branch 1998 and references therein ) . consequently , it appears that the observational indication of the existence of a cosmological constant can not be the result of us being `` fooled '' by different progenitor classes ( this does not exclude the possibility of other evolutionary effects ) . finally , our models indicate that a careful determination of the rates of sne ia as a function of redshift can place significant constraints on the cosmic star formation history , and on the significance of dust obscuration . this work was supported by the russian foundation for basic research grant no . 96 - 02 - 16351 . lry acknowledges the hospitality of the space telescope science institute . ml acknowledges support from nasa grant nag5 - 6857 . we acknowledge helpful discussions with n. chugaj , m. sazhin , and a. tutukov , and useful comments by d. branch .

we discuss the cosmic history of supernovae on the basis of various assumptions and recent data on the star formation history . we show that supernova rates as a function of redshift can be used to place significant constraints on progenitor models , on the star formation history , and on the importance of dust obscuration . we demonstrate that it is unlikely that the current observational indications for the existence of a cosmological constant are merely an artifact of the dominance of different progenitor classes at different redshift intervals . _ subject headings : _ binaries : close stars : formation supernovae : general cosmology : observations

in the last two decades rapid advancement in the theory and applications of complex networks has taken place related to the widespread recognition of their importance in social life , natural sciences and technology @xcite . an important part of this trend was development of research on complex systems in which interactions among their constituent parts are determined by the underlying structure of complex networks @xcite . in this context much effort was devoted to study the effect of the complex structure of interactions on the behavior of generic models of statistical physics exhibiting collective phenomena such as phase transitions . for example , ferromagnetic ( fm ) phase transition in the ising model on complex , possibly heterogeneous networks was studied by means of various analytic @xcite and numerical @xcite methods . also spin glass ( sg ) transition @xcite in the ising and related models on complex networks with quenched disorder of fm and antiferromagnetic ( afm ) interactions was investigated using , e.g. , variants of the replica method @xcite , effective field theory @xcite and monte carlo ( mc ) simulations @xcite . in connection with recent interest in even more complex structures ( `` networks of networks '' ) much attention has been devoted to multiplex networks ( mns ) which consist of a fixed set of nodes connected by various sets of edges called layers @xcite . mns naturally emerge in many social systems ( e.g. , transportation or communications networks ) , and interacting systems on such structures exhibit rich variety of collective behaviors and critical phenomena . for example , percolation transition @xcite , cascading failures @xcite , diffusion processes @xcite , epidemic spreading @xcite , etc . , were studied on mns . also the fm transition in the ising model @xcite as well as diversity of first - order , second order and mixed - order transitions in a related ashkin - teller model @xcite were investigated in the above - mentioned models with the structure of mns . as a natural extension of the above - mentioned research in this paper the sg transition is studied in the ising model with the quenched disorder of the exchange interactions superimposed on the underlying structure of a mn . in sec . 2 the hamiltonian of the model is defined , with spins placed on a fixed set of nodes and with separately generated sets of edges ( layers ) , with possibly different distributions of the degrees of nodes , corresponding to randomly assigned fm and afm exchange interactions ; the layers can have , e.g. , the structure of random erds - rnyi ( er ) graphs @xcite or heterogeneous scale - free ( sf ) networks @xcite and are generated from the so - called static model @xcite . in sec . 3 the thermodynamic properties of the above - mentioned model are investigated by means of the replica method @xcite . the approach used here follows the study of the dilute sg model with infinite - range interactions @xcite and is a direct generalization to the case of mns of a procedure applied successfully to investigate the fm and sg transitions in the ising model on random er graphs @xcite , heterogeneous sf networks @xcite and the fm transition in the ising model on mns @xcite . in sec . 4 the fm and sg transitions from the paramagnetic state are investigated in the above - mentioned model , the corresponding critical temperatures are evaluated from the replica symmetric ( rs ) solution and the effect of the distributions of the degrees of nodes within consecutive layers as well as the influence of the correlations between them on the phase diagram is emphasised . besides , these analytic results are partly compared with mc simulations . in sec . 5 the critical exponent for the sg order parameter in the vicinity of the sg transition temperature is determined semi - analytically for the ising model on mns with different distributions of the degrees of nodes within layers . 6 is devoted to summary and conclusions . mns consist of a fixed set of nodes connected by several sets of edges ; the set of nodes with each set of edges forms a network which is called a layer of a mn @xcite . in this paper only fully overlapping mns are considered , with all @xmath0 nodes belonging to all layers . in the following , for simplicity , mns with @xmath0 nodes and only two layers denoted as @xmath1 , @xmath2 are considered . the layers ( strictly speaking , the sets of edges of each layer ) are generated separately , and , possibly , independently . as a result , multiple connections between nodes are not allowed within the same layer , but the same nodes can be connected by multiple edges belonging to different layers . the nodes @xmath3 are characterized by their degrees @xmath4 , @xmath5 within each layer , i.e. , the number of edges attached to them within each layer . the , possibly heterogeneous , distributions of the degrees of nodes within each layer are denoted as @xmath6 , @xmath7 , and the mean degrees of nodes within each layer as @xmath8 , @xmath9 . in the ising model on a mn with two layers two - state spins @xmath10 are located in the nodes @xmath11 and edges within the layers @xmath1 , @xmath2 connecting pairs of nodes @xmath12 , @xmath13 correspond to exchange interactions with integrals @xmath14 , @xmath15 , respectively . the exchange integrals are quenched random variables . it should be emphasised that in the model under study there is only one spin @xmath16 located in each node which interacts with all its neighbors within all layers . the hamiltonian of the model is @xmath17 where the sums are over all edges belonging to the layer @xmath1 ( @xmath2 ) . following the studies of the dilute ising sg models with infinite - range interactions on random er graphs @xcite and sf networks @xcite in this paper it is assumed that the exchange integrals within each layer can assume only two values @xmath18 ( @xmath19 ) and @xmath20 as well as @xmath21 ( @xmath22 ) and @xmath23 which are assigned to the edges of the layer @xmath1 ( @xmath2 ) with probability @xmath24 and @xmath25 ( @xmath26 and @xmath27 ) , respectively , and that these assignments are independent for the two layers . thus the distributions of the exchange integrals within each layer @xmath28 , @xmath29 are independent and have the form @xmath30 \nonumber\\ p_{r^{(b)}}\left(\left\ { j_{ij}^{(b ) } \right\ } \right ) & = & \prod_{\left ( i , j\right ) \in g^{(b ) } } \left [ r^{(b ) } \delta\left ( j_{ij}^{(b ) } -j^{(b)}\right ) + \left ( 1-r^{(b)}\right ) \delta \left ( j_{ij}^{(b ) } + j^{(b)}\right ) \right ] . \nonumber\\ & & \label{papb}\end{aligned}\ ] ] taking into account the form of the hamiltonian , eq . ( [ ham ] ) , it may be supposed that the sg ising model on a mn can be reduced to the sg ising model on a network with a set of edges being a superposition of the sets of edges of the two layers and a proper four - point distribution of the exchange integrals @xmath31 . however , these two ising models are not equivalent to each other since in a mn the layers are generated separately ( although not necessariliy completely independently ) and thus , e.g. , probabilities for the pairs of nodes to be connected by an edge or statistical averages over different realizations of the sets of edges should be evaluated separately for each layer . this difference is particularly imporatnt in the case of mns with heterogeneous layers , where it was shown in ref . @xcite that even in the simplest case of purely fm interactions with @xmath32 the critical temperatures for the two above - mentioned ising models can differ noticeably . in ref . @xcite sg transition was investigated in the ising model on heterogeneous networks generated from the static model @xcite . using this model networks with a fixed number of nodes @xmath0 and desired distributions of the degrees of nodes can be generated as follows . first , a weight @xmath33 is assigned to each node so that the condition @xmath34 was fulfilled . then , nodes are linked with edges in accordance with the prescribed sequence of weights , by selecting a pair of nodes @xmath12 , @xmath13 ( @xmath35 ) with probablities @xmath33 , @xmath36 , respectively , linking them with an edge and repeating this process @xmath37 times . in this way a network is obtained with the probability that the nodes @xmath12 , @xmath13 are linked by an edge @xmath38 , with the mean degree of nodes @xmath39 , and with the distribution of the degrees of nodes depending on the choice of the weights . in particular , random er graph is obtained if @xmath40 is assumed for all @xmath12 . for a sequence @xmath41 associated with the nodes @xmath3 , where @xmath42 and @xmath43 , sf network is obtained with the distribution of the degrees of nodes @xmath44 , @xmath45 . in an ensemble of networks generated from the static model the mean degree of a given node @xmath12 is @xmath46 . similarly , in this paper the ising model on a mn with layers generated from the static model is studied . the mn with a fixed set of nodes and two layers @xmath1 , @xmath2 is generated by associating weights @xmath47 , @xmath48 with the nodes separately to generate each layer . in this way the layers can have different distributions of the degerees of nodes @xmath6 , @xmath7 . let us note that the numbering of nodes @xmath3 while generating each layer can be assumed the same or different . in the case of random er layers this distinction is unimportant , however , in the case of sf layers it can introduce correlations between the two sequences of weights @xmath47 , @xmath48 , @xmath3 , where now and henceforth @xmath12 denotes the index of the node in a mn , common for all layers . in particular , a mn with independent layers is obtained by randomly and independently associating weights from the two appropriate sets of weights with the nodes and then linking them with edges according to the prescribed sequence of weights within each layer . the starting point to study the thermodynamic properties of the ising model on mns is to evaluate the free energy averaged over a statistical ensemble of mns generated according to a given rule and with given quenched disorder of the exchange integrals . hence , the free energy is @xmath49_{r}\right]_{av}$ ] , where @xmath50 is the partition function for the ising model on a particular mn with a particular distribution of @xmath31 , the average @xmath51_{av}$ ] is taken over all possible random realizations of a set of edges in a mn of a given kind ( i.e. , of the two sets of edges in the separately generated layers ) , and the average @xmath51_{r}$ ] is taken over all possible realizations of the distributions @xmath52 , @xmath53 , eq . ( [ papb ] ) , for fixed sets of edges within each layer @xmath1 , @xmath2 . in the framework of the replica method the free energy is formally evaluated as @xmath54_{r}\right]_{av } -1\right\}/n$ ] . the average of the @xmath55-th power of the partition function is @xmath56_{r } \right]_{av } = { \rm tr}_{\{s^{\alpha}\ } } \left [ \left [ \exp\left ( \beta \sum_{\left ( i , j\right)\in g^{(a ) } } j_{ij}^{(a ) } \sum_{\alpha = 1}^{n}s_{i}^{\alpha}s_{j}^{\alpha}\right ) \exp\left ( \beta \sum_{\left ( i , j\right)\in g^{(b ) } } j_{ij}^{(b ) } \sum_{\alpha = 1}^{n}s_{i}^{\alpha}s_{j}^{\alpha}\right ) \right]_{r}\right]_{av } , \label{zn}\ ] ] i.e. , it is the average of a product of @xmath55 partition functions for non - interacting replicas ( copies ) of the system , the trace @xmath57 is taken over all replicated spins @xmath58 , and @xmath59 is the replica index . as pointed out in ref . @xcite generation of a mn takes place in two stages : first , in which the weights @xmath47 , @xmath48 are separately assigned to the nodes @xmath3 , and second , in which the nodes are connected with edges taking into account the prescribed weights within each layer . at the first stage the weights from the two sets of weights can be assigned to the nodes either independently or certain correlations between the two weights assigned to the same nodes can be present ( e.g. , higher weights from both sets can be assigned to the same nodes ) . such correlations can change substantially the thermodynamic properties of the model , e.g. , the critical temperature for the fm transition @xcite . thus , it is necessary to consider separately classes of mns characterized by given pairs of sequences of weights @xmath47 , @xmath48 , @xmath3 . then the average @xmath51_{av}$ ] in eq . ( [ zn ] ) is evaluated separately for each class , and is taken over all possible realizations of the two layers by connecting the nodes with edges according to the weights @xmath47 , @xmath48 , @xmath3 characterizing this class . if necessary , a sort of further averaging over different classes of mns ( e.g. , over all classes with the same correlation coefficient between the two sequences of weights @xmath47 , @xmath48 , @xmath3 ) can be performed by replacing the sums over @xmath0 nodes by their expected values in the resulting expressions for the critical temperature . for a class of mns with fixed ( correlated or not ) assignment of the weights @xmath47 , @xmath48 to the nodes the sets of edges of each layer are generated independently of each other . thus the average over all realizations of the set of edges of a mn in eq . ( [ zn ] ) can be taken independently over all realizations of the sets of edges in the layers @xmath1 and @xmath2 in accordance with these weights . denoting the respective averages by @xmath51_{av}^{(a)}$ ] , @xmath51_{av}^{(b)}$ ] , taking into account that assignment of the exchange integrals @xmath14 , @xmath15 to the edges of the layers @xmath1 , @xmath2 also takes place independently for each layer and denoting the averages over all possible realizations of the distributions @xmath52 and @xmath53 as @xmath51_{r^{(a)}}$ ] and @xmath51_{r^{(b)}}$ ] , respectively , eq . ( [ zn ] ) can be written as @xmath60_{r } \right]_{av}&= & { \rm tr}_{\{s^{\alpha}\ } } \left\ { \left [ \left [ \exp\left ( \beta \sum_{\left ( i , j\right)\in g^{(a ) } } j_{ij}^{(a)}\sum_{\alpha = 1}^{n}s_{i}^{\alpha}s_{j}^{\alpha}\right ) \right]_{r^{(a ) } } \right]_{av}^{(a ) } \right . \nonumber\\ & \times & \left . \left [ \left [ \exp\left ( \beta \sum_{\left ( i , j\right)\in g^{(b ) } } j_{ij}^{(b)}\sum_{\alpha = 1}^{n}s_{i}^{\alpha}s_{j}^{\alpha}\right ) \right]_{r^{(b ) } } \right]_{av}^{(b)}\right\}. \label{zn1}\end{aligned}\ ] ] the two factors can be evaluated as in ref . @xcite , @xmath61_{r^{(a ) } } \right]_{av}^{(a ) } = \nonumber\\ & & \prod_{i < j } \left\ { \left ( 1-f_{ij}^{(a ) } \right ) + f_{ij}^{(a ) } \left [ \exp\left ( \beta j_{ij}^{(a ) } \sum_{\alpha = 1}^{n}s_{i}^{\alpha}s_{j}^{\alpha}\right ) \right]_{r^{(a ) } } \right\ } = \nonumber\\ & & \exp \left\ { \sum_{i < j } \ln \left [ 1+f_{ij}^{(a ) } \left [ \exp\left ( \beta j_{ij}^{(a ) } \sum_{\alpha = 1}^{n}s_{i}^{\alpha}s_{j}^{\alpha}\right ) -1\right]_{r^{(a ) } } \right ] \right\ } \approx \nonumber\\ & & \exp\left [ \sum_{i < j } nk^{(a ) } v_{i}^{(a)}v_{j}^{(a)}\left [ \exp\left ( \beta j_{ij}^{(a ) } \sum_{\alpha = 1}^{n}s_{i}^{\alpha}s_{j}^{\alpha}\right ) -1 \right]_{r^{(a ) } } \right ] , \label{zn2}\end{aligned}\ ] ] and similarly for the average @xmath62_{r^{(b ) } } \right]_{av}^{(b)}$ ] . then , since @xmath63 , the relation @xmath64_{r^{(a ) } } = \left [ \prod_{\alpha } \cosh \beta j^{(a ) } \left ( 1 + s_{i}^{\alpha}s_{j}^{\alpha } \tanh\beta j^{(a ) } \right ) \right]_{r^{(a)}}\ ] ] can be used in eq . ( [ zn2 ] ) , which yields @xmath65_{r^{(a ) } } \right]_{av}^{(a ) } \propto \nonumber\\ & & \exp\left [ \sum_{i < j } nk^{(a ) } v_{i}^{(a)}v_{j}^{(a ) } \left ( { \bf t}_{1}^{(a ) } \sum_{\alpha } s_{i}^{\alpha}s_{j}^{\alpha } + { \bf t}_{2}^{(a ) } \sum_{\alpha < \beta } s_{i}^{\alpha}s_{i}^{\beta } s_{j}^{\alpha}s_{j}^{\beta } + \ldots \right ) \right ] , \label{zn4}\end{aligned}\ ] ] where @xmath66_{r^{(a ) } } \stackrel{n\rightarrow 0}{\rightarrow } ( 2r^{(a)}-1 ) \tanh \beta j^{(a ) } , \nonumber\\ { \bf t}_{2}^{(a)}&= & \left [ \cosh^{n}\beta j_{ij}^{(a ) } \tanh^{2}\beta j_{ij}^{(a)}\right]_{r^{(a ) } } \stackrel{n\rightarrow 0}{\rightarrow } \tanh^{2 } \beta j^{(a ) } , \label{t1t2}\end{aligned}\ ] ] etc . ; similar expansion can be obtained for the average @xmath67_{r^{(b)}}\right]_{av}^{(b)}$ ] . finally , after applying the hubbard - stratonovich identity to the expressions of the form ( [ zn4 ] ) , separately for the two averages @xmath67_{r^{(a)}}\right]_{av}^{(a)}$ ] , @xmath67_{r^{(b)}}\right]_{av}^{(b)}$ ] , and grouping terms connected with the same nodes @xmath12 it is obtained that @xmath68_{r}\right]_{av } = \nonumber \\ & & \int dq_{\alpha}^{(a ) } \int dq_{\alpha \beta}^{(a)}\ldots \int dq_{\alpha}^{(b ) } \int dq_{\alpha\beta } ^{(b)}\ldots \exp \left [ -nn\beta f \left ( q_{\alpha}^{(a ) } , q_{\alpha\beta}^{(a)},\ldots q_{\alpha}^{(b ) } , q_{\alpha\beta } ^{(b ) } \ldots \right ) \right ] \nonumber \\ & & \equiv \int \ d{\bf q } \exp \left [ -nn\beta f({\bf q } ) \right ] , \label{zn6}\end{aligned}\ ] ] with @xmath69 where @xmath70 is the trace over the replicated spins at node @xmath12 , and @xmath71 and similarily for @xmath72 . the elements of a set @xmath73 , @xmath74 form in a natural way two subsets of the order parameters associated with the two layers of the multiplex network @xmath75 , @xmath76 . the first two order parameters , @xmath77 where the averages are evaluated as @xmath78 are called magnetizations for convenience ; the next two order parameters @xmath79 are called sg order parameters , etc . the simplest rs solution for the order parameters is obtained under the assumption that spins with different replica index are indistinguishable . in the case of the ising model on a mn this solution has a form @xmath80 , @xmath81 , etc . , and @xmath82 , @xmath83 , etc . , for @xmath84 , etc . , where , in general , @xmath85 , @xmath86 , etc . @xcite . assuming the above - mentioned form of the rs solution and truncating the free energy , eq . ( [ zn5 ] ) , at the order of @xmath87 yields @xmath88 where @xmath89.\end{aligned}\ ] ] using once more the hubbard - stratonovich identity and evaluating the trace over @xmath90 yields @xmath91 \frac{1}{\sqrt{2\pi } } \int dz e^{-z^{2}/2}\left[2 \cosh \eta_{i}(z ) \right]^{n } , \label{zi}\ ] ] where @xmath92 in the limit @xmath93 it is possible to expand @xmath94^{n } \approx 1+n \ln \left [ 2\cosh \eta_{i}(z)\right]$ ] . inserting this expansion in eq . ( [ zi ] ) and again expanding @xmath95 in eq . ( [ nbf ] ) yields for @xmath93 @xmath96.\nonumber\\ & & \label{bf}\end{aligned}\ ] ] with @xmath97 given by eq . ( [ bf ] ) the integral in eq . ( [ zn6 ] ) can be evaluated using the saddle point method . for this purpose , the minimum of the function @xmath98 should be found , and the necessary condition for the existence of extremum leads to the following set of self - consistent equations for the order parameters , @xmath99 and two similar equations for @xmath100 , @xmath101 . for small @xmath102 , @xmath100 , @xmath103 , @xmath101 , after expanding the logarithm and evaluating the moments in eq . ( [ bf ] ) the free energy can be written as @xmath104 then the system of equations in eq . ( [ system ] ) leads to the following system of linear equations for @xmath102 , @xmath100 , @xmath103 , @xmath101 , @xmath105 non - zero solutions of the system of eq . ( [ mamb ] ) exist if the determinant is zero . due to the block structure of eq . ( [ mamb ] ) this condition is equivalent to the requirement that the determinant of the system of the first two equations of the above system is zero or the determinant of the last two equations of the above system is zero . from the former condition the critical temperature for the fm transition can be evaluated : the corresponding equation for the critical temperature is quadratic with respect to @xmath106 , @xmath107 , thus it has two solutions of which that with a higher value corresponds to @xmath108 . from the latter condition the critical temperature for the sg transition can be evaluated : the corresponding equation for the critical temperature is biquadratic with respect to @xmath106 , @xmath107 , thus it has four solutions of which the real solution with the highest value corresponds to @xmath109 . in sec . 4.2 - 4.5 both critical temperatures are evaluated for the mn with random er and sf layers . from the above - mentioned procedure , for fixed model parameters , it is possible to determine on the phase diagram the boundary between the paramagnetic andt the fm or sg phase , depending on which of the temperatures @xmath108 , @xmath109 is higher . the boundary between the fm and sg phases runs along the almeida - thouless line at which the fm phase becomes unstable against the occurrence of the reentrant sg phase as the temperature is lowered @xcite . determination of the location of this line on the phase diagram is not straightforward in the case of the ising model on mns for which , in contrast with sg models considered so far , the rs solution is characterized by two sets of order parameters @xmath102 , @xmath110 and @xmath100 , @xmath111 connected with the two layers @xmath1 , @xmath2 ; moreover , it requires numerical solution of a set of four nonlinear equations in eq . ( [ system ] ) . thus , this problem is left for future research and full phase diagrams for the model under study are not presented in this paper . the space of parameters for the ising model on a mn is large and comprises @xmath18 , @xmath21 and the parameters of the layers , e.g. , in the case of sf layers , @xmath112 , @xmath113 , @xmath114 , @xmath115 , @xmath24 , @xmath26 as well as the correlation between the degrees of nodes within the layers @xmath4 , @xmath5 , @xmath3 . in order to constraint the number of independent parameters henceforth all formulae are obtained under the assumptions @xmath116 , @xmath117 ( i.e. , in the layer @xmath1 the interactions are purely fm ) and @xmath118 ( i.e. , in the layer @xmath2 all interactions are purely afm ) ; moreover , mostly the case @xmath119 is considered . under such assumptions it is possible to study the , probably most intriguing , problem of the influence of the difference between the distributions of the degerees of nodes @xmath6 , @xmath7 and of the correlation between degrees of nodes within different layers on the fm and sg transition in the case of balanced fm and afm interactions . for random er layers there is @xmath120 , @xmath3 . from the definition of the magnetizations , eq . ( [ ordpar ] ) , as well as from the first two equations in eq . ( [ mamb ] ) follows that @xmath121 and the equation for the fm critical temperature is linear rather than quadratic with respect to @xmath122 . the result is @xmath123^{-1 } , \label{tfmer}\ ] ] thus @xmath124 for @xmath125 and if the density of edges corresponding to fm interactions is smaller than that of edges corresponding to afm interactions the transition to the fm phase can not occur . from the definition of the sg order parameters , eq . ( [ ordpar1 ] ) , as well as from the last two equations in eq . ( [ mamb ] ) follows that @xmath126 and the equation for the sg critical temperature is linear with respect to @xmath127 . the result is @xmath128^{-1/2 } , \label{tsger}\ ] ] which is always finite and positive . thus for @xmath125 there is only sg transition from the paramagnetic phase , and in the opposite case the transition can be either to the sg or to the fm phase , depending on which of the critical temperatures , @xmath109 or @xmath108 is higher for given @xmath112 , @xmath113 . the mn with two independent sf layers is generated by randomly and independently assigning to the nodes @xmath3 the weights from a set @xmath129 , @xmath130 to generate the layer @xmath1 and from a set @xmath131 , @xmath132 to generate the layer @xmath2 . in this way , the sequences of weights @xmath47 , @xmath48 are uncorrelated . as a result , in eq . ( [ mamb ] ) the sum over the products of weights can be approximated by its expected value , @xmath133 @xcite . this approximation is valid in typical cases of mns with independently generated layers , and is applied instead of averaging the partition function in eq . ( [ zn ] ) over a class of mns with mutually independent sequences of weights assigned to nodes when generating different layers . besides , for @xmath134 ( @xmath135 ) , @xmath136 ( @xmath137 ) by approximating the sum with an integral it is obtained that @xmath138 and similarly for @xmath139 . the critical temperature for the fm transition can be evaluated from the condition that the determinant of a system of the first two equations in eq . ( [ mamb ] ) is zero , which leads to @xmath140 } \right\ } , \label{tcfm1}\ ] ] where @xmath141 ^ 2 -4 k^{(a)}k^{(b)}.\ ] ] in particular , for the two layers with identical distributions of the degrees of nodes @xmath142 , i.e. , with @xmath143 , @xmath144 , @xmath145 , \label{tcfm1eq}\ ] ] i.e. , in this case @xmath146 for @xmath147 ( @xmath148 ) and @xmath149 for @xmath150 ( @xmath151 ) . the temperature for the sg transition can be evaluated from the condition that the determinant of a system of the last two equations in eq . ( [ mamb ] ) is zero , which leads to @xmath152 } \right\}^{1/2 } , \label{tcsg1}\ ] ] where @xmath153 ^ 2 + 4 k^{(a)}k^{(b)}.\ ] ] in particular , for the two layers with identical distributions of the degrees of nodes @xmath154 , \label{tcsg1eq}\ ] ] i.e. , in this case again @xmath155 for @xmath147 ( @xmath148 ) and @xmath156 for @xmath150 ( @xmath151 ) . ( black solid lines ) and for the fm transition @xmath108 ( gray solid lines ) vs. @xmath114 , for @xmath157 and for ( a , b ) the mn with independent sf layers with ( a ) @xmath158 , ( b ) @xmath159 , results of eq . ( [ tcsg1 ] ) , eq . ( [ tcfm1 ] ) , respectively , and for ( c , d ) maximally correlated sf layers with ( c ) @xmath158 , ( d ) @xmath159 , results of eq . ( [ tcsg2 ] ) , eq . ( [ tcfm2 ] ) , respectively , scaledwidth=100.0% ] as an example , in fig . 1(a , b ) the critical temperatures @xmath108 , @xmath109 evaluated from eq . ( [ tcfm1 ] ) and eq . ( [ tcsg1 ] ) , respectively , are shown for fixed @xmath160 . it is assumed that @xmath119 which means that the fm and afm interactions in the mn are balanced ( the number of edges corresponding to @xmath161 in the layer @xmath1 is equal to that corresponding to @xmath162 in the layer @xmath2 ) ; fig . 1(a ) is for small and fig . 1(b ) for high mean degree of nodes within both layers . in the ising model on sf networks only sg transition occurs in the case of balanced fm and afm interactions @xcite . here , in contrast , depending on @xmath114 and the mean degree of nodes transition to the sg or fm phase can occur from the paramagnetic phase . the critical temperature remains finite for @xmath135 . as @xmath163 ( from above ) , i.e. , as the second moment @xmath164 of the distribution @xmath6 diverges , @xmath149 and the transition is to the fm phase . this is probably due to presence of a large number of hubs ( nodes with high degree ) within the layer @xmath1 interacting via fm interactions with many neighbors and thus enforcing global order . for larger @xmath114 and small @xmath119 the transition is to the sg phase , and a tricritical point occurs on the phase diagram ( fig . in contrast , for large @xmath119 there is @xmath165 in the whole range of @xmath114 and the transition is always to the fm phase . in particular , even if the distributions of the degrees of nodes within both layers are the same , @xmath166 and thus @xmath167 , for small @xmath119 the transition is to the sg phase and for high @xmath119 to the fm phase , which is in marked contrast with the above - mentioned case of the ising model on sf networks . the difference is due to the fact that in these two cases the fm and afm interactions are not balanced in the same way . in the insing model on sf networks , on average , half of edges attached to each node corresponds to @xmath168 and half to @xmath169 while in the model on mns with independent layers there are many nodes with high degree within one layer ( hubs ) with many attached edges corresponding , e.g. , to fm interactions and with small degree within the other layer with only few attached edges corrseponding to afm interactions ; i.e. , in the latter case the fm and afm interactions are balanced only globally but not locally . this result , confirmed via mc simulations in sec . 4.6 , emphasises the difference of the critical behavior between the ising model on , possibly heterogeneous , networks and on mns with separately ( in particular , independently ) generated layers . the mn with two maximally correlated sf layers is generated by randomly assigning to the nodes @xmath3 the weights @xmath170 to generate the layer @xmath1 and @xmath171 to generate the layer @xmath2 . in this way , in the statistical ensemble of mns generated in this way the mean degrees of the consecutive nodes within each layer @xmath172 , @xmath173 @xcite are maximally correlated ; as a result , the nodes which have high degree within one layer have also , on average , high degree in the other layer and vice versa . then , for @xmath134 ( @xmath135 ) , @xmath136 ( @xmath137 ) approximating the sum with an integral there is @xmath174 in eq . ( [ mamb ] ) . since all mns generated in this way are equivalent up to the permutation of the indices of nodes , no further averaging as in the case of independent sf layers is necessary . the temperature for the fm transition can be evaluated from the condition that the determinant of a system of the first two equations in eq . ( [ mamb ] ) is zero , which leads to @xmath175^{2 } } - \frac{\left(1-\mu^{(a)}\right)^2}{1 - 2\mu^{(a ) } } \frac{\left(1-\mu^{(b)}\right)^2}{1 - 2\mu^{(b ) } } \right ] } \right\ } , \label{tcfm2}\ ] ] where @xmath141 ^ 2 -4 k^{(a)}k^{(b ) } \frac{\left(1-\mu^{(a)}\right)^2 \left(1-\mu^{(b)}\right)^2}{\left [ 1-\left ( \mu^{(a ) } + \mu^{(b ) } \right)\right]^{2}}.\ ] ] in particular , it can be seen that for the two layers with identical distributions of the degrees of nodes the above - mentioned determinant is equal to 1 for any @xmath176 , thus transition to the fm state can not occur . the temperature for the sg transition can be evaluated from the condition that the determinant of a system of the last two equations in eq . ( [ mamb ] ) is zero , which leads to @xmath177^{2 } } \right ] } \right\}^{1/2 } , \label{tcsg2}\ ] ] where @xmath153 ^ 2 + 4 k^{(a)}k^{(b ) } \frac{\left(1-\mu^{(a)}\right)^2 \left(1-\mu^{(b)}\right)^2}{\left [ 1-\left ( \mu^{(a ) } + \mu^{(b ) } \right)\right]^{2}}.\ ] ] in particular , for the two layers with identical distributions of the degrees of nodes @xmath178 i.e. , in this case again @xmath155 for @xmath147 ( @xmath148 ) and @xmath156 for @xmath150 ( @xmath151 ) . as an example , in fig . 1(c , d ) the critical temperatures @xmath108 , @xmath109 evaluated from eq . ( [ tcfm2 ] ) and eq . ( [ tcsg2 ] ) , respectively , are presented for fixed @xmath160 and small ( fig . 1(c ) ) and high ( fig . 1(d ) ) value of @xmath119 . as in the case of mn with independent layers for @xmath163 there is @xmath149 and the transition is to the fm phase . however , for larger @xmath114 the transition is to the sg phase , independently of the mean degrees of nodes within layers ; thus , there is always the tricritical point on the phase diagram . in particular , in the case of mn with identical distributions of the degrees of nodes within both layers the transition is always to the sg phase , as in the case of the ising model on sf networks with balanced fm and afm interactions . this similarity is due to the fact that in the case of the ising model on a mn with maximally correlated layers the same nodes have high ( or small ) degree within both layers , thus the fm and afm interactions are balanced both globally and locally . the mn with two minimally correlated sf layers is generated by randomly assigning to the nodes @xmath3 the weights @xmath179 , @xmath180 . as a result , the nodes which have high degree within one layer have , on average , low degree in the other layer and @xmath181 in eq . ( [ mamb ] ) . hence , the mn is effectively decomposed into two apparently non - interacting networks corresponding to the layers @xmath1 , @xmath2 , with fm and afm exchange interactions , respectively . as a result , the system of equations in eq . ( [ mamb ] ) is decomposed into four independent equations . from the first two equations two critical temperatures for the fm transition can be obtained as @xmath182 , \nonumber\\ & & t_{c}^{(b)fm}= - j { \rm atanh}^{-1}\left [ \frac{1}{k^{(b)}}\frac{1 - 2\mu^{(b)}}{\left ( 1-\mu^{(b)}\right)^{2 } } \right],\end{aligned}\ ] ] of which @xmath183 is positive and finite for @xmath184 while @xmath185 . from the last two equations in eq . ( [ mamb ] ) the two critical temperatures for the sg transition can be obtained as @xmath186 , \nonumber\\ & & t_{c}^{(b)sg}= j { \rm atanh}^{-1}\left [ \sqrt{\frac{1 - 2\mu^{(b)}}{k^{(b)}}}\frac{1}{1-\mu^{(b ) } } \right],\end{aligned}\ ] ] which are finite and positive for @xmath184 , @xmath187 . there is always @xmath188 , thus , transition from the paramagnetic to the fm or sg phase can occur at @xmath189 as the temperature is lowered , depending on the parameters @xmath112 , @xmath113 , @xmath190 , @xmath191 . , ( a , c , e ) @xmath192 , ( b , d , f ) @xmath159 : ( a , b ) the overlap order parameter @xmath193 , eq . ( [ qoverlap ] ) , vs. @xmath194 , ( c , d ) the magnetization @xmath195 vs. @xmath194 , ( e , f ) the binder cumulant @xmath196 , eq . ( [ b ] ) , vs. @xmath194 , for ( @xmath197 ) @xmath198 , ( @xmath199 ) @xmath200 , ( @xmath201 ) @xmath202 , ( @xmath203 ) @xmath204.,scaledwidth=100.0% ] in order to verify , at least partly , the theoretical predictions of sec . 4.3 mc simulations of the ising model on mns with independent sf layers were performed using the metropolis algorithm and the parallel tempering ( replica exchange ) method @xcite in the form described in ref . @xcite . as the order parameter for the sg transition the absolute value @xmath205 of the overlap parameter @xmath206_{av } \equiv \left [ \langle \tilde{q } \rangle_{t } \right]_{av } \label{qoverlap}\ ] ] is used , where @xmath207 , @xmath176 denote two copies ( replicas ) of the system simulated independently with random initial conditions , @xmath208 denotes the time average for the system on a given mn and @xmath51_{av}$ ] , as in sec . 3 , denotes average over different realizations of the mn with independent sf layers . the critical temperature for the sg transition @xmath109 can be determined from the intersection point of the binder cumulants @xmath196 vs. @xmath194 for different @xmath0 @xcite , where @xmath209_{av}. \label{b}\ ] ] below the critical temperature for the transition from the paramagnetic to the sg phase @xmath205 increases from zero . in contrast , the absolute value @xmath210 of the magnetization @xmath211_{av}$ ] , which is the order parameter for the fm transition , should remain close to zero . on the other hand , below the critical temperature for the transition from the paramagnetic to the fm phase both @xmath205 and @xmath212 should increase from zero . an important prediction in sec . 4.3 is that in the case of mn with independent sf layers with identical distributions of the degrees of nodes @xmath213 for a certain range of @xmath167 the transition from the paramegnetic to the sg phase occurs only for small @xmath119 while for layers with higher mean degree of nodes transition to the fm state is expected . this scenario is in fact observed in mc simulations ; results for @xmath214 and for two values of @xmath119 are shown in fig . 2 . for @xmath192 the sg transition occurs : for @xmath215 increase of @xmath205 can be seen ( fig . 2(a ) ) while @xmath210 remains small and even decreases ( fig . also the value of @xmath216 estimated from the mc simulations ( fig . 2(e ) ) is close to @xmath217 evaluated from eq . ( [ tcsg1eq ] ) . in contrast , for @xmath159 the fm transition occurs : both @xmath205 and @xmath218 increase for @xmath219 ( fig . 2(b , d ) ) and the value of the fm critical temperature obtained from the mc simulations can be assessed as @xmath220 from fig . 2(d ) , which is again with agreement with @xmath221 evaluated from eq . ( [ tcfm1eq ] ) . thus , in this particular case theoretical predictions based on the rs solution are confirmed by mc simulations . below the transition point from the paramagnetic to the sg phase the sg order parameter increases from zero while the magnetization remains close to zero . bleow @xmath109 the sg order parameter is expected to scale as @xmath222 , where @xmath223 . in ref . @xcite it was shown that in the case of the ising model on sf networks the scaling exponent @xmath176 can depend on the parameters of the distribution of the degrees of nodes . in this section this exponent is determined for the ising model on mns with independent layers using a semi - analytic procedure . let us start with the ising model on a mn with two random er layers . in the case of the transition from the paramagnetic to the sg phase @xmath224 below the critical temperature . taking into account that @xmath120 , @xmath3 , @xmath225 from eq . ( [ t1t2 ] ) and @xmath226 ( see sec . 4.2 ) the equations for the sg order parameter , the last two equations in eq . ( [ system ] ) , are reduced to a single equation @xmath227.\ ] ] in the vicinity of @xmath109 it is possible to expand the @xmath228 function with respect to @xmath193 . after evaluating the momenta and retaining only the lowest - order nonlinear term it is obtained that @xmath229 where @xmath230 ( see eq . ( [ tsger ] ) ) and @xmath231 . hence , @xmath232 just below the sg transition temperature , as in the case of the sg transition in the ising model on random er graphs @xcite . let us now consider the ising model on a mn with two independent sf layers . the sg transition temperature is finite , and thus the scaling behavior of the order parameters below @xmath109 can be determined , for @xmath135 , @xmath137 . in the case of the transition from the paramagnetic to the sg phase @xmath224 below the critical temperature and the equations for the sg order parameter , the last two equations in eq . ( [ system ] ) , are @xmath233 , \label{qasg1}\ ] ] and analogous equation for @xmath101 . unfortunately , in this case it is not possible simply to expand the @xmath228 function with respect to @xmath193 due to the occurrence of the terms like @xmath234 , etc . , under the integral which diverge even if the second moments of the distribution of the weights associated with each layer are finite . nevertheless , as shown in appendix b the sum over the indices of nodes on the right - hand side of eq . ( [ qasg1 ] ) can be represented in a form of a converging series expansion with respect to @xmath103 , @xmath101 . first , let us note that in the case of independent sf layers the sum over the indices of nodes in eq . ( [ qasg1 ] ) can be replaced by its expected value , similarily as in sec . 4.3 , and then approximated by an integral , @xmath235 \approx \nonumber\\ & & \sum_{i=1}^{n } n^{-2 } \sum_{k=1}^{n}\sum_{l=1}^{n } v_{k } \tanh^{2}\left [ z \sqrt { n \left ( k^{(a)}{\bf t}_{2}^{(a ) } v_{k } q^{(a ) } + k^{(b ) } { \bf t}_{2}^{(b ) } v_{l } q^{(b)}\right ) } \right ] \approx \nonumber\\ & & \frac{1-\mu^{(a)}}{n^{2 } } \int_{1}^{n}\int_{1}^{n } dy_{k } dy_{l } \left ( \frac{n}{y_{k}}\right)^{\mu^{(a ) } } \tanh^{2}\left [ z \sqrt { \left ( \frac{n}{y_{k}}\right)^{\mu^{(a ) } } q^{(a ) } + \left ( \frac{n}{y_{l}}\right)^{\mu^{(b ) } } q^{(b ) } } \right ] , \nonumber\end{aligned}\ ] ] where @xmath236 , @xmath237 . in the limit @xmath238 and after replacing the variables @xmath239 , @xmath240 eq . ( [ qasg1 ] ) becomes @xmath241 the two - dimesional integral in eq . ( [ qasg2 ] ) can be evaluated using eq . ( [ s ] ) in appendix a with @xmath242 , and the result is given by eq . ( [ sfinal ] ) . inserting this result in eq . ( [ qasg2 ] ) and evaluating the moments it is obtained that @xmath243,\nonumber\\ & & \label{qasg3}\end{aligned}\ ] ] where @xmath244 are given by eq . ( [ taylorcoeff ] ) , @xmath245 by eq . ( [ i11 ] ) , @xmath246 by eq . ( [ i2 ] ) and @xmath247 by eq . ( [ i ] ) in appendix b. the complementary equation for @xmath248 can be obtained from eq . ( [ qasg3 ] ) by replacing @xmath249 with @xmath250 and vice versa . vs. @xmath251 in the neighborhood of the critical temperature for the sg transition for the mn with independent sf layers with @xmath252 and various @xmath115 ( see legend ) , the results were obtained from numerical solution of eq . ( [ qaqbsg1 ] ) for @xmath253 and eq . ( [ qaqbsg2 ] ) for @xmath254 with @xmath255 ( in all cases @xmath256 ) . lines : asymptotic ( for @xmath257 ) least - squares fits to the above - mentioned solutions ( see legend ) in the form of the power scaling law @xmath258.,scaledwidth=60.0% ] let us first consider the case when the sf layers have identical distributions of the degrees of nodes @xmath166 , with @xmath143 , @xmath259 ( @xmath144 ) . then the system of eq . ( [ qasg1 ] ) and thus also eq . ( [ qasg3 ] ) have solution with @xmath226 . in order to determine the critical behavior of @xmath193 near @xmath109 it is necessary to retain only the lowest - order nonlinear term on the right - hand side of eq . ( [ qasg3 ] ) , thus the cases @xmath260 and @xmath261 should be considered separately . for @xmath262 the following equation for @xmath193 is obtained from eq . ( [ qasg3 ] ) , @xmath263 where @xmath264 , @xmath265 ( see eq . ( [ tcsg1eq ] ) ) , @xmath266 and @xmath267 @xmath268 . from eq . ( [ qaqbsg1eq ] ) follows that @xmath269 just below the transition point . this is the same scaling relation as in the case of the sg transition in the ising model on sf networks @xcite , only the critical temperature is different . for @xmath261 the following equation for @xmath193 is obtained from eq . ( [ qasg3 ] ) , @xmath270q^{2}. \label{qaqbsg3eq}\ ] ] hence , @xmath232 just below the sg transition temperature , as in the case of the sg transition in the ising model on sf networks @xcite ; only the critical temperature and the proportionality constant are different . thus , it can be seen that the critical exponent for the sg order parameter exhibits the same scaling behavior in the case of the sg transition in the ising model on a sf networks and on a mn with sf layers with identical distributions of the degrees of nodes . if the sf layers have different distributions of the degrees of nodes the critical exponents for @xmath103 , @xmath101 must be determined from two - dimensional systems of nonlinear equations following from eq . ( [ qasg3 ] ) and from the complementary equation for @xmath248 in which only the lowest - order nonlinear terms are retained . due to complexity of these equations as well as the complex form of @xmath109 , eq . ( [ tcsg1 ] ) , it is not a simple task to determine the scaling behavior of @xmath103 , @xmath101 analytically . hence , below this is done by solving the above - mentioned systems numerically for @xmath103 , @xmath101 vs. @xmath271 . for @xmath272 , @xmath273 the following system of equations for @xmath103 , @xmath101 is obtained from eq . ( [ qasg3 ] ) , @xmath274 it is then possible , e.g. , to evaluate @xmath275 from the first equation and insert it to the second one to obtain a nonlinear equation for @xmath276 which can be solved numerically . the results of this procedure are summarized in fig . 3 . for @xmath277 ( @xmath278 ) the scaling relation @xmath279 is obtained with @xmath280 which agrees well with @xmath281 predicted from eq . ( [ qaqbsg1eq ] ) . for @xmath252 and @xmath282 ( @xmath283 ) the scaling relation @xmath279 is obtained with @xmath284 which is still close to @xmath285 ( the difference can be due to fitting error ) ; thus , the scaling behavior of @xmath103 in the vicinity of @xmath109 is still determined by the lowest - order nonlineatity @xmath286 in eq . ( [ qaqbsg1 ] ) . since in the first approximation @xmath287 the scaling behavior of @xmath101 is the same as that of @xmath103 . for @xmath272 , @xmath288 in the system of equations for @xmath103 , @xmath101 obtained from eq . ( [ qasg3 ] ) the equation for @xmath289 is identical as in eq . ( [ qaqbsg1 ] ) and the second equation is @xmath290 . \label{qaqbsg2}\end{aligned}\ ] ] it is again possible to evaluate @xmath275 from the first equation in eq . ( [ qaqbsg1 ] ) and insert it into eq . ( [ qaqbsg2 ] ) to obtain a nonlinear equation for @xmath276 which can be solved numerically . for @xmath252 and @xmath291 ( @xmath292 ) the scaling relation @xmath279 is obtained with @xmath293 ( fig . 3 ) , again in agreement with @xmath294 ; thus , the scaling behavior of @xmath103 in the vicinity of @xmath109 is again determined by the lowest - order nonlineatity @xmath286 in the first equation in eq . ( [ qaqbsg1 ] ) . for @xmath295 , @xmath254 , in the system of equations for @xmath103 , @xmath101 obtained from eq . ( [ qasg3 ] ) the equation for @xmath248 is identical as in eq . ( [ qaqbsg2 ] ) and the equation for @xmath289 can be obtained from it by replacing @xmath249 with @xmath250 and vice versa . the system of two quadratic equations for @xmath276 , @xmath275 can be solved by evaluating , e.g. , @xmath276 from one equation , inserting it to the other one and solving for @xmath275 numerically . from such solution , independently of @xmath114 , @xmath115 , the scaling relation @xmath296 is obtained with high accuracy , i.e. , the scaling exponent @xmath297 is the same as that resulting from eq . ( [ qaqbsg3eq ] ) valid for @xmath167 . thus , the scaling behavior of @xmath103 in the vicinity of @xmath109 is again determined by the lowest - order nonlineatity @xmath298 in eq . ( [ qaqbsg2 ] ) . it is interesting to note that for @xmath135 , @xmath137 , i.e. , when @xmath109 is finite the last term in eq . ( [ qasg3 ] ) containing @xmath299 is of higher order than the leading nonlinear terms in eq . ( [ qaqbsg1 ] ) and eq . ( [ qaqbsg2 ] ) and can be omitted . let us also mention that taking into account the results of ref . @xcite logarithmic corrections to the scaling behavior of @xmath103 , @xmath101 in the vicinty of @xmath109 can be expected for @xmath114 , @xmath115 being integer numbers . unfortunately , verification of the presence of such correction from numerical solution of the systems of nonlinear equations like eq . ( [ qaqbsg1 ] ) or eq . ( [ qaqbsg2 ] ) is practically impossible , thus this case is not considered in this paper . in this paper the sg and fm transitions in the ising model on mns with both fm and afm interactions were studied using the replica method ; in particular , the mns with the layers in the form of random er graphs and sf networks were considered . the critical temperatures for these transitions from the paramagnetic phase were determined from the rs solution . for the ising model on mns with sf layers it was shown that the transition temperature is finite if the distributions of the degrees of nodes within both layers have a finite second moment , and that depending on the model parameters this transition can be to the fm or sg phase . it was also shown that the correlation between the degrees of nodes within different layers significantly influences the critical temperatures for the fm and sg transitions and thus the phase diagram . in particular , in the case of mn with two independently generated sf layers corresponding to ( balanced ) fm and afm interactions for small mean degrees of nodes within both layers the transition is to the fm or sg phase , depending on the details of the two degree distributions , while for high mean degrees of nodes it is to the fm phase ; this result was confirmed in mc simulations . in contrast , in the case of mns with maximally correlated layers the transition can be to the sg phase also for high mean degrees of nodes within the two layers , depending on the details of the two degree distributions . the scaling behavior for the sg parameter was determined from the rs solution by means of a semi - analytic procedure . in most cases the critical exponent has the universal value @xmath297 , only in the case of sf layers characterized by the distributions of the degrees of nodes with diverging third moment its value becomes dependent on the details of this distribution . application of the replica method to the ising model on mns with both fm and afm interactions leads to many results which have already been reported for the ising model on mns with purely fm interactions , e.g. , the occurrence , in a natural way , of the sets of the order paramaters associated with consecutive layers or the dependence of the critical temperature on the correlations between the degrees of nodes within different layers @xcite . although the methods used in this paper are direct generalization of the ones used in refs . @xcite to the case of mns with possibly heterogeneous layers both the calculations and the results exhibit some peculiar properties due to the fact that the statistical averages must be evaluated over the separately generated layers rather than over the whole network . the problems remaining for future research comprise , e.g. , investigation of the stability of the fm and sg phases , obtaining the full phase diagram for the ising model on mns and determination of the critical behavior of the model at the fm and sg phase borders . in networks generated from the static model there is @xmath39 , @xmath300 @xcite . thus the result of eq . ( [ tcfm1 ] ) and eq . ( [ tcsg1 ] ) can be written in a more general form , @xmath301 } \right\ } \label{tcfm1gen}\ ] ] where @xmath302 and @xmath303 } \right\}^{1/2 } \label{tcsg1gen}\ ] ] where @xmath304 using the moments of the distributions of the degrees of nodes within each layer . it should be noted that the necessary condition for the occurrence of the fm or sg transition is that the critical temperatures @xmath108 , @xmath109 given by eq . ( [ tcfm1gen ] ) and eq . ( [ tcsg1gen ] ) , respectively , are real and positive . in the case of the critical temperature for the sg transition it can be easily shown that this requires that @xmath305 which is also a condition for the occurrence of a giant component in a mn with two independently generated layers @xcite , in which nodes are connected via edges in any layer ( but not necessarily in both layers ) . thus , in the case of a mn with two layers , one with purely fm and the other one with purely afm interactions , the sg transition can appear in a mn above the percolation threshold , in analogy with the case of complex networks @xcite . in contrast , this is not enough for the possibility of appearance of the fm transition , for which higher densities of connections within layers are necessary . it can be expected that eq . ( [ tcfm1gen ] ) and eq . ( [ tcsg1gen ] ) are valid for any multiplex network consisting of independently generated , possibly heterogeneous layers with finite second moments of the distributions of the degrees of nodes ( note , however , that in the case of random er layers the above expressions are not properly determined ; this is since the equations for @xmath108 ( @xmath109 ) are linear ( quadratic ) rather than quadratic ( quartic ) with respect to @xmath306 , see sec . 4.2 ) . in particular , if the distributions of the degrees of nodes within the layers @xmath1 , @xmath2 obey power scaling laws in the form @xmath307 for @xmath308 , @xmath309 for @xmath310 , respectively , with fixed minimum degrees of nodes @xmath311 , @xmath312 the critical temperature can be obtained by inserting in eq . ( [ tcfm1gen ] ) and eq . ( [ tcsg1gen ] ) @xmath313 and similar expressions for the moments of @xmath7 . in this appendix a general expansion formula is derived for a sum of a form @xmath314 using a method which is a generalization of the one from ref . @xcite to the case of two - dimensional integrals . let us assume that @xmath315 , @xmath316 are not integer numbers and , for some @xmath317 , @xmath318 , there is @xmath319 , @xmath320 . the expansion of the function @xmath321 in the taylor series is @xmath322 where the expansion coefficients are @xmath323 the first sum in eq . ( [ taylorexp ] ) can be integrated term by term which yields @xmath324 concerning the remaining terms it should be noted that in the converging taylor series , eq . ( [ taylorexp ] ) , the order of summation and integration can be exchanged . then , e.g. , from integration of the second sum , after evaluating the integral @xmath325 for @xmath326 and dividing in two parts and evaluating the integral @xmath327 for @xmath328 it is obtained that @xmath329 where @xmath330 since @xmath331 the integrals in eq . ( [ i1 ] ) are not singular and the whole series converges . taking into account that , from eq . ( [ taylorcoeff ] ) , @xmath332 \right|_{(0,0 ) } x_{1}^{n_{1 } } = \frac{1}{n_{2 } ! } \left . \frac{\partial^{n_{2}}f}{\partial x_{2}^{n_{2 } } } \left ( x_{1},x_{2 } \right ) \right|_{x_{2}=0 } , \nonumber\\ & & \end{aligned}\ ] ] eq . ( [ i1 ] ) can be rewritten as @xmath333 the third and fourth sum in eq . ( [ taylorexp ] ) can be integrated in a similar way , and finally from eq . ( [ s ] ) it is obtained that @xmath334 , \label{sfinal}\end{aligned}\ ] ] where @xmath335 @xmath336 dx_{1}dx_{2 } \nonumber\\ \label{i}\end{aligned}\ ] ] and the integrals in eq . ( [ i2 ] ) and eq . ( [ i ] ) converge . in particular , it can be seen that for @xmath242 there is @xmath337 and @xmath338 for @xmath339 , thus also @xmath340 from eq . ( [ i2 ] ) and terms corresponding to @xmath341 ( containing @xmath342 ) in the sums in eq . ( [ sfinal ] ) disappear . t. nikoletopoulos , a. c. c. coolen , i. prez castillo , n. s. skantzos , j. p. l. hatchett , and b. wemmenhove , replicated transfer matrix analysis of ising spin models on ` small world ' lattices , j. phys . a : math . 37 ( 2004 ) 64556475 . a. l. ferreira , j. f. f. mendes , and m. ostilli , first- and second - order phase transitions in ising models on small - world networks : simulations and comparison with an effective field theory phys . e 82 ( 2010 ) 011141 . t. castellani , f. krzakala , and f. ricci - tersenghi , spin glass models with ferromagnetically biased couplings on the bethe lattice : analytic solutions and numerical simulations , eur . j. b 47 ( 2005 ) 99108 .

multiplex networks consist of a fixed set of nodes connected by several sets of edges which are generated separately and correspond to different networks ( `` layers '' ) . here , the ising model on multiplex networks with two layers is considered , with spins located in the nodes and edges corresponding to ferromagnetic or antiferromagnetic interactions between them . critical temperatures for the spin glass and ferromagnetic transitions are evaluated for the layers in the form of random erds - rnyi graphs or heterogeneous scale - free networks using the replica method , from the replica symmetric solution . for the ising model on multiplex networks with scale - free layers it is shown that the critical temperature is finite if the distributions of the degrees of nodes within both layers have a finite second moment , and that depending on the model parameters the transition can be to the ferromagnetic or spin glass phase . it is also shown that the correlation between the degrees of nodes within different layers significantly influences the critical temperatures for both transitions and thus the phase diagram . the scaling behavior for the spin glass order parameter is determined by a semi - analytic procedure and it is shown that for the ising model on multiplex networks with scale - free layers the scaling exponent can depend on the distributions of the degrees of nodes within layers . the analytic results are partly confirmed by monte carlo simulations using the parallel tempering algorithm . multiplex networks ; phase transitions ; ising model ; mean - field theory ; replica method .

the existence of dark matter ( dm ) is by now well established from astrophysical observations @xcite . together with the recent wmap results , the cosmological observations have shown that the present universe consists of about 73% dark energy , 23% dark matter , and 4% baryonic matter @xcite . in the standard model ( sm ) of particle physics , there is no cold dm candidate . therefore , one has to extend the sm to account for the existence of dm . the dm candidate is often accompanied by some discrete symmetries to keep it stable , such as the r parity in supersymmetric ( susy ) models and kk parity in universal extra dimension models . although the discrete symmetries are necessary for the dm stability , they may be introduced from different motivations @xcite . in the left - right ( lr ) symmetric gauge model @xcite with spontaneous @xmath1 violation ( scpv ) , the @xmath0 and @xmath1 symmetries are exact before the spontaneous symmetry breaking ( ssb ) . in this case , it is possible that the discrete symmetries @xmath0 and @xmath1 strongly constrain the scalar sector of the model and naturally give stable dm candidates . this possibility has not been emphasized in the literature , due to the fact that most of the popular models such as sm and susy violate @xmath0 maximally . in ref . @xcite , we have shown that the @xmath0 and @xmath1 symmetries can give a stable dm candidate in an extension of a left - right symmetric gauge model with a singlet scalar field @xmath2 . in this model , the @xmath1 odd particle @xmath3 is stable even after the ssb , provided that it does not develop vacuum expectation value ( vev ) . without large fine - tuning , it is difficult to have a successful scpv in the minimal left - right symmetric gauge model with only one higgs bidoublet ( 1hbdm ) @xcite . this is because in the decoupling limit the predicted @xmath1 violating quantity @xmath4 with @xmath5 being a @xmath1 phase angle in the cabibbo - kobayashi - maskawa ( ckm ) matrix is far below the experimentally measured value of @xmath6 from the two b - factories @xcite . in addition , the 1hbdm is also subject to strong phenomenological constraints from low energy flavor changing neutral current ( fcnc ) processes , especially the neutral kaon mixing which pushes the masses of the right - handed gauge bosons and some neutral higgs bosons much above the tev scale @xcite . motivated by the requirement of both spontaneous @xmath0 and @xmath1 violations , we have considered the left - right symmetric gauge model with two higgs bidoublets ( 2hbdm ) @xcite . in the 2hbdm , the additional higgs bidoublet modifies the higgs potential so that the fine - tuning problem in the scpv can be avoided , and the bounds from the fcnc processes can be relaxed . the extra higgs bidoublet may also change the interferences among different contributions in the neutral meson mixings , and lower the bounds for the right - handed gauge boson masses not to be much higher than the tev scale @xcite . such a right - handed gauge boson can be searched at the lhc using the angular distributions of top quarks and the leptons from top quark decays @xcite . in ref . @xcite , we have shown that the discrete symmetries @xmath0 and @xmath1 can be used to stabilize the dm candidate @xmath3 in the 1hbdm and 2hbdm with the scpv . using the observed dm abundance , we can constrain the parameter space and predict the spin - independent ( si ) dm - nucleon elastic scattering cross section . for simplicity , we have only considered the case with no mixing among light neutral higgs bosons in the 2hbdm and the dark matter is heavy . in this paper , we shall demonstrate in detail the mixing effect on the dm direct detection . notice that several new dm annihilation channels can be derived , namely two dm particles may annihilate into a gauge boson and a higgs boson . on the other hand , we are going to extend the dm mass range from @xmath7 gev to @xmath8 gev . as a consequence , one will meet several resonances in the 2hbdm . therefore we shall consider the breit - wigner resonance effect for the determination of the dm relic density @xcite . in addition , we will also consider the dm indirect search in the 1hbdm and 2hbdm . the paper is organized as follows : in section . [ model ] , we outline the main features of the 1hbdm and 2hbdm with a singlet scalar . in sec . [ sec1hbdm ] and sec . [ sec2hbdm ] , we discuss the parameter space , the dm direct search and the dm indirect search in the 1hbdm and 2hbdm , respectively . some conclusions are given in sec . [ conclusion ] . we begin with a brief review of the 2hbdm described in ref . the model is a simple extension to the 1hbdm , which is based on the gauge group @xmath9 . the left- and right - handed fermions belong to @xmath10 and @xmath11 doublets , respectively . the higgs sector contains two higgs bidoublets @xmath12 ( 2,@xmath13,0 ) , @xmath14 ( 2,@xmath13,0 ) and a left(right)-handed higgs triplet @xmath15 ( 3(1),1(3),2 ) with the following flavor contents @xmath16 the introduction of higgs bidoublets @xmath12 and @xmath14 can account for the electroweak symmetry breaking and overcome the fine - tuning problem in generating the scpv in the 1hbdm . meanwhile it also relaxes the severe low energy phenomenological constraints @xcite . motivated by the spontaneous @xmath0 and @xmath1 violations , we require @xmath0 and @xmath1 invariance of the lagrangian , which strongly restricts the structure of the higgs potential . the most general potential containing only the @xmath12 and @xmath17 fields is given by @xmath18-\mu_{3}^{2}[\rm{tr}(\delta_{l}\delta_{l}^{\dagger})+\rm{tr}(\delta_{r}\delta_{r}^{\dagger})]\nonumber\\ & & + \lambda_{1}[\rm{tr}(\phi^{\dagger}\phi)]^{2}+\lambda_{2}\{[\rm{tr}(\tilde{\phi}^{\dagger}\phi)]^{2}+[\rm{tr}(\tilde{\phi}\phi^{\dagger})]^{2}\}+\lambda_{3}[\rm{tr}(\tilde{\phi}^{\dagger}\phi)\rm{tr}(\tilde{\phi}\phi^{\dagger})]\nonumber\\ & & + \lambda_{4}\{\rm{tr}(\phi^{\dagger}\phi)[\rm{tr}(\tilde{\phi}^{\dagger}\phi)+\rm{tr}(\tilde{\phi}\phi^{\dagger})]\}\nonumber\\ & & + \rho_{1}\{[\rm{tr}(\delta_{l}\delta_{l}^{\dagger})]^{2}+[\rm{tr}(\delta_{r}\delta_{r}^{\dagger})]^{2}\}+\rho_{2}[\rm{tr}(\delta_{l}\delta_{l})\rm{tr}(\delta_{l}^{\dagger}\delta_{l}^{\dagger})+\rm{tr}(\delta_{r}\delta_{r})\rm{tr}(\delta_{r}^{\dagger}\delta_{r}^{\dagger})]\nonumber\\ & & + \rho_{3}[\rm{tr}(\delta_{l}\delta_{l}^{\dagger})\rm{tr}(\delta_{r}\delta_{r}^{\dagger})]+\rho_{4}[\rm{tr}(\delta_{l}\delta_{l})\rm{tr}(\delta_{r}^{\dagger}\delta_{r}^{\dagger})+\rm{tr}(\delta_{l}^{\dagger}\delta_{l}^{\dagger})\rm{tr}(\delta_{r}\delta_{r})]\nonumber\\ & & + \alpha_{1}\rm{tr}(\phi^{\dagger}\phi)[\rm{tr}(\delta_{l}\delta_{l}^{\dagger})+\rm{tr}(\delta_{r}\delta_{r}^{\dagger } ) ] + \alpha_{2}\rm{tr } [ ( \tilde{\phi}^{\dagger}\phi)+(\tilde{\phi}\phi^{\dagger})]\rm{tr}[(\delta_{l}\delta_{l}^{\dagger})+(\delta_{r}\delta_{r}^{\dagger})]\nonumber\\ & & + \alpha_{3}[\rm{tr}(\phi\phi^{\dagger}\delta_{l}\delta_{l}^{\dagger})+\rm{tr}(\phi^{\dagger}\phi\delta_{r}\delta_{r}^{\dagger})]\nonumber\\ & & + \beta_{1}[\rm{tr}(\phi\delta_{r}\phi^{\dagger}\delta_{l}^{\dagger})+\rm{tr}(\phi^{\dagger}\delta_{l}\phi\delta_{r}^{\dagger})]+\beta_{2}[\rm{tr}(\tilde{\phi}\delta_{r}\phi^{\dagger}\delta_{l}^{\dagger})+\rm{tr}(\tilde{\phi}^{\dagger}\delta_{l}\phi\delta_{r}^{\dagger})]\nonumber\\ & & + \beta_{3}[\rm{tr}(\phi\delta_{r}\tilde{\phi}^{\dagger}\delta_{l}^{\dagger})+\rm{tr}(\phi^{\dagger}\delta_{l}\tilde{\phi}\delta_{r}^{\dagger } ) ] , \label{vphidelta } % ( 2)\end{aligned}\ ] ] where the coefficients @xmath19 , @xmath20 , @xmath21 , @xmath22 and @xmath23 in the potential are all real as all the terms are self - hermitian . the higgs potential @xmath24 involving @xmath14 field can be obtained by the replacement @xmath25 in eq . ( [ vphidelta ] ) . the mixing term @xmath26 can be obtained by replacing one of @xmath12 by @xmath14 in all the possible ways in eq . ( [ vphidelta ] ) . in order to simplify the discussion , we shall first consider the 1hbdm which already contains the main features of the complete model . then we postpone the discussions on the @xmath14 contributions into section [ sec2hbdm ] . after the ssb , the higgs multiplets obtain nonzero vevs @xmath27 where @xmath28 , @xmath29 , @xmath30 and @xmath31 are in general complex , and @xmath32 gev represents the electroweak symmetry breaking scale . due to the freedom of gauge symmetry transformation , one can take @xmath28 and @xmath31 to be real . to avoid the fine - tuning problem of fermion masses , we require @xmath33 and @xmath34 . the value of @xmath31 sets the scale of left - right symmetry breaking which is directly linked to the right - handed gauge boson masses . @xmath31 is subjected to strong constraints from the @xmath35 , @xmath36 meson mixings @xcite as well as low energy electroweak interactions @xcite . the kaon mass difference and the indirect @xmath1 violation quantity @xmath37 set a bound for @xmath31 around @xmath38 tev @xcite . .the @xmath0 and @xmath1 transformation properties of the higgs particles and their gauge - invariant combinations . + " and - " denote even and odd , respectively . [ cols="^,^,^,^,^,^,^,^,^",options="header " , ] as discussed in sec . [ model ] , an approximate global @xmath39 symmetry on @xmath40 can naturally lead to a light dm mass @xmath41 . here we focus on @xmath8 gev . considering the case @xmath42 , one may find that most of scalar bosons in table [ mass ] are very heavy except the sm - like one @xmath43 . in this case , the possible annihilation products are @xmath44 , @xmath45 and fermion pairs @xmath46 as shown in fig . [ feynman1 ] . for @xmath47-channel annihilation processes , the intermediate particles may be @xmath43 , @xmath48 , @xmath49 and @xmath50 . because of @xmath33 , one may neglect the @xmath50 case . in addition , the @xmath51 contribution is also negligible as @xmath52 . for the @xmath53 annihilation process , the main contribution comes from the @xmath43 exchange diagram . this is because @xmath54 dominantly couples to the very heavy right - handed majorana neutrinos ( the corresponding annihilation process is kinematically forbidden ) . for the @xmath55 processes , the diagram involving @xmath56 is suppressed by @xmath57 . notice that @xmath58 may be the intermediate particle for the @xmath44 case . it is clear that the dominant annihilation processes in fig . [ feynman1 ] are the same as that in the minimal extension of sm with a real gauge singlet scalar when @xmath59 @xcite . in the 1hbdm , the dm annihilation cross sections @xmath60 ( @xmath61 and @xmath62 are the energies of two incoming dm particles ) for different annihilation channels have the following forms : @xmath63 , \label{sigmahh } % ( 7,8,9,10)\end{aligned}\ ] ] where @xmath47 is the squared center - of - mass energy @xcite . the quantity @xmath64 is defined as @xmath65 with @xmath66 . the higgs decay width @xmath67 and @xmath68 are given by @xmath69 from eqs . ( [ sigmaff]-[g1 ] ) seven unknown parameters enter the expression of total annihilation cross section , namely , @xmath70 , @xmath41 , @xmath71 , @xmath72 , @xmath73 , @xmath74 and @xmath31 . for the mass of sm - like higgs , we take @xmath75 gev in the following parts . in fact , one may neglect the squared center - of - mass energy @xmath47 in the terms @xmath76 and @xmath77 since the masses of @xmath78 and @xmath54 are around @xmath31 . in a good approximation , we find that only three independent parameters @xmath79 are relevant to our numerical analysis . here we have used @xmath80 as it is shown in table [ mass ] . in order to obtain the correct dm abundance , one should resolve the following boltzmann equation @xcite : @xmath81 where @xmath82 denotes the dm number density . the entropy density @xmath83 and the hubble parameter @xmath84 evaluated at @xmath85 are given by @xmath86 where @xmath87 gev is the planck energy . @xmath88 is the total number of effectively relativistic degrees of freedom . the numerical results of @xmath88 have been presented in ref . @xcite . here we take the qcd phase transition temperature to be 150 mev . the thermal average of the annihilation cross section times the relative velocity @xmath89 is a key quantity in the determination of the dm cosmic relic abundance . we adopt the usual single - integral formula for @xmath90 @xcite : @xmath91 with @xmath92 where @xmath93 and @xmath94 are the modified bessel functions . @xmath95 and @xmath96 is the internal degrees of freedom for the scalar dark matter @xmath3 . in terms of the annihilation cross section @xmath97 in eqs . ( [ sigmaff]-[sigmahh ] ) , one can numerically calculate the thermally averaged annihilation cross section @xmath89 . finally , we may obtain the dm relic density @xmath98 by use of the result @xmath99 of the integration of eq . ( [ bol ] ) . when the dm mass @xmath41 is larger than the mass of top quark , one will not meet the resonance @xcite and threshold @xcite effects in our model . thus we use the approximate formulas to calculate the dm relic density for @xmath100 . in this case , @xmath89 can be expanded in powers of relative velocity and @xmath101 for nonrelativistic gases . to the first order @xmath102 , where @xmath103 for @xmath104-wave annihilation process @xcite . the approximate formula for @xmath105 is given by @xcite @xmath106_{s/4m_d^2=1 } \ ; , \label{expand } % ( 17)\end{aligned}\ ] ] where @xmath107 and the prime denotes derivative with respect to @xmath108 . @xmath109 and its derivative are all to be evaluated at @xmath110 . then @xmath111 is given by @xcite @xmath112 with @xmath113 - ( n+ 1/2)\ , { \rm ln } \ { { \rm ln } [ 0.038(n+1)(g_{i}/g_*^{1/2 } ) m_{\rm pl } m_d \sigma_0 ] \}. \label{xf } % ( 19)\end{aligned}\ ] ] notice that we take @xmath114 for @xmath115 . as a function of @xmath116 and the dm mass @xmath41 from the observed dm abundance in the 1hbdm . right panels : the predicted dm - nucleon scattering cross section @xmath117 in the 1hbdm with current and future experimental upper bounds . , title="fig:",width=264,height=226 ] as a function of @xmath116 and the dm mass @xmath41 from the observed dm abundance in the 1hbdm . right panels : the predicted dm - nucleon scattering cross section @xmath117 in the 1hbdm with current and future experimental upper bounds . , title="fig:",width=264,height=226 ] as a function of @xmath116 and the dm mass @xmath41 from the observed dm abundance in the 1hbdm . right panels : the predicted dm - nucleon scattering cross section @xmath117 in the 1hbdm with current and future experimental upper bounds . , title="fig:",width=264,height=226 ] as a function of @xmath116 and the dm mass @xmath41 from the observed dm abundance in the 1hbdm . right panels : the predicted dm - nucleon scattering cross section @xmath117 in the 1hbdm with current and future experimental upper bounds . , title="fig:",width=264,height=226 ] in terms of the observed dm abundance @xmath118 @xcite , we numerically solve the boltzmann equation and derive the coupling @xmath119 with different @xmath116 for @xmath120 . the numerical results are shown in fig . [ 1hbdm ] ( upper - left panel ) . due to the resonance contribution , a very small value of the coupling @xmath119 can be derived from the observed dm abundance for the resonance region ( @xmath121 ) . except for the resonance region , one may find @xmath122 . the parameter @xmath116 plays an important role to determine the dm relic density if @xmath123 . for illustration , we also plot the @xmath124 cases which can significantly change the predicted @xmath119 as shown in fig . [ in fact , @xmath119 may be very small ( even to be zero ) for the larger @xmath125 . in this case , the @xmath49-exchange annihilation process is dominant . here we have assumed @xmath119 is positive . if we simultaneously change the signs of @xmath119 and @xmath116 , the negative @xmath119 case may be approximately induced from the positive case . this feature can be well understood from eqs . ( [ sigmahh]-[g1 ] ) . it should be mentioned that the thermally averaged annihilation cross section @xmath89 will significantly change as the evolution of the universe when the dm particle is nearly one - half the mass of a resonance @xcite . this is the breit - wigner resonance effect which has been used to explain the recent pamela @xcite , atic @xcite and fermi @xcite anomalies . notice that the decaying @xmath3 with a lifetime around @xmath126 can also account for the electron and positron anomalies @xcite . here we have considered the breit - wigner resonance effect for the determination of the coupling @xmath119 . for @xmath127 , we use the approximate formulas to scan the whole parameter space @xmath128 and @xmath116 . the allowed parameter space is shown in fig . [ 1hbdm ] ( lower - left panel ) , which gives an allowed range @xmath129 and @xmath130 the central region of this figure is excluded since these points can not provide large enough annihilation cross section to give the desired dm abundance . notice that the approximate global symmetry @xmath39 requires @xmath131 which means the region near @xmath132 is disfavored . for the scalar dark matter , the dm elastic scattering cross section on a nucleon is spin - independent , which is given by @xcite @xmath133 where @xmath134 is the nucleon mass . @xmath135 and @xmath136 are the numbers of protons and neutrons in the nucleus . @xmath137 is the coupling between dm and protons or neutrons , given by @xmath138 where @xmath139 , @xmath140 , @xmath141 , @xmath142 , @xmath143 and @xmath144 @xcite . the coupling @xmath145 between dm and gluons from heavy quark loops is obtained from @xmath146 , which leads to @xmath147 and @xmath148 . in our model , the dm - quark coupling @xmath149 in eq . ( [ fn ] ) is given by @xmath150 because of @xmath151 , we can derive @xmath152 it is worthwhile to stress that @xmath117 is independent of @xmath116 . using the predicted @xmath71 from the observed dm abundance , we straightly calculate the spin - independent dm - nucleon elastic scattering cross section @xmath117 . the numerical results are shown in fig . [ 1hbdm ] ( right panels ) . for @xmath153 , we find that two dm mass ranges can be excluded by the current dm direct detection experiments cdms ii @xcite and xenon10 @xcite . due to the existence of @xmath116 , we can obtain different values of @xmath117 for a given dm mass @xmath41 when the annihilation channel @xmath154 is open . in this case , one can obtain @xmath155 for @xmath156 as shown in fig . [ 1hbdm ] ( lower - right panel ) , which is below the current experimental upper bounds . nevertheless the future experiments xenon100 @xcite , cdms 100 kg @xcite and xenon1 t @xcite can cover most parts of the allowed parameter space . for the region near the resonance point , the predicted @xmath117 is far below the current and future experimental upper bounds . as shown in sec . [ 1hbdma ] , @xmath89 is a key quantity in the determination of the dm cosmic relic abundance . on the other hand , @xmath89 also determines the dm annihilation rate in the galactic halo . it should be mentioned that the dm annihilation in the galactic halo occurs at @xmath157 ( @xmath158 ) . thus we calculate the thermally averaged annihilation cross section at @xmath159 , namely @xmath160 . the numerical results have been shown in fig . [ indirect1 ] for @xmath161 . notice that we can derive the similar results for different values of @xmath116 . one may find @xmath162 for most parts of the parameter space . the enhanced and suppressed @xmath160 on the two sides of the resonance point originate from the breit - wigner resonance effect @xcite . when @xmath41 is slightly less than the @xmath163 boson mass , the channel @xmath164 is open at high temperature , which dominates the total thermally averaged annihilation cross section and determines the dm relic density . however this channel is forbidden in the galactic halo . thus the threshold effect leads to a dip around @xmath163 threshold @xcite . when @xmath165 , one can obtain @xmath166 which is consistent with the usual @xmath47-wave annihilation cross section @xmath167 at the freeze - out temperature @xmath168 . in the 1hbdm . , width=264,height=226 ] in our model , the dm annihilation can generate primary antiprotons which can be detected by the dm indirect search experiments . recently , the pamela collaboration reports that the observed antiproton data is consistent with the usual estimation value of the secondary antiproton @xcite . therefore one can use the pamela antiproton measurements to constrain @xmath160 . in fig . [ indirect1 ] , we have also shown the maximum allowed @xmath160 for the min , med and max antiproton propagation models given in ref . @xcite . then we can find that a very narrow region can be excluded by the pamela antiproton data in our model . in fact , the width of this excluded region is about @xmath169 gev for the med and max cases . when double dm mass @xmath170 is slightly less than the higgs mass @xmath70 , the predicted @xmath117 and @xmath160 are very small which means that it is very difficult to detect the dm signals . we have discussed the higgs singlet @xmath3 as the cold dm candidate in the 1hbdm . in this section , we generalize the previous discussions to the 2hbdm in which the other bidoublet @xmath14 mixes significantly with @xmath12 and @xmath17 . in this case the scpv can be easily realized @xcite . comparing with the previous case , the main differences are that there could be more scalar particles entering the dm annihilation and scattering processes . furthermore , the new contributions from these particles may modify the correlation between the dm annihilation and dm - nucleon elastic scattering cross sections , which leads to significantly different predictions from the other singlet scalar dm models and the previous discussions . as shown in eq . ( [ higgscomponent ] ) , the second higgs bidoublet @xmath14 contains two neutral higgs contents @xmath171 . after the ssb , @xmath171 may obtain the vevs @xmath172 . the squared sum of all the vevs including @xmath173 should still lead to @xmath174 . in this case , it is convenient for us to rotate higgs bidoublets @xmath12 and @xmath14 into @xmath175 where @xmath176 are a pair of light charged higgs bosons . then one can diagonalize the mass matrix of three light neutral higgs @xmath177 and derive three light neutral higgs mass eigenstates . the relation between @xmath177 and three mass eigenstates can be written as @xmath178 where @xmath179 , @xmath180 and so on . due to many unknown parameters in the higgs potential of 2hbdm , we can not explicitly calculate three mixing angles @xmath181 and @xmath182 . for illustration , we consider three representative cases : ( i ) @xmath183 , @xmath184 and @xmath185 ; ( ii ) @xmath186 , @xmath187 and @xmath188 ; ( iii ) @xmath189 , @xmath190 and @xmath191 . the case i means that there is the significant mixing among three light neutral higgs . if all @xmath1 violation phases are absent , we can obtain @xmath187 and @xmath188 . in the case ii , the light higgs @xmath192 is @xmath1 odd which does not mix with @xmath193 and @xmath84 . for the case iii , we only consider the scalar and pseudoscalar mixing , namely @xmath194 . in the 2hbdm , the possible dm annihilation products are @xmath53 , @xmath45 , @xmath195 , @xmath196 and any two of the three neutral states @xmath197 as shown in fig . [ feynman2 ] . for a concrete numerical illustration , we choose all the masses @xmath198 , @xmath199 , @xmath200 gev and @xmath201 gev . for cubic and quartic scalar vertexes , we assume they are the same as that in the 1hbdm . namely , the vertexes of @xmath202 and @xmath203 are set equal to @xmath204 and @xmath205 , respectively . similarly , the cubic scalar vertexes among the light higgs particles @xmath193 , @xmath206 and @xmath176 are set equal to @xmath207 , and the cubic scalar vertexes between @xmath58 and two light higgs particles are assumed to be @xmath208 . it is worthwhile to stress that the heavy higgs particles from @xmath209 may be as the intermediate particles when two dm candidates annihilate into two light higgs bosons . nevertheless we still can use a coupling @xmath116 to describe the contributions of all possible heavy higgs bosons . all annihilation cross sections @xmath97 have been presented in appendix [ appendix.a ] . in the basis of eq . ( [ basis ] ) , the yukawa interactions for quarks are given by @xmath210 where @xmath211 . when both @xmath0 and @xmath1 are required to be broken down spontaneously , the yukawa coupling matrices @xmath212 , @xmath213 , @xmath214 and @xmath215 are complex symmetric . then one may rotate the quark fields and derive the following yukawa interactions relevant to light neutral higgs particles : @xmath216 where @xmath217 and @xmath218 are diagonal matrixes . according to the up and down quark masses , we can obtain @xmath219 and @xmath220 , respectively . in order to avoid the fcnc processes , we assume @xmath221 and @xmath222 are approximate diagonal matrixes due to approximate @xmath39 family symmetries @xcite and require @xmath223 since @xmath221 and @xmath222 do nt contribute the quark masses , the parameter @xmath224 may be very large except the top quark case . and dm - nucleon scattering cross section @xmath117 for three mixing cases in the 2hbdm with @xmath225 and @xmath226 . , title="fig:",width=264,height=226 ] and dm - nucleon scattering cross section @xmath117 for three mixing cases in the 2hbdm with @xmath225 and @xmath226 . , title="fig:",width=264,height=226 ] and dm - nucleon scattering cross section @xmath117 for three mixing cases in the 2hbdm with @xmath225 and @xmath226 . , title="fig:",width=264,height=226 ] and dm - nucleon scattering cross section @xmath117 for three mixing cases in the 2hbdm with @xmath225 and @xmath226 . , title="fig:",width=264,height=226 ] in the 2hbdm , the parameter @xmath224 in eq . ( [ r ] ) controls the yukawa couplings @xmath227 and @xmath228 . furthermore , the parameter @xmath224 will affect the total annihilation cross section and change the predicted coupling @xmath71 . for illustration , we choose the following two scenarios @xmath229 to calculate the allowed coupling @xmath71 from the observed dm abundance . considering three kinds of mixing cases and two @xmath230 scenarios , we plot the allowed coupling @xmath71 for @xmath231 in fig . [ l2hbdm ] ( left panels ) . it is clear that @xmath71 is dependent on the light higgs mixing and the parameter @xmath230 if @xmath232 gev . when dm candidate can annihilate into two light higgs bosons ( @xmath233 gev ) , one can derive the almost same @xmath71 for three kinds of mixing cases and two @xmath230 scenarios , which means that the light higgs mixing and the parameter @xmath230 do not significantly affect the total annihilation cross section . this conclusion can also be applied to @xmath234 as shown in figs . [ r1 ] and [ r5 ] ( left panels ) . for the dm indirect search , the 2hbdm has two enhanced regions for @xmath160 as shown in fig . [ indirect2 ] . therefore the pamela antiproton measurements can exclude two very narrow regions . the predicted @xmath160 is the same as that in the 1hbdm for most parts of parameter space . when @xmath235 , one can still obtain @xmath236 . it is clear that different mixing cases and @xmath230 scenarios lead to the same @xmath160 except the resonance regions . in the 2hbdm . , title="fig:",width=264,height=226 ] in the 2hbdm . , title="fig:",width=264,height=226 ] in the 2hbdm , the dm - quark coupling @xmath149 in eq . ( [ fn ] ) is given by @xmath237 where @xmath238 have been presented in appendix eq . ( [ f1 - 6 ] ) . notice that we have neglected the parameters @xmath239 , @xmath240 and @xmath241 since their contributions to @xmath117 are velocity - dependent . using the predicted @xmath119 in fig . [ l2hbdm ] ( left panels ) , we calculate the spin - independent dm - nucleon elastic scattering cross section @xmath117 for three mixing cases and two @xmath230 scenarios . different from @xmath160 , the predicted @xmath117 obviously depends on the mixing and @xmath230 as shown in fig . [ l2hbdm ] ( right panels ) . although three kinds of mixing cases have the almost same coupling @xmath71 for @xmath242 gev in the @xmath225 scenario , the predicted @xmath117 in the case iii is far less than that in the case i and case ii . this is because that there is cancellation between @xmath243 and @xmath244 in eq . ( [ aq2 ] ) for the case iii . when the dm candidate can annihilate into two light higgs bosons , a large @xmath230 does not obviously affect the predicted coupling @xmath71 . however , the parameters @xmath245 and @xmath246 in eq . ( [ aq2 ] ) will be significantly enlarged . therefore @xmath117 usually increases as @xmath230 increases . the case i clearly demonstrates this feature . the enlarged @xmath117 in the @xmath226 scenario may approach the cdms ii upper bound , which can be used to explain the two possible events observed by the cdms ii @xcite . it is worthwhile to stress that the case ii in the @xmath226 scenario give a smaller @xmath117 than that in the @xmath225 scenario due to the cancellation from the different higgs boson contributions . we conclude that the predicted @xmath117 is significantly dependent on the light higgs mixing and the parameter @xmath230 . for @xmath247 , the same conclusion can also be derived as shown in figs . [ r1 ] and [ r5 ] ( right panels ) . as shown in figs . [ l2hbdm ] , [ r1 ] and [ r5 ] ( right panels ) , the cdms ii @xcite and xenon10 @xcite experiments can exclude the region @xmath248 gev . for @xmath249 gev , our results show an upper bound for @xmath117 which is still below the current experiment upper bounds . the future experiments xenon100 @xcite , cdms 100 kg @xcite and xenon1 t @xcite can cover most parts of the allowed parameter space except the extreme cancellation cases . nevertheless , it is still difficult to detect the dm direct or indirect signals for the resonance regions @xmath250 gev and @xmath251 gev . for three mixing cases in the 2hbdm with @xmath225 . ] for three mixing cases in the 2hbdm with @xmath226 . ] in conclusion , we have investigated a scalar boson @xmath3 as the dm candidate in the left - right symmetric gauge model with two higgs bidoublets , in which the scpv can be easily realized . the stability of dm candidate @xmath3 is ensured by the fundamental symmetries @xmath0 and @xmath1 of quantum field theory . in order to well understand the dm properties in the 2hbdm , we have firstly analyzed the 1hbdm and shown that the predicted dm direct and indirect detection cross sections ( @xmath117 and @xmath160 ) are the same as that in the minimal extension of sm with a real singlet scalar if @xmath59 . when the annihilation channel @xmath154 is open ( @xmath123 ) , the @xmath49 exchange diagram relevant to @xmath116 leads to a continuous dm - nucleon elastic scattering cross sections @xmath117 . comparing with the 1hbdm , there are more scalar particles entering the dm annihilation and scattering processes in the 2hbdm . in the explicit calculations , we have considered three typical mixing cases and two yukawa coupling scenarios ( @xmath225 and @xmath226 ) to analyze the 2hbdm . it has been shown that @xmath160 is not sensitive to the light higgs mixing and yukawa couplings except the resonance regions . however @xmath117 is significantly dependent on the above two factors . in general , @xmath117 can be enhanced by large yukawa couplings and approach the cdms ii upper bound , which can be used to explain the two possible events observed by cdms ii . it should be mentioned that a large yukawa coupling may lead to a very small @xmath117 in the extreme mixing case . our results show that the future dm direct search experiments can cover most parts of the allowed parameter space . the pamela antiproton data can exclude two very narrow regions in the 2hbdm . in addition , we have shown that it is very difficult to detect the dm direct or indirect signals for the resonance regions since the breit - wigner resonance effect simultaneously suppresses @xmath117 and @xmath252 . this work is supported in part by the national basic research program of china ( 973 program ) under grants no . 2010cb833000 ; the national nature science foundation of china ( nsfc ) under grants no . 10975170 , no . 10821504 and no . 10905084 ; and the project of knowledge innovation program ( pkip ) of the chinese academy of science . for the annihilation processes @xmath253 , the annihilation cross section @xmath254 is given by @xmath255 , % ( a1)\end{aligned}\ ] ] where @xmath256 with @xmath257 the parameter @xmath230 has been defined in eq . ( [ r2 ] ) . the decay widths of three light neutral higgs are given by @xmath258 where @xmath259 , @xmath260 and @xmath261 . @xmath262 and @xmath263 have the following forms : @xmath264 if the annihilation productions are a higgs and a gauge boson , we can derive @xmath268^{1.5}}{s } \left| \frac{2 c_z s_x}{s- m_h^2 } - \frac{2 c_x c_z}{s- m_h^2 } \right|^2 \ ; , \nonumber \\ \hat{\sigma}_{z_1 h } & = & \frac{\lambda_{1,d}^2 } { 32 \pi } \frac{\left [ ( s - m_h^2 -m_{z_1}^2)^2 - 4 m_h^2 m_{z_1}^2 \right]^{1.5}}{s } \left| \frac{2 c_x c_z}{s- m_a^2 } - \frac{2 s_z}{s- m_h^2 } \right|^2 \ ; , \nonumber \\ \hat{\sigma}_{z_1 h } & = & \frac{\lambda_{1,d}^2 } { 32 \pi } \frac{\left [ ( s - m_h^2 -m_{z_1}^2)^2 - 4 m_h^2 m_{z_1}^2 \right]^{1.5}}{s } \left| \frac{2 s_z}{s- m_h^2 } - \frac{2 c_z s_x}{s- m_a^2 } \right|^2 \ ; , \nonumber \\ \hat{\sigma}_{w^\pm h^\mp } & = & \frac{\lambda_{1,d}^2 } { 4 \pi } \frac{\left [ ( s - m_{h^\pm}^2 -m_{w_1}^2)^2 - 4 m_{h^\pm}^2 m_{w_1}^2 \right]^{1.5}}{s } \left| \frac{a_1}{s- m_a^2 } + \frac{a_2}{s- m_h^2 } + \frac{a_3}{s- m_h^2 } \right|^2 , % ( a8)\end{aligned}\ ] ] where @xmath269 when two dm candidates annihilate into two higgs particles , we can obtain @xmath270\ ; , \nonumber \\ \hat{\sigma}_{i j } & = & \frac{\lambda_{1,d}^2 } { 8 \pi } \beta_{ij } \left [ g_2 ^ 2 - \frac{8 \lambda_{1,d } v_{\rm ew}^2}{s- m_i^2 - m_j^2 } g_2 f({\xi_{i j } } ) + \frac{8 \lambda_{1,d}^2 v_{\rm ew}^4}{(s- m_i^2- m_j^2)^2 } \left ( \frac{1}{1-\xi_{i j}^2 } + f({\xi_{i j } } ) \right ) \right ] , \nonumber \\ \hat{\sigma}_{h^\pm h^\mp } & = & \frac{\lambda_{1,d}^2 } { 8 \pi } \sqrt{1-\frac{4 m_{h^\pm}^2}{s } } g_2 ^ 2 , % ( a10)\end{aligned}\ ] ] with @xmath271 the subscripts @xmath272 and @xmath273 run over ( @xmath274 ) and ( @xmath275 ) , respectively . the quantity @xmath64 is defined as @xmath276 with @xmath277 . the parameter @xmath278 is given by @xmath279 . e. komatsu _ et al . _ , arxiv:1001.4538 [ astro-ph.co ] . j. c. pati and a. salam , phys . rev . d * 10 * , 275 ( 1974 ) [ erratum - ibid . d * 11 * , 703 ( 1975 ) ] ; r. n. mohapatra and j. c. pati , phys . d * 11 * , 566 ( 1975 ) ; g. senjanovic and r. n. mohapatra , phys . d * 12 * , 1502 ( 1975 ) ; r. n. mohapatra and g. senjanovic , phys . lett . * 44 * , 912 ( 1980 ) ; phys . d * 23 * , 165 ( 1981 ) . r. n. mohapatra , g. senjanovic and m. d. tran , phys . d * 28 * , 546 ( 1983 ) ; f. j. gilman and m. h. reno , phys . rev . d * 29 * , 937 ( 1984 ) ; d. chang , j. basecq , l. f. li and p. b. pal , phys . d * 30 * , 1601 ( 1984 ) ; w. s. hou and a. soni , phys . d * 32 * , 163 ( 1985 ) ; j. basecq , l. f. li and p. b. pal , phys . d * 32 * , 175 ( 1985 ) ; g. ecker and w. grimus , nucl . b * 258 * , 328 ( 1985 ) ; j. basecq and d. wyler , phys . rev . d * 39 * , 870 ( 1989 ) . y. l. wu and y. f. zhou , sci . china * g51 * , 1808 ( 2008 ) [ arxiv:0709.0042 [ hep - ph ] ] ; y. l. wu and y. f. zhou , talk at 4th international conference on flavor physics ( icfp 2007 ) , beijing , china , 24 - 28 sep 2007 j. mod . a * 23 * , 3304 ( 2008 ) [ arxiv:0711.3891 [ hep - ph ] ] ; w. l. guo , l. m. wang , y. l. wu and c. zhuang , phys . d * 78 * , 035015 ( 2008 ) [ arxiv:0805.0401 [ hep - ph ] ] . s. gopalakrishna , t. han , i. lewis , z. g. si and y. f. zhou , arxiv:1008.3508 [ hep - ph ] . d. feldman , z. liu and p. nath , phys . d * 79 * , 063509 ( 2009 ) [ arxiv:0810.5762 [ hep - ph ] ] ; m. ibe , h. murayama and t. t. yanagida , phys . d * 79 * , 095009 ( 2009 ) [ arxiv:0812.0072 [ hep - ph ] ] ; w. l. guo and y. l. wu , phys . d * 79 * , 055012 ( 2009 ) [ arxiv:0901.1450 [ hep - ph ] ] . m. e. pospelov , phys . d * 56 * , 259 ( 1997 ) [ arxiv : hep - ph/9611422 ] ; y. zhang , h. an , x. ji and r. n. mohapatra , phys . d * 76 * , 091301 ( 2007 ) [ arxiv:0704.1662 [ hep - ph ] ] ; a. maiezza , m. nemevsek , f. nesti and g. senjanovic , phys . d * 82 * , 055022 ( 2010 ) [ arxiv:1005.5160 [ hep - ph ] ] . j. mcdonald , phys . d * 50 * , 3637 ( 1994 ) [ arxiv : hep - ph/0702143 ] ; c. p. burgess , m. pospelov and t. ter veldhuis , nucl . b * 619 * , 709 ( 2001 ) [ arxiv : hep - ph/0011335 ] ; w. l. guo and y. l. wu , arxiv:1006.2518 [ hep - ph ] ; and references therein . here we have replaced the incorrect expression of eq . 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we investigate singlet scalar dark matter ( dm ) candidate in a left - right symmetric gauge model with two higgs bidoublets ( 2hbdm ) in which the stabilization of the dm particle is induced by the discrete symmetries @xmath0 and @xmath1 . according to the observed dm abundance , we predict the dm direct and indirect detection cross sections for the dm mass range from 10 gev to 500 gev . we show that the dm indirect detection cross section is not sensitive to the light higgs mixing and yukawa couplings except the resonance regions . the predicted spin - independent dm - nucleon elastic scattering cross section is found to be significantly dependent on the above two factors . our results show that the future dm direct search experiments can cover the most parts of the allowed parameter space . the pamela antiproton data can only exclude two very narrow regions in the 2hbdm . it is very difficult to detect the dm direct or indirect signals in the resonance regions due to the breit - wigner resonance effect .

GRAND CANYON NATIONAL PARK, Ariz. (AP) — Remains believed to be those of a 22-year-old Louisiana woman missing since April have been found in the Grand Canyon. Park officials say rangers found the remains believed to be those of Diana Zacarias of Natchitoches (NAK-uh-tesh), Louisiana, below Pima Point while conducting training Saturday. A multiday search was conducted after Zacarias' family reported her missing April 3. She had arrived on the South Rim on April 2. Park officials say the tentative identification is based on evidence found at the scene and that the remains have been transferred to the Coconino (koh-koh-NEE'-noh) County medical examiner for positive identification. Park officials say that the medical examiner and the National Park Service are investigating the incident and that no additional information is immediately available. ||||| Louisiana Woman Found Dead in Grand Canyon – Four Months After She Was Reported Missing Remains believed to be those of a 22-year-old Louisiana woman were found in the Grand Canyon on Saturday – nearly four months after she was reported missing, PEOPLE confirms.Rangers believe they found the body of Diana Zacarias, of Natchitoches, under Pima Point during their training on July 30, a Grand Canyon National Park spokeswoman tells PEOPLE. The spokeswoman says that the medical examiner will make the "final positive ID."The National Park Service unsuccessfully searched for the woman for several days after she was reported missing on April 3, according to an NPS statement Park officials said Zacarias arrived on the South Rim of the park on April 2 and is believed to have visited Yaki Point and Lookout Studio.No additional details of her death were immediately available, according to multiple reports.Officials with the Louisiana School for Math, Science and the Arts, where Zacarias was once a student, remembered her in a Facebook post "Our deepest condolences are with the Zacarias family," the post read. "Diana was one of three siblings who attended LSMSA. May the family find peace and comfort in this difficult time."Both NPS and the Coconino County medical examiner are investigating the incident, the Associated Press reports.The spokesperson told USA Today that the Grand Canyon sees up to 15 deaths a year, most of them due to heat or other medical issues.The discovery comes nearly a month after 35-year-old Colleen Burns, of Orlando, Florida, fell about 400 feet to her death off of the canyon's Ooh Aah Point. ||||| When Milan Arpino ('17) received her immunizations through the Shots for Tots program at the Ouachita Parish Health Unit, her mom made sure that she had several books to keep her occupied so she would not be afraid. “When I was four years old, I noticed that there weren’t any books at the health unit for other children to read so I asked my mom about it,” said Arpino, a rising senior at the Louisiana School for Math, Science, and the Arts. “She told me that maybe they didn’t ...have any books to bring with them.”

– Authorities believe they've found the body of a woman who disappeared nearly four months ago at the Grand Canyon, the AP reports. According to the Arizona Republic, the family of Diana Zacarias, a 22-year-old from Louisiana, reported her missing April 3. She was last seen at the Grand Canyon's South Rim and had uploaded a photo of herself to social media April 1, giving authorities an idea of where to look. The National Park Service searched for Zacarias for days but was unable to find her. Last Saturday, rangers taking part in training exercises found a body under Pima Point. Authorities believe the body is that of Zacarias based on evidence nearby. A cause of death hasn't been determined. Zacarias was a student at Northwestern State University, where she was majoring in industrial engineering technology, according to a Facebook post by her old high school. WBRZ reports Zacarias was a member of the Northwestern rowing team. "May the family find peace and comfort in this difficult time," her high school states. More than a dozen people die every year at the Grand Canyon, usually due to medical issues or heat. But a 35-year-old Florida woman fell to her death there just last month, according to People.

in this monograph we develop a theory of crossed products that allows for a locally compact group to act on an arbitrary operator algebra , not just a @xmath1-algebra . we establish foundational results , uncover permanence properties and demonstrate important connections between our crossed product theory and various lines of current research in both the non - selfadjoint and the @xmath1-algebra theory . the reader familiar with the non - selfadjoint literature knows well that crossed product type constructions have occupied the theory since its very beginnings . however most constructions in that theory involve the action of a semigroup which rarely happens to be a group , on an operator algebra which is usually a @xmath1-algebra . there is a good reason for this and it goes back to the early work of arveson @xcite . arveson recognized that in order to better encode the dynamics of a homeomorphism @xmath2 acting on a locally compact space @xmath3 , one should abandon group actions and instead focus on the action of @xmath4 on @xmath5 implemented by the positive iterates of @xmath2 . this initiated the study of what peters coined as the semicrossed product @xmath6 @xcite . the study of semicrossed products by @xmath4 , @xmath7 ( the free semigroup on @xmath8 generators ) and other important semigroups has produced a steady stream of important results and continues to this day at an increasing pace and depth @xcite . in this monograph we follow a less - travelled path : we start with an arbitrary operator algebra , preferably non - selfadjoint , and we allow a whole group to act on it . it is remarkable that there have been no systematic attempts to build a comprehensive theory around such algebras even though this class includes all crossed product @xmath1-algebras . admittedly , our interest in group actions on non - selfadjoint operator algebras arose reluctantly as well . indeed , apart from certain important cases ( see , e.g. , @xcite ) , the structure of automorphisms for non - selfadjoint operator algebras is not well understood . our initial approach stemmed from an attempt to settle two open problems regarding semi - dirichlet algebras ( which we do settle using the crossed product ) . we soon realized that even for very elementary " automorphisms ( gauge actions ) , the crossed product demonstrates a behavior that allows for significant results . the monograph is organized in eight chapters , including this introduction which appears as chapter [ intro ] . chapter [ prel ] establishes the terminology used in the monograph and contains many of the fundamental results from operator algebra theory that we require in the sequel . most of the results contained here come from five main sources @xcite , with additional sources mentioned within the chapter . chapter [ prel ] also contains some original material , i.e. , propositions [ prop integral ] and [ extension ] , to be used in later chapters . in chapter [ basic ] we define the various crossed products appearing in the monograph . given a @xmath1-dynamical system @xmath9 there are two natural choices for a crossed product , the ( full ) crossed product @xmath10 and the reduced crossed product @xmath11 . in the general case of an operator algebra @xmath12 there are many more choices , which we call relative crossed products , depending on the various choices of a @xmath1-cover for @xmath12 . after a careful consideration , we single out the appropriate choice for the ( full ) crossed product ( definition [ fulldefn ] ) as the relative crossed product coming from the universal @xmath1-cover @xmath13 of @xmath12 . because all relative reduced crossed products coincide ( corollary [ allrcoincide ] ) , the quest for a reduced crossed product trivializes . with the appropriate definitions at hand , we can now transfer results from the selfadjoint theory to our context . for instance , in theorem [ full raeb ] we generalize to the non - selfadjoint setting a result of raeburn @xcite regarding the universality of the crossed product of @xmath1-algebras . in theorem [ r = f ] we show that if the locally compact group @xmath14 is amenable , then all relative crossed products coincide ; the proof of this result requires the theory of maximal dilations @xcite . in theorem [ naimark ] we give a covariant " generalization of naimark s theorem on positive definite group representations . this allows us to obtain the von neumann - type inequality of corollary [ vonneumann ] . iterated crossed products play a prominent role in the selfadjoint theory . our first task in chapter [ takai ] is to explain how to make sense of an iterated crossed product within the framework of our theory . after accomplishing this , we move on to takai duality . indeed one of the central results of the selfadjoint theory involving iterated crossed products is the takai duality theorem @xcite , which extends the pontryagin duality to the context of operator algebras and @xmath1-dynamical systems . in theorem [ takai duality ] we succeed in extending the takai duality to the context of arbitrary dynamical systems not just selfadjoint . apart from its own interest , this extension has significant applications for the study of semisimplicity for operator algebras , as witnessed in chapter [ semis ] . ( see theorem [ tsemis ] and example [ texam ] . ) one of the immediate consequences of our early theory and a key ingredient in the proof of our takai duality , is the identity @xmath15 ( see theorem [ cmaxthm ] . ) one of the motivating questions of the monograph is the validity of the other identity @xmath16 regarding the @xmath1-envelope of the crossed product . in chapter [ basic ] we verify this identity in the case where @xmath14 is a locally compact abelian group ( theorem [ abelianenv ] ) . in chapter [ dirichlet sect ] we continue this investigation and in theorem [ dirichletenv ] we verify ( [ introident ] ) in the case where @xmath12 is dirichlet but @xmath14 arbitrary . in chapter [ dirichlet sect ] we also present the first application of our theory . in @xcite , davidson and katsoulis made a comprehensive study of dilation theory , commutant lifting and semicrossed products , with the class of semi - dirichlet algebras playing a central role in the theory . at the time of the writing of @xcite , our understanding of the abundance of semi - dirichlet algebras was limited and the following two questions arose regarding them . are there any semi - dirichlet algebras which are not isometrically isomorphic to tensor algebras of @xmath1-correspondences ? are there any semi - dirichlet algebras which are neither tensor algebras of @xmath1-correspondences nor dirichlet algebras ? in theorem [ crossedtensor ] and corollary [ neither ] we answer both questions in the affirmative . a key ingredient in producing these results is theorem [ generatingsemidir ] which asserts that the reduced crossed product of a semi - dirichlet operator algebra is also semi - dirichlet . if one wishes to study semi - dirichlet algebras , then the crossed product is indeed an indispensable tool . in chapter [ semis ] , we uncover another permanence property in the theory of crossed product algebras . in theorem [ firstsemisimple ] we show that if @xmath12 is a semisimple operator algebra and @xmath14 a discrete abelian group , then @xmath10 is semisimple . this raises the question whether the converse is also true . it turns out that in certain cases this is indeed true but in other cases it is not . to demonstrate this we investigate a class of operator algebras which was quite popular in the mid 90s : triangular af algebras @xcite . building on the beautiful ideas of donsig @xcite , we prove theorem [ mainsemisimple ] which states that if @xmath12 is a strongly maximal taf algebra and @xmath14 a discrete abelian group , then the dynamical system @xmath9 is linking if and only if @xmath17 is semisimple . in example [ linking example ] , we present an example of a non - semisimple taf algebra @xmath12 that admits a linking automorphism @xmath18 . therefore @xmath19 is semisimple even though @xmath12 is not , thus refuting the converse of theorem [ firstsemisimple ] . on the other hand , theorem [ tuhfsemisimple ] shows that for tuhf algebras the semisimplicity of @xmath12 and @xmath10 are equivalent properties . we expect more in this direction , with the investigation of other dynamical systems @xmath9 and the semisimplicity of the associated crossed products . we truly envision the study of semisimplicity ( or other permanence properties ) for crossed products as a theory that will parallel in interest and abundance of results that of simplicity for selfadjoint crossed products . as evidence we offer a remarkable , we believe , result which shows that for crossed products by compact abelian groups , the situation of theorem [ firstsemisimple ] reverses . in theorem [ tsemis ] we show that if @xmath10 is a semisimple operator algebra and @xmath14 a compact abelian group , then @xmath12 is semisimple . furthermore , in example [ texam ] we show the converse is not in general true . both these results are accomplished through the use of our non - selfadjoint takai duality . chapter [ hao ] makes a connection with a topic in @xmath1-algebra theory , which is currently under investigation or impacts the work of various authors , including abadie , bedos , deaconu , hao , kaliszewski , katsura , kim , kumjian , ng , quigg , schafhauser and others @xcite . these authors are either using or currently investigating the validity of the hao - ng isomorphism theorem beyond the class of amenable locally compact groups . this is a problem seemingly irrelevant to the non - selfadjoint theory as it involves the functoriality of two crossed product constructions in @xmath1-algebra theory . it is a consequence of our theorem [ hntensor1 ] that the investigation of the previously mentioned authors is equivalent to resolving the identity ( [ introident ] ) for a very special class of non - selfadjoint dynamical systems @xmath9 , where @xmath12 is the tensor algebra of a @xmath1-correspondence and @xmath20 , the action of a locally compact group by generalized gauge automorphisms . actually , theorem [ hntensor1 ] leads to a recasting of the hao - ng isomorphism problem , which we verify in the case of ( not necessarily injective ) hilbert bimodules ( theorem [ hnbim ] ) . it is worth mentioning that the main focus of chapter [ hao ] is not the hao - ng isomorphism problem itself but instead verifying another permanence property for the crossed product : the crossed product of a tensor algebra @xmath12 by a locally compact group @xmath14 of gauge automorphisms remains in the class of tensor algebras . ( we have seen in theorem [ crossedtensor ] that this is not the case when the group @xmath14 acts by arbitrary automorphisms . ) in order to obtain the affirmative answer ( theorem [ hntensor2 ] ) we use a result of independent interest , which we label the extension theorem . the extension theorem ( theorem [ extend ] ) gives a very broad criterion for verifying whether an operator algebra naturally " containing a @xmath1-correspondence @xmath21 is isomorphic to the tensor algebra of @xmath21 . this a very general result with additional applications to appear elsewhere . the monograph closes with chapter [ problems ] , where we list some open problems for further investigation . with each open problem listed , we give a brief commentary intended to help the reader guide himself through the pertinent material or literature . two of these problems concern the classification of crossed products . this a topic which is left untouched in this monograph and we plan to address it in a subsequent work . beyond the specific problems of chapter [ problems ] , this work also suggests two general directions for future research : one abstract " and another one more concrete " . the current @xmath1-algebra literature is occupied with the study of more general concepts of a crossed product , e.g. , crossed products by coactions , twisted actions and much more . this is such a broad area that we will not even be attempting to survey it here ; see however @xcite and the references therein . if one wishes to develop non - commatative duality and the appropriate versions of our non - selfadjoint takai duality of chapter [ takai ] , then the abstract study of these more general crossed products at the non - selfadjoint level is of the highest priority . on the concrete side , the non - selfadjoint operator algebra theory is currently being infused by a wealth of very deep and far - reaching studies . in a broad sense , the current rapid development of free analysis " and free function theory " involves naturally certain non - selfadjoint operator algebras , as witnessed in the works of muhly and solel @xcite , popescu @xcite and others . closer to this monograph , shalit and solel @xcite pioneered recently the study of a new class of operator algebras , the tensor algebras of subproduct systems . these algebras exhibit a very diverse and unexpected behavior as demonstrated in the recent papers @xcite . even for very special cases the study of these algebras relates to topics which are very popular and quite demanding , such as the drury - arveson spaces and algebraic varieties associated with ideals @xcite , stochastic matrices @xcite , subshifts @xcite and more . it seems to us that the tensor algebras of subproduct systems and their peripheral algebras should be the natural place to extend the theory of chapter [ hao ] . in particular it would be very interesting to see how the hao - ng isomorphism problem manifests itself in that context . this of course hinges on understanding what the cuntz - pimsner algebra of a subproduct system should be ; again this is a topic of important current research @xcite . finally a word about the groups appearing in this monograph . our main goal is to develop a comprehensive theory of crossed products that is applicable to all locally compact groups . hence the majority of our work concerns that generality . nevertheless many of our results are new and interesting even in the case where @xmath22 . for instance , this is the case with all ( counter)examples appearing in chapter [ dirichlet sect ] or the semisimplicity results of chapter [ semis ] . a special mention needs to made for chapter [ hao ] . there we took the unusual step of duplicating " proofs in order to give a more elementary and self - contained treatment of the case where @xmath14 is discrete . we believe that this adds to the monograph as it makes very accessible a work that bridges the selfadjoint with the non - selfadjoint theory . the term _ operator algebra _ is understood to mean a norm closed subalgebra of the algebra of all bounded operators acting on a hilbert space . all algebras in this monograph are assumed to be approximately unital , i.e. , they possess a contractive approximate identity . all representations ( and homomorphisms into multiplier algebras , whenever applicable ) will be required to be non - degenerate . on occasion we will need to exploit the richer structure of unital operator algebras . if @xmath12 is an operator algebra without a unit , let @xmath23 . if @xmath24 is a completely isometric homomorphism between non - unital operator algebras , then meyer ( * ? ? * corollary 3.3 ) shows that @xmath25 extends to a complete isometry @xmath26 . this shows that the unitization of @xmath12 is unique up to complete isometry . in the category of unital algebras with morphisms the completely contractive maps , the concept of a dilation of a morphism is defined as follows . let @xmath12 be a unital operator algebra and @xmath27 be a completely contractive map . a _ dilation _ @xmath28 for @xmath29 is a completely contractive map so that @xmath30 . a completely contractive map is called _ maximal _ if it admits no non - trivial dilations . ( since we are within the unital category , all maps so far are either assumed or required to be unital . ) dritschel and mccullough ( * ? ? ? * theorem 1.2 ) have shown that any completely contractive representation @xmath29 of an operator algebra @xmath12 admits a maximal dilation @xmath31 , which also happens to be multiplicative . given an operator algebra @xmath12 , a @xmath1-cover @xmath32 for @xmath12 consists of a @xmath1-algebra @xmath33 and a completely isometric homomorphism @xmath34 with @xmath35 . [ firstequiv ] two @xmath1-covers @xmath36 , @xmath37 , of an operator algebra @xmath12 are said to be _ equivalent _ , denoted as @xmath38 , provided that there exists @xmath39-isomorphism @xmath40 that makes following diagram @xmath41^{j } \\ { { \mathcal{a}}}\ar[u]^{j_1 } \ar[r]_{j_2 } & { { \mathcal{c}}}_2}\ ] ] commutative . given an operator algebra @xmath12 , the @xmath1-envelope @xmath42 is any @xmath1-cover of @xmath12 satisfying the following property : for any other @xmath1-cover @xmath43 of @xmath12 there exists a @xmath39-epimorphism @xmath44 so that @xmath45 , for all @xmath46 . as it turns out the collection of all @xmath1-covers that qualify as the @xmath1-envelope for @xmath12 forms an equivalence class under the equivalence of definition [ firstequiv ] . the concept of the @xmath1-envelope plays a paramount role in abstract operator algebra theory @xcite . if @xmath32 is a @xmath1-cover of a unital operator algebra @xmath12 , then there exists a largest ideal @xmath47 , the _ shilov ideal _ of @xmath12 in @xmath32 , so that the quotient map @xmath48 when restricted on @xmath49 is completely isometric . it turns out that @xmath50 , where @xmath51 is the natural quotient map . a related result asserts that if @xmath52 is a completely isometric representation of a unital operator algebra @xmath12 and @xmath31 a maximal dilation of @xmath29 , then @xmath53 . see @xcite for more details . if @xmath12 is a non - unital operator algebra then we can describe the @xmath1-envelope of @xmath12 by invoking its unitization as follows : if @xmath54 , then @xmath55 , where @xmath56 and @xmath57 . see the proof of ( * ? ? ? * proposition 4.3.5 ) for the precise argument . if @xmath12 is an operator algebra then there exists a @xmath1-cover @xmath58 with the following universal property : if @xmath59 is any completely contractive homomorphism into a @xmath1-algebra @xmath33 , then there exists a ( necessarily unique ) @xmath39-homomorphism @xmath60 such that @xmath61 . the cover @xmath13 is called the maximal or universal @xmath1-algebra of @xmath12 . the equivalence class of this @xmath1-cover also plays a crucial role in abstract operator algebra theory @xcite . see also @xcite and the references therein for more applications of @xmath13 . we list a few more results regarding ( approximately unital ) operator algebras . the interested reader should consult the comprehensive monograph of blecher and le merdy @xcite for more details . by ( * ? ? ? * lemma 2.1.7 ) , the @xmath1-cover of an approximately unital operator algebra @xmath12 is actually unital only when @xmath12 itself is unital . furthermore a contractive approximate unit for @xmath12 is also an approximate unit for any @xmath1-cover @xmath62 of @xmath12 ( * ? ? ? * lemma 2.1.7 ) . if @xmath12 is an operator algebra , then @xmath63 is the multiplier algebra of @xmath12 . for any completely isometric non - degenerate representation @xmath52 , the algebra @xmath64 is completely isometrically isomorphic to @xmath65 via an isomorphism that fixes @xmath12 elementwise ( * ? ? ? * proposition 2.6.8 ) . furthermore , @xmath66 for any @xmath1-cover @xmath33 of @xmath12 @xcite . therefore , @xmath67 is a ( two - sided ) ideal , which is essential both as a left and a right ideal of @xmath68 . let @xmath12 , @xmath69 be operator algebras . a completely contractive homomorphism @xmath70 is said to be a multiplier - nondegenerate morphism , if both @xmath71 $ ] and @xmath72 $ ] are dense in @xmath69 . there are many equivalent formulations of this property based on cohen s factorization theorem ; see ( * ? ? ? * section [ prel].6.11 ) . a multiplier - nondegenerate morphism @xmath70 always admits a unique , unital and completely contractive extension @xmath73 ( * ? ? ? * proposition 2.6.12 ) ; such a map is easily seen to be strictly continuous . finally we need to explain how we make sense of integrals where the integrand is a function taking values in the multiplier algebra of an operator algebra . ( propositions [ raeburnthm ] , [ classifyrepns ] and theorem [ full raeb ] . ) if the integrand is norm continuous , then see ( * ? ? ? * lemma 1.91 ) . otherwise we use the following . [ prop integral ] let @xmath14 be a locally compact group with left - invariant haar measure @xmath74 . let @xmath12 be an operator algebra and let @xmath75 be a strictly continuous function with compact support . then there exists a unique element @xmath76 satisfying @xmath77 for all @xmath46 . furthermore , if @xmath69 is an approximately unital operator algebra and @xmath70 is a completely contractive , multiplier - nondegenerate morphism , then @xmath78 if @xmath12 is a @xmath1-algebra , then the existence and uniqueness of such an element follows from lemma 1.101 in @xcite . we will rely on this result in order to to explain the validity of ( [ integralsense ] ) and ( [ barl ] ) in general . let @xmath33 be a @xmath1-cover for @xmath12 ; as we noticed earlier we have @xmath79 . let @xmath80 be a contractive approximate identity for @xmath12 ( and therefore for @xmath33 as well ) . for any @xmath81 , the functions @xmath82 and @xmath83 can be uniformly approximated by the norm continuous functions @xmath84 , @xmath85 , and @xmath86 , @xmath85 , respectively and so they are norm continuous . hence @xmath87 is strictly continuous in @xmath88 . lemma 1.101 in @xcite implies the existence of an element @xmath89 so that @xmath90 for all @xmath81 . however , the above equations show that for any @xmath46 both @xmath91 and @xmath92 are in @xmath12 and so @xmath76 . in order to establish ( [ barl ] ) , assume that @xmath70 is a multiplier- nondegenerate morphism , i.e. , @xmath71 $ ] and @xmath72 $ ] are dense in @xmath69 . since @xmath69 is also approximately unital , both integrals in ( [ barl ] ) are well - defined . therefore , for arbitrary @xmath46 , @xmath93 , we have @xmath94 a similar argument establishes @xmath95 since @xmath96 is an essential ideal , the conclusion follows . [ multiplier nondeg ] if @xmath97 is a contractive , non - degenerate representation , then it can also be viewed as a morphism @xmath98 , where @xmath99 denotes the compact operators . since @xmath12 is approximately unital , then it follows that @xmath98 is also a multiplier - nondegenerate morphism and so ( [ barl ] ) is applicable for such a @xmath25 . to see the multiplier - nondegeneracy of @xmath25 , let @xmath80 be a contractive approximate identity for @xmath12 . the non - degeneracy of @xmath25 implies that @xmath100 converges strongly to the identity @xmath101 . hence for an @xmath102 , we have @xmath103 in norm and so ( * ? ? ? * lemma 2.1.6 ) implies @xmath104 . therefore @xmath105 \subseteq { { \mathcal{k}}}({{\mathcal{h}}})$ ] is dense . the density of @xmath106 $ ] in @xmath99 is elementary to verify . a @xmath1- correspondence @xmath107 consists of a @xmath1-algebra @xmath33 , a hilbert @xmath33-module @xmath108 and a ( non - degenerate ) @xmath39-homomorphism @xmath109 into the adjointable operators on @xmath21 . two @xmath1-correspondences @xmath110 and @xmath111 are said to be _ unitarily equivalent _ if there exist a @xmath39-isomorphism @xmath112 and a linear surjection @xmath113 so that : * @xmath114 and @xmath115 , * @xmath116 , for all @xmath81 and @xmath117 . in that case we say that the pair @xmath118 implements the unitary equivalence . an isometric ( toeplitz ) representation @xmath119 of a @xmath1-correspondence into a @xmath1-algebra @xmath120 , is a pair consisting of a @xmath39-homomorphism @xmath121 and a linear map @xmath122 , such that 1 . @xmath123 , 2 . @xmath124 , for all @xmath81 and @xmath117 . a representation @xmath125 is said to be _ injective _ iff @xmath31 is injective ; in that case @xmath126 is an isometry . the @xmath1-algebra generated by a representation @xmath119 equals the closed linear span of @xmath127 , where for simplicity @xmath128 and @xmath129 . for any representation @xmath119 there exists a @xmath39-homomorphism @xmath130 , such that @xmath131 . it is easy to see that for a @xmath1-correspondence @xmath107 there exists a universal toeplitz representation , denoted as @xmath132 , so that any other representation of @xmath107 is equivalent to a direct sum of sub - representations of @xmath132 . we define the cuntz - pimsner - toeplitz @xmath1-algebra @xmath133 as the @xmath1-algebra generated by all elements of the form @xmath134 , @xmath81 , @xmath135 . by the universality of @xmath132 the algebra @xmath133 satisfies the following property : for any toeplitz representation @xmath119 of @xmath21 , there exists a representation @xmath136 of @xmath133 , called _ the integrated form of _ @xmath119 , so that @xmath137 , for all @xmath81 , and @xmath138 , for all @xmath139 . ( see ( * ? ? ? * definition 3.1 ) and the subsequent comments . ) we say that a toeplitz representation @xmath125 admits a gauge action if there exists a family @xmath140 of @xmath39-endomorphisms of @xmath141 so that @xmath142 the following result of katsura ( * ? ? ? * theorem 6.2 ) gives an easy to use criterion for verifying that a toeplitz representation @xmath143 _ integrates _ to a faithful representation @xmath144 of @xmath133 . [ gauge invariant uniqueness theorem ] [ giuthm ] let @xmath110 be a @xmath1-correspondence and let @xmath143 a toeplitz representation of @xmath145 that admits a gauge action and satisfies @xmath146 then @xmath144 is a faithful representation of @xmath133 . it is worth giving an example of a concrete toeplitz representation of @xmath110 that will help make some of the results that follow more transparent . for that we need to define first the concept of the stabilized tensor product between @xmath1-correspondences . let @xmath110 and @xmath147 be @xmath1-correspondences . interior _ or _ stabilized tensor product _ , denoted by @xmath148 , is the quotient of the vector space tensor product @xmath149 by the subspace generated by the elements of the form @xmath150 it becomes a pre - hilbert @xmath33-module when equipped with @xmath151 where @xmath152 , @xmath153 and @xmath81 . for @xmath154 we define @xmath155 as the mapping @xmath156 hence @xmath148 becomes a @xmath1-correspondence by defining @xmath157 , @xmath158 . the _ fock space _ @xmath159 over the correspondence @xmath110 is the interior direct sum of the @xmath160 , @xmath161 , with the structure of a direct sum of @xmath1-correspondences over @xmath33 , @xmath162 given @xmath135 , the ( left ) creation operator @xmath163 is defined as @xmath164 where @xmath81 and @xmath165 , for all @xmath161 . for any @xmath81 , we define @xmath166 it is easy to verify that @xmath167 is a toeplitz representation of @xmath168 which is called the _ fock representation _ of @xmath168 . it follows from theorem [ giuthm ] that the representation @xmath169 is actually faithful . given a @xmath1-correspondence @xmath110 , there is a natural non - selfadjoint subalgebra of @xmath133 that plays an important role in this monograph . the _ tensor algebra _ @xmath170 of a @xmath1-correspondence @xmath107 is the norm - closed subalgebra of @xmath133 generated by all elements of the form @xmath134 , @xmath81 , @xmath135 . it is worth mentioning here that @xmath171 also sits naturally inside the cuntz - pimsner algebra @xmath172 associated with the @xmath1-correspondence @xmath21 . this follows from work in @xcite which we now describe . if @xmath110 is a @xmath1-correspondence , then let @xmath173 a representation @xmath143 of @xmath174 is said to be _ covariant _ iff @xmath175 , for all @xmath176 . the universal @xmath1-algebra for all " covariant representations of @xmath174 is the cuntz - pimsner algebra @xmath177 . the algebra @xmath177 contains ( a faithful copy of ) @xmath33 and ( a unitarily equivalent ) copy of @xmath21 . katsoulis and kribs ( * ? ? ? * lemma 3.5 ) have shown that the non - selfadjoint algebra of @xmath177 generated by these copies of @xmath33 and @xmath21 is completely isometrically isomorphic to @xmath178 . furthermore , @xmath179 . see @xcite for more details . the tensor algebras for @xmath1-correspondences were pioneered by muhly and solel in @xcite . they form a broad class of non - selfadjoint operator algebras which includes as special cases peters semicrossed products @xcite , popescu s non - commutative disc algebras @xcite , the tensor algebras of graphs ( introduced in @xcite and further studied in @xcite ) and the tensor algebras for multivariable dynamics @xcite , to mention but a few . due to its universality , the cuntz - pimsner - toeplitz @xmath1-algebra @xmath133 admits a gauge action @xmath180 that leaves @xmath181 elementwise invariant and twists " each @xmath182 , @xmath135 , by a unimodular scalar @xmath183 , that is @xmath184 , @xmath135 . using this action , and reiterating a familiar trick with the fejer kernel , one can verify that each element @xmath185 admits a fourier series expansion @xmath186 where the summability is in the cesaro sense . one of the immediate consequences of ( [ cesaro ] ) is that the diagonal of @xmath178 equals @xmath33 , i.e. , @xmath187 . another consequence now follows . if @xmath174 is a @xmath1-correspondence and @xmath31 a bounded multiplicative linear functional on @xmath33 , then @xmath188 will denote the collection of all bounded multiplicative linear functionals on @xmath178 , whose restriction on @xmath33 agrees with @xmath31 . [ extension ] let @xmath174 be a @xmath1-correspondence and @xmath31 is a bounded multiplicative linear functional on @xmath33 . if @xmath188 is as above , then @xmath188 is either a singleton or it is at least the size of the continuum . due to the gauge action @xmath180 discussed above , @xmath133 admits an expectation @xmath189 onto the fixed point algebra of @xmath180 . when restricted on @xmath178 , the expectation @xmath190 is multiplicative and projects onto @xmath181 . if @xmath31 is a bounded multiplicative linear functional on @xmath33 , then @xmath191 . hence @xmath192 . if @xmath193 are distinct , then at least one of them , say @xmath194 , does not annihilate @xmath21 . but then , @xmath195 , @xmath183 , are all distinct elements of @xmath188 and the conclusion follows . the crossed product of an operator algebra will be formally defined in the next chapter . nevertheless we collect here various known results regarding crossed products of @xmath1-algebras to be used throughout the monograph . our main references are @xcite ; we follow closely @xcite in terms of notation . let @xmath14 be a discrete amenable group , let @xmath33 be a @xmath1-algebra and let @xmath196 be a representation . since @xmath14 is amenable , both the full crossed product @xmath197 and the reduced @xmath198 coincide . on @xmath197 there is a well - defined faithful expectation @xmath199 projecting on @xmath200 , which satisfies @xmath201 for any finite sum of the form @xmath202 , where @xmath203 are the universal unitaries in the multiplier algebra @xmath204 implementing the action of @xmath205 , @xmath206 . if @xmath207 , then the fourier coefficients @xmath208 of @xmath209 are defined by the formula @xmath210 , @xmath206 . it is easy to see that if @xmath211 is a sequence of polynomials in @xmath212 converging to @xmath209 , then @xmath213 , @xmath214 . since the group @xmath14 is amenable , it contains a _ folner net _ , i.e. , a net @xmath215 of finite subsets of @xmath14 so that @xmath216 this allows us to deduce a cesaro type approximation for any @xmath217 using polynomials with coefficients ranging over @xmath208 . [ ceasaroapprox ] let @xmath218 be as above and let @xmath219 . then given @xmath220 there exists a finite set @xmath221 so that @xmath222 in particular , if @xmath223 , @xmath214 , then @xmath224 . by ( * ? * lemma 4.2.3 ) , for any finite set @xmath225 , the map @xmath226 extends to a completely contractive map @xmath227 on @xmath197 . if @xmath207 , then the net @xmath228 converges to @xmath209 , where @xmath229 is a folner net for @xmath14 . choose @xmath230 so that @xmath231 . the conclusion follows now by applying @xmath232 to any sequence @xmath211 of polynomials in @xmath197 converging to @xmath209 . in the case where @xmath14 is a discrete abelian group we can say something more . in that case the pontryagin dual @xmath233 of @xmath14 , equipped with the compact - open topology is compact and therefore it admits a ( normalized ) haar measure @xmath234 . one can then verify that for an @xmath207 we have @xmath235 where @xmath236 is the dual action , i.e. , @xmath237 , @xmath81 , @xmath206 . hence , if @xmath238 is a closed linear space which is left invariant by @xmath239 , then @xmath240 , for any @xmath206 and @xmath241 . in what follows , a _ dynamical system _ @xmath9 consists of an approximately unital operator algebra @xmath12 and a locally compact ( hausdorff ) group @xmath14 acting continuously on @xmath12 by completely isometric automorphisms , i.e. , there exists a group representation @xmath20 which is continuous in the point - norm topology . ( here @xmath242 denotes the collection of all completely isometric automorphisms of @xmath12 . ) the group @xmath14 is equipped with a left - invariant haar measure @xmath74 ; the modular function of @xmath74 will be denoted as @xmath243 . usually @xmath244 , @xmath245 , will be denoted as @xmath246 and on occasion as @xmath247 . now let @xmath218 be a @xmath1-dynamical system and let @xmath248 denote the continuous compactly supported functions from @xmath14 into @xmath33 . then @xmath248 is a @xmath39-algebra in the usual way @xcite . in the sequel , if @xmath81 and @xmath249 then @xmath250 will denote the function @xmath251 , @xmath245 . any covariant representation @xmath252 of @xmath218 induces a representation @xmath253 on @xmath248 , which is called the integrated form of @xmath252 ( * ? ? ? * proposition 2.23 ) . the full crossed product @xmath1-algebra @xmath254 is the completion of @xmath248 with respect to an appropriate supremum norm arising from all integrated covariant representations of @xmath218 . the reduced crossed product @xmath255 is defined using the left regular representation for @xmath14 . see @xcite for more details . in the case of an arbitrary dynamical system @xmath9 , we appeal to the selfadjoint theory described above in order to define crossed product algebras . here we have several options for defining a full or reduced crossed product , depending on the various choices of a @xmath1-cover for @xmath12 . [ admit ] let @xmath9 be a dynamical system and let @xmath32 be a @xmath1-cover of @xmath12 . then @xmath32 is said to be @xmath18-admissible if there exists a group representation @xmath256 which extends the representation @xmath257 note that the representation @xmath258 of definition [ admit ] is automatically continuous over a dense subalgebra of @xmath33 and so an easy @xmath259 argument actually shows that @xmath256 is a continuous group representation . in the sequel , since @xmath258 is uniquely determined by its action on @xmath49 , both ( [ detailona ] ) and its extension @xmath258 will be denoted by the same symbol @xmath18 . [ relativedefn ] let @xmath9 be a dynamical system and let @xmath32 be an @xmath18-admissible @xmath1-cover for @xmath12 . then , @xmath260 and @xmath261 will denote the subalgebras of the crossed product @xmath1-algebras @xmath197 and @xmath198 respectively , which are generated by @xmath262 . one has to be a bit careful with definition [ relativedefn ] when dealing with an _ abstract _ operator algebra . it is common practice in operator algebra theory to denote a @xmath1-cover by the use of set theoretic inclusion . nevertheless a @xmath1-cover for @xmath12 is not just an inclusion of the form @xmath263 but instead a pair @xmath32 , where @xmath33 is a @xmath1-algebra , @xmath264 is a complete isometry and @xmath35 . furthermore , in the case of an @xmath18-admissible @xmath1-cover , it seems that the structure of the relative crossed product for @xmath12 should depend on the nature of the embedding @xmath265 and one should keep that in mind when working with that crossed product . to put it differently , assume that @xmath9 is a dynamical system and @xmath266 , @xmath37 , are @xmath1-covers for @xmath12 . further assume that the representations @xmath267 extend to @xmath39-representations @xmath268 , @xmath37 . it is not at all obvious that whenever @xmath269 ( or even @xmath270 ) , the @xmath1- dynamical systems @xmath271 are conjugate nor that the corresponding crossed product algebras are isomorphic . therefore the ( admittedly ) heavy notation @xmath260 and @xmath272 seems to be unavoidable . we have already encountered the concept of equivalence between @xmath1-covers in definition [ firstequiv ] . indeed our view of @xmath273 and @xmath274 in chapter [ prel ] is essentially that of an equivalence class of @xmath1-covers and not just of a single element . let @xmath9 be a dynamical system and let @xmath275 be an @xmath18-admissible @xmath1-cover for @xmath12 . if @xmath276 is another @xmath1-cover of @xmath12 which is equivalent to @xmath277 , then @xmath278 is also @xmath18-admissible and so both representations @xmath267 extend to @xmath39-representations @xmath268 , @xmath37 . . furthermore @xmath279 via complete isometries that map generators to generators . let @xmath280 be a @xmath39-isomorphism so that the diagram ( [ little triangle ] ) commutes . to see that @xmath276 is @xmath18-admissible simply notice that @xmath281 extends @xmath282 to a @xmath39-automorphism of @xmath283 , for any @xmath245 . hence @xmath278 is also @xmath18-admissible . now note that @xmath265 is _ @xmath14-equivariant _ , i.e. , it implements a conjugacy between the @xmath1-dynamical systems @xmath284 and @xmath285 . indeed , if @xmath286 , @xmath46 , then @xmath287 and since @xmath288 generates @xmath289 as a @xmath1-algebra , @xmath290 , for all @xmath291 . the conjugacy @xmath292 between @xmath284 and @xmath285 implies that the ( full ) crossed product @xmath1-algebras are @xmath39-isomorphic ( * ? ? ? * proposition 2.48 ) . furthermore this isomorphism _ maps generators to generators _ , i.e. , it maps @xmath293 onto @xmath294 , for any @xmath295 . this establishes that @xmath296 and @xmath297 are completely isometrically isomorphic . a similar argument , using ( * ? ? ? * lemma a.16 ) this time , establishes the isomorphism of the operator algebras @xmath298 and @xmath299 . the previous lemma will allow us to adopt a notation lighter than the notation @xmath260 and @xmath272 at least in the case where the @xmath1-covers are coming either from the @xmath1-envelope or from the universal @xmath1-algebra of @xmath12 . indeed [ delicate ] let @xmath9 be a dynamical system and let @xmath266 be @xmath1-covers for @xmath12 with either @xmath300 , @xmath37 , or @xmath301 , @xmath37 . then there exist continuous group representations @xmath268 which extend the representations @xmath302 furthermore @xmath303 and @xmath304 , via complete isometries that map generators to generators . we deal with @xmath13 and the full crossed product . similar arguments work in all other cases as well . the proof essentially follows from the well - known fact that any completely isometric automorphism @xmath305 of @xmath12 extends to a @xmath39-automorphism @xmath31 of @xmath306 . indeed , the defining property of @xmath13 implies the existence of a @xmath39-homomorphism @xmath307 so that @xmath308 . similarly , there exists a @xmath39-homomorphism @xmath309 so that @xmath310 . hence , if @xmath311 , @xmath46 we have @xmath312 i.e. , @xmath313 , and since @xmath12 generates @xmath13 as a @xmath1-algebra , @xmath314 . similarly @xmath315 and so @xmath316 with @xmath308 and so @xmath317 . the previous paragraph implies the existence of @xmath39-automorphisms @xmath318 , @xmath245 , which extend the maps @xmath319 , @xmath37 . since @xmath320 are group representation , the same is true for @xmath321 over a dense subalgebra of @xmath322 . therefore the @xmath323 are group representations . because of the previous two lemmas we can now write @xmath324 , @xmath325 and similarly for the associated reduced crossed products . it turns out that in specific situations there are more crossed products to be associated naturally with the system @xmath326 . this is truly a feature of the non - selfadjoint world . our next results establish basic properties for the crossed product to be used frequently in the rest of the monograph . both results are easy to prove in the case where @xmath14 is discrete but the general case requires some agility . [ cai ] let @xmath9 be a dynamical system and let @xmath32 be an @xmath18-admissible @xmath1-cover for @xmath12 . then the algebras @xmath260 and @xmath327 are approximately unital . consider the collection @xmath328 of all compact neighborhoods of the identity @xmath329 , ordered by inverse set - theoretic inclusion and contained in a fixed compact set @xmath330 . for each such neighborhood @xmath331 , choose a non - negative continuous function @xmath332 with @xmath333 and @xmath334 . set @xmath335 , @xmath85 , where @xmath336 is a contractive approximate identity for @xmath12 ( and therefore for @xmath33 ) . we claim that @xmath337 is a left contractive approximate identity for @xmath248 in the @xmath338-norm . indeed let @xmath81 , @xmath339 and fix an @xmath340 . then , @xmath341 since the supports of the @xmath332 shrink " to @xmath342 , we can choose the @xmath85 large enough so that the @xmath343 are eventually @xmath344-close to @xmath345 , for all @xmath346 . hence for such @xmath85 we have @xmath347 for all @xmath245 . since left translations act continuously on @xmath348 , we can also arrange for these @xmath85 to satisfy , @xmath349 , for all @xmath346 and @xmath245 . hence , @xmath350 however , @xmath351 and so ( [ eq : cai1 ] ) and ( [ eq : cai2 ] ) imply that @xmath352 for all @xmath353 and sufficiently large @xmath85 . from this it is easily seen that @xmath337 is a left contractive approximate identity for @xmath248 in the @xmath338-norm . from the above it follows that @xmath337 is a left contractive approximate identity for @xmath197 and @xmath255 . hence by ( * ? ? ? * lemma 2.1.6 ) we have that @xmath337 is also a right contractive identity and the conclusion follows . let @xmath9 be a dynamical system and let @xmath32 be an @xmath18-admissible @xmath1-cover for @xmath12 . then @xmath254 is a @xmath1-cover for @xmath260 and @xmath255 is a @xmath1-cover for @xmath261 . we verify the first claim only . let @xmath81 and @xmath354 . we will show that if @xmath355 then @xmath356 , for all @xmath46 . this suffices to show that all elementary tensors in @xmath357 belong to @xmath358 and the conclusion then follows from ( * ? ? ? * lemma 1.87 ) . let @xmath337 be the approximate identity of @xmath260 ( lemma [ cai ] ) and let @xmath359 be the covariant homomorphism of @xmath218 into @xmath360 , appearing in ( * ? ? ? * proposition 2.34 ) . then @xmath361 on the other hand , @xmath362 however , @xmath363 , for all @xmath245 , and so @xmath364 . this implies that @xmath365 and the conclusion follows . the crossed product @xmath324 shares an important property which we describe in proposition [ raeburnthm ] below . but first we need a few definitions . a _ covariant representation _ of a dynamical system @xmath9 is a triple @xmath252 consisting of a hilbert space @xmath366 , a strongly continuous unitary representation @xmath367 and a non - degenerate , completely contractive representation @xmath52 satisfying @xmath368 if we insist that the dimension of @xmath366 is at most @xmath369 then the collection of all covariant representations forms a set . ( this is a crude requirement that can be refined further ; for instance if @xmath12 is separable and @xmath14 is countable we can simply ask for @xmath366 to be separable . ) nevertheless the direct sum of all covariant representations on a hilbert space of dimension at most @xmath370 forms a representation @xmath371 that we call the universal covariant representation for @xmath9 . a special class of covariant representations for @xmath9 arises from the left regular representation @xmath372 . if @xmath373 is a completely contractive representation of @xmath12 then on the hilbert space @xmath374 , we define @xmath375 with @xmath376 , @xmath245 , @xmath377 and @xmath378 a representation @xmath379 of the above form will be called a regular covariant representation for @xmath9 . our next result identifies a universal property of @xmath324 and lends support to our subsequent definition [ fulldefn ] . [ raeburnthm ] let @xmath9 be a dynamical system . then * there exists a completely isometric non - degenerate covariant homomorphism @xmath380 of @xmath9 into @xmath381 , * given a non - degenerate covariant representation @xmath252 of @xmath9 , there is a non - degenerate representation @xmath253 of @xmath324 such that @xmath382 and @xmath383 , and , * @xmath384 where @xmath385 let @xmath33 stand for @xmath13 . before embarking with the proof note that the presence of a contractive approximate identity for @xmath10 implies @xmath386 furthermore , the integral ( [ iintegral ] ) is understood as in proposition [ prop integral ] . for @xmath254 such a covariant representation @xmath359 of @xmath218 into @xmath387 exists by ( * ? ? ? * proposition 2.34 ) . we will show that the same pair @xmath359 restricted on @xmath12 works for @xmath388 as well . by ( * ? ? ? * proposition 2.34 ) , @xmath389 for all @xmath390 and @xmath81 . from this , it is immediate that @xmath359 maps @xmath9 into @xmath391 . furthermore , @xmath392 is non - degenerate because @xmath393 is approximate unital and @xmath394 is non - degenerate . hence ( i ) follows . corollary 2.36 in @xcite shows that @xmath395 , @xmath339 , @xmath158 . this implies ( iii ) . it only remains to verify ( ii ) . if @xmath396 is a non - degenerate covariant representation of @xmath9 , then there exists a non - degenerate @xmath39-representation @xmath31 of @xmath33 so that @xmath397 , where @xmath264 is the canonical inclusion . but then @xmath398 for all @xmath46 , and since @xmath33 is generated by @xmath12 , the pair @xmath399 is a covariant representation for @xmath218 . proposition 2.39 in @xcite implies now the existence of a representation @xmath400 , which satisfies the analogous properties of ( ii ) for @xmath254 . if we set @xmath401 , the conclusion follows . the previous proposition shows that any covariant representation @xmath402 for @xmath403 `` integrates '' in a very precise sense to a completely contractive representation @xmath404 of @xmath324 . indeed , @xmath404 is given by the familiar formula @xmath405 our next result shows that this class of representations exhausts all the completely contractive representations of @xmath324 . [ classifyrepns ] let @xmath403 be a dynamical system and let @xmath406 be a non - degenerate completely contractive representation . then there exists a non - degenerate covariant representation @xmath407 of @xmath403 so that @xmath408 . since @xmath324 is approximately unital , the representation @xmath25 is multiplier - nondegenerate , when viewing @xmath409 as the multiplier algebra of the compact operators ( remark [ multiplier nondeg ] ) . let @xmath410 be the canonical ( unital ) extension of @xmath25 by ( * ? ? ? * proposition 2.6.12 ) . we set @xmath411 where @xmath380 is the covariant representation of @xmath9 into @xmath381 appearing in proposition [ raeburnthm ] . now notice that @xmath412 is a covariant representation of @xmath403 . indeed , for every @xmath245 , @xmath413 is a contraction with inverse the contraction @xmath414 , hence a unitary . furthermore the map @xmath415 is strictly continuous as the composition of two such maps . finally @xmath29 is non - degenerate . indeed @xmath392 is non - degenerate so if @xmath336 is a contractive approximate unit for @xmath12 then @xmath416 is a contractive approximate unit for @xmath324 , i.e. , it converges strictly to @xmath417 . since @xmath418 is strictly continuous , we obtain that @xmath419 converges strictly ( and so strongly ) to @xmath101 . hence the non - degeneracy of @xmath29 . by proposition [ raeburnthm ] we obtain the representation @xmath420 that integrates @xmath421 and satisfies the conclusions of that result . if @xmath422 , then @xmath423{will } ) } \end{aligned}\ ] ] and the conclusion follows . we have gathered enough evidence for us now to justify the following definition . [ fulldefn ] if @xmath9 is a dynamical system then @xmath424 in the case where @xmath12 is a @xmath1-algebra , the algebra @xmath425 is nothing else but the full crossed product @xmath1-algebra of @xmath9 . in the general case of an operator algebra @xmath12 , one might be tempted to define @xmath10 as the relative crossed product @xmath325 , by virtue of the fact that @xmath274 is a more tractable ( perhaps more popular ) object than @xmath13 . even though in the case where @xmath12 is selfadjoint , @xmath325 also reduces to the usual full crossed product , in the non - selfadjoint case it is not clear at all that @xmath325 satisfies the universal properties that @xmath426 does . of course , any covariant representation of @xmath427 extends some covariant representation of @xmath9 . the problem is that the converse may not be true , i.e. , a covariant representation of @xmath9 does not necessarily extend to a covariant representation of @xmath427 , as it happens with @xmath13 . as it turns out , the identification @xmath428 is a major open problem in this monograph , which is resolved in the case where @xmath14 is amenable or when @xmath12 is dirichlet . to make the previous paragraph more precise , let us show now that the properties of @xmath10 , as identified in proposition [ raeburnthm ] , actually characterize the crossed product as the universal object for covariant representations of the dynamical system @xmath9 . in the case where @xmath12 is a @xmath1-algebra , this was done by raeburn in @xcite . below we prove it for arbitrary operator algebras , borrowing from the ideas of @xcite and ( * ? ? ? * theorem 2.61 ) . [ full raeb ] let @xmath9 be a dynamical system . assume that @xmath69 is an approximately unital operator algebra such that * there exists a completely isometric non - degenerate covariant representation @xmath429 of @xmath9 into @xmath430 , * given a non - degenerate covariant representation @xmath252 of @xmath9 , there is a completely contractive , non - degenerate representation @xmath431 such that @xmath432 and @xmath433 , and , * @xmath434 where @xmath435 then there exists a completely isometric isomorphism @xmath436 such that @xmath437 where @xmath380 is the covariant representation of @xmath9 appearing in proposition [ raeburnthm ] . we will show that the map @xmath438 where @xmath439 , @xmath440 , is a well - defined map , which is a complete isometry and therefore extends to the desired isomorphism @xmath436 . let @xmath441 be a completely isometric non - degenerate representation and let @xmath442 its canonical extension . let @xmath443 then for any @xmath46 and @xmath339 we have @xmath444 since @xmath25 is a complete isometry , the above shows that ( [ rhodefn ] ) is a well - defined map which is a complete contraction . by reversing the roles of @xmath10 and @xmath69 in the above arguments , we obtain that ( [ rhodefn ] ) is a complete isometry , as desired . it remains to verify ( [ twostooges ] ) . we indicate how to do this with the second identity and we leave the first for the reader . fix a @xmath445 and @xmath245 . an easy calculation using ( [ iintegral ] ) reveals that @xmath446 , where @xmath447 with @xmath448 , @xmath449 . a similar calculation shows that @xmath450 as well . hence for any @xmath46 we have @xmath451 since the linear span of elements of the form @xmath452 , @xmath46 , @xmath339 , is dense in @xmath10 and @xmath10 is essential as a left ideal of @xmath453 , we have @xmath454 , as promised . we need the following [ soelementary ] let @xmath12 be a unital operator algebra and let @xmath455 be a @xmath1-cover for @xmath12 . let @xmath456 be a completely isometric automorphism satisfying @xmath457 . if @xmath458 denotes the shilov ideal of @xmath12 , then @xmath459 . it is a result of hamana @xcite ( see ( * ? ? ? * theorem 5.9 ) for a modern " proof ) that if @xmath47 is any ideal so that the natural quotient map @xmath460 is completely isometric on @xmath49 , then @xmath461 . since @xmath462 clearly satisfies this property , we have @xmath463 . similarly , @xmath464 and so @xmath465 as desired . our next result is a key step in the proof of theorem [ r = f ] . in the proof , we make an essential use of the theory of maximal dilations of dritschel and mccullough @xcite . the reader familiar with the earlier work of kakariadis and katsoulis will recognize the influence of ( * ? ? ? * proposition 2.3 ) in the proof below . [ cis ] let @xmath9 be a unital dynamical system and let @xmath32 be an @xmath18-admissible @xmath1-cover for @xmath12 . if @xmath458 denotes the shilov ideal of @xmath12 , then @xmath466 via a complete isometry that maps generators to generators . notice that by its maximality , the shilov ideal @xmath467 is left invariant by the automorphisms @xmath246 , @xmath245 . therefore we have a continuous representation @xmath468 and the crossed product @xmath469 is meaningful . the statement of the lemma asserts that the association @xmath470 where @xmath471 , @xmath472 , is a well - defined map that extends to a complete isometry . ( note that the map @xmath473 is a well - defined complete isometry . ) let @xmath29 be a faithful representation of @xmath33 on a hilbert space @xmath366 and let @xmath474 be the associated regular covariant representation of @xmath218 . consider the completely isometric map @xmath475 according to the dritschel and mccullough result ( * ? ? ? * theorem 1.2 ) , there is a maximal dilation @xmath476 of @xmath25 which extends uniquely to a representation of @xmath477 such that @xmath478 for all @xmath479 . since @xmath480 , we have that @xmath481 for all @xmath46 . also , @xmath482 , @xmath245 , and so @xmath483 the same is also true for all the matrix norms . since the covariant representation @xmath484 norms @xmath198 , the map in ( [ contraction2 ] ) is well defined and completely contractive . by reversing the roles between @xmath12 and @xmath485 in the previous arguments , we can also prove that ( [ contraction2 ] ) is actually an isometry , and the conclusion follows . the previous lemma applies only to unital dynamical systems . in order to take advantage of it in the general case , we require the following . [ transfer ] let @xmath9 be a dynamical system and assume that @xmath12 does not have a unit . let @xmath32 be an @xmath18-admissible @xmath1-cover for @xmath12 . then the operator algebras generated by @xmath486 and @xmath487 are isomorphic to @xmath488 and @xmath489 respectively via complete isometries that map generators to generators . we address first the case of the full crossed product . since any covariant representation @xmath490 of @xmath218 extends to a covariant representation of @xmath491 , we have from ( * ? ? ? * lemma 2.27 ) that the map @xmath492 is an isometry that extends to a @xmath39-injection of @xmath254 into @xmath493 that maps generators to generators . in particular , this injection maps @xmath488 onto the subalgebra generated by @xmath494 . the case of the reduced crossed product follows from the fact that if @xmath495 is a faithful @xmath39-representation , then @xmath496 where @xmath497 is the unitization of @xmath29 . the following is one of the main results of this chapter and generalizes a classical result from the theory of crossed product @xmath1-algebras to the theory of arbitrary operator algebras . it shows that in the case of an amenable group @xmath14 , the crossed product is a unique object . in particular , it allows us to identify @xmath324 with @xmath325 in a canonical way . [ r = f ] let @xmath9 be a dynamical system with @xmath14 amenable and let @xmath32 be an @xmath18-admissible @xmath1-cover for @xmath12 . then @xmath498 via a complete isometry that maps generators to generators . we begin with the case where @xmath9 is a unital dynamical system . with the understanding that the symbol @xmath499 stands for a complete isometry that sends generators to generators we have @xmath500 because @xmath14 is amenable . on the other hand @xmath501 however both @xmath1-covers @xmath502 and @xmath503 give @xmath504 and so lemma [ delicate ] implies @xmath505 , as desired . in the general case notice that from the above we have @xmath506 via complete isometries that maps generators to generators . in particular these isometries map surjectively the operator algebras generated by @xmath507 inside the crossed products appearing above . the conclusion follows now from lemma [ transfer ] . of course , theorem [ r = f ] does much more than just provide an isomorphism between relative ( full ) crossed products . it also allows us to utilize regular covariant representations for @xmath508 in order to norm the crossed product . indeed [ norming ] let @xmath9 be a dynamical system and assume that @xmath14 is amenable . if @xmath509 is a faithful non - degenerate @xmath39-representation of @xmath504 then @xmath510 is a completely isometric representation of @xmath511 . since @xmath14 is amenable , @xmath510 is a faithful representation of @xmath512 , where @xmath18 is the unique extension of @xmath513 . by the previous results @xmath514 and the conclusion follows part of the proof of theorem [ r = f ] establishes the fact that all relative reduced crossed products coincide with each other , even for non - amenable @xmath14 . stated formally [ allrcoincide ] let @xmath9 be a dynamical system , with @xmath14 an arbitrary locally compact group , and let @xmath32 be an @xmath18-admissible @xmath1-cover for @xmath12 . then , @xmath515 via complete isometries that map generators to generators . if @xmath12 is unital than the result follows from lemma [ cis ] as in the proof of theorem [ r = f ] . if @xmath12 is non - unital , then @xmath516 via complete isometries that map generators to generators . these isometries map surjectively the operator algebras generated by @xmath507 inside the reduced crossed products appearing above . the conclusion follows again from lemma [ transfer ] . in light of corollary [ allrcoincide ] we give the following definition . [ reddefn ] if @xmath9 is a dynamical system then the reduced crossed product of @xmath326 is the operator algebra @xmath517 \(i ) since @xmath518 , it follows that any regular covariant representation of @xmath9 integrates to a continuous representation of @xmath519 . one can actually view @xmath11 as the universal object for the regular covariant representations of @xmath9 . \(ii ) if @xmath9 is a @xmath1-dynamical system then it is well known that any regular covariant representation @xmath520 integrates to a faithful representation of @xmath11 , provided that @xmath29 is faithful . this remains true for arbitrary dynamical systems under the additional requirement that @xmath29 is a maximal , completely isometric map for @xmath12 . ( note that for a @xmath1-algebra @xmath12 , any faithful @xmath39-representation is automatically maximal and completely isometric . ) we will now use the theory we have developed so far to obtain von neumann type inequalities , where the role of the disc algebra is being played now by the crossed product @xmath511 . first we obtain a covariant version of a theorem of naimark and sz .- nagy that applies to arbitrary operator algebras . let @xmath14 be a group and let @xmath521 . we say that @xmath25 is _ completely positive definite _ if for every finite set of elements @xmath522 of @xmath14 , the operator matrix @xmath523 is positive ; if @xmath524 then @xmath25 is said to be _ unital_. note that for a completely positive definite map @xmath521 , the matrix @xmath525 , @xmath245 , is automatically positive and so @xmath526 we need the following [ elementary ] let @xmath527 , @xmath528 , be commuting operators . then @xmath529 for any @xmath530 . note that , @xmath531 as desired in the case where @xmath12 is a @xmath1-algebra , the following result was established by mcasey and muhly in ( * ? ? ? * proposition 4.2 ) . in the generality appearing below , the result is new and its proof requires new arguments . [ naimark ] let @xmath12 be a unital operator algebra , let @xmath14 be a group and let @xmath9 be a dynamical system . let @xmath521 be a unital , strongly continuous and completely positive definite map and let @xmath532 be a unital completely contractive map satisfying @xmath533 then there exists a hilbert space @xmath534 , a strongly continuous unitary representation @xmath535 and a completely contractive map @xmath536 so that @xmath537 and @xmath538 where @xmath539 is the orthogonal projection on @xmath366 . furthermore , @xmath366 reduces @xmath540 . in the case where @xmath31 is multiplicative , @xmath541 is multiplicative as well . since @xmath14 acts completely isometrically on @xmath12 , this action extends to @xmath504 . similarly , since @xmath31 is unital , it extends to a completely positive map on @xmath504 . we reserve the same symbols for these extensions . note that these extensions do not satisfy ( [ covariance ] ) , but their restrictions on the operator system @xmath542 do . indeed , in ( [ covariance ] ) replace @xmath247 with @xmath543 , @xmath544 with @xmath545 and use ( [ naimarktrivial ] ) to obtain @xmath546 and by taking adjoints @xmath547 as desired . for the rest of the proof we concentrate on that system . we start by adopting the ideas of ( * ? ? ? * theorem 4.8 ) in our context . consider the vector space @xmath548 of finitely supported functions from @xmath14 to @xmath366 and define a bilinear function on this space by @xmath549 as in the proof of ( * ? ? ? * theorem 4.8 ) , we observe that @xmath550 and that the set @xmath551 is a subspace of @xmath548 . we let @xmath552 be the completion of @xmath553 with respect to the induced inner product and we identify @xmath366 as a subspace of @xmath552 , via the isometry @xmath554 that satisfies @xmath555 . let @xmath535 be left translation , i.e. , @xmath556 it is easy to see that @xmath557 is a unitary representation and @xmath558 . since @xmath554 is an isometry , we simply write @xmath559 . defining @xmath541 and verifying its properties requires more care . if @xmath560 then we define @xmath561 we need to verify that @xmath541 is well defined . assume that @xmath562 , i.e. , @xmath563 where @xmath564 now if @xmath565 then the covariance condition ( [ covariance ] ) implies that @xmath566 and @xmath567 commute . hence @xmath568 as desired . we now verify that @xmath541 is completely contractive ; this will require an application of schwarz s inequality . let @xmath569 be a contraction and we are to verify that @xmath570 is also a contraction . start by noticing that if @xmath571 , @xmath572_{ij } & 0 & \dots & 0\\ 0 & \big[\rho\big(\alpha_{s_2}^{-1}(a_{ij } ) \big ) \big]_{ij } & \dots & 0\\ \vdots & \vdots & \ddots & \vdots \\ 0 & 0 & \dots & \big[\rho\big(\alpha_{s_m}^{-1}(a_{ij } ) \big ) \big]_{ij}\\ \end{array } \right)\ ] ] is in @xmath573 and @xmath574_{kl } \in m_{mr}(b({{\mathcal{h}}}))$ ] , then ( [ covariance ] ) implies that @xmath575 and @xmath566 commute . furthermore , since @xmath576 is completely contractive , an application of schwarz s inequality implies @xmath577_{ij}^ * \big[\rho\big(\alpha_{s_l}^{-1}(a_{ij})\big ) \big]_{ij } & \leq ( \rho \circ \alpha_{s_l}^{-1 } ) ^{(r)}\left(\big[(a_{ij } ) \big]_{ij}^*\big[(a_{ij } ) \big]_{ij}\right ) \\ & \leq ( \rho \circ \alpha_{s_l}^{-1 } ) ^{(r)}(i_r ) = i_r\end{aligned}\ ] ] and so @xmath578 , i.e. , a is a contraction . now let @xmath579 with @xmath580 . we calculate @xmath581_{ij}h , h \big > & = \sum_{i , j = 1}^{r}\big < \hat{\rho}(a_{ij})(h_j + { { \mathcal{n } } } ) , ( h_i + { { \mathcal{n}}})\big>\\ & = \sum_{i , j=1}^{r}\sum_{k , l=1}^{m}\big < \rho\big(\alpha_{s_k}^{-1}(a_{ij})\big){\varphi}\big(s_k^{-1}s_l\big)h_{jl},h_{ik}\big>\\ & = \big < abx , x\big>,\end{aligned}\ ] ] where @xmath582 with @xmath583 , @xmath584 . an application of lemma [ elementary ] shows now that @xmath585_{ij}h , h \big > \big|&= |\left < ab x , x \right > | \leq \|a\| \left < bx , x \right > \\ & \leq \left < bx , x \right > = \left < h , h \right > \end{aligned}\ ] ] and so @xmath570 is a contraction , as desired . hence @xmath541 is completely contractive ( and so completely positive ) . it remains to verify that @xmath586 reduces @xmath366 ; here lies the reason why we extended the original dynamical system on @xmath587 . it is clear that @xmath588 leaves @xmath366 invariant and since @xmath541 is completely positive , @xmath366 reduces @xmath588 . ( if we had chosen to define @xmath541 only on @xmath12 , then we would only have that @xmath589 leaves @xmath366 invariant . ) note that in the proof of the above theorem , the only reason why we ask for @xmath12 to be unital is to guarantee that the unital completely contractive map @xmath31 extends to a completely positive map on @xmath504 . if @xmath31 is assumed to be multiplicative , such an extension exists without that requirement , because of meyer s result ( * ? ? ? * corollary 3.3 ) . this is implicitly used below in obtaining the promised von neumann inequality . [ vonneumann ] let @xmath9 be a unital dynamical system and assume that @xmath14 is a locally compact amenable group . let @xmath521 be a unital , strongly continuous and completely positive definite map and let @xmath532 be a completely contractive representation satisfying @xmath590 then , for any @xmath422 , we have @xmath591 where @xmath592 is a faithful @xmath39-representation and @xmath474 the associated regular covariant representation of @xmath427 . by theorem [ naimark ] , there exists a hilbert space @xmath593 and a covariant representation representation @xmath594 of @xmath9 , whose compression on @xmath366 gives @xmath595 . hence @xmath596 on the other hand , the representation @xmath594 extends to a covariant representation of the dynamical system @xmath597 . ( see the last paragraph of the proof of proposition [ raeburnthm ] ) . hence , @xmath598 theorem [ r = f ] shows however that on @xmath507 all relative crossed product norms coincide . in particular @xmath599 and the conclusion follows . \(i ) corollary [ vonneumann ] achieves its most pleasing form in the case where @xmath14 is discrete , as in that case ( [ cntnsvonneum ] ) becomes an inequality involving finite sums instead of integrals , i.e. , @xmath600 where @xmath601 and @xmath247 ranges over a finite subset of @xmath14 . \(ii ) we have defined @xmath602 to be a covariant representation of @xmath326 provided that @xmath603 this is of course equivalent to @xmath604 it is important to note that there we have no analogue of theorem [ naimark ] nor corollary [ vonneumann ] for the second set of covariance relations . the reader that has followed us this far should recognize now why we choose to define the crossed product @xmath511 as a universal object with regards to _ arbitrary _ representations of @xmath12 ( definition [ fulldefn ] ) . it is true that had we chosen to work only with the relative crossed product @xmath605 , we would not need to work so hard with the various relative crossed products , including @xmath324 . however , since the allowable " representations of @xmath12 would have been only the @xmath504-extendable ones , the von neumann inequality of corollary [ vonneumann ] would have been unattainable . this added flexibility in our definition for @xmath511 is truly invaluable . corollary [ vonneumann ] also raises the question whether @xmath606 is the best choice " in our von neumann inequality . in other words , we wonder what is the @xmath1-envelope of @xmath511 and @xmath519 . clearly , lemma [ cis ] implies that @xmath607 is a quotient of @xmath608 but beyond that , we do nt know too much . this is going to be a recurrent theme in this monograph . it turns out that even in special cases , the problem of identifying the @xmath1-envelope of the crossed product is intimately related to problems in @xmath1-algebra theory which are currently open , such as the hao - ng isomorphism problem . we will have to say more about that later in this monograph . for the moment , we deal with the case where @xmath14 is an abelian group and @xmath12 is a unital operator algebra . the case where @xmath14 is discrete follows easily from the work we have done so far and from the ideas of either @xcite in the @xmath609 case or more directly from ( * ? ? ? * theorem 3.3 ) , by choosing @xmath610 , @xmath611 and transposing the covariance relations . in the generality appearing below , the result is new and paves the way for exploring non - selfadjoint versions of takai duality . [ abelianenv ] let @xmath9 be a unital dynamical system . if @xmath14 is an abelian locally compact group , then @xmath612 let @xmath33 denote the @xmath1-envelope of @xmath12 . let @xmath613 , @xmath85 , be the common contractive approximate identity of @xmath10 and @xmath254 , as in lemma [ cai ] . the presence of a common approximate identity implies that @xmath10 contains a unit if and only if @xmath254 does ( * ? ? ? * lemma 2.1.7 ) . we will deal only with the case where @xmath10 is non - unital and leave the other case for the reader . let @xmath614 and @xmath615 be the unitizations of @xmath254 and @xmath10 respectively resulting from adjoining a unit to @xmath254 . we claim that @xmath616 by way of contradiction assume that @xmath617 is the shilov ideal for @xmath615 . since both @xmath618 and @xmath10 are invariant by the dual action @xmath619 , the ideal @xmath620 is also @xmath619-invariant . by ( * lemma 3.6 ) @xmath620 is also non - trivial . hence , ( * ? ? ? * corollary 2.2 ) ( or ( * ? ? ? * corollary 3.4 ( i ) ) for non - separable systems ) implies the existence of an @xmath18-invariant ideal @xmath47 so that @xmath621 now note that @xmath622 and furthermore , @xmath623 if @xmath624 , @xmath625 , stands for the left multiplication operator , then for arbitrary @xmath46 , @xmath626 we have @xmath627 where @xmath337 is the contractive approximate unit of @xmath10 appearing in lemma [ cai ] . a matricial variation of the above argument shows that @xmath628 for arbitrary @xmath629 and @xmath630 . therefore it follows that @xmath47 is a boundary ideal for @xmath12 . since @xmath631 , we obtain @xmath632 . but this implies that @xmath633 , a contradiction that establishes ( [ contrenv ] ) . now the @xmath1-algebra generated by @xmath10 inside @xmath614 equals @xmath254 and the conclusion follows . certainly the extension of ( * ? ? ? * corollary 2.2 ) to non - separable systems does not require the heavy machinery of coactions , as it happens in ( * ? ? ? * corollary 3.4 ( i ) ) . nevertheless we have not able to locate an appropriate reference in the literature that does not involve coactions . a standard reference , even for the case of a non - separable system , seems to be ( * ? ? ? * theorem 3.4 ) . however that result too involves the use of coactions . furthermore , even though the proof of ( * ? ? ? * theorem 3.4 ) works for arbitrary dynamical systems , the authors of ( * ? ? ? * theorem 3.4 ) make the blanket assumption that all @xmath1-dynamical systems appearing in their monograph are separable . in chapter [ hao ] we will use the above theorem in order to give a proof of the hao - ng theorem @xcite for locally compact abelian groups . even though most of the non - selfadjoint operator algebras currently under investigation are actually unital , we have gone to great lengths to build a theory of crossed products that encompasses non - unital algebras as well . there is a good reason for that and this becomes apparent in this chapter . both the context of an iterated crossed product and the non - selfadjoint takai duality presented here would be meaningless had we not incorporated non - unital algebras in our theory . let @xmath441 be a completely contractive ( perhaps degenerate ) representation . since @xmath634 is approximately unital , the subspace @xmath635 $ ] reduces @xmath634 . therefore , by restricting on @xmath635 $ ] , we may assume that @xmath25 is actually non - degenerate . ( see ( * ? ? ? * lemma 2.1.9 ) for more details . ) we claim that @xmath637 is a covariant representation of @xmath638 . by taking adjoints in the covariance equation @xmath639 and then setting @xmath640 , we obtain @xmath641 , i.e. , @xmath642 and the conclusion follows . furthermore the @xmath1-representation @xmath643 extends @xmath644 . let @xmath12 be an operator algebra . let @xmath647 be locally compact groups and consider continuous actions @xmath648 and @xmath649 . the iterated crossed product @xmath650 can be described as follows . by lemma [ delicate ] both @xmath305 and @xmath651 extend to actions @xmath652 and @xmath653 respectively , denoted by the same symbols for convenience . now , theorem [ cmaxthm ] shows that @xmath654 where @xmath655 is the canonical map arising from the inclusion " @xmath656 . therefore we may identify @xmath650 with the norm closed subalgebra of @xmath657 generated by @xmath658 . [ doesntmatter ] let @xmath12 be a unital operator algebra . let @xmath647 be locally compact abelian groups and consider continuous actions @xmath648 and @xmath649 . then the iterated crossed product @xmath650 is canonically and completely isometrically isomorphic with the norm closed subalgebra of @xmath660 generated by @xmath661 . by theorem [ r = f ] , we have @xmath662 however , theorem [ abelianenv ] shows that @xmath663 where @xmath664 is the canonical map arising from the inclusion " @xmath665 . this implies the desired identification . before embarking with the takai duality , we need a technical result . let @xmath33 be a @xmath1-algebra , @xmath666 locally compact groups and @xmath667 , @xmath668 continuous actions . then we can view @xmath669 as a dense subspace of the iterated crossed product @xmath670 by associating to a kernel " @xmath671 , the function @xmath672 defined by @xmath673 assuming a compatibility condition for @xmath651 , one can show ( see @xcite ) that actually the subspace @xmath674forms a @xmath39-subalgebra of the iterated crossed product . the compatibility condition requires that @xmath675 is invariant for @xmath651 , and that @xmath676 is continuous with compact support in @xmath677 and @xmath678 . ( for instance , if @xmath679 , for all @xmath680 , then ( [ compatible ] ) is satisfied . ) actually one can show that for functions @xmath681 , @xmath37 , we have @xmath682 how does this transfer to non - selfadjoint algebras ? assume now that the systems @xmath683 and @xmath684 are as in the beginning of this chapter and let @xmath685 . assume further that the compatibility condition is satisfied by @xmath651 , regarding both its action on @xmath675 and on @xmath686 . is invariant for @xmath651 . ] indeed , ( [ product formula ] ) shows that the set in ( [ takai subalg ] ) is a subalgebra of @xmath650 . the density follows from the fact that kernels of the form @xmath688 give @xmath689 and such elements form a total subset of @xmath650 . a particular case of an iterated crossed product comes from the dual action of a locally compact abelian group @xmath14 on the crossed product @xmath10 . here we have a dynamical system @xmath9 , with @xmath14 abelian , and we let @xmath690 , @xmath691 , @xmath692 and @xmath693 . the dual action @xmath619 is defined on @xmath507 by @xmath694 , @xmath422 , @xmath695 . ( by theorem [ r = f ] , it does not matter whether we consider @xmath507 as a subalgebra of @xmath10 or any other relative crossed product . ) let @xmath696 be the right - regular representation of @xmath14 and consider the dynamical system @xmath697 where @xmath698 , @xmath245 . then for the dynamical system @xmath699 , we can form the tensor product dynamical system @xmath700 . [ takai duality ] let @xmath9 be a dynamical system with @xmath14 a locally compact abelian group . then @xmath701 where @xmath702 denotes the compact operators on @xmath703 and @xmath704 is the subalgebra of @xmath705 generated by the appropriate elementary tensors . the proof follows verbatim the plan laid down by williams in ( * ? ? ? * theorem 7.1 ) . what we need to do here is to keep track of where our non - selfadjoint operator algebra is mapped under the various maps appearing in williams proof . ( for the record , williams attributes his proof to raeburn @xcite , with an extra contribution by s. echterhoff . ) let @xmath709 . in ( * lemma 7.2 ) , it is shown that there exists an isomorphism @xmath710 here @xmath711 and the action @xmath712 of @xmath14 ( which also satisfies the compatibility condition ) is given by @xmath713 where @xmath714 , @xmath715 and @xmath695 . actually , @xmath716 is constructed so that on kernels @xmath717 it acts as @xmath718 in the sense that @xmath719 . therefore @xmath716 maps the linear space @xmath720 onto the linear space @xmath721 recall that both @xmath619 and @xmath722 satisfy the compatibility condition and so two applications of lemma [ dense takai ] show that the algebras appearing on the left side of ( [ domain ] ) and ( [ range ] ) are dense in the algebras appearing in the right sides of these relations . hence we have a completely isometric surjection @xmath723

we study crossed products of arbitrary operator algebras by locally compact groups of completely isometric automorphisms . we develop an abstract theory that allows for generalizations of many of the fundamental results from the selfadjoint theory to our context . we complement our generic results with the detailed study of many important special cases . in particular we study crossed products of tensor algebras , triangular af algebras and various associated c@xmath0-algebras . we make contributions to the study of c@xmath0-envelopes , semisimplicity , the semi - dirichlet property , takai duality and the hao - ng isomorphism problem . we also answer questions from the pertinent literature .

accelerating expansion of the universe has been shown from the type ia supernova ( snia ) observations @xcite , cosmic microwave background ( cmb ) anisotropy measurement from wilkinson microwave anisotropy probe ( wmap ) @xcite , and large scale structure from the sloan digital sky survey @xcite . in order to explain this mechanism , theorists introduce an exotic energy component with negative pressure , which is called as dark energy . based on this opinion , a lot of dark energy models have been proposed . one kind of popular model is the unified dark fluid , these models have been put forward and further studied in refs . @xcite . in principle , the equation of state ( eos ) can be determined up to an integration constant by the adiabatic sound speed . the model of zero adiabatic sound speed @xmath10 has been studied in ref . @xcite ; the case of time variable @xmath10 was discussed in ref . @xcite ; the model of constant adiabatic sound speed ( cass)-that is,@xmath11-has been studied in refs . @xcite . in ref . @xcite , xu et al . took the cass model as a whole dark fluid , and found that small values of @xmath4 are favored by using the markov chain monte carlo ( mcmc ) method with snia union 2 @xcite , baryon acoustic oscillation ( bao ) @xcite , and the full cmb information from seven - year wmap data sets @xcite . recently , it has been shown that any unified dark fluid model can be decomposed into pressureless dark matter interacting with a vacuum energy @xcite . following these papers , we want to study the decomposed cass model described by cold dark matter interacting with a vacuum energy . thus , we call the model as idcass ( interacting decomposed dark fluid model with constant adiabatic sound speed ) . the interacting dark energy model can introduce some new features to the structure formation , as one can see in refs . @xcite . in order to explore the possibility of interacting dark energy , it is necessary to consider the effect of the interaction on the structure formation . as for the observational aspect , to break the possible degeneracy of cosmological models , the geometry information ( snia , bao , cmb ) is not enough because the different models may undergo similar background evolution behavior , but the dynamical growth history could be different . therefore , the large scale structure information is a powerful tool to discriminate the dark energy models . via the redshift - space distortion ( rsd ) , the measurement of the growth rate @xmath12 is closely related to the evolutionary speed of matter density contrast @xmath2 , where @xmath13 . it is worth to notice that the growth rate @xmath12 has been used to constrain the dark energy model and to test the growth index in refs . however , considering the cosmological constant and cold dark matter ( @xmath14cdm ) model , the observational values of the growth rate @xmath15 are derived from the redshift - space distortion parameter @xmath16 and the linear bias @xmath17 . it means that the current @xmath18 data is model - dependent and not suitable to constrain the other models . to avoid this issue , @xmath0 will provide a good test of dark energy models ( @xmath1 is the root - mean - square mass fluctuation in spheres with radius @xmath3 mpc ) . the model - independent measurement @xmath0 is firstly proposed to constrain the dark energy models in ref . @xcite . then , in ref . @xcite , xu combined the geometry test with @xmath0 data to constrain the holographic dark energy model and obtained a tight constraint of holographic parameter @xmath19 . furthermore , after _ planck _ , xu parameterized the growth function as @xmath20 and compared the deviation of the growth index @xmath21 in the einstein s gravity theory and modified gravity theory in ref . @xcite . the observational data points of @xmath0 were provided by the 2dfgrs @xcite , wigglez @xcite , sdss lrg @xcite , boss @xcite , 6dfgrs @xcite , and vipers @xcite . the former nine data points were summarized in table 1 of ref . the data point at @xmath22 was recently released by vipers in ref . @xcite . a lower growth rate from rsd than expected from _ planck _ was also pointed out in ref . @xcite . in this paper , the ten data points are shown in table [ tab : fsigma8data ] . .the data points of @xmath0 measured from rsd with the survey references . [ cols="^,^,^",options="header " , ] the unified dark fluid with constant adiabatic sound speed was decomposed into dark matter interacting with vacuum energy . in the synchronous gauge , we introduced an energy flow that was parallel to the four - velocity of the dark matter and obtained the evolution equations of growth rate for the dark matter and baryon . then , we showed the effects on the cmb temperature and matter power spectra for the varied model parameter @xmath4 . when @xmath4 was mean value or zero , from the power spectra , it was difficult to distinguish the idcass model from the @xmath14cdm model . however , due to using the @xmath0 data set of large scale structure information , the evolutionary curves of @xmath0 could break the degeneracy of the models . then , based on the mcmc method , a global fitting was performed on the decomposed model by adopting the cmb information from _ planck _ , bao , snia , and rsd data sets . we obtained a tight constraint for the cosmological parameters . the results for three different cases were shown in table [ tab : total - mean - table ] . obviously , the constraint with rsd data set is tighter than that without rsd data set , which means that the @xmath0 data is very important to the cosmological constraint . with the data set of @xmath0 , the cosmic observational data sets all favor a small interaction which is up to the order of @xmath23 . it means that the idcass model and @xmath14cdm model undergo the similar background evolution behavior . fortunately , the large scale structure information is a powerful tool to discriminate the dark energy models because the dynamical evolution would be different even if they had the same background evolution . in future work , we will continue to study some other dark fluid , such as the generalized chaplygin gas and modified chaplygin gas model , by using the @xmath0 data set . moreover , if the entropy perturbation is considered , a negative adiabatic sound speed is favored , which is different from that of the pure adiabatic case . for the cosmic observations , we hope that some other data points of the growth rate can be found and released which could bring larger improvement into cosmological constraints . a. g. riess _ et al . _ , j. * 116 * , 1009 ( 1998 ) . s. perlmutter _ et al . _ , j. * 517 * , 565 ( 1999 ) . d.n . spergel _ et al . _ , * 148 * , 175 ( 2003 ) . m. tegmark _ et al . _ , j. * 606 * , 702 ( 2004 ) . m. kunz , phys . d * 80 * , 123001 ( 2009 ) ; 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in this paper , a unified dark fluid with constant adiabatic sound speed is decomposed into cold dark matter interacting with vacuum energy . based on markov chain monte carlo method , we constrain this model by jointing the geometry and dynamical measurement . the geometry test includes cosmic microwave background radiation from _ planck _ , baryon acoustic oscillation , and type ia supernovae ; the dynamic measurement is @xmath0 data points which is obtained from the growth rate via redshift - space distortion , and @xmath1 is the root - mean - square amplitude of the density contrast @xmath2 at the comoving @xmath3 mpc scale . the jointed constraint shows that @xmath4 = @xmath5 and @xmath6 = @xmath7 . the cmb and matter power spectra are both similar for the case of @xmath8 mean value and that of @xmath9 . however , the evolutionary curves of @xmath0 are different . this means that , to some extent , the data points of the growth rate could break the degeneracy of the dark energy models .

dipolar bosonic systems are of increasing interest for recent experiments studying the onset of superfluidity in nonideal bose systems and its connection with correlation and quantum degeneracy effects . examples include dipolar gases , as in recent studies of ultra - cold dipolar gases , @xcite indirect excitons in coupled quantum wells @xcite in external electric fields or exciton - polaritons in quantum wells embedded in optical micro - cavities . @xcite due to significant experimental achievements , a superfluid regime of polar molecules is expected to be observed in the near future . @xcite there is also an increasing activity on alkali atom gases where the long - long range dipolar interactions can be generated by excitations to high energy atomic rydberg states ( one electron is excited to a very high principal quantum number ) . the applied moderate electric field can result in a large polarizability and dipole moment . @xcite all these achievements have a direct impact on understanding the properties of bose - condensates dominated by long - range correlation effects . from the theoretical side , the static properties of dipolar bosons have been quite extensively analyzed in recent years . strongly correlated phases of dipolar bosons confined in a harmonic potential have been studied from first principle simulations by lozovik _ et al . _ , @xcite nho _ et al . _ , @xcite pupillo _ et al . , _ @xcite golomedov _ et al . _ @xcite and jain _ et al . _ @xcite 2d homogeneous systems have been analyzed by astrakharchik _ et al . _ @xcite and bchler _ et al . _ @xcite with the prediction that above a critical density a superfluid dipolar gas undergoes a crystallization transition . properties of a dipole solid have been addressed by kurbakov _ et al . _ @xcite the presence of a finite fraction of vacancies and interstitials , in incommensurate crystal , leads to a superfluid response and quasi - equilibrium supersolid phase . in pimc simulations by filinov _ et al . _ @xcite the density - dependence of the transition temperature from a superfluid to a normal gas phase has been analyzed . the composite dipolar bosons , such as indirect excitons ( pairs of electrons and holes spatially separated in semiconductor bilayers ) have been recently studied by bning _ et al . _ @xcite with focus on the effective exciton - exciton interaction and its consequence for the complete phase diagram of excitonic system . relevant experimental parameters to observe exciton crystallization , in a semiconductor quantum well , have been predicted . all these results provides a reliable estimate of the critical temperature and degeneracy parameters required to observe a combined effect of inter - particle correlations and bose statistics in experiment . on the other side , theoretical predictions for dynamic properties , in particular excitation spectra of density fluctuations , are more challenging if performed on a microscopic level . for 3d dipolar superfluids at low densities the rotonization of the excitation spectrum has been predicted from mean - field analyses . @xcite a cigar - shaped trap is a promising candidate for observation of a roton minimum , where the dipole - dipole interaction is anisotropic , and partially attractive . in a quasi 2d trap ( a pancake geometry ) , a roton has a different physical nature and is due to a strong in - plane repulsion of similar oriented dipoles . this regime assumes a high density and goes beyond the mean - field predictions . this calls for a more accurate treatment . the correlated basis functions theory ( cbf ) , originally developed for strongly correlated systems like @xmath2he , has been renewed recently by mazzanti _ et al . _ @xcite to analyze in detail the phonon - roton dispersion of an infinite 2d dipolar gas at @xmath3 . the density range has been identified , where the cbf dispersion ( which includes three - phonon interactions ) deviates from the bijl - feynman @xcite and bogolubov predictions . the upper bound for the phonon - maxon - roton dispersion , derived from the frequency - sum rules , @xcite is mainly in a good agreement . @xcite important extension of the cbf theory to 3d geometry and full anisotropy of the dipole - dipole interaction has been performed by hufnagl _ et al . _ @xcite this study builds an important bridge between the nature of two kinds of rotons caused either by attractive or repulsive tail of the dipole interaction . still the current analyses of the excitation spectrum lack the important regime of finite temperatures ( including @xmath4 ) and treat excitation damping in an approximate way . @xcite with the present analysis we aim to fill this gap and , in addition , discuss the nature of excitations in bose - condensed systems and the role played by a condensate . we start the discussion about the nature of excitations from the model developed for a one - component neutral bec . the properties of the density fluctuation spectrum have been discussed extensively in relation with superfluid liquid @xmath2he . in particular , the temperature ( @xmath5 ) dependence of @xmath0 from inelastic - neutron scattering experiments was compared vs. glide - griffin ( gg ) model based on the dielectric function formalism . @xcite the relation with the dynamic structure factor is written as @xmath6\label{sq},\\ & \chi(q,\omega)=\frac{\tilde\chi(q,\omega)}{1-v(q)\tilde\chi(q,\omega)},\label{chi}\\ & \tilde\chi(q,\omega)=\lambda(q,\omega ) g_1(q,\omega)\lambda(q,\omega)+\tilde\chi_{\rho}(q,\omega)\label{tchi}\end{aligned}\ ] ] where @xmath7 is the irreducible part of dynamic susceptibility @xmath8 , separated into a singular condensate part ( related to single - particle excitations ) and a regular thermal ( multiparticle ) component , present also above @xmath9 . the coupling to the sp spectrum is described by the vertex function @xmath10 and the single - particle green function @xmath11 . the first term in ( [ tchi ] ) vanishes in the normal phase ( @xmath12 ) , with the result @xmath13 , with @xmath14 being the density response of weakly interacting particle - hole excitations , e.g. treated via a lindhard function . the excitation spectrum described by @xmath15 is expected to include for _ small @xmath16 _ a zero sound and acoustic phonons , for _ intermediate @xmath16 _ a maxon - roton branch , and for _ large @xmath16 _ a combination of sharp sp resonances and a broad distribution close to the recoil energy @xmath17 due to the multiple scattering of weakly interacting particle - hole excitations . to fit the experimental observations for @xmath2he by eqs.([sq])-([tchi ] ) , i.e. a _ single phonon - maxon _ dispersion , one suggests that the imaginary parts of @xmath8 and @xmath11 share a common denominator due to the vertex @xmath18 . @xcite as a result the sp and collective excitations can not be distinguished in @xmath0 in the superfluid phase . for @xmath12 the sp spectrum decouples and only the thermal part remains ( @xmath19 ) . the dispersion gets broadened and remains well defined only in the phonon ( low-@xmath16 ) part of the spectrum . in its simple form the dielectric function model failed to predict the double roton feature observed in @xmath2he . therefore , it was necessary to include the mechanism of the quasiparticle - decay processes . this has lead to development of theories beyond the roton minimum . @xcite in his pioneer work , pitaevskii @xcite considered a semi - emperical ansatz for a single - particle green s function @xmath20 which includes the unhybridized feynman - cohen phonon - maxon - roton branch , @xcite @xmath21 , and the self energy , @xmath22 , expressed in terms of the two-(quasi)particle response function @xmath23 and the three - point interaction vertex @xmath24 . the self energy accounts for the typical repulsion by anticrossing of two modes , i.e. the interaction between a single and a pair of quasiparticle excitations . as a result the sp dispersion , beyond the roton , is renormalized and bends to the energy of two roton minimum . this concept has been further successfully developed @xcite by improving both @xmath25 and @xmath26 . in particular , zawadowski et al . @xcite developed the theory of a bound two - roton state . due to hybridization with this state the dispersion splits into two branches . the upper branch consists of heavily damped density excitations with the energy close to the recoil energy @xmath27 . the low - energy branch is due to the sp excitations and saturates slightly below the energy of twice the roton minimum . at low @xmath5 with increasing @xmath16 its weight is transfered to the upper branch . while zawadowski s model provides a good description for low - temperature @xmath2he data by using several fit parameters , it becomes unsatisfactory at high temperatures . the expected decrease of the intensity of the lower ( sp ) branch , by vanishing of the condensate @xmath28 , is not compensated by contribution of atoms above a condensate . this is in a contradiction with the sum rule , @xmath29 , as the static structure factor @xmath30 for @xmath2he was found to be nearly temperature independent for @xmath31 . @xcite further , in some range of @xmath16-wavevectors a fit to the @xmath5-dependent experimental @xmath0-data resulted in the repulsive interaction between two roton excitations , @xcite opposite to the negative coupling constant suggested in the original model . this point , has been resolved by a more elaborated theory @xcite using a t - matrix which allowed the coupling constant to oscillate with @xmath16 . the dielectric function models interpret the roton and the two - roton state as a specific feature of the sp spectrum coupled in @xmath0 in a superfluid phase . the standard procedure to follow is to fit the involved key parameters ( @xmath32 ) of the green s function ( [ gp ] ) to be consistent with the low temperature @xmath0-data . the @xmath5-dependence is neglected and enters only via @xmath28 and the bose function in eq . ( [ sq ] ) . in a similar way , the density response function @xmath33 ( [ tchi ] ) is treated also as @xmath5-independent , and , therefore , is fitted by high temperature data , where the singular condensate part does not contribute . the weak point of this model is the discrepancy with experiments near @xmath9 . the intensity of the sharp peak ( two - roton state ) assigned with the sp excitations ( poles of @xmath11 ) becomes too low as its spectral weight vanishes with @xmath28 . in contrast , a typical experiment on @xmath2he demonstrates a continuous broadening of this peak and nearly conserved integrated spectral weight . also a broad multi - excitation background , related with @xmath33 , extends significantly to low frequencies , as @xmath5 is increased , being in contradiction with the model assumption on its temperature independence . these discrepancies have been reviewed in refs . @xcite the experiments @xcite provided no indication of a well - defined mode ( sp excitations ) suddenly appearing in @xmath0 for @xmath34 due to the first term in eq . ( [ prove1 ] ) . in contrast , they demonstrated that temperature and density dependence of the spectral density in the phonon and roton part of the spectrum can be fitted with just a single - mode susceptibility . in particular , the roton mode demonstrates a rapid attenuation when approaching @xmath9 from below and continues as an overdamped diffusive mode of zero frequency above @xmath9 . the authors concluded `` our results can not be explained using the gg model , unless of course the two components in the gg model hybridize into one ( having one lifetime and excitation energy ) at all temperatures and pressures , independent of the value of @xmath35 '' . @xcite this suggests , that the phonon - roton spectrum must be considered as _ unified branch _ as was done in the original papers by landau , feynman and bogolubov . @xcite however the origin of the excitations and their structure can be different . by rigorous considerations , nepomnyashchy @xcite has demonstrated that a simultaneous presence in the spectrum of both zero sound ( zs ) and sp branch is not possible . at @xmath36 the zs is suppressed and replaced by the sp branch defined by poles of the sp green function . the phonons become identical with the elementary excitations . the sp branch , however , accumulates some properties of the zs branch , such as linear spectrum and independence on @xmath35 . this is in a principle contradiction with the ansatz ( [ tchi ] ) when one uses the substitution @xmath10 . finally , we note that the bogolubov type spectrum can be also derived without involving the gauge symmetry breaking , i.e. also for a normal phase with the conserved gauge symmetry . @xcite this implies that the phonon - maxon - roton dispersion , observed in a superfluid , should be also preserved in the normal phase , once the damping is small . for a 2d dipolar gas , we found that its properties near @xmath9 qualitatively follow that of 3d @xmath2he discussed above . from the comparison of @xmath0 at @xmath37 , we can confirm that the intensity of the two - roton `` plateau '' is unexpectedly too large and does not scale with the zero - temperature condensate fraction once the density is varied . the condensate demonstrates a broad variation @xcite ( @xmath38 ) and this implies , that for @xmath10 in ( [ tchi ] ) , the two - roton peak should be strongly suppressed at high densities , if we assume a roton being solely a sp excitation . in our simulations we do not find any evidence of this behavior . the intensity of the peak is not much reduced when approaching @xmath9 either . formally , in 2d geometry , as considered here , at @xmath39 the condensate fraction should vanish in the thermodynamic limit and no coupling to the sp spectrum is expected . still the two - roton state is observed for @xmath40 and even for @xmath41 at high densities ( but strongly damped ) . the finite size effects are negligible for the considered system sizes ( @xmath42 ) and , therefore , do not influence the imaginary time correction functions used for the reconstruction of the spectral densities ( sec . [ qcorrf ] ) . all observed characteristic spectrum features should remain also in the thermodynamic limit ( except the limit @xmath43 ) . this brings us to a preliminary conclusion that if the two - roton state is a feature of sp spectrum the sufficient condition for the hybridization in @xmath0 is the presence of at least off - diagonal quasi - long range order and a non - zero superfluid density . it is important to mention that , there exists a second viewpoint on roton and different combinations ( roton+roton , roton+maxon , maxon+maxon ) as the intrinsic density excitations related with the short - range particle correlations . @xcite to clarify these important issues one needs to independently access @xmath0 and the sp spectral density @xmath1 for temperatures below and above @xmath9 to indentify how the excitation branches of both spectra are coupled in the superfluid phase and lead to rotonization . this gives motivation for the present analysis . the path integral monte carlo simulations in combination with the stochastic optimization method are used to reconstruct collective and single - particle excitations _ at finite temperatures _ from first principles ( in the linear response regime ) . both should be coupled or form _ a unified branch _ in the density fluctuation spectrum @xmath0 once a system has a condensate or the bose broken symmetry . @xcite whether this prediction remains also valid for 2d bose systems , with the off - diagonal quasi - long range order and only local bose condensate , remains an open issue and calls for further analysis on the level of microscopic simulations . such analyses in application to 2d dipolar gas will be presented in sec . [ disc_spec ] . in particular , we found that at weak and intermediate coupling ( sec . [ weak],[intermediate ] ) the single - particle and the collective ( density fluctuations ) modes have similar dispersion relations in the normal phase ( when they are independent ) . as a result , in the superfluid phase due to the coupling ( eq . [ tchi ] ) both branches become hybridized . in general , the dispersion relation @xmath44 observed in @xmath0 splits into two branches , but the high energy ( multiparticle ) part gets significant broadening in the normal phase . at intermediate @xmath16 ( the maxon - roton region ) the lower branch is shifted to lower energies and its damping is enhanced for @xmath45 . for strongly correlated dipolar gas ( @xmath46 ) our results support the viewpoint on the roton as a collective density mode . while , the sp spectrum @xmath1 shows a well pronounced roton minimum ( denoted as @xmath47 ) , the corresponding energies @xmath48 and @xmath49 are larger than those of the roton - minimum ( @xmath50 ) and two - roton state ( pitaevskii `` plateau '' @xmath51 ) observed in @xmath0 . according to the zawadowski s model , this suggests a strong binding mechanism which currently lacks experimental confirmation in other strongly correlated bose systems ( @xmath2he ) . independent on the presence of the two - roton state , the frequency sum rules ( see appendix [ app ] ) predict a branch near the recoil energy @xmath27 . indeed , the simulations reproduce this branch , however , it is strongly damped , as expected from weakly interacting density quasiparticles . this multiparticle feature is present both below and above @xmath9 . in contrast to @xmath2he , in a dipolar system at high density ( e.g. @xmath46 ) the pitaevskii `` plateau '' appears to be well separated from this multiparticle continuum . similar free - particle like branch is observed in the sp spectrum @xmath1 . based on our results we interpret the two - roton state as a combination of two density rotons ( the poles of the dynamic susceptibility ) as we can observe it also for @xmath52 . the detailed discussion will be presented in sec . [ intermediate],[strong ] . in sec . [ model ] we introduce the model of a 2d dipolar gas . in sec . [ physrel ] physical realizations are listed and experimental parameters are compared with our model . in sec . [ intro2 ] the dynamic structure factor @xmath0 is introduced for a system with bose condensate . in sec . [ qcorrf ] we analyze the structure of the imaginary time correlation functions and their relation with the sp spectral density @xmath1 and @xmath0 . in sec . [ sto ] reconstruction of @xmath1 and @xmath0 using the stochastic optimization procedure is discussed . in sec . [ specsec ] we analyze temperature / density dependence of the momentum distribution and the spectral densities . in sec . [ disc_spec ] we give our interpretation of the different excitation branches observed in @xmath1 , @xmath0 . in sec . [ sum ] we list our conclusions . dipolar bec has been first realized in atomic systems of magnetic dipoles . @xcite new exciting results have been recently reported for dipolar molecules @xcite with the major advantage of significantly larger electric dipole moments . the mean field description of such systems predicts that the dipolar condensates in 3d geometry become dynamically unstable when the dipole interaction dominates the @xmath53-wave scattering contact interaction . @xcite this effect is a consequence of the rotonization of the bogolubov - type spectrum @xcite and leads to an instability of the time - dependent gross - pitaevskii equation . @xcite to avoid this problem and study the behavior of dipolar systems well beyond the mean - field regime with a stable condensate and/or a superfluid phase , we consider a quasi-2d geometry . the dipole moments are oriented along the direction of the strong trap confinement and produce only repulsive interaction @xmath54 . the dipolar forces are assumed to completely dominate the contact interaction , therefore , the latter is neglected in the present model . we assume 2d spatial homogeneity by considering an infinite pancake trap geometry . the evaluated spectrum for the in - plane momentum @xmath16 will be valid for the excitation wavelengths , @xmath55 , bounded by the perpendicular @xmath56 and the in - plane @xmath57 system size , i.e @xmath58 . otherwise , the excitations acquire 3d character . for a quasi-2d model of dipolar condensate , @xcite the perpendicular extension can be estimated by @xmath59 . the dipole moment @xmath60 and particle density @xmath61 are free parameters controlled by external fields and in - plane trap frequencies . the system hamiltonian @xmath62 can be made dimensionless by using the length and energy units : @xmath63 ( the mean interparticle distance ) and @xmath64 . in the canonical ensemble , the thermodynamic properties of ( [ h ] ) are completely defined by the dipole coupling @xmath65 , temperature @xmath66 and particle number @xmath67 . the bose broken - symmetry condition , i.e. @xmath68 , and evaluation of imaginary - time green s functions suggest to use the grand - canonical ensemble . in this case , the worm algorithm @xcite has been employed by fixing a value of the chemical potential @xmath69 and system volume @xmath70 instead of @xmath67 ( see note @xcite ) . indeed , existence of the order parameter , @xmath71 , is related with the fluctuations of a particle number in a condensate state . for a weakly interacting dipolar gas ( @xmath72 ) , we observed significant particle number fluctuations , @xmath73 , with a condensate fraction , @xmath74 . this can lead to some differences between the canonical ensemble ( experimental bec realized in traps ) and the grand - canonical results . the parameters of pimc simulations are from ref . @xcite the dipole coupling ( or density ) , @xmath75 , was varied in the range @xmath76 and temperature @xmath77 . with the known @xmath78-dependence of the critical temperature @xcite ( @xmath79 ) we scan both the superfluid and the normal phase . next we discuss what @xmath78 values are accessible in current experimental realizations . consider the effective radius of dipole - dipole interaction , @xmath80 , corresponding to the distance when the dipolar energy reaches the value of the zero - point kinetic energy , i.e. @xmath81 . the introduced dipolar parameter equals the ratio of two characteristic length scales , @xmath82 . given a value of a magnetic / electric dipole moment ( which enters in @xmath83 ) we can estimate the density required for a specific @xmath78 . the effective dipole interaction radius can be expressed as @xmath84=\frac{149.36}{\epsilon_b } m[\text{u}]\ , p^2[\text{debye}^2],\label{adex}\end{aligned}\ ] ] where @xmath85 is the mass in the unified atomic mass unit , @xmath86 is the dipole moment in the debye . an external electric field aligns dipolar particles leading to a repulsive @xmath87-interaction . several examples are considered below . * _ cold bosonic atoms _ with a permanent magnetic moment @xcite in tight pancake traps . magnetic dipoles are aligned by a magnetic field . a dipolar gas of @xmath88cr with @xmath89 and @xmath90@xmath91 ( @xmath92 ) has @xmath93 . the dipolar interaction will dominate , when the s - wave scattering length ( @xmath94 ) is suppressed to @xmath95 using a high magnetic field feshbach resonance . the resulted coupling , @xmath96 , is close to the analyzed value @xmath72 . the superfluid transition temperature is estimated @xcite to be @xmath97k ( in a 2d geometry ) . + even higher coupling can be achieved in the bose gas of dysprosium @xcite ( @xmath98dy ) with @xmath99 . the evaluation for @xmath100@xmath91 ( @xmath101 ) results in @xmath102 , @xmath103 and @xmath104k . an ultracold dysprosium gas does not suffer from chemical reactions , like certain polar molecules , @xcite and , therefore , is stable at high densities . + very recently , a bose - einstein condensate of erbium ( @xmath105er ) has been reported , @xcite being another promising candidate for experimental realization of strongly correlated dipolar quantum gases . similar to dysprosium , erbium has a large magnetic moment @xmath106 and atomic mass which enhance the dipole interaction radius ( [ adex ] ) . a large dipole moment also allows to reach a high efficiency both in a magneto - optical trapping and subsequent evaporative laser cooling to temperatures @xmath107mk . * _ polar molecules _ @xcite ( rb@xmath108 , cs@xmath108 , @xmath109k@xmath110rb , @xmath111k@xmath110rb ) transfered to the rovibrational ground state with a permanent electric dipole moment , @xmath112 debye , @xcite aligned by an electric field . for @xmath113k@xmath110rb gas with @xmath100@xmath91 and @xmath114 debye , we estimate @xmath115 , @xmath116 , @xmath117k and @xmath118k . high densities and @xmath78-values can be achieved by localizing feshbach molecules in an optical lattice to suppress their collisions and then quenching to a ground state via stimulated raman adiabatic passage . @xcite besides molecule collisions , an upper bound for quantum degeneracy and the dipole coupling @xmath78 is limited by chemical reactions and associated molecule loss rates . @xcite * _ rydberg - dressed atoms _ excited to high principal quantum numbers @xmath119 and confined in two dimensions . @xcite a large dipole moment can be reached in the linear stark regime with the result @xmath120 debye for @xmath121 . we consider an ensemble of ground state atoms excited to high rydberg states with the single - atom excitation probability @xmath122 ( where @xmath123 and @xmath124 are a rabi - frequency and a detuning laser frequency ) . the effect of a local dipole blockade , @xcite i.e. a zero probability to excite more than one atom within a distance @xmath125 , can be included via the reduced hamiltonian of `` superatoms '' , @xcite with the average superatom interaction @xmath126 , where @xmath127 is a typical number of atoms ( in 2d ) within a superatom radius @xmath125 . the latter depends on the properties of the excitation laser ( @xmath128 ) , the gas density @xmath129 and the interaction potential @xmath130 . for estimation , we treat an excitation probability @xmath131 of a many - body system ( modified by correlation effects and defined by @xmath132 ) as that of an uncorrelated gas , i.e. @xmath133 . for a gas of rubidium rydberg atoms ( @xmath110rb ) with the number density @xmath134@xmath91 we estimate @xmath135 ( @xmath136 m ) , but only a half of the superatoms are interacting as they perform rabi oscillations between their ground and excited states . this results in the superatom spacing @xmath137 , and , correspondingly , @xmath138 m and @xmath139 . for low enough temperature a rydberg gas will undergo a crystallization transition , as the coupling is above the critical value @xmath140 . @xcite quantum effects between rydberg - dressed atoms will be relevant for @xmath141 nk , due to low densities . * _ composite bosons _ , e.g. spatially indirect excitons in coupled qws with the exciton temperature in the range @xmath142 k. for typical experimental parameters @xcite ( @xmath143@xmath144 , the inter - well distance @xmath145 , and @xmath146 debye ) from eq . ( [ adex ] ) we estimate @xmath147 and @xmath148 . a maximum dipolar coupling ( @xmath149 ) can be reached below the excitonic mott transition density @xmath150@xmath91 . these estimations show that the systems of ultracold dysprosium ( erbium ) , polar molecules and indirect excitons are good candidates for experimental validations of the present analyses for @xmath151 . we assume that in an experiment a long - lived quantum gas is created and , hence , a thermodynamic description remains valid . further , there should be no noticeable heating , e.g. due to breaking of molecular bonds or recombination of excitonic states . by this assumption , experimental parameters which correspond to different @xmath78-values are listed in tab . [ tab0 ] . .relevant parameters for 2d systems of the dysprosium @xmath98dy ( dy ) , @xmath109k@xmath110rb polar molecules ( m ) and indirect excitons ( ex ) . the assumed dipole moments are , correspondingly , @xmath152 , @xmath153 debye and @xmath154 debye . the dipole coupling @xmath78 is expressed in terms of the in - plane density @xmath129 [ @xmath91 ] . for @xmath40 a system is in a superfluid phase . @xcite the frequency @xmath156 ( @xmath157 ) denotes a characteristic energy scale of collective and single - particle excitations . [ cols="^,^,^,^,^,^,^,^,^,^ " , ] we conclude , from the performed tests , that the reconstruction reliability crucially depends on the relative noise in the input correlation function , @xmath158 . this quantity can be used to qualify reconstructed spectra , in particular , presented in sec . [ dens_ex ] , based on the downgrade of the spectral features analyzed in this section . in general , the relative noise in the density - density correlation function increases with @xmath159 and the @xmath16-vector due to a faster decay of @xmath160 ( see fig . 4a ) . as a result the reconstructed @xmath0 in fig . 7 at large wavevectors becomes less accurate compared to the low momentum part of the spectrum . when only two well separated energy resonances are reconstructed , the peak positions remain stable against the noise ( cf . fig . [ fig : model2 ] ) . a noticeable effect is observed in the half - widths of the peaks . the reconstruction results are more sensitive to the noise level for the overlapping bimodal ( figs . [ fig : model3 ] and [ fig : model4 ] ) and the multipeak distribution ( fig . [ fig : model6 ] ) . as expected , details on how one individual feature ( a peak position and a half - width ) is reconstructed have a strong influence on the rest of the spectral density . even if the low frequency moments are fulfilled with high accuracy @xmath161 , this is not sufficient to guarantee a reliable reconstruction . a large class of solutions @xmath162 can fit within the error - bars the correlation function ( [ gtautest ] ) . the broader is the reference distribution @xmath163 in the frequency space , more `` degrees of freedom '' are allowed to be used in the reconstruction . they can be distributed in many different ways to satisfy the sum rules . as a result the ensemble average can smooth specific features of the reference spectrum . next , consider a taylor expansion of the correlation function @xmath164 from which follows the expansion in the frequency moments @xmath165 several first frequency moments can uniquely specify only a short time asymptotic of @xmath166 , and , in general , all moments are required to reconstruct @xmath166 at the full time scale . vise versa , an exact fit to @xmath167 at all @xmath159 necessarily means that all frequency moments are uniquely defined . however , if there is some uncertainty , i.e. @xmath168 , it can be fulfilled by different expansions in @xmath169 , where the successive terms mutually compensate , due to the sign - alternating prefactor in ( [ wos ] ) . now the shape of @xmath170 is not unique . the upper bound for the lower excitation branch with a negligible damping can be derived using the decomposition of the density - density response function ( imaginary part ) @xmath171=\chi_1(q,\omega)+\chi_2(q,\omega).\label{anz}\end{aligned}\ ] ] it is assumed that the @xmath172-peak quasiparticle contribution with the energy @xmath173 @xmath174\end{aligned}\ ] ] is not overlapping with the multi - particle excitations at higher energies @xmath175 we note that @xmath176 is odd in @xmath177 . the fluctuation dissipation theorem and the detailed balance are written as @xmath178=-\pi \left[1-e^{-\beta \omega } \right ] s(q,\omega),\\ & s(q,-\omega)=e^{-\beta \omega } s(q,\omega).\label{detail}\end{aligned}\ ] ] the dynamic structure satisfies the frequency moments sum rules @xmath179 in the following , the @xmath180-sum rule , the longitudinal @xmath181sum rule @xcite and the compressibility sum rule ( all valid at any @xmath5 ) will be employed @xmath182 these constraints can be used to characterize the quality of experimental / theoretical spectra , i.e. check how well they satisfy the sum rules . the finite - temperature generalization of the zero temperature bijl - feynman upper - bound for lower excitation branch @xcite @xmath183 can be directly derived from the @xmath184-sum rule ( [ f - sum ] ) . the contribution of the negative frequencies , @xmath185 , is important at high temperatures , typically , in the normal phase . by substitution of ( [ anz])-([detail ] ) in ( [ 0-sum])-([f - sum ] ) we end up with @xmath186 according to ( [ case1 ] ) , we can write the inequality @xmath187 the combination of ( [ a1]),([a2]),([a3 ] ) leads to the upper bound @xmath188 where the feynman frequency @xmath189 is defined by @xmath190 an improved upper bound can be derived from the compressibility - sum rule . it was discussed in ref . @xcite and applied to 2d dipolar gases in ref . @xcite by substitution of ( [ anz]-[detail ] ) in ( [ comp ] ) we obtain @xmath191 where we have used that @xmath192 $ ] decays with @xmath177 . this leads to the upper bound @xmath193 with @xmath194 the involved static response function can be directly estimated from the imaginary time density correlation function ( [ g2 ] ) @xmath195 for a dispersion consisting of a single sharp excitation branch the upper bound @xmath196 becomes almost exact , e.g. @xmath72 and fig . [ fig : sdyn1]a - c . for other couplings , the phonon - maxon and roton features are also accurately reproduced ( fig . [ fig : sdyn1]a , [ fig : sdyn2]a , [ fig : sdyn3]a ) . the reason is the damping of high - energy contributions by the factor @xmath197 . this significantly improves the feynman upper bound ( [ feynm ] ) , where the spectral weight of high frequencies scales as @xmath177 . this leads to the general relation , @xmath198 , valid in a superfluid phase for the lower excitation branch . in the long - wavelength limit , we expect that both upper bounds converge to the isothermal sound dispersion , i.e. @xmath199 . then the product of ( [ feynm ] ) and ( [ chiw ] ) results in the compressibility sum rule @xmath200 similar , for @xmath201 ( or @xmath202 ) , from eq . ( [ chiw ] ) we get the limiting value of the static structure factor @xmath203 the offset from zero increases with temperature and decreases with the coupling strength / density ( the sound speed increases with @xmath78 , see tab . [ tab3 ] ) . consider indirect excitons with the dipole length @xmath204 nm at density @xmath129 in a circular trap with the diameter @xmath205 @xmath69 m realized in two coupled gaas qws structure @xmath206 , as in typical realizations . @xcite the dipole coupling can be expressed in the terms of relevant semiconductor parameters as @xmath207 where for gaas we take @xmath208 , the in - plane electron(hole ) mass @xmath209 , the bohr radius @xmath210 nm , the exciton mass @xmath211 . the density @xmath212 @xmath213 will correspond to the inter - exciton separation @xmath214 nm and the coupling @xmath215 . the critical temperature can be taken from ref . @xcite , @xmath216 with @xmath217^{-1}=0.0086(0.106)$ ] k for the considered densities . further , we take into account that in the unpolarized system the spin - degeneracy factor @xmath218 lowers the effective density of particles , @xmath219 , of the same spin projection which can undergo condensation , and , correspondingly , due to the bkt - scaling @xmath220 , we estimate @xmath221 k. the system size equals the trap diameter @xmath222 m . this corresponds to @xmath223 excitons in the trap . for @xmath224 , the lower bound for the condensate will be given by @xmath225 . for this estimation we used the critical exponents from tab . [ tab1 ] and the reduced system size @xmath226 . to observe quantum degeneracy effects , temperature should not be too low ( @xmath227 ) . the momentum distribution in the pre - condensation regime also has a peculiar shape at small momentum ( see fig . [ fig : pmom]a , b , c ) for @xmath228 ( @xmath31 ) if different spin states are included . a simple alternative to reconstruct the dynamic structure factor at high energies , @xmath229 , could be a fit to a suggested analytical form , e.g. to a lorentzian or gaussian @xmath230 , with the so procedure operating with the optimization parameters ( @xmath231 , @xmath232 ) . the reconstructed spectrum in fig . [ fig : sdyn3d ] at high @xmath5 allows such treatment . then , the so method would reduce to the regularization method , like the me . however , there is a priori assumption that the high - energy branch is smooth and broad ( in frequency ) , and there is no overlap with @xmath172-like resonances . the single - particle spectral density @xmath1 in fig . [ fig : adyn3d ] demonstrates the potential difficulty with this approach when we suggest too simple analytical form controlled by only few optimization parameters . therefore , the spectral densities are reconstructed by the linear combination of rectangles , see eq . 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the berezinskii - kosterlitz - thouless transition in 2d dipolar systems has been studied recently by path integral monte carlo ( pimc ) simulations [ a. filinov _ et al . _ , prl * 105 * , 070401 ( 2010 ) ] . here , we complement this analysis and study temperature - coupling strength dependence of the density ( particle - hole ) and single - particle ( sp ) excitation spectra both in superfluid and normal phases . the dynamic structure factor , @xmath0 , of the longitudinal excitations is rigorously reconstructed with full information on damping . the sp spectral function , @xmath1 , is worked out from the one - particle matsubara green s function . a stochastic optimization method is applied for reconstruction from imaginary times . in the _ superfluid regime _ sharp energy resonances are observed both in the density and sp excitations . the involved hybridization of both spectra is discussed . in contrast , in the _ normal phase _ , when there is no coupling , the density modes , beyond acoustic phonons , are significantly damped . our results generalize previous zero temperature analyses based on variational many - body wavefunctions [ f. mazzanti _ et al . _ , prl * 102 * , 110405 ( 2009 ) , d. hufnagl _ et al . _ , prl * 107 * , 065303 ( 2011 ) ] , where the underlying physics of the excitation spectrum and the role of the condensate has not been addressed .

the study of hydrogen interaction with metals has gained an increased interest in the last decade @xcite . the use of metal and semiconductor clusters as components of nanodevices , the development of cluster - based materials and the catalytic properties of clusters are the main reasons for the studies of interaction of atoms and molecules with clusters . understanding hydrogen interaction with clusters is important because of two basic reasons : first , there is a great interest in developing novel hydrogen absorbing nanomaterials for fuel cell applications , second , many of the organic materials and biological systems contain hydrogen which are involved important catalytic reactions . in particular , platinum is one of the most important ingredients in the heterogeneous catalysis of hydrogenation as well as in the catalysis of the co , no@xmath8 , and hydrocarbons . moreover , detailed investigations of the interaction between platinum clusters with hydrogen can contribute to the design of useful hydrogen storage devices . therefore , it is of interest to understand the interaction of one and two h atoms on platinum clusters . a brief summary of the previous theoretical and experimental studies on the pure platinum clusters can be found in our recent publications @xcite . the following references can be added to them : grnbeck and andreoni @xcite have presented a density functional theory ( dft ) study of au@xmath5-au@xmath6 and pt@xmath5-pt@xmath6 clusters in the neutral and anionic states . xiao and wang @xcite have studied pt clusters of up to 55 atoms using dft with a plane wave basis set and tian et al . @xcite have reported the geometrical and electronic structure of the pt@xmath9 cluster in a dft study with a gaussian type basis set . one of the earliest _ ab initio _ studies on the pt - h@xmath5 reaction was published by the group of poulain @xcite in 1986 . the same group carried out theoretical studies on the pt@xmath5-h@xmath5 @xcite , and pt@xmath4-h@xmath5 @xcite interactions later . nakasuji et al . @xcite accomplished an _ ab initio _ study on the reactions of the hydrogen molecule with small pt@xmath0 ( @xmath2=1 - 3 ) clusters . in 1987 , balasubramanian s @xcite calculations on electronic states and potential energy surfaces of pth@xmath5 has been published . later , he and feng @xcite have reported a study on the potential energy surfaces for the pt@xmath5-h and pt - h interactions . the pt@xmath7-h@xmath5 interactions have been studied by dai et al . @xcite and cui et al . @xcite . on the experimental side , molecular beam techniques have been used to investigate the hydrogen molecule interaction with metal surfaces @xcite . the chemical reactivity of metal clusters in gas phase with hydrogen and deuterium has been studied with the laser vaporization technique @xcite . in a most recent study , andrews et al . @xcite have investigated the reaction of pt atoms with h@xmath5 in a laser - ablation experiment and have also performed some dft calculations . in the experiments it is observed that the reactivity of the small metal clusters with the hydrogen and deuterium molecules strongly depends on the size of the small metal clusters @xcite . luntz et al . @xcite found that there are reaction paths with or without very low barriers , leading to the h@xmath5 dissociation on the pt ( 111 ) surfaces . in the present work , we report the results of first - principles total - energy calculations on small platinum clusters with up to two h atoms . we perform dft calculations using gaussian atomic - orbital methods within the generalized gradient approximation for the exchange and correlation to study the interactions in the bare and hydrogenated platinum clusters . the possible minima and ground states , binding energies ( be ) , relative stabilities , and the highest occupied and the lowest unoccupied molecular - orbital ( homo - lumo ) gaps of the pt@xmath0h@xmath1 ( @xmath2=1 - 5 , @xmath3=0 - 2 ) clusters have been calculated . vibrational frequency calculations for each optimized structure has been carried out to differentiate local minima from transition states . the results are compared with previously studied pure platinum and hydrogenated platinum clusters . systematic growth in the atom number allows one to monitor the changes in the structure , dynamics , and electronic properties involved with the size of the clusters . this can provide an understanding of the nature of interaction between hydrogen and pt clusters . dft calculations have been performed by using version 4.7 of the nwchem program @xcite . we have employed the lanl2dz @xcite basis set for the pt atoms , which uses relativistic effective core potentials ( ecp ) to reduce the number of electrons explicitly considered in the calculation , and 6 - 311++g * * basis set for the h atoms . the ecp parameters for platinum and the basis set , as well as similar basis sets to the one employed in this study for the hydrogen have been successfully used in many previous studies @xcite . to examine the effect of the choice of the exchange - correlation functional , we have calculated the properties of h and pt dimers and those of pth diatomic molecule by using different functionals : we have employed pw91pw91 @xcite and bpw91 @xcite functionals within the generalized gradient approximation ( gga ) , svwn5 @xcite functional within the local density approximation ( lda ) , and b3lyp @xcite and b98pw91 @xcite methods as hybrid functionals . at the end of the examination which is discussed in the next section , we have chosen the bpw91 method to study pt@xmath0h@xmath1 clusters . the default nwchem geometry optimization convergence criteria were used in all cases . initial structures have been relaxed without imposing any symmetry constraints . the final structures therefore include possible jahn - teller distortions . whenever the optimized structure has had a symmetry other than @xmath10 , the relaxation process has been repeated with that symmetry constraints starting from the optimized geometry in order to get the electronic state . spin - polarized calculations have been done for the first two multiplicities of the clusters up to pt@xmath4h . thus , singlet and triplet states have been worked out for those having even number of electrons and doublet and quartet states have been worked out for those having odd number of electrons . in addition , we have also studied the quintet states of pt@xmath4h@xmath5 , pt@xmath6 and pt@xmath6h@xmath5 clusters , and sextet states of pt@xmath6h clusters . the reason for this is discussed in sec . [ moment ] . all figures were produced by the chemcraft graphics program @xcite . table [ table1 ] displays the calculated and experimental values of the bond lengths , vibrational frequencies and bes for h and pt dimers and for pth diatomic molecule . the experimental results of h@xmath11 , pt@xmath11 , and pth are from refs . @xcite , refs . @xcite , and refs . @xcite , respectively . in our calculations , the hybrid method b3lyp has produced the nearest bond lengths to the experimental values of both h@xmath11 and pth molecules . however , it has resulted in the worst bond length ( 2.47 @xmath12 ) for pt@xmath11 ( experimental value is 2.33 @xmath12 ) . therefore , it highly underestimates the be of pt dimer by calculating only a half of the experimental value . when a second hybrid functional b98pw91 is considered , it can be seen in table [ table1 ] that although the results for pt@xmath11 are improved as compared to the results of the b3lyp method , it still overestimates the bond length and underestimates the be of the dimer significantly . on the other hand , the svwn5 lda method has produced very good results for the bond lengths of all of the three molecules . however , when the bes are taken into account , it is not favorable , too . it highly overestimates pt@xmath11 and pth bes . we have tried two gga methods for the properties of the three diatomic molecules : pw91pw91 and bpw91 . both of them have resulted in nearly the same bond lengths which are excellent for h@xmath11 and pth , and very good for pt@xmath11 . the errors in the bond length of pt@xmath11 produced by gga methods are only 1.7% . they have also calculated reasonably good bes for pt@xmath11 and pth . pw91pw91 functional has produced a slightly better result for the be of pth than bpw91 . however , the later has calculated much better pt@xmath11 be than the former . therefore , we have decided to employ bpw91 functional in the rest of our calculations . the error produced by the chosen method in the be of h molecule ( 9.5% ) is not very important in the present study since the h atoms in the pt@xmath0h@xmath1 clusters do not bind together as we discuss in the following sections . as a result , we have performed all the remaining computations of the hydrogenated pt clusters at the bpw91/lanl2dz and bpw91/6 - 311++g * * levels of theory . we start to report the obtained results with bare pt clusters . pt@xmath5 : it can be seen from table [ table1 ] and table [ table2 ] that the chosen dft method produces reasonably good results for the be , vibrational frequency and the bond length of the pt dimer . we have determined the electronic state of the dimer as @xmath13 which is not consistent with balasubramanian s @xcite result that a @xmath14 is the ground state . the singlet state turns out to be 1.39 ev less stable than the triplet . both of the references @xcite and @xcite have reported the ground state of the dimer as a triplet , however none of them has given any electronic state . xiao and wang @xcite have calculated 3.52 ev be , 2.34 @xmath12 bond distance and 0.81 ev homo - lumo gap in their dft study with ultrasoft pseudopotentials . the best energy and bond length values of grnbeck and andreoni @xcite obtained by employing blyp exchange correlation functional are 3.58 ev and 2.32 @xmath12 , respectively . for both of these studies , the bond distance values are closer to the experimental data ( 2.33 @xmath12 ) than our result ( 2.37 @xmath12 ) , however the method employed in this work results better in the energy since it calculates 3.36 ev be which is closer to the experimental data ( 3.14 ev ) than the previous calculations . balasubramanian @xcite has reported the obtained pt - pt distance as 2.46 @xmath12 which is the worst among all of the above mentioned references . we have calculated 1.32 ev homo - lumo gap which is significantly higher than the one given in ref . our result for the @xmath15 spin homo - lumo gap ( 0.33 ev ) is in agreement with the calculation of tian et al . @xcite ( 0.3 ev ) . pt@xmath7 : the isomeric structures , symmetries , ground electronic states , total bes , homo - lumo gaps ( @xmath16 spin ) , and the highest and the lowest vibrational frequencies of pt@xmath5-pt@xmath6 clusters are given in table [ table2 ] . the pictures of these isomers and the bond lengths ( in @xmath12 ) in these structures are presented in fig . we have studied the equilateral and isosceles triangle structures of the pt trimer , and found out that the optimized bond lengths of these two geometries are very similar ( see fig . [ pt ] ( 3 - 1 ) and ( 3 - 2 ) ) . therefore , the energy separation between them is very small . all pt - pt distances in the equilateral triangle are 2.53 @xmath12 which can be compared with the result of grnbeck and andreoni @xcite ( 2.41 @xmath12 ) . the ground electronic state of the @xmath17 symmetry is @xmath18 whereas that of @xmath19 symmetry is @xmath20 . the bes and the homo - lumo gaps for both of these structures are 6.57 ev and 1.05 ev , respectively . pt@xmath4 : we have identified three stable structures of pt@xmath4 : a distorted tetrahedron ( 4 - 1 ) , an out of plane rhombus ( 4 - 2 ) , and a planar y - like shape ( 4 - 3 ) . a square isomer has been found to be a first order transition state in our calculations . the distorted tetrahedron with @xmath21 symmetry and @xmath22 electronic state is 0.1 ev more stable than the rhombus , whereas the be of the rhombus is 0.29 ev higher than the be of the third isomer . the homo - lumo gaps and the lowest and highest vibrational frequencies of these clusters can be found in table [ table2 ] . previously , grnbeck and andreoni @xcite have reported the global minimum to be a slightly out of plane rhombus in the triplet . xiao and wang @xcite have found a distorted tetrahedron with @xmath23 symmetry as the lowest energy structure in their plane wave calculations . dai and balasubramanian @xcite have performed mrsdci calculations and a regular tetrahedron in a triplet state was determined to be the ground state . pt@xmath6 : a bridge site capped tetrahedron ( 5 - 1 ) , a rhombus pyramid ( 5 - 2 ) , a trigonal bipyramid ( 5 - 3 ) , an x - like ( 5 - 4 ) and an w - like ( 5 - 5 ) geometries are the low - energy structures of pt@xmath6 . this is the first time , to the best of our knowledge , that the bridge site capped tetrahedron ( 5 - 1 ) is identified as the global minimum of pt@xmath6 . it is in the quintet state and 0.09 ev more stable than the second isomer . the second isomer ( rhombus pyramid ) is also in the quintet state , whereas the other three locally stable structures are in triplet . the homo - lumo gap ( 0.69 ev ) of the lowest energy structure ( 5 - 1 ) is also higher than that of the other isomers . therefore , it is expected to be more stable than the other structures . the be of the rhombus pyramid is 0.07 ev higher than the be of the trigonal bipyramid . the energy separation of the almost planar x - like and w - like structures from the 3d configurations is more than 0.04 ev . in ref . @xcite , blyp calculations have predicted the lowest energy isomer to be the planar w - like shape and lda calculations have placed a distorted square pyramid at low energies . in ref . @xcite , the trigonal bipyramid has been found as the global minimum in the quintet state . according to the results presented here , the claim that 3d geometries for pt tetramer and pentamer are unfavored is not true . in addition , the homo - lumo gaps for pt@xmath5-pt@xmath6 obtained in our calculations ( 1.32 , 1.05 , 0.44 , and 0.69 ev , respectively ) are generally much greater than the previous calculations ( 0.7 , 0.2 , 0.3 , and 0,2 ev in ref . @xcite , and 0.81 , 0.034 , 0.28 , and 0.63 ev in ref . @xcite ) . the relaxed structures and bond lengths of one and two h atoms on small pt clusters are shown in fig . [ pt - h ] , while the symmetries , electronic states , bes , homo - lumo gaps ( @xmath16 spin ) and the highest and the lowest vibrational frequencies are given in table [ table3 ] . pth : considering first the interaction of h with a pt atom will be instructive . we have calculated the be of the pth molecule in the doublet state as 3.28 ev , which is close to the experimental data @xcite of 3.44 ev . in fact , as discussed by balasubramanian and feng @xcite the experimental value should be regarded as only an upper bound . they have reported the ground state be as 3.11 ev by employing the casscf / soci / rci method in 1989 @xcite . we have identified the electronic ground state of the molecule as @xmath24 which is in agrement with both the experimental @xcite and balasubramanian s theoretical results @xcite . andrews et al . @xcite have investigated pth@xmath0 ( @xmath2=1 - 3 ) clusters by employing the b3lyp and bpw91 density functionals with 6 - 311+g * * , 6 - 311++g(3df,3pd ) and aug - cc - pvtz basis sets for h , and lanl2dz and sdd pseudopotentials for pt . in their study , the ground state has been determined as @xmath25 , however no be has been given . we have computed the bond length of pth as 1.528 @xmath12 which is also in very good agreement with the experimental value @xcite of 1.529 @xmath12 . it is determined as 1.55 @xmath12 in ref . @xcite and as 1.531 @xmath12 in ref . @xcite . when the vibrational frequency is considered , the experimental data @xcite is 2294 @xmath26 . our result is 2420 @xmath26 whereas ref . @xcite and ref . @xcite have reported 2177 and 2370 @xmath26 , respectively . it should be noted here that all frequencies given in this work are determined without using any scale factor . if they were scaled by a proper factor for the chosen method , they would be more accurate . the homo - lumo gap of pth is 3.02 ev which is the largest gap among all the clusters we have studied here . since the total energy of pt@xmath5 and h@xmath5 ( 7.66 ev ) is bigger than the energy of 2pth ( 6.56 ev ) , one can expect the abundance of the pth molecule in an environment of atomic hydrogen rather than in an environment of molecular hydrogen . pth@xmath5 : pth@xmath5 has a waterlike structure as shown in fig . [ pt - h ] ( 1b ) with an angle of 85.9@xmath27 . this angle was reported previously as 85@xmath27 by balasubramanian @xcite and as 85.7@xmath27 by andrews et al . @xcite . as in the case of the angle , our result for the bond length ( 1.517 @xmath12 ) is in very good agreement with the previous calculation ( 1.520 @xmath12 ) @xcite . all of these studies ( ref . @xcite , ref . @xcite , and the present paper ) identify the ground state of the pth@xmath5 molecule to be @xmath28 . it can be seen from table [ table3 ] that the be of h on pth ( 3.58 ev ) is 0.30 ev higher than the be of h on pt atom ( 3.28 ev ) . thus , pth@xmath5 is a bit more stable than pth when h separations from these molecules are considered . although the homo - lumo gap of pth@xmath5 ( 2.49 ev ) is smaller than that of pth , it is still a big gap . we have found pth@xmath5 to be 6.86 ev more stable than the ground state pt atom and two ground state h atoms . in order to dissociate h@xmath5 molecule from pth@xmath5 , 2.55 ev is needed . this energy may be compared with earlier calculations : 2.15 ev @xcite , 1.73 ev @xcite , and 2.04 - 2.21 ev @xcite . we have determined the lowest , middle and the highest vibrational frequencies as 793 , 2455 , 2490 @xmath26 . in ref . @xcite , the corresponding frequencies are computed in the following ranges by employing different methods and basis sets : 784 - 805 , 2414 - 2456 , 2455 - 2513 @xmath26 . the h - h distance in pth@xmath5 is 2.07 @xmath12 , which is significantly greater than the bond length of h@xmath5 ( 0.74 @xmath12 ) . therefore , the interaction between pt and h@xmath5 is dissociative . pt@xmath5h : there are two possible ways of h bonding on the pt dimer : on the bridge site ( fig . [ pt - h ] ( 2b ) which is an isosceles triangle ) and on the top site ( fig . [ pt - h ] ( 2c ) which is a planar v - like shape with @xmath23 symmetry ) . different electronic states of the bridge structure have been studied in ref . @xcite before and a @xmath29 state has been identified as the ground state , which is in full agreement with our result . 2.53 @xmath12 of the pt - pt distance and 1.75 @xmath12 of the pt - h distance given in that study can be compared with the present results of 2.50 @xmath12 and 1.71 @xmath12 , respectively . we have determined the ground state of the top structure to be a @xmath30 state . the energy difference between the quartet and doublet states of this geometry is 0.50 ev . the bes of h on the bridge and top sites of pt@xmath5 are 2.73 ev and 2.25 ev , respectively . since these energies are particularly high it can be concluded that pt@xmath5 is a reactive molecule . the bonding on the bridge site is 0.48 ev more favorable than the bonding on the top site . on the other hand , the homo - lumo gap of ( 2c ) structure ( 2.57 ev ) is much greater than that of ( 2b ) structure ( 1.26 ev ) . thus , the further reaction of the isosceles triangle to make pt@xmath5h@xmath5 can occur easier than that of the v - like structure . in the v - like structure , the pt - pt and pt - h distances are reduced to 2.44 @xmath12 and 1.56 @xmath12 . pt@xmath5h@xmath5 : we have identified three stable structures of pt@xmath5h@xmath5 ; ( i ) both h atoms are on the bridge site ( fig . [ pt - h ] ( 2d ) ) , ( ii ) both of them are on the top sites of different pt atoms ( fig . [ pt - h ] ( 2e ) ) , and ( iii ) both of them are on the top site of the same pt atom ( fig . [ pt - h ] ( 2f ) ) . an initial geometry of a bridge - top configuration takes the ( 2e ) form at the end of the optimization process . the singlet states of all of these three structures are more stable than their triplet states . among the three local minima , ( 2e ) form has the biggest be ( 9.29 ev ) . the homo - lumo gap of the ( 2f ) form ( 0.09 ev ) is significantly small , therefore it is expected to react further to make pt@xmath7h@xmath5 or pt@xmath5h@xmath7 . the h - h distance in ( 2f ) is 2.05 @xmath12 which is again much bigger than the bond distance in the h molecule . therefore , the h adsorption on pt dimer is also dissociative . pt@xmath7h : interaction of h on pt@xmath7 is slightly favorable on the bridge site ( fig . [ pt - h ] ( 3b ) ) as compared to the top site ( fig . [ pt - h ] ( 3c ) ) by 0.06 ev . the homo - lumo gap in the ( 3b ) form ( 0.66 ev ) is also greater than the gap in the ( 3c ) form ( 0.19 ev ) . the ground states of both of these structures are doublet . the h bes in these geometries are 2.63 ev and 2.57 ev respectively , which are relatively small when compared to the most of the bes in the other pt@xmath0h@xmath1 clusters . the pt - h distance in the bridge site ( 1.71 @xmath12 , ( 3b ) ) is very similar to the corresponding bridge site distances of the previous clusters , that is pt - h distances in pt@xmath5h ( 2b ) and pt@xmath5h@xmath5 ( 2d ) . the same is true for the typical 1.53 @xmath12 pt - h top site distance in the ( 3c ) form which is very close to the pt - h distances in the ( 1a ) , ( 1b ) , ( 2e ) , and ( 2f ) structures . the only exception of this is the 1.56 @xmath12 pt - h bond length in the ( 2c ) form which can be related to the fact that ( 2c ) structure is a quartet although all the other pt@xmath0h clusters listed above are doublets . in our calculations , we have not found any local minima of pt@xmath7h in which h has a coordination number of three or more . pt@xmath7h@xmath5 : we have identified 9 different local minima of pt@xmath7h@xmath5 ; three bridge - bridge configurations ( fig . [ pt - h ] ( 3d)-(3f ) ) , four bridge - top configurations ( fig . [ pt - h ] ( 3g)-(3j ) ) , and two top - top configurations ( fig . [ pt - h ] ( 3k ) , ( 3l ) ) . in the ( 3d ) geometry the two h atoms are on the same bridge site , whereas in the ( 3e ) and ( 3f ) forms they are on the neighboring sites . the difference between ( 3e ) and ( 3f ) is that in the former case h atoms are on the opposite sides of the pt@xmath7 plane , whereas in the later case they are not . among the four bridge - top configurations , ( 3h ) is the only one having a pt atom bonding to both of the h atoms . in the ( 3 g ) and ( 3j ) geometries the bridge and top site h atoms are on the opposite and on the same sides of the pt@xmath7 plane , respectively . in the ( 3i ) case , all the atoms of the cluster are on the same plane . in one of the top - top configuration , the h atoms are bonded to different pt atoms ( 3k ) . they are bonded to the same pt atom in the other one ( 3l ) . the top - top configurations have greater bes than all the other isomers ( see table [ table3 ] ) . when the two h atoms are bonded to the top site of the same pt atom ( 3l ) , the ground state is a triplet which is different from the singlet ( 2f ) structure of pt@xmath5h@xmath5 . the ( 3l ) structure has the greatest be and homo - lumo gap , and therefore it is the most stable pt@xmath7h@xmath5 cluster that we have investigated in the present work . the h - h distance in it is 1.75 @xmath12 . the be for 2h is 5.51 ev and it is significantly higher than the dissociation energy of h@xmath5 ( 4.75 ev ) . accordingly , hydrogen is likely to be dissociated on pt@xmath7 as well as on pt@xmath5 . among the bridge - top configurations , ( 3h ) structure has higher be than the others . the bridge - top isomers of the pt@xmath7h@xmath5 cluster are generally more stable than its bridge - bridge isomers except that ( 3f ) geometry has greater be than ( 3i ) . pt@xmath4h & pt@xmath4h@xmath5 : h prefers to bind to the ground state pt tetramer on the top site . the isomer with h on the top site ( fig . [ pt - h ] ( 4c ) ) is a quartet and its be is 0.3 ev greater than that of the isomer with h on the bridge site ( fig . [ pt - h ] ( 4b ) ) which is a doublet . the homo - lumo gap of ( 4c ) is also greater than that of ( 4b ) ( see table [ table3 ] ) . thus , ( 4c ) structure is expected to be more stable . in the case of 2h , the most stable structure is a top - top configuration ( fig . [ pt - h ] ( 4h ) ) which is similar to the pt@xmath7h@xmath5 case . the homo - lumo gap of this structure is 0.94 ev and it is higher than that of all the other pt@xmath4h@xmath5 isomers . the h - h distance in ( 4h ) is 1.95 @xmath12 . the 2h be is 5.80 ev . thus , the h absorbtion is again dissociative . the bes of the neighbor bridge - bridge configuration ( 4d ) and the opposite bridge - bridge configuration ( 4e ) are nearly the same . however , ( 4d ) is a triplet whereas ( 4e ) is a singlet . for the bridge - top configurations , the neighboring structure ( 4f ) is 0.1 ev more stable than the opposite structure ( 4 g ) . pt@xmath6h & pt@xmath6h@xmath5 : h can bind to the ground state pt pentamer on three different bridge and two different top sites . top site bonding is favorable in be : ( 5f ) is the lowest energy structure . however the homo - lumo gaps of the bridge site bonded structures are higher than those of top site bonded structures . all pt@xmath6h isomers in table [ table3 ] are in the quartet states . for the bonding of 2h , we have identified three bridge - bridge , four bridge - top , and three top - top locally stable configurations . in each of these 10 optimization processes , we have started from different h locations on the lowest energy structure ( 5 - 1 ) of the pt@xmath6 cluster . however , in three of them ( 5 - 1 ) configuration of the 5 pt atoms changed into some other topologies at the end of the relaxation : the ( 5i ) and ( 5p ) geometries are based on trigonal bipyramid and the ( 5o ) resembles to rhombus pyramid . in agreement with the general trend , the most stable pt@xmath6h@xmath5 isomer is the ( 5p ) top - top structure with the highest be and the highest homo - lumo gap . the h - h distance in ( 5p ) is 1.91 @xmath12 and the 2h be is 5.59 ev . thus , the h absorbtion is still dissociative . while the ground state pt@xmath6h@xmath5 cluster ( 5p ) and three other isomers ( ( 5i ) , ( 5k ) , and ( 5 m ) ) are in quintet states , the other six isomers are in triplet states . similar to the previous clusters , generally bridge - top configurations have higher bes than bridge - bridge structures . figure [ pth ] shows the plot of the be of one and two h atoms on the lowest energy isomers of the pt clusters . the h be is large for most clusters and in particular for clusters with 1 and 4 pt atoms . this is similar when 2h bes are considered . the clusters with 1 , and 4 pt atoms have larger bes for 2h compared to their neighboring sizes . we have further studied the stability of these clusters from the fragmentation channels in which a pt atom , or a pt@xmath5 , or pth molecule is one of the fragments . the fragmentation energies of all of these channels are listed in table [ table4 ] . it is noted that the fragmentation energies are the largest for pt@xmath4h@xmath5 in pt and pth fragmentation channels . therefore , we expect it to be the most stable species . for the pt@xmath5 fragmentation , pt@xmath6h@xmath5 has the highest fragmentation energy . on the other hand , pt@xmath5h@xmath5 and pt@xmath7h@xmath5 have the lowest fragmentation energies for this channel . in this section we discuss the change in the magnetic moment of the hydrogenated platinum clusters when successive h atoms are added to the bare pt clusters . the magnetic moments and the majority and minority spin lumo energies of the lowest energy structures for pt@xmath0h@xmath1 ( @xmath2 = 1 - 5 , @xmath3 = 0 - 2 ) clusters are presented in table [ table5 ] . it can be seen in table [ table5 ] that the successive h addition to pt atom and pt dimer reduces the magnetic moment as in the case of h absorption in bulk pt . however , when the successive h additions to the pt trimer and pentamer are considered , it is observed that as the magnetic moments decrease in the first additions , they increase in the second ones . for the tetramer , the magnetic moment increases in the first addition and decreases in the second . thus , the magnetic moments of certain small pt clusters exhibit an oscillatory change in the successive addition of h atoms . the results obtained in this study confirm the explanation of ashman et al . @xcite that this situation can be understood by looking at the lumo energy differences between the majority and minority spin electrons ( @xmath31 = minority spin lumo energy - majority spin lumo energy ) . when the minority spin lumo energy is much less than the majority spin lumo energy ( when @xmath31 is highly negative ) , the additional electron goes to the spin state with lowest lumo , and reduces the magnetic moment to decrease the cluster s total energy . this is what happens when successive h atoms are added to pt atom and dimer . however , if lumo of minority is slightly less than lumo of majority ( if @xmath31 is greater than a certain value which is around -0.227 ev for pt - h clusters ) , the additional electron may go to majority manifold since the exchange coupling could lead to a rearrangement of the manifolds . this explains the increases in the magnetic moments when h atoms are added to the pt@xmath7h and pt@xmath4 clusters . it should be noted here that nearly a half of the pt@xmath7h@xmath5 isomers in table [ table3 ] are in the singlet , and the others are in the triplet states . similarly , one of the pt@xmath4h isomer is in the doublet and the other is in the quartet states . for pt@xmath6h , the @xmath31 is even positive and therefore we expect that h addition will most probably increase the magnetic moment . in fact , this expectation is confirmed in our results since the lowest energy isomer of the pt@xmath6h@xmath5 is found to be in the quintet state . in summary , we have presented results of studies on the interactions in the bare and hydrogenated platinum clusters . we find that h interacts strongly with pt clusters . the interaction of h@xmath5 molecule with any of the pt clusters studied in the present work is likely to be dissociative . h atoms can bond to pt clusters either on a bridge site or on a top site . we do not find any 3-fold bonding of h to pt clusters . in general , a top site bonding is more favorable than a bridge site bonding . therefore , for the bonding of two h atoms , top - top configurations are more stable than bridge - top and bridge - bridge configurations . among all the clusters we have investigated , we find that pt@xmath4h@xmath5 is the best candidate to be the most stable one . we do not agree with a previous claim that 3d geometries of pt tetramer and pentamer are unfavored . we have identified a distorted tetrahedron and a bridge site capped tetrahedron as the lowest energy structures of pt@xmath4 and pt@xmath6 , respectively . we have also shown that the successive addition of h atoms to pt clusters decreases the magnetic moments of the pt atom and pt dimer , whereas it leads to an oscillatory change in the magnetic moment of pt@xmath7 - pt@xmath6 clusters . this work is financially supported by the scientific and technological research council of turkey , grant no . tbag - hd/38 ( 105t051 ) . i would also like to thank to dr . ersen mete for discussion and comments as well as his valuable computational supports . .[table1]comparison of the calculated and experiment properties of h@xmath5 , pt@xmath5 , and pth . experimental values for the bond lengths , vibrational frequencies and binding energies of h@xmath5 , pt@xmath5 , and pth are from refs . @xcite , refs . @xcite , and refs . @xcite , respectively . [ cols="<,^,^,^,^,^,^,^,^,^ " , ]

we perform density functional theory calculations using gaussian atomic - orbital methods within the generalized gradient approximation for the exchange and correlation to study the interactions in the bare and hydrogenated platinum clusters . the minimum - energy structures , binding energies , relative stabilities , vibrational frequencies and the highest occupied and lowest unoccupied molecular - orbital gaps of pt@xmath0h@xmath1 ( @xmath2=1 - 5 , @xmath3=0 - 2 ) clusters are calculated and compared with previously studied pure platinum and hydrogenated platinum clusters . we investigate any magic behavior in hydrogenated platinum clusters and find that pt@xmath4h@xmath5 is more stable than its neighboring sizes . our results do not agree with a previous conclusion that 3d geometries of pt tetramer and pentamer are unfavored . on the contrary , the lowest energy structure of pt@xmath4 is found to be a distorted tetrahedron and that of pt@xmath6 is found to be a bridge site capped tetrahedron which is a new global minimum for pt@xmath6 cluster . the successive addition of h atoms to pt@xmath0 clusters leads to an oscillatory change in the magnetic moment of pt@xmath7 - pt@xmath6 clusters .

recently , ishida et al . have proposed the covariant @xmath3-classification scheme of hadrons@xcite , which gives covariant quark representations for composite hadrons with definite lorentz and chiral transformation properties . the @xmath3-classification scheme has a unitary symmetry in the hadron rest frame , called `` static @xmath6 symmetry''@xcite , embedded in the covariant @xmath3-representation space , of which tensors can be decomposed into representations of @xmath7 , @xmath8 being the pseudounitary homogeneous lorentz group for dirac spinors . the static @xmath6 contains the dirac spin group @xmath9 in its subgroups and @xmath9 contains two @xmath10 subgroups as @xmath11 , where @xmath12 and @xmath13 are the spin groups concerning the boosting and intrinsic - spin rotation , respectively , of constituent quarks , being connected with decomposition of dirac @xmath14-matrices , @xmath15 . thus the static @xmath6 symmetry includes the chiral @xmath16 symmetry as @xmath17 . this implies that the @xmath3-classification scheme is able to incorporate effectively the effects of chiral symmetry and its spontaneous breaking , essential for understanding of properties of the low - lying hadrons , into what is called a constituent quark model . an essential feature of the @xmath3-classification scheme is to have the static @xmath9 symmetry for light @xmath18 quarks confined inside hadrons . the degree of freedom on the @xmath19-spin , being indispensable for covariant description of spin @xmath20 particles , offers a basis to define the rule of chiral transformation for quark - composite hadrons . since we have the @xmath19-spin degree of freedom , which is discriminated by the eigenvalues of @xmath21 , @xmath22 , in addition to the ordinary @xmath23-spin , the ground states of light - quark @xmath24 mesons are composed of eight @xmath25 multiplets with respective @xmath26 quantum numbers , two pseudoscalars @xmath27 , two scalars @xmath28 , two vectors @xmath29 , and two axial - vectors @xmath30 ( n and e denoting `` normal '' and `` extra '' ) , where each n ( e ) even - parity multiplet is the chiral partner of the corresponding n ( e ) odd - parity multiplet and they form linear representations of the chiral symmetry . since the eigenstates only with the @xmath21-eigenvalue @xmath31 are taken for heavy quarks , we have for heavy - light meson systems two heavy - spin multiplets , @xmath32 and @xmath33 , which are the chiral partner each other , while for heavy - heavy meson systems we have the same @xmath32-spin multiplets as in the conventional nonrelativistic quark model . we try to assign some of the observed mesons to the predicted @xmath24 multiplets , resorting to their @xmath26 quantum numbers and masses . the observed meson data are taken from the particle data group 2004 edition@xcite , except for the following mesons : * @xmath34 . there are several experimental indications of the existence of the @xmath34 reported by the obelix@xcite and lass@xcite collaborations , and others . particle listings and the `` note on the @xmath35 '' in @xcite . ] * @xmath36 . the existence of @xmath36 is claimed in the analysis of the @xmath37 cross section by the snd collaboration@xcite . we accept the existence of these vector mesons as true@xcite . the resulting assignments , though some of them are ambiguous , are shown in table 1 . here we make some comments on these assignments . 1 . the light scalar mesons @xmath38 are assined to the @xmath39-nonet as a chiral partner of the @xmath40-meson @xmath41-nonet . the low - mass vector mesons @xmath42 are assined to the @xmath43-nonet as a chiral partner of the @xmath44-nonet @xmath45 @xmath46 @xmath47 . the axial - vector mesons @xmath48 are assined to the @xmath49-nonet as a chiral partner of the @xmath50-meson @xmath51-nonet . the recent observed mesons @xmath52 are assined to the @xmath33 multiplet as a chiral partner of the @xmath32 multiplet @xmath53@xcite . these newly observed mesons , together with the @xmath23-meson nonet , are the best candidates for the hadronic states with @xmath54 whose existence is expected in the @xmath3 scheme . it is noted that the normal ( n ) and extra ( e ) states with the same @xmath26 generally mix together due to the spontaneous as well as explicit breaking of chiral symmetry and some other mechanism . in the @xmath3-classification scheme heavy - light @xmath55 meson fields , aside from the internal space - time wave functions , are given by @xmath56 with @xmath57 , where @xmath58 represent the local fields for the @xmath59 mesons with @xmath60 , @xmath61 ( @xmath62 ) is the four - momentum ( mass ) of meson fields , and flavor indices are omitted for simplicity . to describe the light - quark pseudoscalar and scalar mesons together with the spontaneous breaking of chiral symmetry , we adopt the @xmath63 linear sigma model , introducing the chiral field @xmath64 defined by @xmath65 with @xmath66 where @xmath67 and @xmath68 ( @xmath69 ) are the scalar ( pseudoscalar ) fields . we now write a chiral - symmetric effective lagrangian which gives the chiral mass splitting between the heavy - light @xmath70 and @xmath4 multiplets through the spontaneous breaking of chiral symmetry@xcite : @xmath71 \label{eq : lnd},\ ] ] where @xmath72 is the dimensionless coupling constant of yukawa interaction in the nonderivative form and the trace is taken over the spinor and flavor indices . when the chiral symmetry is spontaneously broken , @xmath73 has the vacuum expectation value , @xmath74 , where @xmath75 and @xmath76 are related to the pion and kaon decay constants by @xmath77 then the mass splitting between the two multiplets is induced and the mass differences @xmath78 are given by @xmath79 and @xmath80 , which leads to the relation @xmath81 from this relation with the experimental values@xcite , @xmath82 and @xmath83 , we obtain @xmath84 and consequently predict the masses @xmath85 for the @xmath4 @xmath5 mesons , using the measured mass values@xcite of the @xmath86 and @xmath87 mesons . we hereafter refer to these predicted mesons , respectively , as `` @xmath88 '' and `` @xmath89 '' . we could ask experimental data whether there was some evidence for the existence of @xmath88 and @xmath89 . here we check on the recent published data on the @xmath90 and @xmath91 mass distributions in @xmath92 , @xmath93 decays from the belle@xcite and babar@xcite collaborations . * * @xmath90 mass spectrum * : in the belle data mass distribution in figure 3 of @xcite . ] we see an excess of events , a single data point of 20 mev bin , at a mass of 2.13 gev near the predicted mass of the @xmath88 , and so might regard it as an indication of that resonance , though it is natural to think that its data point should be within a statistical error . on the other hand , it would seem to us that the babar data mass distribution in figure 3 ( right ) of @xcite . ] around a mass of 2.1 gev show a typical pattern of interference between two or more resonances . * * @xmath94 mass spectrum * : in the belle data mass distribution in figure 9 of @xcite . ] there is also an excess of events , a single data point of 10 mev bin , at a mass of 2.255 gev near the predicted mass of the @xmath89 , and so it might be an indication of the resonance . although it is not clear , the babar data mass distribution in figure 3 ( left ) of @xcite . ] around a mass of 2.26 gev might show a typical pattern of interference . if the @xmath88 and @xmath89 resonances really exist , their widths have to be narrow , @xmath95 mev , judging from the data mentioned above . the dominant decay modes of these resonances are @xmath90 and @xmath91 , respectively , and thus we examine their single pion transitions . to estimate the widths of @xmath96 and @xmath97 decays , together with @xmath98 , we set up , in addition to the nonderivative interaction @xmath99 in eq . ( [ eq : lnd ] ) , the chiral - invariant effective interaction with the derivative form : @xmath100 \label{eq : ld},\ ] ] where @xmath101 and @xmath102 is the coupling constant with a dimension of @xmath103 , which is related to the axial coupling constant @xmath104 by @xmath105 . the pionic decay widths of the @xmath106 , @xmath107 , and @xmath108 states are derived from @xmath99 and @xmath109 , and the decay widths of @xmath107 and @xmath108 are identical . using the measured value of @xmath110 = 65 \ \mathrm{kev}$]@xcite and @xmath111 from @xmath112 , the coupling @xmath102 is fixed to 3.96 gev@xmath113 ( corresponding to @xmath114 ) , and then we obtain @xmath115 = \gamma [ d_{1}(2250 ) \rightarrow d^ { * } + \pi ] \approx 30 \ \mathrm{mev}.\ ] ] this value is consistent with the speculated widths of the @xmath88 and @xmath89 . we have presented the possible assignments for some of the observed mesons in the covariant @xmath3-classification scheme . it is necessary and important to examine the strong- and radiative - decay@xcite properties of the assigned states in order to establish their assignments . on the basis of these assignments we have also predicted the existence of the low - mass @xmath4 @xmath5 mesons with narrow width , which might have been seen in the recent published data on the @xmath90 and @xmath91 mass distributions from the belle and babar collaborations .

we investigate the chiral mass splitting of parity - doubled @xmath0 states for @xmath1 and @xmath2 meson systems in the @xmath3-classification scheme of hadrons , using the linear sigma model to describe the light - quark pseudoscalar and scalar mesons together with the spontaneous breaking of chiral symmetry , and consequently predict the masses of as - yet - unobserved @xmath4 @xmath5 mesons . we also mention some indications of their existence in the recent published data from the belle and babar collaborations . address = department of engineering science , junior college funabashi campus , nihon university , funabashi 274 - 8501 , japan address = department of engineering science , junior college funabashi campus , nihon university , funabashi 274 - 8501 , japan address = research institute of science and technology , college of science and technology , nihon university , tokyo 101 - 8308 , japan

The attorney for the teen charged in a Pennsylvania school stabbing rampage says the boy's family is not dysfunctional - "They're like the Brady Bunch." A day after a Pennsylvania student rampaged through his high school's hallways, stabbing wildly with two kitchen knives, hints of a motive remain elusive. Who is 16-year-old Alex Hribal, and what troubled him? Hribal was charged as an adult and faces four counts of attempted homicide and 21 counts of aggravated assault related to the 21 people he wounded. Some classmates at Franklin Regional Senior High School describe him as having few friends and being quiet, but also as a "really nice kid." "This is not a dysfunctional family," Hribal's lawyer, Patrick Thomassey, told CNN Thursday. "They're like the Brady Bunch. These parents are active with their two sons, and we're trying to figure out what happened." Murrysville Police Chief Tom Seefeld said investigators haven't yet made sense of the mass stabbing, either. "We believe, through the investigation, that this was random," he told CNN's "New Day." "We don't have anybody that was targeted, as far as we know at this point." The man who stopped the attacker by tacking him is a 60-year-old assistant principal. The administrator, Samuel King, and Hribal are neighbors, living only two houses from each other on the same street. So what led to them coming face to face, not on Sunflower Court, but in the chaos of a nightmarish attack? One thread that police are looking into is the possibility that there was a phone threat the night before, Seefeld said. But there was no immediate evidence found to confirm that such a call was made. The FBI has seized electronics belonging to Hribal, including a computer and cell phone, and will analyze them for any clues, the police chief said. 'Happened so fast' A doctor who treated six of the victims, primarily teens, said at first they didn't know they had been stabbed. "They just felt pain and noticed they were bleeding," said Dr. Timothy VanFleet, chief of emergency medicine at the University of Pittsburgh Medical Center. "Almost all of them said they didn't see anyone coming at them. It apparently was a crowded hallway and they were going about their business, and then just felt pain and started bleeding." One of the victims, Brett Hurt, told reporters Thursday that all he noticed was that a "kid" ran by and hit him on the back. A friend who was with him started screaming. "I didn't really know what was going on at the time," Hurt said. "It was all kind of a blur." As the attacker continued to charge down the crowded hallway, Hurt began to wonder if he was going to survive or die. Speaking from the hospital, Hurt said he suffered a stab wound in the back and a bruised lung. He expected to be released as early as Thursday. He reflected on whether Hribal would have chosen the path he did if he had more friends or a better support group. "I feel he has some issues he has to work out," Hurt said. Hurt's mother said everyone must ask themselves what alienated Hrabi so much that he committed an act like this. Another student at the school who witnessed the attack said the suspect didn't utter a word. "He was very quiet. He just was kind of doing it," Mia Meixner said. "And he had this, like, look on his face that he was just crazy and he was just running around, just stabbing whoever was in his way." Hribal wounded 20 students and a security officer before the assistant principal tackled him. A soundtrack of chaos Murrysville, with a population of about 20,000, is a quiet middle-class enclave roughly 20 miles east of Pittsburgh on U.S. Route 22. "We are so small compared to other communities," said Paula Fisher, who left Pittsburgh to move to Murrysvillealmost 20 years ago. "I came out here purposely to raise my children in a school district that we felt was safe as well as academically sound." Recordings of emergency calls released after the attack provide a soundtrack of sorts to the terror and chaos that played out inside the school. "I don't know what I got going down at school here, but I need some units here ASAP," one officer can be heard saying. Minutes later, in another call, another official breathlessly details casualties: "About 14 patients right now." Then another call for help. "Be advised inside the school we have multiple stab victims," one of the officers said. "So bring in EMS from wherever you can get them." Hoodies as tourniquets Students standing outside the school heard its fire alarm go off. That probably helped get more people out of the building during an evacuation order, Seefeld said. Students were running everywhere, and there was "chaos and panic," he said. Student Matt DeCesare saw two students come out of the school covered in blood. Then he saw teachers running into the building and pulling "a couple of more students out," he said. They had also been stabbed. To stanch the bleeding, the teachers asked the students for their hoodies. "We all took our hoodies off and handed them to the teachers to use as tourniquets to stop the bleeding," DeCesare said. On Thursday, Seefeld praised faculty members for their reaction. Police meet with them often, he said, and the school has plans in place to react to violence. "It all came together," he said. Investigators have finished collecting evidence in the school, he said. "The crime scene was quite bloody." About 50 officers from the FBI and local law enforcement agencies worked on the case, he said. 'I'm not sure he knows what he did' Hribal couldn't seem more normal, the way his lawyer describes him. "I heard these rumors about being bullied. I don't believe that's true," Thomassey said. "I'm sure that at a certain point, we'll find out what caused this. Maybe there is something that was going on at school that I'm not aware of yet or his parents aren't aware of yet." The young man also did not seem to embody the cliche of digitally connected youth. According to Dan Stevens, the county deputy emergency management coordinator, Hribal had a very minor Facebook presence and didn't have much experience on Twitter. Thomassey said he would file a motion to move the case to juvenile court. And he wants a psychiatrist to evaluate his client. "I'm not sure he knows what he did, quite frankly," Thomassey said, adding that Hribal feels remorse. "He's scared. He's a young kid." Westmoreland County District Attorney John Peck argued against bail, saying that there could be no conditions that would protect the community and that Hribal made "statements when subdued by officials that he wanted to die." Hribal is being held without bail at the Westmoreland County juvenile detention center. He was treated for injuries to his hands, police said. One victim 'eviscerated' The students who were hurt range in age from 14 to 17, emergency coordinator Stevens said. The injuries were stabbing-related, such as lacerations or punctures. Four victims were in critical condition Wednesday, including one who was "eviscerated" and may not survive, Peck said. The school said that half a dozen prayer vigils were held overnight, and counseling services are being arranged for students. ||||| MONROEVILLE, Pa. (AP) — One of the victims of a knife attack at a high school near Pittsburgh says he was terrified he might die when he realized he had been stabbed in the back. (Click Prev or Next to continue viewing images.) ADVERTISEMENT (Click Prev or Next to continue viewing images.) Emergency responders gather in the parking lot of the high school on the campus of the Franklin Regional School District where several people were stabbed at Franklin Regional High School on Wednesday,... (Associated Press) Sixteen-year-old Brett Hurt appeared at a hospital news conference Thursday, a day after authorities say fellow student Alex Hribal either stabbed or slashed 21 students and a security guard at Franklin Regional High School in Murrysville. "What was going through my mind?" Hurt said. "Will I survive or will I die." Hurt says he doesn't think he could return to school anytime soon. He says, "I might freeze." Hurt says the whole attack was a blur. He says he met the suspect a couple of times but didn't really know him. Hribal is being held on charges including four counts of attempted homicide. ||||| Alex Hribal, the 16-year-old student who police say stabbed 22 people at his Pennsylvania high school Wednesday, is “confused, scared and depressed,” his attorney told ABC News in an exclusive interview. “I think he understands what he did,” attorney Patrick Thomassey said in an interview with “Good Morning America.” “I don’t think he at this point understands the gravity of what he did. I don’t think he realizes how severely injured some of these people are. And, hopefully, there’s no death involved in any of these. We’re praying that everybody is all right.” Knife-Wielding Pa. Student Wounds at Least 22 in Stabbing Spree High School Stabbing Shocks Community Thomassey said he’s unaware of any signs of Hribal’s being bullied, adding that the teen’s parents are shocked and horrified. “They could not have predicted that this was going to happen,” he said. “They don’t understand how this occurred.” The stabbing spree happened at Franklin Regional High School in Murrysville, a suburb located about 20 miles east of Pittsburgh. Morgan Ritchey, who said she had two classes with Hribal, described him as being “a little misunderstood.” “I just always felt like he had a different side to him that nobody knew and it was, like, hard to uncover,” said Ritchey. Hribal, a sophomore, used two 8-to-10 inch "kitchen-type" "straight" knives in the attack, which started shortly after 7 a.m., police said. Multiple Injuries in Stabbing Spree Murrysville Police Officer William “Buzz” Yakshe, a school resource officer, heard a disturbance in the hallway and joined a school security guard to go find out what was happening, according to a police affidavit. The guard and officer split up. The next time Yakshe saw the guard, he was leaning against a wall, bleeding from his stomach. Sam King, the school’s assistant principal, told police he saw Hribal stab the security guard. King tackled the teen and subdued him while Yakshe handcuffed him. King heard one of the victims say, “I’ve been stabbed,” he told police. Authorities charged Hribal as an adult with four counts of attempted criminal homicide, 21 counts of aggravated assault and one count of possession of weapons on school property. He was arraigned Wednesday and is being held without bail in a juvenile detention center in Westmoreland County. Murrysville Police Chief Thomas Seefeld said someone pulled a fire alarm during the attack, raising attention and getting students and teachers to evacuate. "When we got there we saw a hallway in chaos, as you can imagine," Seefeld said at a news conference. "There was a lot of evidence of blood on the floors and in the hallway, we had students running about, trying to get out of the area." Nate Moore, 15, was stabbed during the rampage and said he had to be treated with 15 stitches. "It was really fast. It felt like he hit me with a wet rag because I felt the blood splash on my face. It spurted up on my forehead," Moore told The Associated Press. Student Gracey Evans said heroes emerged during the attack. "My best friend, he stepped in front of me and in the meantime, he got stabbed in the back protecting me," she said. "You couldn't step a single place without pretty much stepping in blood." At least 22 people were injured after the stabbings at the start of the school day, Westmoreland County emergency management spokesman Dan Stevens said. The motive for the rampage is under investigation. Seefeld said officials were unaware of any warning signs from the suspect, a sophomore at the school. At least four people with injuries emergency management officials described as "serious" were flown to hospitals for treatment. Others were not actually stabbed, he said, and some of their injuries included cuts and scrapes. The Associated Press contributed to this report. ||||| He always seemed to be "the shy kid in the corner," a classmate said. Hours after a startling and savage attack Wednesday morning that left 21 students and a security guard wounded, that was the picture that began to emerge of 16-year-old Alex Hribal, a sophomore at Franklin Regional High School. Armed with two 8-inch knives, he is accused of stabbing and slashing his way through a crowded hallway in an assault that was labeled "bizarre" by both a prosecutor and his own lawyer. Interviews with nearly two dozen students Wednesday evening at various vigils organized by churches yielded precious little background about Alex, who was arraigned on charges of attempted homicide, aggravated assault and weapon possession. Four of his alleged victims remained in critical condition Wednesday night. Many students said they did not know Alex. Others, like sophomore Anissa Park, who knew Alex from elementary school but hadn't talked with him for some time, invariably used the words "shy" and "quiet" to describe him. Some said he was involved in athletics, including dek hockey, track and tennis, though the Pittsburgh Post-Gazette could not confirm those details Wednesday night. Another student who knew Alex, though he spoke on condition of anonymity, said he was stunned by the attack. "I know him pretty well," the boy said, adding that Alex's interests swung toward the usual for a teenage boy, including hockey and video games. "I've never seen any anger from him, ever. ... He never seemed like someone who would do anything violent. He never seems very upset or any of that." His parents could not be reached Wednesday, but Alex's lawyer, Patrick Thomassey, said he had spoken to them about an hour before his arraignment. "They did not foresee this coming. They expressed absolute horror," Mr. Thomassey said, adding that the family's thoughts were with the victims. Mr. Thomassey said the teenager was not a loner nor was he aware of any instances of bullying that would have provoked the attack. "He's scared," Mr. Thomassey said. "He's a young kid. He's 16, looking like he's 12. This is all still new to him." Mr. Thomassey said Alex is a B-plus student from a stable home, describing his family as "like Ozzie and Harriet." "They have dinner together every night," the attorney said. He would not provide details of his discussions with his client. "I'm not sure he knows what he did, quite frankly," Mr. Thomassey said. "Something happened here. There's an issue that maybe nobody knew about." Westmoreland County District Attorney John Peck said during the brief hearing that Alex made some statements after school officials tackled him that indicated he wanted to die. Dan McCool said his 16-year-old daughter, Trinity, was in the hallway as the attack unfolded. "They just know who he is. They don't know necessarily much about him. They just say he was kind of quiet and kept to himself," Mr. McCool said, adding that the terror of what had happened didn't hit him until he went to pick his daughter up at the school, where he was struck by the degree of order and efficiency. "Any time something happens I just try to remain calm. ... When I went down to the school to pick her up after she talked to the FBI, I was breaking up then." Franklin Regional school psychologists were not available Wednesday. Though she would not discuss the Franklin Regional case specifically, Mary Margaret Kerr, chair of administrative and policy studies and a professor of psychology in education and psychiatry at the University of Pittsburgh, said it can be difficult for schools to predict violent behavior in students. She said standard psychological tests haven't been successful in predicting targeted violence in schools, adding that many school attackers had no histories of mental disorders. Ms. Kerr, author of "Strategies for Addressing Behavioral Problems in the Classroom," referenced a report by the U. S. Secret Service and Department of Education on school shootings and school-based attacks dating to 1974. It found that school attacks are rarely impulsive acts, but typically are planned. "The study findings also revealed that there is no 'profile' of a school shooter; instead, the students who carried out the attacks differed from one another in numerous ways," according to a synopsis of the report on the Secret Service website. The study said, however, that most attackers had engaged in prior behavior that concerned at least one adult, and often several adults. Deborah Robinson, director of Pitt's school social worker, home and school visitor certificate program, said threat assessment is "a huge part of what it means to be a school social worker." Obvious signs of trouble could include poor attendance, poor hygiene and an inability or reluctance to connect with other students, though students who display those traits aren't necessarily bound for violence. Indeed, it can be that students who commit violent acts show no warning signs. "It's really unpredictable. You can have a lot of good resources and good things in place and violence can still happen," Ms. Robinson said. This story was written by Robert Zullo based on his reporting and that of staff writers Lexi Belculfine, Molly Born, Rich Lord, Liz Navratil and Mary Niederberger. ||||| PITTSBURGH (KDKA) — A teenage girl is being credited with helping one of the more seriously injured students in Wednesday’s stabbing rampage at Franklin Regional High School, but she says there other people who deserve credit for stepping up during the incident, like her best friend who stepped in front of her during the attack. “If my best friend wouldn’t have step in front of me, I probably would have been injured,” Franklin Regional student Gracey Evans said. “I probably would have been the one that was stabbed and not him. He took the knife for me.” Instead of screams and gunshots, 17-year-old Gracey remembers hearing the eerie and muffled moans of her classmates being stabbed. The person who was going through stabbing everybody, he was just completely silent; said not a word, just complete silence, like a serial killer,” said Gracey. Brett Hurt pushed Gracey out of the way, and then took a knife to the back. But she noticed another student whose wound appeared more serious and instinct kicked in. “Honestly, it was second nature,” Gracey said. “I just knew that it wasn’t right that he was sitting up and because his airway was getting blocked. So, I laid him down and I said I need to get pressure on this wound, so I got a bunch of paper towels that a friend gave me and I just kept pressure on it for about 10 minutes.” When paramedics arrived, she shifted her attention to Brett. “I held his hand the whole time,” Gracey said. “He wouldn’t let go of my hand, even when I was in the ambulance with him.” Gracey’s father is a former school board member. “I am very, very proud of her and everybody that was involved with this,” said Bill Evans, Gracey’s dad. “It’s humbling, it’s shocking.” The healing may already started, but the idea of a typical school day, that notion of normal is changed forever. “There will never be a normal. I know personally, I will never be able to walk down that hallway the same way because my best friend got stabbed in front of me,” said Gracey. “Gracey, she’s getting a lot of the attention, but there were many others she said, and thank everybody and bless you,” added Bill. RELATED LINKS: Tales Of Heroism Emerging From Franklin Regional High School Chaos (4/9/14) More Franklin Regional Stories More Reports by Kym Gable Join The Conversation On The KDKA Facebook Page Stay Up To Date, Follow KDKA On Twitter ||||| Student Josiah Wages, 16, speaks to the media following a stabbing spree at Franklin Regional Senior High School. (Photo: Vincent Pugliese, epa) Hours after a routine school day turned terrifying, students at Franklin Regional High School in Murrysville, Pa., described what they went through during the stabbing rampage that sent 20 people to hospitals today. Some had gone home to feel safe. Some had to be with friends to work through their emotions. As the horror began, students had just arrived for the first class. Some were still outside. Suddenly there was a commotion in the science wing. "At first we just thought it was a group of boys being immature and fighting," said sophomore Cameron Lazor, 16. "Then we saw the blood and realized it was something scary." "I saw a senior girl, and she was gushing blood down her arm." said Mia Meixler, 16, a sophomore. "I didn't think anyone saw her but me, so I tried to help her. I asked if she wanted to go to the nurse. But then all the kids started running and screaming down the hall. A teacher got to the girl and told me to run out." STORY: 'Shy' student held in mass stabbing at Pa. school MORE: Hero in mass stabbing shares hospital selfie Junior Nicole Damico, 16, was on the second floor of the school when the fire alarm went off. She and her friends thought it was a drill, so they slowly made their way downstairs, where they discovered something serious was going on. "We saw two kids down the hall, and it looked like they were play fighting," Nicole said. "I realized that one had a knife, so we sprinted out of the school. I saw one of my peers near the entrance of the school who had blood everywhere. He asked me for help. I just froze and ran out of the school. After that there was chaos." Meanwhile, the suspect began to chase sophomore Trinity McCool, 16, as she and a friend fled. "When he was chasing us, I saw his face — the look in his eyes. I was horrified," she said. Trinity and her friend made it out of the school unharmed, but Trinity said she was rattled by the event and went home. Parents and students embrace near Franklin Regional High School in Murrysville, Pa. (Photo: Sean Stipp, Tribune Review, via AP) "I'm still really just distraught and stressed and scared," she said. Senior Tanya Leeman, 17, had just gotten to school when the fire alarm went off and was still in her car. Her sister, a sophomore, was stuck inside until police let everyone leave four hours later. Because her sister did not have a phone with her, Tanya said, she was worried as she waited to hear that her sister was all right. "I was scared because we didn't know how many kids had gotten slashed or were missing," she said. "It was so unreal for all of us," Tanya said. "We weren't expecting something to happen at Franklin. We watched what happened in Connecticut on TV and thought that would never happen here." Nicole also made it safely out of the school. "Us kids have been through hell and back," she said. "It made me realize that anything could happen at anytime. It was just a regular day." Cameron said he was too shaken up to go home by himself. "I'm with some friends because we didn't want to be alone today," he said. "We can't believe it's real. The whole situation keeps playing over and over in our heads." Mia said, "I think we're all really scared, but it's also nice that our whole community is coming together." Nicole agreed. "Times like these, everyone just freaks out, and you don't know what to do," she said. "My peers have saved people's lives. It started off scary and chaotic, but it's amazing to hear how we've stuck together as a family." Psychiatrist and trauma specialist Steven Berkowitz said all the students, not just those physically injured, will wrestle with the experience — especially those who witnessed the bloody scene. "In these kinds of situations, the psychological casualties usually outnumber the physical casualties," he said. "It's not just the kids who were stabbed, but all the kids at the school." Berkowitz, an associate professor of psychiatry at the University of Pennsylvania's Perelman School of Medicine and the director of the Penn Center for Youth and Family Trauma Response and Recovery, said students and their parents may experience symptoms of psychological distress, including trouble sleeping, intrusive thoughts about the incident and mood swings. In some cases, students may have post-traumatic stress disorder, depression or turn to substance abuse, he said. The children may fear going to school, "and parents will be afraid to send them," Berkowitz said. He advises parents to get their kids back to school and their normal routine. "One of the most important things ... is to get back on the horse. It's really true," he said. "The more you let it interfere with your normal routines, the harder it will be in the long term." Students will have a wide range of responses depending on their physical and emotional connection to the stabbing and their natural emotional makeup. "There are individuals who are going to be more resilient than others," he said. "This is the kind of large-scale event where so many kids were exposed. They saw it. They heard it. They had friends who were hurt. Early interventions and monitoring are really, really key and crucial." Read or Share this story: http://usat.ly/1gMzZcu

– We're starting to get a clearer idea of yesterday's stabbing spree at Franklin Regional High School, and of Alex Hribal, the boy who police say did the stabbing, as students step forward to tell their stories. Here's what we know so far: Gracey Evans, who's been celebrated for potentially saving a victim's life by putting pressure on his wounds, tells KDKA that it's another victim, her best friend, who deserves praise, because he stepped in front of her as the attacker swung. "I probably would have been the one that was stabbed and not him. He took the knife for me." That best friend, 16-year-old Brett Hurt, spoke at a hospital press conference describing his terror at being stabbed in the back. He says he barely knew the attacker, and doesn't think he can go back to school anytime soon, the AP reports. "I might freeze," he says. Sophomore Trinity McCool tells USA Today that the stabber chased her, though he never actually managed to hurt her. "When he was chasing us, I saw this face—the look in his eyes. I was horrified." Alex's lawyer today gave interviews with CNN and ABC to tout his client's virtues. "He's a typical young kid. He's a B+ student. The family is Ozzie and Harriet," Patrick Thomassey says. "All the students liked him. He wasn't a loner. … So there's a reason for it—that's what I'm saying. And we have to get to the bottom of it." Right now, Alex is "confused, scared and depressed," Thomassey said. "I think he understands what he did. I don't think he at this point understands the gravity of what he did." "I've never seen any anger from him, ever," one classmate who says he knows Alex "pretty well" tells the Pittsburgh Post-Gazette. "He never seems very upset or any of that." He says the teen has fairly typical interests like video games and hockey. But another classmate described Alex as "a little misunderstood," adding, "I just always felt like he had a different side to him that nobody knew and it was, like, hard to uncover." Another described him as the "shy kid in the corner."

SECTION 1. SHORT TITLE. This Act may be cited as the ``Satellite Access to Local Stations Act''. SEC. 2. LIMITATIONS ON EXCLUSIVE RIGHTS; SECONDARY TRANSMISSIONS BY SATELLITE CARRIERS WITHIN LOCAL MARKETS. (a) In General.--Chapter 1 of title 17, United States Code, is amended by adding after section 121 the following new section: ``Sec. 122. Limitations on exclusive rights; secondary transmissions by satellite carriers within local markets ``(a) Secondary Transmissions of Television Broadcast Stations by Satellite Carriers.--A secondary transmission of a primary transmission of a television broadcast station into the station's local market shall be subject to statutory licensing under this section if-- ``(1) the secondary transmission is made by a satellite carrier to the public; ``(2) the secondary transmission is permissible under the rules, regulations, or authorizations of the Federal Communications Commission; and ``(3) the satellite carrier makes a direct or indirect charge for the secondary transmission to-- ``(A) each subscriber receiving the secondary transmission; or ``(B) a distributor that has contracted with the satellite carrier for direct or indirect delivery of the secondary transmission to the public. ``(b) Reporting Requirements.--A satellite carrier whose secondary transmissions are subject to statutory licensing under subsection (a) shall, on a semiannual basis, submit to the Register of Copyrights, in accordance with requirements that the Register shall prescribe by regulation, a statement of account, covering the preceding 6-month period, specifying-- ``(1) the names and locations of all television broadcast stations whose signals were secondarily transmitted within the local markets of those stations at any time during that period; and ``(2) the total number of, and addresses provided by, all subscribers receiving those secondary transmissions. ``(c) No Royalty Fee Required.--A satellite carrier whose secondary transmissions are subject to statutory licensing under subsection (a) shall have no royalty obligation for such secondary transmissions. ``(d) Noncompliance With Reporting Requirements.--Notwithstanding subsection (a), the willful or repeated secondary transmission to the public by a satellite carrier of a television broadcast station and embodying a performance or display of a work is actionable as an act of infringement under section 501, and is fully subject to the remedies provided under sections 502 through 506 and 509, if the satellite carrier has not submitted the statement of account required under subsection (b). ``(e) Definitions.--As used in this section-- ``(1) Distributor.--The term `distributor' means an entity that contracts to distribute secondary transmissions from a satellite carrier and, either as a single channel or in a package with other programming, provides the secondary transmission either directly to subscribers or indirectly through other program distribution entities. ``(2) Local market.--The `local market' of a television broadcast station has the meaning given that term in section 337(g) of the Communications Act of 1934. ``(3) Television broadcast station.--The term `television broadcast station' means an over-the-air, commercial, or noncommercial television broadcast station licensed by the Federal Communications Commission under subpart E of part 73 of title 47, Code of Federal Regulations. ``(4) Subscriber.--The term `subscriber' means a person or entity that receives a secondary transmission service by means of a secondary transmission from a satellite and pays a fee for the service, directly or indirectly, to the satellite carrier or to a distributor. ``(5) Other terms.--The terms `satellite carrier' and `secondary transmission' have the meanings given such terms under section 119(d).''. (b) Technical and Conforming Amendments.--The table of sections for chapter 1 of title 17, United States Code, is amended by adding after the item relating to section 121 the following: ``122. Limitations on exclusive rights; secondary transmissions by satellite carriers within local markets.''. SEC. 3. RETRANSMISSION CONSENT. Section 325(b) of the Communications Act of 1934 (47 U.S.C. 325(b)) is amended-- (1) by striking ``(b)(1)'' and all that follows through the end of paragraph (1) and inserting the following: ``(b)(1) No cable system or other multichannel video programming distributor shall retransmit the signal of a broadcasting station, or any part thereof, except-- ``(A) with the express authority of the station; ``(B) pursuant to section 614, in the case of a station electing, in accordance with this subsection, to assert the right to carriage under such section; or ``(C) pursuant to section 337, in the case of a station electing, in accordance with this subsection, to assert the right to carriage under such section.''; and (3) in paragraph (3), by adding at the end the following: ``(C) Within 45 days after the effective date of the Satellite Access to Local Stations Act, the Commission shall commence a rulemaking proceeding to revise the regulations governing the exercise by television broadcast stations of the right to grant retransmission consent under this subsection. Such regulations shall establish election time periods that correspond with those regulations adopted under subparagraph (B). The rulemaking shall be completed within 180 days after the effective date of the Satellite Access to Local Stations Act.''. SEC. 4. MUST-CARRY FOR SATELLITE CARRIERS RETRANSMITTING TELEVISION BROADCAST SIGNALS. Title III of the Communications Act of 1934 is amended by inserting after section 336 the following new section: ``SEC. 337. CARRIAGE OF LOCAL TELEVISION SIGNALS BY SATELLITE CARRIERS. ``(a) Carriage Obligations.--Each satellite carrier providing secondary transmissions of a television broadcast station to subscribers located within the local market of such station shall offer to carry all television broadcast stations located within that local market, subject to section 325(b), except that the carriage obligations of this section shall not apply to satellite carriers that do not retransmit the signals of broadcast television stations pursuant to the statutory license under section 122 of title 17, United States Code. Carriage of additional television broadcast stations within the local market shall be at the discretion of the satellite carrier, subject to section 325(b). ``(b) Duplication Not Required.--Notwithstanding subsection (a), a satellite carrier shall not be required to offer to carry the signal of any local television broadcast station that substantially duplicates the signal of another local television broadcast station which is secondarily transmitted by the satellite carrier, or to offer to carry the signals of more that one local television broadcast station affiliated with a particular broadcast network (as the term is defined by regulation). ``(c) Carriage of All Local Television Stations on Contiguous Channels.--All local television broadcast stations retransmitted by a satellite carrier to subscribers in the stations' local markets shall be made available to subscribers in their local markets on contiguous channels and in a nondiscriminatory manner on any navigational device, on-screen program guide, or menu. ``(d) Compensation for Carriage.--A satellite carrier shall not accept or request monetary payment or other valuable consideration in exchange either for carriage of local television broadcast stations in accordance with the requirements of this section or for channel positioning rights provided to such stations under this section, except that any such station may be required to bear the costs associated with delivering a good quality signal to the principal headend of the satellite carrier. No station carried in accordance with the requirements of this section shall be required to bear the costs of delivering a good quality signal to a location other than the principal headend of the satellite carrier. ``(e) Remedies.-- ``(1) Complaints by broadcast stations.--Whenever a local television broadcast station believes that a satellite carrier has failed to meet its obligations under this section, such station shall notify the carrier, in writing, of the alleged failure and identify its reasons for believing that the satellite carrier is obligated to offer to carry the signal of such station or has otherwise failed to comply with other requirements of this section. The satellite carrier shall, within 30 days after such written notification, respond in writing to such notification and either begin carrying the signal of such station in accordance with the terms requested or state its reasons for believing that it is not obligated to carry such signal or is in compliance with other requirements of this section. A local television broadcast station that is denied carriage in accordance with this section by a satellite carrier may obtain review of such denial by filing a complaint with the Commission. Such complaint shall allege the manner in which such satellite carrier has failed to meet its obligations and the basis for such allegations. A failure by a satellite carrier to carry a local television broadcast station within its local market if there has been a change in that station's local market, or to carry a local broadcast television station that is significantly viewed outside its local market due to technical limitations of that satellite carrier's existing facilities, shall not constitute a failure by the satellite carrier to comply with its obligations under this section. ``(2) Opportunity to respond.--The Commission shall afford such satellite carrier an opportunity to present data and arguments to establish that there has been no failure to meet its obligations under this section. ``(3) Remedial actions; dismissal.--Within 120 days after the date a complaint is filed, the Commission shall determine whether the satellite carrier has met its obligations under this section. If the Commission determines that the satellite carrier has failed to meet such obligations, the Commission shall order the satellite carrier, in the case of an obligation to carry a station, to begin carriage of the station and to continue such carriage for at least 12 months. If the Commission determines that the satellite carrier has fully met the requirements of this section, it shall dismiss the complaint. ``(f) Regulations by Commission.--Within 180 days after the effective date of this section, the Commission shall, following a rulemaking proceeding, issue regulations implementing the requirements imposed by this section. ``(g) Definitions.--As used in this section: ``(1) Television broadcast station.--The term `television broadcast station' means a full-power television broadcast station, and does not include a low-power or translator television broadcast station. ``(2) Local market.--The term `local market' means the designated market area in which a station is located and-- ``(A) for a commercial television broadcast station located in any of the 150 largest designated market areas, all commercial television broadcast stations licensed to a community within the same designated market area are within the same local market; ``(B) for a commercial television broadcast station that is located in a designated market area that is not one of the 150 largest, the local market includes all commercial television broadcast stations licensed to a community within the same designated market area, and may also include any station that is significantly viewed, as such term is defined in section 76.54 of the title 47, Code of Federal Regulations; and ``(C) for a noncommercial educational television broadcast station, the local market includes any station that is licensed to a community within the same designated market area as the noncommercial educational television broadcast station. ``(3) Designated market area.--The term `designated market area' means a designated market area, as determined by the Nielsen Media Research and published in the DMA Market and Demographic Report. ``(4) Principal headend of the satellite carrier.--The term `principal headend of the satellite carrier' means the reception point in the local market of a broadcast television station or in a market contiguous to the local market of a broadcast television station at which the satellite carrier initially receives the signal of the station for purposes of transmission of such signals to the facility which uplinks the signals to the carrier's satellites for secondary transmission to the satellite carrier's subscribers. ``(5) Secondary transmission.--The term `secondary transmission' has the meaning given that term in section 119(d) of title 17, United States Code.''. SEC. 5. EFFECTIVE DATE. This Act and the amendments made by this Act shall take effect on January 1, 1999.

Satellite Access to Local Stations Act - Amends Federal copyright law to cite circumstances under which the secondary transmission by a satellite carrier of a primary transmission of a television broadcast station into the station's local market shall be subject to statutory licensing. Sets forth reporting requirements for a satellite carrier whose secondary transmissions are subject to such licensing requirements. Precludes any royalty obligation for such secondary transmissions. States that noncompliance with such reporting requirements by a satellite carrier of a television broadcast station is actionable as an act of infringement and fully subject to copyright remedies. Amends the Communications Act of 1934 regarding the retransmission of broadcasting station signals. Prohibits cable systems and other multichannel video programming distributors from retransmitting a broadcasting station's signal without the station's express consent. Directs the Federal Communications Commission to commence a rulemaking proceeding to revise regulations governing the exercise by television broadcast stations of the right to grant retransmission consent. Prescribes requirements for the carriage of local television signals by satellite carriers, including: (1) carriage obligations; (2) carriage of all local television stations on contiguous channels and in a nondiscriminatory manner on any navigational device, on-screen guide, or menu; (3) compensation for carriage; and (4) remedies for failure to meet obligations.

a massive black hole ( mbh ) of mass @xmath10 dominates the dynamics of stars within its radius of influence @xmath11 , where @xmath5 is the typical star velocity dispersion at @xmath12 and values quoted correspond to the milky way center @xcite . the steady - state distribution function ( df ) of such stars , first derived ( for simple , discrete stellar mass functions , mfs ) by bahcall and wolf ( 1976 , 1977 ; henceforth bw76,77 ) is useful in the study of galactic centers and possibly globular clusters . in the simple case where all stars have equal mass , bw76 showed that an @xmath13 density cusp forms ; a somewhat flatter cusp was subsequently identified around sga * @xcite . significant mass segregation is expected for realistic mfs ( * ? ? ? * ; * ? ? ? * ; * ? ? ? * and references therein ) , as dynamical friction slows heavy stars that sink towards the mbh while light stars are pushed outwards . this effect is essential in modeling various physical processes , such as tidal disruption @xcite and gravitational wave emission @xcite , and may be used for example to test if intermediate - mass black holes exist in globular clusters @xcite . recently , ( * ? ? ? * henceforth ah09 ) showed strong mass segregation in the limit of a strongly bimodal mf when the mass ratio is large and massive stars are rare . in spite of extensive numerical studies of mass segregation around a mbh ( ah09 and references therein ) , analytical modeling ( bw77 ) is limited to simple , discrete , and extreme mfs where the most massive species constitutes more than half of the star population . most results are limited to few stellar species and to a narrow mass range . in this _ letter _ we analytically study the steady - state single - star df @xmath14 within @xmath15 , for an arbitrary , continuous mf . we confirm our results numerically for a wide range of mfs . following bw76,77 , we assume ( i ) spherical spatial symmetry ; ( ii ) isotropic velocities ; ( iii ) keplerian orbits ; ( iv ) binaries are negligible ; ( v ) small angle , uncorrelated , local scatterings ; ( vi ) loss cone effects can be neglected ; ( vii ) isothermal distribution of unbound stars with temperature @xmath16 ; ( viii ) stars are destroyed when their specific energy drops below a threshold @xmath17 , with @xmath4 the energy . consider the case where all stars have mass @xmath18 . the dimensionless diffusion rate of stars through @xmath19 is ( bw76 ) @xmath20^{3/2}}\,dx ' = { \mbox{const}}{\mbox { .}}\ ] ] the boundary conditions are @xmath21 and @xmath22 . ( [ eq : bw_integral ] ) with these boundary conditions uniquely determines @xmath14 and @xmath23 as shown below . the spatial number density of stars is given by ( bw76 ) @xmath24 eq . ( [ eq : bw_integral ] ) describes the balance between diffusion towards the mbh and replenishment by new stars . bw76 found that @xmath23 is essentially determined by the diffusion rate at a bottleneck near @xmath25 , where the replenishment rate diminishes . as @xmath26 is typically small , one can approximately solve eq . ( [ eq : bw_integral ] ) by setting @xmath27 . we convert eq . ( [ eq : bw_integral ] ) to an ordinary differential equation ( ode ) by repeated operations of differentiation with respect to @xmath19 and isolation of integral terms . this yields a nonlinear , fourth - order ode for @xmath14 , @xmath28 here we defined the local power - law index of @xmath14 , @xmath29 , the local power - law index of @xmath30 , @xmath31 , and the operators @xmath32 \nonumber { \mbox { , } } \end{aligned}\ ] ] where @xmath33 . the boundary conditions at @xmath34 fix @xmath14 and @xmath35 there , so the non - exponential solution @xmath36 is completely determined for given @xmath23 . a unique value of @xmath23 guarantees that @xmath14 vanishes ( for the first time ) at @xmath25 , proving the uniqueness of the steady - state solution ( an `` exercise left for the reader '' by bw76 ) . for a power - law df @xmath37 , eq . ( [ eq : desingle ] ) becomes @xmath38 this compactly reproduces the bw76 results : although a finite , energy - independent flow requires @xmath39 ( * ? ? ? * implying a flow of stars away from the mbh , see bw76 ) , a steady - state with @xmath40 is closer to the actual df because @xmath23 is negligibly small . note that the power - law assumption becomes inconsistent at high energies , where @xmath41 is large . henceforth we assume @xmath27 , justified for single mass stars if @xmath42 . an exponential df with @xmath43 solves eq . ( [ eq : desingle ] ) , but does not satisfy the boundary conditions . for @xmath44 , eq . ( [ eq : desingle ] ) becomes a third order nonlinear ode , @xmath45 with general solution of the form @xmath46 with @xmath47 constants . useful results can be deduced directly from eqs . ( [ eq : odef0 ] ) and ( [ eq : solgeneral ] ) , without determining the analytic properties of @xmath48 . when @xmath8 is much smaller ( larger ) than @xmath49 , eq . ( [ eq : odef0 ] ) becomes approximately @xmath50 ( @xmath51 ) , which corresponds to taking @xmath48 ( taking @xmath52 ) to zero in eq . ( [ eq : solgeneral ] ) . in this case @xmath53 $ ] is either nearly constant , or ( super- ) exponential in @xmath19 . in order to maintain reasonable stellar densities , there must be an approximate balance between the two terms , implying that @xmath54 far from the boundaries . note that for @xmath55 , the six terms of @xmath56 and @xmath57 in eq . ( [ eq : abc_defs ] ) precisely cancel in pairs . for small @xmath19 , where @xmath58 , eq . ( [ eq : odef0 ] ) becomes @xmath50 ; this corresponds to eq . ( [ eq : solgeneral ] ) with @xmath59 , and @xmath60 according to the boundary conditions at @xmath34 . at intermediate energies where approximately @xmath61 , eq . ( [ eq : desingle ] ) becomes @xmath62 , with all other terms smaller by factors @xmath63 ( @xmath64 ) for @xmath65 ( @xmath66 ) , so @xmath67 . at high energies near the disruption energy , @xmath68 is large and negative , eq . ( [ eq : odef0 ] ) becomes @xmath69 and so @xmath70 ; the boundary condition at @xmath25 then yields @xmath71 with @xmath72 . smoothly combining these approximate solutions yields an approximation for the equal mass case , @xmath73^n \exp \left [ \frac{3nx}{x_{max } } \right . \\ & { \!\!\!\!}\left . + 2n\sqrt{3 } \arctan\left ( \frac{1}{\sqrt{3 } } + \sqrt{\frac{4x}{3x_{max } } } \right ) \right ] \end{array } & \mbox{if $ x > x_{ta}$ , } \end{array } \right.\ ] ] with constants @xmath74 and @xmath75 determined for example by continuity of @xmath14 , @xmath76 and its first derivative evaluated at the turn - around energy @xmath77 . the results depend weakly on @xmath78 ; it is natural to fix @xmath79 . the previous paragraph suggests that @xmath80 as @xmath25 increases . numerically solving eq . ( [ eq : bw_integral ] ) yields @xmath81 , where the correction factor @xmath82 approaches unity as @xmath25 becomes large , _ @xmath83 and @xmath84 . it also depends weakly on the energy range used to measure @xmath8 ( here @xmath85 , henceforth ) . figure [ fig : approx_single ] illustrates the approximation . consider stars with variable mass @xmath18 in some range @xmath86 . we generalize the discrete , multiple - mass version of eq . ( [ eq : bw_integral ] ) ( bw77 ) to the continuum limit , @xmath87^{-3/2 } \\ & & \times \left[m f({x},m){\partial}_{{x } ' } f({x}',m ' ) - m ' { \partial}_{{x}}f({x},m)f({x}',m ' ) \right ] { \mbox { , } } \nonumber\end{aligned}\ ] ] where @xmath14 is now the df in @xmath88 phase space . assuming unbound stars with mf @xmath0 , @xmath89 . the density @xmath90 is related to @xmath91 as in eq . ( [ eq : spatial_density ] ) , such that @xmath92 . consider the negligible flow limit @xmath93 , which holds if the mf is not strongly dominated by light stars ( ah09 ) , as shown in [ sec : non_negligible_flow ] . dividing eq . ( [ eq : bw_masses ] ) by @xmath94 and differentiating with respect to @xmath18 we find @xmath95=0 $ ] , implying that @xmath14 must have the functional form @xmath96 with @xmath97 . ( [ eq : fm_form ] ) implies that the local power - law index of @xmath14 , @xmath98 , is linear in @xmath18 for fixed @xmath99 . this result , valid for negligible @xmath23 , generalizes the bw77 result @xmath100 to a continuous mf . setting @xmath27 in eq . ( [ eq : bw_masses ] ) , using eq . ( [ eq : fm_form ] ) , and repeatedly differentiating with respect to @xmath99 and isolating integral terms , yields an ode which , for @xmath44 , becomes @xmath101 here , @xmath8 , @xmath56 and @xmath57 are functionals of @xmath102 and @xmath99 , defined as in the equal mass case ( _ e.g. , _ eq . ( [ eq : abc_defs ] ) ) , and we defined @xmath103 with @xmath104 averaging . the full distribution may be found by solving eq . ( [ eq : ode_masses ] ) for @xmath105 under the boundary conditions @xmath106 and @xmath107 as @xmath108 . note that @xmath109 and @xmath110 . if the mass range is sufficiently narrow or @xmath1 is sufficiently dominated by high masses such that @xmath111 , we recover the equal mass case eq . ( [ eq : odef0 ] ) for the most massive stars . the full distribution then becomes @xmath112 with @xmath113 the df of equal - mass stars ( figure [ fig : approx_single ] ) . in the general case we may proceed as in [ sec : equalmassstars ] : @xmath14 will be constant , vanish or diverge unless the two terms in eq . ( [ eq : ode_masses ] ) are approximately balanced , _ i.e. , _ @xmath114 . if @xmath115 depends only weakly on @xmath99 , this implies a power - law df , @xmath116 . thus , stars with mass equal to the weight - averaged mass @xmath6 tend to have a @xmath55 cusp as in the equal mass case . taking some typical energy @xmath117 with @xmath118 in eq . ( [ eq : define_m0 ] ) , we may calibrate @xmath119 against numerical solutions of eq . ( [ eq : bw_masses ] ) . this yields @xmath120 for a wide range of mfs tested . hence @xmath121 and the full distribution is approximately @xmath122 eqs . ( [ eq : approx_pm2 ] ) and ( [ eq : approx_masses ] ) agree ( to better than a factor of @xmath123 in @xmath14 ) with numerical solutions of eq . ( [ eq : bw_masses ] ) for various mfs , such as the discrete mfs tested by bw77 and ah09 , the salpeter mf ( see figure [ fig : approx_masses ] ) and a wide range of power - law mfs ( see figure [ fig : p0 ] ) . ( [ eq : approx_pm2 ] ) implies that for any mf , @xmath124 is a decreasing function of @xmath125 . in particular , the power - law index of the most massive species , @xmath126 , asymptotically approaches @xmath49 as @xmath127 , so @xmath14 approaches eq . ( [ eq : fmassesp1_4 ] ) . in cases where we may approximate @xmath128 in eq . ( [ eq : define_m0 ] ) , for example if @xmath129 is strongly peaked in a mass range where @xmath130 varies little , we have @xmath131 . for concreteness , consider unbound stars with a power - law mf @xmath132 in some mass range @xmath133 . in this case we recover eq . ( [ eq : ode_masses ] ) with @xmath134 and @xmath135 the incomplete @xmath136-function . the power - law index @xmath124 may be found from eq . ( [ eq : approx_pm2 ] ) , @xmath137 ( for one mass , then using @xmath138 ) . indices @xmath139 , @xmath126 calculated from eq . ( [ eq : ph_power_law ] ) are illustrated in figure [ fig : p0 ] in the @xmath140 plane . for small ( very negative ) @xmath141 we may estimate @xmath8 using the @xmath142 limit where @xmath143 , whence and @xmath144 . ] @xmath145 when @xmath23 can not be neglected , we may eliminate the @xmath146 integral in eq . ( [ eq : bw_masses ] ) by repeated operations of differentiation with respect to @xmath99 and isolation of integral terms . if we assume , in addition , a power - law energy dependence @xmath147 , we arrive at a generalization of eq . ( [ eq : fixed_p0 ] ) , @xmath148 \nonumber \\ & & \ , \times \ , m'{\xi}(m ' ) { x}^{-\frac{3}{2}+p+p ' } dm ' \nonumber \\ & = & \frac{2}{3 } p \left(p-1 \right ) \left(p-\frac{5}{2}\right)q(m ) { \mbox { , } } \end{aligned}\ ] ] with abbrev . @xmath149 and @xmath150 . for @xmath27 and @xmath138 , this reproduces the results of [ sec : negligible_flow ] , @xmath3 . ( [ eq : p_vs_q ] ) suggests that @xmath151 in all cases , otherwise the left hand side becomes large and strongly @xmath99-dependent . figure [ fig : p0 ] shows that the @xmath152 limit is indeed realized if the mf is sufficiently broad and light - dominated . it corresponds to mass segregation stronger even than the saturation value @xmath153 predicted by ah09 in the limit of a strongly bimodal , light - dominated mf where light stars are expected to assume @xmath154 . a variant of eq . ( [ eq : p_vs_q ] ) with @xmath23 eliminated is @xmath155 = 0 \nonumber { \mbox { .}}\end{aligned}\ ] ] adopting a typical specific energy , @xmath156 with @xmath157 , one can solve this equation for @xmath124 with arbitrary @xmath0 , an approximate procedure far simpler than solving eq . ( [ eq : bw_masses ] ) . however , eq . ( [ eq : p_vs_q_xi_indep ] ) typically becomes unstable when the underlying power - law assumption @xmath158 fails . the linear scaling @xmath159 remains approximately valid even when the flow is only marginally negligible . using this ansatz in eq . ( [ eq : p_vs_q_xi_indep ] ) , @xmath124 becomes a root of the quadratic equation @xmath160 with averages weighted by @xmath161 . for light - dominated mfs and massive stars with @xmath162 , the last term dominates and @xmath124 peaks at @xmath9 . for a strongly peaked mf where @xmath163 , eq . ( [ eq : qapprox ] ) yields two solutions : the @xmath27 limit @xmath164 , and a steep solution @xmath165 . ( [ eq : qapprox ] ) suggests the following , numerically supported picture . for mfs peaked at relatively massive stars , the df is approximately given by the @xmath27 result . for more light - dominated mfs , @xmath6 is shifted towards lower masses so the df becomes gradually steeper at any given mass . if the mf is sufficiently extended ( large @xmath166 ) and light - dominated ( _ e.g. , _ small @xmath141 ) , each stellar species of mass @xmath167 eventually achieves maximal steepness @xmath168 . the transition between the @xmath27 and the saturation regimes involves in general an intermediate range of parameters in which the df of this species is no longer a power law in @xmath99 . we may roughly identify this region with the absence of real solutions to eq . ( [ eq : qapprox ] ) , @xmath169 illustrated as areas delimited by solid curves in figure [ fig : p0 ] . after reaching maximal steepness @xmath170 continues to evolve , but its maximal value remains @xmath171 . we have analyzed the distribution of an arbitrary , continuous mf @xmath1 of stars around a mbh . for equal mass stars , we derive a simple approximation for the df @xmath14 , see eq . ( [ eq : approx_single ] ) and figure [ fig : approx_single ] . for mfs not strongly dominated by light stars , where the mass flow can be neglected , we generalize the bw77 linear scaling @xmath138 to continuous mfs . we then derive approximate solutions for @xmath8 ( including its normalization , eq . ( [ eq : approx_pm2 ] ) ) and @xmath14 ( eq . ( [ eq : approx_masses ] ) ) and confirm them numerically ; see figures [ fig : approx_masses ] and [ fig : p0 ] . our results provide a simple yet accurate alternative to solving the full integro - differential equation ( [ eq : bw_masses ] ) . ( [ eq : approx_pm2 ] ) reproduces and generalizes previous fokker - planck calculations such as bw77 , which were limited to a narrow range of parameters . as an illustration , consider sga * with @xmath172 and a model mf with main sequence stars , white dwarfs , neutron stars and black holes , of masses @xmath173 , and relative abundances @xmath174 . ( [ eq : approx_pm2 ] ) then gives @xmath175 so @xmath176 for black holes and @xmath177 for the other species , in agreement with the numerical results of @xcite and ah09 . the df becomes gradually steeper with decreasing @xmath6 , as long as @xmath178 in eq . ( [ eq : determinant ] ) remains positive . for very light - dominated mfs , the power law assumption @xmath179 eventually fails at high masses , roughly where @xmath180 ( contour - enclosed regions in figure [ fig : p0 ] ) . as the mf peak shifts to even lower masses , @xmath181 and the power - law behavior are eventually restored at the high mass end and the df remains very steep , peaking at @xmath182 . this behavior is illustrated in figure [ fig : p0 ] . power law dfs @xmath183 correspond to @xmath184 . as long as the mf is not very light - dominated , stars of mass @xmath6 have @xmath185 ( up to a @xmath186 correction ) and an equal - mass like cusp @xmath187 , while other stars have @xmath188 . if the mf is broad and heavy - dominated , light stars tend towards an energy independent distribution @xmath189 while heavy stars approach @xmath13 . in the opposite , maximally steep limit , heavy stars develop a cusp as steep as @xmath190 , harder than any reported previously , and the number of stars in the cusp depends ( logarithmically ) on the disruption cutoff . we thank g. van de ven , d. keres and y. birnboim for helpful discussions . the research of u.k . was supported in part by nsf grant phy-0503584 , as a friends of the institute for advanced study member . the research of c.h . is supported by a veni fellowship from the netherlands organization for scientific research ( nwo ) . thanks the hospitality of the institute for advanced study , where part of this research took place . is supported by isf grant 928/06 and erc grant 202996 .

we analyze the distribution of stars of arbitrary mass function @xmath0 around a massive black hole ( mbh ) . unless @xmath1 is strongly dominated by light stars , the steady - state distribution function approaches a power - law in specific energy @xmath2 with index @xmath3 , where @xmath4 is the energy , @xmath5 is the typical velocity dispersion of unbound stars , and @xmath6 is the mass averaged over @xmath7 . for light - dominated @xmath1 , @xmath8 can grow as large as @xmath9 much steeper than previously thought . a simple prescription for the stellar density profile around mbhs is provided . we illustrate our results by applying them to stars around the mbh in the milky way .

stress fractures are common injuries most often associated with the participation in sports involving running , jumping , or repetitive stress . in comparison with other locations of stress fractures , a patellar stress fracture was first described in a german journal by muller in 1943 and in an english journal by devas in 1960 . stress fractures of the patella have been described to be represented by 2 different types ; those with a longitudinal fracture of the lateral part and those with a transverse fracture of the distal or middle part . to our knowledge , no report about a stress fracture of the patella has described a transverse fracture of the proximal part . in this report , we describe a case of an extremely rare type of patellar stress fracture , a proximal transverse fracture , in a 9-year - old athlete . informed consent was obtained from the patient and his parents . a 9-year - old boy participated in various sports , including running sprints twice per week for 1.5 years , and engaging in kendo twice per week for 3 years . he presented at a nearby orthopedic clinic 1 month after experiencing left knee pain while playing these sports , without any injury event . he had no subcutaneous hemorrhage and no external injury at the first visit to the clinic . his left knee radiograph showed a transverse fracture of the left proximal patella and a right knee radiograph showed no evidence of fracture ( figure 1 ) , and he was therefore diagnosed to have a transverse stress fracture of the left proximal patella . the femorotibial angle of the left knee was 174 and that of the right knee was 176. the insall and salvati ratio of the left knee was 0.91 and that of the right knee was 0.97 . the roentgenographic patellofemoral congruence was almost normal , because the sulcus angle of the left knee was 138 and the congruence angle was 5. he was treated conservatively for 7 months , with inhibition from playing sports , but without immobilization , such as cast fixation or bracing . however , his left knee pain did not disappear , so he presented to our hospital for treatment . a plain radiograph taken 7 months before the first visit of our hospital . the left knee radiographs ( a , d , f ) revealed a transverse fracture of the proximal patella , whereas the right knee radiographs ( a , c , e ) revealed no evidence of a fracture . the anterior - posterior view ( a , b ) showed that the knees were neither valgus nor varus . the lateral view ( c , d ) showed that neither of the knees had patella alta nor patella infera . the axial view ( e , f ) showed that the patellofemoral congruence was almost normal for the knees . a physical examination revealed no ligamentous laxity , no effusion , no range of motion deficit in his left knee and mildly localized tenderness at the left proximal patella . his left knee radiograph showed a transverse fracture of the proximal patella with nonunion ( figure 2 ) . we made a diagnosis of nonunion of a proximal transverse patellar stress fracture and performed surgery . the left proximal patellar stress fracture was drilled with a 0.88-mm k - wire for freshening of the nonunion portion and was internally fixed using acutrak mini screws ( acumed , hillsboro , or ) . three months after the operation , he had returned to his previous level of sports activity without any complaints . six months after the operation , the left patella fracture was completely united ( figure 3 ) . at 2 years a left knee radiograph taken at the first visit to our hospital revealed nonunion of a proximal transverse patella stress fracture . a left knee radiograph taken 6 months after the operation revealed that the patellar stress fracture was completely united . a 9-year - old boy participated in various sports , including running sprints twice per week for 1.5 years , and engaging in kendo twice per week for 3 years . he presented at a nearby orthopedic clinic 1 month after experiencing left knee pain while playing these sports , without any injury event . he had no subcutaneous hemorrhage and no external injury at the first visit to the clinic . his left knee radiograph showed a transverse fracture of the left proximal patella and a right knee radiograph showed no evidence of fracture ( figure 1 ) , and he was therefore diagnosed to have a transverse stress fracture of the left proximal patella . the femorotibial angle of the left knee was 174 and that of the right knee was 176. the insall and salvati ratio of the left knee was 0.91 and that of the right knee was 0.97 . the roentgenographic patellofemoral congruence was almost normal , because the sulcus angle of the left knee was 138 and the congruence angle was 5. he was treated conservatively for 7 months , with inhibition from playing sports , but without immobilization , such as cast fixation or bracing . however , his left knee pain did not disappear , so he presented to our hospital for treatment . a plain radiograph taken 7 months before the first visit of our hospital . the left knee radiographs ( a , d , f ) revealed a transverse fracture of the proximal patella , whereas the right knee radiographs ( a , c , e ) revealed no evidence of a fracture . the anterior - posterior view ( a , b ) showed that the knees were neither valgus nor varus . the lateral view ( c , d ) showed that neither of the knees had patella alta nor patella infera . the axial view ( e , f ) showed that the patellofemoral congruence was almost normal for the knees . a physical examination revealed no ligamentous laxity , no effusion , no range of motion deficit in his left knee and mildly localized tenderness at the left proximal patella . his left knee radiograph showed a transverse fracture of the proximal patella with nonunion ( figure 2 ) . we made a diagnosis of nonunion of a proximal transverse patellar stress fracture and performed surgery . the left proximal patellar stress fracture was drilled with a 0.88-mm k - wire for freshening of the nonunion portion and was internally fixed using acutrak mini screws ( acumed , hillsboro , or ) . three months after the operation , he had returned to his previous level of sports activity without any complaints . six months after the operation , the left patella fracture was completely united ( figure 3 ) . at 2 years a left knee radiograph taken at the first visit to our hospital revealed nonunion of a proximal transverse patella stress fracture . a left knee radiograph taken 6 months after the operation revealed that the patellar stress fracture was completely united . the location of stress fractures in adult athletes was reported to be the following : 49.1% in the tibia , 25.3% in the tarsal bones , 8.8% in the metatarsal bones , 7.2% in the femur , 6.6% in the fibula , 1.6% in the pelvis , 0.9% in the sesamoids , and 0.6% in the spine ; in children , these were 47% in the tibia , 21% in the fibula , 12% in the femur , 9% in the radius , 9% in the metatarsals , and 3% in the humerus . . there have been 22 case reports of patellar stress fractures in athletes published in the english literature since 1960 . the previously reported cases in the english literature have described 2 different types : a longitudinal fracture type and a transverse fracture type . the longitudinal fractures were described in 6 case reports , all of which were located in the lateral part . transverse fractures were described in the other 16 case reports , 14 of these cases were located in the distal 1/3 and 2 cases were located in the middle 1/3 . in our case , patellar stress fractures have been reported in athletes including soccer players , basketball players , and runners . these sports activities involve the high frequency use of the knee extensor mechanism , repetitively increasing the patellofemoral joint reaction force and patellofemoral contact pressure . as it was demonstrated that an increased patellofemoral joint reaction force was dependent on the increase of the knee flexion angle , we think that the repetitive increase in the patellofemoral joint reaction force due to the kendo , in addition to the sprints , is 1 factor associated with the development of the transverse stress fracture of his left patella . it was previously reported that the contact area of the patella articular surface against the femoral surface was different from the flexion angle of the knee . for example , if the knee was flexed at 30 , 60 , and > 90 to 120 , the patella surface contact , respectively , was in the distal 1/3 area , middle 1/3 area , and proximal 1/3 area . in the present case , the transverse stress fracture occurred in the proximal patella , whereas most reported locations of the transverse stress fractures of the patella were in the distal 1/3 . the radiograph of left lateral patellar view taken 6 months after the operation ( figure 3 ) revealed a subtle , shallow radiolucent area at proximal patella , which may have been the contact point for the creation of the stress fracture . we suggest that the repetitive motion with > 90 of left knee flexion during sprinting and while performing kendo caused the transverse stress fracture of his left proximal patella , because these motion increased the patellofemoral contact pressure for the proximal patellar articular surface , in addition to repetitively increasing the patellofemoral joint reaction force , including the longitudinal traction force for the patella . some methods of surgical treatment for patellar stress fractures have been reported . internal fixation with the tension band technique , the cannulated screw technique , curettage , bone grafting , or drilling have all been reported . in our case , 7 months of conservative treatment , including no sports activities , did not improve the left knee pain . we therefore performed surgical treatment by means of drilling and internal fixation using the cannulated screw technique with acutrak screws for the left knee , because the patient had a nonunion of the proximal patellar transverse stress fracture . postoperatively , the patient was able to return to his previous level of athletic sports activity . therefore , we think that we could successfully treat the nonunion of a transverse stress fracture of the proximal patella with internal fixation using acutrak screws . we herein reported an extremely rare case of transverse stress fracture of the proximal patella . we believe that the repetitive motion with 90 left knee flexion induced by running sprints and participating in kendo caused the transverse stress fracture of the patient 's left proximal patella , because these motions increased the patellofemoral contact pressure for the proximal patellar articular surface , in addition to repetitively increasing the patellofemoral joint reaction force , including the longitudinal traction force on the patella . the nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using acutrak screws , and he was able to return to his previous level of athletic sports activity postoperatively .

abstractamong stress fractures associated with sports activities , patellar stress fracture is rare . regarding patella stress fractures , so far only distal transverse or lateral longitudinal fractures have been reported , but there are no reports of transverse fractures occurring in the proximal patella . we describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year - old athlete.a 9-year old boy , who participated in sports ( sprints and kendo ) presented with left knee pain without any external injury . in plain radiographs , a fracture line was observed in the proximal 1/3 of the left patella , and a patella stress fracture was diagnosed . for treatment , because 7 months of conservative therapy showed no improvement , internal fixation was carried out using acutrak screws , and bone union was thus achieved . three months after the operation , he was able to return to his previous level of athletic sports activity.regarding the mechanism of onset , it is believed that the causes are longitudinal traction force and patellofemoral contact pressure . on the other hand , the contact region of the patella with the femur changes with the flexion angle of the knee . in the current case , the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of > 90 , so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of > 90 , during the sports activities of sprints and kendo . the nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using acutrak screws .

observations of lyman-@xmath2 ( ly@xmath2 ) sources are a powerful probe of the high - redshift universe ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? in particular , the prominence of the ly@xmath2 line at @xmath8 allows for spectroscopic confirmation of redshift measurements of individual distant galaxies . ly@xmath2 sources are also a compelling probe of the cosmic dark ages leading up to reionization see @xcite for a perspective on high-@xmath6 observations . historically , @xcite determined that galaxies from the first billion years after the big bang would be powerful emitters of ly@xmath2 photons , though observations of these sources eluded us for longer than expected . however , robust detections are becoming more regular , especially if the stellar mass is comparable to the milky way or the star formation rate ( sfr ) is elevated ( e.g. sfr @xmath9 ; * ? ? ? * ) . within the earliest galaxies hard uv radiation from massive stars is reprocessed into ly@xmath2 photons ; however , because neutral hydrogen ( hi ) is opaque to the ly@xmath2 line , many of these photons may be resonantly trapped , and consequently suffer significant dust absorption . despite these effects , observations have determined that the ly@xmath2 escape fraction , @xmath10 , actually increases at higher redshifts @xcite . at some point , although the photons are no longer destroyed by dust , they are scattered out of the line of sight and some fraction of the ly@xmath2 emission is lost to the background as their sources become spatially extended ly@xmath2 haloes @xcite . various mechanisms have been explored to explain the unusually high @xmath10 of high-@xmath6 galaxies . in all likelihood this is a result of the complicated resonant line transfer , galactic structure , and peculiar dust properties . for example , multiple scatterings that facilitate excursions to the wings of the frequency profile ; large - scale flows that induce doppler shifts ; and the geometry of dense , dusty clouds within a clumpy interstellar medium that provide pathways for escape ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) . in this work , we push these questions to the very first galaxies ( for a review see * ? ? ? assessing the observability of such early ly@xmath2 sources is nontrivial . indeed , going to higher redshifts introduces physical effects that compete in either strengthening or attenuating the ly@xmath2 signal @xcite . on one hand , the intergalactic medium ( igm ) becomes increasingly neutral at higher @xmath6 , resulting in a more difficult escape for ly@xmath2 photons @xcite . on the other hand , the same igm also becomes increasingly devoid of dust @xcite . furthermore , population iii ( so - called pop iii ) stellar sources are predicted to have been more efficient ionizers , boosting the ly@xmath2 luminosity @xcite . the fact remains that high - redshift ly@xmath2 sources are being observed out to @xmath11 . still , many details regarding the epoch of reionization ( eor ) , or the inhomogeneous phase transition around @xmath12 , are uncertain and may greatly affect interpretations of ly@xmath2 transfer through the igm @xcite . some of the most effective methods for identifying high - redshift objects involve the ly@xmath2 line . in particular , lyman - break galaxies ( lbgs ) are generally massive galaxies for which neutral hydrogen produces a sharp drop in the spectra due to absorption @xcite . lyman-@xmath2 emitters ( laes ) are young , less - massive galaxies with active star formation and strong ly@xmath2 emission @xcite . it is an important frontier to push ly@xmath2 selection methods towards the highest possible redshifts . for galaxies at @xmath13 the neutral fraction of the intervening igm increases enough for their spectra to yield complete absorption of photons blueward of the ly@xmath2 line . this is the well - known `` gunn - peterson trough '' @xcite which is characteristic of lbgs . however , these massive , evolved galaxies become increasingly rare at high redshifts . the lae luminosity function also declines as redshift increases , and the observed trend is robustly established for @xmath14 ( e.g. * ? ? ? * ; * ? ? ? * ) and expected to continue beyond @xmath15 @xcite . because a strong detection of the highly - redshifted ly@xmath2 line requires the emitter to be young and relatively dust free conditions which are naturally expected for the first galaxies laes are likely their typical manifestation . high - redshift ly@xmath2 candidates must be followed up by spectroscopy in order to guard against false positives from foreground contaminants . fortunately , moderate- to high-@xmath6 surveys are underway that will dramatically increase the sample size of ly@xmath2 galaxies and better characterize their statistical properties . for example , the hobby - eberly telescope dark energy experiment ( hetdex ) is a large integral - field spectroscopic survey expected to detect a million laes @xcite . currently , there are several candidates at @xmath16 ( e.g. * ? ? ? * ) , with the highest spectroscopically - confirmed source announced at @xmath17 by @xcite . other records have been found using gamma - ray bursts ( grbs ) , active galactic nuclei ( agn ) , or ( sub-)mm observations of redshifted thermal dust emission @xcite . however , it is unclear how these other selection methods relate to ly@xmath2 predictions . such connections may complement ly@xmath2 observations , even if the phenomena originate from the luminous deaths of individual massive stars ( i.e. grbs ) or are not associated with a ` normal ' activity of the first galaxies ( e.g. agn or high amounts of dust ) . ly@xmath2 radiative transfer within the first galaxies is a timely problem because next - generation facilities will provide high resolution data by the end of the decade . the _ james webb space telescope _ ( _ jwst _ ; * ? ? ? * ) and large - aperture ground - based observatories ) , thirty meter telescope ( tmt ; http://www.tmt.org/[www.tmt.org ] ) , and the european extremely large telescope ( e - elt ; http://www.eso.org/sci/facilities/eelt/[www.eso.org/sci/facilities/eelt ] ) . ] offer the prime avenue for observing ly@xmath2 emission at the high-@xmath6 frontier and will significantly contribute to our understanding of the ionization history at the end of the dark ages @xcite . however , significant progress has also been made on a number of complementary probes of the high-@xmath6 universe . several 21-cm array experiments ) , the murchison wide - field array ( mwa ; http://www.mwatelescope.org/[www.mwatelescope.org ] ) , the precision array to probe the epoch of reionization ( paper ; http://eor.berkeley.edu/[eor.berkeley.edu ] ) , and ultimately the square kilometer array ( ska ; http://www.skatelescope.org/[www.skatelescope.org ] ) . ] are coming online to map the distribution of hi over the course of reionization . the ly@xmath2 and 21-cm lines are related through the wouthuysen - field mechanism for which ly@xmath2 scatterings pump electrons into the excited hyperfine state , thereby coupling the spin and kinetic temperatures @xcite . finally , an ideal complementary ly@xmath2 probe is encoded in the cosmic infrared background ( cib ) because the integrated radiation from all background stars and galaxies has been redshifted to ir wavelengths @xcite . the ly@xmath2 contribution is seen through the correlation of sources across characteristic length scales ( for a review see * ? ? ? a number of authors have studied ly@xmath2 radiative transfer within different contexts . we have greatly benefited from and hope to add to the body of work in this area . a partial list of references include : @xcite . the state of the art is to apply post - processing radiative transfer to realistic hydrodynamical simulations , which is justified for many large scale systems . we use this method in conjunction with semi - analytic models to ascertain the feedback of ly@xmath2 radiation on the galactic assembly process . our focus on the very first galaxies , in their proper cosmological context , is different from previous research that has targeted more massive systems at redshifts close to , or after , reionization ( e.g. * ? ? ? such systems require a statistical description of ly@xmath2 transmission through the igm as described by @xcite and @xcite . photons that scatter out of the line of sight due to the neutral fraction of the igm are effectively lost to the background . therefore , the observability of ly@xmath2 emitters will provide independent constraints on reionization @xcite . measurements of the ly@xmath2 flux from first galaxies depend heavily on the observed line of sight in addition to the properties of the host system and igm . therefore , rather than solving a potentially intractable transfer equation with complex angular dependence we take advantage of monte - carlo radiative transfer techniques to accurately build emergent spectral energy distributions ( seds ) . in order to perform ly@xmath2 simulations we have developed a new massively parallel code called @xmath4 the @xmath0smic @xmath1yman-@xmath2 @xmath3ransfer code . in section [ subsec : rs ] , the basic physics of ly@xmath2 transport is presented . in section [ sec : methodology ] , we discuss the general methodology behind @xmath4 and provide further algorithmic details in section [ sec : schemes ] . in section [ sec : tests ] , the code is tested against both static and dynamic setups . in section [ sec : toy ] , we construct idealized analytical models to explore how fundamental parameters , including halo mass , virialization redshift , bulk velocity , and ionization structure , affect ly@xmath2 transport in the first galaxies . these well - motivated models help test our methods and sensitivity . section [ sec : sim ] describes our implementation of the _ ab initio _ cosmological simulation of @xcite as post - processing conditions for @xmath4 . in section [ sec : results ] we analyze and discuss the emergent line of sight flux distributions and surface brightness profiles for both the idealized analytic cases and the cosmological simulation . finally , in section [ sec : conc ] we reflect on the implications of this study with regard to future ly@xmath2 observations with the _ jwst_. photons with frequencies close to the ly@xmath2 resonance line , corresponding to the transition from the first excited state ( 2p ) to the ground state ( 1s ) , may be absorbed and quickly re - emitted by neutral hydrogen . thus , in optically thick environments ( @xmath19 ) the main mechanism of spatial diffusion is by the rare excursion to the lorentz wing of the spectral line . the cross section @xmath20 and number density @xmath21 describe the optical depth @xmath22 along a photon s path : @xmath23 where @xmath24 specifies the frequency dependence . it is often convenient to express frequency in a dimensionless manner as the number of doppler widths from line centre @xmath25 where @xmath26 hz is the frequency of ly@xmath2 and the thermal doppler width of the profile is @xmath27 . the thermal velocity in terms of @xmath28 is @xmath29 furthermore , if the natural ly@xmath2 line width is @xmath30 hz then the ` damping parameter ' represents the relative broadening of the natural line width : @xmath31 therefore , the final cross section is @xmath32 where @xmath33 is the oscillator strength of the ly@xmath2 transition and the hjerting - voigt function @xmath34 is the dimensionless convolution of lorentzian and maxwellian distributions , @xmath35 for reference , we define the cross section at line centre as @xmath36 @xmath37 . for a region of constant density @xmath21 such as a cell in a computational domain the integral in equation ( [ eq : tau ] ) simplifies to @xmath38 typically , the parameter @xmath39 is much less than unity so the hjerting - voigt function is dominated in the centre by a resonant scattering doppler core , @xmath40 , and the wings are dominated by the lorentzian component , @xmath41 . if the approximate frequency marking the crossover from core to wing is denoted by @xmath42 , i.e. where @xmath43 , then the hjerting - voigt function is roughly @xmath44 see sections [ subsub : h_approx ] and [ subsub : x_cw_approx ] for a more rigorous discussion as well as numerical approximations for @xmath34 and @xmath42 . for most conditions with significant neutral hydrogen density the gas is optically thick to core photons . however , in the wing , @xmath34 can be quite small allowing a photon to escape with greater ease . the approximate optical depth for a wing photon is then @xmath45 which is independent of temperature as is immediately apparent when written in terms of the doppler velocity @xmath46 . note the relation between doppler frequency and velocity : @xmath47 . regions of high column density , @xmath48 pc @xmath49 @xmath50 , may produce very high opacities . the trapped ly@xmath2 photons are therefore exposed to greater extinction from dust . this may be best measured by the optical depth at line centre , which has moderate temperature dependence and can be read from equation ( [ eq : tauh ] ) as @xmath51~t_4^{-1/2}$ ] . the @xmath4 code is based on previous monte - carlo radiative transfer ( mcrt ) algorithms ( see e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? the code reads initial conditions of velocity , density , and temperature for each cell of a three - dimensional grid employing adaptive mesh refinement ( amr ) . sampling the ly@xmath2 emission profile of high opacity systems is possible because acceleration schemes avoid unnecessary computations , e.g. frequent core scatterings . additionally , @xmath4 is massively parallel allowing a greater number of photon packets and therefore less statistical error . section [ sec : methodology ] outlines the general methodology for a ly@xmath2 transport code while section [ sec : schemes ] describes the specific implementations used in @xmath4 . while the monte - carlo method for ly@xmath2 radiative transfer is fairly standard , each portion of section [ sec : schemes ] contains significant discussion or numerical schemes unique to this work . in order to sample ly@xmath2 observables we apply the method described below to individual photon packets . depending on the desired resolution and physical setup a large number of packets may be necessary to obtain statistical convergence . unless otherwise specified the number of photon packets in each simulation is @xmath52 . the initial spatial distribution of ly@xmath2 photons is based on the physical setup , i.e. initial conditions . the first mechanism for producing ly@xmath2 line emission is interstellar recombination as a result of ionizing radiation from hot stars . the second mechanism is collisional excitation of neutral hydrogen , usually resulting from shocks caused by accretion or supernovae . an initialization criterion accounts for photoionizing sources and diffuse emission , both of which may be significant for atomic cooling haloes . however , throughout this work we choose to initialize photons from the central location @xmath53 . the initial direction @xmath54 of each photon is drawn from an isotropic distribution in the rest frame of the embedded source . for convenience , velocities are expressed in terms of the thermal velocity : @xmath55 the photon is emitted at the natural frequency of the ly@xmath2 photon @xmath56 in the rest frame of the atom . to obtain the initial frequency @xmath57 in the moving frame of ambient gas we apply a doppler shift appropriate to the velocity of the atom @xmath58 @xcite @xmath59 to be explicit , @xmath56 is drawn from a lorentzian distribution and the components of @xmath60 are each taken from a maxwellian distribution describing the thermal motion of the ambient gas . although we use the expression in equation ( [ eq : init_freq ] ) , the memory of @xmath57 is quickly lost by multiple scattering events , so for optically thick environments one may simply inject the photon at line centre , or @xmath61 . the propagation distance of any photon is determined by the optical depth @xmath22 drawn from an exponential distribution . this is because the mean optical depth @xmath62 defines the mean free path @xmath63 , or the average distance a photon can travel without being absorbed ( or scattered ) by the intervening medium @xcite . therefore , travel beyond each mean free path becomes less and less probable . formally , the mean free path is then @xmath64 . from equation ( [ eq : tau ] ) the respective optical depths of infinitesimal paths are @xmath65 so the probability of _ no _ interaction is @xmath66 . with @xmath67 partitions of @xmath68 , the numerical representation of discrete intervals , the probability distribution function over the total path is the product @xmath69 which has been normalized so that @xmath70 . the cumulative distribution function is the integrated distribution defined by @xmath71 , which can be inverted to give the optical depth at which an interaction event occurs , @xmath72 where @xmath73 is drawn from a univariate distribution . to perform cartesian - like ray tracing , the monte - carlo method selects a photon with an optical depth @xmath74 according to equation ( [ eq : lnr ] ) . because individual cells are regions of uniform density we may equate this with the calculated optical depth @xmath75 from equation ( [ eq : tauh ] ) to find the propagation distance , i.e. @xmath76 provides @xmath77 . however , this often leads to a scattering which is outside the original cell . therefore , we first calculate the optical depth required to travel through the cell : @xmath78 , where @xmath79 is the distance from the current position to the point where the photon exits the cell . if @xmath80 the ` spent ' optical depth is subtracted from the current optical depth , i.e. @xmath81 . likewise , the current position is updated to @xmath82 and ray tracing continues through the next cell . as photons traverse from cell to cell the temperature @xmath83 and ambient bulk velocity @xmath84 may change . therefore , doppler shifting induces terms of @xmath85 corresponding to a nonrelativistic lorentz transformation , i.e. one where @xmath86 . additionally , the frequency differs between cells due to the @xmath87 scaling relation . the frequency in the new ( primed ) cell is then @xmath88 if @xmath89 the optical depth is ` exhausted ' in the current cell and the photon undergoes a scattering event . the propagation distance is recalculated according to the remaining optical depth , i.e. @xmath90 $ ] . the position is advanced by @xmath91 in the @xmath54 direction and the algorithm proceeds to update the frequency and direction as described in section [ sec : scatter ] . the photon ray traces along a new direction with each subsequent scattering until it ultimately escapes the computational domain . a scattering event changes the photon s frequency according to the atom s velocity @xmath60 , the final @xmath92 and initial @xmath54 directions , and a small recoil effect to satisfy conservation of momentum @xmath93 the recoil parameter @xmath94 is defined as ( see e.g. * ? ? ? * ) @xmath95 which is included but negligible for the applications of this paper . the velocity of the scattering atom is most conveniently expressed in terms of its parallel @xmath96 and perpendicular @xmath97 components . the perpendicular magnitudes are unbiased by the photon s frequency and are therefore drawn from a gaussian , i.e. @xmath98 . however , the magnitude of the parallel velocity @xmath99 is affected by the presence of the resonance line . the distribution function for @xmath100 depends on frequency as the convolution of a gaussian with a doppler - shifted lorentzian peak : @xmath101 which highly favors velocities with @xmath102 for core photons . for wing photons ( @xmath103 ) , however , the probability that an atom has a high enough velocity to doppler shift into resonance becomes vanishingly small , so @xmath104 becomes increasingly gaussian . the angle @xmath105 between the incident and outgoing scattering directions is governed by the phase ( probability ) function @xmath106 where @xmath107 is the degree of polarization for @xmath108 scattering . due to the physical symmetry the phase function is independent of the azimuthal angle @xmath109 . for core photons with @xmath110 the electron transition to the @xmath111 state results in isotropic scattering , i.e. @xmath112 , while the @xmath113 transition results in polarization with @xmath114 @xcite . since a quantum state with angular momentum @xmath115 has a spin multiplicity of @xmath116 , ly@xmath2 photons in the core are excited to the @xmath111 state with @xmath117 probability and the @xmath113 state with @xmath118 probability . nonresonant wing photons on the other hand are dominated by rayleigh scattering because their wavelength is much larger than the bohr radius , @xmath119 , therefore the resultant polarization is maximal , i.e. @xmath120 @xcite . anisotropic scattering is used throughout @xmath4 . the previous section was written with little regard to computational efficiency , something we now seek to remedy . the details are presented in order of introduction , rather than importance . and our approximation for different values of temperature . the crossover from core to wing @xmath42 as given by equ . ( [ eq : xcw ] ) is also shown . bottom panel : a demonstration of the relative per cent error @xmath121 $ ] where @xmath122 is given by equ . ( [ eq : ab ] ) . the yellow , blue , green , and red curves correspond to temperatures of @xmath123 k , @xmath124 k , @xmath125 k and @xmath126 k , respectively . the overlying dashed lines represent the best case scenario when only keeping first order terms in @xmath39 , i.e. using the exact dawson integral.,title="fig : " ] and our approximation for different values of temperature . the crossover from core to wing @xmath42 as given by equ . ( [ eq : xcw ] ) is also shown . bottom panel : a demonstration of the relative per cent error @xmath121 $ ] where @xmath122 is given by equ . ( [ eq : ab ] ) . the yellow , blue , green , and red curves correspond to temperatures of @xmath123 k , @xmath124 k , @xmath125 k and @xmath126 k , respectively . the overlying dashed lines represent the best case scenario when only keeping first order terms in @xmath39 , i.e. using the exact dawson integral.,title="fig : " ] an approximation for the voigt profile is important because @xmath34 is evaluated after every scattering . a substantial effort has gone into studying this profile and implementing efficient algorithms with double precision accuracy see e.g. @xcite and references therein . however , the ly@xmath2 resonance line is a unique application with a specific parameter range , so the approximations used in this work are entirely our own . we require our algorithm to provide better than one per cent accuracy for all frequencies and all realistic temperatures . to do this we first evaluate the integral @xmath34 with special functions and expand to second order in @xmath39 : @xmath127 where the ( complex ) complementary error function is related to the area under a gaussian by @xmath128 and the associated dawson integral is @xmath129 . @xmath4 takes advantage of the fact that @xmath34 is symmetric by first evaluating @xmath130 . then because the behavior of the profile differs for small and large @xmath6 the domain is decomposed into three regions . the ` core ' region is derived by expanding around @xmath131 , while the ` wing ' region is an asymptotic expansion . an intermediate region acts as a smooth transition between the two . the approximations utilize continued fractions in order to maximize the efficiency of a small number of operations , e.g. @xmath132 additions and @xmath133 divisions . see appendix [ appendix : h_approx ] for the implementation of @xmath134 . second and higher order terms in @xmath39 are required to achieve one per cent accuracy for sub - kelvin temperatures . however , since the cmb temperature floor prevents gas from reaching such low temperatures only first order terms are used in @xmath4 . figure [ fig : herror ] demonstrates the relative error , i.e. @xmath121 $ ] , for temperatures ranging from @xmath135 k. as can be seen , the error is well controlled , improving even further for higher temperatures . $ ] , is shown in green . the yellow curve in the insert is @xmath136 as given by equation ( [ eq : xcw ] ) . all curves cover a temperature range of @xmath137 $ ] k. ] the crossover from core to wing @xmath42 determines when @xmath34 changes from a gaussian to a lorentzian . this is important because @xmath42 marks the point where difficulties arise in generating @xmath100 and also identify whether core skipping is necessary ( see sections [ sec : upar ] and [ sec : coreskip ] ) . our calculation assumes that the core and wing limits of @xmath34 compete in their contribution to the profile : @xmath138 equation ( [ eq : xcwa ] ) provides a conservative approximation for @xmath42 , providing a sharp boundary with the core ( see fig . [ fig : herror ] ) . the exact solution can be written in terms of the lower branch of the lambert @xmath139 function , which in turn may be approximated by a low - order rational function with a relative accuracy of less than @xmath140 per cent for the same parameter range as @xmath122 . in summary , our optimal calculation of the core - to - wing crossover frequency is @xmath141 where @xmath142 and @xmath143 $ ] . the relative per cent error is shown in fig . [ fig : xcwerror ] . as described in section [ sec : scatter ] ( cf . equation [ eq : uparf ] ) the distribution for the parallel velocity @xmath100 with respect to the incoming photon is @xmath144 to good approximation this profile resembles a gaussian with a sharp peak around the point @xmath102 ( see fig . [ fig : upar ] ) . unfortunately , @xmath104 is not integrable so we instead use the inverted cumulative distribution function method on a related distribution and employ the rejection method to accept each draw . in this case the comparison function is chosen to be @xmath145 and draws are accepted with a probability of @xmath146 . however , we only employ this algorithm for small frequencies , i.e. @xmath147 , because as @xmath148 increases the method becomes quite inefficient . we learn more about @xmath104 by examining its behavior when @xmath149 . here the peak at @xmath102 is pushed so far into the wing that there are essentially no atoms with speeds fast enough to absorb at the doppler shifted resonance line , i.e. @xmath150 . therefore , we may simply draw from a proper gaussian with a slight modification the peak is shifted by @xmath151 . we demonstrate this by finding the local extrema in the core : @xmath152 here we have assumed @xmath153 . it is straightforward to show @xmath154 so this is a local maximum as expected . therefore , for @xmath155 we draw from a gaussian with mean @xmath151 . as given by equ . ( [ eq : uparf ] ) for different values of incoming frequency @xmath148 . the profile resembles a gaussian with a sharp peak around the point @xmath102 . for large @xmath148 it becomes too improbable for atoms to have velocities high enough to doppler shift into resonance so the peak at @xmath102 disappears and a shifted gaussian is a good approximation . the frequencies sampled are @xmath156 . ] the intermediate region is problematic for either of these methods . therefore , we follow @xcite and use the piecewise comparison function : @xmath157 & \ ; u_\| \leq u_0 \\ g_2 = e^{-u_0 ^ 2 } / \left [ a^2 + ( x - u_\|)^2 \right ] & \ ; u_\| > u_0 \end{cases}\ ] ] where @xmath158 is a separation parameter and the corresponding acceptance fraction is @xmath159 for @xmath160 and @xmath161 for @xmath162 . we now restrict the discussion to positive @xmath148 , which is possible because @xmath163 allows us to recover velocities drawn from negative @xmath148 . the probability that a velocity is less than @xmath158 is @xmath164 where @xmath165 if @xmath166 , a univariate , then @xmath105 is drawn uniformly from the interval @xmath167 $ ] , otherwise @xmath168 $ ] . finally , a velocity candidate , @xmath169 is accepted if another univariate , @xmath170 , is less than the acceptance fraction , i.e. @xmath159 or @xmath161 for each respective region . the algorithm from @xcite works well as long as the probability of the two regions are balanced , i.e. in @xmath4 we attempt to maintain @xmath171 . the reason for this is that @xmath158 controls the acceptance fraction , so if @xmath158 is too small then we do not gain much for larger @xmath148 and conversely if @xmath158 is too large then we defeat the purpose for smaller @xmath148 . the exact value of @xmath172 is very sensitive to both @xmath148 and @xmath39 , so we can only hope for average acceptance rates to be reasonable given the variance in @xmath173 . if we assume @xmath174 then to first order in @xmath39 we have : @xmath175 the behavior of this function is different for core and wing photons . in the core it is reasonable to assume a perturbation from the natural peak location and apply the transformation @xmath176 where @xmath177 admits an analytic solution to the approximate balance of @xmath171 . again , to first order in @xmath39 equation ( [ eq : papprox ] ) becomes @xmath178 the solution in terms of @xmath179 is @xmath180 where the final equality allows the approximation to extend to larger @xmath148 and is used in @xmath4 for @xmath181 . for the region in which the wing dominates , i.e. @xmath182 , the algorithm suffers an identity crisis . as discussed earlier , the high-@xmath148 behavior of @xmath183 approaches a gaussian distribution though each of the candidate @xmath100 samples are from a lorentzian distribution . therefore , the exact value of @xmath158 is less important as long as it is greater than @xmath42 . we test various prescriptions for @xmath184 , also varying initial frequency @xmath148 and temperature @xmath83 , in order to minimize the average number of draws in a simulation . a linear function , matched to the previous region provides sufficient acceptance of candidate random numbers . we use the following separation constant for @xmath185 , denoted the ` wing ' region : @xmath186 figure [ fig : u0p ] demonstrates the fractional probability @xmath187 for drawing @xmath188 given our piecewise prescription of @xmath189 for @xmath181 and @xmath190 for @xmath191 . the efficiency of the algorithm is especially sensitive to frequency . that @xmath188 . this separation captures the behavior of @xmath94 for frequencies above and below the transitional frequency @xmath42 . the axes are frequency @xmath192 and ( log@xmath193 ) temperature @xmath194 k. ] in optically thick regimes photons spend much of their time undergoing core scatterings with negligible diffusion in physical or frequency space . these scatterings can be avoided by only selecting atoms with perpendicular velocity components greater than a critical frequency , i.e. photons have zero mean free path if @xmath195 . following @xcite we employ the box - muller method to generate two independent draws according to : @xmath196 where @xmath197 and @xmath198 are univariates . the speedup time achieved here is significant since the probability of drawing a wing photon is roughly @xmath199 corresponding to skipping roughly @xmath200 core scatterings . the crucial problem is to find an appropriate value for the critical frequency @xmath201 . @xmath4 introduces an algorithm with core - skipping based on both local and nonlocal criteria . this is especially important for high resolution , adaptively structured grids where the range of densities may cover several orders of magnitude . we desire a local determination of @xmath201 that accelerates the code but does not artificially push photons too far into the wings . as noted by @xcite the important parameter is the product @xmath202 so we seek a relation of the form @xmath203 . the model we consider for the near zone environment is that of an optically thick static uniform sphere . this is motivated by the idealized geometry and an analytic solution for the angular averaged intensity @xmath204 at the surface first given by @xcite , @xmath205 which has been normalized to @xmath206 , reflecting an integration over solid angle . the peaks are located at @xmath207 , which is derived by solving the equation @xmath208 , or equivalently @xmath209 with @xmath210 . therefore , the peak heights correspond to @xmath211 . we next expand equation ( [ eq : sphere ] ) around @xmath212 and define @xmath201 for large @xmath202 as the frequency where @xmath213 reaches a small fraction of @xmath214 , giving @xmath215 . thorough tests demonstrate this expression for @xmath201 is valid for all @xmath216 ( see appendix [ appendix : x_crit ] ) . furthermore , it has a negligible effect on the emergent spectrum but greatly reduces the computation time . in summary , @xmath4 uses the following approximation : @xmath217 if the photon is already in the wing we do not use a cutoff because there are no core scatterings to skip . the final ingredient in equation ( [ eq : xcrit ] ) to be explained is how to calculate the product @xmath202 . @xmath4 employs a combination of local and nonlocal estimates of how aggressive to be with core - skipping . as we can not possibly predetermine the escape path of a given photon we instead place a conservative limit on @xmath202 for different lines of sight the local criterion is computed on - the - fly , using the minimum optical depth to the edge of the current cell @xmath218 . however , in highly refined regions ( perhaps with partial ionization ) and for scattering events near cell edges this can be quite small , i.e. if @xmath79 is the minimum distance to the cell boundary equation ( [ eq : tauh ] ) gives @xmath219 it is apparent that if @xmath21 is roughly constant then the only nonlocal quantity needed is the physical size of the system . therefore , the minimum integrated column density along rays emanating from the scattering event sets up an effective sphere with the intensity of equation ( [ eq : sphere ] ) . rather than calculate this at every scattering we combine the cell - based determination with a nonlocal ( nl ) estimate : @xmath220 where the path is followed as long as the relative change in neutral hydrogen density remains less than a prescribed threshold , i.e. @xmath221 . a value of @xmath222 ignores the nonlocal scheme completely and setting @xmath223 is too aggressive , failing to even detect sharp ionization fronts . to avoid double counting the local contribution , the paths originate at the edge of each cell and proceed outward . in practice the paths include at least the six directions of the coordinate axes and possibly more to achieve greater angular coverage . the nonlocal estimate can be computed once for each cell as the initial conditions are read in . @xmath4 currently uses the sum of the local determination @xmath218 and the nonlocal estimate @xmath224 as the value of @xmath202 used in equation ( [ eq : xcrit ] ) . we note that other criteria could be used for estimating @xmath202 . for example , the nonlocal integration might stop if the velocity gradient exceeds the threshold for sobolev escape ; however , in most cases this is a secondary factor with little affect on core - skipping . finally , additional local distances may be used in certain cases . of special interest is to use the jeans length to estimate core - skipping in idealized galactic setups . the jeans length @xmath225 acts as a physical upper limit for the size of a system with uniform density @xmath226 . a primordial gas with mean molecular weight @xmath227 , mass fraction of hydrogen @xmath228 , and density @xmath229 corresponds to a jeans length of @xmath230 and a local @xmath202 of @xmath231 so that @xmath232 for @xmath233 k and @xmath234 . monte carlo codes benefit greatly from parallel computation because each photon packet is an independent event . therefore , the scalability is nearly linear . @xmath4 uses the message passing interface ( mpi ) libraries to implement dynamic load balancing between different processors . this is done because photons that undergo many scatterings take longer to escape . therefore , the master process allocates a reasonable amount of work to each slave , e.g. ( @xmath235% of the photons)/(number of processors ) , until the required number of photons are assigned . the nonlocal determination of @xmath236 for each cell , see equation ( [ eq : ataunl ] ) , is also performed with an efficient parallel computation . at this stage it is important to verify the code against known solutions . we choose tests that are complementary to each other in order to isolate certain key aspects of ly@xmath2 transport . the static test is the well - known neufeld analytical solution for an optically thick homogeneous slab @xcite . the dynamic test is that of an isotropically expanding sphere with different maximal velocities as described by @xcite . of a static , homogeneous slab at @xmath233 k. the central optical depth @xmath237 covers a range of moderate to extreme values , where the yellow , blue , green , and red curves represent @xmath4 simulations using @xmath238 photon packets for @xmath239 , @xmath240 , @xmath241 , and @xmath242 , respectively . the agreement with the approximate analytic solutions ( thin black lines ) is quite good , especially for higher values of @xmath237 . at lower optical depths the underlying assumptions used to derive equation ( [ eq : neufeld ] ) break down , therefore the true measure of this test is the limiting behavior as @xmath237 tends to infinity . bottom panel : face - on line of sight radial surface brightness profiles for the same slabs as calculated by equation ( [ eq : sb ] ) of section [ sub : surface_brightness_construction ] . the scaling is such that the highest optical depth system is unity at the centre , i.e. @xmath243 . the dashed line is a rough analytic fit to guide the eye . , title="fig : " ] of a static , homogeneous slab at @xmath233 k. the central optical depth @xmath237 covers a range of moderate to extreme values , where the yellow , blue , green , and red curves represent @xmath4 simulations using @xmath238 photon packets for @xmath239 , @xmath240 , @xmath241 , and @xmath242 , respectively . the agreement with the approximate analytic solutions ( thin black lines ) is quite good , especially for higher values of @xmath237 . at lower optical depths the underlying assumptions used to derive equation ( [ eq : neufeld ] ) break down , therefore the true measure of this test is the limiting behavior as @xmath237 tends to infinity . bottom panel : face - on line of sight radial surface brightness profiles for the same slabs as calculated by equation ( [ eq : sb ] ) of section [ sub : surface_brightness_construction ] . the scaling is such that the highest optical depth system is unity at the centre , i.e. @xmath243 . the dashed line is a rough analytic fit to guide the eye . , title="fig : " ] the angular averaged intensity @xmath244 for a static one - dimensional uniform slab was derived by @xcite and @xcite . photons are injected at line centre at the origin and continuously scatter until escape occurs at a ` centre - to - edge ' optical depth of @xmath237 . when the bulk motion of the gas is set to zero , @xmath245 , and the recoil effect is ignored , @xmath246 , the emergent spectra are double - peaked and symmetric around the line - central frequency @xmath247 . the intensity at the surface is given by @xmath248 which has been normalized to @xmath206 , reflecting an integration over solid angle . the peaks are located at @xmath249 , which is derived by solving the equation @xmath208 , or equivalently @xmath250 with @xmath210 . therefore , the peak heights correspond to @xmath251 . as can be seen in fig . [ fig : neufeld ] the agreement between numerical and analytic solutions is quite good for high optical depths . for example , at an optical depth of @xmath252 when comparing the simulated profile ( red line ) with the approximate analytic solution ( thin black line ) there is a maximum difference of @xmath253 per cent . the neufeld approximation of equation ( [ eq : neufeld ] ) fails to capture the correct spectra at lower optical depths because core scatterings also contribute to the spatial diffusion of ly@xmath2 photons . therefore , the true measure of this test is the limiting behavior as @xmath237 tends to infinity . the bottom panel of fig . [ fig : neufeld ] demonstrates the face - on radial surface brightness profiles for the same slabs as calculated by equation ( [ eq : sb ] ) of section [ sub : surface_brightness_construction ] . the scaling is such that the highest optical depth system is unity at the centre , i.e. @xmath243 . the dashed line is a rough analytic fit to guide the eye and is given in the figure . the shaded regions represent one standard deviation of uncertainty on @xmath254 due to radial binning . finally , this test has also been performed at other temperatures with similar results , cf . appendix [ appendix : temperature_tests ] . such simulations of ly@xmath2 scatterings through optically thick slabs help measure the effectiveness of the acceleration schemes , cf . appendix [ appendix : x_crit ] . to test the code for the case of a nonzero gas bulk velocity we compare our results to previous simulations with isotropic expansion of a uniform sphere see @xcite . in general , velocity gradients affect ly@xmath2 escape because photons are doppler shifted out of line centre thereby reducing the effective optical depth . in general , even velocity fields on the order of the thermal velocity in photoionized gas ( @xmath255 ) can change the emergent spectrum of ly@xmath2 photons . following @xcite we consider the intensity of an isothermal ( @xmath233 k ) , homogeneous sphere of column density @xmath256 experiencing isotropic expansion . the hubble relation gives the velocity @xmath257 of the gas at the position @xmath258 from the centre of a sphere with radius @xmath73 : @xmath259 where the hubble - like parameter @xmath260 sets the maximal velocity @xmath261 at the edge of the sphere , i.e. @xmath262 . figure [ fig : velocity ] shows the result of this test which demonstrates excellent agreement with @xcite . the static case ( @xmath263 ) also agrees with the analytical solution of @xcite for a static , optically thick spherical `` slab '' . this test is also similar to that of @xcite who calculated the zero - temperature spectrum of a ly@xmath2 source embedded in a neutral , homogeneous igm undergoing hubble expansion . whereas a static solution produces two distinct peaks for blue and red modes of escape , the blue photons are continuously redshifted back to the core and the red mode becomes the only means of escape . this inevitably leads to free streaming on cosmological ( @xmath264mpc ) scales . unfortunately , there is no analytical solution for a medium possessing both thermal and bulk motions . figure [ fig : velocity ] illustrates the effect of increasing @xmath261 , which acts to suppress the blue peak until it disappears entirely by @xmath265 . at first the red peak is pushed further from line centre , however , past a critical @xmath261 the peak approaches the centre again because the velocity gradient facilitates escape . the bottom panel of fig . [ fig : velocity ] shows the ( averaged ) line of sight radial surface brightness profile for each sphere . the scaling is such that the static sphere is unity at the centre , i.e. @xmath243 . the dashed line is a reference for a flat profile to guide the eye . only the largest velocity gradients substantially alter the profile so that the apparent image is much more concentrated toward the centre . galaxy formation is a highly complex process ; however , studying the formation and radiative transport in the first , comparatively simple , systems provides an ideal laboratory for the physics involved @xcite . we here employ two complementary methodologies to represent the structure and dynamics of a first galaxy for @xmath4 first , in section [ sec : toy ] we construct idealized analytic models of these galaxies , and second , in section [ sec : sim ] we extract a virialized halo from an _ ab initio _ cosmological simulation for post - processing . these first galaxy models will then be the input for the radiative transfer calculations discussed in section [ sec : results ] . our idealized models allow us to explore the basic physics by directly adjusting parameters in order - of - magnitude fashion . our cutout from the cosmological simulation , on the other hand , provides us with one representative example of a realistic first galaxy . we can thus gauge the validity of our exploratory toy models . we now explore idealized models for the first galaxies at redshift @xmath266 in preparation for extractions from a cosmological simulation . the number density of hydrogen nuclei @xmath267 is built up from the following assumptions : first , we require spherical symmetry so that @xmath268 . second , we adopt a power law density profile within the galaxy , i.e. @xmath269 out to the edge of the galaxy @xmath270 defined as the point where @xmath267 equals the background igm , @xmath271 . an isothermal law with @xmath272 provides a good description of a virialized system ( e.g. * ? ? ? * ) . finally , we prefer a non - cuspy ` core ' in the centre of the galaxy , meaning the density profile flattens off to a constant density @xmath273 within a core radius of @xmath274 pc . this is inspired by observations of low surface brightness galaxies that suggest a softening in the centre @xcite . in summary , the model is piecewise in the radial coordinate @xmath275 according to : @xmath276 here @xmath271 is the background atomic hydrogen number density derived from a @xmath277cdm model with cosmological parameters taken from the @xcite , and incorporating constraints from the _ wilkinson microwave anisotropy probe _ ( wmap ; * ? ? ? * ) , the _ south pole telescope _ ( spt ; * ? ? ? * ) , and the _ atacama cosmology telescope _ ( act ; * ? ? ? specifically , the hubble constant is taken to be @xmath278 km s@xmath279 mpc@xmath279 while the fractional energy contributions of baryons , matter , and dark energy are @xmath280 , @xmath281 , and @xmath282 , respectively . therefore , @xmath271 is @xmath283 , or @xmath284 where @xmath228 is the mass fraction of hydrogen and @xmath285 is the critical energy density at present . furthermore , the edge of the galaxy is given by solving the equation @xmath286 , which yields a radius of @xmath287 . the density parameter @xmath273 is then found by normalizing the overall mass of hydrogen in the galaxy @xmath288 to some value , e.g. @xmath289 for an atomic cooling halo . the total mass is given by the integral @xmath290 equation ( [ eq : mhtot ] ) is a cubic polynomial in @xmath273 whose solution is not particularly insightful . however , we may expand about large masses @xmath288 to consolidate the leading order terms . these terms provide a relative accuracy in @xmath273 of better than 1 part per billion for masses larger than @xmath291 . for the parameters chosen above this implies a central density of @xmath292 where we have introduced the dimensionless parameter : @xmath293 this term may also be found by dropping the @xmath294 term in equation ( [ eq : mhtot ] ) . the @xmath295 parameter relates the ( leading order ) ratio of core and background densities via @xmath296 and the ratio of core and edge radii via @xmath297 . with this central density the optical depth to ly@xmath2 scattering of the core region is at least @xmath298 , a value that would increase with a larger core radius , a lower temperature , or a more massive system . we are primarily interested in the mass and density of hydrogen , therefore we decided to use @xmath288 in the comparison . the total or virial mass of the galaxy is larger for two main reasons : @xmath299 the mass fraction of hydrogen to baryons is less than unity , i.e. @xmath228 . @xmath300 the contribution of baryonic mass is considerably less than the contribution of dark matter , which is usually more extreme in smaller galaxies . in fact , if a substantial amount of gas is lost through ram pressure stripping or supernova blowout , for example , the baryonic mass may be significantly below the cosmological baryon fraction of @xmath301 per cent @xcite . at any rate we can reasonably relate the virial and total hydrogen masses by @xmath302 . the model above did not include an ionized region around a central star cluster . this is important because ly@xmath2 photons can easily escape such regions . furthermore , a strmgren analysis suggests that the ionized region may be on the order of @xmath303 for a reasonable set of parameters : @xmath304 where we have defined normalized values for ionizing photon rate @xmath305 and density @xmath306 . the normalization used for @xmath307 is a plausible guess at the rate expected from the starbursts residing in the first galaxies ( see section [ sec : central_starburst ] for further discussion ) . the expression was simplified by approximating the total case b recombination rate by @xmath308 cm@xmath5 s@xmath279 @xcite . in order to understand how the ionized region affects ly@xmath2 transfer we need to consider how the full three - dimensional ionization structure evolves in time . the strmgren radius is a good approximation early on when the radiation is bottled up and the ionization rate balances the recombination rate , i.e. @xmath310 . however , as the ionization front moves out , the hii regions blow pockets through which ly@xmath2 photons may escape . therefore , we distinguish between _ early _ ionization scenarios when the hii region is ultra - compact as in equation ( [ eq : stromgren ] ) and _ late _ scenarios when the hii starburst regions have overtaken the entire halo . these cases bracket the entire evolution . the late stages of the ionization structure must be anisotropic because the cosmological filaments guide the ionized bubbles into a butterfly - shaped morphology around the centre . for simplicity we model this as a bipolar cavity . specifically , in addition to the strmgren sphere , our _ late _ scenario also has a biconical region out to @xmath270 . the size of the hii region is determined by the total number of ionizing photons , i.e. @xmath311 . if the photons are produced at a constant rate and the volume of the cone is described by the opening angle @xmath312 from the axis of symmetry then the time to evacuate the cavity is at least of order @xmath313 therefore , the _ late _ scenario corresponds to a time when the biconic region out to @xmath270 is fully ionized see fig . [ fig : idealized_density ] for an edge - on view of the column density through one such halo . for a `` late '' model at a source redshift of @xmath314 with @xmath315 . the spatial scale , in physical kiloparsecs and arcseconds , are provided . the edge - on view of the halo demonstrates the butterfly - shaped ionization structure of the models . for comparison with eq . ( [ eq : t_late ] ) the corresponding ionizing photon rate is @xmath316 , giving a late time lower limit of @xmath317 yr . ] the central starburst provides a feedback mechanism on the host galaxy . in order to motivate a spherically symmetric velocity law we consider the relative strength of the gravitational force @xmath318 to the radiation force @xmath319 . as a first estimate , if we attribute the radiation pressure to thompson scattering in the single - scattering limit , then because of the @xmath320 scaling of both forces , their ratio is of order @xmath321 where @xmath322 and @xmath323 are respectively the total luminosity and mass of the entire cluster . the normalization is chosen to correspond to the mass to light ratio for pop iii stars , i.e. @xmath324 ( see section [ sec : central_starburst ] ) . for simplicity equation ( [ eq : rad_grav ] ) assumes a point source . in reality , the ratio decreases radially from the centre of the gravitational potential as the dark matter halo mass dominates the gravitational force . furthermore , equation ( [ eq : rad_grav ] ) is only applicable to ionized gas , whereas ly@xmath2 scattering occurs in neutral gas so other sources of pressure must also be present for our idealized law . we consider a force multiplier in analogy to that of ( cak ; * ? ? ? * ) originating from many resonant and optically thin lines . the multiplier can amplify the scattering efficiency by many orders of magnitude . thus , the luminosities considered here ( @xmath325 ) may be capable of sustaining radiation - driven winds @xcite . indeed , the ly@xmath2 line alone may be responsible for much of the opacity these winds require @xcite . the cak theory uses mass conservation and momentum balance to arrive at a ` beta law ' with an exponent of @xmath326 for the radial velocity profile @xmath327 where @xmath328 is the size of the source . the terminal velocity @xmath329 is typically larger than the escape velocity @xmath330 by a factor of a couple . plausible values for our models are obtained by requiring that the mass loss rate @xmath331 be less than the maximally efficient mass loss for single scattering @xmath332 for which the radiation momentum is imparted entirely to the gas . in the halo s isothermal region , i.e. @xmath333 , the velocity approaches @xmath329 and @xmath334 so @xmath335 in principle , multiple scattering in the optically thick environment could boost @xmath329 by a factor of the square root of the optical depth , or at least an order of magnitude . however , for simplicity our wind models all assume the velocity profile of equation ( [ eq : wind ] ) with @xmath336 pc , the approximate size of the central star cluster , and @xmath337 , a value comparable to the thermal velocity @xmath338 . we note that our value of @xmath329 is also close to the escape velocity of the system , @xmath339 @xmath340^{1/3}$ ] @xmath341^{1/2}$ ] . for completeness , the original cak force multiplier @xmath342 would need to be reevaluated for h and he lines of gas with primordial composition . it is beyond the scope of this work to do so here but for reference the model of @xcite derives values of @xmath343 and @xmath344 . the parameter @xmath345 is either the electron - scattering optical depth @xmath346 or the sobolev optical depth @xmath347 in static or expanding media , respectively . the density and velocity profiles considered here are not self - consistent in the dynamical sense . however , our simplified @xmath348-model , calibrated in the above fashion , should give us a rough window into the otherwise extremely complex physics of galactic winds ( e.g. * ? ? ? this also avoids overconstructing models that are already quite idealized . finally , the radiation pressure driven winds considered above may require some dust and metals to be present in the ism . however , we have not included dust in these primordial environments . further study on how dust affects ly@xmath2 transfer in anisotropic models should be carried out and is left for future work . still , various mechanisms such as scattering in clumpy media have been proposed to explain why the ly@xmath2 escape fraction is so significant in environments where core depletion seems unavoidable . in fact , @xcite suggest that dust attenuation is unlikely to affect ly@xmath2 escape at @xmath349 . for our purposes , we expect dust to lower the bolometric line flux by at most a factor of a few . for an example of coupling large scale cosmological simulations with dust and radiative transfer models designed to constrain igm ionization and the dust distribution in the ism of early galaxies see @xcite and @xcite . the expression @xmath350 is based on comparing an expanding of the analytical solution for a static uniform sphere to the height of its peak see equation ( [ eq : sphere ] ) . however , the constant of proportionality must be found by empirical tests . the tests were run on many different values of @xmath202 , however , we only show two to demonstrate the validity across the parameter space . the first is for @xmath351 , for which equation ( [ eq : xcrit ] ) gives @xmath352 , while the second is for @xmath353 , where @xmath354 . as can be seen from fig . [ fig : xcrit_test ] , both values produce excellent results . designed to compare different values of @xmath201 . the converged solution ( yellow histogram ) is given by @xmath355 while a low value of @xmath356 provides excellent agreement and is shown in black . a sample of values which are too high and affect the emergent spectrum are @xmath357 and are respectively given by orange , red , and purple dotted histograms . bottom panel : same as the top panel except for @xmath353 . a value of @xmath358 is sufficiently converged for our purposes . an acceptable value of @xmath359 is given by a black line while non - converged values of @xmath360 are again given by the orange , red , and purple dotted histograms . here @xmath202 is large enough that the analytical solution of equ . ( [ eq : sphere ] ) is accurate , so it is included as the green dashed line in the background . both tests used @xmath361 photon packets.,title="fig : " ] designed to compare different values of @xmath201 . the converged solution ( yellow histogram ) is given by @xmath355 while a low value of @xmath356 provides excellent agreement and is shown in black . a sample of values which are too high and affect the emergent spectrum are @xmath357 and are respectively given by orange , red , and purple dotted histograms . bottom panel : same as the top panel except for @xmath353 . a value of @xmath358 is sufficiently converged for our purposes . an acceptable value of @xmath359 is given by a black line while non - converged values of @xmath360 are again given by the orange , red , and purple dotted histograms . here @xmath202 is large enough that the analytical solution of equ . ( [ eq : sphere ] ) is accurate , so it is included as the green dashed line in the background . both tests used @xmath361 photon packets.,title="fig : " ] in order to test the grid structure of the cosmological simulation for edge effects and sensitivity to the extraction size we examine the emergent spectra for cubes with a centre to edge distance of @xmath125 pc , @xmath362 kpc , @xmath132 kpc , and @xmath363 kpc . the largest size represents the radiative transfer through the entire @xmath364 mpc@xmath365 comoving volume . figure [ fig : box_size ] demonstrates the convergence of the flux density @xmath366 toward that of the largest extraction , although there is still a significant variance across different lines of sight due to the inhomogeneous nature of the cosmic structure . in order to demonstrate the `` thermal effects '' on ly@xmath2 radiative transfer , e.g. via the doppler width @xmath372 and core - wing transition @xmath42 , we include two test suites of uniform slabs with varying temperature . the first maintains a constant optical depth at line centre of @xmath373 while the second ensures a fixed column density of @xmath374 @xmath50 , which corresponds to @xmath373 at @xmath375 k. the angular averaged intensity for each model is plotted in fig . [ fig : temperature_tests ] . even though the optical depth or column density is fixed , the product @xmath376 depends on temperature and the emergent spectra is affected . furthermore , we note that although the lorentz wing optical depth is always independent of temperature , @xmath377 and @xmath378 are proportional to @xmath379 and @xmath380 , respectively . ( [ eq : x_f ] ) and ( [ eq : recoil_parameter ] ) demonstrate that for recoil shifting to appreciably affect the ly@xmath2 profile it must be comparable to the typical redistribution at each scattering event . for example , if @xmath381 then under thermally - dominated redistribution we typically have @xmath382 . however , lorentzian - dominated redistribution may become a reasonable approximation at low temperatures . in this case , the scattering atom s parallel velocity component is roughly @xmath383 and the ratio to recoil is significantly reduced for core photons , i.e. @xmath384 . the total relative contribution over all scattering events induces a runaway reddening effect in cold , optically thick environments . radiative transfer . both cases represent the angular averaged intensity as a function of doppler velocity @xmath385 for uniform slabs of varying temperature . for direct comparison between the models the normalization is arbitrary but consistent in all cases . the top panel maintains a constant optical depth at line centre of @xmath373 while the bottom panel ensures a fixed column density of @xmath374 @xmath50 , corresponding to @xmath373 at @xmath233 k. even though the optical depth or column density are fixed , the product @xmath376 depends on temperature and the emergent spectra is affected . the number of photon packets used in these simulations is @xmath386 . ]

we present the @xmath0smic @xmath1yman-@xmath2 @xmath3ransfer code ( @xmath4 ) , a massively parallel monte - carlo radiative transfer code , to simulate lyman-@xmath2 ( ly@xmath2 ) resonant scattering through neutral hydrogen as a probe of the first galaxies . we explore the interaction of centrally produced ly@xmath2 radiation with the host galactic environment . ly@xmath2 photons emitted from the luminous starburst region escape with characteristic features in the line profile depending on the density distribution , ionization structure , and bulk velocity fields . for example , anisotropic ionization exhibits a tall peak close to line centre with a skewed tail that drops off gradually . idealized models of first galaxies explore the effect of mass , anisotropic hii regions , and radiation pressure driven winds on ly@xmath2 observables . we employ mesh refinement to resolve critical structures . we also post - process an _ ab initio _ cosmological simulation and examine images captured at various distances within the 1 mpc@xmath5 comoving volume . finally , we discuss the emergent spectra and surface brightness profiles of these objects in the context of high-@xmath6 observations . the first galaxies will likely be observed through the red damping wing of the ly@xmath2 line . observations will be biased toward galaxies with an intrinsic red peak located far from line centre that reside in extensive hii super bubbles , which allows hubble flow to sufficiently redshift photons away from line centre and facilitate transmission through the intergalactic medium . even with gravitational lensing to boost the luminosity this preliminary work indicates that ly@xmath2 emission from stellar clusters within haloes of @xmath7 is generally too faint to be detected by the _ james webb space telescope _ ( _ jwst _ ) . [ firstpage ] lyman-@xmath2 emission radiative transfer resonant scattering line : profiles cosmology : theory galaxies : formation galaxies : high - redshift

according to the study of world health organization ( who ) , cardiovascular diseases caused 33.7% of all deaths in the world , while other chronic diseases were responsible for 26.5% . globally , it has been estimated that premature deaths resulting from hypertension annually are approximately 7.1 million , which account for 64 million disability - adjusted life years ( dalys ) . hypertension plays a major etiologic role in the development of ischemic heart disease , cerebrovascular disease , and cardiac and renal failure , and it is a significant risk factor for mortality and disability rates throughout the world . dietary patterns carry out extraction and analysis on dietary status overall and consider the interaction between all kinds of foods and nutrients . so dietary patterns represent a broader picture of food and nutrient consumption and may thus be more predictive of diseases risk than individual food or nutrient . furthermore , in addition to studying the role of individual nutrients , dietary patterns have become a focus for nutritional research . factor analysis of dietary patterns helps us understand the proportion of all kinds of foods in dietary intake by dimension reduction . the variable which represents correlation coefficient between foods and patterns is factor loading , and a positive loading designates positive association with the factor , while a negative loading designates negative association with the factor , and the larger the loading of a given food item to the factor , the greater the contribution of that food item to a specific factor . therefore , it is important to examine the dietary pattern and its association with chronic diseases among people in china . however , dietary pattern and its association with hypertension , coronary heart disease , stroke , and other chronic diseases have not been studied in baoji city by now . baoji , a representative city of chinese west , the second largest city in shaanxi province , has eight thousand years of civilization and more than two thousand seven hundred years of built history . the present study was aimed to survey dietary and health status of the residents over 15 years old in baoji city , identify the dietary patterns among chinese adults in baoji , and explore whether these dietary patterns are associated with chronic diseases ( e.g. , hypertension , coronary heart disease , stroke , bone and joint disease , neck and lumbar disease , and cancer ) . then it could provide a scientific basis for recommendations to improve food intakes and for government to formulate nutrition policy . according to the 2010 chinese national chronic diseases survey and the fifth national health service survey , we designed the epidemiology questionnaire of chronic diseases and the related risk factors in baoji city by many discussions , mainly including health interview , two weeks of chronic disease , the family in general , dietary , and body measurement . this study was based on population sampling survey according to the handbook of baoji city of shaanxi province in china , using multistage stratified random sampling from the total baoji population and kish grid method , which was organized by baoji city health bureau and performed by baoji cdc . inclusion criteria were age over 15 years old , residence in baoji city for more than six months , participating in the study voluntarily , and actively cooperating to complete the questionnaire and measurement ; exclusive criteria were age less than 15 years old , nonresidents , and not being able to match with it . a total of 5020 participants were included in this study at 12 counties , excluding the invalid samples , finally remaining 4968 valid samples . among valid samples , men were 2519 ( 50.7% ) , women were 2449 ( 49.3% ) , and mean age ( standard deviation ) was 41.6 ( 16.3 ) years old , coming from the urban and rural regions , respectively , 36.7% and 63.3% . the composition of study population was in accordance with the baoji city population of 2010 according to statistical test ; therefore , we can have the generalization from this study to the general baoji population . presurvey was arranged at one county before the formal investigation ; it provided unified survey methods and achieved excellent effect . height , weight , waist circumference , and blood pressure were obtained using standardized techniques and equipment in the early morning fasting state . height was measured to the nearest 0.1 cm with the subjects standing without shoes . body mass index ( bmi ) was calculated as weight divided by the square of height ( kg / m ) . three measurements were made on all subjects at 5 min intervals , and the average of three times was used in the analysis . all subjects in the survey participated voluntarily , and written informed consent was obtained from all subjects . all aspects of design , train , sample , field investigation , data entry , and check were run through quality control . we investigated the dietary consumption frequency and quantity of participants in the past one year using semiquantitative food frequency questionnaire , converted into grams per person per day , calculated for each nutrient contained in the food with nutrition calculator software , and finally merged into daily nutrient consumption per person . dietary questionnaire contained edible oil , spices , and 27 types of food . in the establishment of the dietary pattern , considering the statistical efficiency , similar food which was particularly small consumption got interpretation and consolidation ( fresh milk , milk powder and yogurt into milk ; pickles , pickled cabbage and sauerkraut into pickled vegetables ; fruit juice drinks and other beverages into beverage ) , and finally we obtained the daily intake of 22 kinds of food . hypertension : systolic blood pressure 140 mmhg or diastolic blood pressure 90 mmhg or previous diagnosis of hypertension , according to chinese guidelines for prevention and treatment of hypertension ( 2010 edition ) ; other chronic diseases information was collected with the self - reported questionnaire which depended on doctors above county level medical institutions diagnosis . epidata 3.1 was used to double input data , and database was analyzed with spss17.0 software after check . we described measurement data by mean standard deviation , using t - test , chi - square test , and anova statistical test , and all analyses performed with p < 0.05 were considered statistically significant . principal component factor analysis was used to identify dietary patterns , with the factors rotated by varimax orthogonal transformation , so as to achieve simpler structure with greater interpretability . factor number was selected mainly according to the following : ( 1 ) eigenvalue > 1.0 ; ( 2 ) the plot pointing out distribution mainly ; ( 3 ) the proportion of variance explained by each factor , but only as a reference ; ( 4 ) the probability of factor extraction . kaiser - meyer - olkin measurement was 0.803 , and bartlett spherical test was p < 0.001 . factor analysis extracted five dietary patterns ; their eigenvalues were all larger than 1.0 , and the five factors of the accumulative variance contribution rate reached 41.124% in table 1 . factor loadings more than 0.20 ( absolute value ) were selected to be analyzed , and factor was named according to the food it contained in dietary pattern to best represent the nature of each factor , respectively : protein , balanced , beans , prudent , and traditional dietary patterns in table 2 . factor 1 was characterized as high positive loadings on fried pasta , beef and mutton , poultry , organ meats , sea foods , dried tofu , seaweed , pickled vegetables , pastry , and beverage . factor 2 had high positive loadings on rice , fried pasta , pork , dairy , eggs , soybean milk , fresh vegetables , pastry , fresh fruit , and beverage . factor 3 had high positive loadings on dried tofu , soybean milk , dry beans , seaweed , and fresh fruit . factor 4 had high positive loadings on whole grains , potatoes , fried pasta , and pickled vegetables . factor 5 showed high positive loadings on wheat , whole grains , fried pasta , pork , fresh vegetables , and pickled vegetables . each factor was divided into q1 ( low percentile ) , q2 ( middle percentile ) , and q3 ( high percentile ) by score ; the higher the score , the more the incline to this dietary pattern . research suggests that every kind of dietary patterns is related to demographic characteristics , different lifestyles , and movement . the demography and body indices across percentiles of the dietary pattern are shown in table 3 . the average age of protein , balanced , and beans dietary patterns in q3 was younger than in q1 , the average age of prudent pattern in q3 was older than that in q1 , and traditional pattern was indifferent ; the bmi of each pattern was indifferent . the waist circumference of protein , balanced , and beans dietary patterns in q3 was longer than in q1 , and prudent and traditional patterns were indifferent ; females of protein and beans patterns in q3 were more than males , and males of prudent and traditional patterns in q3 were more than females ; gender of balanced pattern was indifferent . table 4 shows seven kinds of chronic diseases according to dietary pattern . regarding hypertension , the prevalence rate of protein , balanced , and beans patterns in q3 was significantly lower than in q1 , whereas the prevalence rate of prudent and traditional patterns in q3 was higher than in q1 . regarding coronary heart disease , the prevalence rate of prudent pattern in q3 was higher than in q1 , and the other four patterns were indifferent . regarding stroke , the prevalence rate of protein and balanced patterns in q3 was lower than in q1 , and the other three patterns were indifferent . regarding bone and joint disease , the prevalence rate of balanced and beans patterns in q3 was lower than in q1 , the prevalence rate of prudent pattern in q3 was higher than in q1 , and the other two patterns were indifferent . regarding neck and lumbar disease , the prevalence rate of protein , balanced , and beans patterns in q3 was lower than in q1 , and the other two patterns were indifferent . regarding cancer , the prevalence rate of protein pattern in q3 was higher than in q1 , and the other four patterns were indifferent . at present , there are few researches on the association of dietary nutrition and chronic diseases of baoji city residents , even of shaanxi province or northwest china . through the investigation of diet and health , we find out food nutrients intake , dietary patterns , and association of local chronic diseases . it will provide baseline data for nutritional intervention . in this study , five dietary patterns by factor analysis were identified in a chinese adult population named as protein , balanced , beans , prudent , and traditional patterns . the contribution rate was 16.1% , 7.9% , 7.0% , 5.2% , and 5.0% , respectively , reaching 41.1% of accumulative variance contribution rate , and it was high compared to other dietary studies of cumulative contribution rate of about 30% or less [ 9 , 10 ] . in addition to factor analysis , there are other methods to identify dietary patterns ( e.g. , reduced rank regression ( rrr ) ) . rrr provides linear functions of predictor variables that explain as much of the variation in response variables as possible , whereas factor analysis derives dietary patterns by maximizing the explained variation of all predictor variables . the demography and body indices by dietary pattern found that the age of protein , balanced , and beans dietary patterns was younger , whereas the age of prudent pattern was older ; females were more in protein and beans patterns , while males were more in prudent and traditional patterns . it indicates that young people like protein , balanced , and beans dietary patterns more , and old people like prudent pattern more . there are two kinds of obesity : general obesity which takes bmi as index and abdominal obesity ( also known as central obesity ) which takes waist circumference as index . in this study , the bmi of each pattern was indifferent , whereas the waist circumference was longer in protein , balanced , and beans patterns . we also found that protein , balanced , and beans patterns were associated with reduced prevalence of hypertension and neck and lumbar disease , protein and balanced patterns were associated with reduced prevalence of stroke , balanced and beans patterns were associated with reduced prevalence of bone and joint disease , whereas prudent and traditional patterns were associated with an increased prevalence of hypertension , prudent pattern was associated with an increased prevalence of coronary heart disease and bone and joint disease , and protein pattern was associated with an increased prevalence of cancer . a variety of studies have been implemented to explain the correlations between dietary patterns and hypertension , cardiovascular diseases , stroke , and cancer [ 13 , 14 ] . previous studies that have identified dietary patterns and their association with chronic diseases have been reported from usa [ 1517 ] , canada , germany , portugal , iran , or other asian countries [ 2224 ] . these studies have found that dietary patterns characterized by high intakes of vegetables , fruits , and fish were inversely associated with diseases , whereas dietary patterns characterized by high intakes of red meat , processed meat , refined grains , and fried foods were associated with increased risk . the balanced dietary pattern in present study is similar to the healthy dietary pattern identified in western countries with a comprehensive intake of protein , carbohydrate , and fat , which are associated with the low prevalence of many chronic diseases . a systematic review study indicated that fruits and vegetables concentrates are effective in significantly improving circulating concentrations of antioxidant vitamins , provitamins , and folate and decreasing markers of oxidative stress , which has been associated with a reduced risk of many chronic diseases . high intakes of fruits , vegetables , cereals , fishes , nuts , low - fat dairy products , and poultry in addition to relatively low intakes of fat and sugars appeared to be effective in lowering blood pressures and hypertensions . a dietary pattern with frequent intakes of fruits and dairy products significantly decreased blood pressure among chinese . the dietary approaches to stop hypertension ( dash ) dietary pattern , which is rich in fruit , vegetables , and low - fat dairy products and limits saturated fat , red meat , and sweets , is a success in hypertension control . on the other hand dietary pattern is typically associated with the increased prevalence of chronic diseases such as coronary heart diseases and cancer . a western dietary pattern with a high intake of red and processed meat , butter , oils , fats , sweets and desserts , refined grains , and high - fat dairy was related to a significantly increased risk of cardiovascular disease in western populations . hu reported that the western diet pattern score was positively associated with the fat intake percentage and the prevalence of coronary heart disease . a cohort study in japan also demonstrates that a dietary pattern with high meat intakes was closely related to an increased risk of cardiovascular diseases . in this study , we did not identify the western dietary pattern ; however , the identified prudent pattern rich in whole grains , potatoes , fried pasta , and pickled vegetables was positively associated with the prevalence of coronary heart disease and bone and joint disease . in the present study , the protein dietary pattern was positively associated with cancer , which may be interpreted partly as high meat intakes ( the first three factor loadings : organ meats 0.713 , poultry 0.692 , and beef and mutton 0.643 ) . as to the traditional pattern , baoji traditional dietary pattern rich in whole grains , fried pasta , and vegetables did not show any protective effect on chronic diseases , likely findings from a korean study . firstly , confounding factors could not be avoided as an observational study although we have used multistage stratified random sampling . secondly , there was some potential recall and reporting bias for semiquantitative food frequency questionnaire . future prospective cohort and clinical trials are warranted to verify our findings . in conclusion , five major dietary patterns were identified by factor analysis and were associated with the prevalence of many chronic diseases among chinese adults . the protein dietary pattern was negatively associated with hypertension , stroke , and neck and lumbar disease . the balanced pattern was negatively associated with hypertension , stroke , bone and joint disease , and neck and lumbar disease . the beans pattern was negatively associated with hypertension , bone and joint disease , and neck and lumbar disease . the prudent pattern was positively associated with hypertension , coronary heart disease , and bone and joint disease . , these results need to be confirmed by prospective cohort and clinical trials . on the whole , there are many protective effects with protein , balanced , and beans dietary patterns , so we should encourage baoji city residents to choose protein , balanced , and beans dietary patterns and abandon prudent and traditional patterns to prevent the incidence of hypertension , coronary heart disease , stroke , and other chronic diseases .

objective . this study was aimed to identify the dietary patterns among chinese adults in baoji and explore the association between these dietary patterns and chronic diseases . methods . with multistage stratified random sampling and semiquantitative food frequency questionnaire , the prevalence of chronic disease and dietary intake was investigated in 2013 . we used factor analysis to establish dietary patterns . results . a total of 5020 participants over 15 years old were included in this study . five dietary patterns were identified in baoji named as protein , balanced , beans , prudent , and traditional patterns . there are many protective effects with protein , balanced , and beans dietary patterns on chronic diseases . conclusions . we should encourage baoji city residents to choose protein , balanced , and beans dietary patterns and abandon prudent and traditional patterns .

lesion studies , neurophysiological , neuroanatomical and brain imaging studies have provided wealth of information on basic saccadic circuitry . saccade preparation or planning , triggering , execution and other saccadic functions are under control of distributed neural network involving cortical and subcortical structures . subcortical structures like basal ganglia ( bg ) , superior colliculus ( sc ) , thalamus , brainstem and cerebellum and cortical structures like parietal and frontal cortices are major areas involved in saccadic eye movement [ fig . 1 ] . schematic representation of basic saccadic circuitry . a : dorsolateral prefrontal cortex ( dlpfc ) ; b : frontal eye field ( fef ) ; c : parietal eye field ( pef ) ; d : visual cortex ; e : superior colliculus ( sc ) ; f : brainstem saccade generators ; g : basal ganglia ( bg ) ; h : cerebellum ; i : thalamus brainstem pontine burst neurons ( both inhibitory - ibns and excitatory - ebns , located in paramedian pontomedullary reticular formation or ppmrf and paramedian pontine reticular formation or ppprf respectively ) elicits saccades , which supply motor neurons ( mn ) innervating extraocular muscles . burst activity of ibns and ebns are controlled by omnipause neurons ( opns ) which are present in medial pons . , there are other types of neurons in brainstem known as long - lead burst neurons ( llbns ) mainly concentrated in rostral pons , which are active during saccadic eye movements [ fig . schematic representation of a : brainstem saccade generators ( llbn : long lead burst neuron , opn : omnipause neuron , ebn : excitatory burst neuron , ibn : inhibitory burst neuron , mn : motor neuron , sc : superior colliculus ) sc is the major brainstem saccadic centre in midbrain , which receives inputs from retina ( retino - tectal or extrageniculate pathway ) as well as from basal ganglia and cortex . it plays a major role in both fixation and saccadic eye movement . neurons in rostro - lateral pole of sc are more active during fixation and stop firing during saccades and are modulated by other brain structures [ fig . ablation of sc has been shown to impair saccade generation which recovers after some time but has lasting effects in terms of impairment of longer reaction times . basal ganglia and frontal cortical areas also modulate saccade related neuronal activity in sc . in addition , frontal cortical areas and cerebellum also directly influence pontine burst cells . in bg , caudate nucleus ( cn ) , subthalamic nucleus ( stn ) , substantia nigra pars reticulate ( snr ) , external segment of globus pallidus ( gpe ) and internal segment of globus pallidus ( gpi ) are major components involved in modulating saccadic movement . the main output structure of the bg circuitry is snr which has inhibitory influence on sc through gabaergic neurons and it suppresses saccadic initiation . basal ganglia circuitry involved in saccadic control ( d1 and d2 = dopamine receptors ) cerebral cortex plays a vital role in saccadic eye movements by projecting to bg , sc and directly to pontine burst cells . cortical areas influence saccadic eye movements through projections to cn , which projects to downstream neural circuits via gabaergic projections . cn receives inputs from most of the cortical areas and thalamus . through direct pathway , frontal cortex sends projections to cn , which directly projects to snr , which is gabaergic and sends projections to sc and thalamus . thalamus in turn projects back to cortical areas and thus activation of cortex leads to disinhibition of sc and thalamus via direct pathway . in the indirect pathway , cn projects to gpe which is gabaergic and gpe projects to stn which is excitatory in nature having glutamate as neurotransmitter which projects to snr / gpi . cortical activation increases the inhibitory activity of gpe and in turn causes more excitatory neuronal activity of stn , which further leads to inhibition of sc and thalamus . modulation of neuronal activity of sc by cortical areas and bg circuitry leads to saccadic eye movements that depend upon the tasks demands . since , bg circuitry and sc are under the influence of higher cortical centres , they play an important role in modulating saccadic activity [ fig . cerebral cortex also has a direct influence on saccadic eye movements in addition to influencing saccades through bg circuitry . frontal eye field ( fef ) participates in the production of saccades since micro stimulation of fef at low intensity is known to elicit saccades . it projects to sc , bg and cerebellum . because of this extensive network of fef with different neural structures which are involved in saccade production , fef modulates eye movements , depending upon the task demand . fef is also known to be involved in selecting saccadic goals ( curtis et al . , 2006 ) and generation of reflexive saccades . as suggested by various lesion studies , electrophysiology , tms and fmri , sef is involved in monitoring when subjects are performing saccadic tasks that involve saccadic sequences . supplementary eye field ( sef ) is connected to various cortical regions such as dorsolateral prefrontal cortex ( dlpfc ) , fef and anterior cingulate cortex . this region is involved in attentional processes so it is considered that this area can be associated with saccade and shift of attention without saccade . dlpfc is involved in saccadic eye movements which require short term memory or working memory ( memory guided saccades ) and also in saccades that require decision making . cerebellum is another brain structure which projects to brainstem saccade generators and is considered to be involved in maintaining saccadic accuracy . pd is a motor control disorder due to degeneration of dopaminergic neurons in the snc leading to reduction in dopamine levels . there is increased inhibitory output from bg , which affects thalamo - cortical circuits and sc , leading to motor symptoms like bradykinesia . as a consequence of the general impairment in the motor functions , different saccadic tasks like visually guided reflexive saccades , voluntary and memory guided saccades have been used to study eye movements in pd . abnormal saccadic performance in pd is considered to be due to depletion of dopamine in the caudate nucleus . there is an overall increase in the inhibitory output to sc and thalamus due to increased activity in the indirect pathway leading to more excitatory activity of stn and a decreased activity in the direct pathway leading to increased inhibition of snr / gpi . many studies suggest that stn stimulation has positive effects on saccadic impairment , which is suggestive of dbs playing a critical role in maintaining a balance between information flow through direct and indirect pathway . these studies are discussed in a separate section in this review parkinson disease patients have been tested on reflexive saccadic task where participants fixate at a fixation point at the centre of the screen . saccades are elicited when a sudden peripheral visual target is presented . in the gap task , which is a variant of reflexive saccade task , there is a gap of 200ms between target appearance and disappearance of fixation point . saslow showed a fixation offset effect wherein it was seen that saccadic latencies reduced when the fixation point was removed and a gap was introduced between target appearance and fixation point disappearance . in another variant of reflexive saccade , known as overlap task , another saccadic task uses a cue to elicit saccades where it is presented before the target presentation and it indicates the spatial location of future target appearance [ fig . posner showed that saccadic latencies reduce when the cue is presented before the target presentation . there is inhibition of return ( ior ) effect in which saccadic latencies increase when the time gap between cue and target presentation is increased above 300ms [ fig . 4 ] . fixation duration varies from 1000 - 3000 ms and target duration is around 1000 ms schematic representation of inhibition of return ( ior ) paradigm . soa represents stimulus onset asynchrony , which is time between cue ( yellow box ) and target presentation ( red circle ) . fixation duration varies from 1000 - 3000 ms and target duration is around 1000 ms memory guided saccadic tasks are saccades where subjects are supposed to make saccades to a previously remembered spatial location . predictive saccadic eye movement tasks are used to access subject 's ability to predict target appearance in terms of location and time . antisaccades are voluntary saccades and widely used to access cognitive functions and inhibitory control in clinical conditions . in this saccadic task , subjects are instructed to inhibit saccades towards target and make saccades to a mirror location of the target that is in the opposite direction of the target [ fig . 5 ] . green arrow represents spatial mirror image of the target where subjects are instructed to make saccade . fixation duration varies from 1000 - 3000 ms and target duration is around 1000 ms saccadic eye movements have been widely studied in patients with pd using various tasks . different saccadic paradigms have been used to understand stages of information processing when subjects perform these tasks and how impaired circuitry manifests itself in behaviour in clinical conditions like pd . this section of the review discusses the studies in which saccadic eye movements in parkinson disease patients have been observed and compared with age - matched controls . different results of saccadic performance of pd patients have been observed with no impairments in antisaccades but abnormalities in memory saccades where patients were tested on saccadic tasks . briand and colleagues made pd patients and controls perform on reflexive and voluntary saccadic eye movement tasks . no saccadic impairment in reflexive saccades was found but impairment in voluntary saccadic eye movement tasks was observed . while performing antisaccade tasks , pd patients were found to be slow and made more errors . gain ( ratio of subject 's saccadic amplitude to desired saccadic amplitude ) was also reduced in pd patients in these tasks . segmented saccadic eye movements ( two steps ) was used to measure performance of pd patients and the latency , amplitude was found similar to healthy controls which suggests that pd patients can generate multi saccades which are voluntary . when , moderate to advanced pd patients were investigated on visually guided and voluntary saccades where various parameters like latency , accuracy and peak velocity were determined , it was found that voluntary saccades were more impaired in advanced pd as compared to moderate pd . in one of the studies , pd patients made more directional errors in antisaccade tasks and differential results , where there was impairment in memory guided saccades , were found in short delays in pd patients but when delay was longer there was equivalent performance as controls . results suggest that there are various aspects in impairment of memory guided saccades in pd which need to be carefully studied through further experiments . pd patients are shown to have problems in inhibiting reflexive saccades suggesting executive control deficits in pd . a similar study has shown pd patients to be impaired on visually guided and memory guided saccades and also impaired in suppressing reflexive saccades . reduced latency due to fixation offset effect is considered to be mediated by higher order cognitive processes like attention . when fixation offset effect was measured in patients with pd , impaired cognitive control was reflected as fixation offset effect did nt reduce during antisaccades and more errors were made as compared to controls which is suggestive of impairment of executive control during saccadic eye movements in pd . some studies have shown abnormal facilitation of visually guided and voluntary saccadic eye movements in pd patients . better performance by pd patients was observed on inhibition of return ( ior ) task that involves saccadic elicitation in previously cued and uncued spatial locations . saccadic latencies reduced more in pd group in the perceptual discrimination task as compared to controls suggestive of hyperreflexivity in the pd group . van stockum and coworkers indicated that impairment of voluntary saccades in pd does not happen with reflexive saccade facilitation . pd patients who elicit reflexive saccades at shorter latencies perform similar to control subjects on voluntary saccade task suggesting that pd affects latencies , which is independent of the type of saccadic eye movements . pd patients were hypometric overall and latencies did not correlate with these hypometric saccades . in another study , authors have shown abnormal facilitation of voluntary saccades in perceptual discrimination task in patients with pd as compared to healthy controls . in saccadic eye movement tasks where subjects were asked to make saccades to a fixed sequence of spatial locations , normal healthy subjects made saccades with shorter latencies because they started predicting spatial locations and execution of saccades took place before the target appearance . performance of patients with pd in such saccadic tasks are reported to be impaired which reflects that they are not able to predict saccades . above - mentioned studies indicate an inconsistency in the results as far as performance of pd patients on saccadic tasks is considered . pd patients are impaired in saccadic eye movements as reflected from most of the studies but some studies also suggests performance equivalent to controls and sometimes even facilitation of saccades was observed in patients . thus it is necessary that results should be interpreted in the light of impaired neural circuitry in pd , disease status and saccadic paradigm . various studies have been done to determine effect of medication on saccadic eye movements in patients with pd . corin and coworkers did not find much improvements in saccadic eye movements as only two patients out of twenty nine patients tested showed changes but there was a very poor response in terms of improvements in eye movement dysfunctions . mean latencies of the saccades also reduced in this study but it did nt reach significance level . improvement in saccadic amplitude has been reported where this improvement was seen after ninety minutes of medication . saccadic latency improved mildly when tested after dopaminergic treatment but not to the significant level . nakamura and co - workers investigated twenty - four patients and found only one patient who had reduced saccade velocity and significant improvement in its oculomotor dysfunction after dopaminergic medication . since , majority of the patients did not show any improvement on saccadic parameters , results are inconsistent when beneficial effect of medication on saccadic eye movements are to be considered . step task saccadic paradigm with conditions of no gap or overlap was administered on twenty two pd patients . results suggested increase in saccadic latencies which reflects that medication slowed patients with pd on saccadic tasks . authors discussed their results in terms of neural decision making process considering later model for saccadic eye movements . it was suggested that increased saccadic latencies are due to increased threshold criterion level which is required to take decision for the eye movement . similar results were reported where prolonged response time was observed when pd patients performed on reflexive saccadic task . improvement in saccadic parameters after medication was reflected in reduced error rate when patient performed on voluntary saccadic task which in this case was antisaccade . it was suggested that medication ( levodopa ) helped patients to plan and execute eye movements better which is a reflection of improved impaired frontal - striatal circuitry involved in voluntary eye movements . patients with pd were investigated on reflexive saccadic eye movement tasks where levodopa or dopaminergic treatment prolonged latencies and reduced peak saccadic velocity and enhanced hypometria . review of literature suggests beneficial effects of dopaminergic treatment on saccades in pd in addition to improvement in general motor movements but studies which report no beneficial effect of dopaminergic treatment on saccadic parameters like latency , amplitude and accuracy are also present . further research is required to conclude what aspects of saccadic eye movements are affected by dopaminergic medication . deep brain stimulation ( dbs ) has been reported to have many beneficial effects on the clinical symptoms like bradykinesia , tremors and rigidity of advanced parkinson disease . recently dbs has become a very effective and important tool in the treatment of patients with advanced parkinson disease . in addition to alleviating the motor symptoms of pd , saccadic parameters have also been shown to be differently affected by deep brain stimulation . improvement in accuracy of memory guided saccades with subthalamic ( stn ) bilateral stimulation has been reported . stn dbs did not improve performance of pd patients on visually guided saccadic task ( gap task ) and on the antisaccade task . this study suggests differential effect of dbs in eye movements in pd . in a case report , interruptive eye movements were detected when pd patients with stn dbs off condition were instructed to fixate at the fixation point . such interruptive eye movements were higher in pd patients as compared to age matched control . such movements were reduced when stn dbs was switched on which reflects beneficial effects of deep brain stimulation in eye movements by modulating basal ganglia circuitry . saccadic latencies were reduced and amplitude was enhanced in the on stimulation condition as compared to off condition . visually guided , memory guided and antisaccade task were used to measure performance of pd patients with bilateral stn stimulation on saccadic tasks by fawcett and co - workers . they measured saccadic reaction time and gain and found that saccadic reaction time improved with stn dbs in visually guided saccadic task but not in memory and antisaccadic tasks . on the other hand , stn dbs improved the gain in memory guided and antisaccade tasks but not in visually guided saccades . in one of the electrooculogram ( eog ) study , pd patients with bilateral stn stimulation were instructed to perform on two reflexive saccadic tasks and two volitional saccadic tasks . reflexive saccades included a gap condition ( gap task ) where target appeared after 200ms of fixation point disappearance and with a no gap condition where target appeared simultaneously with fixation point disappearance . pd patients elicited saccades with longer latencies as compared to control subjects in both off and on conditions but dbs significantly reduced saccadic latencies in these patients except for memory guided saccades . stn dbs improved the saccadic gain as compared to no stimulation ( off condition ) but still the patients were hypometric as compared to healthy controls . one of the recent studies reported no beneficial effect of stn dbs on saccadic parameters in terms of latency and amplitude when patients with pd who have undergone stn dbs performed on visually guided saccadic task . most of the studies show improved performance in saccadic tasks by pd with stn dbs but as some studies have reported disparity in performance , further research is required with specific saccadic task modulation for better understanding of effect of dbs on eye movements . parkinson disease patients have been tested on reflexive saccadic task where participants fixate at a fixation point at the centre of the screen . saccades are elicited when a sudden peripheral visual target is presented . in the gap task , which is a variant of reflexive saccade task , saslow showed a fixation offset effect wherein it was seen that saccadic latencies reduced when the fixation point was removed and a gap was introduced between target appearance and fixation point disappearance . in another variant of reflexive saccade , known as overlap task , fixation point remains when sudden peripheral target appears . another saccadic task uses a cue to elicit saccades where it is presented before the target presentation and it indicates the spatial location of future target appearance [ fig . posner showed that saccadic latencies reduce when the cue is presented before the target presentation . there is inhibition of return ( ior ) effect in which saccadic latencies increase when the time gap between cue and target presentation is increased above 300ms [ fig . 4 ] . fixation duration varies from 1000 - 3000 ms and target duration is around 1000 ms schematic representation of inhibition of return ( ior ) paradigm . soa represents stimulus onset asynchrony , which is time between cue ( yellow box ) and target presentation ( red circle ) . fixation duration varies from 1000 - 3000 ms and target duration is around 1000 ms memory guided saccadic tasks are saccades where subjects are supposed to make saccades to a previously remembered spatial location . predictive saccadic eye movement tasks are used to access subject 's ability to predict target appearance in terms of location and time . antisaccades are voluntary saccades and widely used to access cognitive functions and inhibitory control in clinical conditions . in this saccadic task , subjects are instructed to inhibit saccades towards target and make saccades to a mirror location of the target that is in the opposite direction of the target [ fig . 5 ] . green arrow represents spatial mirror image of the target where subjects are instructed to make saccade . different saccadic paradigms have been used to understand stages of information processing when subjects perform these tasks and how impaired circuitry manifests itself in behaviour in clinical conditions like pd . this section of the review discusses the studies in which saccadic eye movements in parkinson disease patients have been observed and compared with age - matched controls . different results of saccadic performance of pd patients have been observed with no impairments in antisaccades but abnormalities in memory saccades where patients were tested on saccadic tasks . briand and colleagues made pd patients and controls perform on reflexive and voluntary saccadic eye movement tasks . no saccadic impairment in reflexive saccades was found but impairment in voluntary saccadic eye movement tasks was observed . while performing antisaccade tasks , pd patients were found to be slow and made more errors . gain ( ratio of subject 's saccadic amplitude to desired saccadic amplitude ) was also reduced in pd patients in these tasks . segmented saccadic eye movements ( two steps ) was used to measure performance of pd patients and the latency , amplitude was found similar to healthy controls which suggests that pd patients can generate multi saccades which are voluntary . when , moderate to advanced pd patients were investigated on visually guided and voluntary saccades where various parameters like latency , accuracy and peak velocity were determined , it was found that voluntary saccades were more impaired in advanced pd as compared to moderate pd . in one of the studies , pd patients made more directional errors in antisaccade tasks and differential results , where there was impairment in memory guided saccades , were found in short delays in pd patients but when delay was longer there was equivalent performance as controls . results suggest that there are various aspects in impairment of memory guided saccades in pd which need to be carefully studied through further experiments . pd patients are shown to have problems in inhibiting reflexive saccades suggesting executive control deficits in pd . a similar study has shown pd patients to be impaired on visually guided and memory guided saccades and also impaired in suppressing reflexive saccades . fixation offset effects have been measured in pd patients . reduced latency due to fixation offset effect is considered to be mediated by higher order cognitive processes like attention . when fixation offset effect was measured in patients with pd , impaired cognitive control was reflected as fixation offset effect did nt reduce during antisaccades and more errors were made as compared to controls which is suggestive of impairment of executive control during saccadic eye movements in pd . some studies have shown abnormal facilitation of visually guided and voluntary saccadic eye movements in pd patients . better performance by pd patients was observed on inhibition of return ( ior ) task that involves saccadic elicitation in previously cued and uncued spatial locations . saccadic latencies reduced more in pd group in the perceptual discrimination task as compared to controls suggestive of hyperreflexivity in the pd group . van stockum and coworkers indicated that impairment of voluntary saccades in pd does not happen with reflexive saccade facilitation . pd patients who elicit reflexive saccades at shorter latencies perform similar to control subjects on voluntary saccade task suggesting that pd affects latencies , which is independent of the type of saccadic eye movements . pd patients were hypometric overall and latencies did not correlate with these hypometric saccades . in another study , authors have shown abnormal facilitation of voluntary saccades in perceptual discrimination task in patients with pd as compared to healthy controls . in saccadic eye movement tasks where subjects were asked to make saccades to a fixed sequence of spatial locations , normal healthy subjects made saccades with shorter latencies because they started predicting spatial locations and execution of saccades took place before the target appearance . performance of patients with pd in such saccadic tasks are reported to be impaired which reflects that they are not able to predict saccades . above - mentioned studies indicate an inconsistency in the results as far as performance of pd patients on saccadic tasks is considered . pd patients are impaired in saccadic eye movements as reflected from most of the studies but some studies also suggests performance equivalent to controls and sometimes even facilitation of saccades was observed in patients . thus it is necessary that results should be interpreted in the light of impaired neural circuitry in pd , disease status and saccadic paradigm . various studies have been done to determine effect of medication on saccadic eye movements in patients with pd . corin and coworkers did not find much improvements in saccadic eye movements as only two patients out of twenty nine patients tested showed changes but there was a very poor response in terms of improvements in eye movement dysfunctions . mean latencies of the saccades also reduced in this study but it did nt reach significance level . improvement in saccadic amplitude has been reported where this improvement was seen after ninety minutes of medication . saccadic latency improved mildly when tested after dopaminergic treatment but not to the significant level . nakamura and co - workers investigated twenty - four patients and found only one patient who had reduced saccade velocity and significant improvement in its oculomotor dysfunction after dopaminergic medication . since , majority of the patients did not show any improvement on saccadic parameters , results are inconsistent when beneficial effect of medication on saccadic eye movements are to be considered . step task saccadic paradigm with conditions of no gap or overlap was administered on twenty two pd patients . results suggested increase in saccadic latencies which reflects that medication slowed patients with pd on saccadic tasks . authors discussed their results in terms of neural decision making process considering later model for saccadic eye movements . it was suggested that increased saccadic latencies are due to increased threshold criterion level which is required to take decision for the eye movement . similar results were reported where prolonged response time was observed when pd patients performed on reflexive saccadic task . improvement in saccadic parameters after medication was reflected in reduced error rate when patient performed on voluntary saccadic task which in this case was antisaccade . it was suggested that medication ( levodopa ) helped patients to plan and execute eye movements better which is a reflection of improved impaired frontal - striatal circuitry involved in voluntary eye movements . patients with pd were investigated on reflexive saccadic eye movement tasks where levodopa or dopaminergic treatment prolonged latencies and reduced peak saccadic velocity and enhanced hypometria . review of literature suggests beneficial effects of dopaminergic treatment on saccades in pd in addition to improvement in general motor movements but studies which report no beneficial effect of dopaminergic treatment on saccadic parameters like latency , amplitude and accuracy are also present . further research is required to conclude what aspects of saccadic eye movements are affected by dopaminergic medication . deep brain stimulation ( dbs ) has been reported to have many beneficial effects on the clinical symptoms like bradykinesia , tremors and rigidity of advanced parkinson disease . recently dbs has become a very effective and important tool in the treatment of patients with advanced parkinson disease . in addition to alleviating the motor symptoms of pd , saccadic parameters have also been shown to be differently affected by deep brain stimulation . improvement in accuracy of memory guided saccades with subthalamic ( stn ) bilateral stimulation has been reported . stn dbs did not improve performance of pd patients on visually guided saccadic task ( gap task ) and on the antisaccade task . this study suggests differential effect of dbs in eye movements in pd . in a case report , interruptive eye movements were detected when pd patients with stn dbs off condition were instructed to fixate at the fixation point . such interruptive eye movements were higher in pd patients as compared to age matched control . such movements were reduced when stn dbs was switched on which reflects beneficial effects of deep brain stimulation in eye movements by modulating basal ganglia circuitry . bilateral stn stimulation improving saccadic parameters in patients with pd has been observed . saccadic latencies were reduced and amplitude was enhanced in the on stimulation condition as compared to off condition . visually guided , memory guided and antisaccade task were used to measure performance of pd patients with bilateral stn stimulation on saccadic tasks by fawcett and co - workers . they measured saccadic reaction time and gain and found that saccadic reaction time improved with stn dbs in visually guided saccadic task but not in memory and antisaccadic tasks . on the other hand , stn dbs improved the gain in memory guided and antisaccade tasks but not in visually guided saccades . in one of the electrooculogram ( eog ) study , pd patients with bilateral stn stimulation were instructed to perform on two reflexive saccadic tasks and two volitional saccadic tasks . reflexive saccades included a gap condition ( gap task ) where target appeared after 200ms of fixation point disappearance and with a no gap condition where target appeared simultaneously with fixation point disappearance . pd patients elicited saccades with longer latencies as compared to control subjects in both off and on conditions but dbs significantly reduced saccadic latencies in these patients except for memory guided saccades . stn dbs improved the saccadic gain as compared to no stimulation ( off condition ) but still the patients were hypometric as compared to healthy controls . one of the recent studies reported no beneficial effect of stn dbs on saccadic parameters in terms of latency and amplitude when patients with pd who have undergone stn dbs performed on visually guided saccadic task . most of the studies show improved performance in saccadic tasks by pd with stn dbs but as some studies have reported disparity in performance , further research is required with specific saccadic task modulation for better understanding of effect of dbs on eye movements . saccadic eye movement is a very important tool to study clinical populations where sensorimotor dysfunctions and cognitive impairments have been reported . it can help us in developing early biological markers for specific pathophysiological state as saccadic eye movement circuitry involves both cortical and subcortical brain areas and saccadic task manipulation gives an insight into the information processing in impaired brain . reflexive and voluntary saccadic tasks provide specific information of brain functioning at different levels in pd . there are conflicting reports of impairment and abnormal facilitation of saccades in case of patients , which can be due to manipulation of saccadic task and disease state but research using saccadic eye movements as a tool in pd patients group has given us valuable information and has increased our understanding about brain functioning in this clinical condition . effect of medication on saccadic eye movement in patients with pd is inconsistent , some showing beneficial effect and others showing worsening of saccadic parameters . there is need of change in strategy to evaluate effect of medication on saccades considering doses , disease stage and age of onset of the disease . most of the studies show that stn deep brain stimulation improves saccadic eye movement parameters in patients with pd . variable results have been found in terms of performance on different saccadic tasks , like visually guided and voluntary tasks , but some consistency in terms of beneficial effects has been observed in the literature .

this review focuses on saccadic eye movement research in parkinson 's disease ( pd ) patients . results from various studies related to parkinson disease and saccades have been discussed in terms of various saccadic parameters like latency , amplitude , velocity and gain . neural circuitry of saccadic eye movements and cognitive processes and it 's relation with altered saccadic performance in parkinson disease has been discussed here . this article also covers various research paradigms commonly used to study saccades . effects of medication on saccadic parameters in pd patients have also been discussed along with the effects of deep brain stimulation of subthalamic nucleus on saccadic performance in pd patients . literature review was done using online pubmed search engine and national medical library .

SECTION 1. FINDINGS. The Congress finds and declares that-- (1) it is the policy of the United States, in fulfillment of its trust responsibility to Indian tribes, to promote Indian self-determination and economic self-sufficiency; (2) the Salt River Pima-Maricopa Indian Community (hereinafter referred to as the ``Community'') has operated the irrigation works within the Community's reservation since November 1997 and is capable of fully managing the operation of these irrigation works; (3) considering that the irrigation works, which are comprised primarily of canals, ditches, irrigation wells, storage reservoirs, and sump ponds located exclusively on lands held in trust for the Community and allottees, have been operated generally the same for over 100 years, the irrigation works will continue to be used for the distribution and delivery of water; (4) considering that the operational management of the irrigation works has been carried out by the Community as indicated in paragraph (2), the conveyance of ownership of such works to the Community is viewed as an administrative action; (5) the Community's laws and regulations are in compliance with section 2(b); and (6) in light of the foregoing and in order to-- (A) promote Indian self-determination, economic self-sufficiency, and self-governance; (B) enable the Community in its development of a diverse, efficient reservation economy; and (C) enable the Community to better serve the water needs of the water users within the Community, it is appropriate in this instance that the United States convey to the Community the ownership of the irrigation works. SEC. 2. CONVEYANCE AND OPERATION OF IRRIGATION WORKS (a) Conveyance.--The Secretary of the Interior, as soon as is practicable after the date of the enactment of this Act, and in accordance with the provisions of this Act and all other applicable law, shall convey to the Community any or all rights and interests of the United States in and to the irrigation works on the Community's reservation which were formerly operated by the Bureau of Indian Affairs. Notwithstanding the provisions of sections 1 and 3 of the Act of April 4, 1910 (25 U.S.C. 385) and sections 1, 2, and 3 of the Act of August 7, 1946 (25 U.S.C. 385a, 385b, and 385c) and any implementing regulations, during the period between the date of the enactment of this Act and the conveyance of the irrigation works by the United States to the Community, the Community shall operate the irrigation works under the provisions set forth in this Act and in accordance with the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450 et seq.), including retaining and expending operations and maintenance collections for irrigation works purposes. Effective upon the date of conveyance of the irrigation works, the Community shall have the full ownership of and operating authority over the irrigation works in accordance with the provisions of this Act. (b) Fulfillment of Federal Trust Responsibilities.--To assure compliance with the Federal trust responsibilities of the United States to Indian tribes, individual Indians and Indians with trust allotments, including such trust responsibilities contained in Salt River Pima- Maricopa Indian Community Water Rights Settlement Act of 1988 (Public Law 100-512), the Community shall operate the irrigation works consistent with this Act and under uniform laws and regulations adopted by the Community for the management, regulation, and control of water resources on the reservation so as to assure fairness in the delivery of water to water users. Such Community laws and regulations include currently and shall continue to include provisions to maintain the following requirements and standards which shall be published and made available to the Secretary and the Community at large: (1) Process.--A process by which members of the Community, including Indian allottees, shall be provided a system of distribution, allocation, control, pricing and regulation of water that will provide a just and equitable distribution of water so as to achieve the maximum beneficial use and conservation of water in recognition of the demand on the water resource, the changing uses of land and water and the varying annual quantity of available Community water. (2) Due process.--A due process system for the consideration and determination of any request by an Indian or Indian allottee for distribution of water for use on his or her land, including a process for appeal and adjudication of denied or disputed distributions and for resolution of contested administrative decisions. (c) Subsequent Modification of Laws and Regulations.--If the provisions of the Community's laws and regulations implementing subsection (b) only are to be modified subsequent to the date of the enactment of this Act by the Community, such proposed modifications shall be published and made available to the Secretary at least 120 days prior to their effective date and any modification that could significantly adversely affect the rights of allottees shall only become effective upon the concurrence of both the Community and the Secretary. (d) Limitations of Liability.--Effective upon the date of the enactment of this Act, the United States shall not be liable for damages of any kind arising out of any act, omission, or occurrence based on the Community's ownership or operation of the irrigation works, except for damages caused by acts of negligence committed by the United States prior to the date of the enactment of this Act. Nothing in this section shall be deemed to increase the liability of the United States beyond that currently provided in the Federal Tort Claims Act (28 U.S.C. 2671 et seq.). (e) Cancellation of Charges.--Effective upon the date of conveyance of the irrigation works under this section, any charges for construction of the irrigation works on the reservation of the Community that have been deferred pursuant to the Act of July 1, 1932 (25 U.S.C. 386a) are hereby canceled. (f) Project No Longer a BIA Project.--Effective upon the date of conveyance of the irrigation works under this section, the irrigation works shall no longer be considered a Bureau of Indian Affairs irrigation project and the facilities will not be eligible for Federal benefits based solely on the fact that the irrigation works were formerly a Bureau of Indian Affairs irrigation project. Nothing in this Act shall be construed to limit or reduce in any way the service, contracts, or funds the Community may be eligible to receive under other applicable Federal law. SEC. 3. RELATIONSHIP TO OTHER LAWS. Nothing in this Act shall be construed to diminish the trust responsibility of the United States under applicable law to the Salt River Pima-Maricopa Indian Community, to individual Indians, or to Indians with trust allotments within the Community's reservation. Passed the House of Representatives October 3, 2000. Attest: Clerk.

Requires the operation of the works consistent with specified standards, including those for: (1) equitable distribution of water; and (2) a due process system for determination of any request for distribution of water. Cancels on the conveyance date any charges for construction of the works that were deferred. Provides that, upon such date, the works shall no longer be considered a BIA irrigation project and will not be eligible for Federal benefits based solely on the fact that the works were formerly such a project.

a sufficient number of observations is needed to ensure the necessary power of a statistical test in a variety of studies ( e.g. , randomized clinical trials).1 thanks to the wide adoption of electronic health records ( ehrs ) and recent developments in distributed data networks ( drns),25 it is technically possible to pull together data from geographically distributed institutions to enable meaningful studies efficiently . for example , united states researchers use clinical and next - generation sequencing ( ngs ) data to study the kawasaki disease , but local samples at rady children s hospital ( affiliated with the university of california , san diego ucsd ) at san diego are limited . international collaborations ( e.g. , with japan and singapore ) but nave procedures that involve patient - level data transferring will increase the privacy risk and may violate the institutional policy of sharing . as an example , unless explicitly requested and institutionally approved , all sensitive patient data must remain on the u.s . department of veterans affairs ( va ) informatics and computing infrastructure ( vinci ) project servers , and only aggregate data without personal identifiers may be transferred from vinci . it is nontrivial to enable cross - institutional collaboration to respect patient privacy and institutional policies.68 sweeney showed that it is possible to recover personal identifiable information ( pii ) through linkage of quasi - identifiers ( e.g. , zip codes , gender , and date of birth ) from a private data set ( e.g. , hospital discharge data ) to data from public data sets ( e.g. , demographics from a voter registry).9 other attack models showed that pii can be inferred under more restrictive conditions by using unforeseen auxiliary information.1012 we recently reviewed privacy technologies to support data sharing for comparative effectiveness research.13 in this review , we explained that most synthetic data generation methods aim to protect privacy by introducing indistinguishability via the following : ( 1 ) sanitizing mechanisms like generalization or suppression of values,1416 and ( 2 ) synthetic answer and data generation mechanisms that perturb the data.1720 these methods involve modifications of the original data and can make the disclosed data less useful for biomedical studies . another line of privacy technology research , which is not related to synthetic data releasing , aims at sharing models without sharing data through secure multiparty computing ( smc),2124 as illustrated in figure 1 . ( smc is a generalized method that enables secure data analysis across partitioned data from multiple institutes . ) these approaches use security - enhanced protocols ( e.g. , transmission of partial statistics through encrypted protocols ) to provide a practical solution for building accurate predictive models through cross - institutional collaboration . several smc - based privacy - preserving , data mining models such as linear regression,25 clustering,26 and support vector machine27 have been developed to handle horizontally partitioned data ( e.g. , data of the same nature that are available at different institutions ) . most relevant to our work are studies related to distributed logistic regression , which is the most popular predictive model in the biomedicine literature . chu et al . introduced a map - reduce approach for logistic regression that enabled distributed model construction,28 but it focused only on parallelization to accelerate the computation as this method arbitrarily allocates data and computation to a cluster of nodes to make the best use of available resources . other articles29,30 discussed privacy - preserving data analysis , but they did not explain how to evaluate the models , e.g. , calculating the hosmer - lemeshow goodness - of - fit test ( hl - test)31 or areas under the receiver operating characteristic ( roc ) curve,32 in a distributed manner . these articles also did not provide a ready - to - use platform or software for biomedical researchers to easily deploy distributed learning frameworks in real health care environments . in this article , we provide details on our recent work in developing collaborative software as a service ( saas ) for the grid logistic regression ( glore ) , previously published as web service for grid logistic regression ( webglore),33 which is based on our previously established algorithm that showed how to build and evaluate a distributed logistic regression model.34 we describe in detail the design and implementation of webglore as an initial pilot effort to assess the feasibility of these methods in practice . we also discuss challenges and enabling factors in translating innovative privacy technology into a prototype system . imagine that an institution a wants to explore the contributing factors to the kawasaki disease , which is a rare condition occurring in children that involves inflammation of the blood vessels . because local observations are limited , a would like to collaborate with external partners ( e.g. , international research institutes ) to build a logistic regression model using more cases to identify critical attributes more reliably . due to the size of the data ( each next generation sequencing sample is about 200 gb ) and the privacy policy of participating institutes ( participants ) , it is not feasible to move patient - level data around or build a centralized repository to meet this need . our glore35 framework , which allows global models to be constructed from distributed data sets without sharing raw data , can handle a use case like this . our framework was motivated by the scalable national network for effectiveness research ( scanner ) project ( http://scanner.ucsd.edu ) and extended from a backbone program that runs on terminals to a web service , which does not require installation , to promote easy access and efficient collaboration in a distributed setting . we designed the system to follow specifications elicited from multiple researchers at ucsd and researchers at cincinnati children s hospital . the web service was briefly described in an application note,33 but it included very few details that are relevant for developers . figure 2 shows a high - level overview of the webglore system . during the design and implementation of webglore , we determined that the following requirements were important : user friendliness : the system needed to be simple to use for biomedical researchers , with no requirements for installation or system configuration.platform independence : the system needed to be deployable in a variety of hosting environments ( i.e. , accommodate different operatin gsystems).security : we needed to ensure information security during information exchange.efficient evaluation : online summarization of global and local models needed to support quick comparisons.enforced authentication : only signed modules ( java applets and servlets ) should interact with one another . user friendliness : the system needed to be simple to use for biomedical researchers , with no requirements for installation or system configuration . platform independence : the system needed to be deployable in a variety of hosting environments ( i.e. , accommodate different operatin gsystems ) . efficient evaluation : online summarization of global and local models needed to support quick comparisons . enforced authentication : only signed modules ( java applets and servlets ) should interact with one another . r ( https://www.dropbox.com/s/gmnrqgifdq9tjd7/glore_r.zip)and java ( https://code.google.com/p/glore/ ) and incrementally improving the user experience by continually interacting with potential users in different stages of the development . during the deployment process , we encountered challenges due to information technology ( it ) infrastructure gaps such as platform compatibility , permission of third - party installation , jsp - applet communication , etc . our original design was a client - side graphical interface for the backbone system that communicated on specified ports , which turned out to be impractical due to a number of disadvantages : ( 1 ) some partners were reluctant to install third party software , ( 2 ) communication through prespecified ports brings security concerns , and ( 3 ) the application may not support all platforms unless implemented individually . these limitations were identified through discussions at an early stage of the development , which avoided extra effort to rectify them later . we ended up developing an applet - servlet architecture , which does not require installation or port specification , to support cross platform deployment and ease of use . we also developed the user interface to allow enough flexibility to meet the demands of potential users . among various enabling factors for translating the innovative privacy - preserving , distributed modeling technology into a working prototype , we identified separating the interface development from algorithm development and integrated resource management ( e.g. , code , document , and calendar ) to be most important . zoho project management ( http://www.zoho.com/projects ) to track tasks and milestones , and leveraged google code ( https://code.google.com ) and apache subversion ( http://subversion.apache.org ) ( a free version control system ) to share code among team members in the development phase . we developed four major modules to handle user registration , initiator task creation , user participation , and collaborative model construction , respectively . figure 4 shows the pipeline of webglore at a high level , which includes four major components ( user authentication , task initialization , user participation , and global optimization ) . these components are elaborated in details figure 5 , which illustrates the workflow from a user s perspective in detail . webglore first checks if a user is registered or not using its user authentication component ( ) . the next component to be activated after authentication is the task initiation component ( ) , which starts with specifying the parameters ( name , expiration date , participants email address , as well as the path of local training data to be linked ) . note that the local computation module ( an applet resides in the java virtual machine ) links to the local data will compute necessary intermediary statistics to be exchanged but no patient - level data leave the host . an important challenge in task initialization is to ensure the consistency of predictive attributes across participants because a single inconsistent attribute can jeopardize the entire learning process . ideally , data should match syntactically ( i.e. , name consistency ) and semantically ( i.e. , value consistency ) . our system supports syntactic validation by checking whether attribute names ( specified by the first row of local data files in our convention ) are consistent to support basic data harmonization . we do not support semantic validation at this point . after passing the syntactic consistency check , the user - initiator can invite participants , who have the same type of data ( i.e. , same attributes ) and want to build a global logistic regression . after a task is initialized , the user participation component ( ) will be activated . each invited participant will receive an email from the glore server ; each one is provided with a unique link ( e.g. , hashed by task name and participant s email ) . the system also memorizes existing collaborators and stores their emails ( in a list for quick retrieval from the invitation panel ) . start calculating , the server begins to interact with all participants , including the task initiator . the system is also responsible for tracking user status ( i.e. , online / offline ) , model learning progress , as well as the value of the log - likelihood ( i.e. , the objective function ) at each step during the computation . when sufficient participants accepted the invitation and got their systems ready ( i.e. , completed the data linkage process ) , the task - initiator can trigger the global computation component ( ) . then , local statistics ( i.e. , gradient , hessian matrix ) will be calculated using these global parameters based on local datasets . the local statistics are transmitted to the central node , which combines the gradients and the hessian matrix to conduct one iteration of the newton ralphson algorithm for optimization . this process is iterated in the distributed manner until global parameters converge or the maximum number of iterations is reached ( http://jamia.bmj.com/content/suppl/2012/04/16/amiajnl-2012-000862.dc1/appendix.pdf ) . the computation process is transparent to participants so they can watch inputs and outputs at each step ( tracked in a panel on the computing web page ) . when the calculation is finished , each participant will receive separate reports that allow he or she to compare the global model to locally trained logistic regression models . note that the global report will only be created once ( automatically by the webglore system ) for each task , and it can be retrieved through a unique url that is accessible only by the task participants . for local reports , individual users click the button get local report that triggers a one - time calculation using the linked local data . there is no information exchange in this step and the computation takes place in the browser ( through the java virtual machine applet ) . each report contains important statistics , graphs , and performance measures such as sensitivity , specificity , area under the roc curve ( auc ) , and hosmer - lemeshow test p - values . the report also shows the plots of the roc curve and of the reliability diagram . webglore is open source , and the code is freely available at https://code.google.com / p / webglore/. on the webglore website , we embedded three short demo videos ( http://dbmi-engine.ucsd.edu/webglore2/instructions.html ) to help first time users . the first one is an introduction of webglore , which walks users through different pages and the authentication process . the second demo is to show how webglore can be used as a standard online logistic regression package , which works for a single user case . the development of webglore is an experience of constantly changing design and architecture to meet the need of potential partners . collaborator provided valuable suggestions to build a secure and easy - to - deploy framework , amenable to the existing healthcare environment . our research partner from duke university commented that comprehensive statistical reports for both local and global models should be provided to facilitate users in conducting comparative effectiveness research . yet another helpful instruction was from edm forum to emphasize on user experience in research computing . all these suggestions are highly valuable and we took them into serious consideration to redesign the system in multiple iterations . as a result , our package evolved from a port - based command - line interface to a heavy - client light - server webservice architecture , which includes necessary elements to meet the suggestions . in specific , webglore carry out computation tasks locally to ensure data privacy and leverages the server to combine results for global analysis . we developed signed communication protocols between servlets and applets using java , as illustrated in figure 5 . the applets are embedded in web pages ( and executed by the java virtual machine ) to handle local computation so that data never leave their host institutions . since only signed applets can execute and communicate with servlets , we can easily check the validity of inputs from participants on the server side . we validated the system using public- and private data sets , which shows the same results as the centralized model . for more details we developed four major modules to handle user registration , initiator task creation , user participation , and collaborative model construction , respectively . figure 4 shows the pipeline of webglore at a high level , which includes four major components ( user authentication , task initialization , user participation , and global optimization ) . these components are elaborated in details figure 5 , which illustrates the workflow from a user s perspective in detail . webglore first checks if a user is registered or not using its user authentication component ( ) . the next component to be activated after authentication is the task initiation component ( ) , which starts with specifying the parameters ( name , expiration date , participants email address , as well as the path of local training data to be linked ) . note that the local computation module ( an applet resides in the java virtual machine ) links to the local data will compute necessary intermediary statistics to be exchanged but no patient - level data leave the host . an important challenge in task initialization is to ensure the consistency of predictive attributes across participants because a single inconsistent attribute can jeopardize the entire learning process . ideally , data should match syntactically ( i.e. , name consistency ) and semantically ( i.e. , value consistency ) . our system supports syntactic validation by checking whether attribute names ( specified by the first row of local data files in our convention ) are consistent to support basic data harmonization . we do not support semantic validation at this point . after passing the syntactic consistency check , the user - initiator can invite participants , who have the same type of data ( i.e. , same attributes ) and want to build a global logistic regression . after a task is initialized , the user participation component ( ) will be activated . each invited participant will receive an email from the glore server ; each one is provided with a unique link ( e.g. , hashed by task name and participant s email ) . the system also memorizes existing collaborators and stores their emails ( in a list for quick retrieval from the invitation panel ) . after participants confirm attendance and the task initiator triggers start calculating , the server begins to interact with all participants , including the task initiator . the system is also responsible for tracking user status ( i.e. , online / offline ) , model learning progress , as well as the value of the log - likelihood ( i.e. , the objective function ) at each step during the computation . when sufficient participants accepted the invitation and got their systems ready ( i.e. , completed the data linkage process ) , the task - initiator can trigger the global computation component ( ) . then , local statistics ( i.e. , gradient , hessian matrix ) will be calculated using these global parameters based on local datasets . the local statistics are transmitted to the central node , which combines the gradients and the hessian matrix to conduct one iteration of the newton ralphson algorithm for optimization . this process is iterated in the distributed manner until global parameters converge or the maximum number of iterations is reached ( http://jamia.bmj.com/content/suppl/2012/04/16/amiajnl-2012-000862.dc1/appendix.pdf ) . the computation process is transparent to participants so they can watch inputs and outputs at each step ( tracked in a panel on the computing web page ) . when the calculation is finished , each participant will receive separate reports that allow he or she to compare the global model to locally trained logistic regression models . note that the global report will only be created once ( automatically by the webglore system ) for each task , and it can be retrieved through a unique url that is accessible only by the task participants . for local reports , individual users click the button get local report that triggers a one - time calculation using the linked local data . there is no information exchange in this step and the computation takes place in the browser ( through the java virtual machine applet ) . each report contains important statistics , graphs , and performance measures such as sensitivity , specificity , area under the roc curve ( auc ) , and hosmer - lemeshow test p - values . the report also shows the plots of the roc curve and of the reliability diagram . webglore is open source , and the code is freely available at https://code.google.com / p / webglore/. on the webglore website , we embedded three short demo videos ( http://dbmi-engine.ucsd.edu/webglore2/instructions.html ) to help first time users . the first one is an introduction of webglore , which walks users through different pages and the authentication process . the second demo is to show how webglore can be used as a standard online logistic regression package , which works for a single user case . the development of webglore is an experience of constantly changing design and architecture to meet the need of potential partners . collaborator provided valuable suggestions to build a secure and easy - to - deploy framework , amenable to the existing healthcare environment . our research partner from duke university commented that comprehensive statistical reports for both local and global models should be provided to facilitate users in conducting comparative effectiveness research . yet another helpful instruction was from edm forum to emphasize on user experience in research computing . all these suggestions are highly valuable and we took them into serious consideration to redesign the system in multiple iterations . as a result , our package evolved from a port - based command - line interface to a heavy - client light - server webservice architecture , which includes necessary elements to meet the suggestions . in specific , webglore carry out computation tasks locally to ensure data privacy and leverages the server to combine results for global analysis . we developed signed communication protocols between servlets and applets using java , as illustrated in figure 5 . the applets are embedded in web pages ( and executed by the java virtual machine ) to handle local computation so that data never leave their host institutions . since only signed applets can execute and communicate with servlets , we can easily check the validity of inputs from participants on the server side . we validated the system using public- and private data sets , which shows the same results as the centralized model . for more details we were able to construct a web service for global logistic regression modeling using distributed data sets that followed design specifications elicited from multiple researchers at ucsd and a collaborator at another institution . because the information exchange required to build the model does not involve transmission of patient - level data , our system has reduced privacy risk when compared to the more common centralization of data followed by local computation of parameters . in addition , the webglore reduces computation time thanks to the parallelization with multiple clients . for example , it does not handle missing values or attribute domain mismatch ( i.e. , when the same attribute has different values in different data sets ) . another limitation is that our system does not handle local site effects ( fixed or random ) . because these effects have the potential to significantly influence results of the analyses , we plan to address them in future work . for a handful of participants , it may be viable to assume fixed cluster effects and learn parameters for additional binary attributes that can represent the unknown factors associated with individual institutions . random effects are more difficult to account for , especially in a distributed setting , and thus will require further investigation . while webglore has limitations , it shows great promise in obtaining accurate analysis results in a distributed and privacy - preserving manner through exchanging aggregated partial estimates across the information - centric networking ( icn ) . it interacts with local data and conducts local computation through the java applet application , which requires certificates from a trusted authority to ensure security ( starting with java 7 update 51 in 2014 , self - signed certificate is blocked by default ) . in addition , some users showed concerns about allowing automated scripts to access sensitive data and transfer information even though the process is transparent . to tackle these concerns , we plan to improve our implementation by supporting asynchronized human - in - the - loop authentication during every information - transmission step , and we plan to migrate the next version of webglore to chrome apps , which is capable as a native application , but as safe as a web page , to mitigate the security issue . innovation in biomedicine requires health care researchers to constantly incorporate and customize state - of - the - art technologies into the available it infrastructure . to make these translational efforts meaningful with a minimal burden to the end users ( researchers , clinicians , patients ) , it is important to expose novel functionality in a natural and intuitive manner . using glore as the basis , we showed how we built and integrated various technologies into a usable framework to support a distributed privacy - preserving modeling . we would like to find more biomedical applications for webglore , and we welcome collaborations in extending it to general purpose , distributed data - analysis applications through the development of a wide range of secure primitives for partition data .

objective : we describe functional specifications and practicalities in the software development process for a web service that allows the construction of the multivariate logistic regression model , grid logistic regression ( glore ) , by aggregating partial estimates from distributed sites , with no exchange of patient - level data.background:we recently developed and published a web service for model construction and data analysis in a distributed environment . this recent paper provided an overview of the system that is useful for users , but included very few details that are relevant for biomedical informatics developers or network security personnel who may be interested in implementing this or similar systems . we focus here on how the system was conceived and implemented.methods:we followed a two - stage development approach by first implementing the backbone system and incrementally improving the user experience through interactions with potential users during the development . our system went through various stages such as concept proof , algorithm validation , user interface development , and system testing . we used the zoho project management system to track tasks and milestones . we leveraged google code and apache subversion to share code among team members , and developed an applet - servlet architecture to support the cross platform deployment.discussion:during the development process , we encountered challenges such as information technology ( it ) infrastructure gaps and limited team experience in user - interface design . we figured out solutions as well as enabling factors to support the translation of an innovative privacy - preserving , distributed modeling technology into a working prototype.conclusion:using glore ( a distributed model that we developed earlier ) as a pilot example , we demonstrated the feasibility of building and integrating distributed modeling technology into a usable framework that can support privacy - preserving , distributed data analysis among researchers at geographically dispersed institutes .

retrieval of tropospheric ozone ( o3 ) concentrations from satellites can be challenging given optical interferences such as clouds , aerosols and the stratospheric o3 layer . state - of - the - art spectrometers and interferometers on board current satellites ranging from the microwave to the ultraviolet bands of the electromagnetic spectrum are used to retrieve total column o3 ( tco ) and vertically - resolved o3 mixing ratios ( beer et al . 2001 ; goldberg et al . 2003 ; levelt et al . 2006 ; waters et al . 2006 ; clerbaux et al . 2009 ; liu et al . the signal collected by satellites from the lower - free troposphere and the boundary layer is small , resulting in coarse vertical resolution ( ~5 km ) at these lower layers and increased uncertainty of the retrieved values ( bowman et al . much work has been conducted to extract the tropospheric column o3 ( tpco ) from the raw irradiances and/or tco measurements ( fishman and larsen 1987 ; ziemke et al . 1998 ; 2006 ; liu et al . 2006 ; schoeberl et al . 2007 ) . the validation of both tpco and tco amounts against independent datasets and/or model simulations have been extensive ( balis et al . 2007 ; worden et al . 2007a ; kroon et al . ; osterman et al . 2008 ; richards et al . 2008 ; antn et al . tes retrievals of vertically resolved o3 are generally biased high between 0 and 20 % in the troposphere when compared to ozonesonde measurements ( nassar et al . 2010 ) , and ozone monitoring instrument ( omi ; also on board aura ) ozone profile retrievals are biased high between 20 and 60 % in the troposphere compared to ozonesonde measurements ( kroon et al . 2011 ) . by combining satellite measurements of different spectral ranges ( infrared and ultraviolet ) , improvements by a factor of two in the sensitivity to the lower tropospheric and boundary layer o3 the inability of the current sun - synchronous , low - earth orbit satellite measurements to resolve o3 concentrations within the boundary layer has limited the application of satellite o3 observations for control and regulation purposes , the study of chemical and physical processes leading to the formation and transport of o3 , and investigations of regional impacts of o3 to the health of humans and the biosphere . instrumentation , retrieval algorithms and data processing have become increasingly sophisticated , resulting in detection of plumes within the troposphere ( kar et al . 2007 ) and observations of impacts of o3 on the biosphere ( fishman et al . the previous studies have relied on either enhanced signals within plumes and/or temporal averaging to detect o3 mixing ratios within the troposphere , limiting the applications to higher frequency ( i.e. diurnal ) processes within the boundary layer . work has been conducted to quantify the correlation between o3 mixing ratios at the surface and partial column o3 amounts in the boundary layer ( 03 km ) using ozonesonde datasets across north america ( chatfield and esswein 2012 ) . the applicability of these correlations to satellite retrievals assumes that satellite retrievals are sensitive to boundary layer atmospheric pollutants . the calculated averaging kernels used in the satellite retrievals within the boundary layer suggest that satellites are not sensitive to boundary layer pollutants ( e.g. bowman et al . similar investigations within a more defined region over a shorter timescale can potentially reveal more information on the extent and processes behind vertical o3 correlations . at present thus , techniques that can extract near - surface information from partial columns within the mid - to - upper troposphere are highly desirable . in this work , we present a promising technique to expand tes capabilities using campaign data from a prototypical pollution regime . we present an investigation of o3 variability and vertical correlations of o3 mixing ratios and partial columns at two sites in the mid - atlantic united states . the results from this study are then used to derive near - surface o3 amounts using existing satellite measurements from the tropospheric emission spectrometer ( tes ) . this work utilizes the extensive set of observations collected as part of nasa s deriving information on surface conditions from column and vertically resolved observations relevant to air quality ( discover - aq ) campaign during july 2011 in the baltimore , md / washington d.c . the campaign consisted of measurements from three aircraft , twelve ground stations , two free - flying and tether balloon systems , and a ship in the chesapeake bay ( data publicly available at http://www-air.larc.nasa.gov/cgi-bin/arcstat-d ) . a subset of these measurements ( described below ) , specifically over edgewood , md ( ew ; lat : 39.4100 , lon : 76.2967 ) approximately 30 km northeast of baltimore , md and beltsville , md ( bv ; lat : 39.0540 , lon : 76.8773 ) approximately 22 km northeast of washington , d.c . the respective proximities of these sites to the chesapeake bay ( ~3 km for ew and 38 km for bv ) allow the investigation of marine layers on upper tropospheric and near - surface o3 correlations . the objective of this study is to use correlation statistics to improve methods of obtaining near - surface o3 from satellite retrievals . the approaches taken within this manuscript apply to an operational satellite , but with further refinements with more campaign statistics , can also enhance retrievals from planned geostationary satellites ( nasa s geostationary coastal and air pollution events , geo - cape ; national research council 2007 ; europe , sentinel-4 ; committee on earth observation satellites 2009 ; ingmann et al . 2012 ; asia , korean geostationary environment monitoring spectrometer , gems and geostationary mission for meteorology and air pollution , gmap - asia ; akimoto et al . 2008 ; tempo , http://science.nasa.gov/missions/tempo/).fig . 1site map of the nasa discover - aq july 2011 campaign in the baltimore , md / washington d.c . an example flight track of the nasa p3-b aircraft is indicated by the white line , with circles representing locations of vertical profiles site map of the nasa discover - aq july 2011 campaign in the baltimore , md / washington d.c . an example flight track of the nasa p3-b aircraft is indicated by the white line , with circles representing locations of vertical profiles a total of 39 ozonesondes were launched at ew and 25 at bv during the campaign . the o3 instrument at ew comprised of an electrochemical concentration cell ( ecc ; droplet measurement technologies , dmt ) containing 1 % solution by mass of potassium iodide ( ki ) in deionized water and fully - buffered ( 0.625 % sodium phosphate and 2.5 % potassium bromide by mass ; komhyr 1986 ) . the dmt sonde is manufactured to the same specifications as the ensci-2z ( environmental science corporation ) sondes flown in prior maryland soundings ( thompson et al . 2009 ) . at bv , a dmt ozonesonde and a 0.5 % ki , the nominal uncertainty of o3 measurements in the troposphere is 5 % ( e.g. deshler et al . 2008 ) , but the uncertainty is dependent on the electrochemical solution strength and ambient pressure . data were collected at 1 hz as the balloon ascends and the data were transmitted in real time to a ground station using an attached radiosonde ( international met systems , imet-1 at ew and vaisala , rs-92 at bv ) . the radiosonde provides pressure , temperature , humidity , wind speed and direction , and georeference information . the pressure , temperature and humidity on the radiosonde are accurate to within 0.5 hpa , 0.2 c and 5 % , respectively . the almost daily ozonesonde launches coincided with aircraft vertical profiles ( discussed below ) during flight days and the approximate overpass of the aura satellite ( ~13:45 lt ) on non - flight days . the mean height at apogee was 31.7 km with an average ascent time of 99 min . maximum distances of the balloon to the respective ground station ranged from 19 to 88 km with a median of 47 km . the distance between the site and the balloon typically peaked at the top of the troposphere . ozonesonde data were validated against coincident aircraft profiles within the boundary layer and the lower free troposphere . the nasa p3-b , a four - turboprop engine aircraft , conducted 45 profiles over ew and 43 profiles over bv during the discover - aq july 2011 campaign . the average minimum and maximum altitudes over which the aircraft flew over ew were 0.3 km and 3.6 km , respectively . a typical spiral of the aircraft was 5 km in diameter and each profile took on average 14 min . on the p3-b , o3 is measured in - situ via the chemiluminescent reaction it undergoes with excess nitric oxide ( no ; ridley et al . 1992 ) . a 2 standard cubic centimeters per minute ( sccm ) flow of pure no is added to the 480 sccm flow of ambient air , and the photons produced are counted using a photomultiplier tube cooled with dry ice . the approximate response time is 1 s and the data are reported at 1 hz . over the course of the discover - aq 2011 campaign , the instrument was calibrated on the ground three times against a teco model 49ps calibrator , and the calibration was stable to a nominal 3 % . given this , and the intrinsic uncertainty in the calibrator , we estimate an overall uncertainty of 5 % in the chemiluminescent measurement of o3 . for the levels of o3 typical of the discover - aq campaign , the precision in the 1-s values is in the range 0.20.4 ppbv , increasing with mixing ratio . ozonesonde measurements of total column , partial column and mixing ratio profiles at ew were compared with nadir - viewing tes observations on board the aura satellite ( beer et al . the level 2 ( version 5 ) o3 products , which consist of global survey and special observation swaths of o3 profiles and total and tropospheric o3 column amounts , were used for these analyses . three special observations occurred within the region during the campaign , focusing on bv , ew and fair hill , md ( another discover - aq ground site ~50 km northeast of ew , lat : 39.7014 ; lon : 75.8600 ) . the swaths have a horizontal resolution at the surface of 5.3 km 8.4 km . ozone mixing ratios are retrieved for 88 pressure levels including the surface with retrievals approximately every 600800 m. the higher number of tropospheric retrievals from tes and higher sensitivity of the instrument to o3 within the troposphere compared to similar satellite products from omi favors using tes data for these analyses . pixels from tes that were within 150 km and 3 h of ozonesonde launch locations were defined as coincident and used for the comparison . these coincidence criteria are stricter than those of previous studies ( e.g. worden et al . a total of 3 tes overpasses were defined as coincident and used in this analysis : one global survey and two special observations ( stares ) over ew and bv . these satellite overpasses were coincident with three ozonesondes launched at ew and two ozonesondes at bv . a total of 28 tes scans were analyzed since the special observations contained between 13 and 14 scans per overpass . the scans were filtered using the reported retrieval master quality flag in addition to the ccurve flag , which represents cases of unrealistic retrievals . three scans on each edge of the special observation overpasses were not included in the analysis ( j. worden , personal communication ) . the average reported precision of the total and tropospheric column o3 amount from tes for the data used are 1.1 % and 5.4 % , respectively , with biases in the tropospheric mid - latitudes between 10 and 20 % ( nassar et al . uncertainties in the o3 measurement from the sondes are a function of altitude typically ranging from 5 to 10 % , however , previous studies have shown a high bias when using the 1 % ki , fully - buffered solution with ensci-2z eccs when compared to a uv photometer during controlled experiments ( barnes et al . 1985 ; johnson et al . 2002 ; smit et al . 2007 ; deshler et al . 2008 ) . sensitivity tests of the o3 response show that the buffer concentration is the major contributing factor towards the high bias ( johnson et al . 2002 ) , most likely due to side reactions involving hypoiodite and perphospate leading to an additional source of iodine ( saltzman and gilbert 1959 ) . using a 1 % solution strength at edgewood , md allowed the opportunity to conduct field observations with coincident in situ measurements to identify the magnitude of the previously identified artifacts . thus , o3 partial pressure data that were collected during discover - aq 2011 at edgewood , md were corrected for this high bias by applying a correction based on the controlled experiments conducted as part of the jlich ozone sonde intercomparison experiment ( josie ) 1998 simulation ( smit et al . the correction presented below is independent of the background corrections and pump flow corrections summarized in johnson et al . the correction was calculated as follows : first , the relative bias profiles observed during josie-1998 were averaged into 5 km vertical bins . the smoothed data were spatially interpolated corresponding to the measured altitudes of each ozonesonde using a cubic spline . the interpolated relative biases were multiplied by each o3 partial pressure measurement and subtracted from the actual measurement . finally , the corrected partial pressures of o3 were converted to a volume mixing ratio using the in situ temperature and pressure measurements . differences between the coincident o3 measurements collected from ozonesondes and in situ measurements from the p3-b using ew and bv profiles were observed ( fig . 2 ) . the data are 100 m bin averages with uncertainties presented every 500 m for clarity . the mean bias ( mb ) and coefficient of variation of the root - mean - squared error ( rmsecv ) averaged over the vertical range of coincident measurements of the uncorrected ozonesonde data from ew referenced to the aircraft measurements are 13.3 % and 13.6 % , respectively . with the correction , the mb and rmsecv become 0.4 % and 9.6 % , within the combined uncertainty ( ~11 % ) of the respective measurements . the mb and rmsecv for beltsville ozonesonde profiles are 6.1 % and 6.9 % , respectively , in agreement with previous controlled simulations using 0.5 % ki , half - buffered solutions ( smit et al . 2007 ) . since the biases were less than the estimated combined uncertainty of the p3-b and sonde o3 measurements and since this correction is strictly to compensate for the previously observed artifacts associated with using a 1 % ki solution , the correction was not applied to the beltsville sonde data . the response time of the ozonesondes are between 20 and 30 s , whereas the response time of the p3-b chemiluminescence ozone instrument is on the order of 1 s. thus , a spatial lag between the ozonesonde and aircraft measurements based on the ascent rate of the balloon is expected . the spatial lag was calculated as the maximum of the un - scaled cross - covariance between the ozonesonde and aircraft measurements . the altitude of the ozonesonde measurement was adjusted downward using the mean ascent rate between the time of measurement ( tm ) and tm minus the lag time . when the lag of the ozonesonde measurements is taken into account and compared with the aircraft measurements , the mb and rmsecv is reduced to 0.1 % and 8.3 % . although the corrections increase the average uncertainty of o3 mixing ratios from ozonesondes throughout the entire ozonesonde profile from 8 % to 9 % , these results show that this correction , based on independent controlled simulations , is sensible for these measurements . the bias correction was applied to all ew ozonesonde measurements hereafter and the response time correction was applied to both ew and bv sondes.fig . 2comparison of percent error between the coincident ozonesondes and p3-b ozone profiles at edgewood , md ( black ) during july 2011 using uncorrected ( dashed ) and corrected ( for chemical artifacts , solid ) data . uncorrected data from beltsville , md is shown ( gray ) . the beltsville profile comparisons do not exceed 2 km due to the airspace limitations placed on the p3-b aircraft . the error bars ( presented every 500 m for clarity ) represent 1 standard deviations calculated from bootstrap statistics comparison of percent error between the coincident ozonesondes and p3-b ozone profiles at edgewood , md ( black ) during july 2011 using uncorrected ( dashed ) and corrected ( for chemical artifacts , solid ) data . the beltsville profile comparisons do not exceed 2 km due to the airspace limitations placed on the p3-b aircraft . the error bars ( presented every 500 m for clarity ) represent 1 standard deviations calculated from bootstrap statistics there is potential for this correction to be applied in the post - processing of past ozonesonde measurements using ecc o3-detection methods and a 1 % ki solution , fully buffered . the challenges faced by long - term o3-monitoring networks such as the global atmospheric watch ( gaw ) , the network for the detection of atmospheric composition change ( ndacc ) and the southern hemisphere additional ozonesondes ( shadoz ; e.g. thompson et al . ( 2003 ) require a standardized approach to o3 measurement so that long - term trends can be accurately deduced ( smit et al . this correction provides the steps for one method of standardizing ecc - sonde types using the fully - buffered 1 % ki solution . it should be noted that the results of this correction are from one inter - comparison experiment extending only up to 5 km and further inter - comparisons , especially in the mid - to - upper troposphere are needed to determine if these methods can generally be extended to other locations and altitudes . although the corrections as described here are used for subsequent analyses in this manuscript , we note that other correction algorithms have been proposed ( e.g. deshler et al . ozone profile shapes are similar over ew and bw ( fig . 3 ) . a local maximum of o3 mixing ratios in the mid - to - top of the boundary layer ( ~2 km ) is observed at both sites , presumably due to a combination of precursor availability , reaction time and surface loss processes . above the boundary layer , o3 decreases due to the general lack of emission and transport of precursors into the lower free troposphere as inferred by steep gradients of species such as formaldehyde , carbon monoxide and nitrogen dioxide measured by the p3-b aircraft above both sites during the campaign ( not shown ) . ozone mixing ratios are relatively constant in the lower free troposphere up to 5 km . above 5 km , the o3 mixing ratios increase with height , presumably due to vertical mixing between the troposphere and the high o3 concentrations of the stratosphere or contributions from o3 production chemistry stemming from upstream north american pollution.fig . 3ozone mixing ratio vertical profiles from all ozonesondes ( gray ) launched during the discover - aq july 2011 campaign over ( a ) edgewood , md and ( b ) beltsville , md . the mean vertical profile ( black line ) was calculated using 100 m bin averages ozone mixing ratio vertical profiles from all ozonesondes ( gray ) launched during the discover - aq july 2011 campaign over ( a ) edgewood , md and ( b ) beltsville , md . the mean vertical profile ( black line ) was calculated using 100 m bin averages tco was calculated using o3 partial pressure measurements from ozonesondes and corrected for the amount between the burst altitude and the top of the atmosphere using a combination of microwave limb sounder and ozonesonde climatological data ( mcpeters and labow 2012 ) . the observed mean tco during the campaign was 337 du with a day - to - day variability of 6 % . the tpco , with the troposphere defined as the lowest altitude of a 2 km thick layer having a lapse rate of 2 k km , on average composes 21 % ( 69 du ) 3 % ( 1 ) of the tco and has a day - to - day variability of 21 % . the tpco is significantly and positively correlated with tco ( r = 0.70 , p - val < 0.01 ) . the variability of partial column o3 amounts within the 13 km , 46 km , and 710 km sub - regions are 27 % , 23 % , and 32 % ( 2 ) over ew and 36 % , 26 % and 38 % over bv , respectively . as expected from the profile analysis , the variability is large within the boundary layer , decreases in the lower free - troposphere , and increases again in the mid - troposphere . throughout the profile , the variability of the partial column o3 amounts is greater over bv compared to ew . the large variabilities in o3 partial columns during this one summer month , especially within the boundary layer , make forecasting this sub - region challenging , the implications of which are discussed below . the tco and tpco measurements from the ozonesondes were compared to the same measurements retrieved from the tes ( table 1 ) . for these analyses , the top of the troposphere was defined using the reported tropopause pressure from the aura tes retrievals . the mean biases ( ozonesondes as reference ) of the tes tco and tpco are 3.2 du ( 1.0 % ) and 0.2 du ( 0.4 % ) , respectively . the coefficient of variations ( rmsecv ) of the tes tco and tpco are 5.2 % and 9.2 % , respectively . tes retrievals of tco and tpco over ew are generally lower than ozonesonde observations , while tes retrievals of tco and tpco over bv are higher than ozonesonde observations . this pattern over bv is also observed in comparisons of ozonesondes with tco and trajectory - enhanced tropospheric ozone residual ( ttor ) products from omi . the results over ew contrast with previous validations of tes ( osterman et al . 2008 ; nassar et al . 2008 ; richards et al . 2010 ) , which find that tes column and profile retrievals , particularly in the troposphere , have a high bias between 0 and 20 % . these differences may be attributed , in part , to increased surface pollution at ew in july , to which satellite measurements are not sensitive and highlights the differences in observations between an intensive campaign such as discover - aq and a more seasonal study . a comparison of tes o3 profile retrievals to coincident ozonesondes show that , qualitatively , the two types of measurements agree well ( fig . the differences between the tes ozone profile retrievals to the a priori show that tes is responding to changes in radiances throughout most of the troposphere , although the responses vary vertically . the differences between the tes profile and the a priori profile are larger in the mid - troposphere ( 710 km ) compared to the boundary layer ( 03 km ) , which is expected based on the limited information the satellite receives from within the boundary layer . in the case of july 14 , the a priori seems to do a better job than the tes profile retrieval when compared to the ozonesondes.table 1comparison of total and tropospheric column amounts of ozone over edgewood and beltsville , md using ozonesonde and tes observationsdate [ utc ] ozonesonde sitetes scan i d [ scan type ] ozonesonde total column [ du ] tes total column [ du ] ozonesonde tropospheric column [ du ] tes tropospheric column [ du ] 2011 - 07 - 07 18:27edgewood13001 global survey 36634375682011 - 07 - 14 18:33edgewood13019 stare beltsville 34432652532011 - 07 - 16 18:21edgewood13043 stare edgewood 34133165612011 - 07 - 14 18:33beltsville13019 stare beltsville 30732645532011 - 07 - 16 18:21beltsville13043 stare edgewood 3163315761fig . 4coincident tes ( gray line ) and ozonesonde o3 mixing ratio profiles over ew ( black line ) and bv ( green line ) during discover - aq in july 2011 . the tes a priori o3 mixing ratio profile ( black dashed ) is shown for each overpass . the times ( utc ) of the tes overpasses and the launch times of the ozonesondes are shown . error bars on tes mixing ratio profiles represent 1 of multiple scans during the stare observations . there were no coincident ozonesonde launches over bv on july 7 comparison of total and tropospheric column amounts of ozone over edgewood and beltsville , md using ozonesonde and tes observations coincident tes ( gray line ) and ozonesonde o3 mixing ratio profiles over ew ( black line ) and bv ( green line ) during discover - aq in july 2011 . the tes a priori o3 mixing ratio profile ( black dashed ) is shown for each overpass . the times ( utc ) of the tes overpasses and the launch times of the ozonesondes are shown . error bars on tes mixing ratio profiles represent 1 of multiple scans during the stare observations . using data from ozonesondes , correlations between upper air o3 and the near - surface o3 from ew and bv were calculated ( fig . 5 ) . data were averaged into 100 m vertical bins , the near - surface representing 0100 m agl and each layer was correlated with the near - surface . the correlation coefficient profiles show 3 laminae . within the boundary layer ( generically as <3 km ) , the correlation between layers aloft and the surface decreases approximately linearly with height at both ew and bv . the decrease of the correlation coefficient in the boundary layer at ew is greater than bv . in the free troposphere ( 310 km ) , the correlation coefficients are approximately constant with height , with an average correlation coefficient of 0.16 0.09 ( 1 ) over ew and 0.50 0.07 ( 1 ) over bv , the correlation over bv being significant at the 95 % confidence level ( p - val = 0.02 ) . above 10 km , there is a decrease in the correlation coefficients and the coefficients become negative in the stratosphere . in the bv ozone correlation profile , o3 mixing ratios in layers aloft significantly ( > 95 % confidence ) correlate with the o3 mixing ratios within the near - surface layer up to 10 km ( fig . 5 bold lines ) . in contrast , ew o3 mixing ratios in layers aloft significantly correlate with the o3 mixing ratios within the near - surface layer up to 3 km.fig . 5vertical profile of correlation coefficients between layers aloft and the surface ( 0100 m ) over edgewood ( black ) and beltsville ( green ) . thicker lines indicate areas where correlations are significant based on 95 % confidence intervals ( p - val < 0.05 ) vertical profile of correlation coefficients between layers aloft and the surface ( 0100 m ) over edgewood ( black ) and beltsville ( green ) . thicker lines indicate areas where correlations are significant based on 95 % confidence intervals ( p - val < 0.05 ) the steeper gradients and the lower values of the correlation coefficients over ew reflect the dynamic complexity of the site due to its proximity to the chesapeake bay , in agreement with past observations ( loughner et al . 2011 ; stauffer et al . 2013 ) . to illustrate , boundary layer heights were calculated for each ozonesonde over ew and bv using a modified lapse rate method ( heffter 1980 ) . the boundary layer height was defined as the lowest layer to exceed a lapse rate of 7 k km and the layer must be above 200 m. ozonesondes that were launched during cloudy or rainy conditions , as determined by radiation measurements at each site and defined as having incoming total irradiance of less than 50 % of the maximum observed daily mean irradiance , were excluded from the analysis . based on this criterion , one bv ozonesonde and five ew ozonesondes were excluded for the boundary layer height analysis . boundary layer heights calculated from ozonesonde data using this method compare somewhat well ( mb = 0.076 km ) with an independent method using a mini micropulse aerosol lidar ( fig . 6a ) . the boundary layer height is obtained from lidar measurements using a gradient technique , since aerosols often are trapped near the surface by the capping inversion layer ( davis et al . figure 6b shows the difference in boundary layer heights over ew and bl as a function of time - of - day . at both sites , the boundary layer height increases throughout the day , as expected . boundary layer heights over bv are often higher and the variability of the boundary layer heights in the afternoon is less compared to over ew . the lower boundary layer heights at ew are the result of thermal internal boundary layers ( tibls ) induced from marine flow ( stauffer et al . tibls act to decouple surface air pollutant concentrations from those aloft , leading generally to the differences in the correlation coefficent profiles between marine ( ew ) and terrestrial ( bv ) observation sites ( fig . 6(a ) comparison of independent methods of calculating the boundary layer height at edgewood , md presented with the 1:1 line and ( b ) boundary layer height as a function of time of day over beltsville , md ( green dots ) and edgewood , md ( black dots ) . a fourth - order polynomial was fit to the data over each site to show average diurnal patterns ( a ) comparison of independent methods of calculating the boundary layer height at edgewood , md presented with the 1:1 line and ( b ) boundary layer height as a function of time of day over beltsville , md ( green dots ) and edgewood , md ( black dots ) . a fourth - order polynomial was fit to the data over each site to show average diurnal patterns correlations between every 100 m layer were considered for ew and bv ( fig . the boundary layer is more decoupled from the lower free troposphere over ew compared to bv , as expected from tibl influences over ew . the correlations show three distinct layers over both sites where adjacent laminae are coupled , shown by the high correlation coefficient triangles these high correlation coefficients in these sub - regions suggest vertical mixing between those layers . the layer correlations were expected within two of the sub - regions : the boundary layer ( 03 km ) and the upper troposphere ( 1014 km ) . the correlations within the mid - troposphere ( 710 km ) is more unexpected since vertical motions within this layer are relatively weaker and occur over larger spatial and temporal scales , and the variability of o3 in the mid - troposphere is small compared to the boundary layer . without more detailed analyses of case studies leading to the high correlations within 710 km , we can only hypothesize based on previous work that these high correlations are due to either : 1 ) strong convection during extreme events , 2 ) large - scale vertical mixing associated with the passage of synoptic fronts or 3 ) long - range transport ( cooper et al . 2006 , 2007 ; gettelman et al . 7(a , c ) correlation coefficients between 100 m layers as measured by ozonesondes over edgewood and beltsville , md . ( b , d ) p - values of the correlations at the respective sites with the significant correlation coefficients ( pval < 0.05 ) shown in red ( a , c ) correlation coefficients between 100 m layers as measured by ozonesondes over edgewood and beltsville , md . ( b , d ) p - values of the correlations at the respective sites with the significant correlation coefficients ( pval < 0.05 ) shown in red the upper boundary layer ( 13 km ) o3 mixing ratios show significant and positive correlations with the mid - troposphere ( 710 km ) o3 mixing ratios over both sites , with average correlations of 0.42 0.09 ( 1 ) at ew and 0.43 0.09 ( 1 ) at bv within the sub - region . median p - values within the region are 0.01 ( interquartile range = 0.000.03 ) and 0.03 ( interquartile range = 0.010.07 ) at ew and bv , respectively . an analysis of the 95 % confidence intervals of the correlation coefficients calculated using a fisher transformation and associated z - statistical test show that most of the correlation coefficients between the mid - troposphere and near - surface are significant ( table 2 ) . the significant correlations between the mid - troposphere and the near - surface are surprising especially at ew since the correlations between the near - surface and the lower free troposphere are not significant . however , this decoupling caused by tibl influence show the complexity of the dynamics and the multiple dynamic and chemical processes occurring in the tropospheric column over a site . this discontinuity suggests that vertical transport is not a contributing factor for the correlations observed between the mid - troposphere and the near - surface . we speculate that synoptic phenomena such as available sunlight for photochemical processes coupled with the availability of precursors may be responsible for the significant correlations observed . given the location of these two sites downwind of major urban areas ( baltimore and washington d.c . ) and the fact that the mid - atlantic region acts as an exhaust pipe for much of the contiguous united states , we speculate the occurrence of ozone precursors such as peroxyacetyl nitrate ( pan ) , carbon monoxide and volatile organic compounds ( vocs ) . these ideas are beyond the scope of this manuscript and are the subject of ongoing investigations . further analyses below attempt to exploit this correlation by deriving near - surface o3 information using partial column o3 retrievals from satellites in the upper troposphere.table 2confidence intervals of correlations observed at each site at specific quantiles between within the mid - tropospheric ( 710 km ) and near - surface ( 13 km ) vertical regionsedgewoodbeltsvillepercentilecorrelation95 % confidence intervalscorrelation95 % confidence intervalsupperlowerupperlower900.540.730.280.540.770.18750.490.700.210.490.740.12500.410.650.110.440.710.05250.360.600.040.370.690.03100.310.570.010.300.620.11 confidence intervals of correlations observed at each site at specific quantiles between within the mid - tropospheric ( 710 km ) and near - surface ( 13 km ) vertical regions analogous to the o3 mixing ratio correlation analyses described above , the partial columns of o3 in the mid - troposphere ( 710 km ; mtpc ) and the near - surface partial columns of o3 ( 13 km ; nspc ) were compared using ozonesonde measurements ( fig . 8) . correlation coefficients between these sub - regions were 0.56 and 0.49 for ew and bv , respectively . having considered the near - surface range between 1 and 3 km above the surface for both ew and bv rather than between 0 and 3 km above the surface increased the ew correlation coefficient by 17 % with no change in the bv correlation coefficient . thus , the impact of tibls at the ew site dramatically impacts partial column correlations . the linear regression statistics are similar at both sites ( table 3 ) , giving confidence that these methods can be extended to other sites in the mid-atlantic.fig . 8scatter plots of near - surface ( 13 km ) partial column ozone and upper troposphere ( 710 km ) partial column ozone using ozonesondes over edgewood , md ( black triangles ) and beltsville , md ( green dots ) . a least - squares regression line was fit to the data over each sitetable 3regression statistics from linear regression of upper tropospheric ( 710 km ) partial column ozone amounts on near - surface ( 13 km ) partial column ozone amounts using ozonesonde observationslinear regression statisticedgewoodbeltsvilleslope0.500.47slope error0.130.17y - intercept [ du]5.75.4correlation coef.0.560.49 p - value0.010.03 scatter plots of near - surface ( 13 km ) partial column ozone and upper troposphere ( 710 km ) partial column ozone using ozonesondes over edgewood , md ( black triangles ) and beltsville , md ( green dots ) . a least - squares regression line was fit to the data over each site regression statistics from linear regression of upper tropospheric ( 710 km ) partial column ozone amounts on near - surface ( 13 km ) partial column ozone amounts using ozonesonde observations further analyses were conducted to derive nspc using mtpc as retrieved from tes using a regression model formulated from independent ozonesonde observations . the sensitivity and vertical resolution of tes is the largest in the 36 km layer as indicated by the averaging kernel profiles ( fig . however , due to the dynamics at ew , no significant o3 correlations were observed between the near - surface and the 36 km layer , thus prediction of nspc using satellite partial columns from 3 to 6 km was not considered for this study and mid - tropospheric ( 710 km ) retrievals of tes were used . the averaging kernels binned into height layers also highlight the sensitivity limitations that satellites have within the boundary layer , further giving merit to the methods presented here . the nspc derivations from tes were compared to coincident nspc measurements from ozonesondes for validation . mtpcs ( in dobson units ) were calculated from tes o3 and pressure profile retrievals using : fig . 9tes averaging kernel profiles from select altitudes , color - coded by altitude bin , during the global survey overpass on 7 july 20111\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ p{c_i}=\frac{{\overline{{{n_i}{c_i}}}\vardelta z}}{{2.69\times { 10^{20 } } } } $ $ \end{document}where ni is the number density in layer i ( in molecules m ) , ci is the mixing ratio in layer i and z is the height of layer i ( in m ) . in this case , prior to the calculation of the mtpcs , the tes o3 and pressure profiles were first linearly interpolated every 500 m and pressures at each height were calculated using the hypsometric equation from the nearest tes retrieved pressure level below . the mb and rmsecv of tes mtpc calculations referenced to ozonesonde measurements is 8.4 % and 9.9 % , respectively ( fig . 10 ) . in general , tes partial columns in the mid troposphere underestimate the observations with a range between 13 % and 2 % . nspcs derived from tes mtpc calculations using the linear regression coefficients presented in table 3 for the respective sites differ from observed nspcs from ozonesondes with a range of 1.3 to 0.9 du ( fig . the relative difference of the tes nspcs ranges between 10 and 10 % , less than the observed variability in the near - surface during the campaign . all the derived nspc values from tes are within 11 % of the ozonesonde observations . the mb and rmsecv for the tes nspc comparisons to ozonesondes are 1.5 % and 8.7 % , respectively . the uncertainty of the derived nspc from satellites is less than the observed variability of partial column o3 amounts in that sub - region . these results show that by utilizing satellite information from the mid - troposphere , a region of the atmosphere in which satellites are more sensitive to changes in radiances and thus atmospheric composition , quantitative information can potentially be obtained with respect to atmospheric pollutants near the surface . the results obtained from this simple linear regression model and associated analyses are encouraging when considering the challenging task of retrieving near - surface o3 information from satellites.fig . 10comparison of measured mtpc o3 from tes ( blue squares ) and ozonesondes ( blue circles ) during a total of 5 coincident tes overpass / ozonesonde launches . additionally , the calculated nspc from tes ( red squares ) and measured nspc from ozonesondes ( red circles ) are compared . error bars represent the propagated uncertainty caused by random errors tes averaging kernel profiles from select altitudes , color - coded by altitude bin , during the global survey overpass on 7 july 2011 comparison of measured mtpc o3 from tes ( blue squares ) and ozonesondes ( blue circles ) during a total of 5 coincident tes overpass / ozonesonde launches . additionally , the calculated nspc from tes ( red squares ) and measured nspc from ozonesondes ( red circles ) are compared . region in july 2011 provided a unique opportunity to inter - compare ozone profiling instrumentation as well as investigate correlations between upper tropospheric and near - surface o3 partial columns and concentrations . comparisons between in situ aircraft o3 profiles and ozonesondes within the boundary layer and the lower free troposphere have confirmed systematic errors in the ozonesonde measurement previously observed in controlled simulations . these systematic errors were corrected using independent methods , reducing the mean bias between the ozonesondes and the in situ aircraft to less than 1 % . variability within o3 profiles is largest within the boundary layer and in the upper troposphere and the o3 profiles at two mid - atlantic sites ( edgewood , md and beltsville , md ) are similar . the day - to - day variability of o3 within the total column is small ( 6 % ) , but is quite large ( 21 % ) when only the tropospheric column , making up ~21 % of the total column , is considered . upper air o3 concentrations are significantly positively correlated to surface ( 0100 m ) o3 up to 10 km at beltsville , md , but only up to 3 km at edgewood , md . the influences of marine layers at edgewood , md decouple the surface layer from those above , thus complicating retrieval algorithms over this site and presumably other coastal sites . however , significant positive correlations between upper troposphere ( 710 km ) and near - surface ( 13 km ) o3 exist over both sites , potentially providing solutions through regression analyses for retrieving near - surface o3 . the results presented in this manuscript were tested using current polar - orbiting o3 profile retrievals from nasa s tes instrument on board the aura satellite , and validated against coincident ozonesonde profiles . mid - troposphere partial columns calculated using ozonesonde and tes o3 profile measurements on average agree to within 20 % . derived nspcs , calculated from a linear regression model formulated from an independent ozonesonde dataset , agree with the ozonesonde observations within 11 % . although the dataset used in these analyses are spatially and temporally limited , the results in this focused study show connections between the mid - troposphere and the near surface , which may not have otherwise been observed . the benefit of the techniques presented here is that they can be applied using existing satellite hardware and retrieval algorithms , as well as future geostationary satellite missions . the use of mid - tropospheric retrievals rather than retrievals from below 3 km has benefits : 1 ) tes is more sensitive within the mid - troposphere compared to the boundary layer and 2 ) the retrievals are less likely to be impacted by clouds . the temporal resolution of the tes measurements at a particular ground site and the focused temporal range of this study limited the number of data samples in which to compare to ozonesondes . these analyses are limited in that they include data from only 64 ozonesondes at two mid - atlantic sites during one month in the summer . however , the intensive nature of these campaigns provides a thorough understanding of the atmospheric composition and the processes involved . work to extend these analyses to other locations and other seasons using long - term ozonesonde observation data from wallops is . , va , boulder , co and more recently completed discover - aq campaigns is in progress . this research identifies the importance of the mid - tropospheric region ( 710 km ) in terms of resolving the near - surface o3 partial column amounts . research to develop algorithms that better quantify the o3 in the mid - troposphere , which utilize multiple wavebands and independent statistical correlations with atmospheric variables , is essential ( moody et al . the continuation of these studies will reduce satellite retrieval uncertainties in the troposphere and allow future geostationary satellite missions to be better utilized .

the current network of ground - based monitors for ozone ( o3 ) is limited due to the spatial heterogeneity of o3 at the surface . satellite measurements can provide a solution to this limitation , but the lack of sensitivity of satellites to o3 within the boundary layer causes large uncertainties in satellite retrievals at the near - surface . the vertical variability of o3 was investigated using ozonesondes collected as part of nasa s deriving information on surface conditions from column and vertically resolved observations relevant to air quality ( discover - aq ) campaign during july 2011 in the baltimore , md / washington d.c . metropolitan area . a subset of the ozonesonde measurements was corrected for a known bias from the electrochemical solution strength using new procedures based on laboratory and field tests . a significant correlation of o3 over the two sites with ozonesonde measurements ( edgewood and beltsville , md ) was observed between the mid - troposphere ( 710 km ) and the near - surface ( 13 km ) . a linear regression model based on the partial column amounts of o3 within these subregions was developed to calculate the near - surface o3 using mid - tropospheric satellite measurements from the tropospheric emission spectrometer ( tes ) onboard the aura spacecraft . the uncertainties of the calculated near - surface o3 using tes mid - tropospheric satellite retrievals and a linear regression model were less than 20 % , which is less than that of the observed variability of o3 at the surface in this region . these results utilize a region of the troposphere to which existing satellites are more sensitive compared to the boundary layer and can provide information of o3 at the near - surface using existing satellite infrastructure and algorithms .

mycetoma is an uncommon chronic granulomatous infective disease of the skin / dermis and subcutaneous tissues . it is predominantly a disease of tropical countries and is named after the region of india ( madurai ) where it was first described in 1842 , also called madura foot , it is caused by true fungi ( eumycetoma ) or by the filamentous bacteria ( actinomycetoma ) . it is characterized by a triad of tumefaction , draining sinuses and the presence of colonial grains in the exudates . eumycetoma is more common in northern india , while actinomycetoma is more common in southern india . a 60-year - old male living in a village about 90 km from pune presented to our hospital with a history of generalized swelling of the left foot of about 11 months duration . the initial lesion had started as a single nodule over the dorsum of the foot and was followed by a second nodule that appeared two months later and a few more nodules subsequently . these lesions , mainly distributed over the dorsum of the foot [ figure 1 ] , then burst to develop sinuses from which there was intermittent discharge of yellow colored granules . over a period of three months , the patient developed pain in the foot that made walking difficult the left foot dorsum of the foot showing healed and active nodules osteomyelitic changes involving the left calcaneum were seen . since there was no discharging sinus at the time of presentation , biopsy was done from the site under ultrasound guidance and the specimen sent for staining and culture . non - acid fast gram - positive narrow filamentous branching bacilli were seen [ figures 2 and 3 ] . gram stain showing colony and discharging granules ( 40 ) gram stain showing colony and discharging granules ( 100 ) the patient was started on trimethoprim - sulphamethoxazole ( 14 mg / kg , twice daily ) along with dapsone ( 1.5 mg / kg , twice daily ) and rifampicin ( 600 mg / day ) . the swelling decreased in size following surgical debridement of one large painful nodule . the patient has been followed up for a period of three months so far and the medication will be continued for a total period of six months or until cure is achieved . mycetoma is a chronic pseudotumourous infection of the skin and subcutaneous tissue , which occasionally involves the bone . it is endemic in the tropics and sub - tropical africa , mexico and india . the incidence of mycetoma in india has been quoted between 5.2% and 35% of the mycetomas . it commonly presents between 20 years and 50 years of age , with a male to female ratio of 2.2:1 . mycetoma typically presents in people who walk barefoot in dry , dusty conditions as was our case . actinomycetoma is caused by a group of filamentous bacteria which include nocardia and streptomyces species . the color of the grains found in the discharge is indicative of the species and helps to initiate appropriate treatment . the foot is the most commonly affected and the dorsal aspect of the left foot for unexplained reasons is more affected . in our patient also , the dorsal aspect of the left foot was affected . the three cardinal features of the disease are tumefaction , formation of sinus tracts and the presence of grains in the affected tissue . our patient presented with a diffuse swelling of the left foot with a nodule and healed sinuses . in the absence of any obvious discharge as was in our case , ultrasonic imaging and fine needle aspiration from the involved area can determine the diagnosis . the simplicity of the technique , makes it useful in epidemiological survey of mycetoma and the detection of early cases in which radiological and serological techniques may be unhelpful . the grains are histologically seen as sulfur granules surrounded by neutrophils which lead to a purulent tissue reaction containing fibroblasts . this prevents the antibiotic from acting on the micro - organisms , hence the need for debridement in certain cases . mycetoma can lead to deformity , amputation and death if not treated promptly and properly . combined drug therapy is preferred to a single drug therapy to avoid resistance and any residual infection . surgical debridement , followed by prolonged appropriate antibiotic therapy for several months is required for actinomycetoma while a combination therapy with trimethoprim - sulfamethoxazole ( 14 mg / kg , twice daily ) , dapsone ( 1.5 mg / kg , twice daily ) and streptomycin ( 14 mg / kg ) has been used along with rifampicin for resistant cases . whatever regimen is used , regular a close follow - up of patients , along with renal , hepatic and hematological assessments and evidence of ototoxicity are mandatory . our patient was treated with trimethoprim- sulphamethoxazole , dapsone and rifampicin and responded to this regime . the patient refused prolonged hospitalization . since he was from a rural area , streptomycin which the patient is being followed - up every month for a period of 6 months and yearly thereafter to detect any recurrence . medical management will continue until he is clinically , radiologically , ultrasonically and cytologically cured . clinical improvements is judged by a reduction in size of the mass and the healing of most of the sinuses . since the progression of the disease is relatively slow and pain free , patients do not report early and are therefore , diagnosed at a very late stage . health education of vulnerable population , especially farmers in tropical countries like india , is , therefore , of the utmost importance . furthermore to be emphasized is the importance of wearing proper footwear while working in fields . early reporting to the primary care physicians and thereafter , an early diagnosis of the disease can lead to a decrease in morbidity .

mycetoma is an uncommon chronic granulomatous infective disease of the skin , dermis and subcutaneous tissues predominantly seen in tropical countries . a patient presented to our hospital with the swelling of the left foot with a healed sinus and a painful nodule . he gave a history of sinuses in the left foot from which there was discharge of yellow granules . culture of the ultrasound guided fine needle aspiration cytology of the nodule revealed growths of nocardia species . the patient was treated with a multi - drug therapy along with debridement of the painful nodule . he experienced symptomatic relief and a regression of the swelling within the three months of follow - up so far . due to the relatively slow progression of the disease , patients are diagnosed at a late stage . hence , emphasis should be placed on health education and the importance of wearing footwear .

America's founding document might be too politically incorrect for Facebook, which flagged and removed a post consisting almost entirely of text from the Declaration of Independence. The excerpt, posted by a small community newspaper in Texas, apparently violated the social media site's policies against hate speech. Since June 24, the Liberty County Vindicator of Liberty County, Texas, has been sharing daily excerpts from the declaration in the run up to July Fourth. The idea was to encourage historical literacy among the Vindicator's readers. The first nine such posts of the project went up without incident. "But part 10," writes Vindicator managing editor Casey Stinnett, "did not appear. Instead, The Vindicator received a notice from Facebook saying that the post 'goes against our standards on hate speech.'" The post in question contained paragraphs 27 through 31 of the Declaration of Independence, the grievance section of the document wherein the put-upon colonists detail all the irreconcilable differences they have with King George III. Stinnett says that he cannot be sure which exact grievance ran afoul of Facebook's policy, but he assumes that it's paragraph 31, which excoriates the King for inciting "domestic insurrections amongst us, and has endeavored to bring on the inhabitants of our frontiers, the merciless Indian Savages." The removal of the post was an automated action, and Stinnett sent a "feedback message" to Facebook with the hopes of reaching a human being who could then exempt the Declaration of Independence from its hate speech restrictions. Fearful that sharing more of the text might trigger the deletion of its Facebook page, The Vindicator has suspended its serialization of the declaration.* In his article, Stinnett is remarkably sanguine about this censorship. While unhappy about the decision, he reminds readers "that Facebook is a business corporation, not the government, and as such it is allowed to restrict use of its services as long as those restrictions do not violate any laws. Plus, The Vindicator is using Facebook for free, so the newspaper has little grounds for complaint other than the silliness of it." Of course, Facebook's actions here are silly. They demonstrate a problem with automated enforcement of hate speech policies, which is that a robot trained to spot politically incorrect language isn't smart enough to detect when that language is part of a historically significant document. None of this is meant as a defense of referring to Native Americans as "savages." That phrasing is clearly racist and serves as another example of the American Revolution's mixed legacy; one that won crucial liberties for a certain segment of the population, while continuing to deny those same liberties to Native Americans and African slaves. But by allowing the less controversial parts of the declaration to be shared while deleting the reference to "Indian savages," Facebook succeeds only in whitewashing America's founding just as we get ready to celebrate it. A more thoughtful approach to Independence Day—for both celebrants and social media companies alike—would be to grapple with those historical demons. Update: Facebook has reportedly restored The Vindicator's declaration post, deeming it to not be a violation of the social media site's community standards and apologizing to the paper for its "incorrect action." ||||| Declaration of Independence: A Transcription Note: The following text is a transcription of the Stone Engraving of the parchment Declaration of Independence (the document on display in the Rotunda at the National Archives Museum.) The spelling and punctuation reflects the original. In Congress, July 4, 1776. The unanimous Declaration of the thirteen united States of America, When in the Course of human events, it becomes necessary for one people to dissolve the political bands which have connected them with another, and to assume among the powers of the earth, the separate and equal station to which the Laws of Nature and of Nature's God entitle them, a decent respect to the opinions of mankind requires that they should declare the causes which impel them to the separation. We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.--That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed, --That whenever any Form of Government becomes destructive of these ends, it is the Right of the People to alter or to abolish it, and to institute new Government, laying its foundation on such principles and organizing its powers in such form, as to them shall seem most likely to effect their Safety and Happiness. Prudence, indeed, will dictate that Governments long established should not be changed for light and transient causes; and accordingly all experience hath shewn, that mankind are more disposed to suffer, while evils are sufferable, than to right themselves by abolishing the forms to which they are accustomed. But when a long train of abuses and usurpations, pursuing invariably the same Object evinces a design to reduce them under absolute Despotism, it is their right, it is their duty, to throw off such Government, and to provide new Guards for their future security.--Such has been the patient sufferance of these Colonies; and such is now the necessity which constrains them to alter their former Systems of Government. The history of the present King of Great Britain is a history of repeated injuries and usurpations, all having in direct object the establishment of an absolute Tyranny over these States. To prove this, let Facts be submitted to a candid world. He has refused his Assent to Laws, the most wholesome and necessary for the public good. He has forbidden his Governors to pass Laws of immediate and pressing importance, unless suspended in their operation till his Assent should be obtained; and when so suspended, he has utterly neglected to attend to them. He has refused to pass other Laws for the accommodation of large districts of people, unless those people would relinquish the right of Representation in the Legislature, a right inestimable to them and formidable to tyrants only. He has called together legislative bodies at places unusual, uncomfortable, and distant from the depository of their public Records, for the sole purpose of fatiguing them into compliance with his measures. He has dissolved Representative Houses repeatedly, for opposing with manly firmness his invasions on the rights of the people. He has refused for a long time, after such dissolutions, to cause others to be elected; whereby the Legislative powers, incapable of Annihilation, have returned to the People at large for their exercise; the State remaining in the mean time exposed to all the dangers of invasion from without, and convulsions within. He has endeavoured to prevent the population of these States; for that purpose obstructing the Laws for Naturalization of Foreigners; refusing to pass others to encourage their migrations hither, and raising the conditions of new Appropriations of Lands. He has obstructed the Administration of Justice, by refusing his Assent to Laws for establishing Judiciary powers. He has made Judges dependent on his Will alone, for the tenure of their offices, and the amount and payment of their salaries. He has erected a multitude of New Offices, and sent hither swarms of Officers to harrass our people, and eat out their substance. He has kept among us, in times of peace, Standing Armies without the Consent of our legislatures. He has affected to render the Military independent of and superior to the Civil power. He has combined with others to subject us to a jurisdiction foreign to our constitution, and unacknowledged by our laws; giving his Assent to their Acts of pretended Legislation: For Quartering large bodies of armed troops among us: For protecting them, by a mock Trial, from punishment for any Murders which they should commit on the Inhabitants of these States: For cutting off our Trade with all parts of the world: For imposing Taxes on us without our Consent: For depriving us in many cases, of the benefits of Trial by Jury: For transporting us beyond Seas to be tried for pretended offences For abolishing the free System of English Laws in a neighbouring Province, establishing therein an Arbitrary government, and enlarging its Boundaries so as to render it at once an example and fit instrument for introducing the same absolute rule into these Colonies: For taking away our Charters, abolishing our most valuable Laws, and altering fundamentally the Forms of our Governments: For suspending our own Legislatures, and declaring themselves invested with power to legislate for us in all cases whatsoever. He has abdicated Government here, by declaring us out of his Protection and waging War against us. He has plundered our seas, ravaged our Coasts, burnt our towns, and destroyed the lives of our people. He is at this time transporting large Armies of foreign Mercenaries to compleat the works of death, desolation and tyranny, already begun with circumstances of Cruelty & perfidy scarcely paralleled in the most barbarous ages, and totally unworthy the Head of a civilized nation. He has constrained our fellow Citizens taken Captive on the high Seas to bear Arms against their Country, to become the executioners of their friends and Brethren, or to fall themselves by their Hands. He has excited domestic insurrections amongst us, and has endeavoured to bring on the inhabitants of our frontiers, the merciless Indian Savages, whose known rule of warfare, is an undistinguished destruction of all ages, sexes and conditions. In every stage of these Oppressions We have Petitioned for Redress in the most humble terms: Our repeated Petitions have been answered only by repeated injury. A Prince whose character is thus marked by every act which may define a Tyrant, is unfit to be the ruler of a free people. Nor have We been wanting in attentions to our Brittish brethren. We have warned them from time to time of attempts by their legislature to extend an unwarrantable jurisdiction over us. We have reminded them of the circumstances of our emigration and settlement here. We have appealed to their native justice and magnanimity, and we have conjured them by the ties of our common kindred to disavow these usurpations, which, would inevitably interrupt our connections and correspondence. They too have been deaf to the voice of justice and of consanguinity. We must, therefore, acquiesce in the necessity, which denounces our Separation, and hold them, as we hold the rest of mankind, Enemies in War, in Peace Friends. We, therefore, the Representatives of the United States of America, in General Congress, Assembled, appealing to the Supreme Judge of the world for the rectitude of our intentions, do, in the Name, and by Authority of the good People of these Colonies, solemnly publish and declare, That these United Colonies are, and of Right ought to be Free and Independent States; that they are Absolved from all Allegiance to the British Crown, and that all political connection between them and the State of Great Britain, is and ought to be totally dissolved; and that as Free and Independent States, they have full Power to levy War, conclude Peace, contract Alliances, establish Commerce, and to do all other Acts and Things which Independent States may of right do. And for the support of this Declaration, with a firm reliance on the protection of divine Providence, we mutually pledge to each other our Lives, our Fortunes and our sacred Honor. Georgia Button Gwinnett Lyman Hall George Walton North Carolina William Hooper Joseph Hewes John Penn South Carolina Edward Rutledge Thomas Heyward, Jr. Thomas Lynch, Jr. Arthur Middleton Massachusetts John Hancock Maryland Samuel Chase William Paca Thomas Stone Charles Carroll of Carrollton Virginia George Wythe Richard Henry Lee Thomas Jefferson Benjamin Harrison Thomas Nelson, Jr. Francis Lightfoot Lee Carter Braxton Pennsylvania Robert Morris Benjamin Rush Benjamin Franklin John Morton George Clymer James Smith George Taylor James Wilson George Ross Delaware Caesar Rodney George Read Thomas McKean New York William Floyd Philip Livingston Francis Lewis Lewis Morris New Jersey Richard Stockton John Witherspoon Francis Hopkinson John Hart Abraham Clark New Hampshire Josiah Bartlett William Whipple Massachusetts Samuel Adams John Adams Robert Treat Paine Elbridge Gerry Rhode Island Stephen Hopkins William Ellery Connecticut Roger Sherman Samuel Huntington William Williams Oliver Wolcott New Hampshire Matthew Thornton Back to Main Declaration Page ||||| UPDATE: Earlier this evening, July 3, the good folks at Facebook restored the post that is the subject of this article. An email from Facebook came in a little after The Vindicator’s office closed today and says the following: “It looks like we made a mistake and removed something you posted on Facebook that didn’t go against our Community Standards. We want to apologize and let you know that we’ve restored your content and removed any blocks on your account related to this incorrect action.” The Vindicator extends its thanks to Facebook. We never doubted Facebook would fix it, but neither did we doubt the usefulness of our fussing about it a little. Somewhere in paragraphs 27-31 of the Declaration of Independence Thomas Jefferson wrote something that Facebook finds offensive. Leading up to Independence Day, The Vindicator challenged its Facebook followers to read the Declaration of Independence. To make it a little easier to digest that short but formidable historic document, the newspaper broke the Declaration down into 12 small bites and one to post each morning from June 24 to July 4. The first nine parts posted as scheduled, but part 10, consisting of paragraphs 27-31 of the Declaration, did not appear. Instead, The Vindicator received a notice from Facebook saying that the post “goes against our standards on hate speech.” Facebook’s notice then asked The Vindicator to review the contents of its page and remove anything that does not comply with Facebook’s policies. The offending passage of the Declaration reads as follows: “He has abdicated Government here, by declaring us out of his Protection and waging War against us. “He has plundered our seas, ravaged our Coasts, burnt our towns, and destroyed the lives of our people. “He is at this time transporting large Armies of foreign Mercenaries to compleat the works of death, desolation and tyranny, already begun with circumstances of Cruelty & perfidy scarcely paralleled in the most barbarous ages, and totally unworthy the Head of a civilized nation. “He has constrained our fellow Citizens taken Captive on the high Seas to bear Arms against their Country, to become the executioners of their friends and Brethren, or to fall themselves by their Hands. “He has excited domestic insurrections amongst us, and has endeavoured to bring on the inhabitants of our frontiers, the merciless Indian Savages, whose known rule of warfare, is an undistinguished destruction of all ages, sexes and conditions.” While The Vindicator cannot be certain exactly what triggered Facebook’s filtering program, the editor suspects it was most likely the phrase “Indian Savages.” Perhaps had Thomas Jefferson written it as “Native Americans at a challenging stage of cultural development” that would have been better. Unfortunately, Jefferson, like most British colonists of his day, did not hold an entirely friendly view of Native Americans. Although, to be honest, there is a good deal in that passage that could be thought hateful. The removal of the post was an automated action. If any human being working at Facebook were to review it, no doubt the post would be allowed, and the editor has searched for a means of contacting Facebook for an explanation or a opportunity to appeal the post’s removal, but it does not appear the folks at Facebook want anyone contacting them. Or, at least, they do not make it easy. The Vindicator has sent Facebook a feedback message. That being the only way found so far to contact the company. According to an article by Facebook Vice President of Global Policy Management Monika Bickert posted to newsroom.fb.com April 24, over the coming year Facebook is “going to build out the ability for people to appeal our decisions.” The first part of which is to provide a means by which users can request additional review of a decision by Facebook to remove a photo, video or post because Facebook found it violated their community standards. However, no such review request option appeared on Facebook’s notice to The Vindicator. While unhappy with Facebook’s action, the editor reminds readers that Facebook is a business corporation, not the government, and as such it is allowed to restrict use of its services as long as those restrictions do not violate any laws. Plus, The Vindicator is using Facebook for free, so the newspaper has little grounds for complaint other than the silliness of it. The problem The Vindicator faces is that it has become dependent, perhaps too dependent, on Facebook to communicate with local residents and to promote the newspaper. Some Vindicator stories posted on thevindicator.com attract thousands of page views, but usually only after links to them are shared on Facebook. Plus, many bits of information are shared by the newspaper through Facebook alone. So, the removal of this morning’s post puts The Vindicator in a quandary about whether to continue with posting the final two parts of the Declaration scheduled for tomorrow and Wednesday. Should Facebook find anything in them offensive, The Vindicator could lose its Facebook page. This is frustrating, but your editor is a historian, and to enjoy the study of history a person must love irony. It is a very great irony that the words of Thomas Jefferson should now be censored in America.

– The Declaration of Independence contains hate speech, according to Facebook's algorithms. Though the social media site eventually allowed the famed historical document to be shared in full, Texas' Liberty County Vindicator ran into trouble while posting fragments of the text on its Facebook page ahead of Independence Day. Facebook's algorithms specifically flagged three words in a line accusing the British monarchy of endeavoring "to bring on the inhabitants of our frontiers, the merciless Indian Savages," claiming the line violated the site's standards on hate speech, per the BBC. "Unfortunately, [Thomas] Jefferson, like most British colonists of his day, did not hold an entirely friendly view of Native Americans," the Vindicator's managing editor, Casey Stinnett, commented after the text was removed. Stinnett wasn't all that upset, though. "The newspaper has little grounds for complaint other than the silliness of it," he wrote. Still, Facebook later restored the content and apologized. "We made a mistake and removed something you posted on Facebook that didn't go against our community standards," the company told the paper. It's an admission surely welcomed by Christian Britschgi at Reason, who accused Facebook of "whitewashing America's founding." While "clearly racist," the flagged line of text "serves as another example of the American Revolution's mixed legacy; one that won crucial liberties for a certain segment of the population, while continuing to deny those same liberties to Native Americans and African slaves," he writes. (A copy of the Declaration was reportedly hidden behind wallpaper.)

SECTION 1. SHORT TITLE. This Act may be cited as the ``Puget Sound Recovery Act of 2009''. SEC. 2. PUGET SOUND. Title I of the Federal Water Pollution Control Act (33 U.S.C. 1251 et seq.) is amended by adding at the end the following: ``SEC. 123. PUGET SOUND. ``(a) Definitions.--In this section, the following definitions apply: ``(1) Comprehensive plan.--The term `comprehensive plan' means the Puget Sound Action Agenda (the comprehensive conservation and management plan for Puget Sound under section 320), including any amendments thereto. ``(2) Council.--The term `Council' means the Puget Sound Program Advisory Council established under subsection (d). ``(3) Director.--The term `Director' means the Director of the Office. ``(4) Office.--The term `Office' means the Puget Sound Program Office established by subsection (b). ``(5) Puget sound partnership.--The term `Puget Sound Partnership' means the agency of the State of Washington (together with its associated councils, boards, and panels) that was formed under authority of State law for the purpose of protecting and restoring Puget Sound and is designated as the management conference for Puget Sound under section 320. ``(b) Program Office.-- ``(1) Establishment.--The Administrator shall establish in the Environmental Protection Agency a Puget Sound Program Office. The Office shall be co-located with the Puget Sound Partnership in the State of Washington. ``(2) Appointment of director.--The Administrator shall appoint a Director of the Office, who, by reason of management experience and technical expertise relating to Puget Sound, shall be highly qualified to support the development and implementation of projects, programs, and studies necessary to implement the comprehensive plan. ``(3) Delegation of authority; staffing.--The Administrator shall delegate to the Director such authority and provide such additional staff as may be necessary to carry out this section. ``(c) Duties.-- ``(1) In general.--In carrying out this section, the Administrator, acting through the Director, shall-- ``(A) assist and support the implementation of the comprehensive plan; ``(B) provide funding and make grants for implementation of the comprehensive plan and projects, programs, and studies consistent with the priorities of the comprehensive plan; ``(C) promote innovative methodologies and technologies that are cost-effective and consistent with the identified goals and objectives of the comprehensive plan and Environmental Protection Agency permitting processes; ``(D) coordinate the major functions of the Federal Government related to the implementation of the comprehensive plan, including projects, programs, and studies for-- ``(i) water quality improvements; ``(ii) wetland, riverine, and estuary restoration and protection; and ``(iii) nearshore and endangered species recovery; ``(E) coordinate the research and planning projects authorized under this section with Federal agencies, State agencies, tribes, universities, and the Puget Sound Partnership's Science Panel, including conducting or commissioning studies considered necessary by the Science Panel for strengthened implementation of the comprehensive plan; ``(F) track progress towards meeting the identified goals and objectives of the comprehensive plan by-- ``(i) implementing and supporting a project, program, and study monitoring system consistent with the performance management system used by the Puget Sound Partnership; and ``(ii) coordinating, managing, and reporting environmental data related to Puget Sound in a manner consistent with methodologies utilized by the Puget Sound Partnership, including, to the extent practicable, making such data and reports on such data available to the public, including on the Internet, in a timely fashion; ``(G) coordinate projects, programs, and studies for the protection of Puget Sound, the Strait of Georgia, and the Strait of Juan de Fuca with Canadian authorities; and ``(H) collect and make available to the public, including on the Internet, publications and other forms of information relating to the environmental quality of Puget Sound. ``(2) Implementation methods.--The Administrator, acting through the Director, may enter into interagency agreements, make intergovernmental personnel appointments, provide funding, make grants, and utilize other available methods in carrying out the duties under this subsection. ``(d) Puget Sound Program Advisory Council.-- ``(1) In general.--The Administrator shall establish a Puget Sound Program Advisory Council to provide advice to the Administrator on the implementation of the identified goals and objectives of the comprehensive plan. ``(2) Composition.--The Council shall consist of the following 2 boards: ``(A) A Federal agency board consisting of representatives of appropriate Federal agencies that may affect or implement projects or programs identified in the comprehensive plan and the Executive Director of the Puget Sound Partnership. The chairperson of the Federal agency board shall be the Director. ``(B) An intergovernmental board consisting of the members of the Leadership Council and the Ecosystem Coordination Board of the Puget Sound Partnership. ``(3) Meetings.--The Council shall meet at least twice per year-- ``(A) to assess the progress of the Office in meeting the identified goals and objectives of the comprehensive plan; ``(B) to identify improvements for meeting the identified goals and objectives of the comprehensive plan; and ``(C) to assess Federal agency budget needs to implement the comprehensive plan. ``(4) Compensation of members.--A member of the Council shall serve without compensation. ``(5) Travel expenses.--Subject to the availability of appropriations, the Administrator shall reimburse a member of the Council for travel expenses, including per diem in lieu of subsistence, at rates authorized for an employee of a Federal agency under subchapter I of chapter 57 of title 5, United States Code, while away from home or the regular place of business of the member in performance of services for the Council. ``(e) Report.--Not later than one year after the date of enactment of this section, and biennially thereafter, the Administrator and the Executive Director of the Puget Sound Partnership, acting jointly, shall submit to Congress a report that-- ``(1) summarizes the progress made in implementing the comprehensive plan and progress towards achieving the identified goals and objectives described in the comprehensive plan; ``(2) summarizes any modifications to the comprehensive plan made in the period immediately preceding such report; ``(3) incorporates specific recommendations concerning the implementation of the comprehensive plan; and ``(4) summarizes the roles and progress of each Federal agency that has jurisdiction in the Puget Sound watershed towards meeting the identified goals and objectives of the comprehensive plan. ``(f) Implementation of Comprehensive Plan.-- ``(1) In general.--The Administrator, acting through the Director and in consultation with the Puget Sound Partnership, shall carry out projects, programs, and studies to implement the comprehensive plan. ``(2) Priority projects, programs, and studies.--The Administrator shall give special emphasis to projects, programs, and studies that are identified as priorities by the Puget Sound Partnership in the comprehensive plan. ``(3) Grants.-- ``(A) In general.--The Administrator, acting through the Director, is authorized to make grants for projects, programs, and studies to implement the comprehensive plan. ``(B) Allocations.--In making grants under this paragraph, the Administrator shall use-- ``(i) 50 percent of the funds appropriated for making grants under this paragraph for a fiscal year to make a comprehensive grant to the Puget Sound Partnership to manage implementation of the comprehensive plan and for allocation by the Puget Sound Partnership to projects, programs, and studies prioritized in the comprehensive plan; and ``(ii) 50 percent of funds appropriated for making grants under this paragraph for a fiscal year to make grants to State and regional water pollution control agencies and entities, federally recognized Indian tribes, State coastal zone management agencies, local governments, and other public or nonprofit private agencies, institutions, or organizations to implement specific projects, programs, and studies identified in the comprehensive plan. ``(4) Federal share.-- ``(A) In general.--The Federal share of the cost of a project, program, or study carried out under this subsection shall be-- ``(i) not more than 50 percent of the cost of a project, program or study; or ``(ii) up to 100 percent of the cost of a project, program, or study if the project, program, or study is located in or specifically affects a distressed community. ``(B) Contributions from non-federal sources.--The non-Federal share of costs required under subparagraph (A) shall be provided from non-Federal sources. ``(5) Distressed community defined.--In this subsection, the term `distressed community' means a community that meets the affordability criteria established by the State in which the community is located, if such criteria is established after public review and comment. ``(g) Annual Budget Plan.--The President, as part of the annual budget of the United States Government, shall submit information regarding each Federal agency involved in Puget Sound protection and restoration, including-- ``(1) an interagency crosscut budget that displays for each Federal agency-- ``(A) the amounts obligated in the preceding fiscal year for protection and restoration projects, programs, and studies relating to Puget Sound; ``(B) the estimated budget for the current fiscal year for protection and restoration projects, programs, and studies relating to Puget Sound; and ``(C) the proposed budget for protection and restoration projects, programs, and studies relating to Puget Sound; and ``(2) a description and assessment of the Federal role in the implementation of the comprehensive plan and the specific role of each Federal agency involved in Puget Sound protection and restoration, including specific projects, programs, and studies conducted or planned to achieve the identified goals and objectives of the comprehensive plan. ``(h) Authorization of Appropriations.--There is authorized to be appropriated to the Administrator to carry out this section $125,000,000 for each of fiscal years 2011 through 2016. Such sums shall remain available until expended.''.

Puget Sound Recovery Act of 2009 - Amends the Federal Water Pollution Control Act (commonly known as the Clean Water Act) to direct the Administrator of the Environmental Protection Agency (EPA) to: (1) establish a Puget Sound Program Office, to be co-located with the Puget Sound Partnership in Washington; and (2) appoint a Director of the Office. Requires the Administrator, acting through the Director, to: (1) assist and support the implementation of the Puget Sound Action Agenda; (2) provide funding and make grants for implementation of the Agenda and related projects; (3) promote methodologies and technologies that are cost-effective and consistent with the goals and objectives of the Agenda and the EPA permitting processes; (4) coordinate the major functions of the federal government relating to the implementation of the Agenda; (5) coordinate the research and planning projects authorized under this Act with federal and state agencies, tribes, universities, and the Puget Sound Partnership's Science Panel; (6) track progress toward meeting the identified goals and objectives of the Agenda; (7) coordinate projects, programs, and studies for the protection of Puget Sound, the Strait of Georgia, and the Strait of Juan de Fuca with Canadian authorities; (8) collect and make available to the public publications and information relating to the environmental quality of Puget Sound; and (9) implement projects, programs, and studies to implement the Agenda. Requires the Administrator to establish a Puget Sound Program Advisory Council to provide advice on the implementation of the Agenda's goals and objectives. Requires the Administrator and the Executive Director of the Puget Sound Partnership to a report, biennially, to Congress on implementation of the Agenda. Allows the Administrator, acting through the Director, to make grants for projects, programs, and studies to implement the Agenda, including a comprehensive grant to the Partnership to manage such implementation. Requires the President, as part of the annual budget, to submit information regarding expenditures and roles of each federal agency involved in Puget Sound protection and restoration.

we have all seen a waterwheel ( fig . [ fig1 ] ) and have an intuitive feel for how it works . consider now an atom in a solid . normally we think of atoms as executing small - amplitude thermal vibrations about their equilibrium positions . that is , we think of them as oscillators . in one dimension an oscillator can only go back and forth . but in 2d or 3d it could run around a circle , provided its natural frequencies along two independent directions are equal . can then the flow of _ electrical current _ somehow be gauged to drive an atom around , in a manner akin to a waterwheel ? schematic of a waterwheel . ] according to an argument by sorbello @xcite this should be possible . when an atom - or more precisely an atomic nucleus - is immersed in a current , incident electrons get scattered . there is a transfer of momentum between the flow and the target , and a resultant force . this force is called the _ electron wind force_. for an isolated scatterer in a free - electron metal it is given by @xmath0 where @xmath1 is the scattering cross section of the target , here is the so - called transport cross section . ] @xmath2 is the fermi momentum of the electrons and @xmath3 is the incident electron particle current density . therefore if we design a closed path that goes through regions of different current density , the net work done by this force need not be zero . one such path is shown in fig . . then the wind force is _ non - conservative _ , with the capacity to continually pump energy into the nuclear motion by driving the nuclei around closed paths in configuration space . a scatterer in an electron current . when the scatterer is inside the metal wire , the current density exerts a force on it - the electron wind force . outside , there is no force . thus , the wind force does non - zero net work around the closed path shown , and can _ drive _ the atom around . ] this possibility began to attract attention in the context of atomic and molecular wires about 10 years ago @xcite , initially with arguments that appeared at odds with each other @xcite , the full resolution of which still requires further work @xcite . after several years of further consideration the non - conservative character of forces on atoms in nanowires was demonstrated microscopically , culminating in the design ( through simulation ) of a single - atom `` waterwheel '' @xcite . the idea was soon extended to waterwheels in abstract spaces spanned by generalized cooperative displacements @xcite . these prospects raise a number of questions . leaving aside the idea of atomic - scale motors , non - conservative forces can have practical repercussions for the _ stability _ of atomic wires . electromigration is a class of phenomena @xcite in which electrical current drives atomic diffusion and rearrangements resulting in the mechanical failure of a conductor . electromigration is traditionally thought of as a thermally - assisted process . but kinetic energy gain into `` waterwheel '' atomic motion under non - conservative forces could be an alternative activation mechanism , and potentially a much more powerful one . these problems are being investigated by a growing number of researchers @xcite with further questions being uncovered all the time . however , the physical - and to an extent mathematical - understanding of forces due to current remains a challenging subject , for a simple reason . a real waterwheel is driven by a classical flow . but in the atomic case it is the quantum electron fluid doing it , and the rotors themselves ( the nuclear subsystem ) have to - or may have to - be considered quantum - mechanically , at least for some aspects of the full problem . force on the other hand is fundamentally a classical notion . combining these partly but not wholly intuitive elements into a physical yet rigorous understanding requires careful considerations . the above works have derived and discussed forces under current from a variety of standpoints . they are fundamentally connected but vary in technical difficulty and physical flavour . the aim of the present discussion is to obtain these forces in a simple way which at the same time retains the essential ingredients needed to capture the principal _ types _ of forces - there are five - along with a picture of the physics behind them . the methods involved should be accessible to physics undergraduates and postgraduates in the physical sciences . the forces we are considering are fundamentally forces on atomic nuclei , or possibly ions . nevertheless we will occasionally speak of atoms and atomic motion , to help visualize the problem . our object is to find these forces under current flow in a generic atomic or molecular wire @xcite as depicted in fig . [ fig3 ] . a conducting nanojunction . circles represent atoms . ] we will do so in steps , introducing briefly the landauer picture of conduction in nanoscale systems on the way . we will approach the problem by low - order time - dependent perturbation theory for the density matrix ( dm ) . the dm for a system with hamiltonian @xmath4 obeys the liouville equation @xmath5\ ] ] whose solution to first order in @xmath6 is @xmath7\,d\tau \label{1}\ ] ] where @xmath8 and @xmath9 . consider a system of quantum electrons and harmonic oscillators with ( for the moment , many - body ) hamiltonian @xmath10 - \sum_{\beta}\,{\hat f}_{\beta}{\hat x}_{\beta } = { \hat h}_{0 } + { \hat v}\ , . \label{heph}\ ] ] @xmath11 describes electrons in the absence of vibrations and the second term in square brackets describes free vibrations ( with @xmath12 a mass - like parameter ) . the two together form the unperturbed hamiltonian @xmath13 . @xmath14 is the electron - oscillator coupling , and will be treated as a perturbation . for the moment the oscillators could represent generalized degrees of freedom , such as unperturbed vibrational normal modes , or individual nuclear degrees of freedom viewed as einstein oscillators . the construction of the coupling @xmath15 from scratch is a difficult - and to an extent open - problem . the systems of interest are infinite , aperiodic and open , with a continuum of electronic states . in addition , interatomic forces under current contain the key non - conservative component highlighted already . these factors require a reconsideration of the usual born - oppenheimer separation @xcite . a possible physical picture of the _ unperturbed _ dynamics is to imagine that nuclei vibrate on a chosen known potential - energy surface ( such as the ground - state born - oppenheimer surface ) , while electrons remain in a current - carrying steady state for each geometry . one can then make a small - amplitude expansion in nuclear displacements about a chosen configuration . a natural choice of expansion point is the equilibrium geometry on the reference surface . however one may consider nearby points , so long as nuclei remain bound and a hamiltonian quadratic in the displacements remains appropriate , at least locally . the resultant coupling then has a dual role : to introduce the additional non - equilibrium current - induced forces , and to generate inelastic electron - phonon scattering . explicit constructions of the coupling are discussed for example in refs . @xcite . in general @xmath15 will be the sum of a 1-body electronic operator and a scalar ( both dependent on the expansion point ) . the electronic part typically is minus the gradient , with respect to nuclear displacements , of a ( possibly screened ) electron - nuclear interaction . alternatively we may think of ( [ heph ] ) as a generic model electron - phonon hamiltonian , while noting that by construction @xmath15 remains the gradient of the interaction with respect to the negative of the conjugate displacement . we will take this view here and will assume further that @xmath15 is purely a 1-body electronic quantity . the resultant calculation is exact in the reference hamiltonian , and is exact also in the perturbation , in the limit of small - amplitude atomic motion . this is important as the response coefficients that characterize current - induced forces below describe that limit . these questions are receiving renewed attention with fresh work on the many - body electron - nuclear schr " odinger equation @xcite . our aim is to calculate the quantity @xmath16 to second order in @xmath17 , and to relate it to the motion of the centroid of the oscillator distribution . the centroid is the collection of mean displacements @xmath18 , with velocities @xmath19 ( not to be confused with the perturbing potential @xmath20 ) . the centroid @xmath21 is what we would interpret as _ classical _ coordinates , in a mixed quantum - classical picture of electron - nuclear dynamics , such as ehrenfest dynamics @xcite . @xmath22 above is the mean force exerted by electrons on degree of freedom @xmath23 . indeed @xmath24\ ] ] and therefore ( as may be expected from the earlier discussion ) @xmath22 is the contribution to the mean rate of change of the momentum of degree of freedom @xmath23 , due to the coupling to electrons @xcite . in other words , @xmath22 is the effective force experienced by the mean displacement @xmath25 , and is what we would calculate for the force on the corresponding classical degree of freedom in the ehrenfest approximation . for the unperturbed density matrix we now make the choice @xmath26 , where @xmath27 describes oscillators in time - evolving wavepackets with @xmath28 below we consider non - interacting electrons . however screening plays an important - and occasionally problematic - role in current - induced forces and electron - phonon scattering . an outline is given in refs . @xcite . next , we substitute into equation ( [ 1 ] ) , trace out the oscillators and trace out all but one electron . the result , for non - interacting electrons , is @xmath29x_{\beta}(\tau ) \,d\tau \label{2}\ ] ] where all operators are now 1-electron operators ( indicated explicitly for the reduced 1-electron dm and by the use of lower - case symbols for other electronic operators ) and @xmath30 is an interaction - picture operator . ) is what we would have written for the perturbed electronic dm due to coupling to classical degrees of freedom with trajectories @xmath21 ; the result , via ( [ f ] ) , are the corresponding forces in the ehrenfest approximation . ] our final task is the choice of unperturbed electronic dm @xmath31 . to this end we now briefly introduce the landauer picture of steady - state transport in mesoscopic systems . the landauer picture ( lp ) of conduction is a powerful construct which - combined with green s function theory - has become the most widely used transport method for nanoscale systems . the lp is summarized in fig . [ fig4 ] . the landauer picture . details are discussed in the text . ] the nanoconductor of interest - the sample - is connected to two perfect leads , each in turn connected through a reflectionless contact to a heat - particle reservoir for electrons . the two reservoirs have different electrochemical potentials , @xmath32 and @xmath33 , and inject carriers into their respective leads with the corresponding energy distributions . formally , the injected carriers in the steady state occupy a set of stationary scattering wavefunctions , two of which are depicted schematically in the figure . a state @xmath34 consists of an incident wave in lead 1 that gets partially transmitted into lead 2 and partially reflected back , and conversely for @xmath35 . bias enters the lp via the _ electrochemical _ potential difference @xmath36 between the _ reservoirs_. we may form the partial density - of - states operators for the two sets of states @xmath37 where @xmath38 are the energies of the respective states . hence we can characterize the lp steady state by the time - independent 1-electron dm @xmath39 where @xmath40 and @xmath41 are the fermi - dirac population functions for electrons arriving from the respective reservoirs , @xmath42 . like the electrochemical potentials @xmath32 and @xmath33 , the temperature @xmath43 therein is a property of the reservoirs . @xmath44 and @xmath45 , and hence all 1-electron properties of the system , may be calculated with the aid of green s functions @xcite . we now set @xmath46 , write @xmath47 } = x_{\beta}(t ) \,\cos{\omega_\beta(\tau -t ) } + [ v_{\beta}(t)/\omega_\beta]\,\sin{\omega_\beta(\tau -t)}$ ] , and substitute into ( [ 2 ] ) and ( [ f ] ) to obtain the second - order forces ) we are free to treat @xmath21 and @xmath48 as the _ actual _ - as opposed to unperturbed - oscillator positions and velocities . ] @xmath49 where @xmath50 \ } \cos{\omega_\beta ( \tau -t)}\,d\tau\ , \label{kd}\\ & & l_{\alpha\beta } = - \frac{1}{{\rm i}\hbar \omega_\beta}\,\int_{0}^{t}\,{\rm tr}\ { { \hat f}_{\alpha } [ { \hat f}_{\beta}(\tau - t),{\hat \rho}_{\rm lp } ] \ } \sin{\omega_\beta ( \tau -t)}\,d\tau \ , . \label{ld}\end{aligned}\ ] ] to evaluate @xmath51 and @xmath52 , we take @xmath53 and use the relations @xmath54 where @xmath55 is the retarded 1-electron green s function . in the integrand in ( [ 2 ] ) , describing decoherence of the dynamics into the distant past . ] the result for @xmath51 and @xmath52 is @xmath56{\hat f}_{\beta}{\hat \rho}_{\rm lp}(\epsilon)\}\,d\epsilon \label{k0 } \\ l_{\alpha\beta } & = & \frac{1}{\omega_\beta}\,{\rm im}\,\int_{-\infty}^{\infty}\,{\rm tr } \{{\hat f}_{\alpha } [ { \hat g}^{+}(\epsilon+\hbar\omega_\beta ) - { \hat g}^{+}(\epsilon-\hbar\omega_\beta ) ] { \hat f}_{\beta}{\hat \rho}_{\rm lp}(\epsilon)\}\,d\epsilon\ , . \label{l0}\end{aligned}\ ] ] in the rest of the discussion of mean forces we will consider a single oscillator frequency , @xmath57 . an example where this situation arises are degenerate , or nearly degenerate , unperturbed normal modes , which are especially strongly coupled by current @xcite . alternatively , we may think of the introduction of @xmath57 as follows . once the full perturbed equations of motion of atoms under current are known , we may recalculate the normal modes to find new modes describing atomic motion in the current - carrying system @xcite . due to the non - conservative current - induced force , which we will discuss shortly , the amplitude of some of the new modes may grow in time and dominate the dynamics . @xmath57 can be the frequency ( or more precisely its real part ) of one of these modes , with indices @xmath23 and @xmath58 labelling atomic degrees of freedom . the forces we are calculating are then the forces on atoms , under motion in that mode . the general case is discussed in @xcite . atomic motion generates electron - hole excitations in the electron gas which act back via the forces on atoms . it turns out that the forces can be written solely in terms of a weighted electron - hole density of states . we introduce the function @xmath59 , which encodes important information about electrons : @xmath60 here the sums include all electron states , i.e. scattering states emerging both from lead 1 and from lead 2 . we use the notation @xmath61 if the state @xmath62 is incident from lead 1 , and likewise for lead 2 . the dynamics is controlled by two green s functions , which only depend on the oscillator frequency and are independent of the details of the electronic system . they are @xmath63 where @xmath64 is an infinitesimal positive quantity . the two force - functions can now be written as @xmath65 we can further symmetrize @xmath59 and write it as a sum of even and odd functions : @xmath66 where @xmath67\quad{\rm and}\quad \lambda^{\rm o}_{\alpha\beta}(\omega ) = \frac{1}{2}\,\left[\lambda_{\alpha\beta}(\omega)-\lambda_{\alpha\beta}(-\omega)\right]\,.\ ] ] since the real and imaginary parts of @xmath68 and @xmath69 are either even or odd , we arrive at the following forms for the functions ( using the notation @xmath70 for the various complex quantities ) : @xmath71\,d\omega\\ l_{\alpha\beta } & = 2\,\frac{1}{\omega_0}\,\int_0^\infty \ , \left [ g''_l(\omega ) { \lambda_{\alpha\beta}^{\rm o}}'(\omega ) + g_l'(\omega){\lambda_{\alpha\beta}^{\rm e}}''(\omega ) \right]\,d\omega\end{aligned}\ ] ] where the two relevant @xmath72-functions are @xmath73 \times \nonumber\\ & \left [ n_f(\epsilon_q-\mu_q)-n_f(\epsilon_p-\mu_p)\right]\delta(\hbar\omega-\epsilon_q+\epsilon_p)\\ { \lambda_{\alpha\beta}^{\rm e}}''(\omega ) = \frac{1}{2}\,&\sum_{p , q}\,\mbox{im}\,\big[\langle \psi_q|\hat{f}_\alpha|\psi_p\rangle\langle \psi_p|\hat{f}_\beta|\psi_q\rangle\big]\times \nonumber\\ & \left [ n_f(\epsilon_q-\mu_q)-n_f(\epsilon_p-\mu_p)\right]\delta(\hbar\omega-\epsilon_q+\epsilon_p)\,.\end{aligned}\ ] ] we note several points . first , both @xmath72-functions are a sum over electron - hole pairs with a total energy @xmath74 . the factors @xmath75 $ ] , together with the delta function , ensure that . each electron - hole pair contribution is weighted by a factor depending on the matrix elements of the force operators . next , by inspection we can see that the function @xmath76 is even with respect to exchange of indices @xmath23 and @xmath58 . the other function , @xmath77 , is odd in these indices . the final , and very important , observation is that at equilibrium , i.e. @xmath78 , the function @xmath77 will vanish . indeed then all states ( right- and left - travelling ) with a given energy @xmath79 enter the expression for @xmath80 with the same occupancy @xmath81 . but , within this degenerate hilbert space , we can always choose a basis with pure real wavefunctions . then @xmath77 , which is composed of the imaginary parts , vanishes . equation ( [ force ] ) shows that matrix @xmath82 describes position - dependent steady - state forces exerted by electrons on nuclear vibrations . they come in two forms : conservative and non - conservative , which we separate below . forces are non - conservative if their `` curl '' is non - zero . the `` curl '' in our case is defined as the tensor @xmath83 which is twice the anti - symmetric part of @xmath51 , @xmath84 the green s function @xmath85 is given by @xmath86\,.\ ] ] hence our final result for the non - conservative force is @xmath87 the force will vanish at equilibrium , since as we have noted the function @xmath88 vanishes in that case . the remaining - symmetric - part of @xmath51 on the other hand gives rise to effective corrections to the equilibrium dynamical response matrix @xcite , and thus to the effective confining potential for nuclei . this correction is also potentially important , as it shifts phonon frequencies . the anti - symmetric part of @xmath82 describes non - conservative forces with the capacity to drive the nuclear subsystem around closed paths . insight into these forces may be gained by evaluating @xmath89 explicitly for a weak scatterer , serving as a test particle , in a current - carrying metal @xcite . if the scattering potential of the test particle is @xmath90 , with @xmath91 , where @xmath92 denotes electron position and @xmath93 is that of the scatterer , then to lowest order in the strength @xmath94 we get @xmath95 here the vector @xmath96 is given by @xmath97\delta(\hbar\omega_0-\epsilon_q+\epsilon_p ) \label{lcurl}\end{aligned}\ ] ] where @xmath98 is the electron density of state @xmath99 at the test - particle position @xmath100 , and @xmath101 is the velocity density of the state , at that position . we will evaluate it for the situation considered in sorbello s argument ( fig . [ fig2 ] ) . we consider a jellium wire with a square cross section of side @xmath102 . the energy eigenstates are travelling waves along the wire axis ( @xmath103 ) and standing waves in the transverse ( @xmath104-@xmath105 ) plane : @xmath106 where @xmath107 is a normalization length . the energy of the state is @xmath108 . the curl of the non - conservative force will be proportional to @xmath109 for small voltages . figure [ fig5 ] shows a vector plot of the curl of the force , in the small - bias , small - frequency limit . we see that the curl is largest in a thin region of width @xmath110 ( the fermi wavelength ) close to the surface . curl of non - conservative force on an impurity in a current - carrying free - electron wire with a square cross section . electrons are flowing out of the page . the sidelength is @xmath111 . ] figure [ fig6 ] shows the @xmath105-component of the curl along a line parallel to the @xmath104-axis , through the wire centre , for the last 5 fermi wavelengths close to the surface , for the cases @xmath112 and @xmath113 . ( the plot runs in the negative @xmath104-direction . ) we see that the curl of the non - conservative force is a surface phenomenon , which is independent of the size of the wire . its origin is the variation in @xmath114 and @xmath115 in equation ( [ lcurl ] ) as we cross the wire surface . an analogous effect will be discussed in connection with another current - induced force below . @xmath105-component of the curl of the force on the impurity close to the surface of the wire , for sidelengths @xmath111 ( blue ) and @xmath116 ( red ) . details are discussed in the text . ] the velocity - dependent forces are controlled by the function @xmath52 . first , we consider the symmetric part . it is given by @xmath117 the function @xmath118 is given by @xmath119\,.\ ] ] hence this velocity - dependent force is @xmath120 this force can do work on the oscillating atoms . the power is @xmath121 which is non - vanishing in general . for most situations the power is negative and energy is transferred from vibrations to electrons . hence the superscript @xmath122 for friction . one can however have systems out of equilibrium where the power in fact is positive @xcite . turning next to the anti - symmetric part , it is given by @xmath123 an anti - symmetric force @xmath124 will do no net work , since the power is @xmath125 this is a force akin to the lorentz force . it can only bend trajectories . it can be related to the berry phase of electrons as the atoms are moving around in the electron gas @xcite , and hence the superscript @xmath126 . the function @xmath127 is even in @xmath128 and is given by @xmath129 this function decays on the frequency scale @xmath57 , and integrates to zero . hence the integral in ( [ lasym ] ) is measuring variations in the electron - hole density of states @xmath77 on the scale @xmath57 . @xmath130 will therefore be sensitive to the frequency structure of the electron - hole density of states , and to features , such as resonances , on the scale of @xmath57 in particular . a flat electron - hole density of states will produce a vanishing `` lorentz '' force . let us evaluate the electronic friction on the weak test scatterer considered earlier , now in an equilibrium homogenous electron gas for simplicity . we need to evaluate the function @xmath131 . the friction will be isotropic , so we only need the case @xmath132 . the result in the small - frequency limit is @xmath133 where @xmath134 is the electron number density . the friction force when the scatterer is moving with velocity @xmath135 therefore is @xmath136 . but physically this situation is the same as if the electron gas were moving past a stationary scatterer , at drift velocity @xmath137 . then the wind force from ( [ fw ] ) is the same as @xmath138 , after we identify @xmath139 as the current density @xmath3 in the rest frame of the scatterer . therefore we arrive at the expected but useful result that for a free - electron metal the friction and the wind force are reciprocals of each other . this result is connected with the relation between the friction and resistivity @xcite , and between resistivity and electromigration forces @xcite . we have seen that a frequency - independent function @xmath77 will not result in a lorentz - like force . we consider our prime example of a particle moving in a flow of electrons in a thin jellium wire . it can be thought of as a set of 1d wires ( or channels ) - one for each transverse electron mode . each channel will have a density of states with a van hove singularity at the bottom of the respective subband . these strong variations of the density of states may provide the frequency dependence of @xmath77 that is needed . we consider again a test scatterer located somewhere in the square cross section of the wire , used earlier . according to the general formula ( [ lorentzforce ] ) , the defect will feel a `` lorentz '' force , @xmath140 , where the `` b''-field has a vector potential given by @xmath141\delta(\hbar\omega-\epsilon_p+\epsilon_{p'})\ , d\omega\,.\end{aligned}\ ] ] the 1-electron state @xmath142 has three quantum numbers @xmath143 , where @xmath144 is the momentum along the wire , while @xmath145 are the transverse - mode quantum numbers , with corresponding mode wavefunctions @xmath146 . it is useful to express energies in terms of the transverse energy scale @xmath147 . the fermi energy is then @xmath148 . likewise , the electron energies are @xmath149 , where @xmath150 . the vector potential can then be written as @xmath151 \nonumber\\ & \kappa\ , \left[n_f(\epsilon_{knm}-\mu_1)-n_f(\epsilon_{knm}-\mu_2)\right]\,{\bf e}_z\end{aligned}\ ] ] where @xmath152 is the unit vector along the wire axis . the integrals can in fact be done analytically at zero temperature . the result is @xmath153 here the sum over @xmath145 is restricted to values such that @xmath154 , and we have assumed that no subband edges fall within the bias window . this result enables the following observations . first , under lateral confinement @xmath155 are standing waves . the resultant interference ripples as a function of transverse position in the wire generate a non - vanishing effective `` magnetic '' field , even in the absence of longitudinal inhomogeneities or backscattering in the conductor . consider next the gross structure of the vector potential . to this end suppose that we average over the ripples due to the confinement , and treat each @xmath155 as a constant inside the wire , dropping to zero outside . this still leaves the dramatic variation in @xmath156 as we cross the wire surface , giving rise to a surface `` magnetic '' field , analogous to the curl of the non - conservative force discussed earlier . therefore the `` lorentz '' forces are of particular interest for surface atoms and adsorbates in metallic nanowires , with departures from the dynamics that might be expected otherwise . we conclude this section with a comment on the range of validity of the present discussion . the perturbative approach above requires restricted mean displacements over long times . this precludes free translation of scattering centres as a type of motion we can consider . in fact , if we allow a maximum typical displacement @xmath157 , then for motion at typical velocity @xmath158 the present approach requires a minimum frequency @xmath159 . conversely , for a given oscillator frequency @xmath128 , we require velocities below @xmath160 . an important avenue - in this context and more generally - is the expansion of the hamiltonian in ( [ heph ] ) to higher order in the oscillator displacements . finally , we may describe the `` lorentz '' force as a dynamical effect in the following sense . keeping all else fixed , the ratio of the current - induced velocity - dependent `` lorentz '' force to the current - induced displacement - dependent non - conservative force scales with frequency as @xmath161 , where @xmath162 is a pertinent electronic energy scale @xcite . therefore in the small - frequency limit the static non - conservative force dominates . as discussed earlier , @xmath22 is the force that enters the so - called ehrenfest approximation . physically , this is the mean force on nuclei , which does not yet tell us anything about force _ noise_. we may immediately infer a key limitation of the ehrenfest approximation . consider a problem with equilibrium electrons at an elevated electronic temperature . then both the non - conservative and lorentz - like force vanish , and we are left with motion under conservative forces , along with the friction , leading to an inevitable loss of energy from the nuclear motion , whatever the nuclear kinetic energies . but this can not be right : hot enough electrons should be delivering energy to the atomic motion , not the other way round . we conclude that there must be a key physical process missing from the ehrenfest approximation . indeed , this is _ spontaneous phonon emission _ @xcite - the primary way for excited electrons to excite atomic vibrations . we conclude further that the missing force noise must be the agent responsible for spontaneous emission and ultimately for electron - phonon thermal equilibration . we can recover this noise by considering the second - order corrections to the equation of motion of the reduced oscillator dm , @xmath163 . to this end we place ( [ 1 ] ) into the many - body liouville equation @xmath164 - \sum_{\beta}\,[{\hat f}_{\beta}{\hat x}_{\beta},{\hat \rho}(t)]\ ] ] and trace out electrons . this gives @xmath165 + { \hat \xi}_1(t ) + { \hat \xi}_2(t ) \label{rhoscdot}\ ] ] where @xmath166 is the harmonic oscillator hamiltonian and the first- and second - order corrections are given by @xmath167\,f_{\beta}^{(0)}(t ) \\ { \hat \xi}_2(t ) & = & - \sum_{\beta } \ , [ { \hat x}_{\beta } , { \hat \phi}_{\beta}(t ) ] \label{xi2}\end{aligned}\ ] ] with @xmath168 and @xmath169\ , \langle \ { { \hat f}_{\beta},{\hat f}_{\alpha}(\tau - t ) \ } \rangle_{t } \,d\tau \nonumber \\ & - & \frac{1}{2{\rm i}\hbar}\,\sum_{\alpha}\int_{0}^{t}\ , \{{\hat x}_{\alpha}(\tau - t),{\hat \rho}_{\rm osc}(t)\}\ , \langle [ { \hat f}_{\beta},{\hat f}_{\alpha}(\tau - t ) ] \rangle_{t } \,d\tau\ , \label{corr } \\ = & - & \frac{1}{2{\rm i}\hbar}\,\sum_{\alpha}\int_{0}^{t } \,[{\hat x}_{\alpha}(\tau - t),{\hat \rho}_{\rm osc}(t)]\ , \langle \ { { \hat f}_{\beta},{\hat f}_{\alpha}(\tau - t ) \ } \rangle_{t } \,d\tau \nonumber \\ & - & \frac{1}{2{\rm i}\hbar}\,\sum_{\alpha}\int_{0}^{t}\ , \{{\hat x}_{\alpha}(\tau - t),{\hat \rho}_{\rm osc}(t)\}\ , \langle [ { \hat f}_{\beta},{\hat f}_{\alpha}(\tau - t ) ] \rangle_{t } \,d\tau\ , . \label{corr1}\end{aligned}\ ] ] errors are of order 3 or higher in the force operators ; @xmath170 is an interaction - picture operator ; @xmath171 denotes averaging in the instantaneous unperturbed dm at time @xmath172 ; commutators are directly convertible to 1-electron form and hence ( [ corr1 ] ) . term 1 in ( [ corr1 ] ) , together with @xmath173 , corresponds to a fictitious perturbation @xmath174 , with @xmath175 an _ effective _ classical random force with mean @xmath176 and with correlation function @xmath177 after averaging over force realizations ( denoted by @xmath178 above ) . now we show that term 2 in ( [ corr1 ] ) corresponds to the forces found earlier . to this end we investigate the wigner function @xmath179 for @xmath180 oscillators . ( here @xmath181 for short , and similarly for @xmath182 and @xmath183 . ) consider the contribution of term 2 to @xmath184 . placing the relation @xmath185 in term 2 in ( [ corr1 ] ) , comparing the integrals with ( [ kd ] ) and ( [ ld ] ) , and substituting back into ( [ xi2 ] ) and thence into ( [ rhoscdot ] ) , we see that the quantity to be wigner - transformed is @xmath186\,.\ ] ] the result is @xmath187 upon comparing with the classical liouville equation , obeyed exactly by the harmonic - oscillator wigner function , @xmath188 where @xmath189 is the total force on degree of freedom @xmath58 , we recover ( [ force ] ) . the extra term on the left in equation ( [ qtilde ] ) is the known correction to the liouville equation required to conserve phase - space probability in the presence of dissipation ( in this case , the electronic friction ) . we note further that care is required in identifying @xmath190 as @xmath191 above , as the two quantities are in general not the same . however any difference between them in the present case involves the force operators , and therefore - within the given order of perturbation theory - the identification is justified . the properties of the force noise and resultant phenomena , such as the thermal equilibration of vibrations with the electron bath and joule heating in nanowires under current , are discussed in detail in ref . @xcite . we consider a single oscillator coupled to an equilibrium electron bath . the only forces present are the harmonic restoring force , the friction and the noise . we will show that the competition between the latter two enables the oscillator to equilibrate with the bath . first we must work out the correlation function ( [ corrf ] ) . the result for non - interacting independent electrons is @xmath192 where as before the indices label 1-electron states with energies @xmath193 . the occupancies @xmath194 are given by the fermi - dirac distribution , @xmath195 , and @xmath196 . we now show that a _ classical _ oscillator , under the above random force and the friction , equilibrates at mean energies that in fact obey the quantum - mechanical bose - einstein distribution . a harmonic oscillator of mass @xmath197 and angular frequency @xmath57 , subjected to an additional external force @xmath198 , undergoes velocity deviations from its native trajectory given by @xmath199 if @xmath198 is the random force above , then the power at time @xmath172 , after averaging and taking the long - time limit , is @xmath200 after some algebra this becomes @xmath201 where @xmath43 is the temperature of the electron bath . we now compare with the friction coefficient from ( [ l0 ] ) , producing the relation @xmath202 which is an expression of the fluctuation - dissipation theorem . setting @xmath203 equal to the power lost to the friction , @xmath204 , produces the steady - state oscillator energy @xmath205 which is the bose - einstein distribution , for the given bath temperature . therefore the _ effective _ classical random force that was _ identified _ within a quantum - mechanical calculation , when applied together with the quantum - mechanical friction to a fictitious classical oscillator , has exactly the properties required to reproduce the behaviour expected from the full interacting quantum problem . one of these properties is the zero - point oscillator energy that survives even in the limit of zero bath temperature . these conclusions furthermore remain valid under non - equilibrium conditions , resulting in a remarkable mapping of quantum phonons coupled to an electron bath onto a classical stochastic problem @xcite . electron - nuclear dynamics in atomic - scale conductors is a challenging problem , combining many - body physics with the description of open quantum systems driven out of equilibrium . a further difficulty , at the root of some of the controversies that the field has experienced , is the conceptual question of what we mean by force under these general conditions and , accordingly , what framework is required for its calculation . the aim of this article is to provide an introduction to elements of the current methodological and physical understanding of forces on nuclei in conducting systems . two of the five forces - the effective conservative confining potential and the electronic friction - are present at equilibrium ( though they collect non - equilibrium corrections ) . so too is the effective random force , responsible for joule heating and electron - phonon equilibration . the non - conservative and `` lorentz '' force are only possible under current . we have aimed at obtaining these forces in a simple way , while illustrating the physics behind them with examples . the analogy with other flows however can be deceptive . the current - induced force on a single defect in jellium ( which is always along the incident particle current ) _ is _ simple , and may be understood directly in terms of momentum transfer on the defect . but for nuclei in a solid current - induced forces can be counter - intuitive , because electrons then undergo multiple scattering in the entire region around a chosen target , with quantum - mechanical interference . this can result in forces on individual atoms with unexpected directions , including situations when the current - induced force on a defect opposes the incident electron `` beam '' . however the possibility of directional generalized angular - momentum transfer to the atomic motion is a general property of current - carrying nanowires , resulting in a potent energy - transfer mechanism . there are several active lines of research into these forces at present : the interplay between the stochastic and the non - conservative force , the properties of these forces in resonant systems ( with sharp energy features ) , the capacity of the non - conservative forces to drive electromigration or mechanical failure . there continually is scope for further fundamental and conceptual work in the area , with a potential practical pay - off , such as the question of whether - and how - one might go about subsuming current - induced forces into effective corrections to semi - empirical interatomic potentials . it is hoped that the present discussion will be of assistance to the general reader in following up past and future work in this field . tnt and dd gratefully acknowledge funding from epsrc ( ep / i00713x/1 ) . jtl acknowledges support from nsfc ( no . 61371015 and 11304107 ) . horsfield a p , bowler d r , fisher a j , todorov t n and montgomery m j 2004 power dissipation in nanoscale conductors : classical , semi - classical and quantum dynamics _ j. phys . : condens . matter _ * 16 * 3609

we revisit the problem of forces on atoms under current in nanoscale conductors . we derive and discuss the five principal kinds of force under steady - state conditions from a simple standpoint that - with the help of background literature - should be accessible to physics undergraduates . the discussion aims at combining methodology with an emphasis on the underlying physics through examples . we discuss and compare two forces present only under current - the non - conservative electron wind force and a lorentz - like velocity - dependent force . it is shown that in metallic nanowires both display significant features at the wire surface , making it a candidate for the nucleation of current - driven structural transformations and failure . finally we discuss the problem of force noise and the limitations of ehrenfest dynamics .