24114301
Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
BRAFV600E is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting “active” protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-RafV600E with an IC50 of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-RafV600E kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-RafV600E-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-RafV600E-positive cells. In B-RafV600E-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-RafV600E-driven tumors.
122921203
Search for the neutral Higgs bosons of the minimal supersymmetric standard model from Z0 decays
We present the results from a search for the light neutral scalar Higgs boson h° and the pseudoscalar Higgs boson A° of the minimal super-symmetric standard model. The analysis is based on a data sample corresponding to 71 000 hadronic Z° decays recorded with the L3 detector at LEP. No evidence for the existence of the neutral Higgs bosons h° and A° has been found. The region of h° and A° masses up to 41.5 GeV is excluded at 95% confidence level.
15702909
The continuum limit of perturbative coefficients calculated with a large field cutoff
Abstract We report MC calculations of perturbative coefficients for lattice scalar field theory in dimensions l, 2 and 3, where the large field contributions are cutoff. This produces converging (instead of asymptotic) perturbative series. We discuss the statistical errors and the lattice effects and sho-kv that accurate calculations are possible even in a crossover region where no approximation works. We show that the field cutoff is also a UV regulator. We point out the relevance for QCD questions discussed by Tomboulis ad Trottier at this conference.
36263241
New optimization methods for converging perturbative series with a field cutoff
We take advantage of the fact that in lambda phi ^4 problems a large field cutoff phi_max makes perturbative series converge toward values exponentially close to the exact values, to make optimal choices of phi_max. For perturbative series terminated at even order, it is in principle possible to adjust phi_max in order to obtain the exact result. For perturbative series terminated at odd order, the error can only be minimized. It is however possible to introduce a mass shift in order to obtain the exact result. We discuss weak and strong coupling methods to determine the unknown parameters. The numerical calculations in this article have been performed with a simple integral with one variable. We give arguments indicating that the qualitative features observed should extend to quantum mechanics and quantum field theory. We found that optimization at even order is more efficient that at odd order. We compare our methods with the linear delta-expansion (LDE) (combined with the principle of minimal sensitivity) which provides an upper envelope of for the accuracy curves of various Pade and Pade-Borel approximants. Our optimization method performs better than the LDE at strong and intermediate coupling, but not at weak coupling where it appears less robust and subject to further improvements. We also show that it is possible to fix the arbitrary parameter appearing in the LDE using the strong coupling expansion, in order to get accuracies comparable to ours.
21618508
Dirac versus Weyl fermions in topological insulators: Adler-Bell-Jackiw anomaly in transport phenomena.
Dirac metals (gapless semiconductors) are believed to turn into Weyl metals when perturbations, which break either time reversal symmetry or inversion symmetry, are employed. However, no experimental evidence has been reported for the existence of Weyl fermions in three dimensions. Applying magnetic fields near the topological phase transition from a topological insulator to a band insulator in Bi1-xSbx we observe not only the weak antilocalization phenomenon in magnetoconductivity near zero magnetic fields (B<0.4  T), but also its upturn above 0.4 T only for E//B. This "incompatible" coexistence between weak antilocalization and "negative" magnetoresistivity is attributed to the Adler-Bell-Jackiw anomaly ("topological" E·B term) in the presence of weak antilocalization corrections.
120388388
Measurement of g(A) and g(V), the neutral current coupling constants to leptons
Abstract We have measured both the rates and the forward-backward asymmetry of l + l − from Z 0 →l + l − (where l= μ , τ ) with the L3 detector. We obtained Γ ll =88±4±3 MeV and the vector neutral current coupling constant, g v =0.00±0.07 and the axial vector neutral current coupling constant, g A =−0.515±0.015.
16866447
Interpreting Helioseismic Structure Inversion Results of Solar Active Regions
Helioseismic techniques such as ring-diagram analysis have often been used to determine the subsurface structural differences between solar active and quiet regions. Results obtained by inverting the frequency differences between the regions are usually interpreted as the sound-speed differences between them. These in turn are used as a measure of temperature and magnetic-field strength differences between the two regions. In this paper we first show that the “sound-speed” difference obtained from inversions is actually a combination of sound-speed difference and a magnetic component. Hence, the inversion result is not directly related to the thermal structure. Next, using solar models that include magnetic fields, we develop a formulation to use the inversion results to infer the differences in the magnetic and thermal structures between active and quiet regions. We then apply our technique to existing structure inversion results for different pairs of active and quiet regions. We find that the effect of magnetic fields is strongest in a shallow region above 0.985R⊙ and that the strengths of magnetic-field effects at the surface and in the deeper (r<0.98R⊙) layers are inversely related (i.e., the stronger the surface magnetic field the smaller the magnetic effects in the deeper layers, and vice versa). We also find that the magnetic effects in the deeper layers are the strongest in the quiet regions, consistent with the fact that these are basically regions with weakest magnetic fields at the surface. Because the quiet regions were selected to precede or follow their companion active regions, the results could have implications about the evolution of magnetic fields under active regions.
119285015
P-V criticality in the extended phase space of Gauss-Bonnet black holes in AdS space
A bstractWe study the P − V criticality and phase transition in the extended phase space of charged Gauss-Bonnet black holes in anti-de Sitter space, where the cosmological constant appears as a dynamical pressure of the system and its conjugate quantity is the thermodynamic volume of the black holes. The black holes can have a Ricci flat (k = 0), spherical (k = 1), or hyperbolic (k = −1) horizon. We find that for the Ricci flat and hyperbolic Gauss-Bonnet black holes, no P − V criticality and phase transition appear, while for the black holes with a spherical horizon, even when the charge of the black hole is absent, the P − V criticality and the small black hole/large black hole phase transition will appear, but it happens only in d = 5 dimensions; when the charge does not vanish, the P − V criticality and the small black hole/large phase transition always appear in d = 5 dimensions; in the case of d ≥ 6, to have the P − V criticality and the small black hole/large black hole phase transition, there exists an upper bound for the parameter $ b=\widetilde{\alpha }{{\left| Q \right|}^{{{-2 \left/ {{\left( {d-3} \right)}} \right.}}}} $, where $ \widetilde{\alpha } $ is the Gauss-Bonnet coefficient and Q is the charge of the black hole. We calculate the critical exponents at the critical point and find that for all cases, they are the same as those in the van der Waals liquid-gas system.
118681206
Solar Models with Revised Abundance
We present new solar models in which we use the latest low abundances and further include the effects of rotation, magnetic fields, and extra-mixing processes. We assume that the extra-element mixing can be treated as a diffusion process, with the diffusion coefficient depending mainly on the solar internal configuration of rotation and magnetic fields. We find that such models can well reproduce the observed solar rotation profile in the radiative region. Furthermore, the proposed models can match the seismic constraints better than the standard solar models, also when these include the latest abundances, but neglect the effects of rotation and magnetic fields.
118311606
A holographic study on vector condensate induced by a magnetic field
A bstractWe study a holographic model with vector condensate by coupling the anti-de Sitter gravity to an Abelian gauge field and a charged vector field in (3 + 1) dimensional spacetime. In this model there exists a non-minimal coupling of the vector field to the gauge field. We find that there is a critical temperature below which the charged vector condenses via a second order phase transition. The DC conductivity becomes infinite and the AC conductivity develops a gap in the condensed phase. We study the effect of a background magnetic field on the system. It is found that the background magnetic field can induce the condensate of the vector field even in the case without chemical potential/charge density. In the case with non-vanishing charge density, the transition temperature raises with the applied magnetic field, and the condensate of the charged vector operator forms a vortex lattice structure in the spatial directions perpendicular to the magnetic field.
18205314
Shock breakout in Type Ibc supernovae and application to GRB 060218/SN 2006aj
Recently, a soft blackbody component was observed in the early X-ray afterglow of GRB 060218, which was interpreted as shock breakout from the thick wind of the progenitor Wolf-Rayet (WR) star of the underlying Type Ic supernova 2006aj. In this paper, we present a simple model for computing the characteristic quantities (including energy, temperature and time duration) for the transient event from the shock breakout in Type Ibc supernovae produced by the core-collapse of WR stars surrounded by dense winds. In contrast to the case of a star without a strong wind, the shock breakout occurs in the wind region rather than inside the star, caused by the large optical depth in the wind. We find that, for the case of a WR star with a dense wind, the total energy of the radiation generated by the supernova shock breakout is larger than that in the case of the same star without a wind by a factor of > 10. The temperature can be either hotter or colder, depending on the wind parameters. The time duration is larger caused by the increase in the effective radius of the star due to the presence of a thick wind. Then, we apply the model to GRB 060218/SN 2006aj. We show that, to explain both the temperature and the total energy of the blackbody component observed in GRB 060218 by the shock breakout, the progenitor WR star has to have an unrealistically large core radius (the radius at optical depth of 20), larger than 100R ⊙ . In spite of this disappointing result, our model is expected to have important applications to the observations on Type Ibc supernovae in which the detection of shock breakout will provide important clues to the progenitors of Type Ibc supernovae.