Many newly observed FQHE features do not agree with a conventional model of composite fermions and reveal a different hierarchy in comparison to monolayer graphene or GaAs 2DEG. We explain the peculiarity of the FQHE hierarchy in the bilayer system in the framework of a topological approach, which includes the composite fermion model as its special case. Inclusion of a topological effect caused by the hopping of electrons between the two sheets in the bilayer system allowed for an explanation of the FQHE hierarchy in the graphene bilayer in satisfactory accordance with the experimental observations.Recent experimental progress in Hall measurements in bilayer graphene in the so-called open-face configuration of boron nitride encapsulated samples, together with the earlier technique of suspended samples, allows for precise observation of the fractional quantum Hall effect (FQHE) in all 4 subbands of the Lowest Landau level (with  It is commonly acknowledged that in the induced by the interaction formation of nonlocal specific correlations in FQHE, the central role is played by an exceptional topology of the planar continuum. An examination of FQHE in graphene is especially challenging. Graphene is perfectly two dimensional but with a pseudo-relativistic band structure. The band electron dynamics in graphene are dominated by the Dirac-like points in the corners of the hexagonal Brillouin zone, where the locally conical-shaped valence band meets the similarly conical-shaped conduction band, resulting in a linear-in-momentum local Hamiltonian2. This leads to non-equidistant LLs structure in the graphene monolayer, with energy proportional to n is number of the LL) instead of the ~n dependence in conventional 2DEG. In bilayer graphene, an interlayer tunnelling of electrons restores the parabolic local energy and almost-equidistant LLs, 3. The specific graphene pseudo-relativistic band structure close to the Dirac points, however, does not influence the topological constraints imposed on trajectories , because the band structure is induced by a local electric interaction-type crystal field, which does not perturb the path topology, and the FQHE is observed in graphene, similarly to conventional semiconductor 2DEG systems.The fractional quantum Hall effect (FQHE) is one of the most spectacular and mysterious quantum phenomena in condensed matter. Despite intensive experimental and theoretical studies of FQHE since the 80 s of the last century, the effect still eludes complete understanding. The FQHE apparently exceeds the conventional framework of local quantum mechanics and displays a trade-off between the Coulomb interaction induced localization and disorder8 reveal significant distinctions from FQHE manifestation in the graphene monolayer12. This is in conflict with a conventional imagination that FQHE is a manifestation of hypothetical composite fermions (CFs)13, i.e., electrons dressed with even number of localized on particles flux quanta of some auxiliary magnetic field. According to CF theory, such effective quasiparticles should be present both in monolayer and bilayer Hall systems, what however, does not agree with experimental observations in bilayer graphene8.In recent years, advances in the manufacturing methods of monolayer and bilayer ultra-clean graphene samples accelerated the development of the Hall experiment in this material, and several new observations of FQHE have been reported. Remarkably, the observations of FQHE in bilayer graphene12 and by the mastering of an independent method for reducing substrate perturbations of graphene layers in samples supported by hexagonal boron nitride (hBN) crystal substrate10. The absence of a substrate (for suspended samples) or the avoidance of lattice mismatch (for hBN substrate) favour the delicate correlations induced by the interaction of 2D electrons, resulting in FQHE manifestation. The triggering role for FQHE organization is played by high electron mobility, well exceeding 100,000 cm2/(Vs) in both abovementioned experimental setups for Hall measurement in graphene.Important progress in the Hall experiment in graphene has been achieved by the invention of a measurement technique for suspended graphene small scrapings (both monolayer and bilayer)2. Moreover, for Dirac points, the specific Berry phase-like shift for chiral 2D carriers additionally influences the LL spectrum, which finally results in the 2. These plateaus in the monolayer graphene occur at the centres of the consecutive LLs (not completely filled LLs)14. In bilayer graphene, an extra degeneracy of the n = 0 and n = 1 oscillatory states in the LLL occurs and the twice as large Berry phase for chiral carriers shifts the IQHE plateau positions to the edges of LLs3. LLs in bilayer graphene are also four-fold spin-valley degenerate, except for the eight-fold degenerate lowest LL (LLL) (due to n = 0 and n = 1 degeneracy in the LLL)15. In the case of monolayer graphene, FQHE features are observed in the first six subbands of LLs with n = 0 and n = 112, which reproduce a hierarchy similar to that in conventional semiconductor 2DEG. In bilayer graphene, observation of FQHE reaches even subbands with n = 2, revealing a different and unexpected FQHE hierarchy there10. Especially interesting are observations of unusual even-denominator fillings for FQHE in bilayer graphene in the LLL, including the most pronounced feature at 4, which does not find any counterpart in monolayer systems. In particular, this state cannot be explained with the CF approach, as for CFs the Hall metal state is predicted at 13.A graphene sheet has regular planar hexagonal crystalline structure with two equivalent sublattices (two carbon atoms in the Bravais cell). This feature, together with the vanishing of the forbidden semiconductor gap at Dirac points, results in the four-fold spin-valley degeneracy of LLs in graphene monolayer18. Within this topological nonlocal braid group approach, we explain the structure of fractional fillings of LL subbands in accordance with experimental data and explain the reason for the insufficiency of the CF model in the bilayer graphene case. The topological braid group approach, formerly developed in refs20, gives the hierarchy of FQHE in agreement with the available experimental data for monolayer Hall systems and can be extended to the bilayer graphene case via identification of topological differences between mono and bilayer situations.In the present paper, we summarize the recent and controversial experimental observations of FQHE in bilayer graphene and compare them with the data for graphene monolayer. We identify the specific topological features that can explain the oddness of the correlated multi-particle states in the bilayer system in accordance with experimental observations. We propose an explanation for the exotic even-denominator fractions for FQHE in the LLL and the whole FQHE hierarchy in bilayer graphene in the framework of the topological commensurability approach3, and is equal to B is the external magnetic field, S is the sample surface, and 2. The Zeeman splitting in graphene is small21 and the valley splitting is small as well2, which results in the 4-fold approximate spin-valley degeneracy (referred to as SU(4) band symmetry). The LLL subbands are divided between particles and holes from the conduction and valence bands2. Hence, the bottom of the LLL is shifted upward by 2 (in terms of the filling factor). Conventionally, filling rates for holes from the valence band are assigned as negative numbers and are mirror reflections of the positive numbers denoting filling rates for electrons in the conduction band. An additional opportunity in graphene, beyond the ability of conventional 2DEG, is a possible control over the transition between particles and holes by the shifting of the Fermi level passing the Dirac point. Experimentally, it is realized by application of a relatively small lateral voltage , which determines the filling rate independently of the magnetic field strength.The massive degeneracy of each LL subband in graphene is the same as in the conventional 2DEG, despite the different LL structure3. As usual in graphene, the division of the LLL subbands equally between particles and holes causes the bottom, for uniformly charged carriers (electrons or holes), to be located in the centre of the 8-fold degenerate LLL. This extra degeneracy of the LLL is caused by the vanishing of energy of both the n = 0 and n = 1 oscillatory Landau states in the bilayer graphene, in contrast to the monolayer one. In the bilayer graphene, the Berry phase shift for chiral particles is also different (twice as large) in comparison to the graphene monolayer and is equal to 2π2. Hence, the consecutive plateaus of IQHE are located in bilayer graphene at integer filling rates, whereas in monolayer graphene were located at half-fillings of LLs3.Due to the interlayer electron hopping the local Hamiltonian for bilayer graphene re-attains the quadratic form with respect to the momentum. Hence, the LL spectrum in bilayer graphene resembles that of the ordinary 2DEG, but with four subbands for each LL level except for the LLL, which has eight-fold degeneracyN < N0, the filling rate, v = N/N0, is fractional  to the conduction band and the magnetic field is strong enough that 22. To implement braid group generators, the cyclotron orbit must be commensurate with the interparticle separation (the details are presented in SI). An archetype of the commensurability is S is the sample surface, N is the number of electrons, and N0 is LL degeneracy), as for 22.To decipher the FQHE hierarchy in this subband in graphene monolayer, we apply the braid group topological approach developed for the ordinary 2DEG systemIn the case of graphene, an important property follows from the fact that cyclotron orbits in graphene are defined by the bare kinetic energy 22 . The commensurability condition, in this case, is as follows: q is an odd integer17). For the LL subband holes, the particle-hole symmetric filling rates Therefore, the cyclotron orbit size in the subband lth particle separation (similarly to in lth LL), whereas the q − 1 antecedent loops take away an integer number of flux quanta (which are commensurate with nearest-neighbouring particles). For lth particles (next neighbours). In this manner, we obtain the hierarchy of fillings for FQHE in this LLL subband in the following form (the same as for the CF model): The next possible commensurability occurs when the last loop of the multi-loop cyclotron orbit is commensurate with every 23, inspired by its fractal-like character and by the Hofstadter’s butterfly picture24, on the other hand. The latter displays the commensurability of 2D cyclotron orbits with the crystalline cell, what, however, requires giant magnetic fields (~105 T), which are out of reach in the experiment24. The commensurability with larger spatial scale, which in case of a diluted Wigner lattice is comparable with the magnetic length, Let us notice that the hierarchy of FQHE filling factors in the LLL of monolayer graphene is similar to the FQHE hierarchy in the conventional 2DEG (GaAs), due to the same commensurability structure in both cases. The role of the commensurability in identification of the FQHE filling factor hierarchy has been noted earlierq-loop orbit q − 1 loops are adjusted to every xth particle . It is noticeable, however, that this series of exotic FQHE filling fractions have not yet been observed in the LLL in graphene, though they are observed in the first LL in monolayer graphene (as will be discussed below).One can also observe that other variants of commensurability may concern multi-loop orbits. Namely, each loop of the multi-loop structure may in principle be adjusted to particle separation in a different and mutually independent manner, matching nearest or next-nearest neighbours under various schemes. One such possibility may correspond to the situation in which n = 0.For lower magnetic fields, the next subband, the last one in the LLL, n = 1. This level has four, electron type subbands. The bare kinetic energy in this LL  is equal to q-loop orbits satisfy the commensurability condition q is an odd integer, which defines the main series for FQHE (multi-loop) in this subband, n = 1 LL subband.In an analogous way, one can consider fillings of the following LLs. The nearest one corresponds to x = 1, 2, 3, i.e., when the cyclotron orbit size exceeds the particle separation. Then, the single-loop orbit (large enough in this subband) can fit with every xth particle (x-order next-nearest neighbours). From this new commensurability opportunity, one finds fractions Simultaneously, in the central part of this higher LL subband, a new type of commensurability is possible, which is not accessible in the LLL. This new commensurability occurs when p-like pairing due to the spin polarization in this subband).Let us note that the special case of the commensurability, n = 1. Moreover, an interesting new possibility for commensurability occurs for q-loop orbits with next-nearest neighbours. The sizes of particular loops in the multi-loop structure may, in general, be adjusted to the interparticle spacing in an independent way, resulting in new filling rates. In particular, this results in the hierarchy n = 1 LL in monolayer graphene at ultra-low temperatures10—cf. Fig. A similar scheme of commensurability may be applied to the following subbands with In bilayer graphene, the topology of braid trajectories changes considerably in comparison to the monolayer system. The bilayer graphene is not strictly two dimensional and this opens a new possibility for the topology of the trajectories, as illustrated in Fig. Two sheets of the bilayer graphene lie at a close distance and electrons can hop between them. Multi-loop cyclotron orbits (and related braids) may thus reside in both layers simultaneously, i.e., loops may be distributed among both sheets. This makes a difference in comparison to the monolayer case because each sheet contributes to the total flux of the external magnetic field independently with its own surface, which strongly affects the cyclotron orbit size and braid commensurability condition. cf. Fig. .4 and cannot be explained by the CF model , and q is an odd integer . After omitting a single loop, the next loops must duplicate the former ones, no matter in which way the loops are distributed between both sheets. Thus, only q − 1 loops take part in the enhancement of the effective q-loop cyclotron orbit size in bilayer graphene, taking into account the same instances of commensurability as in the monolayer case.In general, in a bilayer system, loops of a multi-loop orbit may be located partly in both 2D sheets. To account for this effect in topological terms, adjusted to braid trajectories and commensurability requirements, one must neglect the contribution of a single loop in the multi-loop structure when the total flux of the external field is divided into fractions per loop. This single loop captures its own flux, whereas the remaining loops will share an identical flux—the one which passes through any cyclotron orbit in the monolayer case. Removal of the single loop must be performed independently of how the loops are distributed among two sheets. When we consider a selected loop located in the opposite sheet with respect to the antecedent loop, the next loops must fill both sheets of the bilayer structure as additional loops, regardless their specific distribution. Thus, all these loops, except one, take part in the division of the external field flux in exactly the same manner as in the monolayer case, provided that the selected loop is omitted together with the flux passing through this loop. This trick reduces the bilayer system to a monolayer one in the braid-loop topology sense. Thus, we can write the commensurability condition in the bilayer graphene in the case of too short single-loop cyclotron orbits in the following form  in the first particle-type subband of the LLL, i.e., in the subband 4.It must be emphasized that for multi-loop orbits in bilayer graphene, the total number of loops is still ondition ). Therefmentclass2pt{miniml > 1 describes the lth-order next-nearest neighbours commensurate with the last loop of the q − 1 loops, similarly to the monolayer case  next-nearest neighbours, For holes in this subband , we can write n due to the same size of the cyclotron orbits). A novelty occurs, however, in the next two subbands of the LLL, n = 1, the FQHE main series in the first of these subbands of the LLL, In the following subbands of the LLL, The generalization of this main series for holes in the subband and to the full FQHE hierarchy in this subband is formulated as follows: for subband holes, n = 1 in monolayer graphene), which allows single-loop commensurability with next-nearest neighbours. For x = 1, 2, 3, one obtains the fillings rates x = 1.5 in the above formula, which corresponds to the perfect commensurability of cyclotron orbits of electron pairs with the separation of these pairs at the electron filling rate n = 1, the cyclotron orbits have the same size and the FQHE hierarchy is only shifted by 1 from the antecedent subband.In the subband n = 2, which gives the cyclotron orbit size n = 2 may be larger than the particle separation , the commensurability of this orbit with the next-nearest neighbours ought to be taken into account. As in the monolayer graphene subband with n = 2, one can expect the presence of four (2n) satellite FQHE (single-loop) states, symmetrically located around the central paired state. In the subband n = 2, 1, ↑, these satellite states occur at n = 2—cf. ref.25, whereas in bilayer graphene, the experimental picture is different5. This peculiarity is again caused by the specific topology of the double-sheet structure.The situation changes significantly, however, in the next LL (the first one beyond the LLL). The cyclotron orbits are determined here by the bare kinetic energy with smaller than the orbit size n = 2. Orbits can change only by integer numbers of flux quanta, thus for the initial nominal flux for n = 2, n = 2 in bilayer graphene5—cf. Figs not the particle and hole partners (like the particle n = 2 LL correspond to single-loop braid commensurabilities of nearest and next-nearest (every second) neighbours, respectively. This is confirmed by the asymmetry in the corresponding local minima of Rxx for these pairs, which is observable experimentally5 and illustrates the situation that in states at Rxx at n = 2 and the disappearance of a half-octet of FQHE features in the third subband, together with no features being registered in the fourth subband with n = 2 5, are consistent with this explanation .To solve this puzzle, let us note that in the bilayer system, distinct topological realizations of single-loop orbits may occur that are impossible in the monolayer system. This new opportunity is visualized in Fig. x = 4, 5, 6, 7. Some traces of these features are noticeable in the experiment, as marked in Fig. The orbits reduced due to flux leakage to Bilayer graphene has a different subband structure than monolayer graphene and conventional semiconductor 2DEG, as illustrated in Table n = 0 and n = 1 states results in 8-fold degeneration of the LLL, which is twice the 4-fold spin-valley degeneracy of the LLL in the monolayer case3. The Coulomb interaction causes mixing of the n = 0 and n = 1 states via various schemes induced by stress, deformation, structural imperfections and magnetic field enhancement , which lifts their degeneracy in the LLL in bilayer. After the degeneracy lifting, the order of the subbands with n = 0 and n = 1 occurs to be of particular importance. The sequences n = 0, 1 and n = 1, 0 lead to different FQHE hierarchies. The FQHE hierarchy for the sequence n = 0, 1 is described in paragraph 1.2. However, in the opposite case n = 1, 0, when the n = 1 subband is filled earlier than the n = 0 subband, the hierarchy is different: for the first subband n = 1 and n = 0. The comparison of reverted orderings of the first two LLL subbands is summarized in Table n = 0 is filled earlier than the subband with n = 1. In the inverted ordering of these subbands, the state 4, is shown in Fig. In bilayer graphene, the extra degeneracy of the n = 0, 1 states is lifted in such a way that both levels cross at a certain filling factor v* < 1 . Let us assume, for an example, that the n = 1 subband 5.More precise observations of FQHE in graphene have been recently obtained through improvements of sampling and measurement techniques, including freely suspended graphene sample measurementsn = 1) deviates from the CF picture12. In the bilayer graphene, the incompatibility of the CF model with experimental observations is manifested both in the LLL4 and in higher LLs5. Various scenarios of breaking of the approximate SU(4) spin-valley symmetry in graphene do not solve this problematic situation despite many theoretical attempts, which evidences the insufficiency of the CF model in this case.While the sequence of FQHE fillings in the LLL of monolayer graphene well fits the CF predictions, an explanation of the FQHE filling structure in the next subbands , the following doublets of fillings are observed: 12. The number of centrally located filling rates for FQHE (single-loop) grows with the LL number as 2n  states is of similar strength to that of the IQHE states and is higher in comparison to the FQHE (multi-loop) states, as shown in Fig. The effectiveness of the CF model in the LLL of graphene monolayer is linked with the fact that exclusively in the LLL, cyclotron orbits are always shorter than the interparticle spacing and additional loops are necessary to exchange neighbouring particles along cyclotron braids. These additional loops can be simulated by auxiliary fictitious field flux quanta attached to CFs (as detailed in SI). However, in the case when the more complicated commensurability conditions support particular FQHE states even in the LLL , recently reported10 at In the 4. The commensurability braid group approach for bilayer graphene reproduces all the experimentally observed FQHE hierarchies in the LLL, including the pronounced state at In bilayer graphene, the manifestation of FQHE deviates from the CF picture also in the LLL due to the peculiarity of the double-layer topology caused by interlayer hopping of electrons. As was presented in the paragraph 1.2, in the lowest subband of the LLL in bilayer graphene, even-denominator filling fractions for FQHE appear28, which is also consistent with the commensurability braid group predictions and evidences that this non-CF fraction is caused by the double-layer topology and not by specific material properties of bilayer systems.Let us emphasize that the FQHE state at 8. We propose to explain this effect by the commensurability braid group approach, noting that the occurrence of the Surprisingly, the FQHE state at entclass1pt{minimaentclass1pt{minima5 for the first LL beyond the LLL, i.e., for n = 2 in bilayer graphene . We have explained these astonishing unexpected features, distinct in comparison to conventional 2DEG in n = 2 LLs25, by a specific double-layer topology of bilayer graphene and by an effective leakage of flux due to electron interlayer hopping, as described in paragraph 1.2. The resulting commensurability hierarchy for FQHE in the first LL with n = 2 in the bilayer system (as derived in paragraph 1.2) is perfectly consistent with the experimental data5. We have obtained agreement with topological predictions not only for fractions with denominators 3 and 5 but also with denominators 2 and 4  are not of CF type, because all correspond to single-loop commensurability instances (as is presented in SI in more detail).The most spectacular observations of FQHE in bilayer graphene were reported recently7 for bilayer graphene that is fully encapsulated between two hBN layers, with perpendicular electric field applied by additional bottom and upper electrodes  and they should be completely washed out by the blocking of interlayer hopping, in favour of monolayer-type features with denominator 5 (for n = 2).An interesting opportunity to verify the exceptional bilayer FQHE filling structure due to interlayer hopping of braid trajectories arose from a new architecture in Hall measurement, in which additional vertical voltage is applied to the basal bilayer plane. By varying this voltage, the interlayer hopping of electrons in bilayer graphene can be tuned. The applied voltage can open a band gap at the charge-neutrality point and may change the topology of multi-loop trajectories in the bilayer case, reducing them to instances available in the monolayer case. Such an experiment has been performedx–subband number). For n > 1, these hole partners’ are not actually hole partners, but rather electron single-loop states with every second electron braided. The uncorrelated electrons in these states can scatter and enhance Rxx, in contrast to dual states with single-loop correlation of all electrons. The gradual diminishing of FQHE strength is visible in all subbands with n = 1 of the monolayer graphene10, and in all subbands with n = 2 of the graphene bilayer5. The FQHE energy gain (the activation energy) due to the lowering of the fraction of correlated electrons decreases and eventually drops below the disorder; then the FQHE features disappear in the experiment, as occurred in the fourth subbands of the n = 1 and n = 2 LLs in the monolayer and the bilayer graphene, respectively10, at least down to the lowest temperature range in the experimental setup. In both experiments10, the lowest temperature was 0.5 K. It is quite probable, however, that these very delicate FQHE features might be exposed at mK temperatures. Note also that some FQHE features predicted by the theory may be washed out in experiments by the IQHE re-entrance effect if they are too close to integer fillings (this may concern the poorly visible states at x is the subband number in n = 2 LL subbands in bilayer graphene).The commensurability braid group approach can also be used to explain the experimental observation of the reduction of the FQHE inter-subband relative strength with growing subband number, and of the intra-subband relative strength, when one compares the so-called electron-hole pairs. Both effects correspond to the lowering of the fraction of electrons participating in correlations. This fraction of electrons is further reduced when there are correlated next-nearest electrons, as occurs for ostensible hole partners, e.g., at n = 1 in monolayer graphene, and in the LLL and the first subband (with n = 2) in the bilayer system.We have explained the FQHE hierarchy in graphene in accordance with the recent experimental observations of correlated states, up to the sixth subband in monolayer graphene and up to the eighth subband in its bilayer, revealing deviations from hierarchy schemes known from conventional GaAs 2DEG and apparently going beyond the standard CF model, for subbands with The commensurability of cyclotron braids with interparticle spacing in homogeneous 2D charged systems in a magnetic field is utilized to verify the possibility of arrangement of correlated quantum multiparticle Hall states and to decipher the hierarchy of filling rates for FQHE. By identifying specific topology instances for braids in bilayer graphene caused by the interlayer tunnelling of electrons, we have successfully explained the recent experimental observations of FQHE in the bilayer system. The peculiarity of the FQHE hierarchy, evidenced experimentally in the bilayer graphene in comparison to monolayer graphene and conventional 2DEG, has been clarified in the first eight subbands of the bilayer LL structure.n = 1 there can be present correlated states with single-loop braids that are not equivalent to CFs. The predictions of the braid group commensurability approach reproduce one to one the experimentally observed features in these subbands (n = 1). Simultaneously, the relative strengths of the features, mutually compared intra- and inter-subbands, agree with the theory.In the monolayer graphene, it has been demonstrated that in subbands with n = 2 spin-valley subbands in bilayer graphene is also explained by the same topological arguments, specific to this material. An experimentally observed peculiarity of the FQHE hierarchy in the subbands of the first LL in bilayer graphene with n = 2 (different than in monolayer systems for n = 2 subbands) has been successfully explained in terms of the specific bilayer system topology caused by the interlayer hopping of electrons. By tuning or even blocking the interlayer tunnelling of electrons by application of voltage perpendicularly to the basal plane of graphene bilayer, the predicted phase transition in the FQHE hierarchy has been experimentally demonstrated, which positively evaluated the topological braid group commensurability approach.A similar consistency between the commensurability braid group theory and the experimental observations holds also in the case of the bilayer graphene. The new opportunities for braid group commensurability in the LLL and in higher LLs were identified in the double-sheet system and attributed to the interlayer hopping of electrons, which leads to a different topology than in the monolayer case and in the ordinary FQHE. The even-denominator main line of the fractional filling hierarchy in the LLL of bilayer graphene is derived in this way, in accordance with experimental observations. The unconventional hierarchy of FQHE that was observed recently in The applied braid group commensurability approach to monolayer and bilayer graphene generalizes the conventional CF model. It is confirmed by up-to-date available experimental FQHE observations in graphene on BN substrate, as well as in suspended samples including monolayer graphene up to the sixth spin-valley subband and bilayer graphene up to the eighth spin-valley subband.Supplementary Information


Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors.We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material were selected for PD-L1 IHC analysis using clone E1L3N. PD-L1 expression was evaluated using the combined positive score (CPS). Retrospective chart review was performed. We evaluated the incidence and prognostic value of PD-L1 expression in ESCC at our institution.p-value 0.67). The median overall survival for the PD-L1 positive group, regardless of stage, was 11.5 months versus 7 months for PD-L1 negative group . Patients with limited stage disease with positive PD-L1 had a median survival of 53 months compared to 15 months for patients with PD-L1 negative limited stage .Twelve out 34 cases (35%) had PD-L1 CPS scores ≥1. Ten cases had CPS scores ranging 1–5, whereas 2 cases had CPS scores > 80. The overall response rate to the standard chemotherapy with/without radiotherapy in the PD-L1 positive group was 80% versus 67% for the PDL-1 negative group (This study showed that at least one third of our ESCC tissue samples expressed PD-L1. There was a trend for higher response rates to the standard chemotherapy with/without radiotherapy and improved survival in PD-L1 positive patients. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients. Extrapulmonary small cell carcinomas (ESCC) have an aggressive nature characterized by early, widespread metastases. These cancers are rare with a reported incidence of 0.1 to 0.4% in North America and represent up to 5% of all cases of small cell carcinoma .Disease stage, either limited or extensive, remains the most important prognostic factor for these cancers . Site ofMost treatment recommendations are derived from small single-institution experiences or extrapolated from pulmonary small cell cancer as prospective trials are lacking for this disease , 6. MultCancer immunotherapy targeting the PD-1/PD-L1 pathway is not yet established for ESCC. We evaluated the incidence and the prognostic value of PD-L1 expression in ESCC at our institution. To our knowledge no studies have investigated the value of PD-L1 testing in ESCC.Institutional review board (IRB) approval was obtained. We investigated PD-L1 expression by immunochemistry (IHC) in ESCC diagnosed at University of Massachusetts Medical Center between 1999 and 2016. Forty-five patients with ESCC were identified. From these patients, 34 had specimens with sufficient material for PD-L1 IHC analysis. Specimens included cytology cell blocks, needle core biopsies, and whole tissue sections from resection specimens.Patients included for analysis had a pathologic diagnosis of ESCC and no evidence of lung disease based on chest CT scan at time of diagnosis. Pathologic diagnosis included morphology consistent with small cell carcinoma, and/or positive immunohistochemical staining with synaptophysin, chromogranin, and/or CD56. Well-differentiated neuroendocrine tumors, including carcinoid tumors, were excluded. Disease stage was classified as extensive (ED) or limited (LD), using the Veterans’ Affairs Lung Study Group criteria, by reviewing radiologic records . LD was Immunohistochemical studies were performed on 5-um sections of formalin-fixed, paraffin-embedded tissue. Slides were first deparaffinized, and rehydrated. Antigen retrieval was carried out with 0.01 M citrate buffer at pH 6.0. Slides were heated in a 770-W microwave oven for 14 min, cooled to room temperature, and rinsed in distilled water before staining. All the slides were stained on the Dako Autostainer . The sections were first blocked for endogenous peroxidase activity with an application of Dual Endogenous Block (Dako) for 10 min, followed by a brief buffer wash. The slides were then incubated with primary antibody for 30 min. The rabbit monoclonal antibody to PD-L1  was used at a dilution of 1:500, and diluted with Dako Antibody Diluent (Dako). Following a buffer rinse, sections were incubated with Ultraview Detection  for 30 min. The sections were washed, and treated with a solution of diaminobenzidine and hydrogen peroxide (Dako) for 10 min, to produce the visible brown pigment. After rinsing, a toning solution  was used for 2 min to enrich the color. Following rinsing, the sections were counterstained with hematoxylin, dehydrated, and cover slipped with permanent media. Sections of tonsil, placenta, and classical Hodgkin lymphoma tissue with known positivity for PD-L1 were used as positive controls for staining.PD-L1 IHC scoring was performed using the combined positive score (CPS), previously described for the scoring of PD-L1 in esophageal adenocarcinoma , 13. CPSp > 0.05 accepted as statistically significant.All survival and subgroup analyses were performed using GraphPad Prism software, with curve comparisons performed using log-rank (Mantel-Cox) tests. Kaplan-Meier survival curves were generated using GraphPad Prism software. Response rates to treatment were compared using Fisher test with Demographic characteristics of the patients and the site of origin of their cancers are shown in Table Twelve specimens (35%) showed positive PD-L1 expression  [Table p-value 0.34) [Fig. p-value 0.80) [Table p-value 0.50).All patient with limited stage received a bimodality treatment with chemoradiation. Fifty-six percent of extensive stage patients received chemotherapy. One patient received platinum and irinotecan, while all other patients with extensive disease who received chemotherapy were treated with platinum and etoposide. The other 46% of patients with extensive stage disease received only supportive care with no chemotherapy; 15% of those patients declined chemotherapy, 9% expired before obtaining the final pathology read but received supportive care while in the intensive care unit, and the remainder had very poor performance status with advanced age. Fifteen percent patients had surgical resection of their primary cancer, in the setting of a diagnostic evaluation. The overall response rate in the PD-L1 positive group was 80% versus 67% in the PD-L1 negative group (7) Table . The med34) Fig. . PatientOf the 25 patients who relapsed, 14 patients relapsed after 2007 when the FDA approved Topotecan for relapsed small cell carcinoma of the lung. Two Patients declined additional chemotherapy, two patients received Topotecan without any response and the remaining 10 patients progressed rapidly and didn’t get treated due to poor performance status. None of the patients received second line chemotherapy before 2007.Our data showed that 35% of ESCC tumor samples were positive for PD-L1(CPS ≥1). PD-L1 positive tumors showed a trend toward improved median overall survival and there was separation of survival curves between the PD-L1 positive and negative groups at around 1 year, though not statistically significant.Treatment of ESCC tends to follow the treatment plan utilized for small cell lung cancer. First line treatment with platinum-based chemotherapy remains the standard. Second line treatments are lacking for all patients with small cell carcinomas, regardless of tissue of origin, with topotecan as the only FDA approved drug in the second line setting . ImmunotPD-1/PD-L1 inhibition has shown efficacy in a variety of malignancies in both first line and subsequent therapy –19. ManyTumor PD-L1 status may provide prognostic or predictive information. A recently published clinical trial conducted in patients with advanced non-squamous, non-small-cell lung cancer, demonstrated a higher response rate to chemotherapy in patients whose tumors had high expression of PD-L1 compared to patients whose tumors failed to express PD-L1 , 22. SimThe proposed rational of improved responses in patients with PD-L1 expression could be related to the presence of lymphocytes at the microenvironment of the tumor cells which could be of help to initiate apoptosis and inflammatory reaction, thus enhancing tumor response to chemotherapy and radiation. It is possible that the enhanced cytotoxicity of combination therapy could be due to the release of tumor neoantigens from cells killed by chemotherapy. Combining immunotherapy with chemotherapy as an upfront treatment is of interest at this point for all small cell carcinomas as chemotherapy showed the potential to increase the PD-L1 expression within the tumor microenvironment, which will enhance the responses to PD-1 inhibitors –25.In conclusion, this study demonstrates the incidence of PD-L1 expression in a small cohort of ESCC, and suggests that PD-L1 expression in ESCC may be of prognostic and predictive relevance. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients given the positive expression of PD-L1 in one third of patients in our review.


An energy gap can be opened in the spectrum of graphene reaching values as large as 0.2 eV in the case of bilayers. However, such gaps rarely lead to the highly insulating state expected at low temperatures. This long-standing puzzle is usually explained by charge inhomogeneity. Here we revisit the issue by investigating proximity-induced superconductivity in gapped graphene and comparing normal-state measurements in the Hall bar and Corbino geometries. We find that the supercurrent at the charge neutrality point in gapped graphene propagates along narrow channels near the edges. This observation is corroborated by using the edgeless Corbino geometry in which case resistivity at the neutrality point increases exponentially with increasing the gap, as expected for an ordinary semiconductor. In contrast, resistivity in the Hall bar geometry saturates to values of about a few resistance quanta. We attribute the metallic-like edge conductance to a nontrivial topology of gapped Dirac spectra. The absence of a bandgap in the electronic spectrum of graphene can be overcome by breaking its lattice symmetry. The authors show that the insulating state of gapped graphene is electrically shorted by narrow edge channels exhibiting high conductivity. Egap can be controlled by the displacement field D applied between the two graphene layers. Large gaps were found using optical methodsT) dependences of resistivity ρ at sufficiently high T , ρ at the charge neutrality point (CNP) in gapped graphene is often found to saturate to relatively low values that are incompatible with large Egap  are protected by symmetry of their crystal lattices. If the symmetry is broken by interaction with a substrate13h T refs , 9, 10. gap refs . This diL varying from 300 to 500 nm and the width W from 3 to 5 μm. To ensure highest possible quality2 substrate as a bottom gate  in the x direction perpendicular to the supercurrent flow can be deducedJs(x) changes with opening the gap.We start with discussing behaviour observed for superconductor-graphene-superconductor (SGS) Josephson junctions. Our devices were short and wide graphene crystals that connected superconducting Nb electrodestom gate . For detVtg and Vbg, respectively), it is possible to keep BLG charge neutral while doping the two graphene layers with carriers of the opposite sign  that translates directly into the spectral gap345Egap(D) can be deduced not only theoretically but also measured experimentally, as discussed in section 1 of Ic as the current at which the differential resistance dV/dI deviates from zero above our noise levelIc corresponds to the edge of the dark area outlined by bright contours. At high doping (Fermi energy >Egap) and low T, Ic is found to depend weakly on D, reaching values of a few μA μm−1, in agreement with the previous reports2224Egap  reaching ≈300 nA for the junction shown in D=±0.07 V nm−1, which corresponds to Egap≈7 meV. For larger gaps, Ic becomes smaller than 1 nA and could no longer be resolved because of a finite temperature (down to 10 mK) and background noiseBy varying the top and bottom gate voltages (sign see . This re2224Egap . AccordiIc(B), with increasing D . At zero D, we observe the standard Fraunhofer pattern at the CNP, which is basically similar to that measured at high doping . The phase of the oscillations changes by 90° and the central lobe becomes twice narrower. In addition, the side lobes no longer decay with increasing B but exhibit nearly the same amplitude , which yieldedJs(x) shown in D=0.025 V nm−1 but further increase in D suppresses the bulk current to practically zero, within the experimental accuracy of our FFT analysis  and gapless  MLG. In the gapped device, the supercurrent is suppressed not only at the main CNP but also at secondary CNPs. For all electron and hole concentrations away from the CNPs, both devices exhibit the standard Fraunhofer pattern indicating a uniform supercurrent flow  results in opening of a gap of ≈30 meV at the main CNP–2° resul12010 cm−2 . The fig11 cm−2) and were observed for devices with the top gate being only a few nm away from the graphene plane. The latter facilitates a uniform electric field distribution 2122ribution . Chemicaribution . We alsoribution . The latEgap such that junction's resistance remains well below 1 MOhm allowing superconducting proximity. To address the situation for the larger gaps accessible in BLG devices, we compare their normal transport characteristics in the Corbino and Hall bar geometries. Because the Corbino geometry does not involve edges, such a comparison has previously been exploited to investigate the role of edge transport  as expected for a semiconductor with the gap Egap  found using the Hall bars rapidly saturated below 100 K to values of a few resistance quantum RQ=h/e2 and changed little (by <30%) with decreasing T down 2 K. The saturation behaviour is similar to that observed for conductance along a p–n junction in oppositely biased BLGAnother noteworthy distinction between the two geometries is their temperature dependences at the CNP. For gap Egap . Our meaξ is very long with respect to the lattice constant a. For MLG and BLG, ξ can be estimated as ≈ħv/Egap and ħ/ħ is the reduced Planck constant, v the Fermi velocity in MLG and m the effective mass in BLG. For our typical gaps, ξ is about 10–20 nm, much larger than a. This suggests that wavefunctions of isolated zigzag states should strongly overlap inside the bulk creating a quasi-one-dimensional band. Moreover, because ξ/a≫1, the wavefunctions mostly reside in the bulk where there are little defects, which ensures that impurity bands are effectively protected against backscattering. The situation resembles the modulation doping used to achieve high-carrier mobilities in semiconductor quantum wells. The observed saturation of ρ to ∼RQ and the long-range nonlocal resistance reported previously1617T localization lengths at least an order of magnitude shorter than this scale, localization in the edge channels may be suppressed by a finite T and electron–electron interactions that are prominent especially in low-dimensional conductors. Such delocalization effects have so far not been investigated theoretically. The invoked edge channels would be consistent with our experimental observations. Obviously, the mean free path can vary from sample to sample and strongly depend on fabrication procedures, which may explain only weakly saturating behaviour that was reported in some gapped graphene devices16171322Two possible scenarios for shunting the insulating state of gapped graphene have previously been put forward. Both rely on nontrivial topology of the gapped Dirac spectrum. One of them considers electronic states due to short zigzag segmentsOur results can explain low apparent resistivity often observed for charge-neural gapped graphene at low temperatures, especially in devices made from high-quality graphene in which the bulk is expected to contribute little to either hopping conductivity or backscattering of edge modes5678910112) and then annealed at 300 °C in a forming gas (Ar–H2 mixture) for 3 h. As the next step, we used the standard electron-beam lithography to create a poly (methyl methacrylate) (PMMA) mask that defined contact regions. Reactive ion etching (Oxford Plasma Lab 100) was employed to make trenches in the heterostructure through the mask. We used a mixture of CHF3 and O2, which provided easy lift-off of PMMA, so that metal contacts could be deposited directly after plasma etching. This also allowed us to minimize contamination of the exposed graphene edgesMono- or bilayer graphene crystals were encapsulated between hBN crystals  using the dry transfer technique as detailed previouslyT down to 0.3 K and, for lower T, in a dilution refrigerator with the base temperature of 10 mK (BlueFors Cryogenics). The differential resistance was measured in a quasi-four-terminal configuration (two superconducting leads for driving the current and the other two for measuring voltage) using a low-frequency lock-in technique. All electrical connections to our devices passed through a cold RC filter (Aivon Therma) placed close to the sample and additional AC filters were used outside the cryostats. At large displacement fields, our Corbino devices exhibited high resistivity such that the lock-in technique became inappropriate. In this case, we used dc measurements.All electrical measurements were carried out in a He3 cryostat (Oxford Instruments) for The data that support the findings of this study are available from the corresponding author upon request.How to cite this article: Zhu, M. J. et al. Edge currents shunt the insulating bulk in gapped graphene. Nat. Commun.8, 14552 doi: 10.1038/ncomms14552 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary Figures, Supplementary Notes and Supplementary References


A rare case of ovarian sarcoidosis with peritoneal and omental involvement presenting as an ovarian malignancy is presented. Clinical, laboratory, and radiological evaluation of the patient revealed ascites and high levels of serum CA 125 and CA 15.3. The diagnosis of sarcoidosis was confirmed with pathology findings on tissues obtained during surgical laparotomy. Establishing the diagnosis of sarcoidosis can be treacherous and was complicated in this case by the falsely elevated biomarkers and ascites. Atypical manifestations of sarcoidosis occurring outside typically affected organs make histology necessary in establishing the diagnosis after excluding infectious and neoplastic mimics of the disease. Extrapulmonary sarcoidosis has been reported in several sites; however localization of the disease in the female reproductive system is extremely rare accounting for less than 1% of cases [A 79-year-old, gravida 4, para 2, Caucasian female with a history of weight loss and fatigue for 4 months was referred to our hospital for investigation of her symptoms. Medical history was significant for dyslipidemia and hypertension treated with irbesartan. The physical examination disclosed no abnormalities. Due to concern for malignancy, diagnostic imaging was performed. Chest X-ray was negative. Ultrasound, CT, and MRI of the abdominal area showed the presence of minimal amounts of free liquid in the perihepatic area, in the paracolic sulci, in the right inguinal region, and in the pouch of Douglas, without the involvement of retroperitoneal, paraaortic, and iliac chain lymph nodes. Since the suspicion of malignancy remained high, the gynaecology team ordered cancer biomarkers; testing disclosed a CA 125 value of 225.20 U/ml  and a CA 15.3 value of 73.9 U/ml . Levels of carcinoembryonic antigen were within normal range; that is, CEA levels were 1.43 ng/ml  and carbohydrate antigen 19-9 (CA 19-9) levels were 6,4 U/ml . Cytological examination of the ThinPrep® sample obtained via a transvaginal fine-needle aspiration was negative for malignancy only disclosing an abundance of histiocytes, lymphocytes, white blood cells, and few mesothelial and red blood cells. An exploratory laparotomy was performed; multiple grey-white miliary nodular lesions with a diameter ranging from 0.2 to 1.6 cm were observed on the surface of the left ovary, the uterus, the peritoneum, the omentum, and the small and large intestine. Histological examination of omental and peritoneal biopsies disclosed the presence of noncaseating, nonnecrotic, sarcoid type granulomas containing multinucleated giant cells Figures  containiThe final histological diagnosis was granulomatous, sarcoid type inflammation. Evaluation by an expert pulmonologist revealed no evidence of lung sarcoidosis by CT scan and gallium scanning. The patient was further investigated in the direction of possible extra pulmonary involvement with no abnormal findings revealed. A decision to withhold further therapy was made. The patient is doing well after one year of follow-up without other complications.There was neither family history of sarcoidosis, nor history of immunodeficiency or biological factor therapy. Furthermore, the patient did not mention any occupational or environmental exposure in industrial work associated with beryllium; such exposure has been associated with granuloma formation, pulmonary sarcoidosis, and elevations of Serum Angiotensin-Converting Enzyme (SACE) activity . No histHistology confirmation is necessary for the diagnosis of sarcoidosis occurring outside usually affected organs, for example, the lung. In any case the physician needs to exclude the presence of infectious or neoplastic mimics of the disease. Sarcoidosis has been very rarely described to affect the female genital tract especially the ovaries and even more rarely in relation to a concomitant malignancy –7.In our case peritoneal involvement was also noted which has been described more frequently –10. In sWith regard to the elevated biomarkers the abnormal CA-125 levels are explained by the presence of peritoneal involvement and ascites and have been previously described , 16. It In our report surgical intervention led to the correct diagnosis. Similarly, in previous reports, a provisional diagnosis of ovarian malignancy was excluded by exploratory laparotomy and histological confirmation of sarcoidosis , 13, 19.In conclusion, we describe a rare case of ovarian, peritoneal, and omental sarcoidosis with no lung involvement and abnormally elevated CA 15-3 levels. Cancer biomarkers should not be used to exclude or confirm the diagnosis of cancer or sarcoidosis for the same matter. In our case their use misled the physicians in assuming the presence of a gynecological malignancy. Histological confirmation of the diagnosis is necessary in such difficult cases.


Electrical generation and detection of pure spin currents without the need of magnetic materials are key elements for the realization of full electrically controlled spintronic devices. In this framework, achieving a large spin-to-charge conversion signal is crucial, as considerable outputs are needed for plausible applications. Unfortunately, the values obtained so far have been rather low. Here we exploit the spin Hall effect by using Pt, a non-magnetic metal with strong spin-orbit coupling, to generate and detect pure spin currents in a few-layer graphene channel. Furthermore, the outstanding properties of graphene, with long-distance spin transport and higher electrical resistivity than metals, allow us to achieve in our graphene/Pt lateral heterostructures the largest spin-to-charge output voltage at room temperature reported so far in the literature. Our approach opens up exciting opportunities towards the implementation of spin-orbit-based logic circuits and all electrical control of spin information without magnetic field. Spintronic devices with full electrical control rely on electrical generation and detection of spin currents in the absence of magnetic materials. Here, the authors use Pt, a non-magnetic metal, to generate and detect pure spin currents in a few-layer graphene channel, achieving a remarkable spin-to-charge voltage signal at room temperature. In particular, in the emerging field of spin orbitronics10, by uniquely exploiting the spin-orbit coupling (SOC) in non-magnetic materials, spin-to-charge current conversions have been realized using the spin Hall effect (SHE)13, the Rashba–Edelstein effect15, or the spin-momentum locking in topological insulators17. Magnetization switching of FM elements for memories7 or the recent proposal of a scalable charge-mediated non-volatile spintronic logic18 are applications based on SOC, which can have a strong technological impact.A spintronic device with complete electrical functionality is attractive for its incorporation into the current charge-based integrated circuits. While advances have been made in the electrical control of spin transport19. The efficiency of this spin-to-charge interconversion is given by the spin Hall angle (θSH). As technological applications require large conversions, finding routes to maximize θSH has become a demanding task. The materials with highest reported yields are heavy metals with strong SOC, such as Pt21, Ta5 and W23. Recently, a clear route to enhance θSH of Pt has been unveiled21. Another path that has been explored to maximize the output voltage is the use of higher resistive spin Hall materials, although the potential enhancement is counteracted by the increased shunting of the induced charge current in the less resistive spin transport material, usually Cu or Ag8. It would be desirable to employ these spin-to-charge conversions to efficiently inject and detect pure spin currents in good spin transport materials with higher charge resistance.In the SHE, a pure spin current is generated from a charge current owing to the strong SOC in a non-magnetic material. Reciprocally, the inverse spin Hall effect (ISHE) can be used for spin detection, as a spin current is turned into a measureable charge current24, is theoretically predicted and experimentally demonstrated to be an excellent material for spin transport40. Spin diffusion lengths of up to 90 μm have been reported at room temperature32, a parameter found to be fairly insensitive to temperature39. However, electrical spin injection from FM sources suffers from a lack of reproducibility owing to the required interfacial barriers40, which are usually made of oxides that grow in an island mode on the graphene surface. An efficient and reliable spin injection and detection into such an outstanding spin transport material at room temperature using non-magnetic electrodes is of both fundamental and technological interests.Graphene, due to its weak SOCIn our work, we demonstrate the generation (detection) of a pure spin current in a graphene-based lateral heterostructure by employing the SHE (ISHE) of Pt, avoiding the use of a FM source. Moreover, the large charge resistance of graphene as compared to the standard spin transport metals such as Cu and Ag eliminates completely the shunting effect, generating large output voltages. The spin-to-charge conversion signal in a graphene/Pt lateral device at room temperature is two orders of magnitude larger than the best performing ones previously reported that use metallic channels. Our concept of using charge-to-spin conversion to inject a spin current and spin-to-charge conversion to detect a spin currents in graphene-based devices could open future applications of all electrical control of spin information without magnetic field.n ~ 8 × 1011 cm−2) obtained via exfoliation41, where spins are to be transported. Several ferromagnetic Co electrodes with their respective TiO2 interfacial barriers are placed on top of the flake. The presence of TiO2 between the Co electrode and the graphene channel leads to interface resistances between 10 and 42 kΩ. In addition, Pt wires are placed on top of the graphene channel. We use very resistive Pt with ρPt = 99 (134) µΩcm at 50 (300) K and, therefore, a large spin Hall angle of θSH = 17.8 ± 2.0 (23.4 ± 2.5)%21. Transport measurements are performed in a liquid-He cryostat with a superconducting magnet using a DC reversal technique44. See Methods for details on the device fabrication and measurements.We used the spin absorption method in lateral spin valve (LSV) devices to demonstrate spin generation and detection in graphene via the SHE and ISHE of Pt, respectively  is injected from a Co electrode into the graphene channel, creating a spin accumulation at the Co/graphene interface. This spin accumulation diffuses toward both sides of the graphene channel, creating a pure spin current, which is detected by another Co electrode as a nonlocal voltage (VNL), see Fig. RNL = VNL/IC is high (x direction (Bx) owing to the shape anisotropy of the electrodes . In this case, the pure spin current injected from the Co electrode diffuses along the graphene channel and is mostly absorbed by the Pt wire. In the Pt wire, owing to the ISHE, a charge current perpendicular to both the spin current direction and the spin polarization is created  and, thus, a voltage drop is generated along the Pt wire. The measured voltage normalized to the injected current IC yields the ISHE resistance, RISHE. By sweeping the magnetic field (By) from positive to negative, the magnetization of the Co electrode (as well as the orientation of the spin polarization) rotates, and RISHE reverses sign as shown by the blue curve in Fig. θ13, a value which has been extracted from the Hanle data . The transverse spin current generated in Pt by the SHE has a spin polarization oriented along the y axis, and the spin accumulation in the graphene/Pt interface leads to spin injection into graphene . By employing now the Co electrode as a detector, we are able to measure the pure spin current reaching the Co electrode as a voltage, obtaining the corresponding SHE resistance, RSHE, after normalizing by IC =RISHE(−By) by swapping the voltage and current probes with the same polarity   2) the ementclass2pt{minimλGr ~ 1.2 µm) and its temperature insensitivity. Graphene’s exceptional ability to transport spins remains intact at room temperature, that is, the same amount of spin current arrives to the Pt absorber at different temperatures; Second, although the amount of spin current to be converted remains the same, the efficiency of the conversion (θSH) of Pt increases linearly with temperature from 17.8 ± 2.0% at 50 K to 23.4 ± 2.5% at 300 K21; Third, the resistivity of Pt increases from 99 µΩcm at 50 K to 134 µΩcm at 300 K; and fourth, the negligible shunting of the charge current in Pt by graphene (xPt/Gr ≈ 1). The enhancement of ΔRSCC with increasing temperature mainly benefits from the first three factors, which are constant λGr and increasing θSHρPt product as described in eq  and fourth (negligible shunting) factors. In traditional metallic LSV devices, the resistivity of the metal channel is close or smaller than that of the spin Hall metal, thus x are much lower (0.05–0.36)52, a serious issue preventing large spin-to-charge conversion pointed out recently8. However, in our device with few-layer graphene/Pt heterostructure, xPt/Gr≈1 is close to ideal and the use of more resistive graphene (single or bilayer) is not necessary, as xPt/Gr cannot be further increased. Further improvement to the spin-to-charge conversion could be easily achieved by using high quality graphene devices, where almost two orders of magnitude enhancement of λGr is obtained32, or reducing the spin current dilution into the Pt wire by decreasing its thickness  is not appropriate, because they quantify different outputs. Whereas the former only probes the spin accumulation in the channel through a ferromagnetic tunnel barrier and acts as spin detector, the latter is a measurement of the converted charge current through a transparent interface, which can be potentially utilized  and identified using its optical contrast41. We select flakes with the most convenient shape (long and narrow), regardless of the number of layers, as the excellent spin transport properties do not depend strongly on the number of graphene layers36. The nanofabrication of the device follows two steps of e-beam lithography with electrode metal deposition and lift-off. For the 200-nm-wide Pt wires, 21 nm of Pt were sputtered at 0.6 Ås−1 using 40 W in 3 mTorr of Ar pressure. This deposition condition gives rise to very resistive Pt with ρPt = 99 (134) µΩcm at 50 (300) K. The 35-nm-thick Co electrodes with widths between 150 and 350 nm are deposited in an ultra-high vacuum chamber using e-beam evaporation on top of 6 Å of Ti after the natural oxidation of Ti in air. The presence of TiO2 between the Co electrode and the graphene channel leads to interface resistances between 10 and 42 kΩ.To fabricate our devices, few-layer graphene flakes are first produced by micromechanical cleavage of natural graphite onto 300-nm-thick SiO44.The measurements are performed in a Physical Property Measurement System by Quantum Design, using a DC reversal technique with a Keithley 2182 nanovoltmeter and a 6221 current sourceAll relevant data are available from the authors.Supplementary InformationPeer Review File


As cathode materials for lithium-ion batteries, the nanosheet-assembled V2O5/graphene composite exhibits better rate capability and long-term cycling stability. The V2O5/graphene composites can deliver discharge capacities of 133, 131, and 122 mAh g−1 at 16 C, 32 C, and 64 C, respectively, in the voltage range of 2.5–4.0 V vs. Li/Li+. Moreover, the electrodes can retain 85% of their original capacity at 1C rate after 500 cycles. The superior electrochemical performances are attributed to the porous structures created by the connected V2O5 nanosheets and the electron conductivity improvement by graphene.Transition metal oxides and graphene composites have been widely reported in energy storage and conversion systems. However, the controllable synthesis of graphene-based nanocomposites with tunable morphologies is far less reported. In this work, we report the fabrication of VThe online version of this article (doi:10.1186/s11671-016-1764-3) contains supplementary material, which is available to authorized users. Rechargeable lithium-ion batteries, as one of the most important energy storage devices, have been widely used in consumer electronic devices such as cell phones, laptop computers, and hybrid electrical vehicles. However, the increasing demands for better batteries push the researchers to develop new electrode materials with improved performance including higher energy density, better rate capability, and longer lifespan –3.2O5 is a promising material because of its low cost, abundant resource reservation, and high-energy density [−12–10−13 cm2 s−1) and moderate electrical conductivity (10−12–10−13 S cm−1) limit its electrochemical performance [2O5 nanomaterials, such as nanorods [2O5 is still undressed. More recently, making V2O5 nanocomposites with conductive materials are effective for obtaining high-performance electrode materials. In particular, carbonaceous materials such as carbon nanotubes [2@graphene [2O3@graphene [3O7@graphene [Among the numerous cathode materials, V density . Howevernanorods , nanotubnanorods , nanowirnanorods , nanoshenanorods , 10, nannanorods –13, and nanorods , 15 wereanotubes , 17, mesanotubes , and graanotubes , 19, 20 anotubes –23. In tgraphene , V2O3@grgraphene , and V3Ographene , have be2O5/graphene with different morphologies by a solvothermal approach with subsequent annealing in air. Vanadium precursors with nanosheet or nanoparticle morphology are controllably prepared on the surface of graphene and can be converted into V2O5/reduced graphene oxide nanocomposites with good structural reservation in the calcination process in air. As cathode materials for lithium-ion batteries, the nanosheet-structured V2O5/reduced graphene oxide nanocomposites exhibit much better rate capability and cyclic stability than V2O5 nanoparticles/reduced graphene oxide composites. The relationship between nanostructures and their electrochemical performance is discussed.Herein, we report the structural engineering of V2O5/reduced graphene oxide composite I (V/GO-I).The graphene oxide was made by a modified Hummers method . For the2O5/graphene composite was prepared by adding extra 2 mL deionized (DI) water into the solvothermal solution, keeping other parameters unaltered. The obtained material was designated as nanoparticle-structured V2O5/reduced graphene oxide composite II (V/GO-II).The nanoparticle-assembled Vλ = 1.54178 Å) using a step of 0.02o between 10° and 80° (2θ). The morphologies of the samples were studied by scanning electron microscopy  and transmission electron microscopy . The X-ray diffraction (XRD) patterns of the samples were collected in the range between 10o and 80o with a step size of 0.02°. The weight percentages of graphene in the V2O5/graphene composites were determined by thermogravimetric (TG) analysis with a heating rate of 10 °C min−1. A spectrometer  with a back-illuminated charge-coupled detector attachment was used to record the Raman spectra.The crystal phases were collected using a Rigaku D/max2500 with Cu-Kα radiation  in a weight ratio of 70:20:10 was dispersed in an N-methyl-2-pyrrolidone (NMP) solution to make a slurry, which was coated on aluminum foil and dried in a vacuum oven at 100 °C overnight. The cells were assembled in the glove box  filled with ultra-high-purity argon using polypropylene membrane as the separator, lithium metal as the anode, and 1-M LiPF6 in ethyl carbonate/dimethyl carbonate (1:1 v/v) as the electrolyte. The cyclic voltammetry (CV) measurement was tested on CHI660C , and the galvanostatic discharging/charging experiment was tested on a Land battery tester . The measurements were all carried out in the voltage range of 2.5–4.0 V (vs. Li/Li+). The electrochemical impedance spectrometry (EIS) was carried out on a ZAHNER-IM6ex electrochemical workstation (ZAHNER Co. Germany) in the frequency range of 100 kHz to 10 mHz using the fresh cell.The electrochemical performances of the electrodes were tested in a coin cell assembly (2016 type coin cell). For the electrode preparation, a mixture of V2O5/graphene nanocomposites with diverse self-assembled subunits. As indicated by process I, vanadium precursor nanosheets are grown on the graphene nanosheets first during the solvothermal process, in which vanadium triisopropoxy oxide (VO(OiPr)3) was used as the vanadium resources. The prepared vanadium precursor and graphene composite can be converted into V2O5 and graphene composite with well-preserved structures. Process II indicates the preparation of nanoparticle-assembled vanadium precursor and graphene composite by adding extra 2 mL de-ion water in the solvothermal solution. Thereafter, the precursor composite can be converted into V2O5 nanoparticles and reduced graphene oxide nanocomposites (V/GO-II).Figure 2 phase (space group: P42/mnm (136); a = 0.4556 nm, b = 0.4556 nm, c = 0.285 nm, JCPDS card no. 76-0677). The formation of VO2 phase can be attributed the reduction of V2O5·nH2O by alcohol during solvothermal process, in which V2O5·nH2O is prepared by the hydrolysis of vanadium triisopropoxy oxide with water. The result indicates the structures of the vanadium precursor can be adjusted by the addition of 2 mL de-ion water. The addition of water can speed the hydrolysis reaction between vanadium triisopropoxy oxide and water to form brown colored V2O5·nH2O, which may generate more nucleation on the graphene nanosheets, but sacrificing their parcel growth. However, due to the amorphous feature of the vanadium precursor nanosheets, it is difficult to give the exact reaction during the solvothermal process. The formation of the amorphous nanosheets may be attributed to the decomposition of vanadium triisopropoxy oxide under the condition of high temperature and high pressure during the solvothermal process. Much less nuclei seeds are formed on the reduced graphene oxide and grow continuously to form the nanosheet morphology without the addition of water.Figure 2O5 phase (space group: Pmmn (no. 59); a = 1.1516 nm, b = 0.3565 nm, c = 0.4372 nm, JCPDS card no. 41-1426). The existence of reduced graphene oxides in the composite was confirmed by the Raman results, as shown in Fig. −1 correspond to the typical G and D bands of graphene. Moreover, the intensity ratio between G and D bands become larger, indicating the partial reduction of graphene oxide. All other Raman peaks for the V/GO-I composite and the V/GO-II composite can be characterized on the basis of the vanadium oxide  for V/GO-II composite. The corresponding charge/discharge curves are shown in Additional file −1 at 16C, 32C, 40C and 64C, respectively. When the discharge/charge rates were reset to 1C, high discharge capacity of 139 mAh g−1 can be recovered for both composites. The coulombic efficiency of V/GO-I composite is close to 100% in the whole discharge/charge process.Figure 2O5/graphene composite, which may be attributed to the porous structures created by the nanosheets.Figure 2O5/graphene composites. The V/GO-I composite deliver an initial high specific capacity of 142 mAh g−1 at 2C and retain a capacity of 121 mA h g−1 after 500 cycles. The average capacity fading is only 0.03% per cycle. For comparison, the V/GO-II composite only retains a capacity of 80 mA h g−1 after 500 cycles at the same rate. Additional file −1, respectively, for the V/GO-I composite and the coulombic efficiency can be of 99.6%. After 500 cycles, the plateaus can still be easily detected. Additional file Figure 2O5 and reduced graphene oxide composite. According to the electrochemical analysis results, the nanosheet-assembled V2O5/graphene composite exhibit better rate capability, cycling stability, and lower charge transfer resistance than the nanoparticle-assembled V2O5/graphene composite. The electrochemical performance of V/GO-I composite is also much better than many previously reported V2O5 electrodes, such as hollow structured V2O5 microspheres [2O5 [2O5-based electrodes in this work and from many previous reported literatures. As shown in Table 2O5/r-GO composite exhibit higher capacity and better rate capability than many other V2O5-based electrodes. The excellent rate performance and superior cyclic stability can be attributed to the synergistic effects between V2O5 and graphene substrates, which include the following aspects: (1) the growth of V2O5 nanosheets on reduced graphene oxide can ensure the good electronic conductivity of the electrode materials; (2) the porous space created by the interconnected large nanosheets can improve the accessibility of the electrolyte with the electrode materials; (3) the ultra-thin nanosheet thickness can greatly reduce the Li+ ions diffusion and electron transportation distances; and (4) the porous structure may better accommodate the volume changes upon cycling.Figure ospheres  and threres [2O5 . Table 22O5/reduced graphene oxide composites are synthesized by adjusting the solvothermal condition. The vanadium precursor can grow homogeneously on the reduced graphene oxides and the obtained composites can be converted into V2O5/reduced graphene oxide composites with good structural reservation. As cathode materials for lithium-ion batteries, the nanosheet-assembled V2O5/reduced graphene oxide nanocomposites (V/GO-I) exhibit better rate capability and cycling stability than the nanoparticle-assembled V2O5/graphene nanocomposites (V/GO-II). The superior electrochemical performance is attributed to the synergistic effects between V2O5 nanosheets and reduced graphene oxides.In summary, nanosheet- or nanoparticle-assembled V


Audience response systems (ARS) are increasingly popular; however, their contribution to education is not completely clear. Our study found that scores from review quizzes delivered by an ARS correlate with in-training exam (ITE) scores and are viewed positively by residents. This information may be useful in identifying poor performers early so that targeted educational interventions can be made. The objective was to determine if scores on review quizzes delivered by an ARS correlate with ITE scores and to obtain participant feedback on use of the ARS for ITE preparation.This was a prospective observational study of emergency medicine (EM) residents at six accredited EM residency programs. Subjects included residents who had taken previous ITEs. Subjects participated in bimonthly review sessions using an ARS. Twelve review quizzes were administered, each consisting of 10 multiple-choice questions. After the ITE, subjects completed an attitudinal survey consisting of six Likert-scale items and one “yes/no” item. We used a mixed linear model to analyze the data, accounting for prior 2012 ITE scores and nesting due to institution.Among 192 participants, 135 (70.3%) completed the ITE in both 2012 and 2013; we analyzed their data for the first objective. Results from the mixed linear model indicate that the total mean score on the review quizzes was a significant  predictor of the 2013 ITE after controlling for the 2012 ITE score. One hundred forty-six (76.0%) participants completed the attitudinal survey; 96% of respondents stated that they would like ARS to be used more often in resident education. Respondents felt the sessions aided in learning (mean 7.7/10), assisted in preparation for the ITE (mean 6.7/10), and helped identify content areas of weakness (mean 7.6/10).Our results suggest that scores from review quizzes delivered by an audience response system correlate with in-training exam scores and is viewed positively by residents. To become board certified, emergency physicians must pass the American Board of Emergency Medicine (ABEM) written and oral certification examinations. In preparation, residents take an annual in-training exam (ITE). EM residencies aim for all residents to pass the written examination. As a result, it is common practice for residencies to dedicate specific didactic time as review sessions to improve ITE scores. The amount and method of this preparation is variable. We sought to develop a curriculum using an audience response system (ARS) that could potentially predict how residents would perform on the ITE.There are a number of ARSs available and they are increasingly used for didactic teaching. They involve wireless technology where participants send a response via keypads, clickers or cell phones to a computer that then tallies and projects those responses to the audience. The audience responses to questions or stimuli can be embedded graphically in a PowerPoint lecture providing immediate feedback to the audience about their input. ARS have been shown to improve the effectiveness of didactic lectures by increasing attendance, attention levels, motivation, participation and engagement.8The literature on ARS is clear that students embrace this technology as a learning tool; however, it remains unclear whether participation and tracking of results through an ARS can assist educators in predicting which students will do poorly on an annual comprehensive exam. If such a system could predict those at risk for poor outcomes, early targeted educational interventions could take place. The primary objective of this study was to determine if the results of bi-monthly, written, board-style questions using the ARS were correlated with the annual ITE scores among EM residents from six different programs. In addition, we wanted to determine resident reactions to the use of an ARS for ITE review.What do we already know about this issue?Learners enjoy the use of an audience response system for didactic education. Whether it is valuable in predicting or improving learning is not entirely clear.What was the research question?Do scores on review quizzes delivered in resident conference using an audience response system correlate with scores on the in-training exam?What was the major finding of the study?Review quizzes delivered by an audience response system are viewed positively by residents, and results correlate with in-training exam scores.How does this improve population health?Improvements in the education of core content to residents will likely improve the quality of care delivered by them in the long run.Residents from six EM residency programs accredited by the Accreditation Council for Graduate Medical Education participated in this study. Collaboration was facilitated through the MERC  at CORD (Council of Residency Directors) Program. The ™ ARS.This prospective, multicenter cohort study was conducted from August 2012 to January 2013. Study participants were all the EM residents at each training site that routinely attend conference. They were all consented for participation. No residents were excluded; however, because first-year residents at Harbor-UCLA Medical Center do not attend didactic conference they were not consented and they did not participate. Although the interns at the other sites did not have prior ITE scores for comparison, they were included in the study because they would be participating in the ARS and completing the post-survey. All participants present for the session answered EM board-style questions during didactic conference twice per month for the six months  preceding the ITE in February 2013. Each program has regular didactics that occur on a weekly basis. Residents who were present for the board review  would voluntarily answer the questions via the audience response clickers. Administration of questions was done by a single person at each institution, using the Turning Point TechnologyTopics were chosen a priori based on the list of most commonly asked question topics published by ABEM on their website.™  is a specific audience response product using audience clickers, which send feedback to a receiver with a USB hub that attaches to the computer. It is completely integrated with PowerPoint such that the slideshow appears identical to what residents are accustomed to seeing. Subjects were given a question and multiple-answer choices on the slide. After everyone clicked their answer selection, a graphic display of the percentage or number of subjects who selected each choice was displayed for everyone to see. Participants were not individually identified. Thereafter, a checkmark appeared informing the audience of the correct answer. There wasn’t a scripted discussion of the correct answers, but the administrator of the questions was allowed to explain why the answer was correct and why the other options were incorrect.Turning Point Technologies™. PowerPoint sessions were then sent to the lead investigator at each site. Sessions were consistently administered by the lead investigators  twice a month for six months to cover the 12 most commonly tested topics. If a session could not be administered in the assigned month, the topic was skipped to ensure all participants completed the questions at the same time in their residency training.One investigator (KS) randomly selected the 10 questions for each topic from the topic-specific pool of questions on the RoshReview website. Questions were then placed in a PowerPoint presentation that allowed for use with Turning Point TechnologiesResidents were assigned particular clickers that they used for each session, thereby maintaining a unique identifier that remained de-identified to the study investigators. The answer choice selected by each participant (and correct or incorrect designation) was automatically recorded with the unique identifier of each participant. At the completion of each session, data automatically generated by the ARS was sent to one investigator (KS) for collection.After the ITE, subjects completed a questionnaire to determine their attitudes toward the review sessions delivered by an ARS. The questionnaire consisted of six 10-point Likert-type items and one “yes/no” item. The questions were developed by the research group with attention to content validity through iterative drafts of the survey. Internal structure and response process validity was supported by adherence to survey design principles, review by an educational research expert, and piloting and revision of survey; consistency was determined by Crohnbach’s alpha of 0.81. See list of questions in To control for prior performance on the ITE, we completed this analysis using only residents who had a 2012 ITE score in addition to a 2013 ITE score. Analysis was performed using a nested mixed linear regression model using SAS version 9.3. We calculated the score on each quiz in terms of the percentage correct, and adjusted the total percentage correct on all tests by the total number of tests taken. Scores from incomplete quizzes, defined as less than 7 out of 10 questions answered, were excluded from analysis. The total ITE score in 2013 was the outcome and it was adjusted for each participant’s 2012 ITE score and the participant’s institution. We included all available demographic variables and the institution in the model. For the attitudinal responses, mean ratings with standard deviations for Likert scale items were calculated using Excel. Response rate for the single “yes/no” question was also recorded.p < 0.0001] predictor of the 2013 ITE score after controlling for the 2012 ITE score.A total of 192 residents participated in the study. We included only 135 participants in the primary analysis because 57 participants did not have both a 2012 and 2013 ITE score. Results from the mixed linear model indicate that the total mean score on the review quizzes was a significant [t(127) = 6.68; ± 1.8 on a 10-point scale. They also felt that these sessions aided in learning (mean 7.7 ± 1.8), assisted in preparation for the ITE (mean 6.7 ± 2.1), and helped identify content areas of weakness (mean 7.6 ± 2.0). Participants were equivalent on whether the ARS review sessions prompted them to study more (mean 5.8 ± 2.7).One hundred forty-six participants (76.0%) completed the survey evaluation of the ARS. Of the 146 residents who completed the attitudinal survey, 95.8% (140) stated “yes” they would like ARS to be used more often in resident education. Participants overall enjoyed the ARS review sessions with a mean score of 8.7 This study found a positive correlation between total mean scores on review quizzes delivered by an ARS and ITE scores, after controlling for prior ITE score. These results suggest that review quiz scores may be predictive of ITE scores. Many programs use various forms of “practice tests” or “quizzes” as preparation, but there is little published data in EM to suggest that performance on these tests or quizzes can predict ITE scores.Residents who have done poorly on the ITE are often encouraged or required to complete some form of remediation or targeted educational intervention; this can improve future outcomes.Consistent with prior research on ARS, participants in our study provided positive feedback about this type of educational intervention. This is also not surprising as an ARS allows for increased interactivity and active learning, which are both enjoyable to learners and can positively impact outcomes.13In addition to being engaging and stimulating, the ARS when used for ITE preparation or core content knowledge acquisition for residents has two additional features that are important specifically for group testing, including anonymity and self-assessment. It is clear based on many reports that students value anonymity;Displaying all responses also allows learners to gauge their performance against the group, a critical feature for ITE preparation. There is some evidence to suggest that students like to know how well they are performing relative to their peers.This information will significantly contribute to the current body of knowledge in that we have found a potential predictor of ITE scores in a method that trainees view positivelyThis study has several limitations. Although there are a large number of participants in our study, the number of questions in each session (10) was small. A greater number of questions/topics would likely more accurately stratify resident knowledge base. RoshReview questions that we used do not have validity evidence. It is unclear if these questions correspond accurately to the ITE material. However, the authors, who are all leaders in EM education, provided content validity in the questions used in the review sessions, although item analysis on the questions was not performed.Three of the study sites did not complete all the scheduled quizzes. There were logistical issues with conference scheduling and technical difficulties that prevented site investigators from completing the ARS quizzes within the designated month. Although this is a real limitation of the study, given that there were six sites, multiple sessions and multiple questions, we don’t believe the analysis or study outcome was compromised.We chose to study the ARS as a potential predictor of ITE scores, but certainly paper quizzes or independent computer quizzes with immediate feedback could similarly correlate with performance. Comparing the various evaluation modalities is certainly an area of future research.Finally, as this study only looked at mean total scores across multiple months and quizzes (12 quizzes over six months), we do not know the minimum number of ARS quiz scores necessary  that are correlated with higher ITE scores. This is an area that requires future research.Performance on review quizzes delivered by an audience response system is correlated with resident in-training exam scores. This type of review is viewed positively by residents and can assist residents in identifying areas of weakness and preparing for the in-training exam.