50 research outputs found

    On edge states in semi-infinite quantum Hall systems

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    We consider an electron in two dimensions submitted to a magnetic field and to the potential of impurities. We show that when the electron is confined to a half-space by a planar wall described by a smooth increasing potential, the total Hamiltonian necessarily has a continuous spectrum in some intervals in between the Landau levels provided that both the amplitude and spatial variation of the impurity potential are sufficiently weak. The spatial decay of the impurity potential is not needed. In particular, this proves the occurrence of edge states in semi-infinite quantum Hall systems

    Diamagnetic currents

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    Abstract We study the diamagnetic surface currents of particles in thermal equilibrium submitted to a constant magnetic field. The current density of independent electrons with Boltzmann (respectively Fermi) statistics has a gaussian (respectively exponential) bound for its fall off into the bulk. For a system of interacting particles at low activity with Boltzmann statistics, the current density is localized near to the boundary and integrable when the two-body potential decays as |x|–agr, agr >4, agr>4, in three dimensions. In all cases, the integral of the current density is independent of the nature of the confining wall and correctly related to the bulk magnetisation. The results hold for hard and soft walls and all field strength. The analysis relies on the Feynman-Kac-Ito representation of the Gibbs state and on specific properties of the Brownian bridge process. Partially supported by the Swiss National Foundation for Scienc

    Long Cycles in a Perturbed Mean Field Model of a Boson Gas

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    In this paper we give a precise mathematical formulation of the relation between Bose condensation and long cycles and prove its validity for the perturbed mean field model of a Bose gas. We decompose the total density ρ=ρshort+ρlong\rho=\rho_{{\rm short}}+\rho_{{\rm long}} into the number density of particles belonging to cycles of finite length (ρshort\rho_{{\rm short}}) and to infinitely long cycles (ρlong\rho_{{\rm long}}) in the thermodynamic limit. For this model we prove that when there is Bose condensation, ρlong\rho_{{\rm long}} is different from zero and identical to the condensate density. This is achieved through an application of the theory of large deviations. We discuss the possible equivalence of ρlong0\rho_{{\rm long}}\neq 0 with off-diagonal long range order and winding paths that occur in the path integral representation of the Bose gas.Comment: 10 page

    AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival

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    BACKGROUND: AUTO1 is a fast off-rate CD19-targeting chimeric antigen receptor (CAR), which has been successfully tested in adult lymphoblastic leukemia. Tscm/Tcm-enriched CAR-T populations confer the best expansion and persistence, but Tscm/Tcm numbers are poor in heavily pretreated adult patients. To improve this, we evaluate the use of AKT inhibitor (VIII) with the aim of uncoupling T-cell expansion from differentiation, to enrich Tscm/Tcm subsets. METHODS: VIII was incorporated into the AUTO1 manufacturing process based on the semiautomated the CliniMACS Prodigy platform at both small and cGMP scale. RESULTS: AUTO1 manufactured with VIII showed Tscm/Tcm enrichment, improved expansion and cytotoxicity in vitro and superior antitumor activity in vivo. Further, VIII induced AUTO1 Th1/Th17 skewing, increased polyfunctionality, and conferred a unique metabolic profile and a novel signature for autophagy to support enhanced expansion and cytotoxicity. We show that VIII-cultured AUTO1 products from B-ALL patients on the ALLCAR19 study possess superior phenotype, metabolism, and function than parallel control products and that VIII-based manufacture is scalable to cGMP. CONCLUSION: Ultimately, AUTO1 generated with VIII may begin to overcome the product specific factors contributing to CD19+relapse

    Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

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    Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer

    Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

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    With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches
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