1,012 research outputs found

    Influence of uncorrelated overlayers on the magnetism in thin itinerant-electron films

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    The influence of uncorrelated (nonmagnetic) overlayers on the magnetic properties of thin itinerant-electron films is investigated within the single-band Hubbard model. The Coulomb correlation between the electrons in the ferromagnetic layers is treated by using the spectral density approach (SDA). It is found that the presence of nonmagnetic layers has a strong effect on the magnetic properties of thin films. The Curie temperatures of very thin films are modified by the uncorrelated overlayers. The quasiparticle density of states is used to analyze the results. In addition, the coupling between the ferromagnetic layers and the nonmagnetic layers is discussed in detail. The coupling depends on the band occupation of the nonmagnetic layers, while it is almost independent of the number of the nonmagnetic layers. The induced polarization in the nonmagnetic layers shows a long-range decreasing oscillatory behavior and it depends on the coupling between ferromagnetic and nonmagnetic layers.Comment: 9 pages, RevTex, 6 figures, for related work see: http://orion.physik.hu-berlin.d

    Immediate antiviral therapy appears to restrict resting CD4 + cell HIV-1 infection without accelerating the decay of latent infection

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    HIV type 1 (HIV-1) persists within resting CD4 + T cells despite anti-retroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10 -4) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4 + T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4 + T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4 + T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir

    Classification of temporomandibular joint sounds based upon their reduced interference distribution

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    Temporomandibular joint (TMJ) sounds were recorded in 98 orthodontic retention patients, mean age 19 ± 8–6 (s.d.) years, by interview, auscultation and electronic recording. Sounds were found by auscultation in 41% and by interview in 32% of the subjects, more often in females than in males (P ≀ 0.05). A new method for time-frequency analysis, the reduced interference distribution (RID), was used to classify the electronic sound recordings into five subclasses, RID types 1–5, based upon location and number of their energy peaks. RID types 1–3 had a few energy peaks close in time. RID types 4–5, typical of subjects with crepitation, had multiple energy peaks occurring close in time for a period of 20–300 ms. RID type 1, found in 45% of the subjects, typical of patients with clicking, had its dominant energy peak located in a frequency range ≀600 Hz and was significantly more common in the female than in the male subjects (P≀ 0.01). RID type 2, found in 68% of the subjects, with the dominant peak in the range 600–1200 Hz, and RID type 3, found in 38% of the subjects, with the peak in the frequency range >1200 Hz, were found to have a similar gender distribution. RID type 4, found in 49% of the subjects, had the energy peaks distributed in the frequency range ≀600 Hz. RID type 5, found in 43% of the subjects, more often in females than in males (P≀ 0.05), had the peaks distributed over the whole frequency range from about 30 Hz up to about 3000 Hz. In conclusion, a more detailed classification could be made of the TMJ sounds by displaying the RIDs than by auscultation. This suggests that RID classification methods may provide a means for differentiating sounds indicating different types of pathology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74694/1/j.1365-2842.1996.tb00809.x.pd

    Immunogenicity of AGS-004 Dendritic Cell Therapy in Patients Treated during Acute HIV Infection

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    AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4+ T-cell infection (RCI) was measured by quantitative viral outgrowth assay. Participants demonstrating increased immune response postvaccination were eligible for analytic treatment interruption (ATI). AGS-004 induced a positive immune response defined as ≄2-fold increase from baseline in the number of multifunctional HIV-1 specific CD28+/CD45RA- CD8+ effector/memory cytoxic T-lymphocytes (CTLs) in all six participants. All participants underwent ATI with rebound viremia at a median of 29 days. Immune correlates between time to viral rebound and the induction of effector CTLs were determined. Baseline RCI was low in most participants (0.043-0.767 IUPM). One participant had a >2-fold decrease (0.179-0.067 infectious units per million [IUPM]) in RCI at week 10. One participant with the lowest RCI had the longest ATI. AGS-004 dendritic cell administration increased multifunctional HIV-specific CD28+/CD45RA- CD8+ memory T cell responses in all participants, but did not permit sustained ART interruption. However, greater expansion of CD28-/CCR7-/CD45RA- CD8+ effector T cell responses correlated with a longer time to viral rebound. AGS-004 may be a useful tool to augment immune responses in the setting of latency reversal and eradication strategies

    HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths

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    The Berlin Patient represents the first and only functional HIV cure achieved by hematopoietic stem cell transplant (HSCT). In subsequent efforts to replicate this result, HIV rebounded post-HSCT after withdrawal of antiretroviral therapy. Providing HIV-specific immunity through adoptive T cell therapy may prevent HIV rebound post-HSCT by eliminating newly infected cells before they can seed systemic infection. Adoptive T cell therapy has demonstrated success in boosting Epstein-Barr virus and cytomegalovirus-specific immunity post-HSCT, controlling viral reactivation. However, T cell immunotherapies to boost HIV-specific immunity have been limited by single-epitope specificity and minimal persistence or efficacy in vivo. To improve this strategy, we sought to generate allogeneic HIV-specific T cells from human leukocyte antigen (HLA)-A02+ HIV-negative adult or cord blood donors. We focused on HLA-A02+ donors due to well-characterized epitope restrictions observed in HIV+ populations. We show that multi-antigen HIV-specific T cells can be generated from naive T cells of both cord blood and adults using a reproducible good manufacturing practice (GMP)-grade protocol. This product lysed antigen-pulsed targets and suppressed active HIV in vitro. Interestingly, these cells displayed broad epitope recognition despite lacking recognition of the common HLA-A02-restricted HIV epitope Gag SL9. This first demonstration of functional multi-antigen HIV-specific T cells has implications for improving treatment of HIV through allogeneic HSCT. Patel et al. demonstrate the ability to generate HIV-specific T cells from HIV-seronegative adults and cord blood with a good-manufacturing-practice-compliant strategy. These immunotherapies are multi-antigen specific, display cytotoxicity, and suppress HIV in vitro, providing a promising platform for adoptive T cell therapy in a post-transplant setting

    HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy

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    HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critical for powering clinical trials testing T cell-based immunotherapies. In a cross-sectional study, HIV-specific T cell responses were detectable by ex vivo interferon (IFN)-Îł ELISpot (average ∌1,100 spot-forming units [SFUs]/106 peripheral blood mononuclear cells) in persons living with HIV (PLWH; n = 34), despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication-competent HIV reservoir. T cell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific T cell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific T cell response in suppressed PLWH will enable powered studies of small sizes (e.g., n = 6–12), facilitating rapid and iterative testing for T cell-based immunotherapies against HIV

    Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

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    Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure

    Clinical trial of the anti-PD-L1 antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy

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    Background. Reversing immune exhaustion with an anti-PD-L1 antibody may improve human immunodeficiency virus type 1 (HIV-1)-specific immunity and increase clearance of HIV-1-expressing cells. Methods. We conducted a phase I, randomized, double-blind, placebo-controlled, dose-escalating study of BMS-936559, including HIV-1-infected adults aged >18 to 350 cells/ÎŒL and detectable plasma HIV-1 RNA by single-copy assay. Data on single infusions of BMS-936559 (0.3 mg/kg) versus placebo are described. The primary outcomes were safety defined as any grade 3 or greater or immune-related adverse event (AE) and the change in HIV-1 Gag-specific CD8+ T cell responses from baseline to day 28 after infusion. Results. Eight men enrolled: 6 received 0.3 mg/kg of BMS-936559, and 2 received placebo infusions. There were no BMS- 936559-related grade 3 or greater AEs. In 1 participant, asymptomatic hypophysitis (a protocol-defined immune-related AE) was identified 266 days after BMS-936559 infusion; it resolved over time. The mean percentage of HIV-1 Gag-specific CD8+ T cells expressing interferon Îł increased from baseline (0.09%) through day 28 (0.20%; P = .14), driven by substantial increases in 2 participants who received BMS-936559. Conclusions. In this first evaluation of an immunologic checkpoint inhibitor in healthy HIV-1-infected persons, single lowdose BMS-936559 infusions appeared to enhance HIV-1-specific immunity in a subset of participants

    Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

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    A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure

    Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

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    This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio
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