A fluidized granular medium as an instance of the Fluctuation Theorem

We study the statistics of the power flux into a collection of inelastic beads maintained in a fluidized steady-state by external mechanical driving. The power shows large fluctuations, including frequent large negative fluctuations, about its average value. The relative probabilities of positive and negative fluctuations in the power flux are in close accord with the Fluctuation Theorem of Gallavotti and Cohen, even at time scales shorter than those required by the theorem. We also compare an effective temperature that emerges from this analysis to the kinetic granular temperature.Comment: 4 pages, 5 figures, submited to Physical Review Letters; Revised versio

Breakdown of Energy Equipartition in a 2D Binary Vibrated Granular Gas

We report experiments on the equipartition of kinetic energy between grains made of two different materials in a mixture of grains vibrated in 2 dimensions. In general, the two types of grains do not attain the same granular temperature, Tg = 1/2m v^2. However, the ratio of the two temperatures is constant in the bulk of the system and independent of the vibration velocity. The ratio depends strongly on the ratio of mass densities of the grains, but is not sensitive to the inelasticity of grains. Also, this ratio is insensitive to compositional variables of the mixture such as the number fraction of each component and the total number density. We conclude that a single granular temperature, as traditionally defined, does not characterize a multi-component mixture.Comment: 4 pages, 5 figures, submitted to Physical Review Letters, updated reference

Influenza vaccination stimulates maturation of the human T follicular helper cell response

The differentiation and specificity of human CD

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Genes predisposing to autoimmunity augment constitutive major histocompatibility complex class II-associated presentation of the self-antigen IgG2ab in vivo

The self-antigen IgG2ab is poorly presented to a γ2ab 435–451-reactive I-Ad-restricted T-cell hybridoma unless available in high concentrations or targeted to Fcγ- or complement receptors. Environmental factors, probably the extent of microbial challenge, profoundly influence the constitutive γ2ab/I-Ad presentation in IgCHb, H-2d mice. Here we report also a strong genetic impact. Constitutive presentation was highly efficient in spleen and thymus of (NZB × BXSB)F1 mice, which inherit a predisposition to develop lupus. Presentation correlated with disease progression and the serum levels of IgG2ab and IgG2ab complement factor 3 complexes. The finding that constitutive presentation was by far most efficient in males indicated that it was augmented by the Y chromosome-linked autoimmune acceleration Yaa gene. In line with previous data for healthy mice, constitutive γ2ab/I-Ad presentation was most pronounced in the adherent spleen cell fraction and improved by further enrichment for dendritic cells. Notably, however, whereas in normal mice the γ2ab determinant was undetectable on B cells lacking surface IgG2ab, such B cells contributed considerably to constitutive presentation in (NZB × BXSB)F1 hybrids. Presumably this resulted from complement receptor-mediated internalization of IgG2ab-containing immune complexes formed in lupus. These data add to the evidence that B cells with self-reactive receptors, known to exist in the mature repertoire, may present non-cognate foreign antigen to anti-foreign helper T lymphocytes and thus differentiate into autoantibody-secreting cells, and might likewise account for the polyclonal B-cell activation characteristic of several autoimmune syndromes