We report a detection of the baryon acoustic oscillation (BAO) feature in the three-dimensional correlation function of the transmitted flux fraction in the Lyα forest of high-redshift quasars. The ...study uses 48 640 quasars in the redshift range 2.1 ≤ z ≤ 3.5 from the Baryon Oscillation Spectroscopic Survey (BOSS) of the third generation of the Sloan Digital Sky Survey (SDSS-III). At a mean redshift z = 2.3, we measure the monopole and quadrupole components of the correlation function for separations in the range 20 h-1 Mpc < r < 200 h-1 Mpc. A peak in the correlation function is seen at a separation equal to (1.01 ± 0.03) times the distance expected for the BAO peak within a concordance ΛCDM cosmology. This first detection of the BAO peak at high redshift, when the universe was strongly matter dominated, results in constraints on the angular diameter distance DA and the expansion rate H at z = 2.3 that, combined with priors on H0 and the baryon density, require the existence of dark energy. Combined with constraints derived from cosmic microwave background observations, this result implies H(z = 2.3) = (224 ± 8) km s-1 Mpc-1, indicating that the time derivative of the cosmological scale parameter ȧ = H(z = 2.3)/(1 + z) is significantly greater than that measured with BAO at z ~ 0.5. This demonstrates that the expansion was decelerating in the range 0.7 < z < 2.3, as expected from the matter domination during this epoch. Combined with measurements of H0, one sees the pattern of deceleration followed by acceleration characteristic of a dark-energy dominated universe.
Background & Aims T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB). Methods We ...enrolled 200 adults with CHB who participated in the National Institutes of Health−supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls). Peripheral blood lymphocytes from these subjects were analyzed for T-cell responses (proliferation and production of interferon gamma and interleukin 10) to overlapping hepatitis B virus (HBV) peptides (preS, S, preC, core, and reverse transcriptase), influenza matrix peptides, and lipopolysaccharide. T-cell expression of regulatory markers FOXP3, programmed death-1, and cytotoxic T lymphocyte-associated antigen-4 was examined by flow cytometry. Immune measures were compared with clinical parameters, including physician-defined immune-active, immune-tolerant, or inactive CHB phenotypes, in a blinded fashion. Results Compared with controls, patients with CHB had weak T-cell proliferative, interferon gamma, and interleukin 10 responses to HBV, with increased frequency of circulating FOXP3+ CD127− regulatory T cells and CD4+ T-cell expression of programmed death-1 and cytotoxic T lymphocyte-associated antigen-4. T-cell measures did not clearly distinguish between clinical CHB phenotypes, although the HBV core-specific T-cell response was weaker in hepatitis B e antigen (HBeAg)+ than HBeAg− patients (percent responders: 3% vs 23%; P = .00008). Although in vitro blockade of programmed death-1 or cytotoxic T lymphocyte-associated antigen-4 increased T-cell responses to HBV, the effect was weaker in HBeAg+ than HBeAg− patients. Furthermore, T-cell responses to influenza and lipopolysaccharide were weaker in CHB patients than controls. Conclusions HBV persists with virus-specific and global T-cell dysfunction mediated by multiple regulatory mechanisms, including circulating HBeAg, but without distinct T-cell−based immune signatures for clinical phenotypes. These findings suggest additional T-cell−independent or regulatory mechanisms of CHB pathogenesis that warrant further investigation.
Background & Aims: The pathogenesis of chronic hepatitis C is poorly understood. This study examines the ability of hepatitis C virus (HCV) to infect, replicate in, and produce progeny virus from ...perihepatic lymph nodes in vivo. Methods: Lymph node (LN) biopsy specimens were taken from 20 patients with HCV genotype 1 infection and end-stage liver disease and 20 noninfected negative controls. Sections were probed with HCV RNA strand-specific riboprobes and antibodies specific for HCV core and nonstructural region 3 antigens plus B-cell (CD20) and T-cell (CD2) antigens. In a selected case, HCV quasispecies in serum, peripheral blood mononuclear cells, liver, and perihepatic lymph nodes were analyzed by clonal frequency analysis and sequencing. Results: HCV infection was confirmed in 17 of 20 (85%) of lymph node specimens by in situ hybridization, and HCV replication was confirmed in 50% of cases by detection of HCV replicative intermediate RNA. HCV core and nonstructural 3 antigens were detected in lymph nodes by immunocytochemistry. Infected cell phenotypes were primarily CD20 B cells, although other cell types were positive for HCV replication markers. Quasispecies analysis in one case indicated that 68% of variants circulating in serum were also present in lymphoid tissues, and only 40% of serum variants were identified in liver, documenting a major contribution of lymphoid replication to HCV viremia. Conclusions: HCV lymphotropism provides new insights into the complex pathobiology of chronic hepatitis C in humans. We demonstrate for the first time a major contribution of extrahepatic HCV replication to circulating virus in serum (viremia).
PDF
