Mucosa-associated invariant T cells are systemically depleted in simian immunodeficiency virus-infected rhesus macaques

Mucosa-associated invariant T (MAIT) cells contribute to host immune protection against a wide range of potential pathogens via the recognition of bacterial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although bacterial products translocate systemically in human immunodeficiency virus (HIV)-infected individuals and simian immunodeficiency virus (SIV)-infected Asian macaques, several studies have shown that MAIT cell frequencies actually decrease in peripheral blood during the course of HIV/SIV disease. However, the mechanisms underlying this proportional decline remain unclear. In this study, we characterized the phenotype, activation status, functionality, distribution, and clonotypic structure of MAIT cell populations in the peripheral blood, liver, mesenteric lymph nodes (MLNs), jejunum, and bronchoalveolar lavage (BAL) fluid of healthy and SIV-infected rhesus macaques (RMs). Low frequencies of MAIT cells were observed in the peripheral blood, MLNs, and BAL fluid of SIV-infected RMs. These numerical changes were coupled with increased proliferation and a highly public T cell receptor alpha (TCRα) repertoire in the MAIT cell compartment without redistribution to other anatomical sites. Collectively, our data show systemically decreased frequencies of MAIT cells likely attributable to enhanced turnover in SIV-infected RMs. This process may impair protective immunit

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

An Initial Survey of White Dwarfs in the Sloan Digital Sky Survey

An initial assessment is made of white dwarf and hot subdwarf stars observed in the Sloan Digital Sky Survey. In a small area of sky (190 square degrees), observed much like the full survey will be, 269 white dwarfs and 56 hot subdwarfs are identified spectroscopically where only 44 white dwarfs and 5 hot subdwarfs were known previously. Most are ordinary DA (hydrogen atmosphere) and DB (helium) types. In addition, in the full survey to date, a number of WDs have been found with uncommon spectral types. Among these are blue DQ stars displaying lines of atomic carbon; red DQ stars showing molecular bands of C_2 with a wide variety of strengths; DZ stars where Ca and occasionally Mg, Na, and/or Fe lines are detected; and magnetic WDs with a wide range of magnetic field strengths in DA, DB, DQ, and (probably) DZ spectral types. Photometry alone allows identification of stars hotter than 12000 K, and the density of these stars for 15<g<20 is found to be ~2.2 deg^{-2} at Galactic latitudes 29-62 deg. Spectra are obtained for roughly half of these hot stars. The spectra show that, for 15<g<17, 40% of hot stars are WDs and the fraction of WDs rises to ~90% at g=20. The remainder are hot sdB and sdO stars.Comment: Accepted for AJ; 43 pages, including 12 figures and 5 table

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or

Progenitors of Type Ia Supernovae: Binary Stars with White Dwarf Companions

Type Ia SNe (SNe Ia) are thought to come from carbon-oxygen white dwarfs that accrete mass from binary companions until they approach the Chandrasekhar limit, ignite carbon, and undergo complete thermonuclear disruption. A survey of the observed types of binaries that contain white dwarfs is presented. We propose that certain systems that seem most promising as SN Ia progenitors should be more intensively observed and modeled, to determine whether the white dwarfs in these systems will be able to reach the Chandrasekhar limit. In view of the number of promising single-degenerate systems and the dearth of promising double-degenerate systems, we suspect that single-degenerates produce most or perhaps all SNe Ia, while double-degenerates produce some or perhaps none.Comment: 34 pages, to appear in New Astronomy Review

The Atacama Cosmology Telescope: Cosmology from Galaxy Clusters Detected via the Sunyaev-Zel'dovich Effect

We present constraints on cosmological parameters based on a sample of Sunyaev-Zel'dovich-selected galaxy clusters detected in a millimeter-wave survey by the Atacama Cosmology Telescope. The cluster sample used in this analysis consists of 9 optically-confirmed high-mass clusters comprising the high-significance end of the total cluster sample identified in 455 square degrees of sky surveyed during 2008 at 148 GHz. We focus on the most massive systems to reduce the degeneracy between unknown cluster astrophysics and cosmology derived from SZ surveys. We describe the scaling relation between cluster mass and SZ signal with a 4-parameter fit. Marginalizing over the values of the parameters in this fit with conservative priors gives sigma_8 = 0.851 +/- 0.115 and w = -1.14 +/- 0.35 for a spatially-flat wCDM cosmological model with WMAP 7-year priors on cosmological parameters. This gives a modest improvement in statistical uncertainty over WMAP 7-year constraints alone. Fixing the scaling relation between cluster mass and SZ signal to a fiducial relation obtained from numerical simulations and calibrated by X-ray observations, we find sigma_8 = 0.821 +/- 0.044 and w = -1.05 +/- 0.20. These results are consistent with constraints from WMAP 7 plus baryon acoustic oscillations plus type Ia supernoava which give sigma_8 = 0.802 +/- 0.038 and w = -0.98 +/- 0.053. A stacking analysis of the clusters in this sample compared to clusters simulated assuming the fiducial model also shows good agreement. These results suggest that, given the sample of clusters used here, both the astrophysics of massive clusters and the cosmological parameters derived from them are broadly consistent with current models.Comment: 12 pages, 7 figures. Submitted to Ap

Dative constructions in Romance and beyond

This book offers a comprehensive account of dative structures across languages –with an important, though not exclusive, focus on the Romance family. As is well-known, datives play a central role in a variety of structures, ranging from ditransitive constructions to cliticization of indirect objects and differentially marked direct objects, and including also psychological predicates, possessor or causative constructions, among many others. As interest in all these topics has increased significantly over the past three decades, this volume provides an overdue update on the state of the art. Accordingly, the chapters in this volume account for both widely discussed patterns of dative constructions as well as those that are relatively unknown

Dative constructions in Romance and beyond

This book offers a comprehensive account of dative structures across languages –with an important, though not exclusive, focus on the Romance family. As is well-known, datives play a central role in a variety of structures, ranging from ditransitive constructions to cliticization of indirect objects and differentially marked direct objects, and including also psychological predicates, possessor or causative constructions, among many others. As interest in all these topics has increased significantly over the past three decades, this volume provides an overdue update on the state of the art. Accordingly, the chapters in this volume account for both widely discussed patterns of dative constructions as well as those that are relatively unknown

Dative constructions in Romance and beyond

This book offers a comprehensive account of dative structures across languages –with an important, though not exclusive, focus on the Romance family. As is well-known, datives play a central role in a variety of structures, ranging from ditransitive constructions to cliticization of indirect objects and differentially marked direct objects, and including also psychological predicates, possessor or causative constructions, among many others. As interest in all these topics has increased significantly over the past three decades, this volume provides an overdue update on the state of the art. Accordingly, the chapters in this volume account for both widely discussed patterns of dative constructions as well as those that are relatively unknown

Dative constructions in Romance and beyond

This book offers a comprehensive account of dative structures across languages –with an important, though not exclusive, focus on the Romance family. As is well-known, datives play a central role in a variety of structures, ranging from ditransitive constructions to cliticization of indirect objects and differentially marked direct objects, and including also psychological predicates, possessor or causative constructions, among many others. As interest in all these topics has increased significantly over the past three decades, this volume provides an overdue update on the state of the art. Accordingly, the chapters in this volume account for both widely discussed patterns of dative constructions as well as those that are relatively unknown