303 research outputs found
A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload
BACKGROUND: It has been recently demonstrated that CD8+ T-lymphocyte numbers are genetically transmitted in association with the MHC class I region. The present study was designed with the objective of narrowing the region associated with the setting of CD8+ T-lymphocyte numbers in a population of C282Y homozygous hemochromatosis subjects, in whom a high prevalence of abnormally low CD8+ T-lymphocyte counts has been described. METHODS: The study includes 43 C282Y homozygous subjects fully characterized both phenotypically and genotypically. Clinical characterization includes measurements of iron parameters at diagnosis (transferrin saturation and serum ferritin), total body iron stores and T-cell immunophenotyping determined by flow cytometry. Genetic characterization includes HLA class I alleles (A, B and C) and four additional microsatellite markers (D6S265, D6S2222, D6S105 and D6S2239) spanning 5 Megabases in the 6p21.3 region. RESULTS: Eighty-two extended C282Y carrying haplotypes were defined. Single-locus analysis revealed that the HLA-A region was associated with CD8+ T-cell numbers. Multivariate analysis showed that the combinations of the most common HLA-A alleles (HLA-A*03, -A*02 and -A*01) were associated with significantly lower numbers of CD8+ T-lymphocytes (0.30 ± 0.14 × 10(6)/ml), in comparison with subjects carrying only one copy of those alleles (0.46 ± 0.19 × 10(6)/ml) and subjects without any copy of those alleles (0.79 ± 0.15 × 10(6)/ml;p = 0.0001). No differences were observed in CD8+ T-cell counts among control subjects carrying the same combinations of HLA-A alleles (0.47 ± 0.14; 0.45 ± 0.21 and 0.41 ± 0.17 × 10(6)/ml, respectively), therefore not supporting a direct effect of HLA specificity but rather an indirect association with a locus close to HLA-A. Multivariate analysis showed that the combination of the most common HLA-A alleles also have an impact on the clinical expression of HH in terms of iron stores, in males(p = 0.0009). CONCLUSION: The present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH). It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed
Total blood lymphocyte counts in hemochromatosis probands with HFE C282Y homozygosity: relationship to severity of iron overload and HLA-A and -B alleles and haplotypes
BACKGROUND: It has been reported that some persons with hemochromatosis have low total blood lymphocyte counts, but the reason for this is unknown. METHODS: We measured total blood lymphocyte counts using an automated blood cell counter in 146 hemochromatosis probands (88 men, 58 women) with HFE C282Y homozygosity who were diagnosed in medical care. Univariate and multivariate analyses of total blood lymphocyte counts were evaluated using these variables: sex; age, transferrin saturation, and serum ferritin concentration at diagnosis; units of blood removed by phlebotomy to achieve iron depletion; and human leukocyte antigen (HLA)-A and -B alleles and haplotypes. RESULTS: The mean age at diagnosis was 49 ± 14 years (range 18 – 80 years) in men and 50 ± 13 years (range 22 – 88 years) in women. The correlations of total blood lymphocyte counts with sex, age, transferrin saturation, and serum ferritin concentration at diagnosis, and units of blood removed by phlebotomy to achieve iron depletion were not significant at the 0.05 level. Univariate analyses revealed significant associations between total blood lymphocyte counts and presence of the HLA-A*01, -B*08, and -B*14 alleles, and the A*01-B*08 haplotype. Presence of the A*01 allele, B*08 allele, or A*01-B*08 haplotype were associated with a lower total blood lymphocyte count, whereas presence of the B*14 allele was associated with a greater total blood lymphocyte count. There was an inverse association of total blood lymphocyte count with units of phlebotomy to achieve iron depletion, serum ferritin concentration, and with presence of the A*01-B*08 haplotype. CONCLUSION: We conclude that there is a significant inverse relationship of total blood lymphocyte counts and severity of iron overload in hemochromatosis probands with HFE C282Y homozygosity. The presence of the HLA-A*01 allele or the -B*08 allele was also associated with significantly lower total blood lymphocyte counts, whereas presence of the -B*14 allele was associated with significantly higher total blood lymphocyte counts. In univariate and multivariate analyses, total blood lymphocyte counts were significantly lower in probands with the HLA-A*01-B*08 haplotype than in probands without this haplotype
Very Low Mass Stellar and Substellar Companions to Solar-Like Stars From MARVELS V: A Low Eccentricity Brown Dwarf from the Driest Part of the Desert, MARVELS-6b
We describe the discovery of a likely brown dwarf (BD) companion with a
minimum mass of 31.7 +/- 2.0 M_Jup to GSC 03546-01452 from the MARVELS radial
velocity survey, which we designate as MARVELS-6b. For reasonable priors, our
analysis gives a probability of 72% that MARVELS-6b has a mass below the
hydrogen-burning limit of 0.072 M_Sun, and thus it is a high-confidence BD
companion. It has a moderately long orbital period of 47.8929 +0.0063/-0.0062
days with a low eccentricty of 0.1442 +0.0078/-0.0073, and a semi-amplitude of
1644 +12/-13 m/s. Moderate resolution spectroscopy of the host star has
determined the following parameters: T_eff = 5598 +/- 63, log g = 4.44 +/-
0.17, and [Fe/H] = +0.40 +/- 0.09. Based upon these measurements, GSC
03546-01452 has a probable mass and radius of M_star = 1.11 +/- 0.11 M_Sun and
R_star = 1.06 +/- 0.23 R_Sun with an age consistent with less than ~6 Gyr at a
distance of 219 +/- 21 pc from the Sun. Although MARVELS-6b is not observed to
transit, we cannot definitively rule out a transiting configuration based on
our observations. There is a visual companion detected with Lucky Imaging at
7.7 arcsec from the host star, but our analysis shows that it is not bound to
this system. The minimum mass of MARVELS-6b exists at the minimum of the mass
functions for both stars and planets, making this a rare object even compared
to other BDs.Comment: 15 pages, 15 figures, 5 tables. Accepted for publication in The
Astronomical Journa
Very Low-Mass Stellar and Substellar Companions to Solar-Like Stars from MARVELS I: A Low Mass Ratio Stellar Companion to TYC 4110-01037-1 in a 79-day Orbit
TYC 4110-01037-1 has a low-mass stellar companion, whose small mass ratio and
short orbital period are atypical amongst solar-like (Teff ~< 6000 K) binary
systems. Our analysis of TYC 4110-01037-1 reveals it to be a moderately aged
(~<5 Gyr) solar-like star having a mass of 1.07 +/- 0.08 MSun and radius of
0.99 +/- 0.18 RSun. We analyze 32 radial velocity measurements from the
SDSS-III MARVELS survey as well as 6 supporting radial velocity measurements
from the SARG spectrograph on the 3.6m TNG telescope obtained over a period of
~2 years. The best Keplerian orbital fit parameters were found to have a period
of 78.994 +/- 0.012 days, an eccentricity of 0.1095 +/- 0.0023, and a
semi-amplitude of 4199 +/- 11 m/s. We determine the minimum companion mass (if
sin i = 1) to be 97.7 +/- 5.8 MJup. The system's companion to host star mass
ratio, >0.087 +/- 0.003, places it at the lowest end of observed values for
short period stellar companions to solar-like (Teff ~< 6000 K) stars. One
possible way to create such a system would be if a triple-component stellar
multiple broke up into a short period, low q binary during the cluster
dispersal phase of its lifetime. A candidate tertiary body has been identified
in the system via single-epoch, high contrast imagery. If this object is
confirmed to be co-moving, we estimate it would be a dM4 star. We present these
results in the context of our larger-scale effort to constrain the statistics
of low mass stellar and brown dwarf companions to FGK-type stars via the
MARVELS survey.Comment: 22 pages; accepted in A
The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey
The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic
data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data
release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median
z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar
spectra, along with the data presented in previous data releases. These spectra
were obtained with the new BOSS spectrograph and were taken between 2009
December and 2011 July. In addition, the stellar parameters pipeline, which
determines radial velocities, surface temperatures, surface gravities, and
metallicities of stars, has been updated and refined with improvements in
temperature estimates for stars with T_eff<5000 K and in metallicity estimates
for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars
presented in DR8, including stars from SDSS-I and II, as well as those observed
as part of the SDSS-III Sloan Extension for Galactic Understanding and
Exploration-2 (SEGUE-2).
The astrometry error introduced in the DR8 imaging catalogs has been
corrected in the DR9 data products. The next data release for SDSS-III will be
in Summer 2013, which will present the first data from the Apache Point
Observatory Galactic Evolution Experiment (APOGEE) along with another year of
data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at
http://www.sdss3.org/dr
f(R) theories
Over the past decade, f(R) theories have been extensively studied as one of
the simplest modifications to General Relativity. In this article we review
various applications of f(R) theories to cosmology and gravity - such as
inflation, dark energy, local gravity constraints, cosmological perturbations,
and spherically symmetric solutions in weak and strong gravitational
backgrounds. We present a number of ways to distinguish those theories from
General Relativity observationally and experimentally. We also discuss the
extension to other modified gravity theories such as Brans-Dicke theory and
Gauss-Bonnet gravity, and address models that can satisfy both cosmological and
local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in
Relativity, Published version, Comments are welcom
The VIMOS Public Extragalactic Redshift Survey (VIPERS). Measuring non-linear galaxy bias at z ~ 0.8
Aims. We use the first release of the VImos Public Extragalactic Redshift Survey of galaxies (VIPERS) of 3c50 000 objects to measure the biasing relation between galaxies and mass in the redshift range z = [0.5,1.1]. Methods. We estimate the 1-point distribution function [PDF] of VIPERS galaxies from counts in cells and, assuming a model for the mass PDF, we infer their mean bias relation. The reconstruction of the bias relation is performed through a novel method that accounts for Poisson noise, redshift distortions, inhomogeneous sky coverage. and other selection effects. With this procedure we constrain galaxy bias and its deviations from linearity down to scales as small as 4 h-1 Mpc and out to z = 1.1. Results. We detect small (up to 2%) but statistically significant (up to 3\u3c3) deviations from linear bias. The mean biasing function is close to linear in regions above the mean density. The mean slope of the biasing relation is a proxy to the linear bias parameter. This slope increases with luminosity, which is in agreement with results of previous analyses. We detect a strong bias evolution only for z> 0.9, which is in agreement with some, but not all, previous studies. We also detect a significant increase of the bias with the scale, from 4 to 8 h-1 Mpc, now seen for the first time out to z = 1. The amplitude of non-linearity depends on redshift, luminosity, and scale, but no clear trend is detected. Owing to the large cosmic volume probed by VIPERS, we find that the mismatch between the previous estimates of bias at z 3c 1 from zCOSMOS and VVDS-Deep galaxy samples is fully accounted for by cosmic variance. Conclusions. The results of our work confirm the importance of going beyond the over-simplistic linear bias hypothesis showing that non-linearities can be accurately measured through the applications of the appropriate statistical tools to existing datasets like VIPERS. \ua9 ESO, 2016
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