End-stage renal disease causes skewing in the TCR Vβ-repertoire primarily within CD8+ T Cell subsets

A broad T cell receptor (TCR-) repertoire is required for an effective immune response. TCR-repertoire diversity declines with age. End-stage renal disease (ESRD) patients have a prematurely aged T cell system which is associated with defective T cell-mediated immunity. Recently, we showed that ESRD may significantly skew the TCR Vβ-repertoire. Here, we assessed the impact of ESRD on the TCR Vβ-repertoire within different T cell subsets using a multiparameter flow-cytometry-based assay, controlling for effects of aging and CMV latency. Percentages of 24 different TCR Vβ-families were tested in circulating naive and memory T cell subsets of 10 ESRD patients and 10 age- and CMV-serostatus-matched healthy individuals (HI). The Gini-index, a parameter used in economics to describe the distribution of income, was calculated to determine the extent of skewing at the subset level taking into account frequencies of all 24 TCR Vβ-families. In addition, using HI as reference population, the differential impact of ESRD was assessed on clonal expansion at the level of an individual TCR Vβ-family. CD8+, but not CD4+, T cell differentiation was

End stage renal disease patients have a skewed T cell receptor Vβ repertoire

Background: End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed. Results: A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) - IgG serostatus matched healthy individuals (31.4 %, P < 0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vβ repertoire. More differentiated CD8+ T cells were observed in young ESRD patients with a shifted TCR Vβ repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vβ skewing. Conclusions: ESRD significantly skewed the TCR Vβ repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity

Constraining the Power Spectrum using Clusters

(Shortened Abstract). We analyze a redshift sample of Abell/ACO clusters and compare them with numerical simulations based on the truncated Zel'dovich approximation (TZA), for a list of eleven dark matter (DM) models. For each model we run several realizations, on which we estimate cosmic variance effects. We analyse correlation statistics, the probability density function, and supercluster properties from percolation analysis. As a general result, we find that the distribution of galaxy clusters provides a constraint only on the shape of the power spectrum, but not on its amplitude: a shape parameter 0.18 < \Gamma < 0.25 and an effective spectral index at 20Mpc/h in the range [-1.1,-0.9] are required by the Abell/ACO data. In order to obtain complementary constraints on the spectrum amplitude, we consider the cluster abundance as estimated using the Press--Schechter approach, whose reliability is explicitly tested against N--body simulations. We conclude that, of the cosmological models considered here, the only viable models are either Cold+Hot DM ones with \Omega_\nu = [0.2-0.3], better if shared between two massive neutrinos, and flat low-density CDM models with \Omega_0 = [0.3-0.5].Comment: 37 pages, Latex file, 9 figures; New Astronomy, in pres

Metastability and Transient Effects in Vortex Matter Near a Decoupling Transition

We examine metastable and transient effects both above and below the first-order decoupling line in a 3D simulation of magnetically interacting pancake vortices. We observe pronounced transient and history effects as well as supercooling and superheating between the 3D coupled, ordered and 2D decoupled, disordered phases. In the disordered supercooled state as a function of DC driving, reordering occurs through the formation of growing moving channels of the ordered phase. No channels form in the superheated region; instead the ordered state is homogeneously destroyed. When a sequence of current pulses is applied we observe memory effects. We find a ramp rate dependence of the V(I) curves on both sides of the decoupling transition. The critical current that we obtain depends on how the system is prepared.Comment: 10 pages, 15 postscript figures, version to appear in PR

Consistent interactions of dual linearized gravity in D=5: couplings with a topological BF model

Under some plausible assumptions, we find that the dual formulation of linearized gravity in D=5 can be nontrivially coupled to the topological BF model in such a way that the interacting theory exhibits a deformed gauge algebra and some deformed, on-shell reducibility relations. Moreover, the tensor field with the mixed symmetry (2,1) gains some shift gauge transformations with parameters from the BF sector.Comment: 63 pages, accepted for publication in Eur. Phys. J.

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

A 250 GHz planar low noise Schottky receiver

A planar quasi-optical Schottky receiver based on the quasi-integrated horn antenna has been developed and tested over the 230–280GHz bandwidth. The receiver consists of a planar GaAs Schottky diode placed at the feed of a dipole-probe suspended on a thin dielectric membrane in an etched-pyramidal horn cavity. The diode has a 1.2 Μm anode diameter and a low parasitic capacitance due to the use of an etched surface channel. The antenna-mixer results in a measured DSB conversion loss and noise temperature at 258GHz of 7.2dB±0.5dB and 1310K±70K, respectively, at room temperature. The design is compatible with SIS mixers, and the low cost of fabrication and simplicity makes it ideal for submillimeter-wave imaging arrays requiring a 10–20% bandwidth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44552/1/10762_2005_Article_BF02084284.pd

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium

BACKGROUND: Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth o