T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.

The repertoire of human αβ T-cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8 <sup>+</sup> T cell response to the highly effective YF-17D vaccine. We discover that these A2/LLW-specific CD8 <sup>+</sup> T cells are highly biased for the TCR α chain TRAV12-2. This bias is already present in A2/LLW-specific naïve T cells before vaccination with YF-17D. Using CD8 <sup>+</sup> T cell clones, we show that TRAV12-2 does not confer a functional advantage on a per cell basis. Molecular modeling indicated that the germline-encoded complementarity determining region (CDR) 1α loop of TRAV12-2 critically contributes to A2/LLW binding, in contrast to the conventional dominant dependence on somatically rearranged CDR3 loops. This germline component of antigen recognition may explain the unusually high precursor frequency, prevalence and immunodominance of T-cell responses specific for the A2/LLW epitope

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations

Abstract Background and Objectives Uncertainty exists regarding the optimal dosing regimen for vancomycin in diferent patient populations, leading to a plethora of subgroup-specifc pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specifc patient subgroups. Methods A pooled population-pharmacokinetic model was built in NONMEM based on data from 14 diferent studies in diferent patient populations. Steady-state exposure was simulated and compared across patient subgr

The return on post–compulsory school mathematics study

What are the essential skills learned at school that are required for the labour market? The issue is particularly policy relevant in the UK, where the 16–19 secondary school curriculum (A levels) is undergoing major reform. This paper uses data from the UK to investigate the impact of different academic subjects in secondary school on pupils' subsequent earning, particularly the impact of studying advanced mathematical curricula. We find that individuals with an advanced (A–level) mathematics qualification earn 7%–10% more than similarly educated workers without this qualification, even after controlling for the initial ability of these individuals

Sample selection in a model of female labour supply : an alternative approach

Suggests an alternative and computationally simpler approach of non-random sampling of labour economics and represents an observed outcome of an individual female′s choice of whether or not to participate in the labour market. Concludes that there is an alternative to the Heckman two-step estimator

Educational signalling Empirical aspects of selection policy and labour hiring

SIGLEAvailable from British Library Lending Division - LD:D58502/86 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The economics of UK teacher supply The graduate's decision

SIGLEAvailable from British Library Document Supply Centre- DSC:3597.76(BU-DOE-DP--89/245) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Graduate earnings after six years Who are the winners?

SIGLEAvailable from British Library Document Supply Centre- DSC:3597.76(BU-DOE-DP--89/243) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Self employment among graduates

SIGLEAvailable from British Library Document Supply Centre- DSC:3597.76(BU-DOE-DP--89/244) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Job separations, job tenure and earnings An empirical analysis

SIGLEAvailable from British Library Document Supply Centre- DSC:6100.395(91-09) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Evaluating training schemes Lessons from Britain

SIGLEAvailable from British Library Document Supply Centre-DSC:5142.088(92/4) / BLDSC - British Library Document Supply CentreGBUnited Kingdo