Covariant Quantization of Superstrings Without Pure Spinor Constraints

We construct a covariant quantum superstring, extending Berkovits' approach by introducing new ghosts to relax the pure spinor constraints. The central charge of the underlying Kac-Moody algebra, which would lead to an anomaly in the BRST charge, is treated as a new generator with a new b-c system. We construct a nilpotent BRST current, an anomalous ghost current and an anomaly-free energy-momentum tensor. For open superstrings, we find the correct massless spectrum. In addition, we construct a Lorentz invariant B-field to be used for the computation of the integrated vertex operators and amplitudes.Comment: 30 page

Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield

How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.This study was funded by the Natural Environment Research Council (NERC) under research programme NE/N018125/1 ASSIST–Achieving Sustainable Agricultural Systems www.assist.ceh.ac.uk. ASSIST is an initiative jointly supported by NERC and the Biotechnology and Biological Sciences Research Council (BBSRC). Additional funding for field studies was from the Wessex Biodiversity Ecosystem Services Sustainability (NE/J014680/1) project within the NERC BESS programme. Other data sets were generated from research funded by: (a) the Insect Pollinators Initiative programme funded by BBSRC, Defra, NERC, the Scottish Government and the Wellcome Trust, under the Living with Environmental Change Partnership; (b) Defra project BD5005: Provision of Ecosystem services in the ES scheme; and (c) Irish Government under the National Development Plan 2007–2013 administered by the Irish EPA

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92–0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88–0.94). Conclusions Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Thermal double donor annihilation and oxygen precipitation at around 650°C in Czochralski-grown Si: Local vibrational mode studies

We have used local vibrational mode (LVM) spectroscopy to monitor the formation of oxygen-related thermal double donors (TDDs) at 450°C and their annihilation at 650°C in carbon-lean Czochralski-grown (Cz-) Si crystals. A few samples were treated at 650°C under high hydrostatic pressure. It is found that the annihilation of TDDs at 650°C results not only in a partial recovery of the interstitial oxygen, but also in the appearance of a number of new O-related LVM bands in the range 990-1110 cm-1. The positions of these lines and their shapes are identical to those observed for Cz-Si irradiated with electrons or neutrons and annealed at 600-700°C. Since the lines appear upon annealing out of V O3 and V O4 defects in irradiated samples, they are suggested to arise from V Om (m&amp;gt;4) complexes. In both kinds of samples, pre-annealed and pre-irradiated, the new LVM bands disappear upon prolonged annealing at 650°C while enhanced oxygen precipitation occurs. The V Om defects are suggested to serve as nuclei for oxygen precipitates developing at around 650°C. High hydrostatic pressure is found to enhance further (up to 4-5 times) the oxygen precipitation process at 650°C in the samples pre-annealed at 450°C. © 2005 IOP Publishing Ltd

Divacancy-oxygen and trivacancy-oxygen complexes in silicon: Local vibrational mode studies

Fourier transform infrared absorption spectroscopy was used to study the evolution of multivacancy-oxygen-related defects in the temperature range 200-300 °C in Czochralski-grown Si samples irradiated with MeV electrons or neutrons. A clear correlation between disappearance of the divacancy (V 2) related absorption band at 2767 cm-1 and appearance of two absorption bands positioned at 833.4 and 842.4 cm-1 at 20 K (at 825.7 and 839.1 cm-1 at room temperature) has been found. Both these two emerging bands have previously been assigned to a divacancy-oxygen defect formed via interaction of mobile V2 with interstitial oxygen (O i) atoms. The present study shows, however, that the two bands arise from different defects since the ratio of their intensities depends on the type of irradiation. The 842.4 cm-1 band is much more pronounced in neutron irradiated samples and we argue that it is related to a trivacancy-oxygen defect (V3O) formed via interaction of mobile V3 with Oi atoms or/and interaction of mobile V 2 with VO defects. © (2010) Trans Tech Publications

Trivacancy-oxygen complex in silicon: Local vibrational mode characterization

FTIR study of the evolution of multivacancy-oxygen-related defects in the temperature range 100-350 °C in Czochralski-grown Si samples irradiated with different particles (10 MeV electrons and 5 MeV neutrons) has been carried out. Appearance of two absorption bands positioned at 833.4 and 842.4 cm-1 has been found upon annealing of the divacancy related absorption band at 2767 cm-1. The 833.4 cm-1 band is assigned to a divacancy-oxygen defect. The 842.4 cm-1 band is much more pronounced in neutron irradiated samples and we argue that it is related to a trivacancy-oxygen defect formed via interaction of mobile V3 with Oi atoms. © 2009 Elsevier B.V. All rights reserved