BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although nine BBS genes have been cloned, they explain only 40-50% of the total mutational load. Here we report a major new BBS locus, BBS10, that encodes a previously unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants.     

Multiple newly identified loci associated with prostate cancer susceptibility

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at 相似文献   

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.     

Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal gammadelta T cells

B cells, alphabeta T cells and gammadelta T cells are conserved lymphocyte subtypes encoding their antigen receptors from somatically rearranged genes. alphabeta T cells undergo positive selection in the thymus by engagement of their T cell receptors (TCRs) with self-peptides presented by major histocompatibility complex molecules. The molecules that select gammadelta T cells are unknown. Vgamma5+Vdelta1+ cells comprise 90% of mouse epidermal gammadelta T cells. By mapping and genetic complementation using a strain showing loss of Vgamma5+Vdelta1+ cells due to a failure of thymic selection, we show that this defect is caused by mutation in Skint1, a newly identified gene expressed in thymus and skin that encodes a protein with immunoglobulin-like and transmembrane domains. Skint1 is the prototypic member of a rapidly evolving family of at least 11 genes in mouse, with greatest similarity to the butyrophilin genes. These findings define a new family of proteins mediating key epithelial-immune interactions.     

Ultraconservation identifies a small subset of extremely constrained developmental enhancers

Extended perfect human-rodent sequence identity of at least 200 base pairs (ultraconservation) is potentially indicative of evolutionary or functional uniqueness. We used a transgenic mouse assay to compare the embryonic enhancer activity of 231 noncoding ultraconserved human genome regions with that of 206 extremely conserved regions lacking ultraconservation. Developmental enhancers were equally prevalent in both populations, suggesting instead that ultraconservation identifies a small, functionally indistinct subset of similarly constrained cis-regulatory elements.     

Empirical Bayesian Density Forecasting in Iowa and Shrinkage for the Monte Carlo Era

The track record of a 20‐year history of density forecasts of state tax revenue in Iowa is studied, and potential improvements sought through a search for better‐performing ‘priors’ similar to that conducted three decades ago for point forecasts by Doan, Litterman and Sims (Econometric Reviews, 1984). Comparisons of the point and density forecasts produced under the flat prior are made to those produced by the traditional (mixed estimation) ‘Bayesian VAR’ methods of Doan, Litterman and Sims, as well as to fully Bayesian ‘Minnesota Prior’ forecasts. The actual record and, to a somewhat lesser extent, the record of the alternative procedures studied in pseudo‐real‐time forecasting experiments, share a characteristic: subsequently realized revenues are in the lower tails of the predicted distributions ‘too often’. An alternative empirically based prior is found by working directly on the probability distribution for the vector autoregression parameters—the goal being to discover a better‐performing entropically tilted prior that minimizes out‐of‐sample mean squared error subject to a Kullback–Leibler divergence constraint that the new prior not differ ‘too much’ from the original. We also study the closely related topic of robust prediction appropriate for situations of ambiguity. Robust ‘priors’ are competitive in out‐of‐sample forecasting; despite the freedom afforded the entropically tilted prior, it does not perform better than the simple alternatives. Copyright © 2014 John Wiley & Sons, Ltd.     

Animal deception and the content of signals

In cases of animal mimicry, the receiver of the signal learns the truth that he is either dealing with the real thing or with a mimic. Thus, despite being a prototypical example of animal deception, mimicry does not seem to qualify as deception on the traditional definition, since the receiver is not actually misled. We offer a new account of propositional content in sender-receiver games that explains how the receiver is misled (and deceived) by mimicry. We show that previous accounts of deception, and of propositional content, give incorrect results about whether certain signals are deceptive.     

超薄高分子材料热管(英文)

热管具有远高于大多数金属的导热性能,已被广泛应用于电子元器件的散热方面.由于电子元器件正朝着微型化、薄型化、片式化和高功率等趋势发展,因此散热元件必须同时具备轻薄和高导热系数的特点.本文介绍了一种由高分子材料制造的超薄热管的设计和制造过程.其厚度为0.30 mm,大小为2 cm×6 cm,输入功率为9.54 W时,有效传热系数为541 W/(m K).管壳材料为kapton薄膜,吸液芯和蒸汽腔均由光阻SU8组成,光阻SU8柱子的大小和柱子之间的间隔差异为吸液芯提供了毛细血力;另外,通过原子层积电镀,SU8光阻和kapton薄膜都覆盖上一层极薄的Ti O2膜,改善了表面和吸液芯的亲水性能,同时实现了密封.