PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes

DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.     

Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse

Single-nucleotide polymorphisms (SNPs) have been the focus of much attention in human genetics because they are extremely abundant and well-suited for automated large-scale genotyping. Human SNPs, however, are less informative than other types of genetic markers (such as simple-sequence length polymorphisms or microsatellites) and thus more loci are required for mapping traits. SNPs offer similar advantages for experimental genetic organisms such as the mouse, but they entail no loss of informativeness because bi-allelic markers are fully informative in analysing crosses between inbred strains. Here we report a large-scale analysis of SNPs in the mouse genome. We characterized the rate of nucleotide polymorphism in eight mouse strains and identified a collection of 2,848 SNPs located in 1,755 sequence-tagged sites (STSs) using high-density oligonucleotide arrays. Three-quarters of these SNPs have been mapped on the mouse genome, providing a first-generation SNP map of the mouse. We have also developed a multiplex genotyping procedure by which a genome scan can be performed with only six genotyping reactions per animal.     

大荷载无人机-机器人高压输电线协同检修新方法研究

输电线路带电检修机器人是一种辅助和代替人工进行输电线路带电作业检修的一种智能化装备,其对于提高作业效率、作业可靠性、作业安全性具有重要实际意义,然而机器人在上下线过程中耗费大量的人力物力,大大降低了整体作业效率,机器人上下线问题已经成为制约机器人实用化的一个重要瓶颈。针对上述问题,提出了大荷载无人机(unmanned aerial vehical, UAV)和机器人的输电线协同检修新方法,该系统分为无人机、机器人和联接件,联接件用于联接无人机和机器人,通过电磁铁磁力的控制实现无人机与机器人系统的对接与分离,同时,通过对机器人机械臂系统的运动学建模与分析,得到了作业末端套筒所能到达的运动空间,从而进一步优化机械臂的结构参数,最后,通过硬件系统、软件系统、机械系统的集成设计,开发了机器人物理样机系统,在四分裂输电线路上进行引流板拧紧作业实验。实验结果表明:改系统能够顺利完成四分裂引流板作业任务,具有较强工程实用性,研究结果对于输电线路智能运维管理具有重要理论意义和实际应用价值。     

Modeling the Spatial-temporal Characteristics of Mutual Funds' Herd Behavior

Herd behavior in financial markets often leads to unjustified macroscopic phenomena.However,despite existing studies on modeling herd behavior,how it varies acr...     

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.     

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.     

EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa

Using a positional cloning approach supported by comparative genomics, we have identified a previously unreported gene, EYS, at the RP25 locus on chromosome 6q12 commonly mutated in autosomal recessive retinitis pigmentosa. Spanning over 2 Mb, this is the largest eye-specific gene identified so far. EYS is independently disrupted in four other mammalian lineages, including that of rodents, but is well conserved from Drosophila to man and is likely to have a role in the modeling of retinal architecture.     

Suitable energy platform significantly improves charge separation of g-C_3N_4 for CO_2 reduction and pollutant oxidation under visible-light

The photocatalytic activities of g-C_3N_4 can be significantly improved by increasing life time of the photogenerated charges. Here, in this work we introduced TiO_2 as proper energy platform to accept the photogenerated electrons from g-C_3N_4 during photocatalysis. The nanophotocatalysts formed from the combination of a suitable amount of TiO_2 nanoparticles and g-C_3N_4 nanosheets showed 8.75 and 4.22% enhancement in photocatalytic activities for CO_2 reduction and 2-chlorophenol(2-CP) degradation under visible light illumination as compared to bare g-C_3N_4. Based on the surface photovoltage spectra, photoluminescence spectra and examination of formed hydroxyl radicals, it was confirmed that these enhanced photoactivities were attributed to the much-improved charge separation via the electron transfer from g-C_3N_4 to TiO_2. From trapping experiments,it was found that hydroxyl radicals were the major species involved in the photocatalytic degradation of 2-CP.This study is helpful to synthesize efficient photocatalysts to cope with energy and environmental issues.     

Ammonia borane at high pressures

Ammonia borane has received tremendous research attention in the past decade because of its potential for chemical hydrogen storage. This paper reviews recent studies about the behavior of ammonia borane at high pressures. While much work is still needed to comprehensively understand the pressure influence on this molecular crystal, a phase diagram based on the available experimental and theoretical data is constructed. Raman spectroscopy studies indicate five transitions upon compression up to 65 GPa at ambient temperature. Diffraction experiments and theoretical studies demonstrate that three of these transitions are first-order phase transformations in the sequence of I4mm-Cmc21-P21-（different） P21, and two are iso-structural. A low-temperature phase（Pmn21） and a high-temperature high-pressure phase（Pmna） are also recognized.     

考虑震损的混凝土框架结构改进建模方法

为准确描述震后结构损伤的影响,提出了损伤构件的定量分析方法及震损结构的改进建模方法.首先,从骨架曲线退化及滞回规则退化两方面定义了损伤构件的性能退化指数;然后,基于Park-Ang模型与Kunnath模型,采用统计回归分析方法提出了损伤构件恢复力模型,并对其准确性进行了验证;最后,应用该恢复力模型对震损框架结构进行弹塑性分析.结果 表明:采用Park-Ang模型和Kunnath模型得到的损伤构件恢复力模型均具有较高的准确性;对于所研究的2种构件,滞回曲线力峰值的理论值和试验值误差均小于10％;向完好结构输入组合地震波,向震损结构输入单一地震波,各层位移时程曲线吻合良好,说明采用该恢复力模型进行震损结构建模能够准确分析震损程度及分布对结构抗震性能的影响.