An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

Shank3 mutant mice display autistic-like behaviours and striatal dysfunction

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.     

Characterization and Preparation of Bimetallic Nanoparticles

1 Results Bimetallic particles in the nanometer size range are of substantial interest due to their vast applications in catalysis[1].The synthesis of bimetallic nanoparticles with definite size with a well-control over their nanostructure remains a challenging problem.Thus there exists a great demand for both synthesis and atomic level characterization of nanostructure of bimetallic nanoparticles (NPs).With the recent advent of high-intensity tunable sources of X-rays,now available at synchrotron radia...     

含软弱夹层的强风化泥岩强度及破坏模式试验研究

为研究软弱夹层对边坡失稳的影响,对含软弱夹层的岩体强度及破坏模式进行了理论和试验研究.采用某边坡钻孔芯样分别制备强风化泥岩、泥化夹层、含软弱夹层泥岩3种三轴试样,并进行三轴固结不排水剪试验.结合理论分析,对强风化泥岩、泥化夹层、含软弱夹层泥岩的强度和破坏模式进行了研究,揭示软弱夹层倾角、围压对试样强度和破坏模式的影响规...     

螺噁嗪类化合物光致变色过程抗疲劳性研究进展

螺噁嗪以相对较高的化学稳定性和抗疲劳性而倍受瞩目,在商业和军事领域有着潜在的应用价值。其抗疲劳性能尚达不到商品化要求是目前限制其工业化的主要障碍之一,本文综述了此方面的研究进展。     

关联交叉口短时交通流可预测性分析及组合预测算法

文中首先根据交叉口交通流参数时间序列的相关性对关联交叉口进行定义,给出关联交叉口短时交通流可预测分析的几个定量指标,以及交通流时间序列最大Lya-punov指数的计算方法;然后提出在短时交通流时间序列的可预测分析基础上,选取一组预测模型并建立基于RBF网络的非线性组合预测模型,提出了关联交叉口短时交通流的组合预测算法;最后对实测短时交通流进行仿真试验,结果表明组合预测方法相对于单项预测方法具有更好的预测性能.     

粮食产量影响因素的灰色关联分析及其贡献率比较

运用灰色关联分析的方法,通过对省域(河南省)、市域(安阳市)、县域(滑县)三级粮食产量影响因素(播种面积、有效灌溉面积、农村用电、农用化肥、农用柴油、农药)的灰色关联分析及其贡献率比较,结果表明:有效灌溉面积对市域、省域两级粮食产量的影响均居第一位,农用化肥施用量对县域、市域两级粮食产量的影响均居第二位,农药与其它5个因素相比,对省、市、县三级粮食产量的影响相同,都是最小.农用柴油、农村用电、农用化肥、农药对县、市两级粮食产量的贡献率均居第一、第二、第三、第四位,化肥和农药对省、市、县三级粮食产量的贡献率都据第三和第四位.在此基础上,为不同区域尺度的粮食生产提供了决策依据.表5.参11.     

Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL

Resequencing genes provides the opportunity to assess the full spectrum of variants that influence complex traits. Here we report the first application of resequencing to a large population (n = 3,551) to examine the role of the adipokine ANGPTL4 in lipid metabolism. Nonsynonymous variants in ANGPTL4 were more prevalent in individuals with triglyceride levels in the lowest quartile than in individuals with levels in the highest quartile (P = 0.016). One variant (E40K), present in approximately 3% of European Americans, was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein cholesterol in European Americans from the Atherosclerosis Risk in Communities Study and in Danes from the Copenhagen City Heart Study. The ratio of nonsynonymous to synonymous variants was higher in European Americans than in African Americans (4:1 versus 1.3:1), suggesting population-specific relaxation of purifying selection. Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history.     

Ciliary proteins Fap43 and Fap44 interact with each other and are essential for proper cilia and flagella beating

Cilia beating is powered by the inner and outer dynein arms (IDAs and ODAs). These multi-subunit macrocomplexes are arranged in two rows on each outer doublet along the entire cilium length, except its distal end. To generate cilia beating, the activity of ODAs and IDAs must be strictly regulated locally by interactions with the dynein arm-associated structures within each ciliary unit and coordinated globally in time and space between doublets and along the axoneme. Here, we provide evidence of a novel ciliary complex composed of two conserved WD-repeat proteins, Fap43p and Fap44p. This complex is adjacent to another WD-repeat protein, Fap57p, and most likely the two-headed inner dynein arm, IDA I1. Loss of either protein results in altered waveform, beat stroke and reduced swimming speed. The ciliary localization of Fap43p and Fap44p is interdependent in the ciliate Tetrahymena thermophila.     

基于DEA模型的电子商务网站综合评价与质量诊断

在网络经济时代,电子商务网站运行效率直接关系到企业的生存和发展.电子商务网站评价作为比较网站优劣、指导网站建设的重要方法和手段,受到电子商务领域学术界和企业界的共同关注.本文提出基于DEA的电子商务综合评价与质量诊断方法.该方法避免了各种指标权重确定方法的主观性和不确定性,并在评价基础上对弱DEA有效和非DEA有效商务网站进行质量诊断,指明改进和提高效率的方法与途径.实例分析证实了该方法的有效性和科学性.本文的研究丰富了电子商务评价理论,为当前电子商务网站评价提供了切实可行的技术经济分析方法.