Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration

RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration.     

Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 × 10(-8)), that the genetic basis of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 × 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP associations will be detected for this disease as sample size increases.     

The genome of the extremophile crucifer Thellungiella parvula

Thellungiella parvula is related to Arabidopsis thaliana and is endemic to saline, resource-poor habitats, making it a model for the evolution of plant adaptation to extreme environments. Here we present the draft genome for this extremophile species. Exclusively by next generation sequencing, we obtained the de novo assembled genome in 1,496 gap-free contigs, closely approximating the estimated genome size of 140 Mb. We anchored these contigs to seven pseudo chromosomes without the use of maps. We show that short reads can be assembled to a near-complete chromosome level for a eukaryotic species lacking prior genetic information. The sequence identifies a number of tandem duplications that, by the nature of the duplicated genes, suggest a possible basis for T. parvula's extremophile lifestyle. Our results provide essential background for developing genomically influenced testable hypotheses for the evolution of environmental stress tolerance.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

Internet路由前缀宣告的特征挖掘与分析

基于大量的历史BGP路由表快照,对BGP路由宣告信息进行深度挖掘.提出了前缀宣告稳定性度量方法,验证了绝大多数路由宣告是稳定的,历史上发生的路由劫持事件都是瞬时的(不具备稳定性);设计了前缀宣告的相似性测度算法,对大量历史BGP路由宣告进行了分析,结果表明大多数大型AS宣告的路由前缀具有自相似性,即,同一个AS宣告的多个路由前缀有一定的连续性.基于以上两个特征,从历史路由信息中可进一步提取前缀宣告的可信集,构造BGP路由宣告的可信知识库,为后续的路由前缀劫持检测和路由安全监测提供依据.     

决策支持系统中基于面向对象技术的信息反馈机制设计

利用面向对象的设计思想和方法 ,提出了一种在 DSS中实现信息反馈的方案 ,定义了系统中主要类的组成 ,着重研究了信息反馈对模型选择、策略分析以及策略选择的支持作用 ,分析了含信息反馈的 DSS中的信息流程 ,建立了相应 DSS的结构框架     

连续型模糊PID复合控制器在直流位置伺服系统中的应用

为了实现直流位置伺服系统的高速和高精度位置控制,针对实际伺服系统中存在的非线性、强耦合等各种不确定因素,提出了一种连续型模糊控制算法,以抑制各种非线性因素对被控对象的影响,同时引入传统的PID控制器,进一步改善了系统的稳态性能.通过实际运用表明,该连续型模糊PID复合控制器可以明显地提高直流位置伺服系统的动态性能和稳态精度,同时系统具有较强的适应性和鲁棒性.     

基于正交设计的陶瓷再生混凝土配合比试验

为提高废旧陶瓷的再生利用率,将陶瓷颗粒与陶瓷粉作为再生混凝土骨料与掺合料进行再生利用.运用正交设计的试验方法,以陶瓷粉、陶瓷颗粒、再生细骨料、粉煤灰、硅灰为5因素,每个因素设置4个水平,共设计16组配合比方案,进行抗压、导热等试验,得到陶瓷再生混凝土的强度、导热系数等物理力学参数,并寻找出最优配合比.试验结果表明最佳配合比为:陶瓷粉的质量分数为10%,陶瓷颗粒的质量分数为20%,再生细骨料的质量分数为40%,粉煤灰的质量分数为15%,硅灰的质量分数为5%.