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.     

ANALYSIS AND COMPUTATIONAL ALGORITHM FOR QUEUES WITH STATE-DEPENDENT VACATIONS Ⅱ:M(n)/G/1/K

We study a single-server queueing system with state-dependent arrivals and general service-distribution.or simply M(n)/G/1/K.where the server follows an N policy and takes multiple vacationswhen the system is empty.We provide a recursive algorithm using the supplementary variable tech-nique to munerically compute the stationary queue length distribution of the system.The only inputrequirements are the Laplace-Stieltjes transforms of the service time distribution and the vacation timedistribution.and the state-dependent arrival rate.The computational complexity of the algorithm isO(K~3).     

A robust DNA mechanical device controlled by hybridization topology.

Controlled mechanical movement in molecular-scale devices has been realized in a variety of systems-catenanes and rotaxanes, chiroptical molecular switches, molecular ratchets and DNA-by exploiting conformational changes triggered by changes in redox potential or temperature, reversible binding of small molecules or ions, or irradiation. The incorporation of such devices into arrays could in principle lead to complex structural states suitable for nanorobotic applications, provided that individual devices can be addressed separately. But because the triggers commonly used tend to act equally on all the devices that are present, they will need to be localized very tightly. This could be readily achieved with devices that are controlled individually by separate and device-specific reagents. A trigger mechanism that allows such specific control is the reversible binding of DNA strands, thereby 'fuelling' conformational changes in a DNA machine. Here we improve upon the initial prototype system that uses this mechanism but generates by-products, by demonstrating a robust sequence-dependent rotary DNA device operating in a four-step cycle. We show that DNA strands control and fuel our device cycle by inducing the interconversion between two robust topological motifs, paranemic crossover (PX) DNA and its topoisomer JX2 DNA, in which one strand end is rotated relative to the other by 180 degrees. We expect that a wide range of analogous yet distinct rotary devices can be created by changing the control strands and the device sequences to which they bind.     

数控机床补偿误差的激光干涉仪识别技术

提出了基于数控机床的空间误差模型,用激光干涉仪测量机床工作空间中的对角线位移误差来识别机床空间误差的方法,解决了机床垂直轴roll误差的测量难题。结果表明所提出的方法测量精度高,缩短了测量时间,减少了对光学器件的需求量。     

基于Web的虚拟数控系统的研究与开发

基于服务器／客户模式的的虚拟数控系统体系结构，讨论了虚拟数控系统的建模技术和基于VRML的实现方法，并指出虚拟数控机床的建模是虚拟数控加工过程仿真的实现关键．利用VRML语言、分布式对象技术和Java技术开发和建立了基于Web环境的虚拟数控系统原型。并对系统的开发平台进行了分析和介绍，同时给出了系统的运行实例．研究表明，所开发的系统是可行的和合理的．     

高速弧齿锥齿轮弹流润滑特性分析

以某航空发动机高速弧齿锥齿轮为研究对象,在弧齿锥齿轮加载接触分析基础上,建立起适合弹流润滑分析的动态坐标系。用点弹流润滑理论对高速弧齿锥齿轮在啮合过程中的最大油膜压力和最小油膜厚度变化情况进行描述,寻找出载荷、速度和润滑油粘度等因素对轮齿弹流润滑特性的影响规律。     

基于主曲率匹配的五坐标刀位轨迹优化

为了克服传统五轴加工采用固定走刀方向和后跟角的加工方法的不足,提出了一种基于刀具扫描面与曲面主曲率匹配、以行距最大为目标的走刀方向和后跟角的优化算法,实践证明,这种方法能够优化刀位轨迹,提高加工效率。     

Synthesis from DNA of a molecule with the connectivity of a cube

A principal goal of biotechnology is the assembly of novel biomaterials for analytical, industrial and therapeutic purposes. The advent of stable immobile nucleic acid branched junctions makes DNA a good candidate for building frameworks to which proteins or other functional molecules can be attached and thereby juxtaposed. The addition of single-stranded 'sticky' ends to branched DNA molecules converts them into macromolecular valence clusters that can be ligated together. The edges of these frameworks are double-helical DNA, and the vertices correspond to the branch points of junctions. Here, we report the construction from DNA of a covalently closed cube-like molecular complex containing twelve equal-length double-helical edges arranged about eight vertices. Each of the six 'faces' of the object is a single-stranded cyclic molecule, doubly catenated to four neighbouring strands, and each vertex is connected by an edge to three others. Each edge contains a unique restriction site for analytical purposes. This is the first construction of a closed polyhedral object from DNA.     

Multiple dopamine D4 receptor variants in the human population.

The dopamine D4 receptor structurally and pharmacologically resembles the dopamine D2 and D3 receptors. Clozapine, an atypical antipsychotic that is relatively free of the adverse effects of drug-induced parkinsonism and tardive dyskinesia, binds to the D4 receptor with an affinity 10 times higher than to the D2 and D3 receptors. This may explain clozapine's atypical properties. Here we report the existence of at least three polymorphic variations in the coding sequence of the human D4 receptor. A 48-base-pair sequence in the putative third cytoplasmic loop of this receptor exists either as a direct-repeat sequence (D4.2), as a fourfold repeat (D4.4) or as a sevenfold repeat (D4.7). Two more variant alleles were detected in humans. Expression of the complementary DNA for the three cloned receptor variants showed different properties for the long form (D4.7) and the shorter forms (D4.2, D4.4) with respect to clozapine and spiperone binding. To our knowledge, this is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population. Such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to antipsychotic medication.