Variations on a theme: Clifford’s parallelism in elliptic space

In 1873, W. K. Clifford introduced a notion of parallelism in the three-dimensional elliptic space that, quite surprisingly, exhibits almost all properties of Euclidean parallelism in ordinary space. The purpose of this paper is to describe the genesis of this notion in Clifford’s works and to provide a historical analysis of its reception in the investigations of F. Klein, L. Bianchi, G. Fubini, and E. Bortolotti. Special emphasis is placed upon the important role that Clifford’s parallelism played in the development of the theory of connections.     

铸造工艺仿真设计前处理及过程处理应用技术

以应用ProCAST和MAGMAsoft 2款软件为例，针对铸造工艺仿真设计前处理和过程处理每个环节的主要内容与使用方法进行了较为详细地归纳、分析和总结。提出了处理过程的技术路线，并系统地介绍了每项应用内容的操作平台与使用步骤，从而为高效地应用铸造工艺仿真设计提供理论和技术支持。     

Whole genome sequencing as a means to assess pathogenic mutations in medical genetics and cancer

The past decade has seen the emergence of next-generation sequencing (NGS) technologies, which have revolutionized the field of human molecular genetics. With NGS, significant portions of the human genome can now be assessed by direct sequence analysis, highlighting normal and pathological variants of our DNA. Recent advances have also allowed the sequencing of complete genomes, by a method referred to as whole genome sequencing (WGS). In this work, we review the use of WGS in medical genetics, with specific emphasis on the benefits and the disadvantages of this technique for detecting genomic alterations leading to Mendelian human diseases and to cancer.     

ON THE COLLISION DETECTION PROBLEM OF TWO MOVING OBJECTS DESCRIBED BY ALGEBRAIC SETS

In this paper, the collision problem of two moving objects is investigated. The objects are described by two algebraic sets （ellipses or circles in the paper）. The collision problem discussed involves both static and dynamic case. The static case is that each object moves with known velocity. We use nonlinear programming to decide whether the objects collide. The dynamic case is that each object is controlled by a constraint external force which can be regulated online. For the dynamic case, the collision problem can be modelled as a Minmax problem which can be solved by using differential games. If collision occurs, the time and place of the first collision are given. The moving trajectories are provided in the paper.     

Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions

Systematic genetic interaction studies have illuminated many cellular processes. Here we quantitatively examine genetic interactions among 26 Saccharomyces cerevisiae genes conferring resistance to the DNA-damaging agent methyl methanesulfonate (MMS), as determined by chemogenomic fitness profiling of pooled deletion strains. We constructed 650 double-deletion strains, corresponding to all pairings of these 26 deletions. The fitness of single- and double-deletion strains were measured in the presence and absence of MMS. Genetic interactions were defined by combining principles from both statistical and classical genetics. The resulting network predicts that the Mph1 helicase has a role in resolving homologous recombination-derived DNA intermediates that is similar to (but distinct from) that of the Sgs1 helicase. Our results emphasize the utility of small molecules and multifactorial deletion mutants in uncovering functional relationships and pathway order.     

Cellular internalization of proinsulin C-peptide

Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide, we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at 4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action. Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006     

Structure of astacin and implications for activation of astacins and zinc-ligation of collagenases.

Astacin, a digestive zinc-endopeptidase from the crayfish Astacus astacus L., is the prototype for the 'astacin family', which includes mammalian metallo-endopeptidases and developmentally regulated proteins of man, fruitfly, frog and sea urchin. Here we report the X-ray crystal structure of astacin, which reveals a deep active-site cleft, with the zinc at its bottom ligated by three histidines, a water molecule and a more remote tyrosine. The third histidine (His 102) forms part of a consensus sequence, shared not only by the members of the astacin family, but also by otherwise sequentially unrelated proteinases, such as vertebrate collagenases. It may therefore represent the elusive 'third' zinc ligand in these enzymes. The amino terminus of astacin is buried forming an internal salt-bridge with Glu 103, adjacent to His 102. Astacin pro-forms extended at the N terminus, as observed for some 'latent' mammalian astacin homologues, did not exhibit this 'active' conformation, indicating an activation mechanism reminiscent of trypsin-like serine proteinases.     

基于强跟踪滤波器估计的最优融合方法

在分布式雷达数据处理模式中 ,数据融合是获得较精确的目标轨迹的主要环节。为克服卡尔曼滤波器对初始值敏感、鲁棒性差和对机动目标跟踪性能差的缺陷 ,通过利用各传感器的观测数据 ,采用强跟踪滤波器对目标进行跟踪 ,以改善目标状态估计的精度。对判定源于同一目标的状态估计值 ,给出了一种估计状态线进行性组合的最优融合准则。得出了实际数据的实验结果。     

Variation in FTO contributes to childhood obesity and severe adult obesity

We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.