斯里兰卡的总督列车

卡图那雅克距离斯里兰卡首都科伦坡有几千千米,铁轨一直延伸向天尽头。突然,大地开始颤抖起来,一列蒸汽火车头牵引的红色列车出现在我们面前：这就是路易·蒙巴顿公爵的列车,它像主人的名字一样长。路易·蒙巴顿公爵是大不列颠历史上赫赫有名的英雄之一,他与斯里兰卡的＂姻缘＂要从这列火车说起。     

A Helmholtzian approach to space and time

A slight modification of Helmholtz’s metrical approach to the foundations of geometry leads to the locally Euclidian character of space without restriction of the curvature. A bolder generalization involving time measurement leads to the locally Minkowskian character of spacetime. Some philosophical consequences of these results are drawn.     

Maximum Transfer Distance Between Partitions

In this paper, we study a distance defined over the partitions of a finite set. Given two partitions P and Q, this distance is defined as the minimum number of transfers of an element from one class to another, required to transform P into Q. We recall the algorithm to evaluate this distance and we give some formulae for the maximum distance value between two partitions having exactly or at most p and q classes, for given p and q.     

Supporting Consistency in Linked Specialized Engineering Models Through Bindings and Updating

Currently, some commercial software applications support users to work in an integrated environment. However, this is limited to the suite of models provided by the software vendor and consequently it forces all the parties to use the same software. In contrast, the research described in this paper investigates ways of using standard software applications, which may be specialized for different professional domains. These are linked for effective transfer of information and a binding mechanism is provided to support consistency. The proposed solution was implemented using a CAD application and an independent finite element application in order to verify the theoretical aspects of this work.     

On the necessary truth of the laws of classical mechanics

The idealization of primitive mechanical experience is shown to lead to four mutually related formulations of classical mechanics based on connections, action at a distance, stresses, and collisions. For a given structure of spacetime and a given characterization of mechanical systems, fundamental laws (including Newton's law of acceleration and d’Alembert's principle) are derived from a few general principles regarding the comprehensibility of motion. Special emphasis is placed on the “secular principle,” according to which the evolution of a system at the relevant time scale should not depend on finer details of the applied forces.     

KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron

Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure.     

Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes

Genome-wide association studies have revealed that common noncoding variants in MTNR1B (encoding melatonin receptor 1B, also known as MT(2)) increase type 2 diabetes (T2D) risk(1,2). Although the strongest association signal was highly significant (P < 1 × 10(-20)), its contribution to T2D risk was modest (odds ratio (OR) of ～1.10-1.15)(1-3). We performed large-scale exon resequencing in 7,632 Europeans, including 2,186 individuals with T2D, and identified 40 nonsynonymous variants, including 36 very rare variants (minor allele frequency (MAF) <0.1%), associated with T2D (OR = 3.31, 95% confidence interval (CI) = 1.78-6.18; P = 1.64 × 10(-4)). A four-tiered functional investigation of all 40 mutants revealed that 14 were non-functional and rare (MAF < 1%), and 4 were very rare with complete loss of melatonin binding and signaling capabilities. Among the very rare variants, the partial- or total-loss-of-function variants but not the neutral ones contributed to T2D (OR = 5.67, CI = 2.17-14.82; P = 4.09 × 10(-4)). Genotyping the four complete loss-of-function variants in 11,854 additional individuals revealed their association with T2D risk (8,153 individuals with T2D and 10,100 controls; OR = 3.88, CI = 1.49-10.07; P = 5.37 × 10(-3)). This study establishes a firm functional link between MTNR1B and T2D risk.     

Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma

We performed exome sequencing to detect somatic mutations in protein-coding regions in seven melanoma cell lines and donor-matched germline cells. All melanoma samples had high numbers of somatic mutations, which showed the hallmark of UV-induced DNA repair. Such a hallmark was absent in tumor sample-specific mutations in two metastases derived from the same individual. Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK inhibitors. Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%. Furthermore, missense and nonsense somatic mutations were frequently found in three candidate melanoma genes, FAT4, LRP1B and DSC1.     

基于最优路径的多视场全天自主星图识别

为提高低成本小视场星敏感器在全天自主星图识别模式下的识别成功率,提出一种基于最优路径特征的多视场星敏感器星图识别方法。通过多视场观测星图的星图间识别,得到融合后的星图,设置随机分布在星图中主星邻域内各星的蚁群,以迭代的方法得到遍历各星的最优路径,以路径的几何特征作为与导航星库进行匹配的依据。与现有方法相比,该方法表现出高识别率以及针对位置和亮度噪声良好的鲁棒性。