Patterns of somatic mutation in human cancer genomes

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.     

Murder and the Making of English CSI

We study here the reception by their contemporaries of Antoine de Villon's and étienne de Clave's anti-Aristotelian, almost materialistic and atomistic theses, which they intended to support publicly in Paris in 1624, using (al)chemical experiments to this purpose. After surveying the intellectual context which could have then nourished an atomism based upon (al)chemical experiments, we go on to show how these theses, far from having been perceived as prominently atomistic, were condemned by the contemporaries above all because of the theological implications of their provocative anti-Aristotelism. Alchemy itself was not directly implicated in the case of the theses. On the contrary, the theses were perceived as an alien body within the alchemical tradition.     

A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures

We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine affected individuals, including six probands: two with de novo deletions, two who inherited the deletion from an affected parent and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi and Angelman syndrome region, extending 3.95 Mb distally to BP5. A smaller 1.5-Mb deletion has a proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5-Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is probably responsible for the observed seizure phenotype. The BP4-BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is approximately 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes.     

FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.     

The Effect of Instant Messaging Social Media Platform Characteristics on Consumers'Purchase Intention:An Empirical Study of WeChat

With the rapid development of mobile communication equipment, the significant role of social media platforms is realized in social media marketing. To determine the effect of instant messaging social media platform characteristics on consumers’ purchase intention, we collected We Chat user data and designed an empirical model based on the technology acceptance theory. Analysis of 388 qualified surveys revealed significant positive effects of instant messaging social media platform characteristic...     

A functional RNAi screen for regulators of receptor tyrosine kinase and ERK signalling

Receptor tyrosine kinase (RTK) signalling through extracellular-signal-regulated kinases (ERKs) has pivotal roles during metazoan development, underlying processes as diverse as fate determination, differentiation, proliferation, survival, migration and growth. Abnormal RTK/ERK signalling has been extensively documented to contribute to developmental disorders and disease, most notably in oncogenic transformation by mutant RTKs or downstream pathway components such as Ras and Raf. Although the core RTK/ERK signalling cassette has been characterized by decades of research using mammalian cell culture and forward genetic screens in model organisms, signal propagation through this pathway is probably regulated by a larger network of moderate, context-specific proteins. The genes encoding these proteins may not have been discovered through traditional screens owing, in particular, to the requirement for visible phenotypes. To obtain a global view of RTK/ERK signalling, we performed an unbiased, RNA interference (RNAi), genome-wide, high-throughput screen in Drosophila cells using a novel, quantitative, cellular assay monitoring ERK activation. Here we show that ERK pathway output integrates a wide array of conserved cellular processes. Further analysis of selected components-in multiple cell types with different RTK ligands and oncogenic stimuli-validates and classifies 331 pathway regulators. The relevance of these genes is highlighted by our isolation of a Ste20-like kinase and a PPM-family phosphatase that seem to regulate RTK/ERK signalling in vivo and in mammalian cells. Novel regulators that modulate specific pathway outputs may be selective targets for drug discovery.     

铝合金上热沉积氧化铝–二氧化钛涂层的固体颗粒冲蚀研究

Thermal barrier coatings are widely used as surface modifications to enhance the surface properties of the material and protect from surface degradations such as erosion and corrosion. Ceramic-based coatings are highly recommended to increase wear resistance in the industrial sector. In this paper, an alumina–titania ceramic powder was deposited on an aluminum alloy using an atmospheric plasma spray technique. Experimental investigations were performed to study the behavior and erosion rate of the material. Solid particle erosion studies were performed by varying the particle velocity and particle flow rate. The angle impingement and stand-off distance were constant for comparison. The base metal has a clinging effect and the mass change was negative at a maximum particle flow rate of 4 g·min?1. Under the same process conditions, the coated sample had a reduced lifetime and reached a maximum erosion rate of 0.052 (Δg/g). The solid particle erosion studies confirmed that the base metal aluminum alloy had severe surface damage with erodent reinforcement when compared to the coated samples. The influence of the particle velocity, particle flow rate, and input process parameters were also identified.