Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration

Age-related macular degeneration (AMD) is a common, late-onset disease with seemingly typical complexity: recurrence ratios for siblings of an affected individual are three- to sixfold higher than in the general population, and family-based analysis has resulted in only modestly significant evidence for linkage. In a case-control study drawn from a US-based population of European descent, we have identified a previously unrecognized common, noncoding variant in CFH, the gene encoding complement factor H, that substantially increases the influence of this locus on AMD, and we have strongly replicated the associations of four other previously reported common alleles in three genes (P values ranging from 10(-6) to 10(-70)). Despite excellent power to detect epistasis, we observed purely additive accumulation of risk from alleles at these genes. We found no differences in association of these loci with major phenotypic categories of advanced AMD. Genotypes at these five common SNPs define a broad spectrum of interindividual disease risk and explain about half of the classical sibling risk of AMD in our study population.     

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.     

宏观面内剪切作用下多尺度裂纹模型的耦合闭合解

裂纹在面内剪切荷载作用下,宏观应力场呈反对称分布,微观应力场将不再具有反对称性,可能是面内拉伸与面内剪切的混合型分布.另外,考虑微观裂纹前还有一个刃型位错区,据此建立起一个多尺度嵌套的裂纹模型,可以描述从原子尺度下的刃型位错区过渡到Ⅰ、Ⅱ复合型微观裂纹,再过渡到Ⅱ型宏观裂纹.材料不同尺度下的损伤,通过约束过渡区相连接,引入尺度变换因子的概念,并利用位移连续性条件与应力场匹配条件,求解出多尺度耦合问题的闭合形式的解.通过数值计算,讨论了材料宏观力学性能对不同尺度下各影响因素的的敏感性.研究结果表明,材料破坏机理非常复杂,与作用荷载、不同尺度下缺陷的几何形状、尺寸及材料性能等因素相关.     

挑战粒子物理学作为通向真理的途径

粒子物理学家倾向于把自然界视为具体化的数学 ;而固体物理学家则认为 ,从超导体和超流体等奇异形态到晶体和金属等常见形态 ,物质的许多形式都不能用基本粒子的相互作用来描述     

投射群环

设R是一个环,G是一个有限群,本文定义了一个R上带因子组f的投射群环RG_f,证明了如果RG_f是R的Galois扩张带由G导出的内Galois群G,使得R的中心C是R的C-直和项,则CG_f是C上中心Galois代数;还将F.R.DeMeyer关于Azumaya投射群代数的刻划推广到投射群环RG_f。