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.     

数值学报（2003年第12卷）

本书是由英国剑桥大学出版、发行的不定期专题论文集，每年出版一卷，登载数值分析、计算方法及其应用等方面的高水平创造性研究论文或综述报告，论文作者多为当代相关领域的国际性学术带头人。     

作为非物质文化遗产的南涧彝族“跳菜”

本文根据衡量非物质文化遗产的四条标准：具有突出的历史、文化和科学价值；具有展现中华民族文化创造力的典型性和代表性；具有在一定群体中世代传承、活态存在的特点；具有鲜明特色，在当地有较大影响。结合南涧彝族“跳菜”的实际情况进行比照分析，得出了南涧彝族“跳菜”是一种非物质文化遗产的结论。     

The extent of linkage disequilibrium in Arabidopsis thaliana.

Linkage disequilibrium (LD), the nonrandom occurrence of alleles in haplotypes, has long been of interest to population geneticists. Recently, the rapidly increasing availability of genomic polymorphism data has fueled interest in LD as a tool for fine-scale mapping, in particular for human disease loci. The chromosomal extent of LD is crucial in this context, because it determines how dense a map must be for associations to be detected and, conversely, limits how finely loci may be mapped. Arabidopsis thaliana is expected to harbor unusually extensive LD because of its high degree of selfing. Several polymorphism studies have found very strong LD within individual loci, but also evidence of some recombination. Here we investigate the pattern of LD on a genomic scale and show that in global samples, LD decays within approximately 1 cM, or 250 kb. We also show that LD in local populations may be much stronger than that of global populations, presumably as a result of founder events. The combination of a relatively high level of polymorphism and extensive haplotype structure bodes well for developing a genome-wide LD map in A. thaliana.     

Galileo as a ‘bad theologian’: a formative myth about Galileo’s trial

For 150 years after Galileo’s condemnation in 1633, there were many references to the trial, but no sustained, heated or polarized discussions. Then came the thesis that Galileo was condemned not for being a good astronomer but for being a bad theologian (using Scripture to support astronomical hypotheses); it began in 1784–1785 with an apology of the Inquisition by Mallet du Pan in the Mercure de France and the printing in Tiraboschi’s Storia della letteratura italiana of an apocryphal letter attributed to Galileo but forged by Onorato Gaetani. This thesis is not only untenable and false but inverts and subverts the truth; it proved to be long-lasting and widely accepted; so it may be labeled a myth. It was held by such writers as Bergier; Bergier; B; Feller; Cooper; Purcell; Marini; Reumont; Madden and Duhem. Afterwards, it was generally abandoned, its death knell being pope John Paul II’s speeches in 1979–1992. The myth seems to have acted as a catalyst insofar as its creation encouraged the proliferation of pro-clerical accounts and the articulation of pro-Galilean ones, thus making the discussion of Galileo’s trial the cause célèbre it is today.