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Mutations of the BRAF gene in human cancer 总被引:2,自引:0,他引:2
Davies H Bignell GR Cox C Stephens P Edkins S Clegg S Teague J Woffendin H Garnett MJ Bottomley W Davis N Dicks E Ewing R Floyd Y Gray K Hall S Hawes R Hughes J Kosmidou V Menzies A Mould C Parker A Stevens C Watt S Hooper S Wilson R Jayatilake H Gusterson BA Cooper C Shipley J Hargrave D Pritchard-Jones K Maitland N Chenevix-Trench G Riggins GJ Bigner DD Palmieri G Cossu A Flanagan A Nicholson A Ho JW Leung SY Yuen ST Weber BL Seigler HF Darrow TL Paterson H Marais R Marshall CJ Wooster R 《Nature》2002,417(6892):949-954
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. 相似文献
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This paper presents systematically a method for image compression/decompression viawavelet transform.It consists of filter,quantization and Huffman coding etc..Different methodshave been compared.Finally,some suggestions for further studies are proposed.In fact,the paper isa summary of our recent research. 相似文献
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A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis 总被引:1,自引:0,他引:1
Khor CC Chapman SJ Vannberg FO Dunne A Murphy C Ling EY Frodsham AJ Walley AJ Kyrieleis O Khan A Aucan C Segal S Moore CE Knox K Campbell SJ Lienhardt C Scott A Aaby P Sow OY Grignani RT Sillah J Sirugo G Peshu N Williams TN Maitland K Davies RJ Kwiatkowski DP Day NP Yala D Crook DW Marsh K Berkley JA O'Neill LA Hill AV 《Nature genetics》2007,39(4):523-528
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction. 相似文献
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Iterative methods are popular choices in image reconstruction fields due to their capability of recovering object information from incomplete acquisition data.However,the computation process involves frequent uses of forward and backward projections that are computationally expensive.Past research has proved that a forward projector that can produce high quality images is crucial to achieve a good convergence rate.In this paper a high performance iterative reconstruction framework is introduced,where two mo... 相似文献
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Structure of the intact transactivation domain of the human papillomavirus E2 protein 总被引:8,自引:0,他引:8
Antson AA Burns JE Moroz OV Scott DJ Sanders CM Bronstein IB Dodson GG Wilson KS Maitland NJ 《Nature》2000,403(6771):805-809
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