Somatic mutations affect key pathways in lung adenocarcinoma

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.     

Occurrence and significance of prist-1-ene in kerogen pyrolysates

A SERIES of acylic isoprenoid alkanes, of which pristane and phytane are typical, frequently occurs in crude oils, shales, coals, bitumens and so on. It is generally agreed that the primary source of these compounds is the phytyl side chain of chlorophyll(1,2) although the mechanisms of its incorporation into sediments and its subsequent diagenesis, are not completely understood. At present, little is known about the role of kerogen as a source, or sink, of isoprenoid moieties and we report here that the principal isoprenoid, obtained by the high temperature (600 degrees C) pyrolysis of kerogens has been identified as prist-1-ene.     

Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis.     

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.     

Rare independent mutations in renal salt handling genes contribute to blood pressure variation

The effects of alleles in many genes are believed to contribute to common complex diseases such as hypertension. Whether risk alleles comprise a small number of common variants or many rare independent mutations at trait loci is largely unknown. We screened members of the Framingham Heart Study (FHS) for variation in three genes-SLC12A3 (NCCT), SLC12A1 (NKCC2) and KCNJ1 (ROMK)-causing rare recessive diseases featuring large reductions in blood pressure. Using comparative genomics, genetics and biochemistry, we identified subjects with mutations proven or inferred to be functional. These mutations, all heterozygous and rare, produce clinically significant blood pressure reduction and protect from development of hypertension. Our findings implicate many rare alleles that alter renal salt handling in blood pressure variation in the general population, and identify alleles with health benefit that are nonetheless under purifying selection. These findings have implications for the genetic architecture of hypertension and other common complex traits.     

印刷体藏文识别技术

藏文字符识别是中国的多文种信息处理系统的重要组成部分,本文论述了印刷体藏文识别系统的原理和预处理、识别、后处理过程,分析了文字识别的常用方法及其优缺点和印刷体藏文识别技术,着重分析了印刷体藏文识别中特征提取和分类器设计这两个关键技术,并对藏文识别研究领域今后的研究方向和发展前景提出了自己的看法.     

基于驾驶员眼动分析的事故多发点改造方案评价方法研究

对事故多发点进行改造是减少事故的发生、增强交通安全的重要措施。其中增加标志标线等交通安全设施是常见的改造方式。由于驾驶行为是影响交通安全的重要因素,因此有必要从驾驶员角度对改造效进行评价。研究了某二级公路的事故多发点特点。在现场实验的基础上结合驾驶员眼动注视点的特征分析,分别从驾驶员注视特征、运营速度、改造前后的事故分析,综合评价事故多发点的改造效果。同时分析驾驶员负荷特征,为未来事故多发点的安全改造方案提出可行建议。     

加快推进民族地区城乡公共服务一体化

由于城乡和区域发展不平衡所造成的深层次矛盾突出,民族地区在公共服务领域和其他地区还存在明显的差距。加快推进民族地区城乡公共服务一体化进程,其基本途径是统筹城乡发展,在加快转变经济发展方式中促进城乡一体化,以保障和改善民生为重点,以完善的制度安排和政策体系为保障,加大中央财政在教育、医疗卫生、社会保障、公共基础设施等方面对民族地区的扶持力度,创新社会管理,逐步形成覆盖城乡居民的基本公共服务体系。     

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.     

一种丙烯酸聚合物锅炉水处理药剂性能研究

对一种锅炉水处理药剂的除垢、防垢性能、毒性能等进行了实验。实验得到了该药剂用于防垢时的锅炉原水硬度和用量关系式:y=0.095 1x+0.002 31以及除垢时的用量曲线。实验结果表明:该药剂使用温度广(100~223℃),可钝化锅炉金属,对锅炉蒸汽无污染,可用于食品、药品等对蒸汽品质有特殊要求的工业领域。