Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75)

The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity.     

虚拟示波器及其信号源构建

文章以测控系统中虚拟示波器和信号源的构建为例,详细地讨论了虚拟仪器系统的功能特点,并给出了虚拟仪器系统构建所需要的硬件及软件技术。     

我国工业企业技术创新能力研究

技术创新能力是入世后我国工业企业得以持续发展的根本保证。在介绍了我国工业企业技术创新能力的现状的基础上,分析了影响我国工业企业技术创新能力的因素,最后提出了改进建议。     

试论图书馆联盟在信息网格应用中的作用

介绍了信息网格和图书馆联盟的涵义,阐述了网格技术应用过程中的问题,探讨了图书馆联盟在信息网格应用中的作用,指出图书馆联盟作为图书馆际合作组织,在信息网格时代应利用信息网格技术推动图书馆际间资源共享,提高图书馆信息服务质量和能力,促进信息网格的信息连通,使其逐渐成熟。     

新时期我国经济技术开发区发展的形势、方向和任务研究

经济技术开发区作为一种特殊类型经济功能区,在我国改革开放和经济发展过程中发挥着重要作用,同时也存在许多突出问题。在新形势下,来自经济全球化国际大背景和全面建设小康社会国内大环境的双重影响,使得经济技术开发区面临着新的机遇和挑战。立足国内外经济社会发展变化趋势,应进一步明确我国经济技术开发区中长期发展方向和定位,并在此基础上提出“十一五”及今后一段时期面临的重点任务。     

信息战的发展走向和要求

信息战作为现代高技术条件下战争取胜的基础,世界各国都在积极研究和发展。从世界各国信息战的发展动向、中国面临的形势等方面进行了分析,并提出了加强中国信息战的要求和建议。     

基于有序Logistic回归模型的北京高校男生有氧能力

为探索北京高校男生有氧能力的影响因素,通过随机抽样法抽取134名18~25岁北京高校男生,空腹抽静脉血测血液指标,用德国MetaMax 3B系统实时监测气体代谢,通过线性递增方案测得VO2max相对值。基于Spearman相关、有序Logistic回归等分析方法进行分析处理。结果表明：北京高校男生有序Logistic回归方程：Ln{P(Y≤1|x)/1-P(Y≤1|x)}=-2.757-0.067*X1-0.025*X2+0.066*X3+0.018*X4-0.009*X5;Ln{P(Y≤2|x)/1-P(Y≤2|x)}=-0.771-0.067*X1-0.025*X2+0.066*X3+0.018*X4-0.009*X5（X1=体重、X2=心率(heart rate, HR)、X3=每搏输出量(stroke volume, SVI)、X4=心室射血时间(ventricular ejection time, VET)、X5=血红蛋白(hemoglobin, HGB)）。回归方程模型系数综合检验步(step)、块(block)、模型(model)检验的P值均小于0.01;拟合优度检验的-2对数似然值(-2LL)为159.374,Cox&SnellR2为0.331,NagelkerkeR2为0.373;预测等级1准确率为45.5%,等级2准确率为100%,等级3准确率为100%,综合为81.8%,说明Logistic回归模型性能良好。Hosmer和Lemeshow检验预测值与观望值无显著性差异（P>0.05）。可见北京高校男生定量负荷心功能、血液指标与有氧能力的多元Logistic回归模型拟合度较好,且HR、SVI、VET、HGB是有氧运动能力的重要预测因素。     

聚脲甲醛-生物油微胶囊的研制及性能探究

为研究微胶囊对沥青路面微裂纹的愈合效果,首先利用聚脲甲醛(作为微胶囊壁)和生物油(作为微胶囊心)采用原位聚合法制备微胶囊,采用扫描/透射电子显微镜(SEM/TEM)和热重分析(TGA)探究微胶囊的外观形貌和热稳定性;然后将微胶囊用于制备微胶囊/苯乙烯-丁二烯-苯乙烯(Microcapsule/SBS)复合改性沥青,通过动态剪切流变仪(DSR)和离析试验探究微胶囊的掺加对复合改性沥青路面性能的影响;最后通过延度愈合率试验验证微胶囊的愈合效果,并结合宏微观试验分析其愈合机理。结果表明：微胶囊呈现类球状,且表面较为粗糙,增大了与沥青的接触面积。微胶囊的热稳定性较好,其囊壁可承受沥青混合料生产过程中的高温环境。随着微胶囊的添加,复合改性沥青的低温塑性和耐热性均有所改善。此外,复合改性沥青的储能模量和损失模量也有所提升,即微胶囊的添加提升了SBS改性沥青的黏弹性能,这可能是由于添加的微胶囊与SBS和基质沥青具有很好的相容性,且微胶囊均匀分散在沥青内部并嵌入SBS呈现的网状结构中,这也在离析试验和荧光显微试验中得以证实。当微胶囊的掺量为0.4%时,复合改性沥青的愈合率达到最高。     

球形压头的滑动速度对材料微米划痕响应的影响

在恒定的法向载荷下,使用Rockwell C 120°金刚石压头对聚碳酸酯(PC)、熔融石英、紫铜和镁合金AZ31进行微米划痕测试,研究滑动速度对试样划痕响应的影响.压入深度小于压头的球锥转变深度,确保仅有压头顶端的圆球部分与试样接触.结果表明:随着滑动速度的增加,压入深度、残余深度和划痕沟槽的宽度均非线性减小,划痕硬...