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81.
Gui Y  Guo G  Huang Y  Hu X  Tang A  Gao S  Wu R  Chen C  Li X  Zhou L  He M  Li Z  Sun X  Jia W  Chen J  Yang S  Zhou F  Zhao X  Wan S  Ye R  Liang C  Liu Z  Huang P  Liu C  Jiang H  Wang Y  Zheng H  Sun L  Liu X  Jiang Z  Feng D  Chen J  Wu S  Zou J  Zhang Z  Yang R  Zhao J  Xu C  Yin W  Guan Z  Ye J  Zhang H  Li J  Kristiansen K  Nickerson ML  Theodorescu D  Li Y  Zhang X  Li S  Wang J  Yang H  Wang J  Cai Z 《Nature genetics》2011,43(9):875-878
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.  相似文献   
82.
Canalization, also known as developmental robustness, describes an organism's ability to produce the same phenotype despite genotypic variations and environmental influences. In Drosophila, Hsp90, the trithorax-group proteins and transposon silencing have been previously implicated in canalization. Despite this, the molecular mechanism underlying canalization remains elusive. Here using a Drosophila eye-outgrowth assay sensitized by the dominant Kr(irregular facets-1)(Kr(If-1)) allele, we show that the Piwi-interacting RNA (piRNA) pathway, but not the short interfering RNA or micro RNA pathway, is involved in canalization. Furthermore, we isolated a protein complex composed of Hsp90, Piwi and Hop, the Hsp70/Hsp90 organizing protein homolog, and we demonstrated the function of this complex in canalization. Our data indicate that Hsp90 and Hop regulate the piRNA pathway through Piwi to mediate canalization. Moreover, they point to epigenetic silencing of the expression of existing genetic variants and the suppression of transposon-induced new genetic variation as two major mechanisms underlying piRNA pathway-mediated canalization.  相似文献   
83.
Important to the function of calpains is temporal and spatial regulation of their proteolytic activity. Here, we demonstrate that cytoplasm-resident calpain 2 cleaves human nuclear topoisomerase I (hTOP1) via Ca2+-activated proteolysis and nucleoplasmic shuttling of proteases. This proteolysis of hTOP1 was induced by either ionomycin-caused Ca2+ influx or addition of Ca2+ in cellular extracts. Ca2+ failed to induce hTOP1 proteolysis in calpain 2-knockdown cells. Moreover, calpain 2 cleaved hTOP1 in vitro. Furthermore, calpain 2 entered the nucleus upon Ca2+ influx, and calpastatin interfered with this process. Calpain 2 cleavage sites were mapped at K158 and K183 of hTOP1. Calpain 2-truncated hTOP1 exhibited greater relaxation activity but remained able to interact with nucleolin and to form cleavable complexes. Interestingly, calpain 2 appears to be involved in ionomycin-induced protection from camptothecin-induced cytotoxicity. Thus, our data suggest that nucleocytoplasmic shuttling may serve as a novel type of regulation for calpain 2-mediated nuclear proteolysis.  相似文献   
84.
Railway transportation plays an important role in modern society. As China's massive railway transportation network continues to grow in total mileage and operation density, the energy consumption of trains becomes a serious concern. For any given route, the geographic characteristics are known a priori, but the parameters(e.g., loading and marshaling) of trains vary from one trip to another. An extensive analysis of the train operation data suggests that the control gear operation of trains is the most important factor that affects the energy consumption. Such an observation determines that the problem of energy-efficient train driving has to be addressed by considering both the geographic information and the trip parameters. However, the problem is difficult to solve due to its high dimension, nonlinearity, complex constraints, and time-varying characteristics. Faced with these difficulties, we propose an energy-efficient train control framework based on a hierarchical ensemble learning approach. Through hierarchical refinement, we learn prediction models of speed and gear. The learned models can be used to derive optimized driving operations under real-time requirements. This study uses random forest and bagging – REPTree as classification algorithm and regression algorithm, respectively. We conduct an extensive study on the potential of bagging, decision trees, random forest, and feature selection to design an effective hierarchical ensemble learning framework. The proposed framework was testified through simulation. The average energy consumption of the proposed method is over 7% lower than that of human drivers.  相似文献   
85.
本文分析了TANGO自动布线软件中的PCB文件和AUTOCAD中的DXF文件的构成及其数据格式,对这两种文件间的转换进行了深入的研究,从而找出了它们之间接口的途径,这种接口的实现成功地解决了工程上电路印制板图纸的标准化问题。最后,笔者用C语言实现了接口软件的设计。  相似文献   
86.
为有效提高10 kV配电系统供电可靠性,确保变电所、线路部分检修或故障时减少线路停电次数、缩小停电范围,笔者结合个人多年的实践工作,针对10 kV配网线路的二次核相进行了阐述.  相似文献   
87.
1. INTroDUCTIONThe emergence of JIT (Just in Time) management tee~gy opens up a recency research field for the jobscheduling and production managemellt. As its farther develOPment, the earnness-tardiness job schedulingproblem becomes a hot research point over y6ars. conference [1] gives a review on job scheduling problem withearnness and tardiness penalties. Reference [2] p~s another scheduling problem for minimizing the rangeof lateness on a single machine, and reference [3] giVes a he…  相似文献   
88.
概述了国内外白炭黑工业的发展现状和应用情况,论述了白炭黑的性质及制备方法.指出了我省白炭黑工业目前存在的问题,并提出了具体的建议.  相似文献   
89.
Ecological compensation is becoming one of key and multidiscipline issues in the field of resources and environmental management. Considering the change relation between gross domestic product (GDP) and ecological capital (EC) based on remote sensing estimation, we construct a new quantitative estimate model for ecological compensation, using county as study unit, and determine standard value so as to evaluate ecological compensation from 2001 to 2004 in Zhejiang Province, China. Spatial differences of the ecological compensation were significant among all the counties or districts. This model fills up the gap in the field of quantitative evaluation of regional ecological compensation and provides a feasible way to reconcile the conflicts among benefits in the economic, social, and ecological sectors.  相似文献   
90.
本文从职务侵占犯罪的概念入手,分析其基本特征与该犯罪行为的主观,客观,主体,客体等四大要素。阐述了此类犯罪的构成,通过与其他相关犯罪的比较,使读者能正确把握此类犯罪。  相似文献   
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