A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

煤层冲击倾向性试验及数值模拟

冲击地压是一种特殊的矿山动力现象,而冲击倾向性是煤岩体发生冲击地压的内在因素和必要条件.对松树镇煤矿主采煤层进行冲击倾向性试验,对冲击能量指数、弹性能量指数和动态破坏时间三个煤层冲击能量指标进行分析,得出煤层无冲击倾向性.但对开采煤层数值模拟,得出深部煤层顶部最大主应力值、顶板下沉较大,需要实施一定的防治措施.这为该矿防治冲击地压提供了科学依据.     

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.     

Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation

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.     

Calcium-induced cleavage of DNA topoisomerase I involves the cytoplasmic-nuclear shuttling of calpain 2

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.     

网格计算及其在图像处理中的应用

介绍网格计算的主要技术特点和优势,并探讨网格计算在图像处理中的应用.网格的并行计算能力有效的提高了超分辨率图像处理算法的计算效率,加快算法的运行时间.     

叶片式混输泵气液两相流及性能的数值分析

利用Fluent计算软件在多重参考坐标系下采用欧拉方法的双流体湍流模型计算螺旋轴流式叶片泵内高含气状态下的三维气液两相流场.通过对泵内绝对流速、叶轮相对流速、静态压力、气液两相分布及其相间滑移速度矢量的分析,探讨了气液两相介质在泵内的流动规律.结果显示离心力的作用使叶轮内液相主要在轮缘附近流动,而气相则聚集在轮毂附近;泵导叶内气液两相分离状况有较明显改善.通过与泵性能实验结果对比,验证了文中方法对气液两相叶片式混输泵计算分析的有效性.     

依托地铁发展整合广州站域公共空间资源

广州地铁的网络化发展正在逐步走向成熟,城市公共空间在"以公交为导向"的城市规划理念(TOD)下,依托地铁发展,有效地整合功能和建立有地域性特征的发展模式是其中的关键环节.文中通过对现状和问题的分析、比较研究,用系统科学的方法,提出以地铁车站为核心、步行系统为联系纽带,形成网络化的站域公共空间体系.     

环境温度对CFL增强RC梁承载能力的影响

对温度场中碳纤维薄板(CFL)增强钢筋混凝土(RC)梁在不同破坏模式下的承载能力进行理论分析.研究结果表明,环境温度的变化对CFL增强RC梁的承载能力有一定程度的影响:(1)当环境温度升高30K时,CFL厚度分别为0.1、0.2、0.3和0.4mm的增强RC梁的开裂载荷分别提高了5.37%、10.46%、15.9%和20.94%;(2)CFL厚度为0.1mm和0.2mm的增强RC梁的破坏模式为CFL拉断,其极限承载力随环境温度的升高呈下降趋势,但降低幅度小于3.5%;(3)CFL厚度为0.3mm和0.4mm的增强RC梁的破坏模式为混凝土压碎,其极限承载力随环境温度的升高呈上升趋势,但升高幅度小于3.5%.     

听觉线索引导大鼠空间定位

运用Morris水迷宫实验模式,研究听觉线索在大鼠进行空间定位时的作用.结果显示:听觉线索引导组和对照组动物在4 d内寻找平台的时间和错误率均显著下降.但与对照组动物相比,听觉线索引导组动物寻找隐藏平台的时间和错误率均较低,2组之间具有显著性差异(P<0.05).对动物的轨迹分析发现,听觉线索引导组和对照组动物在水池边缘区域分配的时间不同,提示2组动物寻找平台所用的策略不同.实验结果提示,大鼠能够利用单独的声音线索进行空间定位.