Multispecies-compatible antitumor effects of a cross-species small-interfering RNA against mammalian target of rapamycin

Successful development of sequence-specific siRNA (small interfering RNA)-based drugs requires an siRNA design that functions consistently in different organisms. Utilizing the CAPSID program previously developed by our group, we here designed siRNAs against mammalian target of rapamycin (mTOR) that are entirely complementary among various species and investigated their multispecies-compatible gene-silencing properties. The mTOR siRNAs markedly reduced mTOR expression at both the mRNA and protein levels in human, mouse, and monkey cell lines. The reduction in mTOR expression resulted in inactivation of both mTOR complex I and II signaling pathways, as confirmed by reduced phosphorylation of p70S6K (70-kDa ribosomal protein S6 kinase), 4EBP1 (eIF4E-binding protein 1), and AKT, and nuclear accumulation of FOXO1 (forkhead box O1), with consequent cell-cycle arrest, proliferation inhibition, and autophagy activation. Moreover, interfering with mTOR activity in vivo using mTOR small-hairpin RNA-expressing recombinant adeno-associated virus led to significant antitumor effects in xenograft and allograft models. Thus, the present study demonstrates that cross-species siRNA successfully silences its target and readily produces multispecies-compatible phenotypic alterations-antitumor effects in the case of mTOR siRNA. Application of cross-species siRNA should greatly facilitate the development of siRNA-based therapeutic agents.     

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.     

华西雨屏区不同人工植被类型下土壤氮库及其有效性

为了解华西雨屏区人工植被类型对土壤氮库及其有效性的影响,选取华西雨屏区7种典型人工植被类型：橘树（Glycosmis cochinchinensi5）迹地、橘树林地、巨桉（Eucalyptus grandis）林地、玉米（Zeamays）地、香樟（Cinnamonum camphora）林地、柚子（Citrus mnxima）林地和桃树（Pmnnus persica）林地,于2010年7月分别采集土壤根层与根下层原状土样,分析其氮库及有效性。结果表明,华西雨屏区几种典型人工植被类型均表现出较大的氮库特征,但不同人工植被类型间具有较大的差异。相对于其他植被类型,玉米地根层和根下层土壤氮库均相对较小,而橘树、柚子和桃树林地根层土壤氮库相对较大,巨桉、香樟和桃树林地根下层土壤氮库相对较大。然而,玉米地具有较高的根层土壤铵态氮和硝态氮含量,但巨桉林地具有较低的根下层土壤铵态氮和硝态氮含量。这些结果为区域氮素合理利用、土地利用结构调整以及生态环境建设提供了一定理论依据。     

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.     

海上要地防空反导阵地优度排序研究

针对海上要地防空反导作战中发射阵地优度排序问题,结合要地面积较小、各备选阵地自然环境条件差别不大的实际情况,提出一种以各阵地与保卫目标间距离来衡量阵地优度的评价指标体系构建方法。首次将各己方目标的重要度作为对应评价指标的权值,并提出一种基于网页排名(PageRank, PR)算法的评价指标赋权方法。通过算例仿真可得,本文提出的方法能够给出科学、准确的备选阵地优度排序,为解决海上要地防空反导阵地选择问题提供了一种新思路、新方法。     

Bidirectional Feedback Dynamic Particle Filter with Big Data for the Particle Degeneracy Problem

Particle Filter(PF) is a data assimilation method to solve recursive state estimation problem which does not depend on the assumption of Gaussian noise, and is able to be applied for various systems even with non-linear and non-Gaussian noise. However, while applying PF in dynamic systems, PF undergoes particle degeneracy,sample impoverishment, and problems of high computational complexity. Rapidly developing sensing technologies are providing highly convenient availability of real-time big traffic data from the system under study like never before. Moreover, some sensors can even receive control commands to adjust their monitoring parameters. To address these problems, a bidirectional dynamic data-driven improvement framework for PF(B3 DPF) is proposed.The B3 DPF enhances feedback between the simulation model and the big traffic data collected by the sensors,which means the execution strategies(sensor data management, parameters used in the weight computation,resampling) of B3 DPF can be optimized based on the simulation results and the types and dimensions of traffic data injected into B3 DPF can be adjusted dynamically. The first experiment indicates that the B3 DPF overcomes particle degeneracy and sample impoverishment problems and accurately estimates the state at a faster speed than the normal PF. More importantly, the new method has higher accuracy for multidimensional random systems.In the rest of experiments, the proposed framework is applied to estimate the traffic state on a real road network and obtains satisfactory results. More experiments can be designed to validate the universal properties of B3 DPF.     

环境污染时生物种群的控制问题

本文研究一类受环境污染的单种群系统．本文将毒素输入率作为控制变量，研究线性化单种群系统的最小范数控制问题，给出了一个单种群系统最小范数控制元的存在性定理．     

具有等固有频率的系统主振型的统一求法

关于具有等固有频率的系统的主振型问题,初学者多感到困惑难懂;而迄今为止,几乎国内所有的振动专著,对此问题都未从理论上透彻阐述.本文从理论上系统地、透彻地讨论了这一问题,并论证了一个求相应主振型的统一公式.     

警用脉冲防暴水炮实验系统设计

基于现有实验设备，搭建了科学合理的脉冲防暴水炮试验系统，对其它水炮类装备的实验设计起到了指导作用。