Human metabolic individuality in biomedical and pharmaceutical research

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.     

Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation

Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia. Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)-H(2)O can occur in the mid-troposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.     

基于联合卡尔曼滤波器的燃料电池传感器故障检测与容错研究

介绍了基于多传感器信息融合技术的联合卡尔曼滤波器的结构和算法,并将此方法运用于燃料电池发动机多传感器的复杂系统中．理论分析与仿真结果表明,该联合卡尔曼滤波器设计合理,其融合算法具有全局最优性,能够有效地对燃料电池发动机传感器的故障进行检测,改善了系统的容错能力和复原能力,提高了系统运行的稳定性．     

星系的生命和呼吸

<正>科学家追踪气体随时间和空间的变化,探寻恒星群出生及死亡的方式。天文学家对宇宙的大部分了解来自他们能够看到的东西,因此,他们的理论总是偏爱明亮的恒星和星系。然而,宇宙中的大部分常规物质都是以昏暗的气体形式存在的。称作星系际介质的气体充满星系间的空间;而环星系介质的气体则环绕在星系附近。这两个区域的气体管控星系诞生、成长和死亡,也详细记录了整个宇宙的     

西北地区人口-经济-水环境质量耦合协调发展研究

基于2005～2014年西北五省人口-经济-水环境质量相关数据,构建耦合协调评价指标体系。运用统计学和GIS方法对近10年来西北地区人口-经济-水耦合协调发展的时空演变进行分析,发现2005～2014年,耦合类别变化情况为勉强耦合-初级耦合-中级耦合,耦合协调度持续上升表明三个子系统之间的协调促进作用增强,系统逐步由无序走向有序;近10年来,西北五省耦合协调度均有不同程度提升,其中青海省提升幅度最大,达到了0.44,陕西省提升幅度为0.044,是五省中提升幅度最小的省区;不论是区域整体还是区域内部各个省份,经济和人口对系统的推动作用均逐步增强,而水环境质量则逐步失去对各区域发展的推动力,表明区域发展的动力逐步由资源转向经济和人口,发展的可持续性增强。     

量子全加法器的修改和算法研究

通过与经典全加器的基本模型进行比较后,讨论了一个改进后的量子平面加法器的基本构型.对其原理、组件和算法进行了研究,比较了本加法器两个主要组件与一般量子加法器的不同.作为应用的例,设计了一个n比特量子全加法器的模型,对其具体运算过程和基本功能进行了说明.     

燃料电池内阻在线测试系统研究

内阻是反应燃料电池性能的重要指标,设计燃料电池内阻在线测试系统具有重要意义.但燃料电池内阻具有明显的非线性和时变特性,一般难以精确测量.为了解决这个问题,本文在对燃料电池内阻进行分析的基础上,结合电化学阻抗谱测试思想,提出了一种改进的燃料电池欧姆内阻在线测试法--交流变频调幅测量法,并基于高性能数字信号处理器设计了测试系统硬件电路和软件,得到了较好的测量效果.     

Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity

The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses. Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular signal transduction and immune defence. Received 27 June 2008; received after revision 25 July 2008; accepted 30 July 2008     

Genome-wide genetic association of complex traits in heterogeneous stock mice

Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.