Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.     

Genome-wide detection and characterization of positive selection in human populations

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.     

塔里木河流域中下游典型地物光谱变化规律

由于塔里木河流域中下游距离河道在垂直向的差别,以及气候与人为因素的影响,使植被的空间分布具有异构性.典型地物光谱变化的研究为中下游生态环境的遥感监测提供了基础,实验研究表明:绿色全荣植物中,棉花由于其具有明显绿峰、水分吸收谷和近红外的高反射峰而更加容易识别,其他植物主要差别则集中在550,680,1420 nm附近的反射峰、吸收谷和1920～2500 nm之间的反射率;与绿色植被相比,枯枝的光谱在可见光部分的绿峰和红光吸收谷不明显,但在可见光部分波形有所差别,而与流沙土壤光谱相比,各波段反射率变化较大;对比不同荣枯比例的植物光谱发现,同一种植物随着荣枯配比的变化,除可见光绿峰、近红外反射峰和各水分吸收谷变化外,最明显的是在近红外1420～1820 nm之间和短波红外1920～2500 nm之间反射率随着枯枝的比例增加而明显升高;关于土壤光谱,中下游各断面占主要类型的流沙土光谱相差不大,但是盐碱土和含有一定水分的盐碱土则变化较大,而且反射率基本低于流沙土,结壳土则除在近红外和短波红外部分变化更加平缓而有所差别外,其余波段接近流沙土;同样的土壤背景下,近红外和短波红外部分反射率的差别能够在一定程度上反映覆盖度的变化.     

基于真实三维结构的玉米冠层生化参数垂直分布的定量化分析

为了定量研究作物生化参数在冠层中的垂直分布情况,本文以2000年栾城实验测量的玉米冠层自上而下不同叶位叶片的光谱数据为基础,利用PROSPECT模型进行反演,获得每层叶片的叶绿素(a b)含量、等效水厚度、干物质含量等叶片的生化参数.通过比较发现:玉米冠层叶绿素等含量生化参数具有明显的随高度垂直分层现象,最明显的就是叶片的叶绿素含量,最大和最小叶绿素含量的相对差值甚至可以达到最大值的79.1%.在此基础上,根据实测玉米冠层结构,利用扩展L系统生成玉米真实三维结构冠层场景.通过统计计算每层叶片的生化参数,进而得到冠层生化参数的垂直分布.这为进一步基于冠层光谱的参数反演和定量分析以及农业应用等研究奠定了理论基础.     

基于GIS的地震火灾动态蔓延模拟

用惠更斯原理对震后火灾的动态蔓延过程进行了模拟,并开发了基于GIS的城市地震次生火灾动态蔓延模拟系统,该系统可以模拟单个 或者多个起火点的动态蔓延过程。研究结果可以定量地估计地震次生火灾对城市的危害,从而在最短时间内给救灾应急提供决策依据。     

大型板装配拼接节点试验研究

提出了装配整体式钢筋混凝土大型板一种新的横向拼接节点构造,对9根新型横向连接预制板试件进行试验研究与承载力分析,量测并分析试件的荷载、挠度及应变,观测试件的裂缝发展情况和破坏过程.试件的破坏形态包括弯曲破坏、受剪破坏及轴向拉伸破坏等形式.试验表明,该新型横向连接节点连接可靠,具有良好的承载能力和延性.对新型横向连接节点...     

低矮房屋标准模型的风洞试验研究

以国际通用的低矮建筑标准模型TIU（德州理工大学）模型为研究对象进行风洞试验,寻求适合于低矮房屋风洞试验的风场以及与风洞试验段相匹配的模型缩尺比.首先进行了1:15、1:30和1:45三种缩尺模型的风洞试验,分析了模型尺寸变化对平均、脉动风压系数和堵塞特征的影响,进而在3种不同湍流度分布的B类风场中对1:30缩尺比的模...     

不旋转钢丝绳直线受拉下的物理建模及力学分析

基于微分几何学、弹性力学相关理论,建立了不旋转钢丝绳直线状态受拉力作用下的物理模型,推导了该状态下的受力方程;根据空间螺旋线方程,在三维CAD软件ProE中建立了不旋转钢丝绳的实体模型,并把该实体模型导入ANSYS中进行力学分析,对该模型的正确性进行验证.模型计算结果与有限元分析结果基本一致,验证了该模型的正确性.