Transferability of tag SNPs in genetic association studies in multiple populations

A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world.     

Evaluating and improving power in whole-genome association studies using fixed marker sets

Emerging technologies make it possible for the first time to genotype hundreds of thousands of SNPs simultaneously, enabling whole-genome association studies. Using empirical genotype data from the International HapMap Project, we evaluate the extent to which the sets of SNPs contained on three whole-genome genotyping arrays capture common SNPs across the genome, and we find that the majority of common SNPs are well captured by these products either directly or through linkage disequilibrium. We explore analytical strategies that use HapMap data to improve power of association studies conducted with these fixed sets of markers and show that limited inclusion of specific haplotype tests in association analysis can increase the fraction of common variants captured by 25-100%. Finally, we introduce a Bayesian approach to association analysis by weighting the likelihood of each statistical test to reflect the number of putative causal alleles to which it is correlated.     

Cardiomyocyte growth and sarcomerogenesis at the intercalated disc

Cardiomyocytes grow during heart maturation or disease-related cardiac remodeling. We present evidence that the intercalated disc (ID) is integral to both longitudinal and lateral growth: increases in width are accommodated by lateral extension of the plicate tread regions and increases in length by sarcomere insertion within the ID. At the margin between myofibril and the folded membrane of the ID lies a transitional junction through which the thin filaments from the last sarcomere run to the ID membrane and it has been suggested that this junction acts as a proto Z-disc for sarcomere addition. In support of this hypothesis, we have investigated the ultrastructure of the ID in mouse hearts from control and dilated cardiomyopathy (DCM) models, the MLP-null and a cardiac-specific β-catenin mutant, cΔex3, as well as in human left ventricle from normal and DCM samples. We find that the ID amplitude can vary tenfold from 0.2 μm up to a maximum of ~2 μm allowing gradual expansion during heart growth. At the greatest amplitude, equivalent to a sarcomere length, A-bands and thick filaments are found within the ID membrane loops together with a Z-disc, which develops at the transitional junction position. Here, also, the tops of the membrane folds, which are rich in αII spectrin, become enlarged and associated with junctional sarcoplasmic reticulum. Systematically larger ID amplitudes are found in DCM samples. Other morphological differences between mouse DCM and normal hearts suggest that sarcomere inclusion is compromised in the diseased hearts.     

How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case

The molecular features that dominate the binding mode of agonists by a broadly tuned olfactory receptor are analyzed through a joint approach combining cell biology, calcium imaging, and molecular modeling. The odorant/receptor affinities, estimated through statistics accrued during molecular dynamics simulations, are in accordance with the experimental ranking. Although in many systems receptors recognize their target through a network of oriented interactions, such as H-bonding, the binding by broadly tuned olfactory receptors is dominated by non-polar terms. We show how such a feature allows chemicals belonging to different chemical families to similarly activate the receptors through compensations of interactions within the binding site.     

Geological and palaeontological context of a Pliocene juvenile hominin at Dikika, Ethiopia

Since 1999, the Dikika Research Project (DRP; initiated by Z.A.) has conducted surveys and excavations in badlands that expose Pliocene and Pleistocene sediments south of the Awash River in Ethiopia, between surrounding hominin localities at Hadar, Gona and the Middle Awash region. Here we report our geological mapping and stratigraphic measurement of the DRP area, and the context of a remarkably well-preserved skeleton of the earliest known juvenile hominin at the Dikika DIK-1 locality. Our mapping of the DRP area permits a complete definition of the hominin-bearing Hadar Formation and provides a cohesive structural and tectonic framework defining its relationships to adjacent strata. Our findings reveal the basin-scale tectonic, depositional and palaeoenvironmental history of the area, as well as a clear taphonomic and palaeontological context for the juvenile hominin. Such data are crucial for understanding the environmental context of human evolution, and can be integrated into larger-scale tectonic and palaeoenvironmental studies. Our basin-scale approach to palaeoenvironments provides a means to elucidate the complex geological history occurring at the scale of temporally and geographically controlled fossil point localities, which occur within the rich tectonic and depositional history of the Awash Valley.     

Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide

The molecular machinery responsible for the generation of transport carriers moving from the Golgi complex to the plasma membrane relies on a tight interplay between proteins and lipids. Among the lipid-binding proteins of this machinery, we previously identified the four-phosphate adaptor protein FAPP2, the pleckstrin homology domain of which binds phosphatidylinositol 4-phosphate and the small GTPase ARF1. FAPP2 also possesses a glycolipid-transfer-protein homology domain. Here we show that human FAPP2 is a glucosylceramide-transfer protein that has a pivotal role in the synthesis of complex glycosphingolipids, key structural and signalling components of the plasma membrane. The requirement for FAPP2 makes the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. Thus, by coupling the synthesis of glycosphingolipids with their export to the cell surface, FAPP2 emerges as crucial in determining the lipid identity and composition of the plasma membrane.     

海上更换压载水约束条件及方案的研究

介绍了控制压载水传播有害水生物的国际动态；论述了海上更换压载水的约束条件及加载临界点在确定更换压载水方案中的应用，提出了确定船舶海上更换压载水方案的基本方法及校验方式，为安全有效地更换载水提供了保障。     

超大型船舶旋回性能的探讨

在操纵模拟器上进行大型船舶模拟试验的基础上，结合本科数学实践和多年的航海经历，分析得出了影响超大型船舶旋回性能的主要因素除船型、船速、吃水差、舵面积外，还有舵角和装载状态。     

船用柴油机操纵系统故障诊断专家系统

结合ＭＡＮ Ｂ＆Ｗ Ｓ６０ＭＣ型船用柴油机操纵系统的控制原理和结构特点，建立基于表格表达形式知识库和推理机，由此构造出故障诊断专家系统。该系统对轮机员进行操纵系统故障判断和处理具有重要的意义。     

稀土化合物对聚丙稀结晶形态与热稳定性的影响

采用ＴＧＡ 研究了稀土化合物对聚丙稀的热稳定作用． 通过电镜观察了经铬酸蚀刻的ＰＰ球晶在不同稀土化合物含量下的变化． 用Ｘ 射线衍射法比较了加入稀土化合物前后ＰＰβ结晶峰及结晶度的变化． 结果表明， 在ｗ （ＰＰ） ／ ｗ （ＲＥＣ） ＝ １００／１－０ ～１００／２－０ 范围内， ＰＰ热稳定性较好． ＲＥＣ对ＰＰ还有一定程度的成核作用