A single positively selected West Nile viral mutation confers increased virogenesis in American crows

West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species.     

Forecasting in the presence of level shifts

This article addresses the problem of forecasting time series that are subject to level shifts. Processes with level shifts possess a nonlinear dependence structure. Using the stochastic permanent breaks (STOPBREAK) model, I model this nonlinearity in a direct and flexible way that avoids imposing a discrete regime structure. I apply this model to the rate of price inflation in the United States, which I show is subject to level shifts. These shifts significantly affect the accuracy of out‐of‐sample forecasts, causing models that assume covariance stationarity to be substantially biased. Models that do not assume covariance stationarity, such as the random walk, are unbiased but lack precision in periods without shifts. I show that the STOPBREAK model outperforms several alternative models in an out‐of‐sample inflation forecasting experiment. Copyright © 2005 John Wiley & Sons, Ltd.     

S45C钢轴向-扭转两阶段载荷下的疲劳寿命预测

针对S45C钢进行了一系列拉压载荷与扭转载荷不同加载顺序疲劳试验,用以考察载荷的改变对损伤和寿命的影响.试验结果表明,先拉压后扭转载荷下失效时的损伤值大于1,先扭转后拉压载荷下失效时的损伤值多数小于1,载荷模式和应力水平共同影响着失效时的损伤值.采用线性损伤律、双线性损伤律、损伤曲线方法和Morrow的非线性损伤律进行了寿命预测.从预测结果的比较看,各模型均具有过于安全的预测趋向.     

S-PPM:韩国质量革新计划

从1995年开始实行的韩国质量革新计划(SinglePPM)运动是为了提高从合作企业纳入的产品质量。此项运动的目标是将包括成品不合格率和区域索赔的交货不合格率减少至10ppm以内或100ppm以下。至今,从韩国政府获得S-PPM认证的企业有1053家。这项质量革新计划不单纯是为提高产品质量,而且也为提高企业的信誉度做贡献。     

燃气流量低频脉动下的火焰结构特征

针对一种可降低天然气高温燃烧过程中NOx生成量的脉动供燃料燃烧技术,研究了一个采用燃气流量脉动燃烧方式的射流扩散火焰。采用纹影和直接摄像手段观察了在燃气流量低频率(10Hz以下)脉动工况下的火焰特征及其变化,分析了火焰长度脉动特征和火焰内部结构的周期发展过程。研究发现:火焰内部结构的周期发展过程包括高速(波峰流量)燃气脉冲冲出、增长、燃气惯性冲出、回吸、低速(波谷流量)和高速燃气脉冲的分离、低速脉冲的增长等阶段。其中低速和高速燃气脉冲的分离是单火焰燃烧不稳定的原因。     

Modelling the long QT syndrome with induced pluripotent stem cells

The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death. Here we report the development of a patient/disease-specific human iPSC line from a patient with type-2 LQTS (which is due to the A614V missense mutation in the KCNH2 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes (the characteristic LQTS phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. We then used the LQTS human iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers and late sodium-channel blockers) the disease phenotype. Our study illustrates the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies.     

Fresnel's laws,ceteris paribus

This article is about structural realism, historical continuity, laws of nature, and ceteris paribus clauses. Fresnel's Laws of optics support Structural Realism because they are a scientific structure that has survived theory change. However, the history of Fresnel's Laws which has been depicted in debates over realism since the 1980s is badly distorted. Specifically, claims that J. C. Maxwell or his followers believed in an ontologically-subsistent electromagnetic field, and gave up the aether, before Einstein's annus mirabilis in 1905 are indefensible. Related claims that Maxwell himself did not believe in a luminiferous aether are also indefensible. This paper corrects the record. In order to trace Fresnel's Laws across significant ontological changes, they must be followed past Einstein into modern physics and nonlinear optics. I develop the philosophical implications of a more accurate history, and analyze Fresnel's Laws' historical trajectory in terms of dynamic ceteris paribus clauses. Structuralists have not embraced ceteris paribus laws, but they continue to point to Fresnel's Laws to resist anti-realist arguments from theory change. Fresnel's Laws fit the standard definition of a ceteris paribus law as a law applicable only in particular circumstances. Realists who appeal to the historical continuity of Fresnel's Laws to combat anti-realists must incorporate ceteris paribus laws into their metaphysics.     

基于行为表示矩阵的行为结构计算机推理

在基于功能-行为-结构(FBS)的机械系统概念设计中,行为结构创新的计算机化推理具有重要意义.它在很大程度上决定了执行机构的数量和执行执行机构的输出运动.为了实现行为结构创新的计算机化推理,首先要定量化行为.从计算机辅助行为结构创新的角度,提出了行为结构创新假设,建立行为在行为集合内的表示方法、行为集合分组规则、行为分组法步骤、分组最优评价规则.并给出了实例分析.     

Mantle compensation of active metamorphic core complexes at Woodlark rift in Papua New Guinea

In many highly extended rifts on the Earth, tectonic removal of the upper crust exhumes mid-crustal rocks, producing metamorphic core complexes. These structures allow the upper continental crust to accommodate tens of kilometres of extension, but it is not clear how the lower crust and underlying mantle respond. Also, despite removal of the upper crust, such core complexes remain both topographically high and in isostatic equilibrium. Because many core complexes in the western United States are underlain by a flat Moho discontinuity, it has been widely assumed that their elevation is supported by flow in the lower crust or by magmatic underplating. These processes should decouple upper-crust extension from that in the mantle. In contrast, here we present seismic observations of metamorphic core complexes of the western Woodlark rift that show the overall crust to be thinned beneath regions of greatest surface extension. These core complexes are actively being exhumed at a rate of 5-10 km Myr(-1), and the thinning of the underlying crust appears to be compensated by mantle rocks of anomalously low density, as indicated by low seismic velocities. We conclude that, at least in this case, the development of metamorphic core complexes and the accommodation of high extension is not purely a crustal phenomenon, but must involve mantle extension.