Control of obesity inA vy /a mice by 5α-androstan-17-one

Summary Treating VY/WfL-A ^vy /a mice with 5-androstan-17-one, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented the mice from becoming obese. The weight difference between treated and controlA ^vy /a mice was mainly due to a decreased accumulation of triacylglycerol. The compound did not suppress appetite, had no detectable toxicity and did not affect the lipogenesis rates in the liver and carcass. The weight-controlling effect of 5-androstan-17-one inA ^vy /a mice was reversible upon withdrawal of treatment.The authors wish to thank Mr W.R. Gibson and Drs C.G. Culbertson and P.N. Harris for performing the pathological examinations.     

A Proof of the Duality of the DINA Model and the DINO Model

The Deterministic Input Noisy Output “AND” gate (DINA) model and the Deterministic Input Noisy Output “OR” gate (DINO) model are two popular cognitive diagnosis models (CDMs) for educational assessment. They represent different views on how the mastery of cognitive skills and the probability of a correct item response are related. Recently, however, Liu, Xu, and Ying demonstrated that the DINO model and the DINA model share a “dual” relation. This means that one model can be expressed in terms of the other, and which of the two models is fitted to a given data set is essentially irrelevant because the results are identical. In this article, a proof of the duality of the DINA model and the DINO model is presented that is tailored to the form and parameterization of general CDMs that have become the new theoretical standard in cognitively diagnostic modeling.     

创新策略、设计策略与设计特色——以消费性电子产业为例

创新是企业成长的动力,而设计可以视为企业一项整合资源,也是产品开发成功的关键因素。但在企业实际产品研发过程中,设计要如何运作,才能达到企业创新的目标,是值得探讨的议题。在过去的研究中发现企业在产品设计方面,的确有一些具体的作法。但是实证企业在创新策略与设计策略乃至具体呈现设计特色之关联模型的研究却非常有限。本研究综合过去有关创新策略、设计策略以及设计特色之文献,针对新产品研发部门主管进行问卷调查。再以结构方程模式检验理论模式和观察数据的适配度。研究结果发现:创新策略、设计策略以及设计特色之关联理论模式和观察数据适配。企业之创新策略会影响产品设计特色,同时企业之创新策略会透过设计策略而影响产品设计特色,其中设计策略对设计特色而言,既是自变项又是中介变项。企业经营者所面临的挑战,往往是如何更快速地推出迎合消费市场需求之新产品,并且有效获利。本研究为首次针对这些创新设计策略变项所进行的实证研究,后续将再针对产品创新设计的议题进一步深入研讨。     

Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7

Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics.     

因素空间与模糊决策

以汪培庄的因素空间理论为知识表示的框架，对其公理稍加补充之后提出后馈外延的概念；基于反馈外延，建立了一种面向目标的决策方法。     

Localization of VP4 neutralization sites in rotavirus by three-dimensional cryo-electron microscopy

Three-dimensional structures of several spherical viruses have been determined by electron microscopy and X-ray crystallography. We report here the first three-dimensional structure of the complex between an intact virus and Fab fragments of a neutralizing monoclonal antibody. The antibody is against VP4, one of the two outer capsid proteins of rotaviruses. These large icosahedral viruses cause gastroenteritis in children and young animals and account for over a million human deaths annually. VP4 in these viruses has been implicated in several important functions such as cell penetration, haemagglutination, neutralization and virulence. Here we demonstrate that the surface spikes on rotavirus particles are made up of VP4. Antigenic sites are located near the distal ends of the spikes and two Fab fragments bind to each of the sixty spikes. The mass of the spike indicates that it is a dimer of VP4. The bilobed structure at the distal end of the spike may be involved in both the attachment to the cell and in viral penetration. A novel feature in the virus-Fab complex is the structural difference between the two chemically equivalent Fab fragments on each spike, which could be indicative of variations in the Fab elbow angles.     

气液动六杆机构的分组综合法

本文采用分组综合和优化相结合的方法,讨论了以气液压缸作为主动件的平面六杆Stepheson型机构用作函数发生器的综合方法,全部求解过程采用了线性迭加技术,且设计点数不受待定参数的限制。     

地理信息/地理信息空间系统在全球经济应用中的关键问题

地理空间信息系统和遥感技术是全球经济的两大主要技术.其应用者不再限制在科学研究和政府服务中.地理信息系统被广泛应用在以下领域:市场开发、场地选择、零售商业、金融和银行业、房地产业等等.遥感被应用到保险业务、风险管理、精密农业等等.所有这些应用都发生在全球经济的背景下.全球经济的主要趋势在供货连锁管理方面得以体现出来.一些问题很关键,即教育问题、法律问题、政策与安全问题和经济问题.本文将根据高等教育的历史发展和源于供货连锁管理的原则进一步探讨教育问题.     

A high-resolution map of human chromosome 12

Our sequence-tagged site-content map of chromosome 12 is now integrated with the whole-genome fingerprinting effort. It provides accurate and nearly complete bacterial clone coverage of chromosome 12. We propose that this integrated mapping protocol serves as a model for constructing physical maps for entire genomes.     

Genome sequence of enterohaemorrhagic Escherichia coli O157:H7

The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance.