Translating molecular discoveries into new therapies for atherosclerosis

Atherosclerosis is characterized by the thickening of the arterial wall and is the primary cause of coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. Clinical trials have confirmed that certain lipoproteins and the renin-angiotensin-aldosterone system are important in the pathogenesis of atherosclerotic cardiovascular disease, and that interventions targeted towards these are beneficial. Furthermore, efforts to understand how risk factors such as high blood pressure, dysregulated blood lipids and diabetes contribute to atherosclerotic disease, as well as to understand the molecular pathogenesis of atherosclerotic plaques, are leading to new targets for therapy.     

Oncogenomics and the development of new cancer therapies

Scientists have sequenced the human genome and identified most of its genes. Now it is time to use these genomic data, and the high-throughput technology developed to generate them, to tackle major health problems such as cancer. To accelerate our understanding of this disease and to produce targeted therapies, further basic mutational and functional genomic information is required. A systematic and coordinated approach, with the results freely available, should speed up progress. This will best be accomplished through an international academic and pharmaceutical oncogenomics initiative.     

Prospects for a vaccine against the hepatitis C virus

The recent discovery of natural immunity to the hepatitis C virus and vaccine efficacy in the chimpanzee challenge model has allowed optimism about the development of at least a partly effective vaccine against this heterogeneous pathogen that is responsible for much of the chronic liver disease around the world. The immune systems of some infected individuals can spontaneously clear the virus, whereas other people need treatment with antivirals that work partly by stimulating humoral and cellular immune responses. Therefore, therapeutic vaccine strategies are also being pursued to improve treatment outcome.     

A genetically humanized mouse model for hepatitis C virus infection

Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mouse cells permissive to HCV entry in vitro, we attempted murine humanization via a genetic approach. Here we show that expression of two human genes is sufficient to allow HCV infection of fully immunocompetent inbred mice. We establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class I for HCV uptake. We demonstrate that HCV can be blocked by passive immunization, as well as showing that a recombinant vaccinia virus vector induces humoral immunity and confers partial protection against heterologous challenge. This system recapitulates a portion of the HCV life cycle in an immunocompetent rodent for the first time, opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing HCV entry inhibitors in vivo.     

新经济下企业人力资源管理的挑战与变革

分析了随着新经济的到来，企业人力资源管理面临的挑战与变革问题。指出企业人力资源管理正经历着前所未有的来自全球一体化、信息网络化、知识经济化、组织扁平化与虚拟化等各种力量的挑战和冲击；与此同时，企业人力资源管理也出现了管理地位战略化、管理理念人本化、管理重心知识化、管理手段科学化、管理模式柔性化等巨大的变革。     

TurboC环境中开发汉字应用软件的方法

用ＴｕｒｂｏＣ开发功能丰富的汉字应用软件一直是人们关注的热点。本文通过对ＰＣ－ＤＯＳ与ＣＣ－ＤＯＳ进行比较，论述了用ＴｕｒｂｏＣ实现汉字输入、显示、打印的原理及过程，给出Ｔｕｒ－ｂｏＣ源程序，从而使ＴｕｒｂｏＣ渗透到汉字处理领域。     

浅谈旧城改建和新区开发协同发展

面对城市的快速发展,很多城市存在着旧城改建和新区开发的矛盾,影响了城市的健康发展。文章从旧城改建和新区开发存在的问题出发,阐述了在旧城改建与新区开发时应协调发展的观点,对促进城市整体、健康、协调发展具有积极作用。     

我国民营企业的特点及发展新思路

在改革开放的历程中，我国的民营企业已取得长足的发展，成为中国经济发展的重要推动力．近年来，民营企业快速稳定地发展，但各地区的发展不均衡．民营企业的发展规模日趋扩大，进入了更多的产业领域．特别是民营科技企业近年来得到高速发展，公司制已成为民营企业的主要组成形式．民营企业在今后的发展中要加强自身的文化建设，培育企业的核心竞争力．在我国加入WTO、经济对外开放的同时，应继续扩大对内开放，为民营企业的发展创造公平的竞争环境，拓展民营企业的融资渠道．要大力扶持优势民营企业，增强其国际竞争力．     

我国民营企业的特点及发展新思路

在改革开放的历程中,我国的民营企业已取得长足的发展,成为中国经济发展的重要推动力近年来,民营企业快速稳定地发展,但各地区的发展不均衡.民营企业的发展规模日趋扩大,进入了更多的产业领域.特别是民营科技企业近年来得到高速发展,公司制已成为民营企业的主要组成形式.民营企业在今后的发展中要加强自身的文化建设,培育企业的核心竞争力在我国加入WTO、经济对外开放的同时,应继续扩大对内开放,为民营企业的发展创造公平的竞争环境,拓展民营企业的融资渠道.要大力扶持优势民营企业,增强其国际竞争力.     

地基处理新技术及发展趋势

阐述了目前地基处理的现状与最新发展动态,介绍了地基处理的新方法、新工艺,并提出了地基处理技术方法的研究方向与发展趋势。     

Adaptive immune responses in acute and chronic hepatitis C virus infection

The hepatitis C virus (HCV) persists in the majority of infected individuals and is a significant cause of human illness and death globally. Recent studies have yielded important insights into immunity to HCV, in particular revealing the central role of T cells in viral control and clearance. Other key features of adaptive immune responses remain obscure, including mechanisms by which T cells control HCV replication, the role of antibodies in conferring protection and how cellular and humoral immunity are subverted in persistent infection.     

Mechanism of action of interferon and ribavirin in treatment of hepatitis C

Since the identification of the hepatitis C virus, great strides have been made in the development of an antiviral therapy. As a crucial mediator of the innate antiviral immune response, interferon-alpha (IFN-alpha) was a natural choice for treatment. Whereas treatment with IFN-alpha alone achieved only modest success, the addition of the broad-spectrum antiviral agent ribavirin greatly improved responses. However, half of the infected individuals with chronic disease do not achieve sustained clearance of hepatitis C virus. To optimize current therapeutic strategies and to develop new therapies, a better understanding of the mechanism of action of IFN and ribavirin will be essential.     

培育城市楼宇经济,寻找新的经济增长点

楼宇经济是近几年在城市建设和发展中出现的新名词，是集约利用资源、内涵扩张的一种具体形式。它不但是当代城市经济发展的一大特色，更是现代化城市在新世纪的一种生存状态，其经济能量和重要作用正日益凸现。结合新余实际情况，对新余市发展楼宇经济的意义和对策进行了探讨。     

Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry

Hepatitis C virus (HCV) is a leading cause of cirrhosis and liver cancer worldwide. A better understanding of the viral life cycle, including the mechanisms of entry into host cells, is needed to identify novel therapeutic targets. Although HCV entry requires the CD81 co-receptor, and other host molecules have been implicated, at least one factor critical to this process remains unknown (reviewed in refs 1-3). Using an iterative expression cloning approach we identified claudin-1 (CLDN1), a tight junction component that is highly expressed in the liver, as essential for HCV entry. CLDN1 is required for HCV infection of human hepatoma cell lines and is the first factor to confer susceptibility to HCV when ectopically expressed in non-hepatic cells. Discrete residues within the first extracellular loop (EL1) of CLDN1, but not protein interaction motifs in intracellular domains, are critical for HCV entry. Moreover, antibodies directed against an epitope inserted in the CLDN1 EL1 block HCV infection. The kinetics of this inhibition indicate that CLDN1 acts late in the entry process, after virus binding and interaction with the HCV co-receptor CD81. With CLDN1 we have identified a novel key factor for HCV entry and a new target for antiviral drug development.     

三维超声成像的新技术及发展趋势

三维超声成像是利用超声检测原理无损地显示人体内部形态结构的三维体积成像技术，具有操作安全、使用灵活、形象直观、信息量大以及应用前景广阔等优点，近年来得到较快发展。本文从三维数据的采集技术、三维成像的图象处理技术、三维图象显示技术、专用三维成像处理系统以及其它创新方面分析了三维超声成像的新技术及发展趋势。     

马钢“十一五”新区总图设计探析

马钢“十一五”新区,是一个年产550万t钢规模的系统工程,文章简述了厂址概况,回顾了总图布置方案的优化过程,阐述了总图运输设计的技术特点。     

WTO:外语教改的机遇与挑战

中国加入世界贸易组织为高等院校的外语教学带来了新的机遇和挑战，我们要充分运用外语市场价值的调节机制，改革外语专业课程设置，调动教师“入世”的积极性，努力培养面向21世纪的复合型外语人才。     

网络信息时代个人隐私面临的挑战与对策

计算机技术给人们的工作环境带来了质的变化，而这种高效便捷工作环境的获得是以人们丧失部分个人隐私权为代价的。从隐私权的概念出发，首先分析了计算机网络技术的发展给个人隐私权带来的一系列冲突问题，然后讨论了网络环境下对隐私权的保护措施和对策。     

Modelling how ribavirin improves interferon response rates in hepatitis C virus infection

Nearly 200 million individuals worldwide are currently infected with hepatitis C virus (HCV). Combination therapy with pegylated interferon and ribavirin, the latest treatment for HCV infection, elicits long-term responses in only about 50% of patients treated. No effective alternative treatments exist for non-responders. Consequently, significant efforts are continuing to maximize response to combination therapy. However, rational therapy optimization is precluded by the poor understanding of the mechanism(s) of ribavirin action against HCV. Ribavirin alone induces either a transient early decline or no decrease in HCV viral load, but in combination with interferon it significantly improves long-term response rates. Here we present a model of HCV dynamics in which, on the basis of growing evidence, we assume that ribavirin decreases HCV infectivity in an infected individual in a dose-dependent manner. The model quantitatively predicts long-term response rates to interferon monotherapy and combination therapy, fits observed patterns of HCV RNA decline in patients undergoing therapy, reconciles conflicting observations of the influence of ribavirin on HCV RNA decline, provides key insights into the mechanism of ribavirin action against HCV, and establishes a framework for rational therapy optimization.     

Challenges and Opportunities in Algorithmic Solutions for Re-Balancing in Bike Sharing Systems

In recent years,the booming of the Bike Sharing System (BSS) has played an important role in offering a convenient means of public transport.The BSS is also vie...