From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance

The ATP binding cassette (ABC) superfamily of membrane transporters is one of the largest protein classes known, and counts numerous proteins involved in the trafficking of biological molecules across cell membranes. The first known human ABC transporter was P-glycoprotein (P-gp), which confers multidrug resistance (MDR) to anticancer drugs. In recent years, we have obtained an increased understanding of the mechanism of action of P-gp as its ATPase activity, substrate specificity and pharmacokinetic interactions have been investigated. This review focuses on the functional characterization of P-gp, as well as other ABC transporters involved in MDR: the family of multidrug-resistance-associated proteins (MRP1-7), and the recently discovered ABC half-transporter MXR (also known as BCRP, ABCP and ABCG2). We describe recent progress in the analysis of protein structure-function relationships, and consider the conceptual problem of defining and identifying substrates and inhibitors of MDR. An in-depth discussion follows of how coupling of nucleotide hydrolysis to substrate transport takes place, and we propose a scheme for the mechanism of P-gp function. Finally, the clinical correlations, both for reversal of MDR in cancer and for drug delivery, are discussed.     

重型平台运输车的电液控制系统设计

重型平台运输车的应用日益广泛 ,为满足不断增长的大型产品部件的生产及采用大型部件施工的需求 ,研制了 130t重型平台运输车 阐述了该车所要求的升降、转向模式 ,采用可编程序控制器 (PLC)开发了各模式的电控液动随动控制系统 ,设计了适合于双驾驶室的电气控制电路 ,并对转向系统做了实验室模拟 为整车控制系统的制造及调试提供了可靠的依据     

植物抗缺铁机理研究进展

植物缺铁是一种世界上普遍发生的现象，本综述了近年来植物抗缺铁研究状况，包括缺铁胁迫下植物的生理反应，抗缺铁机制，并在遗传育种和分子生物学方面介绍了当前的抗缺铁研究现状。     

Primary study of a novel Tc-tricarbonyl cocaine analogue as the potential DAT imaging agent

The convenient preparation of organometallic precursor fac-[99mTc(CO)3 (H2O)3] opens a new route to design new radiopharmaceuticals. Based on this precursor, a new cocaine analogue, Tropyn, is designed and synthesized,and “2 1” mixed-ligands approach is used to prepare a neutral complex [^99mTc(CO)3(Tropyn)I]. Biodistribution in mice and rats proves that it has sufficient brain uptake. Rat regional brain biodistribntion indicates that the complex is highly concentrated in the striatum (ST) with rapid clearance in the cortex (CT) and hippocampus (HP), which make it valuable for further investigation as the potential Second-Generation DAT imaging agent.     

业务流程再造中流程成本分析模型研究

根据作业成本法提出了更为实用的流程成本分析方法和模型，运用该模型可以指导企业进行流程成本分析，为企业再造提供更加详细、精确和动态的流程成本信息．研究结果表明，进行充分的业务流程成本分析，可以减少再造的盲目性，降低实施BPR项目的风险．     

作业成本的投入产出分析

作业成本是管理会计学中的概念,投入产出分析是统计学中的概念。产品在生产过程中不仅直接消耗作业,而且还通过消耗别的产品间接消耗作业从而消耗成本,本文旨在探索如何把作业成本合理客观地分配到产品的投入产出中。     

镁素营养研究进展

概述了近年来在原核生物、酵母及高等植物中有关镁素转运蛋白家族及其基因如CorA、Alrp、AtMGT等的研究进展，并对目前研究较少的逆境胁迫下与镁离子有关信号转导的内容也做了简述，且对今后有关的研究趋势作了进一步展望．     

The ABC transporter structure and mechanism: perspectives on recent research

ATP-binding cassette (ABC) transporters are multidomain integral membrane proteins that utilise the energy of ATP hydrolysis to translocate solutes across cellular membranes in all phyla. ABC transporters form one of the largest of all protein families and are central to many important biomedical phenomena, including resistance of cancers and pathogenic microbes to drugs. Elucidation of the structure and mechanism of ABC transporters is essential to the rational design of agents to control their function. While a wealth of high-resolution structures of ABC proteins have been produced in recent years, many fundamental questions regarding the proteins mechanism remain unanswered. In this review, we examine the recent structural data concerning ABC transporters and related proteins in the light of other experimental and theoretical data, and discuss these data in relation to current ideas concerning the transporters molecular mechanism.Received 29 August 2003; received after revision 19 November 2003; accepted 28 November 2003     

New paradigms of CFTR chloride channel regulation

The Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel controls salt and water transport across epithelial tissues. Alterations in the activity of this ion channel lead to two major human diseases: cystic fibrosis (low CFTR activity) and secretory diarrhea (excessive CFTR activity). The goal of this article is to review recent developments in our understanding of two aspects of CFTR biology: (i) interactions between CFTR domains (intramolecular interactions) that control the gating of this epithelial chloride channel and (ii) interactions between CFTR and other proteins (intermolecular interactions) that couple the activity of this ion channel to additional cellular processes in epithelial cells (e.g. membrane traffic). Clarifying the nature of these interactions may lead to the development of novel strategies for treating diseases that involve the CFTR chloride channel. Received 12 October 1999; accepted 31 December 1999     

纳米中药——中药现代化的新途径

纳米中药是近年来迅速发展起来的前沿科技领域,与传统中药比较有其优势及特色。纳米中药的开发需要多学科的合作与研究,是传统中药走向国际化的方向,具有着广阔的前景。