韩国的全球化和行政改革

本文回顾了1997年经济危机后韩国政府采取的改革方案,并做出结论:与普遍的看法相反,韩国政府的大部分改革方案并不是基于新公共管理系统(NPM)的.NPM倡导的打破常规的概念是要把官僚主义者从政府内部的束缚中解放出来,然而韩国政府的改革目标却指向加强官僚政治的内部控制.另一个结论是:以NPM为导向的改革方案不适合韩国政府,因为韩国缺少成功实施NPM方案所应具备的先决条件,如基于规则的政府和充满活力的市场.本文强调了加强官僚政治外部控制机制的重要性.体制僵化、腐败、生产力低下这样的问题长期困扰韩国政府,这些问题不能通过采用NPM所建议的市场原则来解决.因此,本文的结论是:新统治理论是根除这些问题的更为行之有效的方法.     

Unusually strong lipophilicity of ‘fat’ or ‘super’ amino-acids,including a new reference value for glycine

Summary Lipophilic, steric, electronic, and enzyme resistance characteristics of carboranylalanine, adamantylalanine, neopentylglycine and tert-butylglycine are described. The first 2 amino-acids display lipophilicities 2 orders of magnitude higher than tryptophan.This work was supported by research grants to Prof. R. Schwyzer from the Swiss National Science Foundation.     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

Voltage-sensor activation with a tarantula toxin as cargo

The opening and closing of voltage-activated Na+, Ca2+ and K+ (Kv) channels underlies electrical and chemical signalling throughout biology, yet the structural basis of voltage sensing is unknown. Hanatoxin is a tarantula toxin that inhibits Kv channels by binding to voltage-sensor paddles, crucial helix-turn-helix motifs within the voltage-sensing domains that are composed of S3b and S4 helices. The active surface of the toxin is amphipathic, and related toxins have been shown to partition into membranes, raising the possibility that the toxin is concentrated in the membrane and interacts only weakly and transiently with the voltage sensors. Here we examine the kinetics and state dependence of the toxin-channel interaction and the physical location of the toxin in the membrane. We find that hanatoxin forms a strong and stable complex with the voltage sensors, far outlasting fluctuations of the voltage sensors between resting (closed) conformations at negative voltages and activated (open) conformations at positive voltages. Toxin affinity is reduced by voltage-sensor activation, explaining why the toxin stabilizes the resting conformation. We also find that when hanatoxin partitions into membranes it is localized to an interfacial region, with Trp 30 positioned about 8.5 A from the centre of the bilayer. These results demonstrate that voltage-sensor paddles activate with a toxin as cargo, and suggest that the paddles traverse no more than the outer half of the bilayer during activation.