Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Summary Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.     

存在成果溢出和投资溢出下的研发组织分析

将溢出分为研发成果的溢出和研发投资的溢出。根据企业在产品竞争阶段和研发阶段是否合作 ,将企业的研发组织分为 6种不同的情况 ,并对其在不同的溢出类型下的均衡结果分别从技术进步、企业利润和社会福利的不同角度进行了比较。     

周期信号的孔径抖动及其去除

孔径抖动是指模数转换器采样周期之间出现的相位抖动 ,是由各时钟周期边沿出现时刻的不确定性导致的。当输入信号频率较高时孔径抖动是模数转换器信噪比下降的一个重要原因。对数据采集系统中的孔径抖动进行了仿真实验 ,介绍了反卷积算法 ,并利用反卷积算法对周期信号的孔径抖动进行了去除。仿真结果表明该方法是有效可行的     

基于资源约束的项目区域风险回应策略选择研究

根据项目区域风险的特点，从资源约束的角度建立项目区域风险回应策略选择模型，并利用动态规划设计出该模型的分步解法，较为全面科学地得出最优方案。最后，用一个算例说明方法的可行性和有效性。     

Subset threshold autoregression

We develop in this paper an efficient way to select the best subset threshold autoregressive model. The proposed method uses a stochastic search idea. Differing from most conventional approaches, our method does not require us to fix the delay or the threshold parameters in advance. By adopting the Markov chain Monte Carlo techniques, we can identify the best subset model from a very large of number of possible models, and at the same time estimate the unknown parameters. A simulation experiment shows that the method is very effective. In its application to the US unemployment rate, the stochastic search method successfully selects lag one as the time delay and five best models from more than 4000 choices. Copyright © 2003 John Wiley & Sons, Ltd.     

Structure of the detoxification catalyst mercuric ion reductase from Bacillus sp. strain RC607

Several hundred million tons of toxic mercurials are dispersed in the biosphere. Microbes can detoxify organo-mercurials and mercury salts through sequential action of two enzymes, organomercury lyase and mercuric ion reductase (MerA). The latter, a homodimer with homology to the FAD-dependent disulphide oxidoreductases, catalyses the reaction NADPH + Hg(II)----NADP+ + H+ + Hg(0), one of the very rare enzymic reactions with metal substrates. Human glutathione reductase serves as a reference molecule for FAD-dependent disulphide reductases and between its primary structure and that of MerA from Tn501 (Pseudomonas), Tn21 (Shigella), p1258 (Staphylococcus) and Bacillus, 25-30% of the residues have been conserved. All MerAs have a C-terminal extension about 15 residues long but have very varied N termini. Although the enzyme from Streptomyces lividans has no addition, from Pseudomonas aeruginosa Tn501 and Bacillus sp. strain RC607 it has one and two copies respectively of a domain of 80-85 residues, highly homologous to MerP, the periplasmic component of proteins encoded by the mer operon. These domains can be proteolytically cleaved off without changing the catalytic efficiency. We report here the crystal structure of MerA from the Gram-positive bacterium Bacillus sp. strain RC607. Analysis of its complexes with nicotinamide dinucleotide substrates and the inhibitor Cd(II) reveals how limited structural changes enable an enzyme to accept as substrate what used to be a dangerous inhibitor. Knowledge of the mode of mercury ligation is a prerequisite for understanding this unique detoxification mechanism.