Prediction of the structure of a receptor-protein complex using a binary docking method.

To validate procedures of rational drug design, it is important to develop computational methods that predict binding sites between a protein and a ligand molecule. Many small molecules have been tested using such programs, but examination of protein-protein and peptide-protein interactions has been sparse. We were able to test such applications once the structures of both the maltose-binding protein (MBP) and the ligand-binding domain of the aspartate receptor, which binds MBP, became available. Here we predict the binding site of MBP to its receptor using a 'binary docking' technique in which two MBP octapeptide sequences containing mutations that eliminate maltose chemotaxis are independently docked to the receptor. The peptides in the docked solutions superimpose on their original positions in the structure of MBP and allow the formation of an MBP-receptor complex. The consistency of the computational and biological results supports this approach for predicting protein-protein and peptide-protein interactions.     

Short alanine-based peptides may form 3(10)-helices and not alpha-helices in aqueous solution.

Short alanine peptides, containing 16 or 17 residues, appear to form alpha-helices in aqueous solution. But the main spectroscopic analyses used on helical peptides (circular dichroism and nuclear magnetic resonance) cannot distinguish between an alpha-helix (in which the ith residue is hydrogen-bonded to residue i + 4; ref. 9) and the next most common peptide helix, the 3(10)-helix10 (i-->i + 3 hydrogen-bonding). To address this problem we have designed single and doubly spin-labelled analogues of alanine-based peptides in which the nitroxide spin label forms an unbranched side chain extending from the sulphur atom of a cysteine residue. Here we report the circular dichroism, Fourier-transform infrared and electron-spin resonance spectra of these peptides under helix-forming conditions. The infrared absorbance gives an amide I' band with a frequency that is substantially different from that observed for alpha-helices. The electron-spin resonance spectra of doubly labelled helices show that the ranking of distances between side chains, around a single turn (residues 4-8), is inconsistent with an alpha-helical structure. Our experiments suggest that the more likely peptide geometry is a 3(10)-helix.     

浅议中学数学的高观点研究

本文从培养合格的中学数学技师的角度,论述了运用高观点研究初等数学的重要性,提出了此项研究的内容、途径和方法。     

高压CMOS管工艺的设计、模拟和验证

模拟和验证了一种低成本的，以标准CMOS工艺为基础，无需对原工艺流程进行改动的高压工艺技术。讨论了低压器件中的各种击穿机理，相应提出了高压器件中所做出的改进，列举了该工艺技术中所用的特殊版图；对此工艺的应用性进行了二维的工艺和器件模拟；将模拟结果与实际测试结果进行了比较，验证了这种高压工艺技术的实用性。     

A calcium sensor in the sodium channel modulates cardiac excitability.

Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype.     

Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis.

The fragile-X syndrome is the most frequent inherited form of mental retardation, with an incidence of 1 in 1,500 males. It is characterized by the presence of a fragile site at Xq27.3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis. Its mode of inheritance is unusual for an X-linked trait, with incomplete penetrance in both males and females. Some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms, but penetrance is high in sons and daughters of these carrier women. Genetic and physical mapping of the Xq27-q28 region has confirmed that the disease locus is located at or very near the fragile site. Hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination or a mutation that affects reactivation of an inactive X chromosome during differentiation of female germ cells. To detect such rearrangements, or methylation changes that may reflect a locally inactive X chromosome, we used pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus. The probe Do33 (DXS465) detected abnormal patterns in fragile-X patients, but not in normal controls or in non-expressing male transmitters.     

信息技术与学科教学的整合需要研究型教师

信息技术与学科的有效整合需要教师具备整合的基本能力，并成为研究型教师。指出教师要不断更新信息技术知识和技能，利用现代教学设施，依据教学实践开展研究，从而探索出有效的整合模式。     

计算机基础课教学网站开发和建设方案

文章针对计算机基础所面临的不断变化和持续增长 的需求，提出了计算机基础课教学网站的建设方案，介绍了网站的总体结构和创建网站时所使用的主要工具的方法，以及动态WEB的实现技术。     

Effect of 15(R)-15-methyl-prostaglandin E2 on iron absorption in the rat

Summary The administration of 15(R)-15-methyl prostaglandin E₂ (15(R)-15-M-PGE₂) in vivo significantly diminished the uptake of⁵⁹Fe into blood, spleen, liver, femur and dried intestine of rats, whereas acetylsalicylic acid (ASA) increased the counts significantly. This effect of ASA was counteracted by 15(R)-15-M-PGE₂. It is suggested that prostaglandins (PGs) might play an important role in inhibiting iron absorption at the intestinal level.This work was supported by grant No.6638 from CONICET (Argentina). The technical assistance of Mrs María E. Castro and Norma Rizzo is gratefully acknowleged.     

EVA接枝共聚物的制备、分析和应用

为解决大庆管输原油含蜡量高、高黏易凝、对包括 EVA在内的多种原油流动改进剂的化学感受性较差的问题 ,进行了 EVA- 1接枝聚合物的研制 ,包括十二烷基马来仲酰胺的制备及其作为接枝组分与 EVA- 1的合成 .利用红外光谱仪对十二胺、马来酸酐及其反应产物进行分析的结果表明 :十二胺与马来酸酐反应生成了十二烷基马来仲酰胺 .利用核磁共振波谱仪对 EVA- 1及其接枝产物进行分析的结果表明 :EVA- 1与十二烷基马来仲酰胺的接枝反应确实存在 ,接枝率可以达到 1 8.8% .对 EVA- 1及其接枝产物对大庆原油的降凝、降黏效果进行对比的结果表明 ,EVA- 1接枝产物对大庆原油的处理效果好于 EVA- 1 ,从而为新型高效降凝剂的研制提供了新的思路