Computational Design of Novel Allosteric Inhibitors for Plasmodium falciparum DegP

The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated.     

基于"替换法"的汉字加、解密实现技术

文章讨论的基于“替换法”的汉字信息加、解密实现技术,改变了传统的汉字加密结果,使加密后的密文仍是可以识别和再利用的汉字,发送者可以在任何可编辑汉字的通讯设备上发送和接收密文,确保中文信息传输过程中的安全性。加、解密算法实现的代码语言为VFP6.0。     

Optimal inspection and perfect repair

Models are developed for decision making about monitoring andmaintenance of systems whose performance through time is describedby a general stochastic process. The system is monitored andpreventive and corrective maintenance actions are carried outin response to the observed system state. The decision processis simplified by using the maximum process as a decision variable.The models developed generalize age replacement models and othersimple maintenance strategies. The approach can deal with failuresthat prevent the system functioning further, and also failuresthat are defined by regulation or economic considerations. Attentionis restricted to perfect repair and inspection, but the structureprovides the framework for further developments.     

Highly Effective Phenol Hydroxylation over Ti-ZSM-5 Catalyst Prepared Using B-ZSM-5 as Precursor 以B-ZSM-5为母体合成Ti-ZSM-5高效苯酚羟基化催化剂

 以改进方法合成的B-ZSM-5为母体,采用气固相同晶取代法合成了较小晶粒的Ti-ZSM-5分子筛. 考察了样品的物化性能和催化苯酚羟基化性能. 结果表明: 所合成的小晶粒Ti-ZSM-5具有较高的结晶度,尺寸为100~200 nm,且不含锐钛矿型TiO2,对苯酚羟基化反应的催化性能优异.     

Fluorocarbons in the global environment: a review of the important interactions with atmospheric chemistry and physics

Fluorocarbon impact on ozone depletion is reviewed together with the efficacy of the Montreal Protocol in acting to correct the imbalance between stratospheric ozone production and destruction. The Protocol is also helping to reduce global warming: CFCs are shown to be currently the largest fluorocarbon contributors to climate change. Relative contributions to climate change from CFCs and their HFC substitutes are discussed, together with the consequences of control of minor greenhouse gases on an environmental impact which is dominated by carbon dioxide emissions. Both the potencies of the materials for environmental change and their concentrations in the atmosphere are important and are considered here.Trifluoroacetic acid, a minor product of atmospheric decomposition of some HCFCs and HFCs and of the pyrolysis of fluoropolymers, has been shown to be uniformly distributed in seawater to a depth of over 4000 m and so is natural, although the actual source has yet to be identified.The Montreal Protocol is only one example of action to reduce undesirable impact from fluorocarbons. Other, less universal, actions include abatement of fluoroform greenhouse gas emissions from HCFC manufacturing, process changes to eliminate trifluoromethylsulfur pentafluoride emissions from electrochemical fluorination and ceasing manufacture of perfluorooctanyl sulfonate compounds due to their persistence in human tissue.     

Molecular Replacement Studies of Cucurmosin from Cucurbita Moschata:Structure Homology with Trichosanthin

1 INTRODUCTION Many plants contain proteins that are capable of inactivating ribosomes and therefore are called ribosome-inactivating proteins or RIPs[1]. RIPs are RNA N-glycosidases that inactivate ribosomes through a site-specific deadenylation of the large ribosomal RNA[2, 3]. RIPs are also capable of inactivating many nonribosomal nucleic acid substrates and can be considered as polynucleotide: adenosine glycosidases[4～6]. There are two types of RIPs: type I, single chain pr…     

应用置换反应制备高效SERS活性基底研究

利用预处理的铝片和铜片还原硝酸银溶液的方法获得了具有不同表面形貌的银纳米结构.扫描电子显微镜(SEM)图表明反应产物分别为花样和树枝状的银纳米结构.以对羟基苯甲酸(PHBA)作为探针分子,对这种新体系的表面增强拉曼散射(SERS)活性进行了研究,发现该体系是一种非常高效的SERS活性增强基底,并且其SERS活性优于用化学方法制备的银胶.本文对这种新型SERS活性基底的增强机制进行了讨论.     

网络多层语义深度挖掘及流媒体缓存策略研究

对网络音视频数据进行多层次语义的深度挖掘,统计分析用户行为,建立一个流行度预测模型,在此基础上提出智能化的代理缓存替换策略.初步模拟实验表明该策略能提高缓存字节命中率,减短客户端的请求延迟时间.     

对一种可验证无证书环签密方案的攻击

文中对基于双线性对提出的可验证无证书环签密方案的安全性进行了密码分析,指出该方案不能抵抗替换公钥攻击,并给出了一种攻击方法,攻击者利用该攻击可以任意选定一组用户构成一个环对任意选择的消息进行环签密,密文可以顺利通过验证并正确解密,得出该方案是不安全的.