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.     

PCBN刀具及其在切削加工中的应用

介绍了PCBN刀具材料的物理性能和切削性能，阐述了PCBN刀具在不同切削领域应用的特点．并对其关键技术进行了探讨     

可重构制造系统重组过程中设备选择模型的研究

根据生产任务选择加工设备进行制造资源重组是实现可重构制造系统的关键问题之一，由于设备的选择涉及到多种因素，既有定量指标，又有定性指标，传统的依靠人工经验的方法显得力不从心。本文首先结合实际情况，提出了一套设备选择评价体系，通过对模糊判断矩阵采用最小对数二乘法确定各评价因素的权重系数，针对定性指标和定量指标采用不同的方法确定其性能指标值，通过模糊积分对评判指标进行综合评判，最后进行了实例研究。所提出的方法有效地简化了决策过程，为可重构制造系统设备选择提供了一套行之有效的方法。     

铝合金加工用刀具的使用研究（三）

当前我国各机械加工生产厂家引进国外进口设备及生产线较多，实现引进设备及生产线上刀具的国产化以降低生产成本，成为当前国内整个机械加工领域亟待解决的问题。     

Robust Speed Control of a Low Damped Electromechanical System Based on CRONE Control: Application to a Four Mass Experimental Test Bench

Robust speed control of a low damped electromechanical system with backlash is studied, controlled load angular speed being not measured. The proposed control strategy combines a Luenberger observer (load angular speed and load torque disturbance estimations) and a robust CRONE controller. The observer provides estimation of the load angular speed and of the disturbance torque applied on the load. Through the computation of only three independent parameters (as many as a PID controller), the CRONE controller permits to ensure the robust speed control of the load in spite of plant parametric variations and speed observation errors. The proposed control strategy is applied to a four mass experimental test bench.     

维哈柯汉英多媒体触摸咨询应用系统的研制

本文简要介绍了计算机多媒体技术的发展及其主要产品;介绍了《维哈柯汉英多媒体触摸咨询系统制作工具平台PMJL》的开发过程和主要功能;应用该平台研制了《维哈柯汉英多文种多媒体触摸咨询系统》,并结合其制作过程介绍了各种多媒体资源在应用系统中的逻辑关系、组织处理及合成等方法.     

CLIPS中的面向对象程序设计

面向对象作为一种新的程序设计技术也影响着专家系统的研制开发，本文讨论了面向对象技术与专家系统的联系和特点，描述了专家系统工具ＣＬＩＰＳ中的面向对象程序设计技术。     

MIS新思维软件工具的设计与实现

本文针对目前陈旧的管理软件的设计方法提出了一种新的观点,同时探讨了为实现这种新观点而研制的软件工具的设计方法和实现技巧。     

精密镗削头振动模态的实验研究

通过对国产与进Ｄ的同类型精密镗削头振动模态实验研究，找出了这两种精密镗削头的固有振动频率，给出了它们的各阶动画振型图．从这一侧面解释了国产精密镗削头回转精度偏低的原因。     

Experimental Study on the Milling of a Ti Beta 21S

Ti Beta 21S (Ti-15Mo-2.7Nb-3Al-0.2Si) was devel op ed by TIMET in 1989. It is a metastable beta titanium alloy that offers subs tantial weight reductions over other engineering materials. Compared with common beta Ti alloys, it offers the high specific strength, good cold formability, im proved oxidation resistance, elevated temperature strength, creep resistance, an d thermal stability. Besides the common characters of titanium alloy, such as po or heat diffusivity, low elastic modulus, Ti Beta 21S has ...