Identification of Mtb GlmU Uridyltransferase Domain Inhibitors by Ligand-Based and Structure-Based Drug Design Approaches

Targeting enzymes that play a role in the biosynthesis of the bacterial cell wall has long been a strategy for antibacterial discovery. In particular, the cell wall of Mycobacterium tuberculosis (Mtb) is a complex of three layers, one of which is Peptidoglycan, an essential component providing rigidity and strength. UDP-GlcNAc, a precursor for the synthesis of peptidoglycan, is formed by GlmU, a bi-functional enzyme. Inhibiting GlmU Uridyltransferase activity has been proven to be an effective anti-bacterial, but its similarity with human enzymes has been a deterrent to drug development. To develop Mtb selective hits, the Mtb GlmU substrate binding pocket was compared with structurally similar human enzymes to identify selectivity determining factors. Substrate binding pockets and conformational changes upon substrate binding were analyzed and MD simulations with substrates were performed to quantify crucial interactions to develop critical pharmacophore features. Thereafter, two strategies were applied to propose potent and selective bacterial GlmU Uridyltransferase domain inhibitors: (i) optimization of existing inhibitors, and (ii) identification by virtual screening. The binding modes of hits identified from virtual screening and ligand growing approaches were evaluated further for their ability to retain stable contacts within the pocket during 20 ns MD simulations. Hits that are predicted to be more potent than existing inhibitors and selective against human homologues could be of great interest for rejuvenating drug discovery efforts towards targeting the Mtb cell wall for antibacterial discovery.     

Spin Transport in a Rashba Ring-Quantum Dot System Pumped by Microwave Fields

We report a theoretical study on producing electrically spin-polarized current in the Rashba ring with parallel double dots embedded, which are subject to two time-dependent microwave fields. By means of the Keldysh Green's function method, we present an analytic result of the pumped current at adiabatic limit and demonstrate that the interplay between the quantum pumping effectand spin-dependent quantum interference can lead to an arbitrarily controllable spin-polarized current in the device. The magnitude and direction of the charge and spin current can be effectively modulated by system parameters such as the pumping phase difference, Rashba precession phase, and the dynamic phase difference of electron traveling in two arms of ring; moreover, thespin-polarization degree of the charge current can also be tuned in the range [-∞, +∞]. Our findings may shed light on the all-electric way to produce the controllable spin-polarized charge current in the field of spintronics.     

高压静电场促进植物生长技术的研究

高压静电场促进植物生长技术源于自然又高于自然 ,它包括静电种子处理和静电场生长环境等技术 .文章论述了该技术的实施方法 ,并报道了已经取得的初步成果 .     

强激光装置中玻璃疵病在线检测的光学系统设计

介绍了一种用于玻璃疵病在线检测的近摄工作距成像光学系统,其光组结构形式采用了光阑后置的准远心结构形式,主要光学参量为f′=14 mm;在物像距为250 mm约束条件下,物方视场达到90 mm（对角线）;F/number=3.56;光谱适应范围为400~800 nm,对应的空间分辨率为100 lp/mm时,调制传递函数大于0.29.     

扫描环形光斑激光束优化研究

激光束的形状和能量分布限定了激光的应用范围,为满足不同的激光加工需要,必须对激光束进行变换。针对实验室用CO2激光器在热处理方面的应用,提出了激光扫描环形光斑光束优化法。基于温度场叠加原理建立了扫描环形光斑温度场的数学模型,模拟其温度场,可得到其温度分布特性;通过实验研究,分析了聚焦光斑与扫描环形光斑在激光淬火中对材料的热作用效果。结果表明,扫描环形光斑能改善激光热处理硬化层分布。理论和实验研究表明,激光扫描环形光斑技术可以实现激光热处理光束的优化,有一定的应用前景。     

预脉冲对相对论磁控管工作性能的影响分析

在阐述预脉冲产生的基础上,分析了预脉冲带来的一系列影响,包括工和电压波形变化,提前生成等离子体,以及预脉冲阶段放大竞争模式等,这些影响与相对论磁控管起振工作频率相联系,从而直接造成了相对论磁控管的基本性能参数,如脉宽、工作频率及输出功率等变化。结合具体实验,对比了有、无预脉冲条件下相对论磁控管工作性能的差异,对预脉冲的影响因素与相对论磁控管性能之间的联系进行了详细的分析。     

国家治理的家户逻辑：基于田野政治学的分析进路

家户是中国社会的细胞,也是国家治理的基本单元。从历史上看,家户单元以独立的个体家庭的产生为基础,并经由“编户齐民”制度而成熟定型。与其他治理单元不同,家户具有极强的自主性,并从中汲取动能与活力。家户自主性是基于家户自身生存和发展需要而产生的内在能动性,包括意识自主性、目标自主性和行动自主性。中国国家治理的重要特征,不是对家户单元的控制与形塑,而是对家户自主性的认同与调适。家户自主性的产生,主要源于家户单元的自组织特性,包括联结方式的血缘性、个体需求的内生性、组织形态的灵活性以及国家权力的外在性。从历史上看,正是家户单元的自主性治理,为“集家为国”的中国国家治理提供了动力,其不仅创造了灿烂的农业文明,也实现了国家的长治久安。进入近代以后,家户作为国家治理单元的功能不断弱化甚至一度被取代,但其内在价值并未因此消解,反而在改革实践中展现独特魅力与光芒。在推进国家治理体系和治理能力现代化的进程中,应当高度重视家户单元及其蕴含的自主性价值,并赋予其新的时代意义。     

Optimal Conditions for Existence of Vesicles Under Electric Field

Giant vesicles have been of intense interest as the model system for cell membranes. To bring numerous applications of the vesicles into full play, the existence time of the vesicles becomes particularly important. In this work, we explored the existence time of the vesicles in distilled water under four kinds of representative alternative current (AC) electric fields with different energizing time. When the application time of AC electric field reached 1 hour, the existence time of the vesicles reached the maximum value. As the applied electric field time increased, the existence time of the vesicles decreased. Thus, after obtaining the best vesicles on the carbon fiber electrode, disconnecting the external electric field is very necessary. Based on the in situ observation using inverted microscope, the disappearing phenomena of the vesicles were presented. In addition, it is found that vesicles in phosphate buffer solutions (PBSs) can last about 2–3 days when the electric field was applied for 1 hour, which was much longer than that in distilled water.     

Modified null field method for P- and SV-wave scattering from a partially debonded fiber

The modified null field approach to elastic P- and SV-wave scattering (in plane strain) from a partially debonded fiber has been developed. The debonded region on the fiber surface is subjected to traction free boundary conditions, whereas the fiber is assumed to be in welded contact with the host medium elsewhere. Additional null field equations for an elliptical extension of the actual surface of the scatterer are introduced which require additional expansions for the field in the region between the extended mathematical boundary and the actual boundary of the scatterer. The numerical accuracy of the modified null field method has been tested for the case of a perfectly bonded fiber for P- and SV-wave incidence. Scattering cross-section plots are presented for different degrees of debonding.     

Ion beam mixing of α-MoSi2

Abstract

Using molecular dynamics simulation, we study the mixing of an α-MoSi₂ crystal by 1 keV Ar ions. The observed order of magnitude of the mixing is compatible with a spike model of ion beam mixing. The influence of the target surface and of chemical effects are discussed.