低速气流三参数动态测量软件初探

本文采用虚拟仪器概念和技术,构建了三孔探针动态测量系统。该系统集成了高速数据采集、储存及现代数据处理模块,通过该系统可动态显示低马赫数下压气机内部流场的总压、静压、速度矢量等物理参数的变化趋势,并可对动态信号进行时域显示和频域分析。系统还具备自动标定、零漂消除及线性度拟合的功能,实现了流场动态测试技术在线处理与测试同步进行的目的。     

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.     

Analysis of Plant–Plant Interactions Reveals the Presence of Potent Antileukemic Compounds

A method to identify anticancer compounds in plants was proposed based on the hypothesis that these compounds are primarily present in plants to provide them with an ecological advantage over neighboring plants and other competitors. According to this view, identifying plants that contain compounds that inhibit or interfere with the development of other plant species may facilitate the discovery of novel anticancer agents. The method was developed and tested using Magnolia grandiflora, Gynoxys verrucosa, Picradeniopsis oppositifolia, and Hedyosmum racemosum, which are plant species known to possess compounds with cytotoxic activities. Plant extracts were screened for growth inhibitory activity, and then a thin-layer chromatography bioautography assay was conducted. This located the major antileukemic compounds 1, 2, 4, and 5 in the extracts. Once the active compounds were located, they were extracted and purified, and their structures were determined. The growth inhibitory activity of the purified compounds showed a significant correlation with their antileukemic activity. The proposed approach is rapid, inexpensive, and can easily be implemented in areas of the world with high biodiversity but with less access to advanced facilities and biological assays.     

一种新型径向三腔同轴虚阴极振荡器全三维粒子模拟研究

提出了一种新型径向三腔同轴虚阴极振荡器,并进行了数值模拟研究. 研究表明: 这种径向三腔结构在束波转换面进行电场调制,能够大幅提高束波转换效率;同时,由阳极栅网和径向三腔结构构成的谐振装置能有效地抑制模式竞争;另外,由于采用了同轴引出结构,在提高能量引出的同时还能有效吸收漂移管中被利用过的电子,因此这种新型虚阴极振荡器能够获得较高的输出功率. 模拟的电子束电压为400 kV,电流为50 kA,主频为4.5 GHz,峰值功率达到6 GW,平均输出功率为3.1 GW,束波转换效率达到15%. 关键词： 高功率微波 同轴虚阴极振荡器 粒子模拟 束波转换效率     

Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.     

Effect of deuteron density distribution on the deduction of screening potential from the D(d,p)T reaction in Be metals

The D(d,p)T reaction in Be metal environments has been measured to investigate the electron screening effect in metals in an energy region of from 5.5 keV to 10 keV in a center of mass system(CMS)at a temperature of 121 K.The depth distribution of deuteron density in Be metals has an impact on the observed reaction yields.A model of deuteron density distribution in metal has been proposed to obtain the original yields.A screening energy of(116±46)eV has been obtained with the assumed deuteron density distribution model.     

Contribution of Supercritical Fluid Chromatography coupled to High Resolution Mass Spectrometry and UV detections for the analysis of a complex vegetable oil – Application for characterization of a Kniphofia uvaria extract

Lipids are an important and diverse group of naturally occurring organic compounds present in all biological entities. They play many essential roles in the survival of the organisms. Analysis of lipids is extremely complex due to their large variety of chemistries. In this work, we describe an innovative method for the characterization of the lipid composition in a complex and unknown vegetable oil: an extract of Kniphofia uvaria seeds; using Supercritical Fluid Chromatography (SFC) coupled to Atmospheric Pressure Chemical Ionization (APCI), High-Resolution Mass Spectrometry (HRMS) and UV detections. Thanks to the properties of supercritical CO₂ allowing the use of a large number of chromatographic columns, an effective separation for this complex matrix was obtained.     

Global Structure-Acute Toxicity Relationships for Mice Using Structural Parameter Ratios: New Approach to Molecular Design and Screening

Abstract

A method for a preliminary survey of the relationship between molecular structure and performance was described using 1506 random data of structure-acute toxicity for mice (intravenously dosed). The structural patterns of the weakest toxic structures (111) were extracted from the data and the patterns discriminated for 64.2% of the other structures (1395). As for the 826 structures of strongest toxicity, 78.3% were discriminated by these structural patterns. These results were obtained by using structural parameter ratios to describe the structural patterns and the exhaustive elimination process to select the best parameter ratio from many candidates. The results were summarized in the form of a chart which can be used for practical screening for the weakest toxic structures.