Rational design of inhibitors against LpxA protein of Acinetobacter baumannii using a virtual screening method

BackgroundAcinetobacter baumannii is a highly antimicrobial resistant nosocomial pathogen. Resistance to currently used antibiotics has limited effective drugs against this bacterium. This study aimed to propose a rational inhibitor design against the LpxA protein of A. baumannii using a virtual screening method based on a similar structure of ligands.MethodsIn this study, we targeted LpxA protein, which is involved in the early stage of LPS biosynthesis. In the next step, we used Peptide920 and 1,2- Ethanediol as templates to find similar compounds using Drugbank and Zinc15 webservers, respectively. Subsequently, molecular dynamics (MD) simulations were carried out for LpxA protein and two complexes of ZINC895081 and Macrolactam-1 which represented the highest binding affinity and best conformation. Finally, ADMET properties, water solubility and drug-likeness of the desired compounds were evaluated using SwissADME and DruLiTo softwares.ResultsAccording to considered criteria, Drugbank suggested 5 compunds including Ilomastat, Macrolactam-1, Macrolactam-2, Macimorelin, and Oglufanide. On the other hand, Zinc15 webserver suggested 4 compunds including ZINC895048, ZINC895081, ZINC901061 and ZINC1531008. The result of the HDOCK server and Molegro virtual docker (MVD) showed that Macrolactam-1 and ZINC895081 (Citrate) had the highest docking score. In addition, MD simulations showed that ZINC895081 and Macrolactam-1 ligands have the stable binding to the LpxA protein. According to Lipinski's rule, these two compounds are non-carcinogenic, non-toxic and promising inhibitors against LpxA of A. baumannii.ConclusionIt seems that Macrolactam-1 and ZINC895081 (Citrate) are two valuable promising inhibitors against the LpxA protein of A. baumannii. Further in vitro and in vivo experiments are needed to confirm the capabilities of these proposed compounds against A. baumannii.     

Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study,molecular dynamics,and ADMET profiles

Glycogen synthase kinase-3 beta (GSK-3β) regulates glycogen metabolism and many different cellulars, including apoptosis, signaling, and neural. It is a crucial therapeutic receptor in heart disease, type 2 diabetes, and Alzheimer's. In this study, using computational methods, flavonoid compounds were investigated for potential inhibitors against GSK-3β. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3β receptor constructed by homology modeling. Best binding poses were discovered via in silico molecular docking simulation. We surveyed noncovalent interactions among amino acid residues involved in the active site of the modeled Protein and compounds via molecular docking and molecular dynamics (MD).Moreover, ADMET characteristics of best docking conformers have been investigated. The obtained results revealed that compound 1 containing chromenone moiety with binding energy H-bond ?11.4 kcal/mol inhibited effectively binding pocket of the GSK-3β receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3β receptor remained stable throughout 100 ns MD simulation, and also analysis of ADMET profiles revealed that selected compounds had good drug-likeness and pharmacokinetic properties. Hence, it was suggested that compounds with chromenone scaffold could potentially inhibit GSK-3β. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3β inhibitors.     

The virtual element method for a nonhomogeneous double obstacle problem of Kirchhoff plate

This paper is intended to propose and analyze the lowest order conforming and nonconforming virtual element methods (VEMs) for a nonhomogeneous double obstacle problem in fourth-order variational inequality. We first present an abstract framework for the error analysis of an abstract discrete method. Then, we develop the conforming and fully nonconforming VEMs for the previous problem, with the optimal error estimates obtained by using the previous abstract framework combined with two modified interpolation operators and the related estimates. The discrete problem is solved by the primal–dual active set algorithm and the numerical results are in good agreement with theoretical findings.     

基于LabVIEW和PXI的某装备组合故障诊断系统设计

为了解决某装备电子组合故障诊断过程中诊断效率低的问题,设计并研制了基于LabVIEW软件和PXI总线技术的电子组合故障诊断系统。首先,采用PXI总线技术和多通道转换测试技术,将大量被测参数送到固定的测试点;其次,使用LabVIEW编程语言,将组合的所有被测参数一次性全部获取、储存与显示,并依据技术指标给出故障诊断结果和故障排除方法。实验结果表明,该系统具有数据获取快、测试效率高、故障诊断准等优点;经实践应用证明,该故障诊断系统操作简单、携带方便,是对某型装备电子组合进行测试和诊断的理想工具。     

气液两相流中的声速研究

气液两相流在工业各领域中广泛存在,而声速是描述其声学性质的一个重要参数。本文从流体的体积弹性模量的定义出发,推导了气液两相流中的声速随含气率的变化关系式,即混合流体的Wood声速公式,将其声速的部分计算结果和其他作者的实验数据进行了比较,吻合良好。并通过COMSOL有限元模拟软件得到不同气体分布下圆管谐振腔最低阶模式的共振频率,间接数值模拟研究了含气率对声速的影响。模拟结果与理论计算结果一致,当气液两相流中含气率较低时,声速随含气率的增大急剧减小。本研究结果为确定声速与气液两相流中的含气率间的关系提供了参考依据。     

全息波导显示构型设计(英文)

针对全息波导显示系统中输入光栅、转折光栅和输出光栅的光栅参量不一致,导致系统设计和光栅制作难度增大的问题.对比正常配置和锥形配置下的光栅方程,可得全息波导显示系统中全息光栅具有相同周期需要满足转向光栅60°锥形配置.由此提出波导侧面装有反射镜的三光栅单波导板显示构型,其中三个光栅周期完全相同,输入光栅和转向光栅条纹走向一致.使用光学设计软件CODE V对该构型进行仿真,验证了该构型的可行性.与传统全息波导显示构型相比,侧面反射镜的光路折叠作用使得该构型系统无效显示面积和耦合效率损失减小;三个光栅周期相同且输入光栅和转向光栅条纹走向一致,可以降低系统设计和全息光栅制作难度.该构型可以用于虚拟现实显示或者头戴式显示.     

Dislocation theory as a physical field theory

Dislocations are the elementary carriers in many situations of plastic flow. Since they can be seen, counted and typified, e.g. in the electron microscope, and since their presence changes the state of the (elastoplastic) medium, the dislocations have the status of a physical state quantity. In spite of this a continuum theory of elastoplasticity can be built up which does not use the concept of dislocation. However, disregarding the dislocations implies approximation, and this approximation is not always good, in spite of the smallness of the dislocation diameter (order atomic distance). It is discussed how a field theory of dislocations can be developed which takes full account of the dislocational degrees of freedom.

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Sommario In molte situazioni le dislocazioni sono i portatori puntiformi del flusso plastico. Poiché esse possono essere viste, contate e classificate, per esempio mediante il microscopio elettronico, e poiché la loro presenza cambia lo stato del mezzo (elastoplastico), le dislocazioni svolgono il ruolo di una variabile di stato. Nonostante ciò, si può formulare una teoria dell'elastoplasticità che non usa il concetto di dislocazione. Tuttavia, il trascurare le dislocazioni comporta un'approssimazione, e tale approssimazione non è sempre buona nonostante la piccolezza delle dislocazioni (dell'ordine della distanza interatomica). Si discute come si possasviluppare una teoria di campo delle dislocazione che tenga conto completo del loro grado di mobilità.

     

Estimation of speed of sound in dual-layered media using medical ultrasound image deconvolution

The speed of sound in soft tissues is usually assumed to be 1540 m/s in medical pulse-echo ultrasound imaging systems. When the true speed is different, the mismatch can lead to distortions in the acquired images, and so reduce their clinical value. Previously we reported a new method of sound-speed estimation in the context of image deconvolution. Unlike most other sound-speed estimation methods, this enables the use of unmodified ultrasound machines and a normal scanning pattern. Our approach was validated for largely homogeneous media with single sound speeds. In this article, we demonstrate that sound speeds of dual-layered media can also be estimated through image deconvolution. An ultrasound simulator has been developed for layered media assuming that, for moderate speed differences, the reflection at the interface may be neglected. We have applied our dual-layer algorithm to simulations and in vitro phantoms. The speed of the top layer is estimated by our aforesaid method for homogeneous media. Then, when the layer boundary position is known, a series of deconvolutions are carried out with dual-layered point-spread functions having different lower-layer speeds. The best restoration is selected using a correlation metric. The error level (e.g., a mean error of −9 m/s with a standard deviation of 16 m/s) for in vitro phantoms is found to be not as good as that of our single-speed algorithm, but is comparable to other local speed estimation methods where the data acquisition may not be as simple as in our proposed method.