Virtual screening of eighteen million compounds against dengue virus: Combined molecular docking and molecular dynamics simulations study

Dengue virus is a major issue of tropical and sub-tropical regions. Dengue virus has been the cause behind the major alarming epidemics in the history with mass causalities from the decades. Unavailability of on-shelf drugs for the prevention of further proliferation of virus inside the human body results in immense number of deaths each year. This issue necessitates the design of novel anti-dengue drug. The protease enzyme pathway is the critical target for drug design due to its significance in the replication, survival and other cellular activities of dengue virus. Therefore, approximately eighteen million compounds from the ZINC database have been virtually screened against nonstructural protein 3 (NS3). The incremental construction algorithm of Glide docking program has been used with its features high throughput virtual screening (HTVS), standard precision (SP), extra precision (XP) and in combination of Prime module, induced fit docking (IFD) approach has also been applied. Five top-ranked compounds were then selected from the IFD results with better predicted binding energies with the catalytic triad residues (His51, Asp75, and Ser135) that may act as potential inhibitors for the underlying target protease enzyme. The top-ranked compounds ZINC95518765, ZINC44921800, ZINC71917414, ZINC39500661, ZINC36681949 have shown the predicted binding energies of −7.55, −7.36, −8.04, −8.41, −9.18 kcal/mol, respectively, forming binding interactions with three catalytically important amino acids. Top-docking poses of compounds are then used in molecular dynamics (MD) simulations. In computational studies, our proposed compounds confirm promising results against all the four serotypes of dengue virus, strengthening the opportunity of these compounds to work as potential on-shelf drugs against dengue virus. Further experimentation on the proposed compounds can result in development of strong inhibitors.     

Adaptive output feedback tracking control of stochastic nonlinear systems with dynamic uncertainties

In this paper, adaptive output feedback tracking control is developed for a class of stochastic nonlinear systems with dynamic uncertainties and unmeasured states. Neural networks are used to approximate the unknown nonlinear functions. K‐filters are designed to estimate the unmeasured states. An available dynamic signal is introduced to dominate the unmodeled dynamics. By combining dynamic surface control technique with backstepping, the condition in which the approximation error is assumed to be bounded is avoided. Using It ô formula and Chebyshev's inequality, it is shown that all signals in the closed‐loop system are bounded in probability, and the error signals are semi‐globally uniformly ultimately bounded in mean square or the sense of four‐moment. Simulation results are provided to illustrate the effectiveness of the proposed approach. Copyright © 2014 John Wiley & Sons, Ltd.     

Utilizing linguistically enhanced keystroke dynamics to predict typist cognition and demographics

Entering information on a computer keyboard is a ubiquitous mode of expression and communication. We investigate whether typing behavior is connected to two factors: the cognitive demands of a given task and the demographic features of the typist. We utilize features based on keystroke dynamics, stylometry, and “language production”, which are novel hybrid features that capture the dynamics of a typists linguistic choices. Our study takes advantage of a large data set (~350 subjects) made up of relatively short samples (~450 characters) of free text. Experiments show that these features can recognize the cognitive demands of task that an unseen typist is engaged in, and can classify his or her demographics with better than chance accuracy. We correctly distinguish High vs. Low cognitively demanding tasks with accuracy up to 72.39%. Detection of non-native speakers of English is achieved with F₁=0.462 over a baseline of 0.166, while detection of female typists reaches F₁=0.524 over a baseline of 0.442. Recognition of left-handed typists achieves F₁=0.223 over a baseline of 0.100. Further analyses reveal that novel relationships exist between language production as manifested through typing behavior, and both cognitive and demographic factors.     

Matrix expression and vaccination control for epidemic dynamics over dynamic networks

This paper investigates epidemic dynamics over dynamic networks via the approach of semi-tensor product of matrices. First, a formal susceptible-infected-susceptible epidemic dynamic model over dynamic networks (SISED-DN) is given. Second, based on a class of determinate co-evolutionary rule, the matrix expressions are established for the dynamics of individual states and network topologies, respectively. Then, all possible final spreading equilibria are obtained for any given initial epidemic state and network topology by the matrix expression. Third, a sufficient and necessary condition of the existence of state feedback vaccination control is presented to make every individual susceptible. The study of illustrative examples shows the effectiveness of our new results.     

数值模拟法在隧道涌水量预测中的应用

隧道涌水量的预测是规划公路、铁路线路很重要的一个环节。随着隧道设计水平、施工技术的提高以及施工机械的进步,采用长大隧道乃至特长大埋深越岭隧道的设计方案越来越多,使隧道涌水量的预测问题变得日益突出和迫切需要解决。以某实际隧道工程为例,提出了运用水文地质数值模拟法计算隧道涌水量的新方法。将该地区的水文地质特征参数与现场监测数据选定后,可得到一种适用于该地区的水文地质地下水模型。通过与传统方法的预测结果比较后,证明了该方法的合理性。     

基于系统动力学的煤矿物联网模型研究设计

采用系统动力学方法研究了煤矿系统中的安全管理与控制问题,找出了煤矿安全管理系统中各要素之间的复杂关系,建立起系统关系网,然后结合物联网技术,构建起一个更加完整的智能矿山管理系统。该研究设计可为煤炭企业管理和科研人员提供一种新的研究思路和设计参考。     

Patchy solution of a Francis–Byrnes–Isidori partial differential equation

The solution to the nonlinear output regulation problem requires one to solve a first‐order partial differential equation, known as the Francis–Byrnes–Isidori equations. In this paper, we propose a method to compute approximate solutions to the Francis–Byrnes–Isidori equations when the zero dynamics of the plant are hyperbolic and the exosystem is two dimensional. With our method, we are able to produce approximations that converge uniformly to the true solution. Our method relies on the periodic nature of two‐dimensional analytic center manifolds. Copyright © 2012 John Wiley & Sons, Ltd.     

基于SD模型的深圳市水资源承载力研究

基于深圳市社会、经济、环境现状,在综合考虑水资源质和量的基础上,采用系统动力学方法建立深圳市水资源承载力模型,并对深圳市水资源承载力进行计算评价,结论是深圳市水资源承栽力普遍小于1。通过对16种方案的计算比较,提出进行产业结构调整、提高污水处理水平、提高节水程度、加强人口控制可以有效地提高深圳市水资源承载力,到2030年,其值能接近于1。     

NUMERICAL STUDY OF HYDRODYNAMICS OF MULTIPLE TANDEM JETS IN CROSS FLOW

The hydrodynamics of a single jet and four tandem jets in a cross flow are simulated by using the Computational Fluid Dynamics (CFD) software Fluent. The realizable model is used to close the Reynolds-Averaged equations. The flow characteristics of the jets, including the jet trajectory, the velocity field and the turbulent kinetic energy are obtained with various jet-to-cross flow velocity ratios in the range of 2.38-17.88. It is shown that a single jet penetrates slightly deeper than the first jet in a jet group at the same , although the difference decreases with the decrease of . It is also found that the way in which the velo-city decays along the centerline of the jet is similar for both a single jet and the first jet in a group, and the speed of the decay increases with the decrease of . The downstream jets in a group are found to behave differently due to the sheltering effect of the first jet in the group. Compared with the first jet, the downstream jets penetrate deeper into the cross flow, and the velocity decays more slowly. The circulation zone between the two upstream jets in the front is stronger than those formed between the downstream jets. The Turbulent Kinetic Energy (TKE) sees a distinct double-peak across the cross-sections close to each nozzle, with low values in the jet core and high values in the shear layers. The double-peak gradually vanishes, as the shear layers of the jet merge further away from the nozzle, where the TKE assumes peaks at the jet centerline.