Multiple QSAR and molecular modelling for identification of potent human adenovirus inhibitors

This study has investigated docking-based 2D- and 3D-quantitative structure-activity relationships (QSARs) for a range of 53 hydroxybenzamide analogues as anti- Human adenoviruses (HAdVs). The best 3D-QSAR (Schrodinger, LLC, NY, 2020) and 2D-QSAR models were obtained for the training set and were found to be statistically significant, with cross-validated coefficients (q²) of 0.6775 and 0.7875, and coefficients of determination (r²) of 0.8106 and 0.8122, respectively. Our in-silico docking and virtual screening studies revealed significant higher binding affinity of dataset molecule 34 (-141.444 ​kcal/mol) and hit ZINC01088642 (-114.357 ​kcal/mol) with 4PIE protein than the standard drugs. In in-silico ADME/toxicity studies, molecule 34 and proposed hit ZINC01088642 were found safe with good intestinal absorption, aqueous solubility, medium blood–brain barrier (BBB), no eye corrosion, no skin irritancy, and non-mutagenic profiles. Molecular dynamics analysis showed good stability of complex, hit ZINC01088642 with protein, 4PIE over the simulation period of 20 ns. We believe that further experimental, as well as in-vitro investigation, will shed more lights on the identification of ZINC01088642 as a potential human adenovirus agent.     

Targeting tribbles homolog 3 (TRIB3) protein against type 2 diabetes for the identification of potential inhibitors by in silico screening

Tribbles homolog 3 (TRIB3) protein is inhibiting the insulin signaling by directly binding to the Akt/PKB leading to insulin resistance in the pancreas causing type 2 diabetes mellitus. Hence, TRIB3 protein is considered as a possible drug target for the new lead identification against type 2 diabetes. In the present study, the homology model of TRIB3 protein was generated to explore its biochemical function and molecular interactions in the new lead identification. The energy minimization of TRIB3 protein was carried out and evaluated by validation protocols for structure reliability. The druggable binding site of TRIB3 protein was identified for the virtual screening and molecular docking studies. The Asinex-fragments library of 22634 small molecules was docked at TRIB3 active site using the Glide module to identify new chemical entities. A total of 9 molecules were identified as final hits from virtual screening and their potency was ranked using Glide score, Glide energies, and residues interactions. The 6 prioritized lead molecules were further optimized using AutoDock, Prime MM/GBSA, and percentage of human oral absorption for the identification of potential leads. The molecules L2, L5, and L6 are identified as lead inhibitors and are showing consistent interactions with key residues Glu194 and Lys196 of TRIB3 protein. The identified potential leads were analyzed by ADME properties for their drug likeness and HergIC50 values are predicted for the prevention of preclinical failures. The present work sheds light on the identification of the best lead molecules against TRIB3 protein and offers a route to design as novel potential drug candidates for T2DM.     

On the Logical Status of the Virtual Work Law

The law of virtual work (VWL) is probably the first law in the history of mechanics; it is previous to the one on the lever, though not completely distinct from it. Here I will discuss the logical status of VWL, that is whether it is an autonomous principle or a theorem of some sort of mechanics. The problem is complicated by the fact that up to now no universally recognised expression has been accepted for it. From this article the problematical nature of VWL demonstrability is quite clear when the mechanics does not characterise completely the constraints. Italian schools in the XVIII century, even if we do not take Lagrange into consideration, had an important role, both in the development of VWL and in the discussion of its role.     

弹性力学问题的虚边界元-配点法

本文提出虚边界方法,建立了离散化虚边界元-配点法,给出了离散化求系数的积分解析式。本文方法完全避免了边界奇异积分及其复杂耗时的运算,成功地提高了普通边界元法(以下简称边界元法)中边界附近区域内包括边界上解的精度,保留了边界元法的优点并扬弃了其弱点。边界元间接法是本文方法中的一个特例。数值算例表明,程序可靠,节省机时,计算精度较高。     

Variance of the virtual displacement

We show that the affine structure of the 3-dimensional space is deeply enmeshed with the static laws expression. The relevance of tensorial rules for calculus in mechanics is thus enhanced. The virtual work principle is stated precisely but a little twist is given to the usual statements: the tensorial nature of the so-called virtual displacement vector is asserted to be covariant. To cite this article: C. Vallée et al., C. R. Mecanique 332 (2004).

Résumé

Nous montrons que la structure affine de l'espace tridimensionnel est fortement imbriquée avec l'expression des lois de la statique. La pertinence de l'application des règles du calcul tensoriel à la mécanique est ainsi renforcée. Le principe des travaux virtuels est établi précisément avec une seule entorse aux exposés classiques : la nature tensorielle de l'habituel vecteur déplacement virtuel est affirmée covariante. Pour citer cet article : C. Vallée et al., C. R. Mecanique 332 (2004).     

Foam Self-Clarification Phenomenon: An Experimental Investigation

This paper is focused on the capabilities of gas–liquid foams to attenuate acoustic waves. It is postulated that the sound attenuation phenomenon in foams is largely governed by the hydrodynamic resistance of the Plateau-Gibbs channels (PGC) to the flow of liquid through them. It is shown that the addition of solid particles to gas–liquid foams has opposite effects depending on the concentration of the added solid particles. As long as the concentration of the added solid particles is smaller than a certain critical value the sound attenuation coefficient increases and as a result in the sound velocity decreases. However, if the concentration of the added solid particles becomes larger than this critical value the attenuation coefficient decreases and the sound velocity increases. When the concentration of the solid particles reaches some critical value, the particles block the Plateau-Gibbs channels and stop the filtration. As a result the attenuation coefficient of the sound wave decreases while the sound velocity, in such three-phase foams, increases. The point at which the sound wave stops attenuating and its velocity starts to increase is known as the point of self-clarification. Based on this postulate and on the results of our preliminary tests the present study provides a plausible explanation to the above-mentioned contradicting effect, and the self- clarification phenomenon.     

The (S−1,S) inventory model and its counterparts in queueing theory

We explore the relationship between the ($S?1,S$) inventory model and three well-known queueing models: the Erlang loss system, the machine-repair model and a two-node Jackson network. Exploiting this relationship allows us to obtain key performance measures of the ($S?1,S$) model, like the so-called virtual outdating time, the number of items on the shelf in steady state, the long-run rate of unsatisfied demands and the distribution of the empty shelf period.     

基于线上线下结合的无机定性分析实验教学

针对在实验室开设定性分析实验受到的制约,设计并开设了"无机化合物的性质与鉴定"虚拟实验,以作为常规无机定性分析实验的重要补充和扩展。虚拟实验和传统实验一并开设,构成线上线下结合的教学模式,完善知识体系,全面培养学生的无机定性分析能力。     

Sound transmission from stiffened double laminated composite plates

An analytical model is developed to investigate the sound transmission loss from orthogonally rib-stiffened double laminated composite plates structure under a plane sound wave excitation, in which first order shear deformation theory is presented for laminated composite plates. By using the space harmonic approach and virtual work principle, the sound transmission loss is described analytically. The validity and feasibility of the model are verified by comparing the present theoretical predictions with numerical results published previously. The influences of structure geometrical parameters on sound transmission loss are subsequently presented. Through numerical results, it can be concluded that the proposed analytical model is accurate and simple in solving the vibroacoustic behavior of an orthogonally rib-stiffened double laminated composite plates.     

Simple laser vision sensor calibration for surface profiling applications

Due to the relatively large structures in the Oil and Gas industry, original equipment manufacturers (OEMs) have been implementing custom-designed laser vision sensor (LVS) surface profiling systems as part of quality control in their manufacturing processes. The rough manufacturing environment and the continuous movement and misalignment of these custom-designed tools adversely affect the accuracy of laser-based vision surface profiling applications. Accordingly, Oil and Gas businesses have been raising the demand from the OEMs to implement practical and robust LVS calibration techniques prior to running any visual inspections. This effort introduces an LVS calibration technique representing a simplified version of two known calibration techniques, which are commonly implemented to obtain a calibrated LVS system for surface profiling applications. Both calibration techniques are implemented virtually and experimentally to scan simulated and three-dimensional (3D) printed features of known profiles, respectively. Scanned data is transformed from the camera frame to points in the world coordinate system and compared with the input profiles to validate the introduced calibration technique capability against the more complex approach and preliminarily assess the measurement technique for weld profiling applications. Moreover, the sensitivity to stand-off distances is analyzed to illustrate the practicality of the presented technique.