Role of Vertex Index in Substructure Identification and Activity Prediction: A Study on Antitubercular Activity of a Series of Acid Alkyl Ester Derivatives

Tuberculosis (TB) is a life threatening disease caused due to infection from Mycobacterium tuberculosis (Mtb). That most of the TB strains have become resistant to various existing drugs, development of effective novel drug candidates to combat this disease is a need of the day. In spite of intensive research world-wide, the success rate of discovering a new anti-TB drug is very poor. Therefore, novel drug discovery methods have to be tried. We have used a rule based computational method that utilizes a vertex index, named `distance exponent index (D-x)' (taken x = -4 here) for predicting anti-TB activity of a series of acid alkyl ester derivatives. The method is meant to identify activity related substructures from a series a compounds and predict activity of a compound on that basis. The high degree of successful prediction in the present study suggests that the said method may be useful in discovering effective anti-TB compound. It is also apparent that substructural approaches may be leveraged for wide purposes in computer-aided drug design.

Computational Study of the Formation of Short Centrosymmetric N-center dot center dot center dot S Supramolecular Synthon and Related Weak Interactions in Crystalline 1,2,4-Triazoles

A comprehensive analysis of the crystal packing and the energetic features of a series of four biologically active molecules belonging to the family of substituted 4-(benzylideneamino)-3-(4-fluoro-3-phenoxyphenyl)-1H-1,2,4-triazole-5-(4 H)-thione derivatives have been performed based on the molecular conformation and the supramolecular packing. This involves the formation of a short centrosymmetric R-2(2)(8) NH...S supramolecular synthon in the solid state, including the presence of CH...S, CH...O, CH...N, CH...F, CH...Cl, CF...FC, CCl...ClC, and CH...pi intermolecular interactions along with pp stacking to evaluate the role of noncovalent interactions in the crystal. The presence of such synthons has a substantial contribution toward the interaction energy (-18 to -20 kcal/mol) as obtained from the PIXEL calculation, wherein the Coulombic and polarization contribution are more significant than the dispersion contribution. The geometrical characteristics of such synthons favor short distance, and the population of related molecules having these geometries is rare as has been obtained from the Cambridge Structural Database (CSD). Furthermore, their interaction energies have been compared with those present in our molecules in the solid state. The topological characteristics of the NH...S supramolecular synthon, in addition to related weak interactions, CH...N, CH...Cl, CF...FC, and CCl...ClC, have been estimated using the quantum theory of atoms in molecules (QTAIM). In addition, an analysis of the Hirshfeld surface and associated fingerprint plots of these four molecules also have provided a platform for the evaluation of the contribution of different atom...atom contacts, which contribute toward the packing of the molecules in solids.

The effect of gamma-gamma ` interface on the tensile and shear strengths of nickel-based superalloys: A first-principles study

First-principles density functional theory has been used to evaluate the shear and cleavage strength in terms of Griffith work and generalized stacking fault energy (GSF) of (001) plane for gamma, gamma' and gamma-gamma' system as a function of distance from the gamma/gamma' interface. Calculation of Griffith work suggests higher cleavage energy for bulk gamma as compared to gamma' while the GSF calculation suggests higher shear strength for bulk gamma' as compared to gamma. It has been found that the shear strength of the cubic plane of the gamma/gamma' interface is marginally lower than those of bulk gamma and gamma' phases. (C) 2014 Elsevier B.V. All rights reserved.

Sensitivity of polarization fluctuations to the nature of protein-water interactions: Study of biological water in four different protein-water systems

Since the time of Kirkwood, observed deviations in magnitude of the dielectric constant of aqueous protein solution from that of neat water (similar to 80) and slower decay of polarization have been subjects of enormous interest, controversy, and debate. Most of the common proteins have large permanent dipole moments (often more than 100 D) that can influence structure and dynamics of even distant water molecules, thereby affecting collective polarization fluctuation of the solution, which in turn can significantly alter solution's dielectric constant. Therefore, distance dependence of polarization fluctuation can provide important insight into the nature of biological water. We explore these aspects by studying aqueous solutions of four different proteins of different characteristics and varying sizes, chicken villin headpiece subdomain (HP-36), immunoglobulin binding domain protein G (GB1), hen-egg white lysozyme (LYS), and Myoglobin (MYO). We simulate fairly large systems consisting of single protein molecule and 20000-30000 water molecules (varied according to the protein size), providing a concentration in the range of similar to 2-3 mM. We find that the calculated dielectric constant of the system shows a noticeable increment in all the cases compared to that of neat water. Total dipole moment auto time correlation function of water < dM(W) (0)delta M-W (t) > is found to be sensitive to the nature of the protein. Surprisingly, dipole moment of the protein and total dipole moment of the water molecules are found to be only weakly coupled. Shellwise decomposition of water molecules around protein reveals higher density of first layer compared to the succeeding ones. We also calculate heuristic effective dielectric constant of successive layers and find that the layer adjacent to protein has much lower value (similar to 50). However, progressive layers exhibit successive increment of dielectric constant, finally reaching a value close to that of bulk 4-5 layers away. We also calculate shellwise orientational correlation function and tetrahedral order parameter to understand the local dynamics and structural re-arrangement of water. Theoretical analysis providing simple method for calculation of shellwise local dielectric constant and implication of these findings are elaborately discussed in the present work. (C) 2014 AIP Publishing LLC.

First-Principles Study on Structural Stability of Belite

A first-principles study was carried out to investigate the stability of the crystal structure of beta-form belite (beta-C2S) substituted by Sr atoms as trace impurities for Ca atoms in CaOx polyhedra. The effect of the connection types of CaOx polyhedral, in the form of common-edge bond and common-face bond, upon the crystal stability is described. The Ca-Ca interatomic distance closely relates to the hydraulic activity of beta-C2S. The beta-C2S substituted by an Sr atom for Ca(1) atoms having seven Ca-O bonds is energetically more stable than that substituted by an Sr atom for Ca(2) atoms having eight Ca-O bonds. The Sr-doped beta-C2S having a common face bond with SrOx polyhedra is energetically more favorable and results in structural stability compared with that having a common edge bond with SrOx polyhedra.

Global response sensitivity analysis using probability distance measures and generalization of Sobol's analysis

The study introduces two new alternatives for global response sensitivity analysis based on the application of the L-2-norm and Hellinger's metric for measuring distance between two probabilistic models. Both the procedures are shown to be capable of treating dependent non-Gaussian random variable models for the input variables. The sensitivity indices obtained based on the L2-norm involve second order moments of the response, and, when applied for the case of independent and identically distributed sequence of input random variables, it is shown to be related to the classical Sobol's response sensitivity indices. The analysis based on Hellinger's metric addresses variability across entire range or segments of the response probability density function. The measure is shown to be conceptually a more satisfying alternative to the Kullback-Leibler divergence based analysis which has been reported in the existing literature. Other issues addressed in the study cover Monte Carlo simulation based methods for computing the sensitivity indices and sensitivity analysis with respect to grouped variables. Illustrative examples consist of studies on global sensitivity analysis of natural frequencies of a random multi-degree of freedom system, response of a nonlinear frame, and safety margin associated with a nonlinear performance function. (C) 2015 Elsevier Ltd. All rights reserved.

Modeling Study on the Characteristics of Laminar and Turbulent Argon Plasma Jets Impinging Normally upon a Flat Plate in Ambient Air

Modeling study is performed to compare the flow and heat transfer characteristics of laminar and turbulent argon thermal-plasma jets impinging normally upon a flat plate in ambient air. The combined-diffusion-coefficient method and the turbulence-enhanced combined-diffusion-coefficient method are employed to treat the diffusion of argon in the argon-air mixture for the laminar and the turbulent cases, respectively. Modeling results presented include the flow, temperature and argon concentration fields, the air mass flow-rates entrained into the impinging plasma jets, and the distributions of the heat flux density on the plate surface. It is found that the formation of a radial wall jet on the plate surface appreciably enhances the mass flow rate of the ambient air entrained into the laminar or turbulent plasma impinging-jet. When the plate standoff distance is comparatively small, there exists a significant difference between the laminar and turbulent plasma impinging-jets in their flow fields due to the occurrence of a large closed recirculation vortex in the turbulent plasma impinging-jet, and no appreciable difference is found between the two types of jets in their maximum values and distributions of the heat flux density at the plate surface. At larger plate standoff distances, the effect of the plate on the jet flow fields only appears in the region near the plate, and the axial decaying-rates of the plasma temperature, axial velocity and argon mass fraction along the axis of the laminar plasma impinging-jet become appreciably less than their turbulent counterparts.

Pull-in Instability Study of Carbon Nanotube Tweezers Under the Influence of Van der Waals Forces

The pull-in instability of two nanotubes under van der Waals force is studied. The cantilever beam with large deformation model is used. The influence of nanotube parameters such as the interior radius, the gap distance between the two nanotubes, etc, on the pull-in instability is studied. The critical nanotube length is determined for each specific set of nanotube parameters. The Galerkin method is applied to discretize the governing equations, and it shows good convergence.

Study on Mechanical Properties of Nanocrystal Surface Layer of an Aluminum Alloy

The nanocrystal surface layer of an aluminum alloy induced by High Speed Shot Peening (HSSP) was investigated in this paper. The results of nanoindentation experiment show that the elastic modulus and the hardness of nanocrystal surface layer increased,by 8% and 20%, respectively. The elastic modulus and the hardness appear to be independent of the distance from nanocrystalized surface and the process time.

Dependence of collision frequency on distance between two hard-sphere particles estimated by computer simulation

A Monte Carlo simulation is performed to study the dependence of collision frequency on interparticle distance for a system composed of two hard-sphere particles. The simulation quantitatively shows that the collision frequency drops down sharply as the distance between two particles increases. This characteristic provides a useful evidence for the collision-reaction dynamics of aggregation process for the two-particle system described in the other reference.

Study on flow characteristics of solid/liquid system in lysozyme crystal growth

During the process of lysozyme protein crystallization with batch method, the macroscopic flow field of solid/liquid system was observed by particle image velocimetry (PIV). Furthermore, a normal growth rate of (110) face and local flow field around a single protein crystal were obtained by a long work distance microscope. The experimental results showed that the average velocity, the maximal velocity of macroscopic solid/liquid system and the velocity of local flow field around single protein crystal were fluctuant. The effective boundary layer thickness delta(eff), the concentration at the interface Q and the characteristic velocity V were calculated using a convection-diffusion model. The results showed that the growth of lysozyme crystal in this experiment was dominated by interfacial kinetics rather than bulk transport, and the function of buoyancy-driven flow in bulk transport was small, however, the effect of bulk transport in crystal growth had a tendency to increase with the increase of lysozyme concentration. The calculated results, also showed that the order of magnitude of shear force was about 10(-21) N, which was much less than the bond force between the lysozyme molecules. Therefore the shear force induced by buoyancy-driven flows cannot remove the protein molecules from the interface of crystal.

Combustion tube studies of dust flame acceleration

A new pneumatic dispersion system for obtaining a good quality uniform dust suspension in a horizontal dust combustion tube was developed. The effect of three different dispersion techniques on self-sustained dust flame acceleration in such a combustion tube was examined. The importance of the dispersion quality in the test tube for maintaining a self-sustained dust flame acceleration was demonstrated. A combustion tube for studies of flame acceleration in fine aluminum dust-air mixture and its transition to detonation under industrial ignition conditions was constructed in the course of the present study. It consists mainly of an initiation section and a test section. The initiation section must be equipped in a well-developed dispersion system for creating a good dispersion condition in the test tube. The length of this section is 3 meters. The test tube requires only to distribute uniformly the dust over the bottom of the tube prior to the experiment. The aluminum dust spherical in shape with 6 mu m in diameter was used for tests. Experimental results demonstrated that the increase in flame velocity is roughly linear through the entire length of the test tube. The highest flame propagation velocity in fine aluminum dust-air mixture approaches some 1200m/s at a distance of 4.8m from the ignition plate.

Evaluation of the conventional surveying equipment applied to deformation analysis of heritage buildings. A case study: the bell tower of Santa María la Blanca church in Agoncillo (La Rioja, Spain)

Contributed to: "Measuring the Changes": 13th FIG International Symposium on Deformation Measurements and Analysis; 4th IAG Symposium on Geodesy for Geotechnical and Structural Enginering (Lisbon, Portugal, May 12-15, 2008).

A study of the intertidal sea anemones of the Monterey Bay region

This is a student paper done for a University of California Berkeley Zoology class. Since UCB didn't have its own marine lab at the time, it rented space at Hopkins Marine Station where this work was done. Cadet Hand earned his Ph.D. from Berkeley and went on to become Director of the Bodega Marine Laboratory. (PDF contains 36 pages)

Modeling Study of Shrouding Gas Effects on a Laminar Argon Plasma Jet Impinging Upon a Flat Substrate in Air Surroundings

With the laminar plasma materials processing as the research background, modeling study is conducted concerning the effects of argon shroud on the characteristics of the laminar argon plasma jet impinging normally upon a flat substrate located in air surroundings. It is shown that adding shrouding gas is an effective method to reduce and control the entrainment of ambient air into the laminar plasma jet. The shrouding gas flow rate or velocity, the injection slot width and the stand-off distance of the substrate appreciably affect the air contents in the plasma near the substrate surface.