Molecular dynamics study of the interface between water and 2-nitrophenyl octyl ether

We present results of molecular dynamics simulations of the interface between water and 2-nitrophenyl octyl ether (NPOE). This system is analyzed in detail using a procedure to calculate intrinsic profiles of several important properties (density, radial distribution functions, hydrogen bonds, molecular orientation, self-diffusion). The interface was found to be molecularly sharp but corrugated by thermal fluctuations. Using a method based on capillary wave theory, we have estimated the interfacial tension and obtained good agreement with values calculated from the virial route. The results were compared to simulations of the water/nitrobenzene interface. The presence of an alkyl chain in NPOE introduces an added degree of hydrophobicity, which causes an increase in the interfacial tension. Furthermore, interfacial NPOE molecules are less organized than nitrobenzene and show a distinct dynamic response. These results shed light on the observed differences between these two organic liquids in electrochemical studies.     

Computational chemistry approach for the early detection of drug-induced idiosyncratic liver toxicity

Idiosyncratic drug toxicity (IDT), considered as a toxic host-dependent event, with an apparent lack of dose response relationship, is usually not predictable from early phases of clinical trials, representing a particularly confounding complication in drug development. Albeit a rare event (usually <1/5000), IDT is often life threatening and is one of the major reasons new drugs never reach the market or are withdrawn post marketing. Computational methodologies, like the computer-based approach proposed in the present study, can play an important role in addressing IDT in early drug discovery. We report for the first time a systematic evaluation of classification models to predict idiosyncratic hepatotoxicity based on linear discriminant analysis (LDA), artificial neural networks (ANN), and machine learning algorithms (OneR) in conjunction with a 3D molecular structure representation and feature selection methods. These modeling techniques (LDA, feature selection to prevent over-fitting and multicollinearity, ANN to capture nonlinear relationships in the data, as well as the simple OneR classifier) were found to produce QSTR models with satisfactory internal cross-validation statistics and predictivity on an external subset of chemicals. More specifically, the models reached values of accuracy/sensitivity/specificity over 84%/78%/90%, respectively in the training series along with predictivity values ranging from ca. 78 to 86% of correctly classified drugs. An LDA-based desirability analysis was carried out in order to select the levels of the predictor variables needed to trigger the more desirable drug, i.e. the drug with lower potential for idiosyncratic hepatotoxicity. Finally, two external test sets were used to evaluate the ability of the models in discriminating toxic from nontoxic structurally and pharmacologically related drugs and the ability of the best model (LDA) in detecting potential idiosyncratic hepatotoxic drugs, respectively. The computational approach proposed here can be considered as a useful tool in early IDT prognosis.     

Mechanistic studies on the formation of glycosidase-substrate and glycosidase-inhibitor covalent intermediates

Glycoside hydrolases catalyze the breaking of the glycosidic bond. This type of bond fashioned between two monosaccharides is very stable, and the polymers created are involved in multiple cellular processes, being crucial to life. In this article, computational methods were used to study the first step of the mechanism of reaction of retaining glycoside hydrolases in atomic detail. The systems modeled included a simplified reaction center and a small substrate/inhibitor. Using DFT calculations we were able to corroborate and provide molecular-level detail to the dissociative mechanism proposed in the literature. The role of the hydrogen bridge between the nucleophile and the C(2)--OH group of the ring was also investigated. Therefore, we concluded that this bridge is responsible for lowering the activation barrier by 5.1 kcal mol(-1) with functional BB1K/6-311+G(2d,2p), and the absence of the bridge explains, at least in part, the inhibitory effect of fluoro-substituted glycosides in the -2 position. The hydrogen bridge could also be involved in favoring the ring distortion verified in the transition state, and the dissociative character of the reaction mechanism. Using the NBO method, point atomic charges were calculated. In the transition state, the positive charge generated in the sugar ring is distributed nearly equally between the anomeric carbon and the ring oxygen, through a partial double bond involving the two atoms.     

The influence of a weak magnetic field in the Renormalization-Group functions of (2 + 1)-dimensional Dirac systems

The experimental observation of the renormalization of the Fermi velocity v _F as a function ofdoping has been a landmark for confirming the importance of electronic interactions ingraphene. Although the experiments were performed in the presence of a perpendicularmagnetic field B, the measurements are well described by arenormalization-group (RG) theory that did not include it. Here we clarify this issue, forboth massive and massless Dirac systems, and show that for the weak magnetic fields atwhich the experiments are performed, there is no change in the renormalization-groupfunctions. Our calculations are carried out in the framework of the Pseudo-quantumelectrodynamics (PQED) formalism, which accounts for dynamical interactions. We includeonly the linear dependence in B, and solve the problem using two differentparametrizations, the Feynman and the Schwinger one. We confirm the results obtainedearlier within the RG procedure and show that, within linear order in the magnetic field,the only contribution to the renormalization of the Fermi velocity for the massive casearises due to electronic interactions. In addition, for gapped systems, we observe arunning of the mass parameter.     

Painlevé–Gullstrand coordinates for the Kerr solution

We construct a coordinate system for the Kerr solution, based on the zero angular momentum observers dropped from infinity, which generalizes the Painlevé–Gullstrand coordinate system for the Schwarzschild solution. The Kerr metric can then be interpreted as describing space flowing on a (curved) Riemannian 3-manifold. The stationary limit arises as the set of points on this manifold where the speed of the flow equals the speed of light, and the horizons as the set of points where the radial speed equals the speed of light. A deeper analysis of what is meant by the flow of space reveals that the acceleration of free-falling objects is generally not in the direction of this flow. Finally, we compare the new coordinate system with the closely related Doran coordinate system.     

Boron nitride nanotubes as templates for half-metal nanowires

We investigate by means of a GGA + U implementation of density functional theory the electronic and structural properties of magnetic nanotubes composed of an iron oxide monolayer and (n,0) boron nitride (BN) nanotubes, with n ranging from 6 to 14. The formation energy per FeO molecule of FeO covered tubes is smaller than the formation energy of small FeO nanoparticles, which suggests that the FeO molecules may cover the BN nanotubes rather than aggregating locally. Both GGA (PBE) and Van der Waals functionals predict an optimal FeO-BN interlayer distance of 2.94 ?. Depending on the diameter of the tube, novel electronic properties for the FeO covered BN nanotubes were found. They can be semiconductors, intrinsic half-metals or semi-half-metals that can become half-metals if charged with either electrons or holes. Such results are important in the spintronics context.     

Ionic and radical adsorption on the Au(hkl) surfaces: A DFT study

Adsorption of several ionic and non-ionic species (OH^?, O, O^?, O^2?, H, H⁺ and H^?) on the low-index Miller Au(hkl) surfaces has been investigated by means of density functional theory based methods. The stability order for adsorptions on the three surfaces decreases with the increasing of the coordination number of the outermost gold atoms in each surface, i.e., Au(110) > Au(100) > Au(111), which is in agreement with the experimental evidences. The detailed COOPs analysis of the various adsorption sites for all adsorbates in the surface with the most stable adsorption(s), Au(110), evidenced that adsorption in the gold surfaces may be a function of particle size and charge and substantiates the variability in the order of preferences sites for the adsorption of the different species found in these low-index Miller Au(hkl) surfaces. This variability increases with the increasing of the stability of the adsorptions on the gold surfaces, i.e., the Au(110) presents more variability in the order of preferences sites for the adsorption of different species.     

Turbulent Flow with Embedded Vortical Structures Induced by Vortex Generators in a Cascade

Presented work is the next step after several experimental examinations of vortex generator influence on a flow separation occurring on a model of the NACA 63A421 airfoil with deflected simple flap. In this stage of research the vortices produced by vortex generators (VGs) were studied using Particle Image Velocimetry technique (PIV) and numerical simulations. Vane type VGs with two spacings among VGs pairs in straight channel with turbulent flow were tested. The average velocity flow field, peak of vorticity and circulation decay downstream of VGs were evaluated. (© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Costing a Finite Minimal Repair Replacement Policy

In this paper an integral equation technique is used to evaluate the expected cost for the period (0, t] of a policy involving minimal repair at failure with replacement after N failures. This cost function provides an appropriate criterion to determine the optimal replacement number N* for a system required for use over a finite time horizon. In an example, it is shown that significant cost savings can be achieved using N* from the new finite time horizon model rather than the value predicted by the usual asymptotic model.