On Exactly Marginal Deformations Dual to BB-Field Moduli of IIB Theory on SE5_5

The complex dimension of the space of exactly marginal deformations for quiver CFTs dual to IIB theory compactified on $Y^{p,q}$ is known to be generically three. Simple general formulas already exist for two of the exactly marginal directions in the space of couplings, one of which corresponds to the sum of the (inverse squared of) gauge couplings, and the other to the $\beta$-deformation. Here we identify the third exactly marginal direction, which is dual to the modulus $\int B_{2}$ on the gravity side. This identification leads to a relation between the field theory gauge couplings and the vacuum expectation value of the gravity modulus that we further support by a computation related to the chiral anomaly induced by added fractional branes. We also present a simple algorithm for finding similar exactly marginal directions in any CFT described by brane tiling, and demonstrate it for the quiver CFTs dual to IIB theory compactified on $L^{1,5,2}$ and the Suspended Pinch Point.Comment: 28 pages, JHEP style. v2: minor corrections, added references and acknowledgements. v3: a number of speculative comments regarding the application of the Konishi anomaly equation to our problem are removed. v4: the proposal in Eq. (2.4) added back as a conjectur

Routes to drug design via bioisosterism of carboxyl and sulfonamide groups

© 2017 2017 Future Science Ltd. Aim: The similarity in the biological function of the bioisosteric pair, carboxyl and sulfonamide functional groups, is studied using the quantitative tool, average electron density of the bioisosteric moiety in drug molecules and the qualitative tool, electrostatic potential. Results/methodology: Five different capping groups (methyl, phenyl, chlorine, hydrogen and amine) were considered to investigate the effect of the environment on the properties of the bioisosteres. The molecules were considered in their neutral and anionic forms to account for the change in pH depending on the medium of the drug-receptor interactions. Conclusion: The new developed approach, average electron density, is not only advantageous as a qualitative descriptor, it is also more consistent compared with the conventionally accepted method, electrostatic potential, especially for the anions

Atomic and molecular properties of nonclassical bioisosteric replacements of the carboxylic acid group

© 2020 Drug design is fraught with challenges as small differences in the structure of a drug molecule can significantly affect its biological activity. Bioisosteres are interchangeably used to adjust pharmacokinetic and pharmacodynamic properties without affecting the biological activity of the drug. While electrostatic potential maps (EPMs) are typically used to show the similarity in the \u27key and lock\u27 interactions between a drug and its receptor, they are limited to qualitative comparisons. Methodology & results: Using the quantum theory of atoms in molecules, quantitative similarities among nonclassical bioisosteres of carboxylic acid were evaluated. Conclusion: The similarity in the bioisosteric groups was captured with the average electron density tool which generated remarkably close average electron densities regardless of the capping group, the isodensity values or the protonation state of the molecule. The similarities among bioisosteres was less obvious using the EPM tool

Evaluating dispersion forces for optimization of van der Waals complexes using a non-empirical functional

© 2016 The Author(s) Published by the Royal Society. All rights reserved. Modelling dispersion interactions with traditional density functional theory (DFT) is a challenge that has been extensively addressed in the past decade. The exchange-dipole moment (XDM), among others, is a non-empirical add-on dispersion correction model in DFT. The functional PW86+PBE+XDM for exchange, correlation and dispersion, respectively, compromises an accurate functional for thermochemistry and for van der Waals (vdW) complexes at equilibrium and non-equilibrium geometries. To use this functional in optimizing vdW complexes, rather than computing single point energies, it is necessary to evaluate accurate forces. The purpose of this paper is to validate that, along the potential energy surface, the distance at which the energy is minimum is commensurate with the distance at which the forces vanish to zero. This test was validated for 10 rare gas diatomic molecules using various integration grids and different convergence criteria. It was found that the use of either convergence criterion, 10-6 or 10-8, in Gaussian09, does not affect the accuracy of computed optimal distances and binding energies. An ultrafine grid needs to be used when computing accurate energies using generalized gradient approximation functionals. This article is part of the themed issue \u27Multiscale modelling at the physics-chemistry-biology interface\u27

Binding energies of van der Waals complexes at non-equilibrium geometries

© 2019 Elsevier B.V. In density functional theory (DFT), many methods have been developed to accurately capture the dispersion interactions in weakly-bound systems. The focus, however, has been mainly on complexes at equilibrium geometries. The purpose of this study is to assess the performance of the functional PW86 + PBE + XDM on van der Waals (vdW) complexes at non-equilibrium geometries. The well balanced S66x8 database published by Hobza\u27s group is used. This database includes 66 complexes at eight different separations ranging from 10% compression to 200% stretching with respect to the equilibrium geometries. The overall root mean square percent error (RMSPE) on this database using aug-cc-pVTZ is 14.58%

Conjunctivitis: A Systematic Review

Conjunctivitis is a commonly encountered condition in ophthalmology clinics throughout the world. In the management of suspected cases of conjunctivitis, alarming signs for more serious intraocular conditions, such as severe pain, decreased vision, and painful pupillary reaction, must be considered. Additionally, a thorough medical and ophthalmic history should be obtained and a thorough physical examination should be done in patients with atypical findings and chronic course. Concurrent physical exam findings with relevant history may reveal the presence of a systemic condition with involvement of the conjunctiva. Viral conjunctivitis remains to be the most common overall cause of conjunctivitis. Bacterial conjunctivitis is encountered less frequently and it is the second most common cause of infectious conjunctivitis. Allergic conjunctivitis is encountered in nearly half of the population and the findings include itching, mucoid discharge, chemosis, and eyelid edema. Long-term usage of eye drops with preservatives in a patient with conjunctival irritation and discharge points to the toxic conjunctivitis as the underlying etiology. Effective management of conjunctivitis includes timely diagnosis, appropriate differentiation of the various etiologies, and appropriate treatment

The influence of base pair tautomerism on single point mutations in aqueous DNA

The relationship between base pair hydrogen bond proton transfer and the rate of spontaneous single point mutations at ambient temperatures and pressures in aqueous DNA is investigated. By using an ensemble-based multiscale computational modelling method, statistically robust rates of proton transfer for the A:T and G:C base pairs within a solvated DNA dodecamer are calculated. Several different proton transfer pathways are observed within the same base pair. It is shown that, in G:C, the double proton transfer tautomer is preferred, while the single proton transfer process is favoured in A:T. The reported range of rate coefficients for double proton transfer is consistent with recent experimental data. Notwithstanding the approximately 1000 times more common presence of single proton transfer products from A:T, observationally there is bias towards G:C to A:T mutations in a wide range of living organisms. We infer that the double proton transfer reactions between G:C base pairs have a negligible contribution towards this bias for the following reasons: (i) the maximum half-life of the G*:C* tautomer is in the range of picoseconds, which is significantly smaller than the milliseconds it takes for DNA to unwind during replication, (ii) statistically, the majority of G*:C* tautomers revert back to their canonical forms through a barrierless process, and (iii) the thermodynamic instability of the tautomers with respect to the canonical base pairs. Through similar reasoning, we also deduce that proton transfer in the A:T base pair does not contribute to single point mutations in DNA

Degré d’impact des aménagements hydrauliques sur le ruissellement et le transport solide dans une région semi aride : cas des micro-bassins dans le haut Isser, Algérie

L’érosion est un ensemble de processus variables dans le temps et dans l'espace. La variation se fait en fonction des conditions écologiques et des mauvaises conditions de gestion de la terre par l'homme. C’est pourquoi la lutte antiérosive intéresse divers acteurs dont les intérêts ne sont pas forcément compatibles. Ses effets sont conséquents sur les ressources en eau par la réduction de la capacité de stockage des barrages et la mauvaise qualité de l’eau, d’une part, et sur le sol par la perte de sa fertilité, d’autre part. En Algérie septentrionale, ce phénomène est crucial. De nombreux chercheurs se sont penchés pour traiter ce problème ; que ce soit dans l’aspect de quantification que dans celui de la lutte anti-érosive. Nous avons tenté d’approcher le phénomène dans ces deux aspects, en prenant comme zone d’étude les micro-bassins 'expérimentaux de Beni Slimane, dans le bassin versant de lOued Isser. L’intensité de l’érosion hydrique sur ce bassin versant s’explique par la prédominance des terrains marneux, des ruissellements concentrés et un couvert végétal quasi inexistant. L’impact des aménagements  hydrauliques sur le ruissellement a été démontré sur les micros bassins expérimentaux. C’est dans cette optique que s’inscrit l’objectif de ce travail, vu l’importance que revêt la région par rapport à son alimentation en eau potable de la capitale, d’une part, et à une agriculture florissante, d’autre part.Mots-clés : capacité de stockage, érosion, ruissellement, impact, micros bassins expérimentau

Adenine-thymine tautomerization under the influence of strong homogeneous electric fields

© the Owner Societies 2018. The effect of strong electric fields on the tautomerization of the adenine-thymine (AT) base pair in DNA is explored using density functional theory. It was found that the AT base pair is not likely to undergo a double proton transfer reaction even in the presence of electric fields ranging from 5.14 × 108 to 5.14 × 109 V m-1. This conclusion holds true in Gibbs energies computed at 25 °C or 37 °C. Energy correction terms to the electronic energy, such as total internal energy, Gibbs energy, zero-point energy, enthalpy and entropy corrections, were investigated in detail to pinpoint the major contributors to the low probability of the AT tautomerization. It was found that the entropy corrections are the least significant, while zero-point energy and Gibbs energy corrections can be large enough to thermodynamically inhibit the DPT in AT