Evaluation of RBFs for volume data interpolation in CFD

A greedy method for choosing an optimum reduced set of control points is integrated with RBF interpolation and evaluated for the purpose of interpolating large‐volume data sets in CFD. Given a function defined at a set of points, the greedy method selects a small subset of these points that is sufficient to keep the interpolation error at all the remaining points below a chosen bound. This is equivalent to a type of data compression and would have useful storage, post‐processing, and computational applications in CFD. To test the method in terms of both the point selection scheme and the suitability of reduced control point volume interpolation, a trial application of the interpolation to velocity fields in CFD volume meshes is considered. To optimise the point selection process, and attempt to be able to capture multiple length scales, a variable support radius formulation has also been included. Structured and unstructured mesh cases are considered for aerofoils, a wing case and a wing‐body case. For smooth volume functions, the method is shown to work well, producing accurate velocity interpolations using a very small number of the cells in the mesh. For general complex fields including large gradients, the method is still shown to be effective, although large gradients require more interpolation points to be used.Copyright © 2013 John Wiley & Sons, Ltd.     

Glutamine: fructose-6-phosphate amidotransferase (GFAT): homology modelling and designing of new inhibitors using pharmacophore and docking based hierarchical virtual screening protocol

Glutamine: fructose-6-phosphate amidotransferase (GFAT), also termed GFPT1 and GFAT1, catalyzes the first committed step of the hexosamine biosynthesis pathway in mammals and consequently plays an important role in type 2 diabetes. In the present study, a combination of pharmacophore modelling, homology modelling, and molecular docking analysis was performed to design new glutamine competitive inhibitors of human GFAT, and to investigate important interaction details of inhibitor molecules. A pharmacophore model of GFAT inhibitors was developed, subsequently validated, and utilized for the screening by the PHASE database to identify new molecules. Afterwards, homology modelling was performed to construct the glutamine-binding site of the GFAT protein. The modelled active site was utilized to dock the studied molecules to investigate important receptor-ligand interactions and to scrutinize database-screened molecules on the basis of essential interactions. This systematic in silico protocol helped us to identify new molecules that would be explored for the treatment of type 2 diabetes and its complications.     

Viscosity Mixing Rules for Binary Systems Containing One Ionic Liquid

In this work the applicability of four of the most commonly used viscosity mixing rules to [ionic liquid (IL)+molecular solvent (MS)] systems is assessed. More than one hundred (IL+MS) binary mixtures were selected from the literature to test the viscosity mixing rules proposed by 1) Hind (Hi), 2) Grunberg and Nissan (G–N), 3) Herric (He) and 4) Katti and Chaudhri (K–C). The analyses were performed by estimating the average (absolute or relative) deviations, AADs and ARDs, between the available experimental data and the predicted ideal mixture viscosity values obtained by means of each rule. The interaction terms corresponding to the adjustable parameters inherent to each rule were also calculated and their trends discussed.     

Case Studies With Mathematical Modeling of Free-Radical Multi-Component Bulk/Solution Polymerizations: Part 1

In part 1 of this series of two extensive overviews of multi-component polymerization case studies, we present mathematical modelling results with experimental confirmations. The case studies are from free-radical, bulk and/or solution polymerizations, covering the range from homo- to hexa-polymerization at both regular and elevated temperature levels, i.e., without and with possible depropagation steps. The model eventually tackles complex polymerization features, ranging from conversion-time histories to more esoteric multi-component composition and/or sequence length profiles. Part 2 of the series will describe more complicated situations with depropagation and composition control policies, all relying solely on a unique monomer/polymer database of physico-chemical properties and other characteristics, with no further parameter adjustment. These database items will be cited in tables in part 2 of the series.     

Interaction of Naproxen with Crystalline and Amorphous Methylated β-Cyclodextrin in the Liquid and Solid State

Abstract

Interactions of naproxen (NAP) with amorphous, randomly methylated β-cyclodextrin at a degree of substitution per anhydroglucose unit of 1.8 (RAMEB) and with crystalline heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) were studied in aqueous solution and in the solid state using, respectively, phase-solubility analysis (at 25 °C, 37 °C and 47 °C) and differential scanning calorimetry (DSC) supported by X-ray powder diffractometry. RAMEB and DIMEB displayed similar solubilizing and complexing abilities towards NAP, suggesting analogous inclusion modes of the drug in the host cavity in aqueous solution. Differences were instead observed in interactions in the solid state, where the amorphizing capacity of RAMEB toward NAP (evaluated by DSC) was about twice that of DIMEB at each drug-to-carrier ratio. Assuming that inclusion complexation is also involved in solid-state interactions, molecular modelling accounted for the experimental results in terms of structural features of DIMEB, i.e. the particular inwards orientation of O-6-C-8 groups of three alternate glucoses on the primary hydroxyl side which hampers a deep penetration of NAP in the DIMEB cavity in the solid state. On the contrary, no obstruction of the cavity apparently occurs with RAMEB due its noncrystalline state. The aqueous dissolution rate of NAP from NAP-RAMEB and NAP-DIMEB blends containing 0.59, 0.73, 0.85, and 0.92 mass fraction of carrier linearly increased at decreasing drug-to-carrier ratios. The improvement was 5 to 20 times (from powders) and 50 to 200 times (from discs) the dissolution rate of NAP alone for both carrier. Therefore the choice of the amorphous RAMEB in pharmaceutical formulations can be recommended mainly for economic reasons, though the anhydrous and non-hygroscopic nature of crystalline DIMEB might be of particular advantage in case of moisture sensitive formulations.     

Investigation of the complexation of essential oil components with cyclodextrins

The formation of inclusion complexes of six essential oil (EO) components (β-caryophyllene, cis-ocimene, trans-ocimene, sabinene hydrate (thujanol), γ-terpinene and α-terpineol) with six cyclodextrins (CDs) (α-CD, β-CD, γ-CD, HP-β-CD, RAMEB and CRYSMEB) was investigated by using static headspace-gas chromatography and UV–visible spectroscopy. Retention studies showed that CDs could efficiently reduce the volatility of EO components except for β-caryophyllene with α-CD. In this case, no inclusion complex was detected while for other compounds the formation of 1:1 inclusion complexes was observed. Results revealed that the inclusion stability mainly depends on geometric complementarity between encapsulated molecule and CD's cavity. Molecular modelling was used to investigate the complementarities between host and guest. Thus, CDs could efficiently be regarded as promising encapsulants for EO components leading to improve their application in cosmetic, pharmaceutical and agriculture fields.     

ToxML,a data exchange standard with content controlled vocabulary used to build better (Q)SAR models

Development of accurate quantitative structure–activity relationship (QSAR) models requires the availability of high quality validated data. International regulations such as REACH in Europe will now accept (Q)SAR-based evaluations for risk assessment. The number of toxicity datasets available for those wishing to share knowledge, or to use for data mining and modelling, is continually expanding. The challenge is the current use of a multitude of different data formats. The issues of comparing or combining disparate data apply both to public and proprietary sources. The ToxML project addresses the need for a common data exchange standard that allows the representation and communication of these data in a well-structured electronic format. It is an open standard based on Extensible Markup Language (XML). Supporting information for overall toxicity endpoint data can be included within ToxML files. This makes it possible to assess the quality and detail of the data used in a model. The data file model allows the aggregation of experimental data to the compound level in the detail needed to support (Q)SAR work. The standard is published on a website together with tools to view, edit and download it.     

QSAR Study on Binding Affinity of PATs (Rodenticides) to the [3H]-Mepyramine-Labelled H1 Receptor In Rat and Guinea Pig Brain

Abstract

The binding of a series of PAT analogues (rodenticides) to the [³H]-mepyramine-labelled H₁ receptor in rat and guinea pig brain was investigated topologically using negentropy (N), molecular redundancy (MRI), first-order molecular connectivity (¹X _v ), Wiener (W), and Szeged (Sz) indices. Multiple regression analyses showed that MRI provided excellent results upon introduction of indicator parameters. Predictive ability of the proposed models was discussed using cross-validation parameters.