Investigating microcrystalline cellulose crystallinity using Raman spectroscopy

Cellulose - Microcrystalline cellulose (MCC) is a semi-crystalline material with inherent variable crystallinity due to raw material source and variable manufacturing conditions. MCC crystallinity...     

Generation of substituted styrenes via Suzuki cross-coupling of aryl halides with 2,4,6-trivinylcyclotriboroxane

The synthesis of functionalized styrene derivatives can be readily achieved utilizing a Suzuki cross-coupling protocol between aryl halides and 2,4,6-trivinylcyclotriboroxane-pyridine complex. The scope and limitations of the procedure were demonstrated by investigation of an array of ortho-substituted aryl halides.     

DICE: exploiting <Emphasis Type="Italic">all</Emphasis> bivariate dependencies in binary and multary search spaces

Although some of the earliest Estimation of Distribution Algorithms (EDAs) utilized bivariate marginal distribution models, up to now, all discrete bivariate EDAs had one serious limitation: they were constrained to exploiting only a limited O(d) subset out of all possible \(O(d^{2})\) bivariate dependencies. As a first we present a family of discrete bivariate EDAs that can learn and exploit all \(O(d^{2})\) dependencies between variables, and yet have the same run-time complexity as their more limited counterparts. This family of algorithms, which we label DICE (DIscrete Correlated Estimation of distribution algorithms), is rigorously based on sound statistical principles, and particularly on a modelling technique from statistical physics: dichotomised multivariate Gaussian distributions. Initially (Lane et al. in European Conference on the Applications of Evolutionary Computation, Springer, 1999), DICE was trialled on a suite of combinatorial optimization problems over binary search spaces. Our proposed dichotomised Gaussian (DG) model in DICE significantly outperformed existing discrete bivariate EDAs; crucially, the performance gap increasingly widened as dimensionality of the problems increased. In this comprehensive treatment, we generalise DICE by successfully extending it to multary search spaces that also allow for categorical variables. Because correlation is not wholly meaningful for categorical variables, interactions between such variables cannot be fully modelled by correlation-based approaches such as in the original formulation of DICE. Therefore, here we extend our original DG model to deal with such situations. We test DICE on a challenging test suite of combinatorial optimization problems, which are defined mostly on multary search spaces. While the two versions of DICE outperform each other on different problem instances, they both outperform all the state-of-the-art bivariate EDAs on almost all of the problem instances. This further illustrates that these innovative DICE methods constitute a significant step change in the domain of discrete bivariate EDAs.     

Rapid analysis of antimicrobial metabolites monoacetylphloroglucinol and 2,4-diacetylphloroglucinol using capillary zone electrophoresis

A rapid capillary electrophoretic (CE) method was developed for the determination of phloroglucinol compounds, monoacetylphloroglucinol (MAPG) and 2,4-diacetylphloroglucinol (DAPG), in microbial supernatants of Pseudomonas fluorescens F113 over a 24-h growth cycle. Prior to electrophoretic separation, solid-phase extraction of supernatant samples on octadecylsilica for the purpose of sample cleanup is recommended. The optimum electrophoretic conditions were found to be 25 mM sodium tetraborate running buffer at pH 9.3, temperature at 25 degrees C with an applied voltage of 25 kV. The capillary was an Agilent fused-silica capillary of total length 33 cm x 50 microm inner diameter, 375 microm outer diameter, with effective length 24.5 cm. While MAPG and DAPG were monitored at selected wavelengths in the range of 214-320 nm, analysis at 214 nm was used and a CE separation time of less than 2 min was achieved. A partial method validation study was performed in accordance with European Agency for Evaluation of Medicinal Products (EMEA) guidelines. The method displayed linearity over the investigated range of 10-200 microg/mL, with limits of detection of 1.2 microg/mL for MAPG and 1.3 microg/mL for DAPG.     

Resin Swelling in Mixed Solvents Analysed using Hansen Solubility Parameter Space

The swelling of resins (Merrifield and HypoGel 200) in mixtures of two solvents was generally found not to vary linearly with the relative amount of each solvent in the mixture. Hansen solubility parameter (HSP) space could be used to define high, medium and low swelling regions for each resin. The variation of resin swelling with binary solvent composition could then be explained based on the HSP parameters of the two solvents and the way in which the line connecting the points corresponding to the two pure solvents bisected the swelling region for the resin. The applicability of the methodology was demonstrated by showing that an appropriate mixture of two green solvents was more effective for solid-phase peptide synthesis on Merrifield resin than use of either individual solvent and could completely replace the use of traditional polar aprotic and chlorinated solvents for this application. It was also shown that the high resin swelling area of Merrifield resin can be used to predict mixtures of green solvents that will dissolve linear, unfunctionalised polystyrene.     

Thermodynamic properties of inhomogeneous fluids

A general method, the method of variation under extension, is presented for expressing the thermodynamic properties of an inhomogeneous fluid as functionals of the local number density, when given a density functional for the total thermodynamic grand potential of the fluid. The method is demonstrated in detail for the van der Waals square-gradient density functional and for the nonlocal density functional which arises in the theory of fluids with long-ranged pair potentials or in the mean-field theory of penetrable-sphere models. As specific examples, we consider the planar and spherical interface between two fluid phases, the line of contact of three fluid phases, the contact line between two surface phases and the planar interface between a solid and fluid.     

Approved drug mimics of short peptide ligands from protein interaction motifs

Most biological functions are regulated through complex networks of transient protein interactions, and, thus, finding effective ways to modulate them would represent an important step towards defining the next generation of drugs. In this study, we set out to determine if existing approved drugs may represent a good source of compounds from which initial lead inhibitors of protein-protein interactions mediated by short peptide regions may be drawn. Peptide structures were defined in terms of pharmacophores and searched against U.S. Food and Drug Administration (FDA)-approved drugs to identify similar compounds. The top ranking matches (using a score that corrects root-mean-square deviation (rmsd) for the number of matched pharmacophores and for the number of drug rotatable bonds) included a number of nuclear receptor ligands that matched allosterically to the corepressor binding site of peroxisome proliferator-activated receptor alpha (PPARalpha). The top ranking drug matches were docked to the peptide-binding site using AUTODOCK. The majority of the top-ranking matches showed a negative estimated free energy change upon binding that is comparable to, or greater than, that of the original peptide. We conclude that the usage of certain approved drugs may represent a useful strategy in inhibiting specific protein-protein interactions. Such a strategy may benefit from the increased likelihood that developed compounds might have favorable bioactivity and safety profiles in clinical use.