PK/DB: database for pharmacokinetic properties and predictive in silico ADME models

The study of pharmacokinetic properties (PK) is of great importance in drug discovery and development. In the present work, PK/DB (a new freely available database for PK) was designed with the aim of creating robust databases for pharmacokinetic studies and in silico absorption, distribution, metabolism and excretion (ADME) prediction. Comprehensive, web-based and easy to access, PK/DB manages 1203 compounds which represent 2973 pharmacokinetic measurements, including five models for in silico ADME prediction (human intestinal absorption, human oral bioavailability, plasma protein binding, bloodbrain barrier and water solubility).

The specificity of frutalin lectin using biomembrane models

Frutalin is a homotetrameric alpha-D-galactose (D-Gal)-binding lectin that activates natural killer cells in vitro and promotes leukocyte migration in vivo. Because lectins are potent lymphocyte stimulators, understanding the interactions that occur between them and cell surfaces can help to the action mechanisms involved in this process. In this paper, we present a detailed investigation of the interactions of frutalin with phospho- and glycolipids using Langmuir monolayers as biomembrane models. The results confirm the specificity of frutalin for D-Gal attached to a biomembrane. Adsorption of frutalin was more efficient for the galactose polar head lipids, in contrast to the one for sulfated galactose, in which a lag time is observed, indicating a rearrangement of the monolayer to incorporate the protein. Regarding ganglioside GM1 monolayers, lower quantities of the protein were adsorbed, probably due to the farther apart position of D-galactose from the interface. Binary mixtures containing galactocerebroside revealed small domains formed at high lipid packing in the presence of frutalin, suggesting that lectin induces the clusterization and the forming of domains in vitro, which may be a form of receptor internalization. This is the first experimental evidence of such lectin effect, and it may be useful to understand the mechanism of action of lectins at the molecular level. (C) 2010 Elsevier B.V. All rights reserved.

Comparative study of liponucleosides in Langmuir monolayers as cell membrane models

Liponucleosides may assist the anchoring of nucleic acid nitrogen bases into biological membranes for tailored nanobiotechnological applications. To this end precise knowledge about the biophysical and chemical details at the membrane surface is required. In this paper, we used Langmuir monolayers as simplified cell membrane models and studied the insertion of five lipidated nucleosides. These molecules varied in the type of the covalently attached lipid group, the nucleobase, and the number of hydrophobic moieties attached to the nucleoside. All five lipidated nucleosides were found to be surface-active and capable of forming stable monolayers. They could also be incorporated into dipalmitoylphosphatidylcholine (DPPC) monolayers, four of which induced expansion in the surface pressure isotherm and a decrease in the surface compression modulus of DPPC. In contrast, one nucleoside possessing three alkyl chain modifications formed very condensed monolayers and induced film condensation and an increase in the compression modulus for the DPPC monolayer, thus reflecting the importance of the ability of the nucleoside molecules to be arranged in a closely packed manner. The implications of these results lie on the possibility of tuning nucleic acid pairing by modifying structural characteristics of the liponucleosides. (C) 2010 Elsevier B.V. All rights reserved.

Three-dimensional, fully adaptive simulations of phase-field fluid models

We present an efficient numerical methodology for the 31) computation of incompressible multi-phase flows described by conservative phase-field models We focus here on the case of density matched fluids with different viscosity (Model H) The numerical method employs adaptive mesh refinements (AMR) in concert with an efficient semi-implicit time discretization strategy and a linear, multi-level multigrid to relax high order stability constraints and to capture the flow`s disparate scales at optimal cost. Only five linear solvers are needed per time-step. Moreover, all the adaptive methodology is constructed from scratch to allow a systematic investigation of the key aspects of AMR in a conservative, phase-field setting. We validate the method and demonstrate its capabilities and efficacy with important examples of drop deformation, Kelvin-Helmholtz instability, and flow-induced drop coalescence (C) 2010 Elsevier Inc. All rights reserved

Phenolic matrices and sisal fibers modified with hydroxy terminated polybutadiene rubber: Impact strength, water absorption, and morphological aspects of thermosets and composites

The aim of the present work was to investigate the toughening of phenolic thermoset and its composites reinforced with sisal fibers, using hydroxyl-terminated polybutadiene rubber (HTPB) as both impact modifier and coupling agent. Substantial increase in the impact strength of the thermoset was achieved by the addition 10% of HTPB. Scanning electron microscopy (SEM) images of the material with 15% HTPB content revealed the formation of some rubber aggregates that reduced the efficiency of the toughening mechanism. In composites, the toughening effect was observed only when 2.5% of HTPB was added. The rubber aggregates were found located mainly at the matrix-fiber interface suggesting that HTPB could be used as coupling agent between the sisal fibers and the phenolic matrix. A composite reinforced with sisal fibers pre-impregnated with HTPB was then prepared; its SEM images showed the formation of a thin coating of HTPB on the surface of the fibers. The ability of HTBP as coupling agent between sisal fibers and phenolic matrix was then investigated by preparing a composite reinforced with sisal fibers pre-treated with HTPB. As revealed by its SEM images, the HTPB pre-treatment of the fibers resulted on the formation of a thin coating of HTPB on the surface of the fibers, which provided better compatibility between the fibers and the matrix at their interface, resulting in a material with low water absorption capacity and no loss of impact strength. (C) 2009 Elsevier B.V. All rights reserved.