Immobilized pH gradient gel cell to study the pH dependence of drug lipophilicity

An experimental setup to study the pH dependence of standard ion-transfer potentials at the water/NPOE interface is presented. The system is composed of a microhole generated by laser photoablation in a 12-microm polyethylene terephthalate film, the aqueous phase consisting of a commercial immobilized pH gradient gel reswelled in electrolyte solution and a droplet of organic solution. Two electrodes are used, an Ag/AgCl aqueous electrode and an Ag/AgTPBCl organic electrode. This setup is applied to the study of two ionizable compounds (pyridine, 2,4-dinitrophenol). Thermodynamic parameters such as the standard transfer potential, the Gibbs energy of transfer, and the partition coefficients of the ionized forms as well as the neutral forms of these drug compounds are evaluated by differential pulse voltammetry. The data obtained are summarized in ionic partition diagrams, which are a useful tool for predicting and interpreting the transfer behavior of ionized drugs at the liquid/liquid interfaces mimicking the biological membranes.     

The School of Pharmacy Geneva-Lausanne (EPGL) - the first ten years

With the creation of the School of Pharmacy Geneva-Lausanne (EPGL) in 2003, cantons Geneva and Vaud pooled their resources with the objective of reinforcing the research and teaching in the pharmaceutical sciences. Its core research units cover all aspects of fundamental pharmaceutical research and include collaborative research with the University Hospitals of Geneva and Lausanne.     

Grid Technology Reliability for Flash Flood Forecasting: End-user Assessment

The flash flood forecasting is one of the most important challenges for research in hydrology. The anticipation of extreme hydrological scenarios through rainfall–runoff models is still limited, mainly because of the high uncertainty of rainfall forecasts, as of limited computing resources. The authors propose to simulate an ensemble of potential hydrological scenarios in order to support the forecaster’s decision-making process. The developed applicative layer takes advantage of the computing capabilities of Grid technology, significantly enhancing the management of independent modelling operations in an operational lead time. A set of experimentations is deployed in order to firstly assess efficiency of this applicative layer and secondly to gauge more broadly the potentialities of Grid to handle flood crisis management operations. Finally, in managing more than one hundred hydrological simulations simultaneously, this experimental platform opens new perspectives for the improvement of hydrological forecast modelling, limited up to now by the lack of computing resources.     

Direct quantification of fatty acids in dairy powders with special emphasis on trans fatty acid content

In this study a validated procedure for accurate determination of fatty acids in dairy products, with special emphasis on total trans fatty acids (TFA) content is presented. Dairy fat naturally contains 4–6% of trans fatty acids, mainly trans-octadecenoic acids (i.e. vaccenic acid), and 0.3–1.5% of conjugated linoleic acids (CLA). The proposed procedure does not require lipid extraction, and transesterification of lipids could be carried out directly on dairy products. Optimal analytical conditions have been developed to allow accurate determination of TFA content without prior fractionation of cis/trans FAME isomers by thin-layer chromatography. The methodology requires the use of a highly polar open tubular capillary column having at least 100 m length. CLA and other fatty acids from C4:0 (butyric) acid to long-chain polyunsaturated fatty acids (LC-PUFAs) could also be analyzed. Therefore, the methodology presented is versatile and could be used for both targeted analysis (e.g. determination of TFA in dairy products) and determination of the broad fatty acid profile in dairy products.     

Segmentation of discrete point clouds using an extensible set of templates

We present an algorithm for segmenting a discrete three-dimensional point-set (i.e., partitioning an input discrete point-set into appropriate subsets). The algorithm consists in the iteration of two main steps which are: fitting the parameters of template primitives from a user-specified list of primitives and extracting the points from the input point-set matching the best fitted primitive. We illustrate the results of applying our algorithm to several examples of three-dimensional point-sets.     

Development of molecular hydrogen-bonding potentials (MHBPs) and their application to structure–permeation relations

Hydrogen bonds are major forces of recognition in biochemistry and molecular pharmacology; they are an essential component of intermolecular interactions and determine to a significant extent the 3D-structure of bio-macromolecules. To explore three-dimensional H-bonding properties, a new tool called Molecular Hydrogen-Bonding Potentials (MHBPs) was created. The development of this tool is based on a stepwise procedure similar to the one used successfully to generate the Molecular Lipophilicity Potential (MLP). First, a H-bonding fragmental system was developed starting from published solvatochromic parameters. An atomic H-bonding donor fragmental value () is associated to each hydrogen atom in a polar moiety. Similarly, an atomic H-bonding acceptor fragmental value (β) is associated to each polar atom. A distance function and an angle function were defined to take into account variations of the MHBPs in space. The fragmental system and the geometric functions were then combined to generate the MHBPs. These are calculated at each point of an adequate molecular surface or on a three-dimensional grid. The MHBPs were compared with GRID interactions energies and correlated with success to oral drug absorption data. Available examples demonstrate that the MHBPs are a promising computational tool in drug design. Their combination with CoMFA and VolSurf is being studied.     

Diversity of the Volatile Organic Compounds Emitted by 55 Species of Tropical Trees: a Survey in French Guiana

Volatile organic compounds (VOCs) are produced by a broad range of organisms, from bacteria to mammals, and they represent a vast chemical diversity. In plants, one of the preeminent roles of VOCs is their repellent or cytotoxic activity, which helps the plant deter its predators. Most studies on VOCs emitted by vegetative parts have been conducted in model plant species, and little is known about patterns of VOC emissions in diverse plant communities. We conducted a survey of the VOCs released immediately after mechanical damage of the bark and the leaves of 195 individual trees belonging to 55 tropical tree species in a lowland rainforest of French Guiana. We discovered a remarkably high chemical diversity, with 264 distinct VOCs and a mean of 37 compounds per species. Two monoterpenes (α-pinene and limonene) and two sesquiterpenes (β-caryophyllene and α-copaene), which are known to have cytotoxic and deterrent effects, were the most frequent compounds in the sampled species. As has been established for floral scents, the blend of VOCs is largely species-specific and could be used to discriminate among 43 of the 55 sampled species. The species with the most diverse blends were found in the Sapindales, Laurales, and Magnoliales, indicating that VOC diversity is not uniformly distributed among tropical species. Interspecific variation in chemical diversity was caused mostly by variation in sesquiterpenes. This study emphasizes three aspects of VOC emission by tropical tree species: the species-specificity of the mixtures, the importance of sesquiterpenes, and the wide-ranging complexity of the mixtures.     

Optimization of a passive structure for active vibration isolation: an interval-computation- and constraint-propagation-based approach

This article is concerned with the optimization of the mechanical structure of a one-degree-of-freedom vibration isolator. An efficient optimization algorithm based on an interval-computation method is used. The authors’ general objective is to include and develop an optimization step in the pre-design process of a smart structure. In this article, the idea of this pre-design is to obtain, very quickly and very simply, the global structural geometry of the passive isolation device. For this purpose, a simplified mathematical model is built, which describes the main natural mode shapes of the suspension device. The method is applicable to large-scale dynamic systems for a first optimization process step because it's clearly an effective time-saving optimization approach. The results obtained are quite sufficient for a first pre-design step. For a real case scenario, the optimized structure is applied to a numerical active vibration control process.