EADock: docking of small molecules into protein active sites with a multiobjective evolutionary optimization.

In recent years, protein-ligand docking has become a powerful tool for drug development. Although several approaches suitable for high throughput screening are available, there is a need for methods able to identify binding modes with high accuracy. This accuracy is essential to reliably compute the binding free energy of the ligand. Such methods are needed when the binding mode of lead compounds is not determined experimentally but is needed for structure-based lead optimization. We present here a new docking software, called EADock, that aims at this goal. It uses an hybrid evolutionary algorithm with two fitness functions, in combination with a sophisticated management of the diversity. EADock is interfaced with the CHARMM package for energy calculations and coordinate handling. A validation was carried out on 37 crystallized protein-ligand complexes featuring 11 different proteins. The search space was defined as a sphere of 15 A around the center of mass of the ligand position in the crystal structure, and on the contrary to other benchmarks, our algorithm was fed with optimized ligand positions up to 10 A root mean square deviation (RMSD) from the crystal structure, excluding the latter. This validation illustrates the efficiency of our sampling strategy, as correct binding modes, defined by a RMSD to the crystal structure lower than 2 A, were identified and ranked first for 68% of the complexes. The success rate increases to 78% when considering the five best ranked clusters, and 92% when all clusters present in the last generation are taken into account. Most failures could be explained by the presence of crystal contacts in the experimental structure. Finally, the ability of EADock to accurately predict binding modes on a real application was illustrated by the successful docking of the RGD cyclic pentapeptide on the alphaVbeta3 integrin, starting far away from the binding pocket.

Détection et analyse des sites de vente de GBL sur Internet: perspectives en matière de renseignement criminel

cette étude présente une méthodologie de détection et d'analyse de sites de vente en ligne de GBL (gamma-butyrolactone, un précurseur du GHB : gamma-hydroxybutyrate). La veille de ces sites nécessite de définir des stratégies de collecte efficientes. Elle implique, de surcroît, la conception de systèmes capables d'accueillir et structurer les données collectées dans une mémoire de travail adaptée pour mettre en évidence des relations entre les sites et ainsi mieux comprendre le marché de distribution. Trente-neuf sites vendant de la GBL ont été détectés. Il a été observé que le marché en ligne de la GBL semble plutôt stable entre 2010 et 2011. De plus, quatre-vingt pourcent des sites sont hébergés aux Pays-Bas où la substance n'est pas prohibée. Six groupes, reliant au total dix-sept sites, ont été identifiés sur la base d'informations directement collectées à partir des sites.

Consideraciones sobre las formas de producción industrial en Cataluña 1936-1938

La gran cantidad de libros y papeles escritos alrededor de la guerra civil aspañola 1936-1939 han prestado relativamente poca atención al examen de la evolución económica de esapaña durante aquellos años y, más en particular, al desarrollo de la actividad económica y de los modos de producción industrial en Cataluña durante el mismo período, que, así pues, por un conjunto de circunstancias han quedado, en algunos aspectos, marginados de dichos estudios. [. . .]

A classificação industrial e sua importância na análise setorial

O presente artigo tem como objetivo apresentar conceitos acerca das classificações industriais, mostrando-se a importância dos sistemas de classificações e a necessidade de correlação entre as classificações dos diferentes países. As classificações internacionais são baseadas na "Família Internacional de Classificações Econômicas e Sociais", que englobam atividades econômicas, produtos, consumo, educação, emprego, entre outras. Sua abrangência em relação às classificações de atividades e de produtos envolve as "classificações de referência (como a ISIC e a CPC), as classificações derivadas (como a NACE e a CPA) e as classificações relacionadas (como a ANZIC e a NAICS), cuja harmonização é realizada por gestores de classificação, como o INDEC, da Argentina, o INE, de Portugal, e o IBGE, do Brasil. As classificações de atividades e de produtos na economia constituem instrumento básico para obtenção de informações e análise dos dados estatísticos.

A regional Industrial Symbiosis methodology and its implementation in Geneva, Switzerland

The Agenda 21 for the Geneva region is the results from a broad consultation process including all local actors. The article 12 stipulates that « the State facilitates possible synergies between economic activities in order to minimize their environmental impacts » thus opening the way for Industrial Ecology (IE) and Industrial Symbiosis (IS). An Advisory Board for Industrial Ecology and Industrial Symbiosis implementation was established in 2002 involving relevant government agencies. Regulatory and technical conditions for IS are studied in the Swiss context. Results reveal that the Swiss law on waste does not hinder by-product exchanges. Methodology and technical factors including geographic, qualitative, quantitative and economical aspects are detailed. The competition with waste operators in a highly developed recycling system is also tackled.The IS project develops an empirical and systematic method for detecting and implementing by-products synergies between industrial actors disseminated throughout the Geneva region. Database management tool for the treatment of input-output analysis data and GIS tools for detecting potentials industrial partners are constantly improved. Potential symbioses for 17 flows (including energy, water and material flows) are currently studied for implementation.

Method for Estimating the Magnitude and Frequency of Floods at Ungaged Sites on Unregulated Rural Streams in Iowa, HR-268, 1987

This report provides techniques and procedures for estimating the probable magnitude and frequency of floods at ungaged sites on Iowa streams. Physiographic characteristics were used to define the boundaries of five hydrologic regions. Regional regression equations that relate the size of the drainage area to flood magnitude are defined for estimating peak discharges having specified recurrence intervals of 2, 5, 10, 25, 50, and 100 years. Regional regression equations are applicable to sites on streams that have drainage areas ranging from 0.04 to 5,150 square miles provided that the streams are not affected significantly by regulation upstream from the sites and that the drainage areas upstream from the sites are not mostly urban areas. Flood-frequency characteristics for the mainstems of selected rivers are presented in graphs as a function of drainage area.

Níveis de resíduo industrial de fécula da mandioca na alimentação de suínos em crescimento e terminação

Foram conduzidos dois experimentos para avaliação da inclusão do resíduo industrial de fecularia da mandioca (RIFM) em dietas para suínos em crescimento e terminação. No experimento 1, foram avaliados quatro níveis de RIFM (0; 6,67; 13,33 e 20,00%) na dieta de suínos em crescimento. A inclusão do RIFM na dieta provocou efeito cúbico sobre o ganho de peso médio diário (GPMD, P<0,01, R² =0,80, y=804-54,06x+6,03x²-0,19x³), peso médio ao final do crescimento (PMFC, P<0,01, R² =0,79, y=60,47-2,87x+0,33x²-0,01x³) e efeito linear sobre o consumo diário de ração (CRD, P<0,04, R² = 0,74, y=2090-136x). O peso médio ao abate (PMA) foi afetado de forma quadrática (P<0,05, R² = 0,69, y=98,88-1,28x+0,05x²). No experimento 2, o RIFM foi avaliado em quatro níveis (0, 10, 20 e 30%) de inclusão na dieta de suínos em terminação. Nenhum desses níveis de RIFM afetou (P>0,10) o desempenho dos suínos. Concluiu-se que a inclusão do RIFM na dieta de suínos em crescimento, à partir de 6,67%, provoca redução do desempenho. Na fase de terminação, o desempenho não é afetado pela inclusão do RIFM até o nível de 30% da dieta.

Experimental analysis and computer prediction of CTF/NFI transcription factor DNA binding sites.

Accurate prediction of transcription factor binding sites is needed to unravel the function and regulation of genes discovered in genome sequencing projects. To evaluate current computer prediction tools, we have begun a systematic study of the sequence-specific DNA-binding of a transcription factor belonging to the CTF/NFI family. Using a systematic collection of rationally designed oligonucleotides combined with an in vitro DNA binding assay, we found that the sequence specificity of this protein cannot be represented by a simple consensus sequence or weight matrix. For instance, CTF/NFI uses a flexible DNA binding mode that allows for variations of the binding site length. From the experimental data, we derived a novel prediction method using a generalised profile as a binding site predictor. Experimental evaluation of the generalised profile indicated that it accurately predicts the binding affinity of the transcription factor to natural or synthetic DNA sequences. Furthermore, the in vitro measured binding affinities of a subset of oligonucleotides were found to correlate with their transcriptional activities in transfected cells. The combined computational-experimental approach exemplified in this work thus resulted in an accurate prediction method for CTF/NFI binding sites potentially functioning as regulatory regions in vivo.

Flood-Plain and Channel Aggradation at Selected Bridge Sites in the Iowa and Skunk River Basins, Iowa, HR-350, 1996

Flood-plain and channel-aggradation rates were estimated at selected bridge sites in central and eastern Iowa using four aggradation-measurement methods. Aggradation rates were quantified at 10 bridge sites on the Iowa River upstream of Coralville Lake and at two bridge sites in the central part of Skunk River Basin. Measurement periods used to estimate average aggradation rates ranged in length from 1 to 98 years and varied among methods and sites. A direct comparison cannot be made between aggradation rates calculated using each of the four measurement methods because of differences in time periods and aggradational processes that were measured by each method.

Which anatomical sites should be sampled for screening of methicillin-resistant Staphylococcus aureus carriage by culture or by rapid PCR test?

The nose is the anatomical site usually recommended for methicillin-resistant Staphylococcus aureus (MRSA) screening. Other sites are also recommended, but are more controversial. We showed that the sensitivities of MRSA detection from nasal swabs alone were 48% and 62% by culture or by rapid PCR test, respectively. These percentages increased to 79% and 92% with the addition of groin swabs, and to 96% and 99% with the addition of groin and throat swabs. In conclusion, neither by culture nor by rapid PCR test is nose sampling alone sufficient for MRSA detection. Additional anatomical sites should include at least the groin and throat.