Les grilles pour le développement médical

PCSV, présenté par V. Breton, à paraître dans les Comptes-Rendu de la ConférenceLe développement récent des sciences et technologies de l'information et de la communication permet aujourd'hui la création de véritables infrastructures pour le calcul et le stockage de données hétérogènes à l'échelle régionale, nationale et internationale. Ces infrastructures, appelées grilles informatiques, permettront bientôt d'utiliser les ressources informatiques mutualisées avec autant de facilité que nous utilisons aujourd'hui l'électricité. L'utilisation des grilles afin d'accélérer la découverte de médicaments est une voie très prometteuse pour l'avenir. Par cette approche in silico, le nombre de molécules ainsi que la vitesse de test peuvent être grandement augmentés induisant un coût moindre de développement de médicaments. Du 11 Juillet au 31 Août 2005, l'expérience WISDOM (Wide In Silico Docking On Malaria) a permis de tester rien moins qu'un million de ligands (médicaments potentiels) pour le traitement du paludisme: 1700 ordinateurs à travers le monde ont ainsi été associés à cette démarche permettant de réaliser en un mois ce qui aurait nécessité 80 ans sur un ordinateur classique. L'analyse des résultats est en cours. Par cette approche, on peut souhaiter également que les maladies orphelines puissent bénéficier d'un intérêt nouveau de la part des industries pharmaceutiques, à travers notamment la baisse du coût de développement d'un médicament, principal obstacle actuellement à leur mobilisation

Demonstration of In Silico docking at a large scale on grid infrastructure

présenté par N. Jac

Escherichia coli lacking the AcrAB multidrug efflux pump also lacks nonproteinaceous, PHB–polyphosphate Ca2+ channels in the membrane

AbstractPHB(polyP) complexes bind calcium and form calcium channels in the cytoplasmic membrane in Escherichia coli and are likely to be important in Ca2+ homeostasis in this organism. E. coli N43, which lacks the AcrA component of a major multidrug resistance pump, was shown to be defective in calcium handling, with an inability to maintain submicromolar levels of free Ca2+ in the cytoplasm. Therefore, using an N-phenyl-1-napthylamine (NPN)-dependent fluorescence assay, we measured temperature-dependent phase transitions in the membranes of intact cells. These transitions specifically depend on the presence of PHB(Ca2+polyP) complexes. PHB(Ca2+polyP) channel complexes, particularly in stationary phase cultures, were detected in wild-type strains; however, in contrast, isogenic acrA− strains had greatly reduced amounts of the complexes. This indicates that the AcrAB transporter may have a novel, hitherto undetected physiological role, either directly in the membrane assembly of the PHB complexes or the transport of a component of the membrane, which is essential for assembly of the complexes into the membrane. In other experiments, we showed that the particular defective calcium handling detected in N43 was not due to the absence of AcrA but to other unknown factors in this strain

TIMASSS : The IRAS16293-2422 Millimeter And Submillimeter Spectral Survey: Tentative Detection of Deuterated Methyl Formate (DCOOCH3)

High deuterium fractionation is observed in various types of environment such as prestellar cores, hot cores and hot corinos. It has proven to be an efficient probe to study the physical and chemical conditions of these environments. The study of the deuteration of different molecules helps us to understand their formation. This is especially interesting for complex molecules such as methanol and bigger molecules for which it may allow to differentiate between gas-phase and solid-state formation pathways. Methanol exhibits a high deuterium fractionation in hot corinos. Since CH3OH is thought to be a precursor of methyl formate we expect that deuterated methyl formate is produced in such environments. We have searched for the singly-deuterated isotopologue of methyl formate, DCOOCH3, in IRAS 16293-2422, a hot corino well-known for its high degree of methanol deuteration. We have used the IRAM/JCMT unbiased spectral survey of IRAS 16293-2422 which allows us to search for the DCOOCH3 rotational transitions within the survey spectral range (80-280 GHz, 328-366 GHz). The expected emission of deuterated methyl formate is modelled at LTE and compared with the observations.} We have tentatively detected DCOOCH3 in the protostar IRAS 16293-2422. We assign eight lines detected in the IRAM survey to DCOOCH3. Three of these lines are affected by blending problems and one line is affected by calibration uncertainties, nevertheless the LTE emission model is compatible with the observations. A simple LTE modelling of the two cores in IRAS 16293-2422, based on a previous interferometric study of HCOOCH3, allows us to estimate the amount of DCOOCH3 in IRAS 16293-2422. Adopting an excitation temperature of 100 K and a source size of 2\arcsec and 1\farcs5 for the A and B cores, respectively, we find that N(A,DCOOCH3) = N(B,DCOOCH3) ~ 6.10^14 /cm2. The derived deuterium fractionation is ~ 15%, consistent with values for other deuterated species in this source and much greater than that expected from the deuterium cosmic abundance. DCOOCH3, if its tentative detection is confirmed, should now be considered in theoretical models that study complex molecule formation and their deuteration mechanisms. Experimental work is also needed to investigate the different chemical routes leading to the formation of deuterated methyl formate

Search for Interstellar Water in the Translucent Molecular Cloud toward HD 154368

We report an upper limit of 9 x 10^{12} cm-2 on the column density of water in the translucent cloud along the line of sight toward HD 154368. This result is based upon a search for the C-X band of water near 1240 \AA carried out using the Goddard High Resolution Spectrograph of the Hubble Space Telescope. Our observational limit on the water abundance together with detailed chemical models of translucent clouds and previous measurements of OH along the line of sight constrain the branching ratio in the dissociative recombination of H_3O+ to form water. We find at the $3\sigma$ level that no more than 30% of dissociative recombinations of H_3O+ can lead to H_2O. The observed spectrum also yielded high-resolution observations of the Mg II doublet at 1239.9 \AA and 1240.4 \AA, allowing the velocity structure of the dominant ionization state of magnesium to be studied along the line of sight. The Mg II spectrum is consistent with GHRS observations at lower spectral resolution that were obtained previously but allow an additional velocity component to be identified.Comment: Accepted by ApJ, uses aasp

Modeling water emission from low-mass protostellar envelopes

Within low-mass star formation, water vapor plays a key role in the chemistry and energy balance of the circumstellar material. The Herschel Space Observatory will open up the possibility to observe water lines originating from a wide range of excitation energies.Our aim is to simulate the emission of rotational water lines from envelopes characteristic of embedded low-mass protostars. A large number of parameters that influence the water line emission are explored: luminosity, density,density slope and water abundances.Both dust and water emission are modelled using full radiative transfer in spherical symmetry. The temperature profile is calculated for a given density profile. The H2O level populations and emission profiles are in turn computed with a non-LTE line code. The results are analyzed to determine the diagnostic value of different lines, and are compared with existing observations. Lines can be categorized in: (i) optically thick lines, including ground-state lines, mostly sensitive to the cold outer part; (ii) highly excited (E_u>200-250 K) optically thin lines sensitive to the abundance in the hot inner part; and (iii) lines which vary from optically thick to thin depending on the abundances. Dust influences the emission of water significantly by becoming optically thick at the higher frequencies, and by pumping optically thin lines. A good physical model of a source, including a correct treatment of dust, is a prerequisite to infer the water abundance structure and possible jumps at the evaporation temperature from observations. The inner warm (T>100 K) envelope can be probed byhighly-excited lines, while a combination of excited and spectrally resolved ground state lines probes the outer envelope. Observations of H218O lines, although weak, provide even stronger constraints on abundances.Comment: 17 pages with an online appendix of 6 pages. Accepted by A&A. Several figures are too large for astro-ph. These can be downloaded from http://www.strw.leidenuniv.nl/~kempen/water.ph