Grid Added Value to Address Malaria

Through this paper, we call for a distributed, internet-based collaboration to address one of the worst plagues of our present world, malaria. The spirit is a non-proprietary peer-production of information-embedding goods. And we propose to use the grid technology to enable such a world wide "open source" like collaboration. The first step towards this vision has been achieved during the summer on the EGEE grid infrastructure where 46 million ligands were docked for a total amount of 80 CPU years in 6 weeks in the quest for new drugs.Comment: 7 pages, 1 figure, 6th IEEE International Symposium on Cluster Computing and the Grid, Singapore, 16-19 may 2006, to appear in the proceeding

Tracing early evolutionary stages of high-mass star formation with molecular lines

Despite its major role in the evolution of the interstellar medium, the formation of high-mass stars (M > 10 Msol) is still poorly understood. Two types of massive star cluster precursors, the so-called Massive Dense Cores (MDCs), have been observed, which differ in their mid-infrared brightness. The origin of this difference is not established and could be the result of evolution, density, geometry differences, or a combination of these. We compare several molecular tracers of physical conditions (hot cores, shocks) observed in a sample of mid-IR weak emitting MDCs with previous results obtained in a sample of exclusively mid-IR bright MDCs. The aim is to understand the differences between these two types of object. We present single-dish observations of HDO, H2O-18, SO2 and CH3OH lines at lambda = 1.3 - 3.5 mm. We study line profiles and estimate abundances of these molecules, and use a partial correlation method to search for trends in the results. The detection rates of thermal emission lines are found to be very similar between mid-IR quiet and bright objects. The abundances of H2O, HDO (1E-13 to 1E-9 in the cold outer envelopes), SO2 and CH3OH differ from source to source but independently of their mid-IR flux. In contrast, the methanol class I maser emission, a tracer of outflow shocks, is found to be strongly anti-correlated with the 12 micron source brightnesses. The enhancement of the methanol maser emission in mid-IR quiet MDCs may indicate a more embedded nature. Since total masses are similar between the two samples, we suggest that the matter distribution is spherical around mid-IR quiet sources but flattened around mid-IR bright ones. In contrast, water emission is associated with objects containing a hot molecular core, irrespective of their mid-IR brightness. These results indicate that the mid-IR brightness of MDCs is an indicator of their evolutionary stage.Comment: 15 pages, 6 figures, 11 tables, accepted for publication in A&A the 11/06/201

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

The Water Vapor Abundance in Orion KL Outflows

We present the detection and modeling of more than 70 far-IR pure rotational lines of water vapor, including the 18O and 17O isotopologues, towards Orion KL. Observations were performed with the Long Wavelength Spectrometer Fabry-Perot (LWS/FP; R~6800-9700) on board the Infrared Space Observatory (ISO) between ~43 and ~197 um. The water line profiles evolve from P-Cygni type profiles (even for the H2O18 lines) to pure emission at wavelengths above ~100 um. We find that most of the water emission/absorption arises from an extended flow of gas expanding at 25+-5 kms^-1. Non-local radiative transfer models show that much of the water excitation and line profile formation is driven by the dust continuum emission. The derived beam averaged water abundance is 2-3x10^-5. The inferred gas temperature Tk=80-100 K suggests that: (i) water could have been formed in the "plateau" by gas phase neutral-neutral reactions with activation barriers if the gas was previously heated (e.g. by shocks) to >500 K and/or (ii) H2O formation in the outflow is dominated by in-situ evaporation of grain water-ice mantles and/or (iii) H2O was formed in the innermost and warmer regions (e.g. the hot core) and was swept up in ~1000 yr, the dynamical timescale of the outflow.Comment: Accepted for publication in ApJ letters [2006 August 7] (5 pages 2, figures, not edited

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

présenté par N. Jac

Grid enabled virtual screening against malaria

34 pages, 5 figures, 3 tables, to appear in Journal of Grid Computing - PCSV, à paraître dans Journal of Grid ComputingWISDOM is an international initiative to enable a virtual screening pipeline on a grid infrastructure. Its first attempt was to deploy large scale in silico docking on a public grid infrastructure. Protein-ligand docking is about computing the binding energy of a protein target to a library of potential drugs using a scoring algorithm. Previous deployments were either limited to one cluster, to grids of clusters in the tightly protected environment of a pharmaceutical laboratory or to pervasive grids. The first large scale docking experiment ran on the EGEE grid production service from 11 July 2005 to 19 August 2005 against targets relevant to research on malaria and saw over 41 million compounds docked for the equivalent of 80 years of CPU time. Up to 1,700 computers were simultaneously used in 15 countries around the world. Issues related to the deployment and the monitoring of the in silico docking experiment as well as experience with grid operation and services are reported in the paper. The main problem encountered for such a large scale deployment was the grid infrastructure stability. Although the overall success rate was above 80%, a lot of monitoring and supervision was still required at the application level to resubmit the jobs that failed. But the experiment demonstrated how grid infrastructures have a tremendous capacity to mobilize very large CPU resources for well targeted goals during a significant period of time. This success leads to a second computing challenge targeting Avian Flu neuraminidase N1

Deubiquitylating Enzymes and DNA Damage Response Pathways

Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes. The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways. It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention. The synthetic lethal approach provides exciting opportunities for the development of targeted therapies to treat cancer: most tumours have lost critical DDR pathways, and thus rely more heavily on the remaining pathways, while normal tissues are still equipped with all DDR pathways. Here, we review key deubiquitylating enzymes (DUBs) involved in DDR pathways, and describe how targeting DUBs may lead to selective therapies to treat cancer patients