10,503 research outputs found
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
Large Scale In Silico Screening on Grid Infrastructures
Large-scale grid infrastructures for in silico drug discovery open
opportunities of particular interest to neglected and emerging diseases. In
2005 and 2006, we have been able to deploy large scale in silico docking within
the framework of the WISDOM initiative against Malaria and Avian Flu requiring
about 105 years of CPU on the EGEE, Auvergrid and TWGrid infrastructures. These
achievements demonstrated the relevance of large-scale grid infrastructures for
the virtual screening by molecular docking. This also allowed evaluating the
performances of the grid infrastructures and to identify specific issues raised
by large-scale deployment.Comment: 14 pages, 2 figures, 2 tables, The Third International Life Science
Grid Workshop, LSGrid 2006, Yokohama, Japan, 13-14 october 2006, to appear in
the proceeding
A Geographical Location Model for Targeted Implementation of Lure-and-Kill Strategies Against Disease-Transmitting Mosquitoes in Rural Areas
Outdoor devices for luring and killing disease-transmitting mosquitoes have been proposed as potential com- plementary interventions alongside existing intra-domiciliary methods namely insecticide treated nets and house spraying with residual insecticides. To enhance effectiveness of such outdoor interventions, it is essential to optimally locate them in such a way that they target most of the outdoor mosquitoes. Using odour-baited lure and kill stations (OBS) as an example, we describe a map model derived from: 1) com-munity participatory mapping conducted to identify mosquito breeding habitats, 2) entomological field studies conducted to estimate outdoor mosquito densities and to determine safe distances of the OBS from human dwellings, and 3) field surveys conducted to map households, roads, outdoor human aggregations and landmarks. The resulting data were combined in a Ge- ographical Information Systems (GIS) environment and analysed to determine optimal locations for the OBS. Separately, a GIS-interpolated map produced by asking community members to rank different zones of the study area and show where they expected to find most mosquitoes, was visually compared to another map interpolated from the entomological survey of outdoor mosquito densities. An easy-to-interpret suitability map showing optimal sites for placing OBS was produced, which clearly depicted areas least suitable and areas most suitable for locating the devices. Comparative visual interpretation of maps derived from interpolating the community knowledge and entomological data revealed major similarities between the two maps. Using distribution patterns of human and mosquito populations as well as characteristics of candidate outdoor interventions, it is possible to readily determine suitable areas for targeted positioning of the interventions, thus improve effectiveness. This study also highlights possibilities of relying on community knowledge to approximate areas where mosquitoes are most abundant and where to locate outdoor complementary interventions such as odour-baited lure and kill stations for controlling disease-transmitting mosquitoes.\u
High Throughput Virtual Screening with Data Level Parallelism in Multi-core Processors
Improving the throughput of molecular docking, a computationally intensive
phase of the virtual screening process, is a highly sought area of research
since it has a significant weight in the drug designing process. With such
improvements, the world might find cures for incurable diseases like HIV
disease and Cancer sooner. Our approach presented in this paper is to utilize a
multi-core environment to introduce Data Level Parallelism (DLP) to the
Autodock Vina software, which is a widely used for molecular docking software.
Autodock Vina already exploits Instruction Level Parallelism (ILP) in
multi-core environments and therefore optimized for such environments. However,
with the results we have obtained, it can be clearly seen that our approach has
enhanced the throughput of the already optimized software by more than six
times. This will dramatically reduce the time consumed for the lead
identification phase in drug designing along with the shift in the processor
technology from multi-core to many-core of the current era. Therefore, we
believe that the contribution of this project will effectively make it possible
to expand the number of small molecules docked against a drug target and
improving the chances to design drugs for incurable diseases.Comment: Information and Automation for Sustainability (ICIAfS), 2012 IEEE 6th
International Conference o
Design of trials for interrupting the transmission of endemic pathogens
Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up.; A generic model of disease transmission was used to simulate infections in stepped wedge cluster-randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs for providing generalizable causal inferences about the impact of such interventions, including measurements of the contamination effects. The simulations were applied to the geography of Rusinga Island, Lake Victoria, Kenya, the site of the SolarMal trial on the use of odor-baited mosquito traps to eliminate Plasmodium falciparum malaria. These were used to compare variants in the proposed SWCRT designs for the SolarMal trial.; Measures of contamination effects were found that could be assessed in the simulated trials. Inspired by analyses of trials of insecticide-treated nets against malaria when applied to the geography of the SolarMal trial, these measures were found to be robust to different variants of SWCRT design. Analyses of the likely extent of contamination effects supported the choice of cluster size for the trial.; The SWCRT is an appropriate design for trials that assess the feasibility of local elimination of a pathogen. The effects of incomplete coverage can be estimated by analyzing the extent of contamination between arms in such trials, and the estimates also support inferences about causality. The SolarMal example illustrates how generic transmission models incorporating spatial smoothing can be used to simulate such trials for a power calculation and optimization of cluster size and randomization strategies. The approach is applicable to a range of infectious diseases transmitted via environmental reservoirs or via arthropod vectors
Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?
The organization and mining of malaria genomic and post-genomic data is
highly motivated by the necessity to predict and characterize new biological
targets and new drugs. Biological targets are sought in a biological space
designed from the genomic data from Plasmodium falciparum, but using also the
millions of genomic data from other species. Drug candidates are sought in a
chemical space containing the millions of small molecules stored in public and
private chemolibraries. Data management should therefore be as reliable and
versatile as possible. In this context, we examined five aspects of the
organization and mining of malaria genomic and post-genomic data: 1) the
comparison of protein sequences including compositionally atypical malaria
sequences, 2) the high throughput reconstruction of molecular phylogenies, 3)
the representation of biological processes particularly metabolic pathways, 4)
the versatile methods to integrate genomic data, biological representations and
functional profiling obtained from X-omic experiments after drug treatments and
5) the determination and prediction of protein structures and their molecular
docking with drug candidate structures. Progresses toward a grid-enabled
chemogenomic knowledge space are discussed.Comment: 43 pages, 4 figures, to appear in Malaria Journa
Innovative in silico approaches to address avian flu using grid technology
The recent years have seen the emergence of diseases which have spread very
quickly all around the world either through human travels like SARS or animal
migration like avian flu. Among the biggest challenges raised by infectious
emerging diseases, one is related to the constant mutation of the viruses which
turns them into continuously moving targets for drug and vaccine discovery.
Another challenge is related to the early detection and surveillance of the
diseases as new cases can appear just anywhere due to the globalization of
exchanges and the circulation of people and animals around the earth, as
recently demonstrated by the avian flu epidemics. For 3 years now, a
collaboration of teams in Europe and Asia has been exploring some innovative in
silico approaches to better tackle avian flu taking advantage of the very large
computing resources available on international grid infrastructures. Grids were
used to study the impact of mutations on the effectiveness of existing drugs
against H5N1 and to find potentially new leads active on mutated strains. Grids
allow also the integration of distributed data in a completely secured way. The
paper presents how we are currently exploring how to integrate the existing
data sources towards a global surveillance network for molecular epidemiology.Comment: 7 pages, submitted to Infectious Disorders - Drug Target
Shared Value in Emerging Markets: How Multinational Corporations Are Redefining Business Strategies to Reach Poor or Vulnerable Populations
This report illuminates the enormous opportunities in emerging markets for companies to drive competitive advantage and sustainable impact at scale. It identifies how over 30 companies across multiple sectors and geographies design and measure business strategies that also improve the lives of underserved individuals
- …