Towards data warehousing and mining of protein unfolding simulation data

OBJECTIVES: The prediction of protein structure and the precise understanding of protein folding and unfolding processes remains one of the greatest challenges in structural biology and bioinformatics. Computer simulations based on molecular dynamics (MD) are at the forefront of the effort to gain a deeper understanding of these complex processes. Currently, these MD simulations are usually on the order of tens of nanoseconds, generate a large amount of conformational data and are computationally expensive. More and more groups run such simulations and generate a myriad of data, which raises new challenges in managing and analyzing these data. Because the vast range of proteins researchers want to study and simulate, the computational effort needed to generate data, the large data volumes involved, and the different types of analyses scientists need to perform, it is desirable to provide a public repository allowing researchers to pool and share protein unfolding data. METHODS: To adequately organize, manage, and analyze the data generated by unfolding simulation studies, we designed a data warehouse system that is embedded in a grid environment to facilitate the seamless sharing of available computer resources and thus enable many groups to share complex molecular dynamics simulations on a more regular basis. RESULTS: To gain insight into the conformational fluctuations and stability of the monomeric forms of the amyloidogenic protein transthyretin (TTR), molecular dynamics unfolding simulations of the monomer of human TTR have been conducted. Trajectory data and meta-data of the wild-type (WT) protein and the highly amyloidogenic variant L55P-TTR represent the test case for the data warehouse. CONCLUSIONS: Web and grid services, especially pre-defined data mining services that can run on or 'near' the data repository of the data warehouse, are likely to play a pivotal role in the analysis of molecular dynamics unfolding data

Validity and reliability of a health care service evaluation instrument for tuberculosis

OBJECTIVE To evaluate the validity and reliability of an instrument that evaluates the structure of primary health care units for the treatment of tuberculosis. METHODS This cross-sectional study used simple random sampling and evaluated 1,037 health care professionals from five Brazilian municipalities (Natal, state of Rio Grande do Norte; Cabedelo, state of Paraíba; Foz do Iguaçu, state of Parana; Sao José do Rio Preto, state of Sao Paulo, and Uberaba, state of Minas Gerais) in 2011. Structural indicators were identified and validated, considering different methods of organization of the health care system in the municipalities of different population sizes. Each structure represented the organization of health care services and contained the resources available for the execution of health care services: physical resources (equipment, consumables, and facilities); human resources (number and qualification); and resources for maintenance of the existing infrastructure and technology (deemed as the organization of health care services). The statistical analyses used in the validation process included reliability analysis, exploratory factor analysis, and confirmatory factor analysis. RESULTS The validation process indicated the retention of five factors, with 85.9% of the total variance explained, internal consistency between 0.6460 and 0.7802, and quality of fit of the confirmatory factor analysis of 0.995 using the goodness-of-fit index. The retained factors comprised five structural indicators: professionals involved in the care of tuberculosis patients, training, access to recording instruments, availability of supplies, and coordination of health care services with other levels of care. Availability of supplies had the best performance and the lowest coefficient of variation among the services evaluated. The indicators of assessment of human resources and coordination with other levels of care had satisfactory performance, but the latter showed the highest coefficient of variation. The performance of the indicators “training” and “access to recording instruments” was inferior to that of other indicators. CONCLUSIONS The instrument showed feasibility of application and potential to assess the structure of primary health care units for the treatment of tuberculosis

Substrates specialization in lipid compounds and hydrocarbons of <i>Marinobacter</i> genus

International audienceThe impact of petroleum contamination and of burrowing macrofauna on abundances of Marinobacter and denitrifiers was tested in marine sediment mesocoms after 3 months incubation. Quantification of this genus by qPCR with a new primer set showed that the main factor favoring Marinobacter abundance was hydrocarbon amendment followed by macrofauna presence. In parallel, proportion of nosZ-harboring bacteria increased in the presence of marcrofauna. Quantitative finding were explained by physiological data from a set of 34 strains and by genomic analysis of 16 genomes spanning 15 different Marinobacter-validated species (Marinobacter hydrocarbonoclasticus, Marinobacter daeopensis, Marinobacter santoriniensis, Marinobacter pelagius, Marinobacter flavimaris, Marinobacter adhaerens, Marinobacter xestospongiae, Marinobacter algicola, Marinobacter vinifirmus, Marinobacter maritimus, Marinobacter psychrophilus, Marinobacter lipoliticus, Marinobacter manganoxydans, Marinobacter excellens, Marinobacter nanhaiticus) and 4 potential novel ones. Among the 105 organic electron donors tested in physiological analysis, Marinobacter pattern appeared narrow for almost all kinds of organic compounds except lipid ones. Strains of this set could oxidize a very large spectrum of lipids belonging to glycerolipids, branched, fatty acyls, and aromatic hydrocarbon classes. Physiological data were comforted by genomic analysis, and genes of alkane 1-monooxygenase, haloalkane dehalogenase, and flavin-binding monooxygenase were detected in most genomes. Denitrification was assessed for several strains belonging to M. hydrocarbonoclasticus, M. vinifirmus, Marinobacter maritinus, and M. pelagius species indicating the possibility to use nitrate as alternative electron acceptor. Higher occurrence of Marinobacter in the presence of petroleum appeared to be the result of a broader physiological trait allowing this genus to use lipids including hydrocarbon as principal electron donors