A data management system for structural genomics

BACKGROUND: Structural genomics (SG) projects aim to determine thousands of protein structures by the development of high-throughput techniques for all steps of the experimental structure determination pipeline. Crucial to the success of such endeavours is the careful tracking and archiving of experimental and external data on protein targets. RESULTS: We have developed a sophisticated data management system for structural genomics. Central to the system is an Oracle-based, SQL-interfaced database. The database schema deals with all facets of the structure determination process, from target selection to data deposition. Users access the database via any web browser. Experimental data is input by users with pre-defined web forms. Data can be displayed according to numerous criteria. A list of all current target proteins can be viewed, with links for each target to associated entries in external databases. To avoid unnecessary work on targets, our data management system matches protein sequences weekly using BLAST to entries in the Protein Data Bank and to targets of other SG centers worldwide. CONCLUSION: Our system is a working, effective and user-friendly data management tool for structural genomics projects. In this report we present a detailed summary of the various capabilities of the system, using real target data as examples, and indicate our plans for future enhancements

Evidence for Coexistence of Bulk Superconductivity and Itinerant Antiferromagnetism in the Heavy Fermion System CeCo(In1−x_{1-x}Cdx_x)5_5

In the generic phase diagram of heavy fermion systems, tuning an external parameter such as hydrostatic or chemical pressure modifies the superconducting transition temperature. The superconducting phase forms a dome in the temperature-tuning parameter phase diagram, which is associated with a maximum of the superconducting pairing interaction. Proximity to antiferromagnetism suggests a relation between the disappearance of antiferromagnetic order and superconductivity. We combine muon spin rotation, neutron scattering, and x-ray absorption spectroscopy techniques to gain access to the magnetic and electronic structure of CeCo(In$_{1-x}$Cd$_x$)$_5$ at different time scales. Different magnetic structures are obtained that indicate a magnetic order of itinerant character, coexisting with bulk superconductivity. The suppression of the antiferromagnetic order appears to be driven by a modification of the bandwidth/carrier concentration, implying that the electronic structure and consequently the interplay of superconductivity and magnetism is strongly affected by hydrostatic and chemical pressure.Comment: Article + Supplementary information 33 pages, 13 figure

Dynamique de spin dans le supraconducteur non conventionnel CeCoIn

Cette thèse porte sur l'étude de la dynamique de spin dans CeCoIn5 et plus précisément sur l'étude de la "résonance de spin" dans ce composé. CeCoIn5 est le composé à fermions lourds à base de cérium ayant la température de supraconductivité la plus élevé ( Tc = 2.3 K) et présente une supraconductivité non-conventionnelle avec un gap de type d_{x^2-y^2}. Dans l'état supraconducteur, le spectre des excitations magnétiques est radicalement modifié avec l'apparition d'un excitation particulièrement intense appelé "Résonance de spin". Ce type d'excitations a déjà été découvert dans les supraconducteurs haute-températures, dans d'autres composés à fermions lourds et également dans les nouveaux supraconducteurs au Fer. Dans cette thèse, nous étudions l'évolution de la résonance de spin en présence d'un champ magnétique et avec l'introduction d'impuretés magnétiques et non-magnétiques. D'après notre étude, les impuretés vont influer sur la résonance de spin via le gap supraconducteur, en effet la présence d'impuretés diminue le gap supraconducteur et l'énergie de la résonance de spin va diminuer de manière proportionnelle. L'influence du champ magnétique est délicate à considérer mais nos recherches porteraient vers un splitting Zeeman de la résonance de spin en accord avec les modèles développés pour les cuprates.In this thesis, the spin dynamics of CeCoIn5 has been studied by inelastic neutron scattering. CeCoIn5 presents the highest critical temperature ( Tc = 2.3 K) among heavy fermion Ce-based compounds and shows an unconventionnal supraconductivity with a $d_{x^2-y^2}$-wave gap. The magnetic excitation spectra is radically changed in the supraconducting state with the apparition of an intense excitation named "Spin resonance". This kind of excitation has already been discovered in high-Tc superconductors and even in the new Iron-based superconductors. In this thesis, we focused on the evolution of the spin resonance with the application of a magnetic field and the introduction of magnetic and non-magnetic impurities. From our study, the main effect of impurities is to decrease the superconducting gap which leads to a proportionnal decrease of the resonance energy. The case of magnetic field is more difficult and our researchs suggest a Zeeman splitting of the spin resonance in agreements with the models developped for the cuprates.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system.

OBJECTIVES: To evaluate rotavirus vaccination in Malaysia from the household's perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes. METHODS: The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model. RESULTS: We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles. CONCLUSION: We propose that universal vaccination complements health financing reforms in strengthening Universal Health Coverage (UHC). ECEA provides an important tool to understand the implications of vaccination for UHC, beyond traditional considerations of economic efficiency

Mini-dystrophin Expression Down-regulates IP3-mediated Calcium Release Events in Resting Dystrophin-deficient Muscle Cells

We present here evidence for the enhancement, at rest, of an inositol 1,4,5-trisphosphate (IP3)–mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(−)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, the number of sites discharging calcium (release site density [RSD]) was quantified and found more elevated in SolC1(−) than in SolD(+) myotubes. Variations of membrane potential had no significant effect on this difference, and higher resting [Ca2+]i in SolC1(−) (Marchand, E., B. Constantin, H. Balghi, M.C. Claudepierre, A. Cantereau, C. Magaud, A. Mouzou, G. Raymond, S. Braun, and C. Cognard. 2004. Exp. Cell Res. 297:363–379) cannot explain alone higher RSD. The exposure with SR Ca2+ channel inhibitors (ryanodine and 2-APB) and phospholipase C inhibitor (U73122) significantly reduced RSD in both cell types but with a stronger effect in dystrophin-deficient SolC1(−) myotubes. Immunocytochemistry allowed us to localize ryanodine receptors (RyRs) as well as IP3 receptors (IP3Rs), IP3R-1 and IP3R-2 isoforms, indicating the presence of both RyRs-dependent and IP3-dependent release systems in both cells. We previously reported evidence for the enhancement, through a Gi protein, of the IP3-mediated calcium signaling pathway in SolC1(−) as compared to SolD(+) myotubes during a high K+ stimulation (Balghi, H., S. Sebille, B. Constantin, S. Patri, V. Thoreau, L. Mondin, E. Mok, A. Kitzis, G. Raymond, and C. Cognard. 2006. J. Gen. Physiol. 127:171–182). Here we show that, at rest, these regulation mechanisms are also involved in the modulation of calcium release activities. The enhancement of resting release activity may participate in the calcium overload observed in dystrophin-deficient myotubes, and our findings support the hypothesis of the regulatory role of mini-dystrophin on intracellular signaling