Contribution des facteurs génétiques et non génétiques au niveau de vitamine D chez des individus infectés par le VIH

La vitamine D est connue pour son rôle dans le métabolisme osseux et dans des nombreux autres systèmes. La fréquence de carence en vitamine D est élevée dans la population générale, et elle est encore plus élevée chez les individus infectés par le VIH. Des nombreuses études ont recherché les facteurs qu'influencent la concentration plasmatique de 25(OH)D dans la population générale. Notre travail a pour but d'analyser la contribution des facteurs génétiques et non génétiques qu'influencent le niveau de 25(OH)D plasmatique chez des individus infectés par le VIH. La population de notre étude est constituée par 552 patients de la SHCS d'ethnie caucasienne et ayant eu au moins une mesure de la concentration plasmatique de 25(OH)D. Nous avons développé un modèle de pharmacocinétique des populations pour étudier la contribution de chaque facteur inclus dans nos analyses. Les facteurs analysés étaient: le sexe, l'âge, le poids, le BMI, la hauteur, la saison, le tabagisme et 7 SNPs associés au niveau de 25(OH)D identifiés par les études d'association pangénomique. Ces SNPs sont situés sur 4 gènes impliqués dans le métabolisme de la vitamine D. Nous observons dans cette population une prévalence élevée de carence en vitamine D: 78.8% des patients ont eu des taux de 25(OH)D insuffisants et 53.1% avaient une déficience de 25(OH)D. De plus, nous observons que le niveau plasmatique de 25(OH)D est associé de façon statistiquement significative avec: la période de l'année (p≈3.42x10−42), le BMI (p≈0.006), le tabagisme (p≈0.009) et le SNP rs2282679 (p≈0.0035). Ce dernier se trouve sur le gène GC, qui est responsable du codage pour la transcription de la DBP, protéine qui sert au transport des métabolites de la vitamine D dans le plasma. Ces éléments nous permettent d'expliquer 8% de la variabilité interindividuelle totale des taux de 25(OH)D retrouvée dans cette population. Une grande partie de la variabilité interindividuelle doit encore être expliquée, mais notre étude nous a permis, d'un côté de confirmer l'influence de certains facteurs identifiés dans la population générale sur une population spécifique qui est particulièrement à risque de développer une carence en vitamine D et, de l'autre côté d'examiner la contribution des polymorphismes génétiques au métabolisme de la vitamine D. Les efforts pour comprendre toujours davantage les causes de carence en vitamine D sont importants pour pouvoir identifier les individus plus à risque, de façon à prévenir et mieux prendre en charge une condition qui est source importante de morbidité et de mortalité et qui est facile à traiter

Enhancing the Coherence of a Spin Qubit by Operating it as a Feedback Loop That Controls its Nuclear Spin Bath

In many realizations of electron spin qubits the dominant source of decoherence is the fluctuating nuclear spin bath of the host material. The slowness of this bath lends itself to a promising mitigation strategy where the nuclear spin bath is prepared in a narrowed state with suppressed fluctuations. Here, this approach is realized for a two-electron spin qubit in a GaAs double quantum dot and a nearly ten-fold increase in the inhomogeneous dephasing time $T_2^*$ is demonstrated. Between subsequent measurements, the bath is prepared by using the qubit as a feedback loop that first measures its nuclear environment by coherent precession, and then polarizes it depending on the final state. This procedure results in a stable fixed point at a nonzero polarization gradient between the two dots, which enables fast universal qubit control.Comment: Journal version. Improved clarity of presentation and more concise terminology. 4 pages, 3 figures. Supplementary document included as ancillary fil

Smoke in the water : the use of tariff policy flexibility in crises

As the economic crisis deepens and widens, fears of a return to the protectionist spiral of the 1930s become more common. However, an important difference between the 1930s and today is the existence of the World Trade Organization and the legal limits it imposes on the protectionist responses members can pursue. The objective of this paper is threefold. First, to assess the extent to which applied tariff can legally be raised without violating tariff-bound obligations, and compare it with what is economically possible. Second, to examine what has been the protectionist response of individual countries when facing an economic crisis since the creation of the WTO. Finally, to predict how far the protectionist responses will go during the current crisis. Results suggest that the policy space left when looking at what is economically possible is indeed quite large. However, in the recent past very little of the available policy space has been used by countries suffering from an economic crisis. Our predictions for the current crisis are modest tariff hikes in the order of 8 percent.International Trade and Trade Rules,Trade Policy,Free Trade,Debt Markets,Access to Finance

Probabilistic framework for multiaxial LCF assessment under material variability

The influence of material variability upon the multiaxial LCF assessment of engineering components is missing for a comprehensive description. In this paper, a probabilistic framework is established for multiaxial LCF assessment of notched components by using the Chaboche plasticity model and Fatemi-Socie criterion. Simulations from experimental results of two steels reveal that the scatter in fatigue lives can be well described by quantifying the variability of four material parameters Ï\u83fâ\u80²,εfâ\u80²,b,c. A procedure for choosing the safety factor for fatigue design has been derived by using first order approximation

Semi-classical model for the dephasing of a two-electron spin qubit coupled to a coherently evolving nuclear spin bath

We study electron spin decoherence in a two-electron double quantum dot due to the hyperfine interaction, under spin-echo conditions as studied in recent experiments. We develop a semi-classical model for the interaction between the electron and nuclear spins, in which the time-dependent Overhauser fields induced by the nuclear spins are treated as classical vector variables. Comparison of the model with experimentally-obtained echo signals allows us to quantify the contributions of various processes such as coherent Larmor precession and spin diffusion to the nuclear spin evolution.Comment: 14 Pages, some equations were corrected; Published July 27, 201

Nuclear localization of mouse fibroblast growth factor 2 requires N-terminal and C-terminal sequences

In vertebrates, different isoforms of fibroblast growth factor 2 (FGF2) exist, which differ by their N-terminal extension. They show different localization and expression levels and exert distinct biological effects. Nevertheless, genetic inactivation of all FGF2 isoforms in the mouse results in only mild phenotypes. Here, we analyzed mouse FGF2, and show that, as in the human, mouse FGF2 contains CTG-initiated high molecular-weight (HMW) isoforms, which contain a nuclear localization signal, and which mediate localization of this isoform to the nucleus. Using green fluorescent protein-FGF2 fusions, we furthermore observed, that C-terminal deletions disable nuclear localization of the short low-molecular-weight (LMW) 18-kDa isoform. This loss of specific localization is accompanied by a loss in heparin binding. We therefore suggest that, first, localization of mouse FGF2 is comparable to that in other vertebrates and, second, FGF2 contains at least two sequences important for nuclear localization, a nuclear localization sequence at the N terminus which is only contained in the HMW isoform, and another sequence at the C terminus, which is only required for localization of the LMW 18-kDa isofor

Discussion of models for LCF small crack growth

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Assessment of multiaxial fatigue life prediction methodologies for Inconel 718

Abstract Fatigue life prediction methodologies for the assessment of the structural integrity of safety critical components in modern turbine engines require a close integration of advanced multiaxial fatigue life prediction procedures and of specific multiaxial tests, representative of the service conditions of turbine engine components and materials. The objective of the research work presented in this paper is to extend currently employed methodologies for the assessment of fatigue strength of turbine engines disks by integrating suitable multiaxial fatigue criteria and test results of multiaxial fatigue experiments conducted on Inconel 718 material at temperatures similar to those experienced by the disc materials during service. Smooth tubular specimens of Inconel 718 have been employed for conducting tension/torsion strain controlled high temperature fatigue tests. Specimens have been cut out from forged parts utilised for the production of engine discs, thus preserving the typical properties of disc materials (microstructure, basic mechanical properties, etc.). Different models/criteria have been evaluated by comparing fatigue life predictions and multiaxial fatigue experiments. It's well known that agreement of life predictions with experimental life is strongly affected not only by the choice of the multiaxial fatigue criteria but also by the way the reference fatigue data are integrated in the criteria. Therefore, specific multiaxial fatigue tests have been carried out, in order to validate and to improve the assessment capabilities of the lifing procedures. Moreover, multiaxial fatigue tests permit advances in the basic understanding of materials behaviour that might be utilised in the processes of declaring component service lives

Immunoglobulin domains in Escherichia coli and other enterobacteria: from pathogenesis to applications in antibody technologies

The immunoglobulin (Ig) protein domain is widespread in nature having a well-recognized role in proteins of the immune system. In this review, we describe the proteins containing Ig-like domains in Escherichia coli and entero-bacteria, reporting their structural and functional properties, protein folding, and diverse biological roles. In addition, we cover the expression of heterolo-gous Ig domains in E. coli owing to its biotechnological application for expression and selection of antibody fragments and full-length IgG molecules. Ig-like domains in E. coli and enterobacteria are frequently found in cell surface proteins and fimbrial organelles playing important functions during host cell adhesion and invasion of pathogenic strains, being structural components of pilus and nonpilus fimbrial systems and members of the intimin/invasin family of outer membrane (OM) adhesins. Ig-like domains are also found in periplasmic chaperones and OM usher proteins assembling fimbriae, in oxidoreductases and hydrolytic enzymes, ATP-binding cassette transporters, sugar-binding and metal-resistance proteins. The folding of most E. coli Ig-like domains is assisted by periplasmic chaperones, peptidyl prolylcis/transisomerases and disulfide bond catalysts that also participate in the folding of antibodies expressed in this bacterium. The technologies for expression and selection of recombinant antibodies in E. coli are described along with their biotechnological potential.This work has been supported by Grants of the Spanish Ministry of Science and Innovation (BIO2008-05201; BIO2011-26689), the Autonomous Community of Madrid (S-BIO-236-2006; S2010-BMD-2312), CSIC (PIE 2011 20E049), ‘la Caixa’ Foundation, and the VI Framework Program from the European Union (FP6-LSHB-CT-2005-512061 NoE ‘EuroPathogenomics’).Peer reviewe