Nouveaux traitements de l'hépatite C: aspects pharmacologiques et potentiel d'interaction [New hepatitis C treatments: pharmacological considerations and potential for drug interactions].

Progress in the understanding of the hepatitis C virus life cycle allowed the development of new, very promising antiviral therapies. Although these new drugs have a favourable profile in terms of efficacy, tolerance and interaction potential, their prescription in the setting of comedication and impaired renal or hepatic function remains a challenge. Here, we provide a summary of pharmacological considerations, focusing on sofosbuvir, simeprevir and daclatasvir. A better understanding of their metabolic pathways and transporters may help the prescriber to identify and manage drug interactions especially in patients under immunosuppressive or anti-HIV therapy. Recommendations for the prescription of these drugs in specific situations are also discussed.

DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.

Detection of viral nucleic acids is central to antiviral immunity. Recently, DAI/ZBP1 (DNA-dependent activator of IRFs/Z-DNA binding protein 1) was identified as a cytoplasmic DNA sensor and shown to activate the interferon regulatory factor (IRF) and nuclear factor-kappa B (NF-kappaB) transcription factors, leading to type-I interferon production. DAI-induced IRF activation depends on TANK-binding kinase 1 (TBK1), whereas signalling pathways and molecular components involved in NF-kappaB activation remain elusive. Here, we report the identification of two receptor-interacting protein (RIP) homotypic interaction motifs (RHIMs) in the DAI protein sequence, and show that these domains relay DAI-induced NF-kappaB signals through the recruitment of the RHIM-containing kinases RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI-induced NF-kappaB activation. Importantly, RIP recruitment to DAI is inhibited by the RHIM-containing murine cytomegalovirus (MCMV) protein M45. These findings delineate the DAI signalling pathway to NF-kappaB and suggest a possible new immune modulation strategy of the MCMV.

Interaction of prechilling, temperature, osmotic stress, and light in Picea abies seed germination

Summary

Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity : a role for microglia

The neuroprotective effect of neuropeptide Y (NPY) receptor activation was investigated in organotypic mouse hippocampal slice cultures exposed to the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Exposure of 2-week-old slice cultures, derived from 7-day-old C57BL/6 mice, to 8 microm AMPA, for 24 h, induced degeneration of CA1 and CA3 pyramidal cells, as measured by cellular uptake of propidium iodide (PI). A significant neuroprotection, with a reduction of PI uptake in CA1 and CA3 pyramidal cell layers, was observed after incubation with a Y(2) receptor agonist [NPY(13-36), 300 nm]. This effect was sensitive to the presence of the selective Y(2) receptor antagonist (BIIE0246, 1 microm), but was not affected by addition of TrkB-Fc or by a neutralizing antibody against brain-derived neurotrophic factor (BDNF). Moreover, addition of a Y(1) receptor antagonist (BIBP3226, 1 microm) or a NPY-neutralizing antibody helped to disclose a neuroprotective role of endogenous NPY in CA1 region. Cultures exposed to 8 microm AMPA for 24 h, displayed, as measured by an enzyme-linked immunosorbent assay, a significant increase in BDNF. In such cultures there was an up-regulation of neuronal TrkB immunoreactivity, as well as the presence of BDNF-immunoreactive microglial cells at sites of injury. Thus, an increase of AMPA-receptor mediated neurodegeneration, in the mouse hippocampus, was prevented by neuroprotective pathways activated by NPY receptors (Y(1) and Y(2)), which can be affected by BDNF released by microglia and neurons.

Interaction analysis and psychology: A dialogical perspective

Interaction analysis is not a prerogative of any discipline in social sciences. It has its own history within each disciplinary field and is related to specific research objects. From the standpoint of psychology, this article first draws upon a distinction between factorial and dialogical conceptions of interaction. It then briefly presents the basis of a dialogical approach in psychology and focuses upon four basic assumptions. Each of them is examined on a theoretical and on a methodological level with a leading question: to what extent is it possible to develop analytical tools that are fully coherent with dialogical assumptions? The conclusion stresses the difficulty of developing methodological tools that are fully consistent with dialogical assumptions and argues that there is an unavoidable tension between accounting for the complexity of an interaction and using methodological tools which necessarily "monologise" this complexity.

Ferromagnetic instabilities in neutron matter at finite temperature with the Skyrme interaction

The properties of spin-polarized neutron matter are studied at both zero and finite temperature using Skyrme-type interactions. It is shown that the critical density at which ferromagnetism takes place decreases with temperature. This unexpected behavior is associated to an anomalous behavior of the entropy that becomes larger for the polarized phase than for the unpolarized one above a certain critical density. This fact is a consequence of the dependence of the entropy on the effective mass of the neutrons with different third spin component. A new constraint on the parameters of the effective Skyrme force is derived if this behavior is to be avoided.

Transition to parenthood: The role of social interaction and endogenous networks

Empirical studies indicate that the transition to parenthood is influenced by an individual's peer group. To study the mechanisms creating interdepen- dencies across individuals' transition to parenthood and its timing we apply an agent-based simulation model. We build a one-sex model and provide agents with three different characteristics regarding age, intended education and parity. Agents endogenously form their network based on social closeness. Network members then may influence the agents' transition to higher parity levels. Our numerical simulations indicate that accounting for social inter- actions can explain the shift of first-birth probabilities in Austria over the period 1984 to 2004. Moreover, we apply our model to forecast age-specific fertility rates up to 2016.

System-level Support for Mobile Ad hoc Communications: an Algorithmic & Practical Approach

A mobile ad hoc network (MANET) is a decentralized and infrastructure-less network. This thesis aims to provide support at the system-level for developers of applications or protocols in such networks. To do this, we propose contributions in both the algorithmic realm and in the practical realm. In the algorithmic realm, we contribute to the field by proposing different context-aware broadcast and multicast algorithms in MANETs, namely six-shot broadcast, six-shot multicast, PLAN-B and ageneric algorithmic approach to optimize the power consumption of existing algorithms. For each algorithm we propose, we compare it to existing algorithms that are either probabilistic or context-aware, and then we evaluate their performance based on simulations. We demonstrate that in some cases, context-aware information, such as location or signal-strength, can improve the effciency. In the practical realm, we propose a testbed framework, namely ManetLab, to implement and to deploy MANET-specific protocols, and to evaluate their performance. This testbed framework aims to increase the accuracy of performance evaluation compared to simulations, while keeping the ease of use offered by the simulators to reproduce a performance evaluation. By evaluating the performance of different probabilistic algorithms with ManetLab, we observe that both simulations and testbeds should be used in a complementary way. In addition to the above original contributions, we also provide two surveys about system-level support for ad hoc communications in order to establish a state of the art. The first is about existing broadcast algorithms and the second is about existing middleware solutions and the way they deal with privacy and especially with location privacy. - Un réseau mobile ad hoc (MANET) est un réseau avec une architecture décentralisée et sans infrastructure. Cette thèse vise à fournir un support adéquat, au niveau système, aux développeurs d'applications ou de protocoles dans de tels réseaux. Dans ce but, nous proposons des contributions à la fois dans le domaine de l'algorithmique et dans celui de la pratique. Nous contribuons au domaine algorithmique en proposant différents algorithmes de diffusion dans les MANETs, algorithmes qui sont sensibles au contexte, à savoir six-shot broadcast,six-shot multicast, PLAN-B ainsi qu'une approche générique permettant d'optimiser la consommation d'énergie de ces algorithmes. Pour chaque algorithme que nous proposons, nous le comparons à des algorithmes existants qui sont soit probabilistes, soit sensibles au contexte, puis nous évaluons leurs performances sur la base de simulations. Nous montrons que, dans certains cas, des informations liées au contexte, telles que la localisation ou l'intensité du signal, peuvent améliorer l'efficience de ces algorithmes. Sur le plan pratique, nous proposons une plateforme logicielle pour la création de bancs d'essai, intitulé ManetLab, permettant d'implémenter, et de déployer des protocoles spécifiques aux MANETs, de sorte à évaluer leur performance. Cet outil logiciel vise à accroître la précision desévaluations de performance comparativement à celles fournies par des simulations, tout en conservant la facilité d'utilisation offerte par les simulateurs pour reproduire uneévaluation de performance. En évaluant les performances de différents algorithmes probabilistes avec ManetLab, nous observons que simulateurs et bancs d'essai doivent être utilisés de manière complémentaire. En plus de ces contributions principales, nous fournissons également deux états de l'art au sujet du support nécessaire pour les communications ad hoc. Le premier porte sur les algorithmes de diffusion existants et le second sur les solutions de type middleware existantes et la façon dont elles traitent de la confidentialité, en particulier celle de la localisation.

Double folding with a density-dependent effective interaction and it s analytical approximation

The real part of the optical potential for heavy ion elastic scattering is obtained by double folding of the nuclear densities with a density-dependent nucleon-nucleon effective interaction which was successful in describing the binding, size, and nucleon separation energies in spherical nuclei. A simple analytical form is found to differ from the resulting potential considerably less than 1% all through the important region. This analytical potential is used so that only few points of the folding need to be computed. With an imaginary part of the Woods-Saxon type, this potential predicts the elastic scattering angular distribution in very good agreement with experimental data, and little renormalization (unity in most cases) is needed.

1/c expansion of a separable model of direct-interaction type

The properties of a proposed model of N point particles in direct interaction are considered in the limit of small velocities. It is shown that, in this limit, time correlations cancel out and that Newtonian dynamics is recovered for the system in a natural way.

Premartensitic transition driven by magnetoelastic interaction in bcc ferromagnetic Ni2MnGa

We show that the magnetoelastic coupling between the magnetization and the amplitude of a short wavelength phonon enables the existence of a first order premartensitic transition from a bcc to a micromodulated phase in Ni2MnGa. Such a magnetoelastic coupling has been experimentally evidenced by ac susceptibility and ultrasonic measurements under an applied magnetic field. A latent heat around 9 J/mol has been measured using a highly sensitive calorimeter. This value is in very good agreement with the value predicted by a proposed model.