Neurofilaments and NFL-TBS.40-63 peptide penetrate oligodendrocytes through clathrin-dependent endocytosis to promote their growth and survival in vitro.

International audience

Population-E

Social inequalities in health are a major public concern. Some of theseinequalities are currently not well documented, and are thus largely absentfrom debate. One important health issue is renal disease and access tothe corresponding therapies (dialysis and renal transplant). These twotherapeutic options have very different consequences in terms of labourmarket participation and physical well-being. Renal transplants offerpatients an enhanced quality of daily life and a longer life expectancy, butthis option is limited by organ availability. Here, drawing on two recentsurveys, Christian Baudelot, Yvanie Caillé, Olivier Godechot and SylvieMercier examine socially differentiated access to these two therapiesand explore the underlying mechanisms. At each stage in the diseaseand its treatment, a cumulative process puts the least educated patientsat a disadvantage in terms of access to a kidney transplant.

[France's margins and the necessary territorial attractiveness].

International audience

Asymptotic preserving and time diminishing schemes for rarefied gas dynamic

In this work, we introduce a new class of numerical schemes for rarefied gas dynamic problems described by collisional kinetic equations. The idea consists in reformulating the problem using a micro-macro decomposition and successively in solving the microscopic part by using asymptotic preserving Monte Carlo methods. We consider two types of decompositions, the first leading to the Euler system of gas dynamics while the second to the Navier-Stokes equations for the macroscopic part. In addition, the particle method which solves the microscopic part is designed in such a way that the global scheme becomes computationally less expensive as the solution approaches the equilibrium state as opposite to standard methods for kinetic equations which computational cost increases with the number of interactions. At the same time, the statistical error due to the particle part of the solution decreases as the system approach the equilibrium state. This causes the method to degenerate to the sole solution of the macroscopic hydrodynamic equations (Euler or Navier-Stokes) in the limit of infinite number of collisions. In a last part, we will show the behaviors of this new approach in comparisons to standard Monte Carlo techniques for solving the kinetic equation by testing it on different problems which typically arise in rarefied gas dynamic simulations.

Multiscale Schemes for the BGK--Vlasov--Poisson System in the Quasi-Neutral and Fluid Limits. Stability Analysis and First Order Schemes

This paper deals with the development and the analysis of asymptotically stable and consistent schemes in the joint quasi-neutral and fluid limits for the collisional Vlasov-Poisson system. In these limits, the classical explicit schemes suffer from time step restrictions due to the small plasma period and Knudsen number. To solve this problem, we propose a new scheme stable for choices of time steps independent from the small scales dynamics and with comparable computational cost with respect to standard explicit schemes. In addition, this scheme reduces automatically to consistent discretizations of the underlying asymptotic systems. In this first work on this subject, we propose a first order in time scheme and we perform a relative linear stability analysis to deal with such problems. The framework we propose permits to extend this approach to high order schemes in the next future. We finally show the capability of the method in dealing with small scales through numerical experiments.

Resilience and Urban Risk Management

International audience

[The France of margins: a very small population or significance?]

International audience

Innovations organisationnelles et radicales, Le cas de deux grandes firmes de l’informatique émergente

National audience

L’orientation locale des politiques scientifiques : entre coopérations et enfermement. Une illustration en Champagne-Ardenne

National audience

La politique des pôles de compétitivité ou la question de l’articulation entre compétitivité des entreprises et compétitivité des territoires

National audience

Grande vitesse ferroviaire et développement économique local : une revue de la littérature (article)

National audience

Biosynthesis and mode of action of ribosomally synthesized and post-translationally modified antimicrobial peptides

One of the greatest sources of biologically active compounds is natural products. Often these compounds serve as platforms for the design and development of novel drugs and therapeutics. The overwhelming amount of genomic information acquired in recent years has revealed that ribosomally synthesized and post-translationally modified natural products are much more widespread than originally anticipated. Identified in nearly all forms of life, these natural products display incredible structural diversity and possess a wide range of biological functions that include antimicrobial, antiviral, anti-inflammatory, antitumor, and antiallodynic activities. The unique pathways taken to biosynthesize these compounds offer exciting opportunities for the bioengineering of these complex molecules. The studies described herein focus on both the mode of action and biosynthesis of antimicrobial peptides. In Chapter 2, it is demonstrated that haloduracin, a recently discovered two-peptide lantibiotic, possesses nanomolar antimicrobial activity against a panel of bacteria strains. The potency of haloduracin rivals that of nisin, an economically and therapeutically relevant lantibiotic, which can be attributed to a similar dual mode of action. Moreover, it was demonstrated that this lantibiotic of alkaliphile origin has better stability at physiological pH than nisin. The molecular target of haloduracin was identified as the cell wall peptidoglycan precursor lipid II. Through the in vitro biosynthesis of haloduracin, several analogues of Halα were prepared and evaluated for their ability to inhibit peptidoglycan biosynthesis as well as bacterial cell growth. In an effort to overcome the limitations of in vitro biosynthesis strategies, a novel strategy was developed resulting in a constitutively active lantibiotic synthetase enzyme. This methodology, described in Chapter 3, enabled the production of fully-modified lacticin 481 products with proteinogenic and non-proteinogenic amino acid substitutions. A number of lacticin 481 analogues were prepared and their antimicrobial activity and ability to bind lipid II was assessed. Moreover, site-directed mutagenesis of the constitutively active synthetase resulted in a kinase-like enzyme with the ability to phosphorylate a number of peptide substrates. The hunt for a lantibiotic synthetase enzyme responsible for installing the presumed dehydro amino acids and a thioether ring in the natural product sublancin, led to the identification and characterization of a unique post-translational modification. The studies described in Chapter 4, demonstrate that sublancin is not a lantibiotic, but rather an unusual S-linked glycopeptide. Its structure was revised based on extensive chemical, biochemical, and spectroscopic characterization. In addition to structural investigation, bioinformatic analysis of the sublancin gene cluster led to the identification of an S-glycosyltransferase predicted to be responsible for the post-translational modification of the sublancin precursor peptide. The unprecedented glycosyltransferase was reconstituted in vitro and demonstrated remarkable substrate promiscuity for both the NDP-sugar co-substrate as well as the precursor peptide itself. An in vitro method was developed for the production of sublancin and analogues which were subsequently evaluated in bioactivity assays. Finally, a number of putative biosynthetic gene clusters were identified that appear to harbor the necessary genes for production of an S-glycopeptide. An additional S-glycosyltransferase with more favorable intrinsic properties including better expression, stability, and solubility was reconstituted in vitro and demonstrated robust catalytic abilities.

TGV, développement local et taille des villes. Une analyse en termes d’innovation de services

National audience

Pourquoi les « effets » TGV sont-ils différents selon les territoires ? L’hétérogénéité au cœur du triptyque « Innovations, Territoires et Stratégies »

National audience

Lignes ferroviaires à grande vitesse et dynamiques locales : une analyse comparée de la littérature (article)

National audience