This paper presents an original stochastic method of optimization (PGSL) for optimum design of truss struc- tures. PGSL (Probabilistic Global Search Lausanne , developed at the Swiss Federal Institute of Techn ology at Lausanne) has been interfaced with a finite element code, the n applied and tested on several size optimization p roblems of plane truss structures. This method uses a probability distribu tion function (PDF) to sample the search space and select the best struc- ture. A PDF represents the probability of finding a good solution at any given point in the search dom ain. The better solu- tions are more likely to be found in the neighbourh ood of good solutions; hence, probabilities are inc reased in regions where good solutions are found. The main advantage of this method is to avoid the sensitivity analysis and to converge to the global optimum.
The mammalian circadian clock, whose central component is located in the suprachiasmatic nucleus of the hypothalamus (SCN), orchestrates rhythmic events in metabolism, physiology and behavior. Adaptation of the organism to its environment requires precise adjustment of the clock to the 24 h astronomical time, primarily by the light/dark cycle. Photic synchronization acts on both the molecular loops which trigger circadian oscillations and the phasing of the multiple SCN cellular oscillators whose coordination permits elaboration of the rhythmic message that will be distributed throughout the organism. It is concomitant with structural plastic events characterized by day/night rearrangements of the SCN neuronal-glial network. The two main sources of SCN efferents, namely the VIP (vasoactive intestinal peptide)-synthesizing neurons which are major integrators of photic signals and the AVP (arginine-vasopressin)-synthesizing neurons which are known to importantly contribute to conveying rhythmic messages to brain targets, are involved in these mechanisms. Over the light/dark cycle, they indeed undergo ultrastructural changes in the extent of their membrane coverage by glial, axon terminal and/or somato-dendritic elements. These structural rearrangements appear to be dependent on light entrainment, as the rhythmic expression in SCN of glial fibrillary acidic protein (GFAP), a marker for brain astrocytes whose changing expression has proved to be a reliable index of neuronal-glial plasticity, is disrupted under constant darkness. Glucocorticoid hormones, which are known as important endocrine outputs of the clock, are required to maintain amplitude of the SCN GFAP rhythm to normal values, indicating that they modulate astrocytic plasticity within the SCN and, therefore, nycthemeral changes of the configuration of its neuronal-glial network. The view that such plastic events may subserve synchronization of the clock to the light-dark cycle is reinforced by other data showing that the daily fluctuations of circulating glucocorticoids actually are involved in modulation of light effects, contributing to the resistance of the circadian timing system to variations of the photoperiod. It is thus proposed that the capacity of the clock to integrate cyclic variations of the environment rely on the inherent capacity of the SCN to undergo neuronal-glial plasticity.
The threat posed by bioweapons (BW) could lead to the re-emergence of such deadly diseases as plague or smallpox, now eradicated from industrialized countries. The development of recombinant antibodies allows tackling this risk because these recombinant molecules are generally well tolerated in human medicine, may be utilized for prophylaxis and treatment, and because antibodies neutralize many BW. Recombinant antibodies neutralizing the lethal toxin of anthrax, botulinum toxins and the smallpox virus have in particular been isolated recently, with different technologies. Our approach, which uses phage-displayed immune libraries built from non-human primates (M. fascicularis) to obtain recombinant antibodies, which may later be super-humanized (germlinized), has allowed us to obtain such BWs-neutralizing antibodies.
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. [Treatment of information on personal health data for research purposes: nobody should ignore the law.] Catherine Bonaïti-Pellié, Patrick Arveux, Agathe Billette de Villemeur, Nicolas Dantchev, Alexis Elbaz, Elisabeth Fabre-Guillevin, Jeanne Fresson, Christine Saura, Marie-Josèphe Saurel-Cubizolles, Jean-Louis Serre, et al.
> Que l’on soit homme, chauve-souris, oiseau, poisson, escargot ou plante, nous avons tous elabore des moyens de fuite pour echapper a nos predateurs. Nous nous servons de nos jambes pour courir, de nos ailes pour voler, de nos nageoires, de notre coquille lorsque notre locomotion est trop lente et de nos epines lorsque nous sommes enracines. Nous avons aussi imagine des couleurs, des zebrures, des pigments pour nous camoufler. Cependant, face a des ennemis comme les virus, les bacteries ou les parasites, la fuite ou le camouflage sont inef ficaces et, au cours de l’evolution, notre systeme immunitaire a adapte une reponse aux agressions par ces pathogenes. Betes, bestioles, plantes, creatures des airs, de l’eau et de la terre ont developpe des strategies diverses, mais non depourvues d’analogies, en particulier dans leur fonctionnalite, pour se defendre contre les pathogenes. Dans une serie d’articles illustrant quelques exemples au fil des prochains numeros de Medecine/Sciences, vous decouvrirez l’odyssee du systeme immunitaire a travers les especes (➜). Cette serie fait echo au cours « Les systemes immunitaires dans l’evolution des especes » donne en 2008 au College de France par le Professeur Philippe Kourilsky (Chaire d’Immunologie Moleculaire)1. Ce cours s’est acheve le 8 avril 2008 par un colloque, « l’Arche de Noe du systeme immunitaire », organise par Dominique Buzoni-Gatel (Inra) et Philippe Kourilsky, et auquel ont participe les auteurs de cette serie2. Probablement sous la pression d’agents infectieux et peut-etre d’autres facteurs environnementaux, le systeme immunitaire a evolue pour conferer aux differentes especes les meilleures chances de survie. Il a du s’adapter pour eliminer rapidement et efficacement le danger. Pour cela, il se doit d’etre divers et flexible, regule, econome en energie et de ne pas reagir aux antigenes du soi.
Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family that is expressed and secreted by glandular cells and found in the secondary granules of neutrophils from which it is released in infected tissues and blood during the inflammatory process. Initially described as an iron-binding molecule with bacteriostatic properties, Lf is now known to be a multifunctional or multi-tasking protein. It is a major component of the innate immune system of mammals. Its protective effects range from direct anti-microbial activities against a large panel of microorganisms including bacteria, viruses, fungi, and parasites, to anti-inflammatory and anti-cancer activities. While iron chelation is central to some of the biological functions of Lf, other activities involve interactions of Lf with molecular and cellular components of both hosts and pathogens. Its powerful antimicrobial activities, immunomodulatory properties and prevention of septic shock, anti-carcinogenic functions and its growing importance in iron delivery and bone growth, combined with the data obtained either by in vivo studies or clinical trials, make this molecule and its derivatives very promising tools for health or nutritional applications.