Canton de Ballon

Ce programme de prospection s’insère dans l’étude du potentiel archéologique de 13 communes et fait suite à l’inventaire diachronique réalisé en 1991. Il tend à fournir, en marge de la réalisation de la carte archéologique, une suite de monographies thématiques. Celles-ci permettront, a posteriori, l’analyse historique de micro-terroirs. D’autre part, une action a été menée afin de sensibiliser les habitants à la connaissance et à la protection de leur patrimoine. Le canton de Ballon est une ..

Canton de Ballon – Fortifications en terre

L’étude des fortifications en terre du canton de Ballon, commencée en 1992, s’est poursuivie durant l’année 1993. L’effort a porté sur plusieurs secteurs géographiques n’ayant fourni aucun site par le passé ou ne possédant pas de sources archivistiques recensées. Globalement les recherches mettent en évidence de très nombreuses « maisons fortes », exerçant la domination territoriale de quelques châtellenies. Un type particulier de mottage à tertre bas se rencontre communément sur les berges d..

Topology of Schwann cells and sympathetic innervation along preglomerular vessels: A confocal microscopic study in protein S100B/EGFP transgenic mice

International audienceSchwann cells (Sc), associated axons, and nearby vascular endothelium constitute a functional trilogy of major importance during the development and regrowth of peripheral vascular nerves. The goal of the present study is to provide a technique of triple fluorescence confocal imaging of these cell types along renal preglomerular vessels. We took advantage of a protein S100B/EGFP transgenic mouse to visualize Sc. The endothelium was labeled with an intravenous injection of fluorescently tagged lectin, and after tissue processing, adrenergic nerves were revealed with an antibody against the marker protein synaptophysin. As a validation step, we found that EGFP-positive perivascular cells with prominent cell bodies and extensive, multidirectional cell processes were protein S100B positive. They were identified as Sc and indirectly assumed to be unmyelinated Sc. By contrast, we found strong EGFP expression in proximal epithelial cells and in the epithelium lining thin limbs of Henle. This epithelial fluorescence was not associated with immunoreactive protein S100B and thus corresponded to ectopic EGFP expressions in this mouse strain. Sc were organized in bundles or as a meshwork surrounding the preglomerular vasculature from arcuate arteries to afferent arterioles. No Sc were detected in the medulla. Although most Sc were closely apposed to adrenergic varicosities, many varicosities were not associated with detectable Sc processes. The present technique, and the capacity of confocal microscopy to yield three-dimensional imaging, allow the study of the microtopology of Sc and related sympathetic axons in the renal perivascular interstitiu

Canton de Ballon

Cette prospection, menée par des membres du Centre allonnais de prospections et de recherches archéologiques (CAPRA), a porté sur un ensemble de communes du canton de Ballon situées à la confluence de la Sarthe et de l’Orne Saosnoise. Les recherches, menées de manière diachronique en 1991, ont permis de mettre en évidence plusieurs sites nouveaux (le nombre exact ne peut être précisé, le rapport annuel n’étant pas encore parvenu) qui devront faire l’objet de vérifications et de contrôles en 1..

The composition of Event-B models

The transition from classical B [2] to the Event-B language and method [3] has seen the removal of some forms of model structuring and composition, with the intention of reinventing them in future. This work contributes to thatreinvention. Inspired by a proposed method for state-based decomposition and refinement [5] of an Event-B model, we propose a familiar parallel event composition (over disjoint state variable lists), and the less familiar event fusion (over intersecting state variable lists). A brief motivation is provided for these and other forms of composition of models, in terms of feature-based modelling. We show that model consistency is preserved under such compositions. More significantly we show that model composition preserves refinement

Integration of Gravitational Torques in Cerebellar Pathways Allows for the Dynamic Inverse Computation of Vertical Pointing Movements of a Robot Arm

Several authors suggested that gravitational forces are centrally represented in the brain for planning, control and sensorimotor predictions of movements. Furthermore, some studies proposed that the cerebellum computes the inverse dynamics (internal inverse model) whereas others suggested that it computes sensorimotor predictions (internal forward model).This study proposes a model of cerebellar pathways deduced from both biological and physical constraints. The model learns the dynamic inverse computation of the effect of gravitational torques from its sensorimotor predictions without calculating an explicit inverse computation. By using supervised learning, this model learns to control an anthropomorphic robot arm actuated by two antagonists McKibben artificial muscles. This was achieved by using internal parallel feedback loops containing neural networks which anticipate the sensorimotor consequences of the neural commands. The artificial neural networks architecture was similar to the large-scale connectivity of the cerebellar cortex. Movements in the sagittal plane were performed during three sessions combining different initial positions, amplitudes and directions of movements to vary the effects of the gravitational torques applied to the robotic arm. The results show that this model acquired an internal representation of the gravitational effects during vertical arm pointing movements.This is consistent with the proposal that the cerebellar cortex contains an internal representation of gravitational torques which is encoded through a learning process. Furthermore, this model suggests that the cerebellum performs the inverse dynamics computation based on sensorimotor predictions. This highlights the importance of sensorimotor predictions of gravitational torques acting on upper limb movements performed in the gravitational field

Crystal polymorphism in fragment-based lead discovery of ligands of the catalytic domain of UGGT, the glycoprotein folding quality control checkpoint

None of the current data processing pipelines for X-ray crystallography fragment-based lead discovery (FBLD) consults all the information available when deciding on the lattice and symmetry (i.e., the polymorph) of each soaked crystal. Often, X-ray crystallography FBLD pipelines either choose the polymorph based on cell volume and point-group symmetry of the X-ray diffraction data or leave polymorph attribution to manual intervention on the part of the user. Thus, when the FBLD crystals belong to more than one crystal polymorph, the discovery pipeline can be plagued by space group ambiguity, especially if the polymorphs at hand are variations of the same lattice and, therefore, difficult to tell apart from their morphology and/or their apparent crystal lattices and point groups. In the course of a fragment-based lead discovery effort aimed at finding ligands of the catalytic domain of UDP–glucose glycoprotein glucosyltransferase (UGGT), we encountered a mixture of trigonal crystals and pseudotrigonal triclinic crystals—with the two lattices closely related. In order to resolve that polymorphism ambiguity, we have written and described here a series of Unix shell scripts called CoALLA (crystal polymorph and ligand likelihood-based assignment). The CoALLA scripts are written in Unix shell and use autoPROC for data processing, CCP4-Dimple/REFMAC5 and BUSTER for refinement, and RHOFIT for ligand docking. The choice of the polymorph is effected by carrying out (in each of the known polymorphs) the tasks of diffraction data indexing, integration, scaling, and structural refinement. The most likely polymorph is then chosen as the one with the best structure refinement Rfree statistic. The CoALLA scripts further implement a likelihood-based ligand assignment strategy, starting with macromolecular refinement and automated water addition, followed by removal of the water molecules that appear to be fitting ligand density, and a final round of refinement after random perturbation of the refined macromolecular model, in order to obtain unbiased difference density maps for automated ligand placement. We illustrate the use of CoALLA to discriminate between H3 and P1 crystals used for an FBLD effort to find fragments binding to the catalytic domain of Chaetomium thermophilum UGGT

The Inactivation Principle: Mathematical Solutions Minimizing the Absolute Work and Biological Implications for the Planning of Arm Movements

An important question in the literature focusing on motor control is to determine which laws drive biological limb movements. This question has prompted numerous investigations analyzing arm movements in both humans and monkeys. Many theories assume that among all possible movements the one actually performed satisfies an optimality criterion. In the framework of optimal control theory, a first approach is to choose a cost function and test whether the proposed model fits with experimental data. A second approach (generally considered as the more difficult) is to infer the cost function from behavioral data. The cost proposed here includes a term called the absolute work of forces, reflecting the mechanical energy expenditure. Contrary to most investigations studying optimality principles of arm movements, this model has the particularity of using a cost function that is not smooth. First, a mathematical theory related to both direct and inverse optimal control approaches is presented. The first theoretical result is the Inactivation Principle, according to which minimizing a term similar to the absolute work implies simultaneous inactivation of agonistic and antagonistic muscles acting on a single joint, near the time of peak velocity. The second theoretical result is that, conversely, the presence of non-smoothness in the cost function is a necessary condition for the existence of such inactivation. Second, during an experimental study, participants were asked to perform fast vertical arm movements with one, two, and three degrees of freedom. Observed trajectories, velocity profiles, and final postures were accurately simulated by the model. In accordance, electromyographic signals showed brief simultaneous inactivation of opposing muscles during movements. Thus, assuming that human movements are optimal with respect to a certain integral cost, the minimization of an absolute-work-like cost is supported by experimental observations. Such types of optimality criteria may be applied to a large range of biological movements

Design of modulatory peptides against chemokines

Chemotactic cytokines or chemokines are small signalling proteins responsible for the recruitment of leukocytes to sites of inflammation. Although, chemokines are critical to orchestrate effective immune response, many have been associated to several inflammatory disorders. Despite being recognised as therapeutic target, no efficient treatments targeting the chemokine network for inflammatory diseases are available to date. This is attributed with the complexity of the many and varied chemokine interactions with themselves, their receptors and glycosaminoglycans on extracellular matrix. Thus, the pharmaceutical industry dogma of “one molecule, one target” is rendered ineffective against this network. Evasins are small tick saliva proteins that can bind and neutralise several chemokines, therefore allowing the tick to feed on their host for days without sparking an immune response. The potential of Evasins as effective anti-inflammatory agents was proven in many pre-clinical disease models. The interest in Evasins led to the discovery of a novel Evasin, P672, that can bind a wide range of CC chemokines. This work describes the discovery of peptides inspired by the chemokine binding site of P672. These peptides were shown to neutralise several chemokines and exhibited in vivo anti-inflammatory activity. A novel generation of P672-inspired peptides were designed and exhibited multiple chemokine-binding properties with increased human plasma resistance. Finally, P672/chemokine interfaces were mapped using peptide display techniques informing on P672 binding sites and its mode of action to neutralise chemokines. This work demonstrates the exciting potential of utilising Evasin/chemokine interaction studies with informed mode of action as starting points for anti-inflammatory peptide development