Reinforced sol–gel thermal barrier coatings and their cyclic oxidation life

Cyclic oxidation life enhancement of sol–gel thermal barrier coatings is obtained via the reinforcement of the controlled micro-crack network that forms during the initial sintering of the deposit. Two different sol–gel methods are used to fill in the process-induced cracks, namely dipcoating and spray-coating. Filling parameters, for instance the number of passes or the viscosity of the sol are adjusted, using various techniques such as profilometry and microstructural analysis, to optimise crack filling. Cyclic oxidation tests are implemented at both 1100C and 1150C to investigate the efficiency of the various reinforcement procedures developed and address the influence of the specific microstructure on the oxidation behaviour

Allosteric Modulators of GABAB Receptors: Mechanism of Action and Therapeutic Perspective

γ-aminobutyric acid (GABA) plays important roles in the central nervous system, acting as a neurotransmitter on both ionotropic ligand-gated Cl--channels, and metabotropic G-protein coupled receptors (GPCRs). These two types of receptors called GABAA (and C) and GABAB are the targets of major therapeutic drugs such as the anxiolytic benzodiazepines, and antispastic drug baclofen (lioresal®), respectively. Although the multiplicity of GABAA receptors offer a number of possibilities to discover new and more selective drugs, the molecular characterization of the GABAB receptor revealed a unique, though complex, heterodimeric GPCR. High throughput screening strategies carried out in pharmaceutical industries, helped identifying new compounds positively modulating the activity of the GABAB receptor. These molecules, almost devoid of apparent activity when applied alone, greatly enhance both the potency and efficacy of GABAB agonists. As such, in contrast to baclofen that constantly activates the receptor everywhere in the brain, these positive allosteric modulators induce a large increase in GABAB-mediated responses only WHERE and WHEN physiologically needed. Such compounds are then well adapted to help GABA to activate its GABAB receptors, like benzodiazepines favor GABAA receptor activation. In this review, the way of action of these molecules will be presented in light of our actual knowledge of the activation mechanism of the GABAB receptor. We will then show that, as expected, these molecules have more pronounced in vivo responses and less side effects than pure agonists, offering new potential therapeutic applications for this new class of GABAB ligands

Characterisation of thermal barrier sensor coatings synthesised by sol–gel route

Further improvements in the efficiency of gas turbines are recognised to come from increases in turbine entry temperatures. Accurate temperature measurements are crucial to achieve these increases whilst maintaining reliability and economic component life. The combination of phosphor thermometry and thermal barrier coating (TBC) technology has led to the development of functional temperature sensor coatings which have several advantages over conventional temperature measurement techniques. Developments in sol–gel processing indicate that this method could be used for the production, or particularly, the repair of TBCs in the future. This paper demonstrates, for the first time, that sol–gel processing can be used to make sensor TBCs. The optimum concentration of SmO1.5 was 2 wt.% in YSZ to achieve the brightest phosphorescence emission. Above this concentration the overall intensity of the emission reduces and the transitions from 4F3/2 were suppressed. Furthermore, a similar suppression of these transitions was observed when the product of the sol–gel was heat treated to 1100 ◦C. This was concluded to be due to a higher degree of crystallinity allowing a greater interaction between the dopant ions. The dependence of the phosphorescence spectrum on heat treatment temperature provides the first indication that YSZ produced through sol–gel could be used to detect historic temperatures. An evaluation of the subsurface measurement and temperature capabilities has shown that the phosphorescence can be detected from relatively thin layers, 20 µm, even under 50 µm of undoped YSZ coating. Although the temperature detection range, 400–700 ◦C, is too low for advanced TBCs the material could be used in low temperature regimes or for health monitoring purposes

Group III metabotropic glutamate receptors inhibit hyperalgesia in animal models of inflammation and neuropathic pain

International audienceGlutamate plays a key role in modulation of nociceptive processing. This excitatory amino acid exerts its action through two distinct types of receptors, ionotropic and metabotropic glutamate receptors (mGluRs). Eight mGluRs have been identified and divided in three groups based on their sequence similarity, pharmacology and G-protein coupling. While the role of group I and II mGluRs is now well established, little is known about the part played by group III mGluRs in pain. In this work, we studied comparatively the involvement of spinal group III mGluR in modulation of acute, inflammatory and neuropathic pain. While intrathecal injection of ACPT-I, a selective group III mGluR agonist, failed to induce any change in vocalization thresholds of healthy animals submitted to mechanical or thermal stimuli, it dose-dependently inhibited the nociceptive behavior of rats submitted to the formalin test and the mechanical hyperalgesia associated with different animal models of inflammatory (carrageenan-treated and monoarthritic rats) or neuropathic pain (mononeuropathic and vincristine-treated rats). Similar effects were also observed following intrathecal injection of PHCCC, a positive allosteric modulator of mGlu4. Antihyperalgesia induced by ACPT-I was blocked either by LY341495, a nonselective antagonist of mGluR, by MAP4, a selective group III antagonist. This study provide new evidences supporting the role of spinal group III mGluRs in the modulation of pain perception in different pathological pain states of various etiologies but not in normal conditions. It more particularly highlights the specific involvement of mGlu4 in this process and may be a useful therapeutic approach to chronic pain treatment

Processing, repairing and cyclic oxidation behaviour of sol–gel thermal barrier coatings

Sol–gel Thermal Barriers Coatings (TBCs) are manufactured using the dip-coating technique optimised in terms of process parameters including sol formulation, rate of withdrawing and heat treatment. The specific mechanisms of sol–gel TBCs, deposited on either NiAl or NiPtAl bond-coated superalloy substrates, are described. The possibility to reinforce and stabilise the crack network formed during the heat treatment or the first oxidation cycles using supplementary dip-coatings and appropriate process parameters is investigated. It is shown that implementing this technique that can be further regarded as an attractive way for repairing TBCs, significantly improves the cyclic oxidation behaviour of the multi-materials systems

Adsorption des protéines sur les nanomatériaux. Biochimie et physico-chimie d'un nouveau stress

Les nanomatériaux posent de nouvelles questions en termes de toxicologie humaine et environnementale et représentent une nouvelle interface avec le milieu biologique aux propriétés spécifiques. De nombreuses inconnues demeurent, en particulier à l échelle moléculaire, pour permettre d expliquer certains mécanismes de toxicité. Lorsqu elles entrent en contact avec le milieu biologique, les nanoparticules se couvrent d une couche de protéines adsorbées. Celle-ci leur confère une nouvelle identité biologique qui contrôle la réponse cellulaire et leur devenir au sein de l organisme. Nous avons étudié l adsorption de protéines modèles sur la silice nanostructurée. Après avoir caractérisé la silice nanoporeuse et les nanoparticules de silice utilisées, l adsorption de la myoglobine, de l hémoglobine et des protéines d un extrait cellulaire de levure a été étudiée afin de déterminer les paramètres physico-chimiques et thermodynamiques de l adsorption des protéines sur la silice. Un enrichissement en résidus basiques, regroupés en clusters de charge, favorise l adsorption des protéines grâce à la formation d interactions électrostatiques avec la surface chargée de la silice, indépendamment de la charge globale de la protéine. A l inverse, un enrichissement en résidus aromatiques est défavorable à l adsorption car ces résidus forment des interactions p-p qui rigidifient la structure de la protéine. L identification des protéines adsorbées et non adsorbées à partir d un milieu complexe pourrait également être utilisée pour les études de toxicité cellulaire. A partir de l étude de la structure, de la dynamique et de l activité de la myoglobine et de l hémoglobine adsorbées sur les nanoparticules de silice, nous avons cherché à définir l état d une protéine adsorbée. L étude de la structure, réalisée par dichroïsme circulaire, spectroscopie UV-visible, d absorption X, infrarouge, fluorescence et microcalorimétrie, montre une perte partielle de structure importante des protéines adsorbées associée à une grande hétérogénéité de conformations, sans modification majeure de la structure de l hème. Deux sites potentiels d interaction entre myoglobine et nanoparticules de silice ont été identifiés à l aide d une technique de cartographie de surface par irradiation. L étude de la dynamique de la myoglobine adsorbée par diffusion élastique et inélastique de neutrons a permis de montrer que l adsorption s accompagnait d une diminution importante de la flexibilité de la protéine. Malgré la perte de structure, la metmyoglobine adsorbée conserve une activité de fixation de ligands très proche de celle de la protéine libre. L hémoglobine adsorbée présente de façon inattendue une augmentation de son affinité pour l oxygène et une diminution de sa coopérativité, sans dissociation du tétramère. Cet effet est reproductible lors de l adsorption de l hémoglobine humaine, de l hémoglobine pontée DCL et de l hémoglobine mutée S. Deux effecteurs permettent par ailleurs de moduler l affinité de l hémoglobine adsorbée. Aussi importantes soient-elles, les modifications de structure et d activité observées sont entièrement réversibles après désorption dans des conditions douces. L adsorption des hémoprotéines sur les nanoparticules de silice représente véritablement un nouveau type de stress avec résilience pour les protéines en termes de relations entre structure, dynamique et activité.Nanomaterials raise new questions in environmental and human toxicology and represent a novel interface with specific properties with the biological medium. Several unknown remain to explain all the mechanisms of toxicity, especially at the molecular lever. When they enter the biological medium, nanoparticles get covered by a protein corona. This corona yields to a new biological identity that controls the cellular response to nanoparticles and their fate in the organism. We studied the adsorption of model proteins on nanostructured silica. The first part is dedicated to the characterization of nanoporous silica and silica nanoparticles that we used. Then the adsorption of myoglobin, hemoglobin and protein mixture from yeast cells was studied to determine the thermodynamic and physical-chemical parameters of protein adsorption on silica. The enrichment of basic residues, gathered in charge clusters, favors the adsorption of proteins by the formation of electrostatic interactions with the charged surface of silica, independently of the global charge of the protein. On the contrary, the enrichment in aromatic residues is unfavorable to protein adsorption because they form p-p interactions that rigidify the protein structure. The identification of adsorbed and non-adsorbed proteins from a complex medium could also be used for cellular toxicity studies. From the study of the structure, the dynamics and the activity of myoglobin and hemoglobin adsorbed on silica nanoparticles, we tried to define the state of an adsorbed protein. The structural study, based on circular dichroism, fluorescence, infrared, X-ray and UV-visible spectroscopy and microcalorimetry, shows a substantial partial structure loss of adsorbed proteins together with a high conformational heterogeneity, without major modifications of the heme structure. Two potential interaction sites of myoglobin with silica nanoparticles have been identified by a footprinting technique. The study of adsorbed myoglobin dynamics by elastic and inelastic neutron scattering highlighted the important decrease of protein dynamics that occurs upon adsorption. However, despite the structure loss, adsorbed metmyoglobin retains almost all of its activity of ligand binding. Unexpectedly, adsorbed hemoglobin shows an increase of its oxygen affinity and a decrease of its cooperativity, without any dissociation of the tetramer. This effect can be reproduced on human hemoglobin, cross-linked DCL hemoglobin and variant S hemoglobin. Besides, two effectors allow modulating the affinity of adsorbed hemoglobin. Despite the extent of structural and activity changes, all these modifications are entirely reversible upon desorption in soft conditions. The adsorption of hemoproteins on silica nanoparticles depicts a new sort of stress with resilience for proteins in terms of structure, dynamics and activity relationship.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

A New Family of Receptor Tyrosine Kinases with a Venus Flytrap Binding Domain in Insects and Other Invertebrates Activated by Aminoacids

Background: Tyrosine kinase receptors (RTKs) comprise a large family of membrane receptors that regulate various cellular processes in cell biology of diverse organisms. We previously described an atypical RTK in the platyhelminth parasite Schistosoma mansoni, composed of an extracellular Venus flytrap module (VFT) linked through a single transmembrane domain to an intracellular tyrosine kinase domain similar to that of the insulin receptor. Methods and Findings: Here we show that this receptor is a member of a new family of RTKs found in invertebrates, and particularly in insects. Sixteen new members of this family, named Venus Kinase Receptor (VKR), were identified in many insects. Structural and phylogenetic studies performed on VFT and TK domains showed that VKR sequences formed monophyletic groups, the VFT group being close to that of GABA receptors and the TK one being close to that of insulin receptors. We show that a recombinant VKR is able to autophosphorylate on tyrosine residues, and report that it can be activated by L-arginine. This is in agreement with the high degree of conservation of the alpha amino acid binding residues found in many amino acid binding VFTs. The presence of high levels of vkr transcripts in larval forms and in female gonads indicates a putative function of VKR in reproduction and/or development. Conclusion: The identification of RTKs specific for parasites and insect vectors raises new perspectives for the control of human parasitic and infectious diseases

Sol–gel thermal barrier coatings: Optimization of the manufacturing route and durability under cyclic oxidation

A new promising and versatile process based on the sol–gel transformation has been developed to deposit yttria-stabilised thermal barrier coatings. The non-oriented microstructure with randomly structured pore network, resulting from the soft chemical process, is expected to show satisfactory thermo-mechanical behaviour when the TBC is cyclically oxidized. First stage of the research consists of optimizing the processing route to generate homogeneous microstructure and controlled surface roughness. The objective is to reduce, as much as possible, the size and depth of the surface cracks network inherent to the process. Indeed, the durability of the TBC when cyclically oxidized strongly depends on the sharpness of those cracks that concentrate thermo-mechanical stresses and generate detrimental propagation resulting in spallation. Cyclic oxidation tests are performed using a cyclic oxidation rig instrumented with CCD cameras to monitor in a real time basis the mechanism of crack propagation and spallation. The impact of various parameters either directly related to the processing route, e.g. the intimate microstructure of the TBC and the TBC thickness, or to the thermal loading, e.g. the oxidation temperature and the cumulated hot time, on the durability of the TBC is investigate