Microstructure evolutions of a niobium stabilized austenitic stainless steel (316Nb) during representative thermomechanical treatments of forging process

Les travaux de thèse ont permis de consolider et de compléter les connaissances sur les mécanismes de déformation et les évolutions microstructurales à chaud d’un acier inoxydable austénitique 316Nb. Comprendre la variation du comportement microstructural observée sur différentes pièces obtenues par forge libre permettra de pérenniser les connaissances et d’optimiser les gammes de forgeage. Du fait d’une variabilité de l’état de recristallisation, mise en évidence sur des pièces d’essai, et de son impact sur les propriétés mécaniques, des traitements thermomécaniques simplifiés sont réalisés en laboratoire afin de comprendre la genèse de ces différents états métallurgiques. L’influence de la température, du taux et de la vitesse de déformation ainsi que de la vitesse de refroidissement après l’essai (distinction entre les mécanismes dynamiques et post-dynamiques) est tout d’abord étudiée. De multiples passes de déformation, dans des conditions isothermes et anisothermes, sont ensuite appliquées afin de suivre les évolutions post-dynamiques de la microstructure entre les passes. Le rôle du traitement thermique post-déformation sur la microstructure (recristallisation statique) est étudié. Enfin, l’effet de la microstructure initiale, en termes de taille de grains et de composition chimique, notamment la teneur en niobium en solution solide, a été considéré.La recristallisation dynamique ne domine pas l’évolution de la microstructure, de par notamment une restauration dynamique avancée et une taille de grains élevée. Néanmoins, aux hautes températures et pour de faibles taux de déformation, une migration dynamique des joints de grains conduit à la formation progressive de nouveaux grains recristallisés. La recristallisation post-dynamique est très dépendante des conditions de déformation. A composition chimique donnée, la taille de grains (dans la gamme 60 – 250 µm) affecte peu la cinétique de recristallisation dynamique et post-dynamique. L’augmentation de la teneur en niobium de la solution solide entraîne, via sans doute un effet de traînage de soluté et une éventuelle modification de l’énergie de défaut d’empilement à haute température, un retard considérable de l’apparition de la recristallisation. Au cours du traitement thermique post-déformation, l’état de recristallisation final est essentiellement dépendant de la composition chimique (teneur en niobium de la solution solide et présence de ferrite δ résiduelle). Les précipités de niobium générés dans les conditions de déformation usuelles n’ont pas d’influence directe sur la cinétique de recristallisation.Mechanical properties and microstructure of 316Nb austenitic stainless steel may show some variability in hot forging products. This work aimed at improving knowledge about hot deformation mechanisms and microstructural evolution of this steel. Obtaining a homogeneous microstructure requires deep understanding of the hot deformation behaviour and mechanisms. In thick-walled components, both work hardening, dynamic recovery and recrystallization govern hot workability. Static and post-dynamic phenomena can induce further metallurgical evolution during interpass time and cooling. The influence of deformation temperature, strain, strain rate, cooling rate on recrystallization mechanisms has been studied by using hot torsion tests. Multiple-pass tests with isothermal and non-isothermal interpass allowed understanding post-dynamic mechanisms. Static phenomena were investigated using various annealing conditions. The effects of initial microstructural features such as grain size and chemical composition, specifically niobium solute content, on the hot deformation behaviour were eventually considered.The extent of dynamic recovery, coarse initial grain size, solute drag, and pinning of grain boundaries by fine Nb(C,N) particles strongly hinder dynamic recrystallization which does not dominate the metallurgical evolution over the range studied, in contrast to results reported on 316 steel. However, bulging of grain boundaries as a prelude to dynamic recrystallization was observed at low strains and high temperature. Grain boundary serrations progressively lead to the formation of subgrain boundaries, then of new high angle boundaries. A particular dynamic recrystallization mechanism explains progressive elimination of annealing twins. Interaction with dislocations depends on locally activated slip systems and whether they are common to both twin and parent grain. At moderate strain levels, post-dynamic recrystallization occurs by rapid growth of nuclei that depends on deformation temperature, and applied strain and strain rate. For a given chemical composition, neither dynamic nor post-dynamic recrystallization is affected by the initial grain size over the range studied. Increasing the free niobium content promotes solute drag and niobium carbide precipitation, which significantly delay recrystallization. The microstructure after annealing essentially depends on the availability of solute atoms such as niobium and on residual δ-ferrite. Nb(C,N) precipitates formed during hot deformation do not significantly influence recrystallization kinetics

Hot deformation behaviour and recrystallization mechanisms in a niobium stabilized austenitic stainless steel

International audience316Nb austenitic stainless steels are used in nuclear industry for their excellent corrosion resistance and high temperature mechanical properties. In thick-walled components, work hardening, dynamic recovery and recrystallization govern hot workability. Static recovery and static or post-dynamic recrystallization can induce further metallurgical evolution during cooling. In addition, solute atoms and niobium-rich precipitates may significantly affect recrystallization mechanisms. Obtaining a homogeneous microstructure requires deep understanding of the hot deformation behaviour and mechanisms of this material. The influence of hot deformation conditions on recrystallization was determined from torsion tests. Metallographic and electron backscatter diffraction examinations showed extended dynamic recovery, which delays dynamic recrystallization. A particular dynamic recrystallization mechanism explains progressive elimination of annealing twin boundaries. Coarse initial grain size, solute drag, and pinning of grain boundaries and dislocations by fine Nb(C,N) particles hinder dynamic recrystallization which is not the dominant microstructural evolution mechanism in the studied conditions

Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox

International audienceHydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and identify both which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work provides thus the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows to obtain compounds equally stable in human and rodent models

The Alzheimer susceptibility gene BIN1 induces isoform-dependent neurotoxicity through early endosome defects

The Bridging Integrator 1 (BIN1) gene is a major susceptibility gene for Alzheimer's disease (AD). Deciphering its pathophysiological role is challenging due to its numerous isoforms. Here we observed in Drosophila that human BIN1 isoform1 (BIN1iso1) overexpression, contrary to human BIN1 isoform8 (BIN1iso8) and human BIN1 isoform9 (BIN1iso9), induced an accumulation of endosomal vesicles and neurodegeneration. Systematic search for endosome regulators able to prevent BIN1iso1-induced neurodegeneration indicated that a defect at the early endosome level is responsible for the neurodegeneration. In human induced neurons (hiNs) and cerebral organoids, BIN1 knock-out resulted in the narrowing of early endosomes. This phenotype was rescued by BIN1iso1 but not BIN1iso9 expression. Finally, BIN1iso1 overexpression also led to an increase in the size of early endosomes and neurodegeneration in hiNs. Altogether, our data demonstrate that the AD susceptibility gene BIN1, and especially BIN1iso1, contributes to early-endosome size deregulation, which is an early pathophysiological hallmark of AD pathology