Blocking TGF-β signaling pathway preserves mitochondrial proteostasis and reduces early activation of PDGFRβ+ pericytes in aristolochic acid induced acute kidney injury in wistar male rats

The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target.In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN.Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily.At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro.The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

Influence of Amorphous Phase Separation on the crystallization mechanisms in the BaO-TiO2-SiO2 system

The control of microstructures is a major challenge to enhance the properties of base glasses. More specifically, the controlled crystallization of glasses through a Prior Amorphous Phase Separation (APS) may be an elegant way to ensure a bulk process. Glasses in the BaO-TiO2-SiO2 system undergo APS for specific composition ranges. The interfaces created can have a significant effect on the crystallization behavior since it allows bulk nucleation of fresnoite to be obtained, instead of surface crystallization. This phenomenon can enhance optical properties such as blue photoluminescence, particularly interesting for plasma screen applications. The aim of this work is to compare the crystallization behavior with and without prior APS. The microstructures were investigated using Scanning and Transmission Electron Microscopy (SEM & TEM). Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (DRX) were also used to characterize the crystallization process. The prior APS is shown to have a major influence for the glass compositions investigated Consequently, a modeling effort is presently being carried out in order to determine the immiscibility region, in order to compare compositions closer to the immiscibility boundary.info:eu-repo/semantics/nonPublishe

A thermodynamic assessment of the liquid immiscibility in the BaO-TiO2-SiO2 system using the Ionic Two Sublattice Model

Présentation séminaire Thermo-Calc (Leuven)info:eu-repo/semantics/nonPublishe

Influence of phase separation on the crystallization behavior of glass-ceramics in the BaO-TiO2-SiO2 system

Glass ceramics are of growing interest due to their enhanced properties comparing to the base glasses. The control of microstructures is consequently a major challenge in those systems. Even if it has been the topic of vigorous debates over the last decades, the possible role of a prior amorphous phase separation (APS) on the subsequent crystallization has not yet been clarified. This study focuses on the interplay between amorphous phase separation and the crystallization of fresnoite in glasses pertaining to the BaO-TiO2-SiO2 system. These glasses are known to undergo subliquidus phase separation via binodal or spinodal mechanisms for specific composition ranges in the ternary phase diagram. This process eventually leads to a final microstructure consisting of silica-rich droplets within a glassy matrix. The prior amorphous phase separation may have a significant effect on the subsequent nucleation and growth of crystals and furthermore on their morphology. Indeed, glasses with compositions falling outside the immiscibility gap have been reported to crystallize as strongly oriented crystals whereas glasses undergoing a prior APS lead to finer and randomly oriented crystals. This could be considered as an elegant way to improve optical properties such as the blue photoluminescence of fresnoite, particularly interesting for plasma screen applications. The aim of this work is to compare the crystallization behavior of glasses (i) with and (ii) without prior amorphous phase separation and also (iii) with the stoichiometric composition of fresnoite. This particular glass composition is well-known to bulk crystallize and to show high photoluminescence. The prior amorphous phase separation is shown to have a major influence for the glass compositions investigated. The microstructures of bulk samples are investigated using Scanning and Transmission Electron Microscopy. Differential Scanning Calorimetry and X-Ray Diffraction are also used to characterize the crystallization process on powder samples. The possible influence of the various interfaces present within the microstructure is investigated. In particular, the role of free surfaces or of droplets/matrix interfaces is scrutinized. Their respective influence on the nucleation and growth of fresnoite crystals is discussed in detail.info:eu-repo/semantics/publishe

Les forges de Bignan : un site mérovingien

International audienc

THERMODYNAMIC ASSESSMENTS OF THE LIQUID IMMISCIBILITIES IN THE BAO-SIO2 AND TIO2-SIO2 SYTEMS USING THE IONIC TWO SUBLATTICE MODEL

Glass-ceramics in the BaO-SiO2-TiO2 system exhibit strong photoluminescence properties due to the fresnoite phase formation. This effect can be enhanced by controlling a prior amorphous phase separation, which promotes the formation of finer crystals. The thermodynamic stability and metastability of the liquid phase in this system are critical information in order to design optimal compositions and processes of the glass exhibiting the maximum photoluminescence effect. However, the liquid phase in the BaO-SiO2-TiO2 system has never been assessed in the past and there is a lack of experimental data. Corresponding sub-binary systems were evaluated in literature but using different thermodynamic models: the BaO-SiO2 system was performed on the basis of the structural model for silicate melts and glasses [1] and the TiO2-SiO2 binary system using a Margule type excess polynomial model [2]. The BaO-TiO2 system was already assessed by using the Ionic Two Sublattice model [3]. To construct a ternary description of the BaO-SiO2-TiO2 system, the Ionic Two Sublattice model was used in this work to first describe liquid phases in both BaO-SiO2 and TiO2-SiO2 systems. Available experimental data from literature were evaluated to assess the thermodynamic parameters of these liquid phases by the CALPHAD method. The assessments were conducted using a PARROT module of the Thermo-Calc software. A set of optimized parameters was obtained and calculated phase diagrams related to the stable and metastable liquid miscibility gaps in the BaO-SiO2 and TiO2-SiO2 are consistent with experimental data as shown in Figure 1 and Figure 2. The validity of liquidus projection interpolations into the ternary system by Muggianu’s model is investigated. Discussion is further expanded to experiments and the parameter assessment required for the prediction of the resulting BaO-SiO2-TiO2 equilibrium diagrams.[1] A. Romero-Serrano et al. Thermodynamic modeling of the BaO-SiO2 binary melts. Glass Phys. and Chem. 2010, Vol.36 n°2, pp.171-178.[2] M. Kirschen, C. DeCapitani, Immiscible silicate liquids in the system SiO2-TiO2-Al2O3. Eur.J.Mineral, 1999, Vol.11, pp.427-440.[3] X. Lu, Z. Jin, Thermodynamic assessment of the BaO-TiO2 quasibinary system. Calphad. Pergamon, 2000, Vol.24, 3, pp.319-338.info:eu-repo/semantics/nonPublishe

Crystallization behavior of glass-ceramics in the BaO-TiO2-SiO2 system

Glass ceramics are of growing interest due to their enhanced properties compared to the base glasses. The control of microstructures is consequently a major challenge in those systems. A glass with the stoichiometric composition of fresnoite (Ba2TiSi2O8) has been reported by Cabral et al. to show a very large nucleation rate leading to the formation of nanometric crystals. Komatsu et al. reported that transparent nanocrystallized glasses exhibit blue/white photoluminescence by UV excitation, demonstrating that fresnoite has a significant potential as luminescent material. Furthermore, it was recently reported by Hijiya et al. that non stoichiometric compositions included inside the miscibility gap in the phase diagram allow enhancing the photoluminescence properties; the heterogeneous crystallization is finer, providing an enhancement of the fluorescence effect. The possible role of a prior Amorphous Phase Separation (APS) on the subsequent crystallization has been the topic of vigorous debates over the last decades and has not yet been clarified. This study proposes to focus on the interplay between APS and the crystallization of fresnoite by comparing the crystallization behavior of the stoichiometric composition with two non-stoichiometric ones, one outside the miscibility gap and one inside. The crystallization mechanism is studied using Differential Scanning Calorimetry. It reveals that interfaces created by the APS have no effect on the crystallization mechanism since both non-stoichiometric compositions exhibit surface crystallization. The evolution of the microstructure is investigated by conventional Scanning Electron Microscopy (SEM). It confirms the surface crystallisation mechanism and the very limited role of APS. However, the final microstructures depend on the compositions investigated. The size of the crystals become finer when the silica content is increased and the composition falls inside the miscibility gap. Two possible scenarios are proposed to explain the formation of oriented but finer microstructures: the presence of amorphous silica-rich droplets or a higher viscosity, both disturbing the dendritic growth of fresnoite observed for the non-stoichiometric composition. In order to explore those hypotheses, the microstructures of bulk samples with prior APS are investigated more deeply by coupling SEM to local crystallographic orientation mapping using Electron BackScatterred Diffraction techniques to scrutinize the local orientation around the droplets at the early and final stages of crystallization. High Resolution Transmission Electron Microscope coupled with Electron Energy Loss Spectroscopy is also used in order to characterize the nanoscale composition gradients at the interface between the matrix and the droplets both in the amorphous state and after the crystallization of fresnoite. In order to minimize the effect of composition and the associated viscosity change, two specific glass compositions are further investigated. They are chosen such that they are very close but fall respectively inside and outside the miscibility gap. Their final microstructures are compared.info:eu-repo/semantics/nonPublishe

Influence of amorphous phase separation on the crystallization behavior of glass-ceramics in the BaO-TiO2-SiO2 system

The possible role of a prior amorphous phase separation on the subsequent crystallization has been the topic of vigorous debates over the last decades and has not yet been clarified, especially regarding the role of the interfaces created by the phase separation. This study proposes to focus on the interplay between a prior amorphous phase separation and the crystallization of fresnoite in the BaO-TiO2-SiO2 system. The crystallization behavior of a non-stoichiometric composition inside the miscibility gap (called APS) is compared with the stoichiometric composition (called FRES) and a non-stoichiometric composition outside the miscibility gap (called NoAPS). The crystallization mechanisms are compared using differential thermal analysis (DTA) by calculating the Avrami parameters and the activation energies as a function of the particle size. The DTA study shows that the two non-stoichiometric compositions exhibit a pronounced surface crystallization behavior whereas FRES undergoes bulk nucleation. This is supported by a multi-scale microstructure characterization. Furthermore, this study demonstrates that the amorphous phase separation and the associated interfaces do not play any significant role in the nucleation step. Moreover, transmission electron microscope (TEM) and local orientation measurements show that the growth of the dendrites in not hindered by the SiO2-rich droplets. The final stage of crystallization of APS is tentatively explained by two compositions effects that must be further investigated: the viscosity effect and the formation of a eutectic.SCOPUS: ar.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe