70 research outputs found

    Ti3SiC2-Cf composites by spark plasma sintering: Processing, microstructure and thermo-mechanical properties

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    MAX phases, and particularly Ti3SiC2, are interesting for high temperature applications. The addition of carbon fibers can be used to reduce the density and to modify the properties of the matrix. This work presents the densification and characterization of Ti3SiC2 based composites with short carbon fibers using a fast and simple fabrication approach: dry mixing and densification by Spark Plasma Sintering. Good densification level was obtained below 1400 °C even with a high amount of fibers. The reaction of the fibers with the matrix is limited thanks to the fast processing time and depends on the amount of fibers in the composite. Bending strength at room temperature, between 437 and 120 MPa, is in the range of conventional CMCs with short fibers and according to the resistance of the matrix and the presence of residual porosity. Thermo-mechanical properties of the composites up to 1500 °C are also presented.This work has received funding from the European Union’s Horizon2020 “Research and innovation programme” under grant agreement No 685594 (C3HARME

    Development of electric resistance sintering process for the fabrication of hard metals: Processing, microstructure and mechanical properties

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    This work presents the development of the Electrical Resistance Sintering (ERS) process for the fabrication of hard metals. The compositions of the materials produced were WC with 6 and 10 wt% of Co. In addition to the specific characteristics of the technology, the characterization of the produced parts is presented and compared to materials obtained by conventional processes. The parts produced by ERS present densities comparable to the ones obtained by conventional methods. The microstructural comparison shows a considerable grain size reduction in the ERS materials which consequently brings a hardness increase. ERS materials show similar fracture toughness to conventional ones. The very fast sintering allows performing the process without any protective atmosphere, therefore making this process very attractive for the production of materials that need to be sintered under non-oxidising environments. The total duration of the cycle, including heating, holding time and cooling is few seconds. Finally, some considerations about the scale up and possible industrialization of the technology are explained.This work is financially supported by the Seventh Framework Program of the Commission of the European Communities under project EFFIPRO contract no. NMP2-SL-2013-608729

    Changes of pd oxidation state in pd/al2o3 catalysts using modulated excitation drifts

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    Infrared spectroscopy is typically not used to establish the oxidation state of metal-based catalysts. In this work, we show that the baseline of spectra collected in diffuse reflectance mode of a series of Pd/Al2O3 samples of increasing Pd content varies significantly and reversibly under alternate pulses of CO or H2 and O2. Moreover, these baseline changes are proportional to the Pd content in Pd/Al2O3 samples exhibiting comparable Pd particle size. Similar measurements by X-ray absorption spectroscopy on a different 2 wt.% Pd/Al2O3 confirm that the baseline changes reflect the reversible reduction-oxidation of Pd. Hence, we demonstrate that changes in oxidation state of metal-based catalysts can be determined using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and that this behavior is part of the spectral changes that are returned by experiments under operando conditions

    One-step in vitro generation of ETV2-null pig embryos

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    Each year, tens of thousands of people worldwide die of end-stage organ failure due to the limited availability of organs for use in transplantation. To meet this clinical demand, one of the last frontiers of regenerative medicine is the generation of humanized organs in pigs from pluripotent stem cells (PSCs) via blastocyst complementation. For this, organ-disabled pig models are needed. As endothelial cells (ECs) play a critical role in xenotransplantation rejection in every organ, we aimed to produce hematoendothelial-disabled pig embryos targeting the master transcription factor ETV2 via CRISPR-Cas9-mediated genome modification. In this study, we designed five different guide RNAs (gRNAs) against the DNA-binding domain of the porcine ETV2 gene, which were tested on porcine fibroblasts in vitro. Four out of five guides showed cleavage capacity and, subsequently, these four guides were microinjected individually as ribonucleoprotein complexes (RNPs) into one-cell-stage porcine embryos. Next, we combined the two gRNAs that showed the highest targeting efficiency and microinjected them at higher concentrations. Under these conditions, we significantly improved the rate of biallelic mutation. Hence, here, we describe an efficient one-step method for the generation of hematoendothelial-disabled pig embryos via CRISPR-Cas9 microinjection in zygotes. This model could be used in experimentation related to the in vivo generation of humanized organs

    A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells

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    Altres ajuts: European Research Council (ERC); EIT Health under grant ID 20366 (R2U-Tox-Assay); IBEC Faster Future program (A por la COVID-19); European Regional Development Fund (FEDER); Gobierno de Navarra, Departamento de Desarrollo Económico y Empresarial (AGATA 0011-1411-2020-000011, DIANA 0011-1411-2017-000029); Ministerio de Economía y Competitividad (MINECO); IBEC International PhD Programme "La Caixa" Severo Ochoa fellowships (LCF/BQ/SO16/52270019); start-up funds from the College of Medicine at the University of Florida, Gainesville; T. von Zastrow Foundation; the FWF Wittgenstein award (Z 271-B19); the Austrian Academy of Sciences and the Canada 150 Research Chairs Program (F18-01336); the Canadian Institutes of Health Research COVID-19 (F20-02343, F20-02015); Swiss National Science Foundation fellowship (P400PM_194473/1); Swedish Research Council (2018-05766); the Innovative Medicines Initiative 2 Joint Undertaking (JU 101005026); Ayudas Fundación BBVA a Equipos de Investigación Científica SARS-CoV-2 y COVID-19 through the project "Identifying SARS-CoV-2-host cell interactions exploiting CRISPR-Cas9-engineered human organoids: through the development of specific therapies against COVID19"; Fundació la Marató de TV3 (201910-31 and 202125-3).It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism

    Loss of the matrix metalloproteinase-10 causes premature features of aging in satellite cells

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    © 2023 Bobadilla Muñoz, Orbe, Abizanda, Machado, Vilas, Ullate-Agote, Extramiana, Baraibar Churio, Aranguren, Cantero, Sáinz Amillo, Rodríguez, Ramos García, Romero Riojas, Vallejo-Illarramendi, Paradas, López de Munain, Páramo, Prósper and Pérez-Ruiz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Aged muscles accumulate satellite cells with a striking decline response to damage. Although intrinsic defects in satellite cells themselves are the major contributors to aging-associated stem cell dysfunction, increasing evidence suggests that changes in the muscle-stem cell local microenvironment also contribute to aging. Here, we demonstrate that loss of the matrix metalloproteinase-10 (MMP-10) in young mice alters the composition of the muscle extracellular matrix (ECM), and specifically disrupts the extracellular matrix of the satellite cell niche. This situation causes premature features of aging in the satellite cells, contributing to their functional decline and a predisposition to enter senescence under proliferative pressure. Similarly, reduction of MMP-10 levels in young satellite cells from wild type animals induces a senescence response, while addition of the protease delays this program. Significantly, the effect of MMP-10 on satellite cell aging can be extended to another context of muscle wasting, muscular dystrophy. Systemic treatment of mdx dystrophic mice with MMP-10 prevents the muscle deterioration phenotype and reduces cellular damage in the satellite cells, which are normally under replicative pressure. Most importantly, MMP-10 conserves its protective effect in the satellite cell-derived myoblasts isolated from a Duchenne muscular dystrophy patient by decreasing the accumulation of damaged DNA. Hence, MMP-10 provides a previously unrecognized therapeutic opportunity to delay satellite cell aging and overcome satellite cell dysfunction in dystrophic muscles.This work was supported by Red de Terapia Celular (TerCel) RD16-0011-0005 Instituto de Salud Carlos III convocatoria 2016, Convocatoria de Redes Temáticas Cooperativas de Investigación en Salud; CIBERONC; Instituto de Salud Carlos III-FEDER, CIBERONC, Fondo de Investigaciones Sanitarias (PI18/01152), (PI19/00065), and CIBERCV (CB16/11/00371). GC is supported by a postdoctoral fellowship funded by Consejería de Salud y Familias, Junta de Andalucía and Programa Operativo Fondo Social Europeo de Andalucía 2014-2020 (RH0046-2020).Peer reviewe

    The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

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    The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

    Space propulsion components based on Gamma TiAl based alloys by combustion synthesis + compation route

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    Intermetallic compounds of Ti-Al system and alloys based on such compounds are materials of rapidly growing technological importance. Such alloys have relatively high yield strength at elevated temperatures, advanced creep characteristics, and good oxidation/corrosion resistance. Several methods have been utilized in the synthesis of Ti-Al intermetallic compounds. These include conventional melting and casting processes and powder metallurgical techniques. The latter include mechanical alloying, plasma-rotating electrode processes, and inert gas atomization (which all have been recently proposed as methods of preparing titanium aluminides in powder form). In all of these approaches, a subsequent step is required to obtain products with the desired density and shape. Over past years, a search for new synthetic approaches to intermetallides (including titanium aluminide and related materials) has led, among others, also to the technique of Self-propagating High-temperature Synthesis (SHS). This is an alternative powder technique for the production of intermetallics. This process requires a large exothermic enthalpy of formation for the desired intermetallic compound. Because of a low caloricity of reaction between Ti and Al, the classical SHS reaction between these metals can be initiated only upon preliminary heating of a green mixture. For this reason, the best results in synthesis of titanium aluminides were attained by combining SHS with some kinds of internal influence, such as heating up to the ignition temperature, mechanoactivation of green mixture, SHS followed by hot isostaic pressing (HIP), SHS in electromagnetic field, etc. This work studied and optimized the SHS-densification route for the synthesis of Gamma TiAl based Intermetallic (GE alloy: 48Ti-48Al-2Cr-Nb) using two different combustion modes: forced SHS + compaction and thermal explosion + compaction. A complete metallurgical characterization of the product was done: phase analysis, density, chemical analysis, microstructure and mechanical properties (tensile strength). The developed material and manufacturing process is a potential candidate to be used as turbine blades for ARIANNE VULCANE engine.Peer reviewe

    PM Based Titanium Matrix Composites for Aerospace Applications: Processing, Mechanical Properties and Scale Up

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    The reinforcement of titanium with a hard phase is an efficient way to increase the stiffness and strength of conventional titanium alloys. The high reactivity of titanium is a critical challenge in the processing of Titanium Matrix Composites (TMCs). For this reason, Powder Metallurgy is considered a very promising route for the manufacturing of TMCs. In this work, a master alloy (Ti-TiC) was developed by combustion synthesis. This alloy was further blended with conventional titanium alloy and the final consolidation was performed by Spark Plasma Sintering. In addition to the processing details, microstructural and thermomechanical characterization is presented. Materials obtained present higher Young Modulus and strength than conventional Ti-6Al-4V, with higher thermal conductivity and maintaining similar thermal expansion coefficient (CTE). The good corrosion resistance of the material makes it a candidate for possible applications in aerospace. This work presents also the scale up of the process to obtain aerospace demonstrators.This work was carried out within the frame work of the projects: ‘‘Development and Characterization of Advanced Metal Matrix Composites (Hybrid-MMs)’’) and “Hybrid Titanium Matrix Composites (TMC) for aero engines applications (AIRTMC) both supported by ESA (European Space Agency
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