A novel procedure for the evaluation of new refractories for aluminium furnaces

Refractory materials for aluminium industry are designed to be resistant to different degrees of thermal, mechanical and chemical wear. The refractory wall thickness reduction during service life increases the heat losses through walls, decreasing the thermal efficiency of the furnace. Last developments are focused on obtaining refractories with better performance and improved insulation properties. On this regard, a novel procedure has been developed to compare the thermal and chemical performance of different refractories. This procedure includes comparing the resistance of the refractory to molten aluminium, determining corundum and cracks appearance, and measuring the internal and external wall temperatures of a testing furnace using thermography. These temperature measurements make possible to estimate the wall thermal conductivity together with its evolution in time and also validate its simulation modelling in order to be used in future furnace designs. Two refractories have been tested by this procedure for comparative purposes; a commercial alumina castable and an improved alumina castable with better insulation propertiesEuropean Commission - Seventh Framework Programme for Research (FP7)

Development of a simulation procedure for the evaluation of new refractories for aluminium furnaces

Refractory materials for aluminium industry are designed to be resistant to different degrees of thermal, mechanical and chemical wear. The refractory wall thickness reduction during service life increases the heat losses through walls decreasing the thermal efficiency of the furnace. Last developments are focused on obtaining refractories with better performance and improved insulation properties. On this regard, a simulation procedure has been developed to compare the thermal and chemical performance of different refractories during end use. This procedure includes measuring the internal and external wall temperatures of a testing furnace using thermography, and comparing the resistance to liquid aluminium determining the corundum and cracks appearance. Two refractories have been tested by this procedure for comparative purposes; a commercial alumina castable and an improved alumina castable with better insulation properties.European Commission's Seventh Framework Programme for Research (FP7

Microstructural Evolution as a Function of Increasing Aluminum Content in Novel Lightweight Cast Irons

In the context of the development of new lightweight materials, Al-alloyed cast irons have a great potential for reducing the weight of the different part of the vehicles in the transport industry. The correlation of the amount of Al and its effect in the microstructure of cast irons is not completely well established as it is affected by many factors such as chemical composition, cooling rate, etc. In this work, four novel lightweight cast irons were developed with different amounts of Al (from 0 wt. % to 15 wt. %). The alloys were manufactured by an easily scalable and affordable gravity casting process in an induction furnace, and casted in a resin-bonded sand mold. The microstructural evolution as a function of increasing Al content by different microstructural characterization techniques was studied. The hardness of the cast irons was measured by the Vickers indentation test and correlated with the previously characterized microstructures. In general, the microstructural evolution shows that the perlite content decrease with the increment of wt. % of Al. The opposite occurs with the ferrite content. In the case of graphite, a slight increment occurs with 2 wt. % of Al, but a great decrease occurs until 15 wt. % of Al. The addition of Al promotes the stabilization of ferrite in the studied alloys. The hardness obtained varied from 235 HV and 363 HV in function of the Al content. The addition of Al increases the hardness of the studied cast irons, but not gradually. The alloy with the highest hardness is the alloy containing 7 wt. % Al, which is correlated with the formation of kappa-carbides and finer perlite.This work has been partially funded by the Basque Government through the project Elkartek LION: KK-2019/0004

Grain-Size Prediction Model in Aluminum Castings Manufactured by Low-Pressure Technology

The grain refinement in a real casting manufactured by Low Pressure Die Casting (LPDC) such as wheels and steering knuckles depends on the grain-refinement potential of the metal and the geometry of the part/process parameters.For this study, the effect of the cooling rate on the AlSi7Mg alloy with different metal qualities in terms of grain refinement was tested. The grain size has been metallographically evaluated in cylindrical test pieces and in the real wheels and steering knuckles manufactured at the Mapsa and Fagor Ederlan foundries. The Thermolan®-Al system has been used to evaluate the nucleation potential in terms of grain size on a standard cup. The grain size has been modeled taking into account the effect of the cooling rate measured in the center of the cylindrical test parts and the different grain-size potential. Different grades of refinement have been tested. The grain size measured in a real casting (wheel and steering knuckle) was used to calibrate the model for a real part in LPDC for different grain-size potential

Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide

While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34 + progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS. The hematopoiesis of patients with del(5q) Myelodysplastic Syndromes is composed of a mixture of cells with and without the deletion. Here, the authors show that del(5q) and non-del(5q) cells share similar transcriptional alterations, with del(5q) cells presenting additional lesions. Moreover, hematological response to lenalidomide is associated with the reversal of some transcriptional lesions in both del(5q) and non-del(5q) cells

Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia

Despite the potential of CAR-T therapies for hematological malignancies, their efficacy in patients with relapse and refractory Acute Myeloid Leukemia has been limited. The aim of our study has been to develop and manufacture a CAR-T cell product that addresses some of the current limitations. We initially compared the phenotype of T cells from AML patients and healthy young and elderly controls. This analysis showed that T cells from AML patients displayed a predominantly effector phenotype, with increased expression of activation (CD69 and HLA-DR) and exhaustion markers (PD1 and LAG3), in contrast to the enriched memory phenotype observed in healthy donors. This differentiated and more exhausted phenotype was also observed, and corroborated by transcriptomic analyses, in CAR-T cells from AML patients engineered with an optimized CAR construct targeting CD33, resulting in a decreased in vivo antitumoral efficacy evaluated in xenograft AML models. To overcome some of these limitations we have combined CRISPR-based genome editing technologies with virus-free gene-transfer strategies using Sleeping Beauty transposons, to generate CAR-T cells depleted of HLA-I and TCR complexes (HLA-IKO/TCRKO CAR-T cells) for allogeneic approaches. Our optimized protocol allows one-step generation of edited CAR-T cells that show a similar phenotypic profile to non-edited CAR-T cells, with equivalent in vitro and in vivo antitumoral efficacy. Moreover, genomic analysis of edited CAR-T cells revealed a safe integration profile of the vector, with no preferences for specific genomic regions, with highly specific editing of the HLA-I and TCR, without significant off-target sites. Finally, the production of edited CAR-T cells at a larger scale allowed the generation and selection of enough HLA-IKO/TCRKO CAR-T cells that would be compatible with clinical applications. In summary, our results demonstrate that CAR-T cells from AML patients, although functional, present phenotypic and functional features that could compromise their antitumoral efficacy, compared to CAR-T cells from healthy donors. The combination of CRISPR technologies with transposon-based delivery strategies allows the generation of HLA-IKO/TCRKO CAR-T cells, compatible with allogeneic approaches, that would represent a promising option for AML treatment

Precariedad, exclusión social y diversidad funcional (discapacidad): lógicas y efectos subjetivos del sufrimiento social contemporáneo (III). Innovación docente en Filosofía

El PIMCD Precariedad, exclusión social y diversidad funcional (discapacidad): lógicas y efectos subjetivos del sufrimiento social contemporáneo (III). Innovación docente en Filosofía se ocupa de conceptos que generalmente han tendido a ser eludidos en la enseñanza académica de filosofía. Se trata de la tercera edición de un PIMCD que ha venido recibiendo financiación en las últimas convocatorias PIMCD UCM, de los que se han derivado publicaciones colectivas publicadas por Ediciones Complutense y Siglo XXI