Analysis of different structural steelwork solutions for an industrial building

[Resumen] En este proyecto se ha realizado el diseño, cálculo y optimización de la estructura metálica de una nave industrial. Además del cálculo de una serie de variantes de la misma. Se trata de una estructura biempotrada constituida por 8 pórticos formados por perfiles IPE y HEA. Su luz estructural será de 22 metros con separación entre pórticos de 6 metros alcanzando así una longitud total de 42 metros. En lo que respecta a la altura de pilares, será de 7 metros en la parte exterior y de 8,1 metros en coronación.[Resumo] Neste proxecto realizouse o deseño, cálculo e optimización da estrutura metálica dunha nave industrial. Ademais do cálculo dunha serie de variantes da mesma. Trátase dunha estrutura biempotrada constituida por 8 pórticos fomados por perfís IPE e HEA. A luz estrutural será de 22 metros con separación entre pórticos de 6 metros acadando así unha lonxitude total de 42 metros. No que respecta a á altura de piares, será de 7 metros na parte exterior e de 8,1 metros en coroación.[Abstract] In this project, the design, calculation and optimisation of the metallic structure of a warehouse has been carried out. In addition, a series of variants of the same will be calculated. It is a biembedded structure composed of 8 porticoes formed by IPE and HEA profiles. Its structural light will be 22 meters with separation between porticoes of 6 meters thus reaching a total length of 42 meters. Regarding the height of the pillars, it will be 7 meters on the outside and 8,1 meters in coronation.Traballo fin de grao (UDC.EPS). Enxeñaría en tecnoloxías industriais. Curso 2021/202

siRNA screen of microglia to identify neuroprotective drug targets in Parkinson´s disease

The uploaded accepted version corresponds to pages E183-E184 of the publication "GLIA Bilbao 2015: Abstracts Oral Presentations, Posters, Indexes" available at https://doi.org/10.1002/glia.22870.Question: Neuroinflammation is a fundamental process contributing to the death of dopaminergic neurons in Parkinson´s Disease (PD). During this process, activated microglia secrete cytotoxic substances which lead to neuronal death. Therefore, we are looking for the molecular mechanism that reverses the inflammatory activation of microglia, since this knowledge would be essential to protect from neurodegeneration. Methods and Results: Very interestingly our previous data (Neubrand et al., 2014) indicate that adipose derived mesenchymal stem cells (ASCs) exert important anti-inflammatory actions on microglia. We observed that microglia exposed to ASCs or their secreted factors (conditioned medium, CM) underwent a dramatic cell shape change into a highly elongated morphology (Fig 1A), similar to the phenotype of microglia observed in a healthy brain. The elongation induced by ASCs was associated with a decrease of the pro-inflammatory cytokine TNFalpha (Fig 1B) as well as with an upregulation of neurotrophic factors. Thus, ASC stimulated microglia represent an ideal tool to study the intracellular events necessary for the transition from inflammatory activated to non-inflammatory neuroprotective microglia. In this way we have already identified the small RhoGTPases Rac1 and Cdc42, which are important regulators of the actin cytoskeleton, as essential molecules in this transition (Fig 1C). Since these molecules represent possible drug targets to induce the reversion of neurotoxic microglia to neuroprotective ones, we are currently performing an siRNA screen to identify the molecular players of this ASC-induced reversion. Because this transition is easily detectable by light microscopy (see Figs 1A and C) and changes in the cell shape are intrinsically related to changes of the cytoskeleton, we are carrying out a microscopy-based screen of the major cytoskeletal regulators. In addition, we are including in the screen the regulators of microglia-specific activation/inflammatory pathways as siRNA targets. Conclusion: Our project is the first siRNA screen performed in primary microglia and we aim to identify a list of molecules that are specifically implicated in the reversion from activated to neuroprotective microglia. Since positive hits would represent potential neuroprotective drug targets, the outcome of this screen opens up a variety of novel investigation lines and therapies in PD or other neurodegenerative diseases

Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model

Aims. To study the influence of P-glycoprotein (P-glycoprotein, ABCB1, MDR1) function on placental transfer of lopinavir with ritonavir at different albumin concentrations. Methods. Cotyledons were perfused with lopinavir, ritonavir, and the internal control antipyrin, at various albumin concentrations (10, 30, 40 g/L). After the control phase of each experiment, the P-glycoprotein inhibitor ciclosporin A was added at middle perfusion (45 minutes). Fetal Transfer Rate (FTR) and Clearance Index (CLI) were compared between the 2 phases. Results. In the control phase, the clearance index of lopinavir decreased from 0.401 ± 0.058 to 0.007 ± 0.027, as albumin concentrations increased from 10 g/L to higher concentrations (30, 40 g/L). When adding ciclosporin A at physiological albumin concentrations, the clearance index of lopinavir increased significantly 10.3 fold (95% of CI difference [−0.156, −0.002], P = .046) and became positive for ritonavir. Conclusions. Even at high albumin concentrations, inhibition of placental P-glycoprotein increased placental transfer of lopinavir, suggesting that this efflux pump actively reduces placental transfer of the drug. This mechanism may play a role in fetal exposure to maternal antiretroviral therapy

Bioprinting decellularized breast tissue for the development of three-dimensional breast cancer models

The tumor extracellular matrix (ECM) plays a vital role in tumor progression and drug resistance. Previous studies have shown that breast tissue-derived matrices could be an important biomaterial to recreate the complexity of the tumor ECM. We have developed a method for decellularizing and delipidating a porcine breast tissue (TDM) compatible with hydrogel formation. The addition of gelatin methacrylamide and alginate allows this TDM to be bioprinted by itself with good printability, shape fidelity, and cytocompatibility. Furthermore, this bioink has been tuned to more closely recreate the breast tumor by incorporating collagen type I (Col1). Breast cancer cells (BCCs) proliferate in both TDM bioinks forming cell clusters and spheroids. The addition of Col1 improves the printability of the bioink as well as increases BCC proliferation and reduces doxorubicin sensitivity due to a downregulation of HSP90. TDM bioinks also allow a precise three-dimensional printing of scaffolds containing BCCs and stromal cells and could be used to fabricate artificial tumors. Taken together, we have proven that these novel bioinks are good candidates for biofabricating breast cancer models.Peer ReviewedPostprint (published version

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Ciudad de Bogotá, D.C.

El Diplomado de Profundización Acompañamiento Psicosocial en Escenarios de Violencia, tiene como objetivo brindar herramientas que permitan analizar, comprender y abordar diferentes situaciones de violencia donde la integridad física y emocional de un individuo o comunidad se ven vulnerados, en el mismo, se pueden encontrar diferentes relatos realmente impactantes, ya que el conflicto armado de Colombia no distingue edades, raza, géneros, etnias, etc. En el presente documento se evidenciará el desarrollo de diferentes actividades, las cuales son elaboradas teniendo en cuenta uno de los relatos donde se evidencia la historia de vida de “Carlos Arturo” y la comunidad de “Peñas Coloradas” los cuales han sufrido directamente el conflicto armado en Colombia y pese a esto, han sido casos que han fortalecido a las víctimas y desarrollado habilidades sociales como la resiliencia y habilidades individuales como la potenciación de sus recursos. Para el caso de "Carlos Arturo" se plantean una serie de interrogantes dentro de las cuales se evidencian tres tipos de preguntas (circulares, reflexivas y estratégicas) las cuales tienen como objetivo abordar el relato e historia de vida de una manera profesional y empática. Finalmente, se realiza un informe analítico donde se abordan cada uno de los casos de violencia trabajados desde el uso de la Fotovoz como técnica que permite conocer y comprender algunas problemáticas sociales de los contextos.The diploma course on deepening psychosocial accompaniment in scenarios of violence, aims to provide tools to analyze, understand and address different situations of violence where the physical and emotional integrity of an individual or community are violated, in it, you can find different really shocking stories, since the armed conflict in Colombia does not distinguish ages, race, gender, ethnic groups, etc. In this document, the development of different activities will be evidenced, which are elaborated taking into account one of the stories where the life story of "Carlos Arturo" and the community of "Peñas Coloradas" are evidenced, which have directly suffered the conflict. armed in Colombia and despite this, there have been cases that have strengthened the victims and developed social skills such as resilience and individual skills such as the empowerment of their resources. In the case of "Carlos Arturo" a series of questions are raised within which three types of questions are evidenced (circular, reflective and strategic) which aim to address the story and life story in a professional and empathic way. Finally, an analytical report is made where each of the cases of violence worked from the use of Photovoice as a technique that allows knowing and understanding some social problems of the contexts are addressed

Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases

This research was funded by the Andalusian Government, Spain (grant no. P20-01255 to M.D. and FEDER program grant no. A1-CTS-324-UGR18 to M.R.S.) and by the Spanish Ministry for Economy and Competition, Spain (grant no. SAF2017-85602-R and PID2020-119638RB-I00, both to E.G.-R.). A.I.S.-C. was the awardee of a Research Starting Fellowship for master´s students at the University of Granada, Spain. The APC was funded by MDPI.Neurological disorders, including neurodegenerative diseases, are often characterized by neuroinflammation, which is largely driven by microglia, the resident immune cells of the central nervous system (CNS). Under these conditions, microglia are able to secrete neurotoxic substances, provoking neuronal cell death. However, microglia in the healthy brain carry out CNS-supporting functions. This is due to the ability of microglia to acquire different phenotypes that can play a neuroprotective role under physiological conditions or a pro-inflammatory, damaging one during disease. Therefore, therapeutic strategies focus on the downregulation of these neuroinflammatory processes and try to re-activate the neuroprotective features of microglia. Mesenchymal stem cells (MSC) of different origins have been shown to exert such effects, due to their immunomodulatory properties. In recent years, MSC derived from adipose tissue have been made the center of attention because of their easy availability and extraction methods. These cells induce a neuroprotective phenotype in microglia and downregulate neuroinflammation, resulting in an improvement of clinical symptoms in a variety of animal models for neurological pathologies, e.g., Alzheimer’s disease, traumatic brain injury and ischemic stroke. In this review, we will discuss the application of adipose tissue-derived MSC and their conditioned medium, including extracellular vesicles, in neurological disorders, their beneficial effect on microglia and the signaling pathways involved.Andalusian Government, Spain P20-01255FEDER program grant no. A1-CTS-324-UGR18Spanish Ministry for Economy and Competition, Spain (grant no. SAF2017-85602-R and PID2020-119638RB-I00)Research Starting Fellowship for master´s students at the University of Granada, SpainMDP

Cells

Stem cells isolated from the apical papilla of wisdom teeth (SCAPs) are an attractive model for tissue repair due to their availability, high proliferation rate and potential to differentiate in vitro towards mesodermal and neurogenic lineages. Adult stem cells, such as SCAPs, develop in stem cell niches in which the oxygen concentration [O] is low (3-8% compared with 21% of ambient air). In this work, we evaluate the impact of low [O] on the physiology of SCAPs isolated and processed in parallel at 21% or 3% O without any hyperoxic shock in ambient air during the experiment performed at 3% O. We demonstrate that SCAPs display a higher proliferation capacity at 3% O than in ambient air with elevated expression levels of two cell surface antigens: the alpha-6 integrin subunit (CD49f) and the embryonic stem cell marker (SSEA4). We show that the mesodermal differentiation potential of SCAPs is conserved at early passage in both [O], but is partly lost at late passage and low [O], conditions in which SCAPs proliferate efficiently without any sign of apoptosis. Unexpectedly, we show that autophagic flux is active in SCAPs irrespective of [O] and that this process remains high in cells even after prolonged exposure to 3% O

End-to-end process of hollow spacecraft structures with high frequency and low mass obtained with in-house structural optimization tool and additive manufacturing

In the space sector the most decisive elements are: mass reduction, cost saving and minimum lead time; here, structural optimization and additive layer manufacturing (ALM) fit best. The design must be driven by stiffness, because an important requirement for spacecraft (S/C) structures is to reduce the dynamic coupling between the S/C and the launch vehicle. The objective is to create an end-to-end process, from the input given by the customer to the manufacturing of an aluminum part as light as possible but at the same time considerably stiffer while taking the full advantage of the design flexibility given by ALM. To design and optimize the parts, a specialized in-house tool was used, guaranteeing a load-sufficient material distribution. Using topological optimization, the iterations between the design and the stress departments were diminished, thus greatly reducing the lead time. In order to improve and lighten the obtained structure a design with internal cavities and hollow beams was considered. This implied developing of a procedure for powder evacuation through iterations with the manufacturer while optimizing the design for ALM. The resulted part can be then manufactured via ALM with no need of further design adjustments. To achieve a high-quality part with maximum efficiency, it is essential to have a loop between the design team and the manufacturer. Topological optimization and ALM work hand in hand if used properly. The team achieved a more efficient structure using topology optimization and ALM, than using conventional design and manufacturing methods