Càlcul estructural d'un edifici d'oficines en zona sísmica

En el present projecte es realitza el càlcul de l’estructura d’un edifici destinat a oficines i situat en una zona altament sísmica, en la ciutat de Granada, concretament en el terme municipal de la Maracena. L’edifici consta de planta baixa, dues plantes, terrat accessible i coberta. Inicialment s’estudien les diferents tipologies estructurals amb les corresponents avantatges i inconvenients, i posteriorment s’opta per la solució més adient, estructura de formigó armat amb pòrtics en les dues direccions i llosa massissa. El càlcul de l’estructura s’ha dut a terme de forma manual, amb l’ajuda de programes informàtics per a l’obtenció dels esforços de cadascun dels elements estructurals. S’han realitzat estudis en 2 dimensions, i per a una millor precisió, en quan a resultats, s’ha estudiat l’estructura en 3 dimensions. La corresponent comprovació s’ha realitzat seguint els mètodes prescrits per la Instrucció EHE i altra bibliografia. Els passos seguits són els següents: - Predimensionat de l’estructura. - Dimensionat i armat dels elements estructurals amb la corresponent comprovació. - Càlcul de la fonamentació. - Dimensionat i armat d’escales. Tots els procediments de càlcul i resultats s’exposen en la memòria i els corresponents annexes de càlcul, a la vegada que apareixen de forma gràfica als plànols. Aquest projecte també inclou un estudi d’impacte mediambiental i un apartat de prescripcions constructives particulars. El plec de condicions i el pressupost d’execució del projecte es mostren en els annexes

Proteomics and the genetics of sperm chromatin condensation

Spermatogenesis involves extremely marked cellular, genetic and chromatin changes resulting in the generation of the highly specialized sperm cell. Proteomics allows the identification of the proteins that compose the spermatogenic cells and the study of their function. The recent developments in mass spectrometry (MS) have markedly increased the throughput to identify and to study the sperm proteins. Catalogs of thousands of testis and spermatozoan proteins in human and different model species are becoming available, setting up the basis for subsequent research, diagnostic applications and possibly the future development of specific treatments. The present review intends to summarize the key genetic and chromatin changes at the different stages of spermatogenesis and in the mature sperm cell and to comment on the presently available proteomic studies

Enzymatic inhibitors for combined antitumoral therapy in gynaecological cancers

Gynaecological cancers are pathologies originated in women's reproductive organs. There are different types depending on which organ are we referring to. Usually, when cancer is diagnosed at an early stage, it can be treated successfully through surgery although a complementary therapy is inevitable including radiation and chemotherapy. However, cancer relapse in most gynaecological cancer cases are recurrent leading to acquired chemoresistance of the tumour during their progression meaning that cells lose sensitivity to drugs specifically cancer stem cells (CSCs). CSCs represent a small subpopulation within a tumour that have stemness properties and acquire modifications to reject drugs. Here, combinatorial and targeted treatment aims to be tested as a solution to overcome chemoresistance phenomenon. The convergence of signalling pathways and their importance have led to the assessment of inhibitors in those components. Based on the hypothesis that chemotherapy combined with an inhibitor makes treatment more effective avoiding chemoresistance and making cells sensitive to it, the main goal is to develop this combination of drugs for treatment of gynaecological cancers. In a three-year project, target is identified through bioinformatic tools and validated performing a knockout with CRISPR/Cas9 system. Besides, CSCs are successfully isolated through CD133 and ALDH complementary methods. Promising targets are PI3K and ALDH due to its significant role. Then, it is essential to evaluate hit compound that can inhibit target enzyme interacting with it. In silico, a library of inhibitors is narrowed taking into account its properties. Later, this library of inhibitors is tested in vitro screening interactions with PI3K and ALDH as well as cell assays. CSCs proliferation and cytotoxicity are analysed to assess if the main objective of recovering the sensitivity is fulfilled. Considering Lipinski parameters and IC50 values, remarkable compounds are PF-04691502 and Disulfiram inhibiting PI3K and ALDH, respectively. Both combined with paclitaxel show a synergic effect recovering sensitivity in CSCs.Els càncers ginecològics són patologies originades en els òrgans reproductius de les dones. Existeixen diferents tipus segons l'òrgan a què ens referim. En general, quan el càncer es diagnostica en una etapa primerenca, es pot tractar amb èxit mitjançant cirurgia, encara que és inevitable una teràpia complementària que inclogui radiació i quimioteràpia. No obstant això, la recaiguda del càncer en la majoria dels casos de càncer ginecològic és recurrent, el que porta a la quimioresistència adquirida de el tumor durant la seva progressió, el que significa que les cèl·lules perden sensibilitat als medicaments, específicament a les cèl·lules mare del càncer (CSCs). Les CSCs representen una petita subpoblació dins d'un tumor que té propietats de cèl·lula mare i adquireix modificacions per rebutjar les drogues. Aquí, el tractament combinatori i dirigit té com a objectiu ser provat com una solució per superar el fenomen de quimioresistència. La convergència de les vies de senyalització i la seva importància han portat a l'avaluació d'inhibidors en aquests components. Basats en la hipòtesi que la quimioteràpia combinada amb un inhibidor fa que el tractament sigui més efectiu evitant la quimioresistència i fent que les cèl·lules siguin sensibles a ell, l'objectiu principal és desenvolupar aquesta combinació de medicaments per al tractament de càncers ginecològics. En un projecte de tres anys, l'objectiu s'identifica a través d'eines bioinformàtiques i es valida realitzant un knockout amb el sistema CRISPR/Cas9. A més, les CSCs s'aïllen amb èxit a través dels mètodes complementaris CD133 i ALDH. Les molècules diana prometedores són PI3K i ALDH causa del seu important paper. Llavors, és essencial avaluar els compostos líders que poden inhibir l'enzim interactuant amb ell. In silico, una biblioteca d'inhibidors es redueix tenint en compte les seves propietats. Més tard, aquesta biblioteca d'inhibidors es prova les interaccions in vitro amb PI3K i ALDH, així com assajos cel·lulars. La proliferació de CSC i la citotoxicitat s'analitzen per avaluar si es compleix l'objectiu principal de recuperar la sensibilitat. Tenint en compte els paràmetres de Lipinski i els valors de IC50, els compostos líder són PF-04691502 i Disulfiram que inhibeixen PI3K i ALDH, respectivament. Tots dos combinats amb paclitaxel mostren un efecte sinèrgic que recupera la sensibilitat en les CSCs.Los cánceres ginecológicos son patologías originadas en los órganos reproductivos de las mujeres. Existen diferentes tipos según el órgano al que nos refiramos. Por lo general, cuando el cáncer se diagnostica en una etapa temprana, se puede tratar con éxito mediante cirugía, aunque es inevitable una terapia complementaria que incluya radiación y quimioterapia. Sin embargo, la recaída del cáncer en la mayoría de los casos de cáncer ginecológico es recurrente, lo que lleva a la quimiorresistencia adquirida del tumor durante su progresión, lo que significa que las células pierden sensibilidad a los medicamentos, específicamente a las células madre del cáncer (CSCs). Las CSCs representan una pequeña subpoblación dentro de un tumor que tiene propiedades de célula madre y adquiere modificaciones para rechazar las drogas. Aquí, el tratamiento combinatorio y dirigido tiene como objetivo ser probado como una solución para superar el fenómeno de quimiorresistencia. La convergencia de las vías de señalización y su importancia han llevado a la evaluación de inhibidores en esos componentes. Basado en la hipótesis de que la quimioterapia combinada con un inhibidor hace que el tratamiento sea más efectivo evitando la quimiorresistencia y haciendo que las células sean sensibles a él, el objetivo principal es desarrollar esta combinación de medicamentos para el tratamiento de cánceres ginecológicos. En un proyecto de tres años, el objetivo se identifica a través de herramientas bioinformáticas y se valida realizando un knockout con el sistema CRISPR/ Cas9. Además, las CSCs se aíslan con éxito a través de los métodos complementarios CD133 y ALDH. Las moléculas diana prometedoras son PI3K y ALDH debido a su importante papel. Entonces, es esencial evaluar los compuestos líderes que pueden inhibir la enzima interactuando con él. In silico, una biblioteca de inhibidores se reduce teniendo en cuenta sus propiedades. Más tarde, esta biblioteca de inhibidores se prueba las interacciones in vitro con PI3K y ALDH, así como ensayos celulares. La proliferación de CSC y la citotoxicidad se analizan para evaluar si se cumple el objetivo principal de recuperar la sensibilidad. Teniendo en cuenta los parámetros de Lipinski y los valores de IC50, los compuestos líderes son PF-04691502 y Disulfiram que inhiben PI3K y ALDH, respectivamente. Ambos combinados con paclitaxel muestran un efecto sinérgico que recupera la sensibilidad en las CSCs

Genome-wide association meta-analysis of cocaine dependence: shared genetics with comorbid conditions

Cocaine dependence is a complex psychiatric disorder that is highly comorbid with other psychiatric traits. Twin and adoption studies suggest that genetic variants contribute substantially to cocaine dependence susceptibility, which has an estimated heritability of 65-79%. Here we performed a meta-analysis of genome-wide association studies of cocaine dependence using four datasets from the dbGaP repository (2085 cases and 4293 controls, all of them selected by their European ancestry). Although no genome-wide significant hits were found in the SNP-based analysis, the gene-based analysis identified HIST1H2BD as associated with cocaine-dependence (10% FDR). This gene is located in a region on chromosome 6 enriched in histone-related genes, previously associated with schizophrenia (SCZ). Furthermore, we performed LD Score regression analysis with comorbid conditions and found significant genetic correlations between cocaine dependence and SCZ, ADHD, major depressive disorder (MDD) and risk taking. We also found, through polygenic risk score analysis, that all tested phenotypes are significantly associated with cocaine dependence status: SCZ (R2 = 2.28%; P = 1.21e-26), ADHD (R2 = 1.39%; P = 4.5e-17), risk taking (R2 = 0.60%; P = 2.7e-08), MDD (R2 = 1.21%; P = 4.35e-15), children's aggressive behavior (R2 = 0.3%; P = 8.8e-05) and antisocial behavior (R2 = 1.33%; P = 2.2e-16). To our knowledge, this is the largest reported cocaine dependence GWAS meta-analysis in European-ancestry individuals. We identified suggestive associations in regions that may be related to cocaine dependence and found evidence for shared genetic risk factors between cocaine dependence and several comorbid psychiatric traits. However, the sample size is limited and further studies are needed to confirm these results

Los gigantes tecnológicos conquistan el audiovisual. El caso de Amazon Prime Video

Los grupos tecnológicos GAFAM —Google, Amazon, Facebook, Apple y Microsoft— destacan por su relevancia, presencia e influencia creciente en diferentes sectores, entre ellos el audiovisual. Destacamos el caso de Amazon, ya que no solo está consolidando su posición dentro del ecosistema mediático mediante la plataforma Amazon Prime Video —APV—, sino que ha dado un paso sin precedentes entre los GAFAM, con la compra en mayo de 2021 de Metro Goldwyn Mayer. El objetivo principal de la presente investigación es realizar un estudio detallado del caso de APV, teniendo en cuenta la particularidad de Amazon como grupo tecnológico ecosistémico. Para ello, se aborda el análisis de la evolución del grupo, su caracterización y ámbitos de actuación. A partir de ahí, se estudia el impacto de APV sobre el sector audiovisual de streaming. Se adopta el estudio de caso como técnica de investigación cualitativa para explicar, a través de diversas fuentes, el fenómeno Amazon y su incursión en el streaming audiovisual.GAFAM technology groups stand out for their relevance, presence, and increasing influence in different sectors, including the audiovisual industry. We highlight the case of Amazon, as it is not only consolidating its position within the media ecosystem through the Amazon Prime Video —APV— platform, but has also taken an unprecedented step among GAFAMs, with the purchase of Metro Goldwyn Mayer in May 2021. The main objective of this research is to carry out a detailed study of the APV case, taking into account the particularity of Amazon as an ecosystemic technology group. To this end, we will analyze the evolution of the group, its features and areas of action. From there, the impact of APV on the audiovisual streaming sector is studied. The case study is adopted as a qualitative research technique to explain, through various sources, the Amazon phenomenon and its incursion into audiovisual streaming

MIR-9, miR-153 and miR-124 are down-regulated by acute exposure to cocaine in adopaminergic cell model and may contribute to cocaine dependence

Cocaine is one of the most used psychostimulant drugs worldwide. MicroRNAs are post-transcriptional regulators of gene expression that are highly expressed in brain, and several studies have shown that cocaine can alter their expression. In a previous study, we identified several protein-coding genes that are differentially expressed in a dopaminergic neuron-like model after an acute exposure to cocaine. Now, we used the prediction tool WebGestalt to identify miRNA molecules potentially involved in the regulation of these genes. Using the same cellular model, we found that seven of these miRNAs are down-regulated by cocaine: miR-124-3p, miR-124-5p, miR-137, miR-101-3p, miR-9-5p, miR-369-3p and miR-153-3p, the last three not previously related to cocaine. Furthermore, we found that three of the miRNA genes that are differentially expressed in our model (hsa-miR-9-1, hsa-miR-153-1 and hsa-miR-124-3) are nominally associated with cocaine dependence in a case-control study (2,085 cases and 4,293 controls). In summary, we highlighted novel miRNAs that may be involved in those cocaine-induced changes of gene expression that underlie addiction. Moreover, we identified genetic variants that contribute to cocaine dependence in three of these miRNA genes, supporting the idea that genes differentially expressed under cocaine may play an important role in the susceptibility to cocaine dependence

An inline optic sensor technology to determine milk pH in yogurt manufacturing

Accurate determination of yogurt fermentation end-point (i.e., the end of the fermentation process at pH = 4.6) is essential for yogurt manufacturing. As a result of the high complexity of milk fermentation induced by lactic acid bacteria, an inadequate fermentation end-point selection could significantly compromise manufacturing cost and the final yogurt quality. Currently, acid coagulation to produce yogurt in the industry is monitored from discontinuous pH measurements that are measured manually every 10-15 minutes, a laborious and inaccurate techniquePostprint (published version

Improved thermal management in HKUST-1 composites upon graphite flakes incorporation: Hydrogen adsorption properties

HKUST-1-based composites have been synthesized through the incorporation of synthetic graphite flakes in the MOF synthesis media. The presence of flakes gives rise to high quality HKUST-1 crystals, combining different morphologies (octahedral-shape crystals, cauliflower-shape crystals and truncated pyramids). The incorporation of graphite in the composites improves the structural stability of the embedded nanocrystals upon a conforming step at 377 kg/cm2 (0.5 tons), with limited structural damage (below 10% BET surface area reduction as compared to the 40% observed for pure HKUST-1). Furthermore, composites exhibit a significant improvement in thermal management, associated with the excellent thermal and electrical properties of the graphite microdomains incorporated. The improved stability of the composites is also reflected in the adsorption performance for hydrogen at atmospheric pressure and cryogenic temperatures, with a significant preservation of the adsorption properties (gravimetric capacity, <15% decrease vs powders) in the monoliths containing graphite. The best adsorption performance is achieved with sample HKUST-1@10GF, in monolithic form, with a volumetric excess uptake at 0.1 MPa and −195 °C close to 18.7 g/L. This value is among the best described in the literature for monolithic MOFs under similar adsorption conditions.Authors would like to acknowledge financial support from Ministerio de Ciencia e Innovación (Project PID2019-108453GB-C21), Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana (project CIPROM/2021/022) and European Union: Horizon Europe (project MOST-H2; Grant agreement no. 101058547). M. R.-C. and M. M. thank the project PID2019-104379RB-C22 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” for financial support. Authors would like to thank Imerys Graphite & Carbon Ltd. (Dr. Raffaele Gilardi) for the supply of the graphite flakes

Insights into the sperm chromatin and implications for male infertility from a protein perspective

Male germ cells undergo an extreme but fascinating process of chromatin remodeling that begins in the testis during the last phase of spermatogenesis and continues through epididymal sperm maturation. Most of the histones are replaced by small proteins named protamines, whose high basicity leads to a tight genomic compaction. This process is epigenetically regulated at many levels, not only by posttranslational modifications, but also by readers, writers, and erasers, in a context of a highly coordinated postmeiotic gene expression program. Protamines are key proteins for acquiring this highly specialized chromatin conformation, needed for sperm functionality. Interestingly, and contrary to what could be inferred from its very specific DNA-packaging function across protamine-containing species, human sperm chromatin contains a wide spectrum of protamine proteoforms, including truncated and posttranslationally modified proteoforms. The generation of protamine knock-out models revealed not only chromatin compaction defects, but also collateral sperm alterations contributing to infertile phenotypes, evidencing the importance of sperm chromatin protamination toward the generation of a new individual. The unique features of sperm chromatin have motivated its study, applying from conventional to the most ground-breaking techniques to disentangle its peculiarities and the cellular mechanisms governing its successful conferment, especially relevant from the protein point of view due to the important epigenetic role of sperm nuclear proteins. Gathering and contextualizing the most striking discoveries will provide a global understanding of the importance and complexity of achieving a proper chromatin compaction and exploring its implications on postfertilization events and beyond. This article is categorized under: Reproductive System Diseases > Genetics/Genomics/Epigenetics Reproductive System Diseases > Molecular and Cellular Physiology