Don't Break the Axis: Placental Inflammation Leads to Congenital Heart Disease.

This study was supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV [Centro de Investigación Biomedica en Red]) financed by MCIN/AEI/10.13039/501100011033 (Ministerio de Ciencia e Innovación/La Agencia Estatal de Investigación). The Centro Nacional de Investigaciones Cardiovasculares is supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S), financed by MCIN/ AEI/10.13039/501100011033.S

DACH1-Driven Arterialization: Angiogenic Therapy for Ischemic Heart Disease?

J.L. de la Pompa is supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV) from the Spanish Ministry of Science, Innovation and Universities.S

Procesos Gaussianos para problemas de regresión y estimación de la incertidumbre

En muchos problemas de regresión, surge la necesidad de no sólo predecir un valor, sino dar también un intervalo de confianza o incertidumbre, porque en el problema en cuestión las mediciones realizadas tengan ruido o las observaciones se vean influenciadas por otras que desconocemos o simplemente no podamos medir. Por ello, en este Trabajo Fin de Máster se estudiarán los procesos Gaussianos en regresión pues dan una distribución a la predicción, permitiéndonos calcular intervalos de incertidumbre. En este Trabajo Fin de Máster hemos realizado primero un estudio de algunos algoritmos de aprendizaje automático como la regresión lineal, los perceptrones multicapa, las SVR o la regresión lineal Bayesiana; esto nos ha permitido comparar y comprender mejor a los procesos Gaussianos. Posteriormente, hemos estudiado los procesos Gaussianos en regresión así como su hiperparametrización; además, hemos analizado y ampliado la teoría de los procesos Gaussianos censurados. Experimentalmente, nos interesa ver cómo de buena es la predicción de los procesos Gaussianos comparándola con otros algoritmos de aprendizaje automático y cómo de buenos son los intervalos que obtenemos con los procesos Gaussianos. Para ello hemos realizado los experimentos en dos problemas: la predicción de energía eólica en Sotavento, que es un parque eólico situado en Galicia y la predicción de energía eólica total en España peninsular. En resumen, hemos observado que la predicción de los procesos Gaussianos de media cero es un poco peor que la de una SVR; no obstante, hemos visto que la hiperparametrización del núcleo que hemos realizado para los procesos Gaussianos la podemos llevar a la SVR, permitiéndonos usar núcleos más complicados y reducir el coste computacional. En los intervalos de confianza, hemos visto que a los intervalos de incertidumbre del proceso Gaussiano les hacía falta una calibración y con ella obtenemos resultados buenos; también hemos visto que no merece la pena modelizar los intervalos de incertidumbre con los residuos de una SVR pues obtenemos unos resultados peores que con el proceso Gaussiano de manera directa. Finalmente, como resultado del TFM se ha obtenido la publicación Gaussian Process Kernels for Support Vector Regression in Wind Energy Prediction aceptada en el congreso IDEAL 2018.In many regression problems, we need not only to predict a value, but also give a con dence interval or uncertainty, because in the problem we're trying to solve, the measurements could have noise or the target variables are in uenced by variables that we do not know or we simply can not measure. For this reason, in this Master Thesis we have studied Gaussian Processes in regression since they give a distribution to the prediction, allowing us to calculate intervals of uncertainty. In this Master Thesis we rst have made a study of some machine learning algorithms such as linear regression, multilayer perceptrons, SVR or Bayesian linear regression; which has allowed us to compare and better understand Gaussian Processes. Subsequently, we have studied Gaussian Processes in regression as well as their hyperparametrization; in addition, we have analyzed and expanded the theory of censored Gaussian Processes. Experimentally, we were interested in rating how good is the prediction of Gaussian Processes by comparing it with other machine learning algorithms and how good were the intervals we obtain with Gaussian Processes. For this, we have done the experiments in two problems: the prediction of wind energy production in Sotavento, which is a wind farm located in Galicia and the prediction of the total wind energy production in Peninsular Spain. In summary, we have observed that the prediction of Gaussian Processes of zero mean is slightly worse than the prediction of a SVR; however, we have seen that the hyperparametrization of the kernel that we have made with Gaussian Processes, can be carried to the SVR, allowing us to use more complicated kernels and reduce the computational cost of SVR. In the con dence intervals, we have seen that the uncertainty intervals of Gaussian process needed a calibration and with it we obtained good results; we have also seen that it is not worth to model the intervals of uncertainty with the residuals of an SVR because we obtain worse results than with Gaussian process directly. Finally, as a result of this Master Thesis it will be published the following paper: Gaussian Process Kernels for Support Vector Regression in Wind Energy Prediction which is accepted in the IDEAL 2018 conference

Los efectos visuales digitales en la cinematografía

Los efectos visuales digitales en la cinematografí

Midkine-a Regulates the Formation of a Fibrotic Scar During Zebrafish Heart Regeneration.

Unlike the hearts of mammals, the adult zebrafish heart regenerates after injury. Heart cryoinjury in zebrafish triggers the formation of a fibrotic scar that gradually degrades, leading to regeneration. Midkine-a (Mdka) is a multifunctional cytokine that is activated after cardiac injury. Here, we investigated the role of mdka in zebrafish heart regeneration. We show that mdka expression was induced at 1-day post-cryoinjury (dpci) throughout the epicardial layer, whereas by 7 dpci expression had become restricted to the epicardial cells covering the injured area. To study the role of mdka in heart regeneration, we generated mdka-knock out (KO) zebrafish strains. Analysis of injured hearts showed that loss of mdka decreased endothelial cell proliferation and resulted in an arrest in heart regeneration characterized by retention of a collagenous scar. Transcriptional analysis revealed increases in collagen transcription and intense TGFβ signaling activity. These results reveal a critical role for mdka in fibrosis regulation during heart regeneration.This study was supported by Grants PID2019-104776RB-I00, CB16/11/00399 (CIBER CV) and RD16/0011/0021 (TERCEL) from the Spanish Ministry of Science, Innovation and Universities (MCIU) and Grants from the Fundación BBVA (Ref.: BIO14_298), Fundación La Marató (Ref.: 20153431) and the European Commission through CardioNeT (Ref.: 28600) from the European Commission to JLP. DG held a Ph.D. fellowship linked to the Grant CardioNeT grant. The cost of this publication was supported in part with funds from the European Regional Development Fund. The CNIC was supported by the Instituto de Salud Carlos III (ISCIII), the MCIU and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505).S

El desarrollo de habilidades para la comunicación con enfoque socio-profesional en estudiantes de carreras pedagógicas. (Original)

The present work aims at socializing the results of a research conducted by its authors, in which a curricular framework for the development of communication skills with a socio-professional approach in teachers-to-be was proposed. In order to elaborate the framework, the authors took into account the main skills a teacher should have, so an organization of linguistic, sociolinguistic, strategic and discourse knowledge was proposed, in relation to the pedagogical knowledge teachers have. There were established four levels from a socio-professional dimension, which allowed the development of communication skills for teaching. A concept about this matter was provided; and premises were established to accomplish this goal. The framework proposed has an integrated and systemic character. The proposal has had a positive impact on the training of future teachers, who made up its population and the faculty in charge of this work, resulting evaluated as pertinent and necessary for a better professional performance. It has been generalized to students of majors of another profile from the use of the elective curriculum. It has also been part of the postgraduate improvement of professionals from different areas.El presente trabajo tiene como objetivo socializar los resultados de la investigación realizada por su autora, en la cual se propuso un modelo curricular encaminado al desarrollo de las habilidades para la comunicación con enfoque socio-profesional en estudiantes de carreras pedagógicas. Para su concepción se tuvieron en cuenta las principales habilidades que en este sentido debe poseer un profesor, y se propuso su organización desde los saberes lingüísticos, sociolingüísticos, estratégicos y discursivos en relación con los saberes pedagógicos. Se establecieron cuatro niveles que permiten, desde una dimensión socio-profesional, el desarrollo de habilidades para la comunicación en la profesión pedagógica. Se reconceptualizó este término y se declararon premisas que guían lo anterior. El modelo se caracteriza por su carácter integrador y sistemático.La propuesta ha tenido un impacto positivo para la formación de los futuros profesores, que conformaron su población y en el claustro encargado de esta labor, resultando evaluado como pertinente y necesario para un mejor desempeño profesional. Se ha generalizado a estudiantes de carreras de otro perfil a partir de la utilización del currículo optativo electivo. Ha formado parte de la superación posgraduada de profesionales de diferentes áreas

Sistema de costeo ABC y su incidencia en la rentabilidad de la empresa V&V Cerro Blanco S. A. C., Bambamarca, 2020

El presente trabajo de investigación tiene como objetivo general analizar de qué manera el sistema de costeo ABC incide en la rentabilidad de la empresa V&V Cerro Blanco S.A.C. Bambamarca, 2020. La importancia del estudio radicó en la necesidad que tiene la empresa para la determinación de sus costos, con el fin de conocer su rentabilidad real. El estudio tiene un enfoque cuantitativo, diseño no experimental y tipo descriptivo-no experimental, la población estuvo conformada por todo el personal de la empresa y la muestra es igual a la población; las técnicas utilizadas para recolectar información se utilizó el análisis documental y la encuesta, mediante los instrumentos de ficha de registro y cuestionario de preguntas, este último fue evaluado por un experto en el tema. Asimismo, se determinó que el costo de producción unitario con la aplicación del sistema de costeo ABC, es de 0.29 céntimos, menor que al determinado por el método de costeo tradicional; mostrando un aumento en la rentabilidad financiera de 12.92% y 6.62% en rentabilidad económica. Finalmente, el sistema de costeo ABC incide positivamente en la rentabilidad de la empresa V&V Cerro Blanco S.A.C – Bambamarca, 2020, mediante una adecuada distribución de sus costos, ayudando a la toma de decisiones acertadas

Cooperative Response to Endocardial Notch Reveals Interaction With Hippo Pathway.

BACKGROUND The endocardium is a crucial signaling center for cardiac valve development and maturation. Genetic analysis has identified several human endocardial genes whose inactivation leads to bicuspid aortic valve formation and calcific aortic valve disease, but knowledge is very limited about the role played in valve development and disease by noncoding endocardial regulatory regions and upstream factors. METHODS We manipulated Notch signaling in mouse embryonic endocardial cells by short-term and long-term coculture with OP9 stromal cells expressing Notch ligands and inhibition of Notch activity. We examined the transcriptional profile and chromatin accessibility landscape for each condition, integrated transcriptomic, transcription factor occupancy, chromatin accessibility, and proteomic datasets. We generated in vitro and in vivo models with CRISPR-Cas9-edited deletions of various noncoding regulatory elements and validated their regulatory potential. RESULTS We identified primary and secondary transcriptional responses to Notch ligands in the mouse embryonic endocardium, and a NOTCH-dependent transcriptional signature in valve development and disease. By defining the changes in the chromatin accessibility landscape and integrating with the landscape in developing mouse endocardium and adult human valves, we identify potential noncoding regulatory elements, validated selected candidates, propose interacting cofactors, and define the timeframe of their regulatory activity. Additionally, we found cooperative transcriptional repression with Hippo pathway by inhibiting nuclear Yap (Yes-associated protein) activity in the endocardium during cardiac valve development. CONCLUSIONS Sequential Notch-dependent transcriptional regulation in the embryonic endocardium involves multiple factors. Notch activates certain noncoding elements through these factors and simultaneously suppresses elements that could hinder cardiac valve development and homeostasis. Biorxviv: https://www.biorxiv.org/content/10.1101/2023.03.23.533882v1.full.S

Fuentes renovables de energía para el desarrollo sostenible en la UEB Calisur en Río Cauto (Original)

Renewable energies play a fundamental role in the efficiency and competitiveness of agro-industries. Therefore, its use is necessary in order to achieve more profitable companies and in balance with the environment. The practice of shrimp farming is part of this group of agro-industries, among which the UEB Calisur stands out in the country for its extension and profitability, which has shown relevant economic results and environmental recognition, but has a group of weaknesses in this regard. that limit a higher performance focused on difficulties with the water supply, energy insufficiency and the improvement and training of its personnel. The objective of this article is to socialize the technological proposal proposed by a group of actions focused on the use of renewable energy sources to attend to the main problems detected and resulting from the research carried out. For the latter, theoretical and empirical methods were used in the epistemological foundation, the diagnosis and the elaboration and evaluation of the proposal. Attention to this problem and its inclusion within the entity's strategy will allow a reduction, greater conservation of natural resources and care for the environment, as well as greater efficiency in terms of achieving sustainable local development.Las energías renovables juegan un papel fundamental en la eficiencia y competitividad de las agroindustrias. Se hace necesario, por tanto, su uso, a fin de lograr empresas más rentables y en equilibrio con el medio ambiente. La práctica de la camaronicultura forma parte de este grupo de agroindustrias, dentro de las que se destaca en el país, por su extensión y rentabilidad, la UEB Calisur. Esta ha mostrado relevantes resultados económicos y reconocimientos ambientales, pero posee un grupo de debilidades en este sentido que limitan un mayor rendimiento, enfocadas hacia el abasto de agua, la insuficiencia energética y la superación y capacitación de su personal. El presente artículo tiene como objetivo socializar la propuesta tecnológica que plantea un grupo acciones dirigidas al uso de las fuentes renovables de energía para la atención a los principales problemas detectados resultantes de la investigación realizada. Para esta última se utilizaron métodos teóricos, empíricos y estadísticos en la fundamentación epistemológica, el diagnóstico y la elaboración y valoración de la propuesta. La atención a esta problemática y su inclusión dentro de la estrategia de la entidad permitirá una reducción de los costos, una mayor conservación de los recursos naturales y cuidado del medio ambiente, así como mayor eficiencia en función del logro de un desarrollo local sostenible

Morphogenesis of myocardial trabeculae in the mouse embryo

Formation of trabeculae in the embryonic heart and the remodelling that occurs prior to birth is a conspicuous, but poorly understood, feature of vertebrate cardiogenesis. Mutations disrupting trabecular development in the mouse are frequently embryonic lethal, testifying to the importance of the trabeculae, and aberrant trabecular structure is associated with several human cardiac pathologies. Here, trabecular architecture in the developing mouse embryo has been analysed using high-resolution episcopic microscopy (HREM) and three-dimensional (3D) modelling. This study shows that at all stages from mid-gestation to birth, the ventricular trabeculae comprise a complex meshwork of myocardial strands. Such an arrangement defies conventional methods of measurement, and an approach based upon fractal algorithms has been used to provide an objective measure of trabecular complexity. The extent of trabeculation as it changes along the length of left and right ventricles has been quantified, and the changes that occur from formation of the four-chambered heart until shortly before birth have been mapped. This approach not only measures qualitative features evident from visual inspection of 3D models, but also detects subtle, consistent and regionally localised differences that distinguish each ventricle and its developmental stage. Finally, the combination of HREM imaging and fractal analysis has been applied to analyse changes in embryonic heart structure in a genetic mouse model in which trabeculation is deranged. It is shown that myocardial deletion of the Notch pathway component Mib1 (Mib1(flox/flox); cTnT-cre) results in a complex array of abnormalities affecting trabeculae and other parts of the heart.This work was supported by funding to TJM from the Medical Research Council (U117562103); to JCM by the Higher Education Funding Council for England; to JLdlP and GL by grants SAF2010-17555 and SAF2013-45543-R from the Spanish Ministry of Economy and Competitiveness (MINECO); and to GC by a research fellowship at the University College London Biomedical Research Centre from the UK National Institutes of Health Research Cardiometabolic Programme.S