Uncovering correlated variability in epigenomic datasets using the Karhunen-Loeve transform.

BACKGROUND: Larger variation exists in epigenomes than in genomes, as a single genome shapes the identity of multiple cell types. With the advent of next-generation sequencing, one of the key problems in computational epigenomics is the poor understanding of correlations and quantitative differences between large scale data sets. RESULTS: Here we bring to genomics a scenario of functional principal component analysis, a finite Karhunen-Loève transform, and explicitly decompose the variation in the coverage profiles of 27 chromatin mark ChIP-seq datasets at transcription start sites for H1, one of the most used human embryonic stem cell lines. Using this approach we identify positive correlations between H3K4me3 and H3K36me3, as well as between H3K9ac and H3K36me3, so far undetected by the most commonly used Pearson correlation between read enrichment coverages. We uncover highly negative correlations between H2A.Z, H3K4me3, and several histone acetylation marks, but these occur only between principal components of first and second order. We also demonstrate that levels of gene expression correlate significantly with scores of components of order higher than one, demonstrating that transcriptional regulation by histone marks escapes simple one-to-one relationships. This correlations were higher in significance and magnitude in protein coding genes than in non-coding RNAs. CONCLUSIONS: In summary, we present a methodology to explore and uncover novel patterns of epigenomic variability and covariability in genomic data sets by using a functional eigenvalue decomposition of genomic data. R code is available at: http://github.com/pmb59/KLTepigenome

Aplicación de problemas resueltos de circuitos digitales combinacionales bajo Android

Este proyecto consiste en la realización de una aplicación para dispositivos Android. En ella se desarrollará una guía de problemas y un tutorial sobre circuitos digitales combinacionales. Los problemas han sido elegidos de la Guía de la asignatura Circuitos Electrónicos Digitales de la Escuela Politécnica Superior de la Universidad Autónoma de Madrid (EPS UAM). El principal objetivo de la aplicación es ofrecer a los alumnos una guía de ejercicios de síntesis de circuitos, adaptados para ser resueltos en una pantalla de tamaño normal de un teléfono móvil. Además, permite corregir los ejercicios automáticamente cuando el usuario lo desee, ofrece ayudas para la resolución de los mismos y permite compartir las soluciones con otros usuarios. La aplicación se ha desarrollado en inglés y se encuentra publicada en Google Play.This project consists in the realization of an Android application. It will develop an exercise guide and a tutorial about combinational circuits. The exercises have been chosen of the subject Circuitos Electrónicos Digitales of the Escuela Politécnica Superior, Universidad Autónoma de Madrid. The main objective, is to offer a guide for the students with exercises of circuit synthesis, adapted to be solved in a normal screen of a smartphone. Besides, users can check the solution when they want to, also there are tips for helping in the exercise resolution and is possible to share solutions with others users. Application is posted on Google Play and is written in English

Initiation of stem cell differentiation involves cell cycle-dependent regulation of developmental genes by Cyclin D.

Coordination of differentiation and cell cycle progression represents an essential process for embryonic development and adult tissue homeostasis. These mechanisms ultimately determine the quantities of specific cell types that are generated. Despite their importance, the precise molecular interplays between cell cycle machinery and master regulators of cell fate choice remain to be fully uncovered. Here, we demonstrate that cell cycle regulators Cyclin D1-3 control cell fate decisions in human pluripotent stem cells by recruiting transcriptional corepressors and coactivator complexes onto neuroectoderm, mesoderm, and endoderm genes. This activity results in blocking the core transcriptional network necessary for endoderm specification while promoting neuroectoderm factors. The genomic location of Cyclin Ds is determined by their interactions with the transcription factors SP1 and E2Fs, which result in the assembly of cell cycle-controlled transcriptional complexes. These results reveal how the cell cycle orchestrates transcriptional networks and epigenetic modifiers to instruct cell fate decisions.This work was supported by the European Research Council grant Relieve IMDs and the Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V.). A.B. was funded by the British Heart Foundation Ph.D. Studentship. S.P. was funded by a Federation of European Biochemical Societies long-term fellowship and a InnovaLiv EuFP7 grant. S.P. and L.V. conceived the research and wrote the manuscript. S.P. and A.B. performed the experiments. P.M. performed bioinformatic analyses.This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via http://dx.doi.org/10.1101/gad.271452.11

Effects of bonding on the performance of optical fiber strain sensors

[EN] The structural health monitoring (SHM) of existing buildings, structures, and infrastructures has become increasingly important in recent years, while the interest of the scientific community is focused on the use of new high-performance technologies. Fiber optic sensors have become particularly attractive, thanks to their potential for monitoring strain in smart structures. The performance of this new technology depends to a large extent on the bonding technique used for its manufacture. Although the related literature has identified a correlation between some efficiency issues and the geometrical parameters of the bonding and mechanical properties of the materials adopted, the phenomenon is still not completely understood. This paper describes an in-depth study of the geometrical and mechanical parameters that influence the efficiency of optical fiber point sensors' surface bonding by synergistically related techniques such as computational simulation, experimental tests, sensor manufacturing, and data analysis. The paper's novelty is fourfold: (1) the investigation of the strain transfer mechanism of surface-bonded fiber optic sensors by considering, for the first time, all the parameters influencing the phenomenon through a considerable number of finite element (FE) analyses (117 three-dimensional FE models); (2) the development of a series of bonding efficiency predictive models; (3) the design of a specific laboratory test to validate the computational outcomes; and (4) the definition of useful guidelines for effective bonding manufacturing in order to maximize the performance of these sensors when acquiring monitoring data.Project Manufacturing Education and Training Governance Model; Universitat Politecnica de Valencia, Grant/Award Number: PAID-01-18; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: DIMENSION TEC2017-88029-R; H2020 Marie SklodowskaCurie Actions, Grant/Award Number: 722509Floris, I.; Sangiorgio, V.; Adam, JM.; Uva, G.; Rapido, M.; Calderón García, PA.; Madrigal-Madrigal, J. (2021). Effects of bonding on the performance of optical fiber strain sensors. Structural Control and Health Monitoring. 28(9):1-23. https://doi.org/10.1002/stc.278212328

La inclusión educativa en el ámbito universitario. El diseño curricular universal

1. Introducción La sociedad, como sucedió tiempos atrás con revoluciones agrícolas e industriales, se encuentra inmersa en un proceso de cambio y revolución protagonizado por el conocimiento, siendo éste la clave de la competitividad y el éxito. El dinamismo personal, económico y social se sustenta en el valor añadido que aporta el conocimiento. Por ello, debe ser objetivo primordial la difusión del mismo, trabajando en el acceso a la educación y en el progreso formativo de la población. La universidad ha sido siempre la cuna del conocimiento y en una sociedad bajo esa revolución, el papel de la institución debe, por tanto, ser superior. El acceso a la formación debe configurarse como prioritario en los avances sociales. Por otro lado, si hablamos de sociedad actual, no debemos olvidar la realidad existente de la diversidad. El panorama social viene establecido por un conjunto de individuos con diferentes capacidades, orígenes étnicos, formas de relaciones personales y afectivas, etc. Somos un común de seres con diferentes perfiles y características, lo que obliga a una construcción social bajo el diseño para todos, definido por la Organización de las Naciones Unidas como “el diseño de productos, entornos, programas y servicios que puedan utilizar todas las personas, en la mayor medida posible, sin necesidad de adaptación ni diseño especializado.” (ONU, 2006). Una sociedad de diversidad y conocimiento, que requiere el fomento y el acceso universal a la educación, para lo que es necesario la elaboración de planes de estudio con un diseño curricular inclusivo. La universidad se constituye como un microcosmos de la sociedad de la que forma parte, siendo necesario incorporar la igualdad de oportunidades, la accesibilidad universal y el diseño para todos (Briceño, 1989). La UNESCO define la educación inclusiva como un modelo que responde a la diversidad de necesidades de todos los estudiantes, sin adaptación de los estudiantes al sistema educativo, ni del sistema a los estudiantes individualmente, sino como un sistema global que tenga en cuenta la diversidad de perfiles. La universidad debe ser útil y contribuir al desarrollo de la inclusión educativa. Para ello, es necesario que el profesorado cuente con las herramientas y conocimientos suficientes para diseñar curriculum académicos inclusivos, que no requieran de adaptaciones individuales y concretas, sino que engloben la diversidad de características y necesidades.Universidad a Distancia de Madrid (UDIMA)2022-2

Skills and practices of pharmacy staff for dispensing of drugs with fiscalized substances in drugstores and pharmacies

OBJETIVE To evaluate the skills and practices of pharmacy staff during the dispensing of tramadol (drug with fiscalized substance) in drugstores and pharmacies in Medellin, Colombia. METHODS A cross-sectional study was performed. The simulated patient technique was used. The main outcomes included the information provided on the dispensed drug (tramadol), the use of tools to provide information, and the information provided on drug precautions and use recommendations. RESULTS We visited 305 drugstores and pharmacies. The average dispensing time was 2.3 min (SD 1.1 min). In nine drugstores and pharmacies (3.0%), tramadol was not dispensed because it was not in stock. In 17 drugstores and pharmacies (5.7%), the simulated patients were actively informed by the dispensing pharmacy staff; of these, 16 provided oral information and one provided oral and written information. Eight patients (2.7%) received information regarding tramadol use. However, 99% of patients were not informed about tramadol side effects such as dependence, sedation, or hypnosis, and none of the simulated female patients were informed on the precautions related to tramadol use during pregnancy or lactation. CONCLUSIONS Communication skills and appropriate practices of pharmacy staff are critical to patient self-care. However, this study shows their difficulty in counseling about precautions and use recommendations of drugs with fiscalized substances. These outcomes could inform future studies focusing on the rational use of these drugs in drugstores and pharmacies. It is necessary to improve the pharmacy staff competencies through continuing education programs, to facilitate access to information and training