Nutrigenómica: Análisis experimental, integrativo y desarrollo de una plataforma de minería de datos

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Física Aplicada. Fecha de lectura: 11-12-2019La Nutrigenómica, ciencia que estudia el potencial de los alimentos y sus compuestos bioactivos para alterar la expresión de los genes, podría explicar la capacidad de la dieta para modular nuestra salud. Plataformas especializadas como Gene Expression Omnibus (GEO) reúnen multitud de datos de expresión génica generados por tecnologías ómicas, y contienen resultados de experimentos que analizan los cambios de expresión génica en células humanas tras su tratamiento con distintos alimentos y compuestos bioactivos. El análisis integrativo de estos datos ofrece la posibilidad de profundizar en el conocimiento de las bases moleculares que gobiernan el binomio dieta-salud. Esta tesis trata de contribuir al estudio del potencial nutrigenómico de los alimentos y sus compuestos bioactivos. Inicialmente, se ha demostrado como el consumo de una dieta suplementada en hidroxitirosol, principal fitoquímico fenólico bioactivo del aceite de oliva virgen, es capaz de regular la expresión de cuatro micro ARN’s in vivo en el hígado de ratón, con potenciales implicaciones biológicas. Tras ello, se han recopilado y analizado datos resultantes de experimentos de nutrigenómica, disponibles en GEO, para construir una base de datos de expresión diferencial de genes. El análisis integrativo de esta base de datos ha permitido identificar una firma molecular de 18 genes con potenciales propiedades anticancerígenas. Finalmente, se ha completado la base de datos inicial con nuevos datos y definido las firmas moleculares de los experimentos incluidos, para desarrollar una plataforma de minería de datos en nutrigenómica. La plataforma se presenta en forma de una aplicación web, accesible públicamente (www.nutrigenomedb.org). Mediante el uso de tablas y gráficos interactivos, esta plataforma permite explorar el nivel de expresión diferencial de genes a nivel celular en respuesta al tratamiento con alimentos y sus compuestos bioactivos. Mediante un algoritmo de comparación de patrones de expresión, las firmas moleculares externas pueden compararse con las incluidas en la base de datos de nutrigenómica, lo que permite identificar mecanismos moleculares en común que explicarían los efectos beneficiosos de determinados alimentos. A través de un caso de uso, se demuestra como la aplicación desarrollada permite conectar una firma molecular provocada por el Amlodipino, un fármaco usado para el tratamiento de la hipertensión, con una firma molecular obtenida tras un tratamiento con un extracto de romero. Además el análisis funcional de los genes implicados en esta conexión identifica la represión de genes involucrados en actividades de transporte transmembrana de iones como el principal mecanismo molecular responsable de la conexión identificada.Nutrigenomics, the science in charge of studying the effects of foods and their bioactive compounds on gene expression, offers great possibilities for explaining how diet is able to modulate human health. Multiple omic experiments, available at Gene Expression Omnibus (GEO) database, have generated gene expression data following treatment of human cell lines with different foods and their bioactive compounds. Exploration of such data in an integrative manner offers excellent possibilities for gaining insights into the molecular basis governing the diet-health binomial. This doctoral thesis focuses on the nutrigenomic potential of foods and their bioactive compounds. We started showing that hydroxytyrosol, the main bioactive compound from virgin olive oil, is able to modulate the expression of 4 micro RNA’s in vivo on mouse liver, with potential biological outcomes. Then we have collected and analyzed nutrigenomics experiments publicly available in GEO database, in order to build a gene expression database. Integrative analysis of such database allowed us to identify a molecular signature of 18 genes with potential anticancer properties. Finally, this database has been updated with new data, and molecular signatures defining the gathered experiments have been obtained, in order to build up a nutrigenomics data mining platform. Such a platform is presented as an open web application (www.nutrigenomedb.org). Through its web interface, users are able to explore differential gene expression data at cellular level, in response to different treatments with a variety of foods and their bioactive compounds, by using data tables and interactive visualizations. In addition, external gene signatures can be connected with hosted nutrigenomics molecular signatures using a gene pattern-matching algorithm. We further demonstrate how the application is able to connect a molecular signature triggered by a cellular treatment with Amlodipine, a drug used to treat hypertension, with a molecular signature corresponding to a cellular treatment with a rosemary extract. A functional analysis of the genes connecting both treatments identifies the downregulation of a set of genes related to ion transmembrane transport activities as the main underlying molecular mechanism in common.El autor agradece la financiación de la Agencia Estatal de Investigación y Fondos Europeos FEDER (AGL2016-78922-R) a través del proyecto titulado: “Modulación terapéutica de ARNs no codificantes a través de componentes bioactivos de la dieta: impacto sobre la regulación fisiopatológica del metabolismo lipídico intestinal”. También la de la Fundación Ramón Areces (CIVP18A3888) a través del proyecto titulado: “Modulación de exosomas transportadores de miRNAs y lncRNAs para la comunicación intercelular como herramienta terapéutica frente a la dislipidemia”. El autor agradece también a IMDEA Alimentación el contrato financiado por fondos FEDER Europeos así como fondos de la Comunidad de Madrid

Research data services (RDS) in Spanish academic libraries

Research data services (RDS) are actions undertaken to provide researchers with support, advising, training, information, a technological infrastructure and a regulatory framework with respect to research data management (RDM) throughout the life cycle of the data. The implementation of RDS is an activity that is becoming increasingly important within the functions carried out by academic and research libraries. The aim of this study is to provide a snapshot of the research data services implemented in academic libraries in public universities in Spain, identifying the number and types of services deployed. We conducted a Website Content Analysis of the libraries of the 48 Spanish public universities to discover which RDS they are implementing and promoting. The results show that, despite a lack of institutional policies regarding research data, libraries are deploying these new services, albeit unevenly in terms of both the number of services and the type of support provided. Services related to development of the data management plan (DMP) and preservation of the data in repositories predominate. This inventory is presented as a first step towards learning the level of RDS implementation in Spanish academic libraries, providing a partial perspective and leading the way to exploring other aspects in greater depth in future studies.This work has been supported by the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with UC3M in the line of Excellence of University Professors (EPUC3M02), and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation)

Reversibility of Symmetric Linear Cellular Automata with Radius r = 3

The aim of this work is to completely solve the reversibility problem for symmetric linear cellular automata with radius r = 3 and null boundary conditions. The main result obtained is the explicit computation of the local transition functions of the inverse cellular automata. This allows introduction of possible and interesting applications in digital image encryption.This research was funded by Ministerio de Ciencia, Innovación y Universidades (MCIU, Spain), Agencia Estatal de Investigación (AEI, Spain), and Fondo Europeo de Desarrollo Regional (FEDER, UE) under project TIN2017-84844-C2-2-R (MAGERAN) and project SA054G18 supported by Consejería de Educación (Junta de Castilla y León, Spain)

On the Optimal Control of a Malware Propagation Model

An important way considered to control malware epidemic processes is to take into account security measures that are associated to the systems of ordinary differential equations that governs the dynamics of such systems. We can observe two types of control measures: the analysis of the basic reproductive number and the study of control measure functions. The first one is taken at the beginning of the epidemic process and, therefore, we can consider this to be a prevention measure. The second one is taken during the epidemic process. In this work, we use the theory of optimal control that is associated to systems of ordinary equations in order to find a new function to control malware epidemic through time. Specifically, this approach is evaluate on a particular compartmental malware model that considers carrier devices.This research has been partially supported by Ministerio de Ciencia, Innovación y Universidades (MCIU, Spain), Agencia Estatal de Investigación (AEI, Spain), and Fondo Europeo de Desarrollo Regional (FEDER, UE) under project with reference TIN2017-84844-C2-2-R (MAGERAN) and the project with reference SA054G18 (MASEDECID) supported by Consejería de Educación (Junta de Castilla y León, Spain). J.D. Hernández Guillén is supported by University of Salamanca (Spain) and Banco Santander under a doctoral grant

Estudio retrospectivo sobre artroplastia total de rodilla: cirugía navegada y cirugía robótica

RESUMENEl objetivo de este estudio es comparar los resultados clínicos y radiológicos obtenidos mediante artroplastia total de rodilla navegada y artroplastia total de rodilla robótica , así como comparar el tiempo quirúrgico empleado en ambas técnicas.MATERIAL Y MÉTODOS Realizamos un estudio monocéntrico, observacional longitudinal retrospectivo de cohortes históricas en el que analizamos 48 pacientes, 24 sometidos a cirugía navegada de atroplastia de rodilla y 24 a cirugía robótica en el servicio de Cirugía Ortopédica y Traumatología del Hospital Universitario Miguel Servet. Se realizaron a cargo del mismo cirujano . Se recogieron datos de los resultados clínicos y radiográficos pre y postquirúrgicos , analizándose con el programa SPSS Stadistics 20 .RESULTADOSNo se obtuvieron diferencias estadísticamente significativas en cuanto a la comparación de los parámetros clínicos valorados (escala Knee Society Score, escala WOMAC y cuestionario de salud SF12) entre la artroplastia de rodilla robótica y la navegada. En el análisis de los resultados radiológicos observados (ángulo femorotibial mecánico, valgo fisiológico femoral, ángulo tibial proximal y pendiente tibial) tampoco se observaron diferencias estadísticamente significativas. Finalmente, tampoco existieron diferencias en el tiempo quirúrgico empleado entre ambas técnicas<br /

Del modelo de desarrollo económico al paradigma del desarrollo humano: una apuesta al papel del arte y las humanidades en el pensamiento de Martha Nussbaum

This document encapsulates the thinking emanating from the permanent seminar: "Resignification of the Humanities in Higher Education" held at the Center for Humanities and Social Sciences at the University of Santo Tomas, Bucaramanga, Colombia, held this time in the reading book: Not for profit: Why democracy needs the humanities, from the Martha C. Nussbaum (2010). Allows a critical approach to the situation of the humanities and the arts in democracies, silent and gradually permeated by the models of economic development, while eliciting a careful review of the role of the humanities in the context of higher education and moves the action from the humanities at the university.Este documento condensa las reflexiones derivadas del seminario permanente, “Resignificación de las Humanidades en la Educación Superior”, realizado por los profesores del Departamento de Humanidades de la Universidad Santo Tomás, Bucaramanga, Colombia, a través de la lectura del libro Sin fines de lucro: por qué la democracia necesita de las humanidades, de Martha Nussbaum (2010). Desde una mirada crítica, se revisa el papel de las humanidades y las artes en el aporte a las democracias que están permeadas, silenciosa y progresivamente, por los modelos de desarrollo económico. Plantea así, una revisión cuidadosa del papel de las humanidades en el contexto de la educación superior

The reversibility of cellular automata on trees with loops

[EN] In this work the notion of linear cellular automata on trees with loops is introduced and the reversibility problem in some particular cases is tackled. The explicit expressions of the inverse cellular automata are computed

7 Li ( p , n ) 7 Be cross section from threshold to 1960 keV and precise measurement of the 197 Au ( n , γ ) spectrum-averaged cross section at 30 keV

Background: The 7 Li(p, n) 7 Be reaction is one of the most used nuclear reaction for accelerator-based neutron sources. There are few experimental cross section data in the double-value energy region and they are discrepant, as are the reaction yields. Purpose: We derive the 7 Li(p, n) 7 Be reaction cross section, and measure with small uncertainty the 197Au(n, γ ) 198Au spectrum-averaged cross section at neutron energy around 30 keV. Method: By irradiating Li metal targets over the proton energy range of 1879 to 1960 keV, thick target yields were measured using the generated 7 Be activity. Based on the theoretical description of the reaction yield, accelerator parameters and reaction cross sections are derived. Gold foils were activated with the neutron field generated by the (p, n) reaction on a Li target at a proton energy of about a half keV above the reaction threshold. Results: The thick target yield is well reproduced when the Breit-Wigner single-resonance formula for s-wave particles is used to describe the reaction cross section. The ratio between neutron and proton widths was found to be equal to n/p = 5.4 1 − Tth/Tp. The detailed balance principle is used to obtain the cosmologically important time-reversed 7 Be(n, p) 7 Li reaction cross section. The measured 197Au(n, γ ) 198Au spectrum-averaged cross section agrees with the value calculated from the ENDF/B-VIII.0 library. Conclusions: We demonstrated the feasibility of deriving the 7 Li(p, n) 7 Be reaction cross section from the thick target yield. Using the ratio between neutron and proton widths obtained in this work reduces the uncertainty in calculating the reaction cross section to a factor of 2.3.International Atomic Energy Agency Contract No. 17883. G.M.-

Growth mode transition involving a potential-dependent isotropic to anisotropic surface atom diffusion change. Gold electrodeposition on HOPG followed by STM

The electrodeposition of gold on highly oriented pyrolytic graphite (HOPG) from acid aqueous solutions was studied by using electrochemical techniques complemented with ex-situ scanning tunneling microscopy (STM). The kinetics of gold electrodeposition is consistent with a nucleation and three-dimensional growth process under diffusion control from the solution side. As the applied potential moves in the negative direction, the gold crystal density increases, and the crystal shape changes from a Euclidean to a dendritic fractal morphology. This transition can be assigned to the anisotropic surface diffusion of gold adatoms induced by the applied electric potential. A model including a potential-dependent energy barrier at step edges accounts for the morphology transition for gold electrodeposition on HOPG.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA)Facultad de Ciencias Exacta

Status of the LEgnaro NeutrOn Source facility (LENOS)

Abstract LENOS is a new facility under development at Laboratori Nazionali di Legnaro (LNL). It is based on a new technic for neutron beam shaping in accelerator based neutron sources. The main advantage of this method is to be able to shape the primary charged-particle beam to a defined energy distribution that, impinging on a neutron producing target, generates the desired neutron spectra at the sample position. Together with the proton energy distribution, other degrees of freedom are used to obtain the desired neutron energy spectra, e.g. the angular distribution of produced neutrons, the nuclear reactions used for the neutron spectra production, and the convolution of neutron spectra coming from different target materials. The main advantage of this new approach is the good control over the energy and spatial distribution of the produced neutron spectrum avoiding most of the problems due to neutron moderation, since it is easier to work with charged particles than with neutrons. The goal of the LENOS facility is to obtain a Maxwell-Boltzmann neutron energy spectrum with tunable temperature and a high neutron flux at sample position by using the 7Li(p,n) reaction. To maximize the neutron flux a very narrow primary proton beam has to be used, so the target has to remove a very high specific power. Currently available lithium targets are inadequate to sustain the high specific power that needs to be dissipated in the LENOS facility. A dedicated target based on micro-channel geometry and liquid metal cooling has been developed and tested. This contribution describes the status of the LENOS facility