Project Management in the Fourth Industrial Revolution. Beer production project

El objetivo de este documento es encontrar soluciones a los problemas de gestión de proyectos que surgen como consecuencia de la cuarta revolución industrial, que está cambiando la industria tal y como la conocemos y nos sitúa en un punto crítico de adaptación a una nueva realidad que traerá consigo grandes oportunidades y también grandes riesgos. Además, la gestión de los nuevos proyectos 4.0 supondrá un reto de comunicación entre expertos en tecnologías y lenguajes informáticos muy diferentes, por lo que este documento destaca los elementos a tener en cuenta en la revolución tecnológica y estudia cómo gestionar un proyecto en una Smart factory.The aim of this document is to find solutions to the project management problems that arise as a result of the fourth industrial revolution, which is changing industry as we know it and places us at a critical point of adaptation to a new reality that will bring great opportunities as well as great risks. In addition, the management of new 4.0 projects will pose a challenge for communication between experts in very different technologies and computer languages, which is why this document highlights the elements to be taken into account in the technological revolution and studies how to manage a project in a Smart factory.Hochschule Albstadt-SigmaringenGrado en Ingeniería en Organización Industria

Characterising epithelial tissues using persistent entropy

In this paper, we apply persistent entropy, a novel topological statis- tic, for characterization of images of epithelial tissues. We have found out that persistent entropy is able to summarize topological and geomet- ric information encoded by -complexes and persistent homology. After using some statistical tests, we can guarantee the existence of signi cant di erences in the studied tissues.Ministerio de Economía y Competitividad MTM2015-67072-

An integrative approach to the evolution of melaninbased traits in birds

Organisms can respond to changes in environmental conditions by modulating gene expression through the action of epigenetic modifications to maintain cellular homeostasis. This adaptive response can lead to phenotypic plasticity and thus avoid the oxidative stress that environmental changes may induce. In that sense, the evolution of phenotypic traits may be mediated by environmental oxidative stress. Pigmentation phenotypes, in particular, are regulated by genes whose expression may be modulated by environmental conditions, helping organisms to deal with stressful environments. Therefore, understanding environmental influences on gene expression that may be adaptive is key to obtain a comprehensive view of pigmentation phenotype evolution. Melanin is the most common pigment in animals. The synthesis of melanin is a physiological process intimately related to oxidative stress. Particularly, the synthesis of the yellow-reddish form of the melanin is dependent on the concentration of the main antioxidant in the cell, glutathione. Therefore, the consumption of a valuable antioxidant makes pheomelanin synthesis a constraining process when antioxidants are required for other vital processes. However, in the absence of environmental oxidative stress, pheomelanin synthesis may contribute to cysteine homeostasis, which is toxic if in excess. In that sense, it seems that pheomelanin synthesis is a physiological mechanism intimately related to oxidative stress that may help organisms to adapt to stressful environments. If the genes that regulate pheomelanin synthesis are susceptible to epigenetic modifications, their expression, and that of the associated pigmentation phenotype, may be modified according to environmental conditions and thus drive adaptive responses. Here I used a multidisciplinary and integrative approach to get a better understanding of the evolution of melanin-based traits. In particular, the aim of this thesis is to determine if the synthesis of melanin is susceptible to epigenetic modifications that provide birds phenotypic plasticity to adjust pigmentation phenotypes to the prevailing environmental conditions (Section 1) and thus obtain a comprehensive view of plumage diversity evolution (Section 2). To determine if birds adjust the pigmentation phenotype to the prevailing environmental conditions, experiments in captivity and natural populations under varying environmental conditions were conducted (Section 1). Environmental conditions that induce oxidative stress modulated the expression of genes involved in pheomelanin synthesis (Chapter III) through the action of epigenetic modifications (Chapters I and II), and this avoided the expected oxidative damage. Phenotypes resulting from a genetic predisposition to produce large amounts of pheomelanin creates weak physiological conditions but also more lability in pigment production, making pheomelanin-based coloration phenotypically plastic (Chapter IV). Thus, it seems that although pheomelanin synthesis induces chronic oxidative damage in birds with plumage profusely covered by this pigment, its plastic regulation under stress can even decrease damage levels. Dealing with stressful environments can then have consequences for both physiology and the pigmentation phenotype. To avoid changes in the pigmentation phenotype, however, the expression of the main gene involved in pheomelanin synthesis can be reversed after stress disappearance (Chapter V). This makes the regulation of pheomelanin synthesis an adaptive strategy to avoid the evolutionary consequences of external phenotypic changes, as mating preferences can be based on the intensity of pheomelanin-based plumage coloration (Chapter VI). Therefore, pheomelanin synthesis seems to represent an adaptive physiological mechanism that allows animals (birds) to deal with environmental stress and maintain cellular homeostasis, which may or may not result in a modification of the pigmentation phenotype. A comprehensive view of the evolution of melanin-based plumage was obtained by developing phylogenetic analyses (Section 2). At an interspecific level, a negative association between color heterogeneity and the level of expression of different melanin forms seems to provide a physiological solution to obtain diverse plumage coloration (Chapter VII). This is because producing several forms of melanin, which is required to generate several colors, is more physiologically constraining than producing a single or few melanin forms. However, differences in plumage coloration do not only occur between species of birds, but also through different life stages within the same species. In particular, during juvenile stages, organisms suffer less relative physiological stress than adults and are more prone to experience systemic excess cysteine, as they may have lower requirements for antioxidant protection. Thus, juvenile pheomelanin-based plumage coloration has evolved more frequently in birds with strictly carnivorous diets, which may make them more susceptible to experience excess cysteine, likely as a detoxifying strategy (Chapter VIII). Pheomelanin pigmentation is not only favored under certain physiological conditions, but also under exposure to certain environmental factors. The exposure to high levels of elemental sulfur in the soil favors the production of pheomelanin in the plumage of different species of birds, likely by an influence of increased intracellular thiols during plumage development, at least in areas with high volcanic activity such as Iceland (Chapter IX). Together, these three final chapters provide novel views of melanin-based pigmentation in a phylogenetic context, thus helping to understand how bird phenotypic diversity has evolved. In sum, this thesis provides an integrative approach to the evolution of melanin-based traits. In particular, pheomelanin synthesis seems to have evolved as a physiological mechanism that provides phenotypic plasticity to birds and allows them to adjust the pigmentation phenotype to environmental conditions, which can be mediated by epigenetic modifications. This thesis thus contributes to a better understanding of bird phenotypic diversity by adopting a multidisciplinary approach that integrates phylogenetic analyses and experimental procedures conducted in natural and experimental populations.Los organismos pueden responder a cambios ambientales modulando la expresión de algunos genes mediante la acción de modificaciones epigenéticas para mantener así la homeostasis celular. Esta respuesta adaptativa puede alterar la morfología, fisiología y/o comportamiento (plasticidad fenotípica) y en consecuencia evitar el estrés oxidativo que los cambios en el ambiente pueden desencadenar. Es por ello que se ha propuesto que la evolución de los rasgos fenotípicos podría estar regulada por el estrés oxidativo ambiental. Los fenotipos de pigmentación, en particular, están regulados por genes cuya expresión puede estar modulada por las condiciones ambientales, lo que ayuda a los organismos a lidiar con ambientes estresantes. Por lo tanto, comprender las influencias ambientes en la expresión génica que pueden ser adaptativas es clave para obtener una visión integral de la evolución del fenotipo de pigmentación. La melanina es el pigmento más común presente en los animales. Su síntesis representa un proceso fisiológico íntimamente relacionado con el estrés oxidativo. En particular, la síntesis de la forma rojiza de la melanina está íntimamente relacionada con la concentración plasmática del principal antioxidante celular, el glutatión. Por lo tanto, el consumo de un antioxidante valioso durante la síntesis de la feomelanina convierte a este proceso fisiológico en un limitante cuando los antioxidantes circundantes son requeridos para otros procesos vitales. Sin embargo, en ausencia de estrés oxidativo ambiental, la síntesis de feomelanina podría contribuir a mantener la homeostasis de cisteína, la cual es tóxica si está en exceso. En este sentido, la síntesis de feomelanina parece ser un mecanismo fisiológico íntimamente relacionado con el estrés oxidativo que puede estar implicado en la adaptación a ambientes estresantes. Si los genes que regulan la síntesis de feomelanina son susceptibles a modificaciones epigenéticas, su expresión y el fenotipo de pigmentación asociado podrían ser modificados de acuerdo con las condiciones ambientales y así desencadenar respuestas adaptativas. Es por ello que utilicé un enfoque integrativo y multidisciplinario para obtener una visión global de la evolución de los rasgos melánicos. En particular, el objetivo de esta tesis es determinar si la síntesis de melanina es susceptible a modificaciones epigenéticas que proporcionen a las aves plasticidad fenotípica para ajustar el fenotipo de pigmentación a las condiciones ambientales predominantes (Sección 1) y así obtener una visión integral de la evolución de la diversidad del plumaje (Sección 2). Para determinar si las aves ajustan la coloración del plumaje de acuerdo con las condiciones ambientales se realizaron procedimientos experimentales tanto en cautividad como en poblaciones naturales bajo diferentes condiciones ambientales (Sección 1). En condiciones ambientales que promueven el estrés oxidativo, la expresión de los genes implicados en la síntesis de feomelanina fue modulada (Capítulo III) mediante modificaciones epigenéticas (Capítulos I y II), lo cual evita el daño oxidativo esperado. Los fenotipos que resultan de una predisposición genética a producir grandes cantidades de feomelanina crean condiciones fisiológicas débiles, pero también más labilidad en la producción de diferentes pigmentos, lo que hace que la coloración a base de feomelanina sea fenotípicamente plástica (Capítulo IV). Por lo tanto, a pesar de que la síntesis de feomelanina induce daño oxidativo crónico en las aves con un plumaje profusamente cubierto por este pigmento, su regulación bajo condiciones que inducen estrés puede incluso disminuir los niveles de daño. Enfrentarse a entornos estresantes puede tener consecuencias tanto en la fisiología como en el fenotipo de pigmentación. Para evitar cambios en el fenotipo de pigmentación, sin embargo, la expresión del gen principal involucrado en la síntesis de feomelanina puede revertirse después de la desaparición del estrés (Capítulo V).Esto hace que la regulación de la síntesis de feomelanina sea una estrategia adaptativa para evitar las consecuencias evolutivas que conllevarían los cambios en el fenotipo externo, ya que las preferencias de apareamiento en algunas especies de aves parecen basarse en la intensidad de la coloración del plumaje a base de feomelanina (Capítulo VI). Por lo tanto, la síntesis de feomelanina representaría un mecanismo fisiológico adaptativo que le permite a los animales (aves) lidiar con el estrés ambiental y mantener la homeostasis celular, lo cual puede resultar o no en una modificación del fenotipo de pigmentación. En la Sección 2, se obtuvo una visión completa de la evolución del plumaje a base de melanina mediante el desarrollo de análisis filogenéticos. A nivel interespecífico, una asociación negativa entre la heterogeneidad del color y el nivel de expresión de las diferentes formas de melanina parece proporcionar una solución fisiológica para obtener diversa coloración del plumaje (Capítulo VII). Esto se debe a que producir varias formas de la melanina, lo cual es necesario para sintetizar varios colores, es más limitante que producir una sola o pocas formas de melanina para pigmentar el plumaje. Sin embargo, las diferencias en la coloración del plumaje no solo ocurren entre especies, sino que también suelen darse a lo largo de diferentes estadios en la vida de una misma especie. En particular, durante la etapa juvenil los organismos son menos propensos a sufrir estrés fisiológico que los adultos y por tanto más vulnerables a sufrir un exceso de cisteína a nivel sistémico ya que tienen menos requisitos de protección antioxidante. Por lo tanto, la coloración del plumaje juvenil a base de feomelanina ha evolucionado más frecuentemente en aves con dietas estrictamente carnívoras, lo que las hace más susceptibles a experimentar un exceso de cisteína, probablemente como una estrategia desintoxicante (Capítulo VIII). La pigmentación feomelánica no solo se ve favorecida frente a ciertas condiciones fisiológicas, sino también ante la exposición de ciertos factores ambientales. La exposición a altos niveles de azufre en el suelo favorece la producción de feomelanina en el plumaje de diferentes especies de aves, probablemente por una influencia de los altos niveles intracelulares de compuestos tiol durante el desarrollo del plumaje, al menos en áreas con una alta actividad volcánica como Islandia (Capítulo IX). Estos tres capítulos aportan una visión novedosa sobre la pigmentación a base de melanina en un contexto filogenético, lo que ayuda a comprender cómo ha evolucionado la diversidad fenotípica de las aves. En resumen, esta tesis proporciona una visión integral de la evolución de los rasgos melánicos. En particular, la síntesis de feomelanina parece haber evolucionado como un mecanismo fisiológico que brinda plasticidad fenotípica a las aves y les permite ajustar su fenotipo de pigmentación a las condiciones ambientales, lo cual puede estar modulado por modificaciones epigenéticas. Por lo tanto, esta tesis contribuye a una mejor compresión de la diversidad fenotípica en aves mediante un enfoque multidisciplinario que integra tanto análisis filogenéticos como procedimientos experimentales realizados en poblaciones experimentales y naturales

Persistent entropy: a scale-invariant topological statistic for analyzing cell arrangements

In this work, we develop a method for detecting differences in the topological distribution of cells forming epithelial tissues. In particular, we extract topological information from their images using persistent homology and a summary statistic called persistent entropy. This method is scale invariant, robust to noise and sensitive to global topological features of the tissue. We have found significant differences between chick neuroepithelium and epithelium of Drosophila wing discs in both, larva and prepupal stages. Besides, we have tested our method, with good results, with images of mathematical tesselations that model biological tissues

Experimental study of MIMO-OFDM transmissions at 94 GHz in indoor environments

Millimeter wave (mm-wave) frequencies have been proposed to achieve high capacity in 5G communications. Although meaningful research on the channel characteristics has been performed in the 28, 38and 60 GHz bands ─in both indoor and short-range scenarios─,only a small number of trials (experiments) have been carried out in other mm-wave bands. The objective of this work is to study the viability and evaluate the performance of the 94 GHz frequency band for MIMO-OFDM transmission in an indoor environment. Starting from a measurement campaign, the performance of MIMO algorithms is studied in terms of throughput for four different antenna configurations.This work was supported in part by the Ministerio de Economía y Competitividad MINECO, Spain under Grant TEC2016-78028-C3-2-P, and in part by the European FEDER funds

D-mannose transport and metabolism in isolated enterocytes

D-mannose transport and metabolism has been studied in enterocytes isolated from chicken small intestine. In the presence of Na+, the mannose taken up by the cells either remains free, is phosphorylated, is catabolized to H2O, or becomes part of membrane components. The mannose remaining free in the cytosol is released when the cells are transferred to an ice bath. The Na+-dependent D-mannose transport is electrogenic and inhibited by ouabain and dinitrophenol; its substrate specificity differs from SGLT-1 transporter. The Glut2 transporter inhibitors phloretin and cytochalasin B added following 30-min mannose uptake reduced the previously accumulated D-mannose, whereas these two agents increased the cell to external medium 3-O-methyl-glucose (3-OMG) concentration ratio. D-mannose efflux rate from preloaded D-[2-3H]-mannose enterocytes is Na+-independent. Phloretin did not affect D-mannose efflux rate, whereas it inhibited that of 3-OMG. Neither mannose uptake nor efflux rate were affected by fructose. It is concluded that part of the mannose taken up by the enterocytes is rapidly metabolized and that enterocytes have two D-mannose transport systems: one is concentrative and Na+-dependent and the other is Na+-independent and passive.Dirección General de Investiagación Científica y Técnica PM99-012

Messenger RNA Fluctuations and Regulatory RNAs Shape the Dynamics of Negative Feedback Loop

Single cell experiments of simple regulatory networks can markedly differ from cell population experiments. Such differences arise from stochastic events in individual cells that are averaged out in cell populations. For instance, while individual cells may show sustained oscillations in the concentrations of some proteins, such oscillations may appear damped in the population average. In this paper we investigate the role of RNA stochastic fluctuations as a leading force to produce a sustained excitatory behavior at the single cell level. Opposed to some previous models, we build a fully stochastic model of a negative feedback loop that explicitly takes into account the RNA stochastic dynamics. We find that messenger RNA random fluctuations can be amplified during translation and produce sustained pulses of protein expression. Motivated by the recent appreciation of the importance of non--coding regulatory RNAs in post--transcription regulation, we also consider the possibility that a regulatory RNA transcript could bind to the messenger RNA and repress translation. Our findings show that the regulatory transcript helps reduce gene expression variability both at the single cell level and at the cell population level.Comment: 87.18.Vf --> Systems biology 87.10.Mn --> Stochastic models in biological systems 87.18.Tt --> Noise in biological systems http://www.ncbi.nlm.nih.gov/pubmed/20365787 http://www.weizmann.ac.il/complex/tlusty/papers/PhysRevE2010.pd

Incorporating boundary conditions in a stochastic volatility model for the numerical approximation of bond prices

Producción CientíficaIn this paper, we consider a two-factor interest rate model with stochastic volatil-ity, and we assume that the instantaneous interest rate follows a jump-diffusionprocess. In this kind of problems, a two-dimensional partial integro-differentialequation is derived for the values of zero-coupon bonds. To apply standardnumerical methods to this equation, it is customary to consider a boundeddomain and incorporate suitable boundary conditions. However, for thesetwo-dimensional interest rate models, there are not well-known boundary con-ditions, in general. Here, in order to approximate bond prices, we propose newboundary conditions, which maintain the discount function property of thezero-coupon bond price. Then, we illustrate the numerical approximation ofthe corresponding boundary value problem by means of an alternative directionimplicit method, which has been already applied for pricing options. We testthese boundary conditions with several interest rate pricing models.MEC-FEDER Grant MTM2017-85476-C2-P, Junta de Castilla y León Regional Grants VA041P17 (with European FEDERFunds), VA138G18 y VA148G1

Health Related Quality of Life in Coronary Patients.

The increase observed in the survival of patients with ischemic cardiopathy, together with the effect of the disease on the social, professional, and family life of those suffering from it, have led researchers to consider that the traditional ways of measuring morbidity and mortality are not adequate for assessing the potential benefits of health care interventions. For this reason, there is common agreement on the need to use an indicator of subjective assessment of health, and of health related quality of life (HRQL), as a complementary criterion for monitoring the results of medical interventions in these patients. The term "quality of life" (QoL) or health related quality of life (HRQL) came into use during the 1970s as a multidimensional concept reflecting the overall subjective condition of the physical and mental welfare of the individual, which is a consequence not only of the disease but also of the family and social conditions forming the patient’s environment. The assessment of these patients’ HRQL has been tackled by several authors using both disease-specific and generic instruments such as the Nottingham Health Profile, the Sickness Impact Profile, the SF-36 or the SF-12 health questionnaire. Both types of instrument have advantages and disadvantages, and they may provide additional information since they quantify the patient’s overall health. Using different multidimensional measures, poorer HRQL has been observed in patients with Acute Myocardial Infarction (AMI) and angina pectoris than in other populations, and these differences have been related to low social class, female sex, the presence of mental disorders and the severity of the clinical condition. Measuring changes in the HRQL of coronary patients is also important as a way of assessing interventions and predicting needs for social care, because it has been shown that the focus of attention in the immediate period following a cardiac attack is generally the physical functioning, but following discharge from hospital and in the longer term, general health, vitality, social and emotional functions could be at least as important. In this chapter, we aim to provide an overview of the concept of HRQL and the usefulness of this measure from the perspective of a coronary patient. Likewise, we intend to review the main instruments used to assess HRQL and we analyse the factors that have been seen to affect the quality of life of these patients