Modulation of hepatic lipoprotein metabolism by dietary procyanidins

INTRODUCTIONDuring the past decade, Nutrition research has been subjected to a shift of focus, from epidemiology and physiology to the comprensión of the molecular basis of nutrients actions.Thus, the new "-omics" disciplines transcriptomics, proteomics or metabolomics, provide the tools to understand the molecular mechanisms involved in the modulation of gene expression by nutrients. The study of the beneficial properties of wine procyanidins has not avoided this shift of focus. Thus, from the initial studies which defined the "French paradox", to nowadays, a wide array of studies have been focused in defining the properties of the non-alcoholic components of red wine, mainly flavonoids, a family of polyphenolic compounds. The objectives of this thesis have been to define the molecular mechanisms by which grape procyanidins modulate the hepatic metabolism of lipoproteins, reducing the risk of cardiovascular disease and other pathologies which basis is found in the dysregulation of the lipoprotein metabolism.SUMMARYIn the present thesis, the effect of procyanidins in the hepatic lipoprotein metabolism has been studied. With this objective, HepG2, HeLa and CV-1 cells have been used as invitro models. In vivo studies have been performed in Wistar rats and C57BL6 mice, wild-type and transgenic mice lacking SHP (NR0B2) and FXR (NR5H1).RESULTS1. Procyanidins improve plasma lipid profile in the postprandial phase in rats. A single oral dose of procyanidins decreases plasma triglycerides and ApoB levels to 50% of control values. In addition LDL-Cholesterol is significantly reduced, thus improving the atherosclerotic risk index.2. Procyanidins display a triglyceride-lowering effect both in vivo and in vitro. In rat and mouse, procyanidin treatment triggers a hypotriglyceridemic response. In HepG2 cultures, procyanidins down-regulate the secretion of triglycerides and ApoB, thus showing that these flavonoids act directly on hepatic cells. This fact strongly suggests that, in vivo, a direct action of procyanidins on the liver contributes to their hypotriglyceridemic response.3. Nuclear receptor Small Heterodimer Partner (SHP) is a target of procyanidins in hepatic cells. Procyanidins modulate the expression of SHP, rapidly increasing its expression in rat liver as well as in HepG2 cultured cells.4. SHP mediates the triglyceride-lowering activity of procyanidins in vitro and in vivo. When SHP expression is silenced in HepG2 or abolished in SHP-null mice, procyanidins lose their hypotriglyceridemic activity. In contrast, in SHP-silenced HepG2 cells, procyanidins are still able to reduce apoB secretion. Hence, procyanidins reduce triglyceride via a SHP-dependent mechanism, whereas they reduce apoB in a SHPindependent manner.5. Nuclear receptor Farnesoid X Receptor (FXR) is an essential mediator of the hypotriglyceridemic action of procyanidins upstream SHP. Oral gavage of procyanidins to FXR-null mice have not a hypotriglyceridemic effect. Moreover, luciferase based in vitro assays showed that procyanidins increase the transcriptional activity of FXR. Thus, FXR is an essential component of the signalling pathway used by procyanidins to elicit the triglyceride lowering effect.6. Key genes of the inflammation process are targets of procyanidins in liver, in the postprandial phase. Oral administration of procyanidins to rats rapidly downregulates the expression, in liver, of transcription factor Egr1, a mediator of the hepatic inflammatory response, and several acute-phase proteins, namely haptoglobin, fibrinogen B and alpha-1 antitrypsin. In addition, expression of DUSP6, a component of the ERK1/2 subfamily of MAPK, is repressed by this treatment. Nfkbia, a repressor of NF-kB activity, is overexpressed upon procyanidin treatment. This expression pattern strongly suggests that procyanidins attenuate the pro-inflammatory state associated to the postprandial phase.INTRODUCCIÓNDurante la pasada década, la investigación en nutrición se ha visto sujeta a un cambio en sus objetivos, pasando de los estudios basados en la fisiología y la epidemiología a la comprensión de las bases moleculares implicadas en las acciones biológicas de los nutrientes. Así, las nuevas disciplinas, como la biología molecular o las "-omics", transcriptómica, proteómica o metabolómica, proporcionan las herramientas para el estudio de los mecanismos moleculares implicados en la modulación génica por nutrientes.El estudio de las propiedades beneficiosas del vino no ha evitado este cambio de foco. Así, desde los primeros estudios que definieron la "paradoja francesa", hasta la actualidad, una ámplia gama de estudios se han dedicado a definir las propiedades de los componentes no alcohólicos del vino, mayoritariamente, los Flavonoides, una familia de compuetos polifenólicos. El objetivo de esta tesis ha sido definir los mecanismos moleculares mediante los cuales las procianidinas de uva modulan el metabolismo de lipoproteínas en el hígado, disminuyendo así el riesgo cardiovascular y diferentes patologías cuya base se encuentra en la desregulación del metabolismo lipoproteico.MEMORIADurante esta tesis se ha estudiado el efecto de las procianidinas sobre el metabolismo lipoproteico en el hígado. Con este objetivo se han usado líneas celulares como modelo in vitro, tanto hepatocitos (HepG2) como líneas accesorias (HeLa y CV-1). Como modelos para el estudio de las procianidinas in vivo se han usado ratas de la cepa Wistar y ratones de la cepa C57BL6, tanto wild-type como dos líneas de transgénicos, Knockout para SHP (NR0B2) y FXR (NR5H1).RESULTADOSSe han obtenido los siguientes resultados:Las procianidinas de uva disminuyen los niveles de lipoproteínas ricas en triglicéridos, así como mejoran los índices de riesgo cardiovascular en ratas.Estos efectos se deben a la modulación de la expresión génica en el hígado, tejido adiposo y músculo entre otras acciones.El mecanismo por el cual las procianidinas disminuyen las lipoproteínas ricas en triglicéridos ha sido estudiado in Vitro (HepG2) e in vivo (C57BL6 wild-type y knockout para SHP). Se han definido dos mecanismos principales. El primero implica la señalización de las procianidinas por una vía dependiente de SHP (Small heterodimer partner, NR0B2), un receptor nuclear. El segundo mecanismo es independiente de SHP e inhibe la expresión de MTP (enzima controlador de la síntesis de lipoproteínas) y consecuente secreción de un menor número de lipoproteínas de muy baja densidad (VLDL).Por encima de SHP, se ha definido FXR (Farnesoid X receptor) como sensor de las procianidinas mediante el uso de ratones C57BL6 KO para FXR y sistemas reporter basados en luciferasa. Estableciendo que el mecanismo de señalización de las procianidinas pasa por FXR, que a su vez induce la expresión de SHP y este inhibe la expresión de SREBP1, factor de transcripción clave para la síntesis de lípidos, disminuyendo así la cantidad de lípidos hepáticos y, consecuentemente, la secreción de lipoproteínas.DISCUSIÓNLa modulación del metabolismo de lipoproteínas es el principal objetivo para el tratamiento de las diferentes patologías relacionadas con dislipemias. Así, la definición de las procianidinas de uva como agentes hipolipidémicos, las convierte en un componente de la dieta de alta importancia para prevenir y mejorar una ámplia gama de patologías, desde la aterogénesis hasta otros estados metabólicos alterados, causantes de la resistencia a la insulina o el síndrome metabólico.Por otro lado, el establecimiento de los mecanismos moleculares implicados en los efectos de las procianidinas de uva, aumenta el conocimiento sobre estos compuestos, así como su aplicabilidad en diferentes estados metabólicos alterados. De esta manera, se ha propuesto que la activación de FXR podría usarse como una estrategia en el tratamiento de la hiperlipidemia o la resistencia a la insulina. Así, las procianidinas emergen como un importante agente terapéutico, cuya importancia radica en la amplia presencia de estos compuestos en la dieta

A Model for developing an academic activity index for higher education instructors based on composite indicators

The assessment of the teacher performance is a subject of criticism due to the lack of a well-establish methodology. This study develops an overall score to measure the dimensions that encompass the academic activities. To that end, a Benefit-of-the-doubt model is proposed. The advantage of this technique is the flexibility in the weights, so that the model selects for each teacher the most favourable set of weights. Furthermore, the paper proposes the barycentric coordinate system as a method to classify the teachers in clusters depending on their contribution to the dimensions. A specific pie chart has been proposed as an efficient way to report the contribution of the teachers to the dimensions and the overall teacher performance

Improving Vegetables' Quality in Small-Scale Farms Through Stakeholders' Collaboration

[EN] Small farms are responsible for 80% of theworld¿s agricultural production although they have difficulties to meet the market quality requirements. Corporate social responsibility (CSR) programs where modern retailers invest in empowering small farmers have been implemented obtaining an increase of the supply chain (SC) profits in cases where supply and demand are balanced. In this paper, a MILP model based onWahyudin et al. (In: Proceedings of the international multiconference of engineers and computer scientists, Hong Kong, pp. 877¿882, [1]) to select the investments to carry out by modern retailers, and the product flow through the SC in situations of supply and demand imbalance is proposed. Its objective is to find out if collaboration programs have a positive impact on SC profits when supply and demand are not balanced. This model allows for the rejection of demand and product wastes. Results show that collaboration programs positively impact on the SC profits and consumer satisfaction level when there is an imbalance between demand and supply.The first author acknowledges the partial support of the Programme of Formation of University Professors of the Spanish Ministry of Education, Culture, and Sport (FPU15/03595), and the partial support of Project Development of an integrated maturity model for agility, resilience and gender perspective in supply chains (MoMARGE). Application to the agricultural sector. Ref. GV/2017/025, funded by the Generalitat Valenciana. The other authors acknowledge the partial support of Project 691249, RUC-APS: Enhancing and implementing Knowledge based ICT solutions within high Risk and Uncertain Conditions for Agriculture Production Systems, funded by the EU under its funding scheme H2020-MCSA-RISE-2015.Esteso, A.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2020). Improving Vegetables' Quality in Small-Scale Farms Through Stakeholders' Collaboration. Lecture Notes in Management and Industrial Engineering. 95-103. https://doi.org/10.1007/978-3-030-44530-0_12S95103Wahyudin RS, Hisjam M, Yuniaristanto, Kurniawan B (2015) An agri-food supply chain model for cultivating the capabilities of farmers in accessing capital using corporate social responsibility program. In: Proceedings of the international multiconference of engineers and computer scientists, Hong Kong, pp 877–882Lowder SK, Skoet J, Raney T (2016) The number, size, and distribution of farms, smallholder farms, and family farms worldwide. World Dev 87:16–29Sutopo W, Hisjam M, Yuniaristanto (2011) An agri-food supply chain model for cultivating the capabilities of farmers accessing market using social responsibility program. Int Sch Sci Res Innov 5(11):1588–1592Sutopo W, Hisjam M, Yuniaristanto (2012) An agri-food supply chain model to enhance the business skills of small-scale farmers using corporate social responsibility. Makara J Technol 16(1):43–50Sutopo W et al (2013a) A goal programming approach for assessing the financial risk of corporate social responsibility programs in agri-food supply chain network. Proc World Congr Eng 2013:732–736Sutopo W, Hisjam M, Yuniaristanto (2013b) An agri-food supply chain model to empower farmers for supplying deteriorated product to modern retailer. In: IAENG transactions on engineering technologies: special issue of the international multiconference of engineers and computer scientists 2012. Springer Netherlands, Dordrecht, 189–202Grillo H, Alemany MME, Ortiz A, Fuertes-Miquel VS (2017) Mathematical modelling of the order-promising process for fruit supply chains considering the perishability and subtypes of products. Appl Math Model 49:255–278Sutopo W, Hisjam M, Yuniaristanto (2013c) Developing an agri-food supply chain application for determining the priority of CSR program to empower farmers as a qualified supplier of modern retailer. In: 2013 World Congress on Engineering and Computer Science, pp 1180–1184Esteso A, Alemany MME, Ortiz A (2017) Conceptual framework for managing uncertainty in a collaborative agri-food supply chain context. Working conference on virtual enterprises. Springer, Cham, pp 715–72

Métodos y Modelos Deterministas e Inciertos para la Gestión de Cadenas de Suministro Agroalimentarias

[EN] The market for agricultural products has grown substantially. At the same time, social concern in food issues such as food safety, food quality, traceability and sustainability is constantly increasing. These reasons have pointed out the need of new models and tools to manage the agri-food supply chains while considering the characteristics that differentiate them from other industrial supply chains as well as the uncertainties present in the sector. Thus, the aim of this paper is to present the current status of a project which mains objectives are to describe the complexity faced by agri-food supply chain decision makers, and to develop new tools based on mathematical programming models to help the decision making process in agri-food supply chain planning. These models novelty will include the consideration of the inherent characteristics of agri-food supply chains and the sources of uncertainty present in the sector. The proposed models and tools will be applied to a real agri-food supply chain in order to prove their validity and applicability and to compare the results obtained by deterministic and uncertain tools.[ES] El mercado de productos agrícolas está en continuo crecimiento, al igual que la preocupación social en temas alimentarios como la calidad y seguridad alimentaria. Esto genera la necesidad de desarrollar modelos y herramientas para gestionar las cadenas de suministro agroalimentarias de manera ajustada y teniendo en cuenta sus características y fuentes de incertidumbre inherentes. Este articulo presenta el estado actual de un proyecto cuyos principales objetivos son: describir la complejidad enfrentada por los decisores de las cadenas de suministro agroalimentarias, y desarrollar nuevas herramientas basadas en programación matemática para apoyar la toma de decisiones en este sector.This research has been supported by the Program of Formation of University Professors (FPU) of the Spanish Ministry of Education, Culture and Sport (FPU15/03595)Esteso, A.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2017). Deterministic and Uncertain Methods and Models for Managing Agri-Food Supply Chain. Dirección y organización (Online). (62):41-46. http://hdl.handle.net/10251/108673S41466

Helical spin thermoelectrics controlled by a side-coupled magnetic quantum dot in the quantum spin Hall state

We study the thermoelectric response of a device containing a pair of helical edge states contacted at thesame temperature T and chemical potential μ and connected to an external reservoir, with different chemicalpotential and temperature, through a side quantum dot. Different operational modes can be induced by applyinga magnetic field B and a gate voltage Vg at the quantum dot. At finite B, the quantum dot acts simultaneously asa charge and a spin filter. Charge and spin currents are induced, not only through the quantum dot, but also alongthe edge states. We focus on linear response and analyze the regimes, which we identify as charge heat enginesor refrigerator, spin heat engine, and spin refrigerator.Fil: Roura Bas, Pablo Gines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Arrachea, Liliana del Carmen. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Kavli Institute for Theoretical Physics; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fradkin, Eduardo. University of Illinois at Urbana; Estados Unido

Enhanced thermoelectric response in the fractional quantum Hall effect

We study the linear thermoelectric response of a quantum dot embedded in a constriction of a quantum Hall bar with fractional filling factors ν=1/m within Laughlin series. We calculate the figure of merit ZT for the maximum efficiency at a fixed temperature difference. We find a significant enhancement of this quantity in the fractional filling in relation to the integer-filling case, which is a direct consequence of the fractionalization of the electron in the fractional quantum Hall state. We present simple theoretical expressions for the Onsager coefficients at low temperatures, which explicitly show that ZT and the Seebeck coefficient increase with m.Fil: Roura Bas, Pablo Gines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Arrachea, Liliana del Carmen. Freie Universität Berlin; Alemania. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fradkin, Eduardo. University of Illinois at Urbana; Estados Unido

Conceptual framework for designing agri-food supply chains under uncertainty by mathematical programming models

This is an Author's Accepted Manuscript of an article published in [include the complete citation information for the final version of the article as published in the International Journal of Production Research (2018) © Taylor & Francis, available online at: http://doi.org/10.1080/00207543.2018.1447706[EN] Agri-food sector performance strongly impacts global economy, which means that developing optimisation models to support the decision-making process in agri-food supply chains (AFSC) is necessary. These models should contemplate AFSC¿s inherent characteristics and sources of uncertainty to provide applicable and accurate solutions. To the best of our knowledge, there are no conceptual frameworks available to design AFSC through mathematical programming modelling while considering their inherent characteristics and sources of uncertainty, nor any there literature reviews that address such characteristics and uncertainty sources in existing AFSC design models. This paper aims to fill these gaps in the literature by proposing such a conceptual framework and state of the art. The framework can be used as a guide tool for both developing and analysing models based on mathematical programming to design AFSC. The implementation of the framework into the state of the art validates its. Finally, some literature gaps and future research lines were identified.This first author was partially supported by the Programme of Formation of University Professors of the Spanish Ministry of Education, Culture, and Sport [grant number FPU15/03595]; the partial support of Project 'Development of an integrated maturity model for agility, resilience and gender perspective in supply chains (MoMARGE). Application to the agricultural sector.' Ref. GV/2017/025, funded by the Generalitat Valenciana. The other authors acknowledge the partial support of Project 691249, RUC-APS: Enhancing and implementing Knowledge based ICT solutions within high Risk and Uncertain Conditions for Agriculture Production Systems, funded by the EU under its funding scheme H2020-MSCA-RISE-2015.Esteso, A.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2018). Conceptual framework for designing agri-food supply chains under uncertainty by mathematical programming models. International Journal of Production Research. 56(13):4418-4446. https://doi.org/10.1080/00207543.2018.1447706S44184446561

Implementación de un gadget OpenSocial para mensajería instantánea

El presente proyecto pretende abordar un problema básico dentro del mundo médico cómo es la comunicación instantánea mediante la mensajería en un entorno social. La aplicación implementada permite a los usuarios de una red social comunicarse entre sí añadiendo un gadget OpenSocial de mensajería instantánea a su red social desde cualquier dispositivo que permita ejecutar un navegador. Este gadget OpenSocial se integra en la red social y aprovecha sus características sociales para extraer listas de amigos y usuarios y de esta manera poder conectarlos entre sí mediante el protocolo XMPP utilizando un servidor Openfire. Aprovechando las ventajas que ofrece utilizar un protocolo de comunicación potente como XMPP, el gadget nos ofrecerá servicios más allá de la propia mensajería instantánea que nos permiten interaccionar con los otros usuarios de la red social. La aplicación incorpora también un servicio de presencia donde el usuario podrá establecer su disponibilidad en cualquier momento y un servicio de suscripción donde poder establecer nuevas conexiones con otros integrantes de la red social y que a su vez nos permite conocer la presencia de estos usuarios en la aplicación. Con todos estos ingredientes, se pretende marcar un punto de apoyo que mejore la calidad y la productividad del trabajo de los profesionales sanitarios.Ingeniería de Telecomunicació

Diagnòstic precoç de l’Alzheimer a través de l’anàlisi verbal

Treballs Finals de Grau de Lingüística. Facultat de Filologia. Universitat de Barcelona, Curs: 2015-2016, Tutor: Albert Bastardas. Director: Faustino Diéguez[cat] Seguint una nova corrent d’estudi anomenada pragmàtica clínica, dedicada a la descripció i anàlisi dels fenòmens pragmàtics en l’àmbit de les patologies i demències, aquest treball consisteix en una verificació de dues teories sobre la relació entre la gestualitat i el llenguatge verbal. En aquest cas s’ha fet un estudi sobre l’anàlisi quantitativa i qualitativa del llenguatge de cinc grups de subjectes: controls sans, subjectes amb deteriorament cognitiu lleu executiu i temporo-medial, i malalts d’Alzheimer en fase moderada (GDS4) i moderada-greu (GDS5). L’objectiu principal de l’estudi és detectar tendències en la part verbal del llenguatge que facin possible un diagnòstic precoç de l’Alzheimer, la demència que afecta més població i per la qual encara no hi ha cap cura efectiva. Els resultats, tot i no ser concloents, mostren uns resultats significatius que permeten proposar d’incloure l’anàlisi de la gestualitat i el llenguatge en les proves pel diagnòstic precoç de l’Alzheimer. A més, les dades obtingudes demostren que l’anàlisi de les paraules òmnibus relacionades amb l’anàlisi de la gestualitat podrien permetre diferenciar de forma objectiva un estadi de predemència, d’una malaltia d’Alzheimer i d’un deteriorament cognitiu que no evolucionarà a demència.[eng] Following a new study trend called clinical pragmatic, which focuses on the description and analysis of the pragmatic phenomena in the disease and dementia fields, this project consists in the extension and verification of two theories about the relationship between gesticulation and spoken language. In this case, a study about a quantitative and qualitative analysis of the language of five groups of individuals has been run. The groups are: healthy controls, subjects with a executive and medial-temporal mild cognitive impairment, and patients with Alzheimer’s Disease moderate (GDS4) and moderate-severe (GDS5) stages. The main aim of the study is to detect trends in the spoken part of the language that enable to make an Alzheimer’s early diagnosis, which is the dementia that affects more population and it does not have an effective cure yet. The results, despite not being conclusive, show significant evidence, which allows to propose the introduction of the gesture and language analysis on the Alzheimer’s early diagnosis test. Moreover, data obtained proofs that the omnibus words analysis related to the one of gesticulation could allow to subjectively differentiate a pre-dementia state, from an Alzheimer disease, and from a cognitive deterioration that will not evolve into a dementia

Effectiveness of a Multifactorial Intervention in the First 1000 Days of Life to Prevent Obesity and Overweight in Childhood: Study Protoco

(1) Background: Obesity is a global health problem, and its prevention must be a priority goal of public health, especially considering the seriousness of the problem among children. It is known that fetal and early postnatal environments may favor the appearance of obesity in later life. In recent years, the impact of the programs to prevent obesity in childhood has been scarce. The aim of this research is to evaluate the effectiveness of an intervention based on the concept of early programming. (2) Methods: Non-randomized controlled trial design. Inclusion criteria are: two-year-old infants whose gestational period begins in the 14 months following the start of the intervention, and whose mothers have made the complete follow-up of their pregnancy in the same clinical unit of the study. The intervention will be developed over all the known factors that affect early programming, during pregnancy up to 2 years of life. Data will be collected through a data collection sheet by the paediatricians. A unibivariate and multivariate analysis of the data will be carried out. (3) Ethics and dissemination: The trial does not involve any risk to participants and their offspring. Signed informed consent is obtained from all participants. Ethical approval has been obtained. (4) Results: It is expected that this study will provide evidence on the importance of the prevention of obesity from the critical period of the first 1000 days of life, being able to establish this as a standard intervention in primary care