Desarrollo de una librería para el aprendizaje federado bajo una arquitectura peer-to-peer

[Resumen]: En la última década, la evolución del Machine Learning ha sido muy próspera, necesitando los modelos más fructíferos ser nutridos por grandes volúmenes de datos. A menudo, la obtención y gestión de estos datos es complicada, siendo generalmente escasos y sujetos a medidas de privacidad. El Federated Learning implica un cambio de paradigma en el entrenamiento de modelos de Machine Learning. Este nuevo enfoque permite realizar el proceso de aprendizaje sobre datos distribuidos entre una gran cantidad de clientes. A pesar de que esta novedosa técnica trae consigo numerosas ventajas, una de sus grandes limitaciones es la necesidad de un servidor que orqueste todo el proceso de aprendizaje, suponiendo un único punto de falla. Así mismo, se necesitará disponer de una gran infraestructura para hacer escalables estos sistemas. Para tratar de solventar estas desventajas, surgirán nuevas aproximaciones denominadas Decentralized Federated Learning, siendo una de las soluciones más prometedoras el uso de redes peer-to-peer. Ante la inexistencia de alguna librería de soporte al Decentralized Federated Learning, en este proyecto, se propone el desarrollo de una librería de propósito general que permita el Federated Learning sobre redes peer-to-peer, empleando el protocolo Gossip. El uso del protocolo Gossip garantizará la tolerancia a fallos en la red peer-to-peer, creando un ecosistema descentralizado, escalable y robusto. La librería busca dar soporte a toda clase de dispositivos, haciendo especial hincapié en su facilidad de uso y ampliación futura. Además de permitir el despliegue, ésta, posibilita la ejecución de simulaciones, haciendo posible la realización de pruebas en entornos controlados. Para el desarrollo, se ha hecho uso de la metodología ágil SCRUM. Las iteraciones centrales se han destinado a la implementación del sistema, mientras que la inicial y final se han dedicado a la preparación del proyecto y realización de pruebas respectivamente. En las diversas pruebas realizadas, se han empleado los datasets de MNIST y FEMNIST, obteniendo resultados realmente similares a ejecuciones equivalentes con entrenamientos clásicos.[Abstract]: In the last decade, the evolution of Machine Learning has been really thriving. The most productive models need to be fed by a large volume of data. Obtaining and managing these data is often complicated, as they are generally scarce and subject to privacy measures. Federated Learning implies a paradigm shift in the training of Machine Learning models. This new approach allows us to carry out the learning process on data which are distributed among a large number of clients. In spite of the fact that this new technique has numerous advantages, one of its great limitations is the need for a server that orchestrates the entire learning process, assuming a single point of failure. Moreover, a large infrastructure will be necessary to make these systems scalable .In order to solve these disadvantages, new approaches called Decentralized Federated Learning will emerge, and one of the most promising solutions will be the use of peer-to-peer networks. Given the lack of any library to support Decentralized Federated Learning, this project proposes the development of a general purpose library that allows Federated Learning over peer-to-peer networks, using the Gossip protocol. The use of the Gossip protocol will guarantee fault tolerance in the network, creating a decentralized, scalable and robust ecosystem. The library will seek to support all kinds of devices, with special emphasis on ease of use and future expansion. In addition to allowing deployment, it will enable the execution of simulations, making it possible to perform tests in controlled environments. The agile SCRUM methodology has been used for this development. The central iterations have been used to the implementation of the system, while the initial and final iterations have been respectively dedicated to project preparation and testing. The MNIST and FEMNIST datasets have been used in the different tests carried out, obtaining results that are really similar to equivalent executions with classic training.Traballo fin de grao (UDC.FIC). Enxeñaría Informática. Curso 2021/202

Regulación de la formación de gotas lipídicas por ácido araquidónico en monocitos humanos: importancia del ácido graso

Las gotas lipídicas son orgánulos compuestos por un núcleo de lípidos neutros rodeado de una monocapa de fosfolípidos. Su formación está implicada en numerosas enfermedades, como la aterosclerosis. Se ha descrito que la formación de gotas lipídicas en monocitos circulantes es un factor de riesgo en el desarrollo temprano de esta enfermedad. En este trabajo se muestra que el ácido araquidónico induce una rápida formación de gotas lipídicas en monocitos humanos, dependiente de la síntesis de novo de ácidos grasos, así como de la activación de la fosfolipasa A2 de grupo IVA. Entre los ácidos grasos que se incorporan a las gotas lipídicas destaca el ácido graso 16:1n-9, que podría constituir un buen marcador de la formación de estos orgánulos. En el trabajo se demuestra que este ácido graso se sintetiza a partir del ácido oleico y presenta un robusto comportamiento antiinflamatorio en modelos de ratón.Departamento de Bioquímica y Biología Molecular y Fisiologí

Lipin-1 integrates lipid synthesis with proinflammatory responses during TLR activation in macrophages

Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase involved in the de novo synthesis of phospholipids and triglycerides. Using macrophages from lipin-1-deficient animals and human macrophages deficient in the enzyme, we show in this work that this phosphatase acts as a proinflammatory mediator during TLR signaling and during the development of in vivo inflammatory processes. After TLR4 stimulation lipin-1-deficient macrophages showed a decreased production of diacylglycerol and activation of MAPKs and AP-1. Consequently, the generation of proinflammatory cytokines like IL-6, IL-12, IL-23, or enzymes like inducible NO synthase and cyclooxygenase 2, was reduced. In addition, animals lacking lipin-1 had a faster recovery from endotoxin administration concomitant with a reduced production of harmful molecules in spleen and liver. These findings demonstrate an unanticipated role for lipin-1 as a mediator of macrophage proinflammatory activation and support a critical link between lipid biosynthesis and systemic inflammatory responses.This work was supported by the Spanish Ministry of Science and Innovation (Grants SAF2007-60055, SAF2010-18831, and BFU2010-18826) and the Regional Government of Castile and Leon (Grants BIO39/VA04/10 and CSI168A12-1). L.P. and G.L. were supported by predoctoral fellowships from the Spanish Ministry of Science and Innovation (Plan de Formación de Personal Investigador and Plan de Formación de Profesorado Universitario programs). M.V. was supported by a predoctoral fellowship from the Regional Government of Castile and Leon. E.E. was supported by a predoctoral fellowship from the Spanish National Research Council (Junta de Ampliación de Estudios Program). C.G. was supported by a predoctoral fellowship from the University of Valladolid.Peer Reviewe

El silenciamiento de GPAT2 en células MDA-MB-231 afecta el remodelado del ácido araquidónico

La síntesis de novo de glicerolípidos en células de mamífero comienza con la acilación del glicerol-3-fosfato. Este paso esta catalizado por la glicerol-3-fosfato aciltransferasa (GPAT); hasta el momento se han clonado cuatro genes que codifican GPATs. La GPAT2, se clonó por homología de secuencia con GPAT1, sin embrago hemos demostrado que presenta características que la distinguen notablemente de las otras GPATs: se comporta como un antígeno cáncer/ testículo (expresión selectiva en testículo y en tumores de distintas localizaciones), presenta una expresión transitoria en un estadío particular de la meiosis y promueve el fenotipo tumoral incrementando la proliferación y supervivencia celular. Si bien los mecanismos mediante los cuales GPAT2 ejerce su rol funcional, tanto en condiciones fisiológicas como patológicas, no se han dilucidado, nuestros resultados previos indican que juega un rol relevante en el metabolismo del ácido araquidónico.Facultad de Ciencias Médica

El silenciamiento de GPAT2 en células MDA-MB-231 afecta el remodelado del ácido araquidónico

La síntesis de novo de glicerolípidos en células de mamífero comienza con la acilación del glicerol-3-fosfato. Este paso esta catalizado por la glicerol-3-fosfato aciltransferasa (GPAT); hasta el momento se han clonado cuatro genes que codifican GPATs. La GPAT2, se clonó por homología de secuencia con GPAT1, sin embrago hemos demostrado que presenta características que la distinguen notablemente de las otras GPATs: se comporta como un antígeno cáncer/ testículo (expresión selectiva en testículo y en tumores de distintas localizaciones), presenta una expresión transitoria en un estadío particular de la meiosis y promueve el fenotipo tumoral incrementando la proliferación y supervivencia celular. Si bien los mecanismos mediante los cuales GPAT2 ejerce su rol funcional, tanto en condiciones fisiológicas como patológicas, no se han dilucidado, nuestros resultados previos indican que juega un rol relevante en el metabolismo del ácido araquidónico.Facultad de Ciencias Médica

El silenciamiento de GPAT2 en células MDA-MB-231 afecta el remodelado del ácido araquidónico

La síntesis de novo de glicerolípidos en células de mamífero comienza con la acilación del glicerol-3-fosfato. Este paso esta catalizado por la glicerol-3-fosfato aciltransferasa (GPAT); hasta el momento se han clonado cuatro genes que codifican GPATs. La GPAT2, se clonó por homología de secuencia con GPAT1, sin embrago hemos demostrado que presenta características que la distinguen notablemente de las otras GPATs: se comporta como un antígeno cáncer/ testículo (expresión selectiva en testículo y en tumores de distintas localizaciones), presenta una expresión transitoria en un estadío particular de la meiosis y promueve el fenotipo tumoral incrementando la proliferación y supervivencia celular. Si bien los mecanismos mediante los cuales GPAT2 ejerce su rol funcional, tanto en condiciones fisiológicas como patológicas, no se han dilucidado, nuestros resultados previos indican que juega un rol relevante en el metabolismo del ácido araquidónico.Facultad de Ciencias Médica

Sequestration of 9-hydroxystearic acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a protective mechanism for colon carcinoma cells to avoid apoptotic cell death

Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-HSA levels in human colorectal tumors are diminished when compared with normal adjacent tissue. Since this decrease could be compatible with an escape mechanism of tumors from 9-HSA-induced apoptosis, we investigated different features of the utilization of this hydroxyfatty acid in colon. We show that in colorectal tumors and related cell lines such as HT-29 and HCT-116, 9-HSA is the only hydroxyfatty acid constituent of branched fatty acid esters of hydroxyfatty acids (FAHFA), a novel family of lipids with anti-inflammatory properties. Importantly, FAHFA levels in tumors are elevated compared with normal tissue and, unlike 9-HSA, they do not induce apoptosis of colorectal cell lines over a wide range of concentrations. Further, the addition of 9-HSA to colon cancer cell lines augments the synthesis of different FAHFA before the cells commit to apoptosis, suggesting that FAHFA formation may function as a buffer system that sequesters the hydroxyacid into an inactive form, thereby restricting apoptosis.This research was funded by the Spanish Ministry of Economy, Industry and Competitiveness, grant numbers SAF2016-80883-R and SAF2015-73000-EXP. C.G. was funded by a predoctoral fellowship from the University of Valladolid (Plan de Formación de Personal Investigador). CIBERDEM is an initiative of Instituto de Salud Carlos IIIWe acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)Peer reviewe

Towards a comprehensive characterisation of the human internal chemical exposome: Challenges and perspectives

The holistic characterisation of the human internal chemical exposome using high-resolution mass spectrometry (HRMS) would be a step forward to investigate the environmental AE tiology of chronic diseases with an unprecedented precision. HRMS-based methods are currently operational to reproducibly profile thousands of endogenous metabolites as well as externally-derived chemicals and their biotransformation products in a large number of biological samples from human cohorts. These approaches provide a solid ground for the discovery of unrecognised biomarkers of exposure and metabolic effects associated with many chronic diseases. Nevertheless, some limitations remain and have to be overcome so that chemical exposomics can provide unbiased detection of chemical exposures affecting disease susceptibility in epidemiological studies. Some of these limitations include (i) the lack of versatility of analytical techniques to capture the wide diversity of chemicals; (ii) the lack of analytical sensitivity that prevents the detection of exogenous (and endogenous) chemicals occurring at (ultra) trace levels from restricted sample amounts, and (iii) the lack of automation of the annotation/identification process. In this article, we discuss a number of technological and methodological limitations hindering applications of HRMS-based methods and propose initial steps to push towards a more comprehensive characterisation of the internal chemical exposome. We also discuss other challenges including the need for harmonisation and the difficulty inherent in assessing the dynamic nature of the internal chemical exposome, as well as the need for establishing a strong international collaboration, high level networking, and sustainable research infrastructure. A great amount of research, technological development and innovative bio-informatics tools are still needed to profile and characterise the "invisible" (not profiled), "hidden" (not detected) and "dark" (not annotated) components of the internal chemical exposome and concerted efforts across numerous research fields are paramount

Secondary Metabolites of Marine Microbes: From Natural Products Chemistry to Chemical Ecology

Marine natural products (MNPs) exhibit a wide range of pharmaceutically relevant bioactivities, including antibiotic, antiviral, anticancer, or anti-inflammatory properties. Besides marine macroorganisms such as sponges, algae, or corals, specifically marine bacteria and fungi have shown to produce novel secondary metabolites (SMs) with unique and diverse chemical structures that may hold the key for the development of novel drugs or drug leads. Apart from highlighting their potential benefit to humankind, this review is focusing on the manifold functions of SMs in the marine ecosystem. For example, potent MNPs have the ability to exile predators and competing organisms, act as attractants for mating purposes, or serve as dye for the expulsion or attraction of other organisms. A large compilation of literature on the role of MNPs in marine ecology is available, and several reviews evaluated the function of MNPs for the aforementioned topics. Therefore, we focused the second part of this review on the importance of bioactive compounds from crustose coralline algae (CCA) and their role during coral settlement, a topic that has received less attention. It has been shown that certain SMs derived from CCA and their associated bacteria are able to induce attachment and/or metamorphosis of many benthic invertebrate larvae, including globally threatened reef-building scleractinian corals. This review provides an overview on bioactivities of MNPs from marine microbes and their potential use in medicine as well as on the latest findings of the chemical ecology and settlement process of scleractinian corals and other invertebrate larvae