Imaging the Human Immunological Synapse

The purpose of the method is to generate an immunological synapse (IS), an example of cell-to-cell conjugation formed by an antigen-presenting cell (APC) and an effector helper T lymphocyte (Th) cell, and to record the images corresponding to the first stages of the IS formation and the subsequent trafficking events (occurring both in the APC and in the Th cell). These events will eventually lead to polarized secretion at the IS. In this protocol, Jurkat cells challenged with Staphylococcus enterotoxin E (SEE)-pulsed Raji cells as a cell synapse model was used, because of the closeness of this experimental system to the biological reality (Th cell-APC synaptic conjugates). The approach presented here involves cell-to-cell conjugation, time-lapse acquisition, wide-field fluorescence microscopy (WFFM) followed by image processing (post-acquisition deconvolution). This improves the signal-to-noise ratio (SNR) of the images, enhances the temporal resolution, allows the synchronized acquisition of several fluorochromes in emerging synaptic conjugates and decreases fluorescence bleaching. In addition, the protocol is well matched with the end point cell fixation protocols (paraformaldehyde, acetone or methanol), which would allow further immunofluorescence staining and analyses. This protocol is also compatible with laser scanning confocal microscopy (LSCM) and other state-of-the-art microscopy techniques. As a main caveat, only those T cell-APC boundaries (called IS interfaces) that were at the right 90° angle to the focus plane along the Z-axis could be properly imaged and analyzed. Other experimental models exist that simplify imaging in the Z dimension and the following image analyses, but these approaches do not emulate the complex, irregular surface of an APC, and may promote non-physiological interactions in the IS. Thus, the experimental approach used here is suitable to reproduce and to confront some biological complexities occurring at the ISThis work was supported by grants from the Spanish Ministerio de Economía y Competitividad (MINECO), Plan Nacional de Investigación Científica (SAF2016-77561-R to M.I., which was in part granted with FEDER-EC funding). We acknowledge Facultad de Medicina (UAM) and Departamento de Audiovisuales of the Facultad de Medicina for their support and the facilities provided to produce the vide

Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells

Multivesicular bodies (MVB) are endocytic compartments that enclose intraluminal vesicles (ILVs) formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, ILVs are secreted as Fas ligand-bearing, pro-apoptotic exosomes following T cell receptor (TCR)-induced fusion of MVB with the plasma membrane at the immune synapse (IS). In this study we show that protein kinase C δ (PKCδ), a novel PKC isotype activated by diacylglycerol (DAG), regulates TCR-controlled MVB polarization toward the IS and exosome secretion. Concomitantly, we demonstrate that PKCδ-interfered T lymphocytes are defective in activation-induced cell death. Using a DAG sensor based on the C1 DAG-binding domain of PKCδ and a GFP-PKCδ chimera, we reveal that T lymphocyte activation enhances DAG levels at the MVB endomembranes which mediates the association of PKCδ to MVB. Spatiotemporal reorganization of F-actin at the IS is inhibited in PKCδ-interfered T lymphocytes. Therefore, we propose PKCδ as a DAG effector that regulates the actin reorganization necessary for MVB traffic and exosome secretion

Reporte de Mercados Financieros - Primer trimestre de 2023

El Banco de la República (Banrep) genera información para la toma de decisiones, la rendición de cuentas y la difusión al público. En particular, el \textit{Reporte de Mercados Financieros} está enmarcado dentro del principio de difusión al público y contribuye a cumplir con el servicio que presta el Banco de ofrecer información e investigación económica de calidad. En línea con lo anterior, este reporte busca proveer al público un análisis general del comportamiento y las tendencias de los mercados financieros nacionales e internacionales. Adicionalmente, señala los principales factores que permiten explicar el comportamiento de dichos mercados y sus interacciones, sí como una descripción de los principales cambios en política monetaria y decisiones de los bancos centrales a nivel mundial. El entorno económico global en el que se desenvuelven los mercados que este reporte estudia, continúa inmerso en un escenario de bajas perspectivas de crecimiento, una inflación que sigue sorprendiendo por su alta persistencia, tensiones geopolíticas y la presencia de factores de riesgo en el frente financiero que pueden materializarse ante un escenario macroeconómico más complejo. Por su parte, los agentes del mercado han balanceado diferentes fuentes de información para discernir acerca de la posible senda de la política monetaria global, dados sus efectos en los distintos mercados. Sin embargo, al final del primer trimestre de 2023 primó la expectativa de una postura menos contractiva por parte de la Fed, teniendo en cuenta que aunque las autoridades han manifestado su valoración sobre la resiliencia del sector bancario tras la quiebra de algunos bancos regionales, se percibe una alta reactividad de los inversionistas ante las noticias sobre el desempeño de los sectores económicos, la inflación, el mercado laboral y la dinámica del crédito y, por tanto, en las condiciones financieras en EE.UU (Ver Entorno Internacional). Con respecto a la evolución de las variables macroeconómicas y las expectativas de la evolución de la política monetaria futura en el contexto local, los agentes del mercado descuentan para 2023 una senda de inflación decreciente y una desaceleración en la dinámica económica consistente con perspectivas de una postura de política monetaria contractiva por parte del Banrep. En este entorno, el mercado descuenta para el segundo trimestre del año el fin del ciclo de incrementos de la tasa de interés de referencia por parte del Banrep así como el inicio de reducciones en la tasa de interés hacia el segundo semestre del año (Ver política monetaria y mercado monetario local). Con respecto al mercado de deuda pública local, este presentó un comportamiento favorable, superior a los pares de la región, que contrasta con su comportamiento durante 2022, en línea con la reducción en las perspectivas de tasa de política monetaria de la Fed y una mayor liquidez de este mercado. En todo caso, las tasas en este mercado sugieren un costo de financiamiento relativamente elevado (ver Mercado de deuda pública interna y externa – Gráfico 1). El mercado monetario exhibió amplios niveles de liquidez que se corrigieron durante el periodo. Al mismo tiempo, persiste una alta percepción de riesgo país, que coincide con la permanencia de fuentes de vulnerabilidad externa y fiscal, así como con la incertidumbre sobre el desenlace de la agenda de reformas del gobierno (Ver Percepción de riesgo a nivel local). Como consecuencia, los inversionistas extranjeros realizaron ventas de títulos de deuda pública en el trimestre, aunque se observó un comportamiento volátil y las ventas fueron realizadas por algunos agentes puntuales y estuvieron concentradas en algunas referencias específicas. Por su parte, para la deuda privada, se identifica un fuerte dinamismo del mercado de CDTs en el periodo reciente, mientras que las colocaciones en otros títulos de deuda privada siguen perdiendo dinamismo (Ver Mercado de deuda privada). En este reporte se estudia los factores que pudieron guiar el fuerte aumento del diferencial entre los CDTs y los TES en el periodo reciente. Se encuentran indicios de una posible relación entre el spread con factores tales como la tasa de política monetaria y sus expectativas, unas mayores expectativas de inflación, un alto crecimiento de la cartera acompañado de la entrada en vigor del CFEN, una alta concentración en el mercado de tenedores de CDT y una mayor percepción de riesgo (Ver Recuadro 1. Análisis del spread entre las tasas de los CDT y TES). En cuanto al mercado cambiario, el peso colombiano se apreció y volvió a niveles no vistos en cerca de seis meses, en línea con correcciones en la fortaleza del dólar a nivel internacional. No obstante, sus niveles se mantienen aún desviados de las monedas de los países pares de la región (Ver Mercado Cambiario – Gráfico 1). Finalmente, el mercado accionario local, continúa exhibiendo un desempeño débil en comparación con los pares de la región, en un entorno de baja liquidez. Las acciones del sector bancario, que tienen un peso importante sobre índice local presentaron caídas importantes, en línea con las referencias globales, ante los eventos adversos en algunas entidades financieras de EE. UU. y Suiza (Ver Mercado accionario – Gráfico 1)

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Bonfa, Eloisa. Universidade de Sao Paulo; BrasilFil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; MéxicoFil: Izcovich, Ariel. Hospital Alemán; ArgentinaFil: Popoff, Federico. Hospital Aleman; ArgentinaFil: Criniti, Juan M.. Hospital Alemán; ArgentinaFil: Vásquez, Gloria. Universidad de Antioquia; ColombiaFil: Massardo, Loreto. Universidad San Sebastián; ChileFil: Duarte, Margarita. Hospital de Clínicas; ParaguayFil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; MéxicoFil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amigo, Mary Carmen. Centro Médico Abc; MéxicoFil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; BrasilFil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; PerúFil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; VenezuelaFil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; EcuadorFil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; ColombiaFil: Molina, José Fernando. Centro Integral de Reumatología; ColombiaFil: Neira, Oscar. Universidad de Chile; ChileFil: Silva, Clóvis A.. Universidade de Sao Paulo; BrasilFil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; UruguayFil: Gómez Puerta, José A.. Hospital Clinic Barcelona; EspañaFil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; ArgentinaFil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; BrasilFil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Drenkard, Cristina. University of Emory; Estados UnidosFil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cavalcanti, André. Universidade Federal de Pernambuco; BrasilFil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; UruguayFil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; VenezuelaFil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; BrasilFil: Eraso Garnica, Ruth M.. Universidad de Antioquia; ColombiaFil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; ColombiaFil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Robaina Sevrini, Ricardo. Universidad de la República; UruguayFil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rosario, Violeta. Hospital Docente Padre Billini; República DominicanaFil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; ArgentinaFil: Appenzeller, Simone. Universidade Estadual de Campinas; BrasilFil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; BrasilFil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Naranjo, Luis A.. Universidad de Antioquia; ColombiaFil: González Bello, Yelitza C.. Ceibac; MéxicoFil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Cairoli, Ernesto. Universidad de la República; UruguayFil: Conti, Silvana M.. Hospital Provincial de Rosario; ArgentinaFil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Borba, Eduardo F.. Universidade de Sao Paulo; BrasilFil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; ArgentinaFil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; BrasilFil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; BrasilFil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; BrasilFil: Da Silva, Nilzio A.. Universidade Federal de Goiás; BrasilFil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; BrasilFil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; BrasilFil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; BrasilFil: Llanos, Carolina. Universidad Católica de Chile; ChileFil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El SalvadorFil: Garcia De La Torre, Ignacio. Hospital General de Occidente; MéxicoFil: Pineda, Carlos. Instituto Nacional de Rehabilitación; MéxicoFil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Danza, Alvaro. Hospital Pasteur Montevideo; UruguayFil: Guibert Toledano, Marlene. Medical-surgical Research Center; CubaFil: Reyes, Gil Llerena. Medical-surgical Research Center; CubaFil: Acosta Colman, Maria Isabel. Hospital de Clínicas; ParaguayFil: Aquino, Alicia M.. Hospital de Clínicas; ParaguayFil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República DominicanaFil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; MéxicoFil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; ChileFil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unido

Función de PKCδ sobre la secreción de exosomas en linfocitos T colaboradores

[Hipótesis y objetivos] Basándonos en los antecedentes explicados, nuestra hipótesis se basa en la idea de que PKCδ, se activa por un aumento en los niveles de DAG tras la activación del TCR, provocando una serie de cambios (fosforilación) en proteínas nucleadoras de actina como la FMNL1, miembro de la familia de las forminas, lo que produce una remodelación de la F-actina tanto a nivel de sinapsis como alrededor del MTOC y de los cuerpos multivesiculares (MVB), que forman parte del aparato de secreción de la célula. De esta manera, en la zona central de la sinapsis se formará una región central desprovista de F-actina que permitirá el paso de vesículas de secreción como los MVBs. Al mismo tiempo, los niveles de F-actina disminuirán alrededor de MTOC y de los MVBs permitiendo su polarización hacia la IS. Por ello, nuestros objetivos son: 1.Determinar los cambios que ocurren en el citoesqueleto de actina (tanto en sinapsis como alrededor del MTOC) tras la formación de la sinapsis en célula viva, y comprobar si la interferencia enPKCδ afecta dichos procesos. 2.Determinar si la interferencia en PKCδ afecta la fosforilación de FMNL1. 3.Determinar la localización subcelular de FMNL1, fosforilado y sin fosforilar, así como la colocalización de éstos con respecto a PKCδ y F-actina.Peer reviewe

Imaging the Human Immunological Synapse

The purpose of the method is to generate an immunological synapse (IS), an example of cell-to-cell conjugation formed by an antigen-presenting cell (APC) and an effector helper T lymphocyte (Th) cell, and to record the images corresponding to the first stages of the IS formation and the subsequent trafficking events (occurring both in the APC and in the Th cell). These events will eventually lead to polarized secretion at the IS. In this protocol, Jurkat cells challenged with Staphylococcus enterotoxin E (SEE)-pulsed Raji cells as a cell synapse model was used, because of the closeness of this experimental system to the biological reality (Th cell-APC synaptic conjugates). The approach presented here involves cell-to-cell conjugation, time-lapse acquisition, wide-field fluorescence microscopy (WFFM) followed by image processing (post-acquisition deconvolution). This improves the signal-to-noise ratio (SNR) of the images, enhances the temporal resolution, allows the synchronized acquisition of several fluorochromes in emerging synaptic conjugates and decreases fluorescence bleaching. In addition, the protocol is well matched with the end point cell fixation protocols (paraformaldehyde, acetone or methanol), which would allow further immunofluorescence staining and analyses. This protocol is also compatible with laser scanning confocal microscopy (LSCM) and other state-of-the-art microscopy techniques. As a main caveat, only those T cell-APC boundaries (called IS interfaces) that were at the right 90° angle to the focus plane along the Z-axis could be properly imaged and analyzed. Other experimental models exist that simplify imaging in the Z dimension and the following image analyses, but these approaches do not emulate the complex, irregular surface of an APC, and may promote non-physiological interactions in the IS. Thus, the experimental approach used here is suitable to reproduce and to confront some biological complexities occurring at the IS.This work was supported by grants from the Spanish Ministerio de Economía y Competitividad (MINECO), Plan Nacional de Investigación Científica (SAF2016-77561-R to M.I., which was in part granted with FEDER-EC funding)

Las fronteras del istmo

Obra organizada en torno a seis ejes principales que estudian la importancia de comparar las fronteras y los tipos de gestión desde el punto de vista geopolítico, histórico y antropológico; las tramas de la organización del espacio actual; la influencia en la evolución de las sociedades debido a la violencia política y los conflictos armados; los movimientos migratorios internacionales; la integración política y económica y finalmente los lazos comunitarios y de las identidades relacionados con las vivencias fronterizas

XVII International Congress of Control Electronics and Telecommunications: "Advanced Science, Technology and Innovation to move towards a new socio-technical system: Sustainable Social Transformation"

Contenido: Approach to the diagnostic of cesarean birth using bio-inspired models. ; Design of a tool in a virtual reality environment to manipulate anatomical models. ; The effect of COVID-19 restrictions on the electricity price forecasting models. ; Depression prevention through artificial intelligence. ; State of the art in Prototypes as complements to the learning of the Colombian Sign Language (LSC). ; A computational proposal for gene expression deterministic analysis in associated disorders to depression and anxiety. ; Evaluation of postural stability from the predictability of the measurement of the center of pressure. ; Psychophysiological Analysis of Sound Stimuli.; Delphi method for the identification of relevant variables in the development of low-power photovoltaic solar projects. ; Socioeconomic impact of a refrigerator powered by a photovoltaic system in La Guajira. ; Energy Efficiency: characteristics that allow the reduction of greenhouse gases in. ; Possibilities for the implementation of a bioreactor from organic waste. ; Energy Potential with Small Hydroelectric Power Plants in Non- interconnected Zones of Colombia. ; Energy Potential in Photovoltaic Solar Solutions in Non-Interconnected Areas of Colombia. ; Photovoltaic system, towards the energy transition from home. ; Blockchain model to increase the transparency of public sector processes. ; Intelligent agricultural irrigation prescription system based on sensor networks and crop modeling. ; Design and implementation of a digital modulation classification system using intelligent algorithms. ; A mobile application proposal to minimize intermediation during agricultural process distribution of products in supply chain. ; Accompanying strategy for the social appropriation of new technologies in vulnerable agricultural communities: case in communities producing Gulupas fruits (Passiflora edulis Sims). ; Predictive model of transparency as an indicator of Public Policies. ; Smart system for recognition of ripening level in blackberry fruits. ; Project-based learning as an alternative methodology for technological education in electronics. ; Design and construction of an automated system for N. ; Four bar mechanisms (FBM) and their Software-Based applications: a reviewFT aquaponic culture of Red Carp and Crespa Lettuce. ; Intelligent search implementation for the construction of states of the art: a python application. ; Indoor and Outdoor propagation models on 5G environments: state of the art. ;The electronic detection of offenders (DOO) in the District Secretary of mobility of Bogotá: a step forward in the configuration of the concept of digital citizenship in Colombia. ; Monitoring through ICT of Mobility: technological collaborative feature to incorporate IoT in a Smart City. ; Characterization model of asphalt mixtures using digital image processing. ; Review: identification of diseases and/or pests in fruit trees through image processing techniques and artificial intelligence. ; VRS applicated to Nasa Yuwe language. ; Application of Pix2Pix for edge reconstruction in images. ; Brushless DC Motor Control System for Active Myoelectric Prosthesis. ; Implementation of a Water Conductivity Measuring System. ; 2 DOF robot programmed with MatLab® (guide and Peter Corke) and Arduino uno for writing alphabetical characters. ; Simulator of the behavior of the center of mass in a quadruped robot. ; Biomimetic prototype for flapping movement of batsContent: Contenido: Approach to the diagnostic of cesarean birth using bio-inspired models. ; Design of a tool in a virtual reality environment to manipulate anatomical models. ; The effect of COVID-19 restrictions on the electricity price forecasting models. ; Depression prevention through artificial intelligence. ; State of the art in Prototypes as complements to the learning of the Colombian Sign Language (LSC). ; A computational proposal for gene expression deterministic analysis in associated disorders to depression and anxiety. ; Evaluation of postural stability from the predictability of the measurement of the center of pressure. ; Psychophysiological Analysis of Sound Stimuli.; Delphi method for the identification of relevant variables in the development of low-power photovoltaic solar projects. ; Socioeconomic impact of a refrigerator powered by a photovoltaic system in La Guajira. ; Energy Efficiency: characteristics that allow the reduction of greenhouse gases in. ; Possibilities for the implementation of a bioreactor from organic waste. ; Energy Potential with Small Hydroelectric Power Plants in Non- interconnected Zones of Colombia. ; Energy Potential in Photovoltaic Solar Solutions in Non-Interconnected Areas of Colombia. ; Photovoltaic system, towards the energy transition from home. ; Blockchain model to increase the transparency of public sector processes. ; Intelligent agricultural irrigation prescription system based on sensor networks and crop modeling. ; Design and implementation of a digital modulation classification system using intelligent algorithms. ; A mobile application proposal to minimize intermediation during agricultural process distribution of products in supply chain. ; Accompanying strategy for the social appropriation of new technologies in vulnerable agricultural communities: case in communities producing Gulupas fruits (Passiflora edulis Sims). ; Predictive model of transparency as an indicator of Public Policies. ; Smart system for recognition of ripening level in blackberry fruits. ; Project-based learning as an alternative methodology for technological education in electronics. ; Design and construction of an automated system for N. ; Four bar mechanisms (FBM) and their Software-Based applications: a reviewFT aquaponic culture of Red Carp and Crespa Lettuce. ; Intelligent search implementation for the construction of states of the art: a python application. ; Indoor and Outdoor propagation models on 5G environments: state of the art. ;The electronic detection of offenders (DOO) in the District Secretary of mobility of Bogotá: a step forward in the configuration of the concept of digital citizenship in Colombia. ; Monitoring through ICT of Mobility: technological collaborative feature to incorporate IoT in a Smart City. ; Characterization model of asphalt mixtures using digital image processing. ; Review: identification of diseases and/or pests in fruit trees through image processing techniques and artificial intelligence. ; VRS applicated to Nasa Yuwe language. ; Application of Pix2Pix for edge reconstruction in images. ; Brushless DC Motor Control System for Active Myoelectric Prosthesis. ; Implementation of a Water Conductivity Measuring System. ; 2 DOF robot programmed with MatLab® (guide and Peter Corke) and Arduino uno for writing alphabetical characters. ; Simulator of the behavior of the center of mass in a quadruped robot. ; Biomimetic prototype for flapping movement of bat

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy