78 research outputs found

    Chaotic dynamics in coupled resonator sequences

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    Optically induced thermal and free carrier nonlinearities in silicon micro-ring resonator influence their behavior. They can be either deleterious by making them instable and by driving their resonances out of the designed wavelengths, or enabler of different applications. Among the most interesting one, there are optical bistability and self induced oscillations. These lead to all optical logic, signal modulation, optical memories and applications in neural networks. Here, we theoretically and experimentally demonstrate that when many resonators are coupled together, thermal and free carrier nonlinearities induce also chaos. The chaotic dynamics are deeply analyzed using experimentally reconstructed phase space trajectories and the tool of Lyapunov exponents

    Deamidation drives molecular aging of the SARS-CoV-2 spike protein receptor-binding motif

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    The spike protein is the main protein component of the SARS-CoV-2 virion surface. The spike receptor-binding motif mediates recognition of the human angiotensin-converting enzyme 2 (hACE2) receptor, a critical step in infection, and is the preferential target for spikeneutralizing antibodies. Post-translational modifications of the spike receptor-binding motif have been shown to modulate viral infectivity and host immune response, but these modifications are still being explored. Here we studied asparagine deamidation of the spike protein, a spontaneous event that leads to the appearance of aspartic and isoaspartic residues, which affect both the protein backbone and its charge. We used computational prediction and biochemical experiments to identify five deamidation hotspots in the SARS-CoV-2 spike protein. Asparagine residues 481 and 501 in the receptor-binding motif deamidate with a half-life of 16.5 and 123 days at 37°C, respectively. Deamidation is significantly slowed at 4°C, indicating a strong dependence of spike protein molecular aging on environmental conditions. Deamidation of the spike receptor-binding motif decreases the equilibrium constant for binding to the hACE2 receptor more than 3.5-fold, yet its high conservation pattern suggests some positive effect on viral fitness. We propose a model for deamidation of the full SARS-CoV-2 virion illustrating how deamidation of the spike receptor-binding motif could lead to the accumulation on the virion surface of a nonnegligible chemically diverse spike population in a timescale of days. Our findings provide a potential mechanism for molecular aging of the spike protein with significant consequences for understanding virus infectivity and vaccine development.Fil: Lorenzo Lopez, Juan Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Defelipe, Lucas Alfredo. European Molecular Biology Laboratory; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Aliperti Car, Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Niebling, Stephan. European Molecular Biology Laboratory; Alemania. Centre for Structural Systems Biology; AlemaniaFil: Custódio, Tânia F.. European Molecular Biology Laboratory; Alemania. Centre for Structural Systems Biology; AlemaniaFil: Löw, Christian. European Molecular Biology Laboratory; Alemania. Centre for Structural Systems Biology; AlemaniaFil: Schwarz, Jennifer J.. European Molecular Biology Laboratory; AlemaniaFil: Remans, Kim. European Molecular Biology Laboratory; AlemaniaFil: Craig, Patricio Oliver. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Lisandro Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: García Alai, María. European Molecular Biology Laboratory; Alemania. Centre for Structural Systems Biology; AlemaniaFil: Sánchez Miguel, Ignacio Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Alonso, Leonardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentin

    Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells.

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    Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, we describe that postsynaptic DCs switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor Ccr7 as a proof-of-concept gene that is increased in postsynaptic DCs. Consistent with our epigenomic observations, postsynaptic DCs migrate more efficiently toward CCL19 in vitro and display enhanced homing to draining lymph nodes in vivo. This work describes a previously unknown DC population whose transcriptomics, epigenomics, and migratory capacity change in response to their cognate contact with T cells.This study was supported by grant SAF2017-82886-R from the Spanish Ministry of Economy and Competitiveness (MINECO), grant S2017/BMD-3671-INFLAMUNE-CM from the Comunidad de Madrid, a grant from the Ramon Areces Foundation “Ciencias de la Vida y la Salud” (XIX Concurso-2018), a grant from Ayudas Fundacion BBVA a Equipos de Investigacion Cientifica (BIOMEDICINA-2018), the Fundacio Marato TV3 (grant 122/C/2015), “la Caixa” Banking Foundation (HR17-00016), BIOIMID (PIE13/041) from Instituto de Salud Carlos III, CIBER Cardiovascular (CB16/11/00272), and Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). D.C.-F. is supported by a Fellowship from “la Caixa” Foundation (LCF/BQ/DR19/11740010). I.F.-D. is supported by a Fellowship from the Spanish Ministry of Science, Innovation, and Universities (FPU15/02539). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015- 0505). Funding agencies did not intervene in the design of the studies, with no copyright over the study.S

    Extensive Sheep and Goat Production: The Role of Novel Technologies towards Sustainability and Animal Welfare

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    [EN] Sheep and goat extensive production systems are very important in the context of global food security and the use of rangelands that have no alternative agricultural use. In such systems, there are enormous challenges to address. These include, for instance, classical production issues, such as nutrition or reproduction, as well as carbon-efficient systems within the climate-change context. An adequate response to these issues is determinant to economic and environmental sustainability. The answers to such problems need to combine efficiently not only the classical production aspects, but also the increasingly important health, welfare, and environmental aspects in an integrated fashion. The purpose of the study was to review the application of technological developments, in addition to remote-sensing in tandem with other state-of-the-art techniques that could be used within the framework of extensive production systems of sheep and goats and their impact on nutrition, production, and ultimately, the welfare of these species. In addition to precision livestock farming (PLF), these include other relevant technologies, namely omics and other areas of relevance in small-ruminant extensive production: heat stress, colostrum intake, passive immunity, newborn survival, biomarkers of metabolic disease diagnosis, and parasite resistance breeding. This work shows the substantial, dynamic nature of the scientific community to contribute to solutions that make extensive production systems of sheep and goats more sustainable, efficient, and aligned with current concerns with the environment and welfareSIThe CECAV authors acknowledge financial support of the research unit, which was financed by the National Funds from FCT, the Portuguese Foundation for Science and Technology (FCT), project number UIDB/CVT/00772/2020. Financial support from FCT (Fundação para a Ciência e a Tecnologia, Lisboa, Portugal) in the form of infrastructural funding to LEAF (UID/AGR/04129) and PhD grants SFRH/BD/143992/2019 (DM Ribeiro) and 2021.07638.BD (L Sacarrão-Birrento). Author L.E.H.C. acknowledges funding from the Agencia Estatal de Investigación (Spain) (RYC2019- 027064-I/AEI/10.13039/501100011033

    El cambio climático y las condiciones ambientales en los partidos de La Plata, Berisso y Ensenada, provincia de Buenos Aires: aspectos preliminares

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    Se presentan las tareas iniciales realizadas en relación al proyecto Efectos del cambio climático en las condiciones ambientales de los Partidos de Berisso, Ensenada y La Plata, que es financiado por la Universidad Nacional de La Plata en el marco del programa de “Proyectos de innovación y transferencia en áreas prioritarias (PIT-AP). Con este proyecto, iniciado en 2011, se propone avanzar en el conocimiento y evaluación de la influencia que generan los cambios climáticos en las condiciones ambientales del borde sur del Río de La Plata. Estos cambios pueden producir importantes efectos en el desarrollo socioeconómico y en los riesgos a que se encuentra sometida esta región. Debido a la escasez de datos básicos y la falta de un conocimiento adecuado de las condiciones ambientales de la región, se están realizando los estudios geológicos, geomorfológicos, hidrológicos, ecológicos y topográficos necesarios para el modelado de posibles escenarios de los cambios climáticos

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

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    Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

    Search for single production of vector-like quarks decaying into Wb in pp collisions at s=8\sqrt{s} = 8 TeV with the ATLAS detector

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    Measurements of top-quark pair differential cross-sections in the eμe\mu channel in pppp collisions at s=13\sqrt{s} = 13 TeV using the ATLAS detector

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