Prospects of Detecting Non-thermal Protons in Solar Flares via Lyman Line Spectroscopy: Revisiting the Orrall-Zirker Effect

Solar flares are efficient particle accelerators, with a substantial fraction of the energy released manifesting as non-thermal particles. While the role that non-thermal electrons play in transporting flare energy is well studied, the properties and importance of non-thermal protons is rather less well understood. This is in large part due to the paucity of diagnostics, particularly at the lower-energy (deka-keV) range of non-thermal proton distributions in flares. One means to identify the presence of deka-keV protons is by an effect originally described by \cite{1976ApJ...208..618O}. In the Orrall-Zirker effect, non-thermal protons interact with ambient neutral hydrogen, and via charge exchange produce a population of energetic neutral atoms (ENAs) in the chromosphere. These ENAs subsequently produce an extremely redshifted photon in the red wings of hydrogen spectral lines. We revisit predictions of the strength of this effect using modern interaction cross-sections, and numerical models capable of self-consistently simulating the flaring non-equilibrium ionization stratification, and the non-thermal proton distribution (and, crucially, their feedback on each other). We synthesize both the thermal and non-thermal emission from \lya\ and \lyb, the most promising lines that may exhibit a detectable signal. These new predictions are are weaker and more transient than prior estimates, but the effects should be detectable in fortuitous circumstances. We degrade the \lyb\ emission to the resolution of the Spectral Imaging of the Coronal Environment (SPICE) instrument on board Solar Orbiter, demonstrating that though likely difficult, it should be possible to detect the presence of non-thermal protons in flares observed by SPICE.Comment: Accepted for publication in The Astrophysical Journa

Antiarrhythmic mechanisms of Malbec wine and resveratrol in isolated rat heart

Oxidative stress during myocardial reperfusion contributes to ventricular arrhythmias onset. We aim to evaluate the antiarrhythmic effect of Malbec wine and resveratrol and compare them with the synthetic antioxidant tiron. Since alcohol use is controversial, we also assessed dealcoholized wine.Isolated hearts from male Sprague Dawley rats were perfused with Krebs-Henseleit solution added with: Malbec wine (5 ml/L), resveratrol (10 μM,) compared to controls with alcohol (0.5 ml/L); dealcoholized wine (5 ml/L), tiron (10 mM) were compared with controls without alcohol. Epicardial action potentials were analyzed during basal state, regional ischemia and reperfusion (10 minutes each period). The incidence of arrhythmias was determined. Te antioxidant effect was assessed in left ventricle homogenates and expressed as a percentage of inhibition of the ABTS?+ radical.Malbec wine and resveratrol reduced reperfusion arrhythmias in 56% and 50%, respectively, compared to 100% incidence in the control group with alcohol. Dealcoholized wine reduced arrhythmias to 50% compared to non-alcoholic control (90.5%), but tiron did not protect (69%). Te free radicals inhibitory effect increased with all the compounds (resveratrol 54.2%, tiron 43.2%, Malbec wine 42.9%, dealcoholized wine 40.2%) with respect to the control groups (with alcohol 23.5%, without alcohol 21.2%). Resveratrol shortened action potential duration and prevented ischemic depolarization. Malbec prevented ischemic-induced action potential shortening. We conclude that Malbec wine and resveratrol are antiarrhythmic beyond their antioxidant properties. Alcohol content or was not essential. Protection from ischemic action potential changes could be relevant to the antiarrhythmic effect of both resveratrol and wine.Fil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Perdicaro DJ. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Parra, M. Universidad Nacional de Cuyo Facultad de Ciencias Médicas; ArgentinaFil: Carrión AM. Universidad Nacional de Cuyo Facultad de Ciencias Médicas; ArgentinaFil: Miatello RM. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Renna NF. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ponce Zumino AZ. Universidad Nacional de Cuyo Facultad de Ciencias Médicas; ArgentinaFil: Vazquez Prieto M. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Diez ER. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia

Frontotemporal dementia (FTD) is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro FTD disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of FTD astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development

The time scale of recombination rate evolution in great apes

We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471-475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10-15Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- And between-species genome-wide recombination rate variation in several close relatives

Relaciones interculturales, mercado de trabajo y localización socio-espacial de los inmigrantes bolivianos que residen en áreas urbanas y periurbanas de la ciudad de Córdoba

Este proyecto estudiará los procesos de segmentación del mercado laboral y de segregación socio-espacial de los inmigrantes bolivianos en áreas urbanas y peri-urbanas de la ciudad de Córdoba, y las maneras en que dichos procesos son justificados a través de estereotipos basados en distinciones culturales y/o raciales. Focalizaremos sobre las relaciones de desigualdad y de explotación que signan el mercado de trabajo y otros espacios de sociabilidad en el contexto actual de acumulación del capital. Nos planteamos las siguientes hipótesis: 1) Los inmigrantes bolivianos que residen en la ciudad de Córdoba se vinculan, como mano de obra no calificada, con un mercado laboral informal segmentado étnicamente, en el marco de procesos discriminatorios basados en estereotipos étnico-raciales. 2) Algunos inmigrantes bolivianos lograron cierta movilidad económicoproductiva, convirtiéndose en patrones de sus co-nacionales en diferentes sectores (construcción, horticultura, comercio informal, industria de indumentaria), hecho que es facilitado por la activación de redes migratorias. 3) Los estereotipos sobre los bolivianos son re-significados y, a veces, confrontados por agentes vinculados con los medios y con organismos gubernamentales y no gubernamentales. 4) La segregación residencial es otro mecanismo discriminatorio que favorece la exclusión de los inmigrantes trabajadores. Nuestro objetivo principal es caracterizar los diferentes ámbitos laborales en los que se desempeñan los inmigrantes bolivianos en la ciudad de Córdoba y conceptualizar las relaciones inter e intra culturales que se dan en ese marco, teniendo en cuenta la incidencia de: las redes migratorias, las trayectorias migratorias y laborales, y la heterogeneidad de los capitales de los inmigrantes; la localización socio-espacial de los lugares de trabajo y de otros espacios de sociabilidad; y, las maneras en que diversos agentes reproducen o confrontan los estereotipos sobre los bolivianos. Se aplicará una estrategia de triangulación de métodos y de técnicas. Desde un enfoque cuantitativo analizaremos los aspectos socio-demográficos de la población de origen boliviano que reside en la ciudad de Córdoba, teniendo en cuenta su inserción laboral y ubicación socio-espacial en áreas urbanas y peri-urbanas. Se analizarán periódicos de edición provincial y aquellos editados por organizaciones de inmigrantes bolivianos en Córdoba y en Buenos Aires. Se caracterizarán las acciones y políticas destinadas a inmigrantes bolivianos. Se realizarán estudios etnográficos de casos en las áreas urbanas y peri-urbanas en donde residen y/o trabajan inmigrantes bolivianos. Se desarrollarán talleres destinados a inmigrantes bolivianos con el objetivo de reflexionar sobre sus derechos laborales y sus derechos como inmigrantes.Fil: Pizarro, Cynthia Alejandra. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; ArgentinaFil: Fontana, Silvia Esther. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; ArgentinaFil: Conrero, Sofía. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; ArgentinaFil: Universidad Católica de Córdoba; Argentina

A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity

The costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with Fc gamma R interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8(N)/(C)EGa1, consisting of three anti-4-1BB single-chain variable fragments and three anti-EGFR single-domain antibodies positioned in an extended hexagonal conformation around the collagen XVIII homotrimerization domain. The1D8(N)/(C)EGa1 trimerbody demonstrated high-avidity binding to 4-1BB and EGFR and a potent in vitro costimulatory capacity in the presence of EGFR. The trimerbody rapidly accumulates in EGFR-positive tumors and exhibits anti-tumor activity similar to IgG-based 4-1BB-agonistic mAbs. Importantly, treatment with 1D8(N)/(C)EGa1 does not induce systemic inflammatory cytokine production or hepatotoxicity associated with IgG-based 4-1BB agonists. These results implicate Fc gamma R interactions in the 4-1BB-agonist-associated immune abnormalities, and promote the use of the non-canonical antibody presented in this work for safe and effective costimulatory strategies in cancer immunotherapy

Mapping child growth failure across low- and middle-income countries

Child growth failure (CGF), manifested as stunting, wasting, and underweight, is associated with high 5 mortality and increased risks of cognitive, physical, and metabolic impairments. Children in low- and middle-income countries (LMICs) face the highest levels of CGF globally. Here we illustrate national and subnational variation of under-5 CGF indicators across LMICs, providing 2000–2017 annual estimates mapped at a high spatial resolution and aggregated to policy-relevant administrative units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the World Health 10 Organization’s ambitious Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and rates of progress exist across regions, countries, and within countries; our maps identify areas where high prevalence persists even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where subnational disparities exist and the highest-need populations reside, these geospatial estimates can support policy-makers in planning locally 15 tailored interventions and efficient directing of resources to accelerate progress in reducing CGF and its health implications

Mapping disparities in education across low- and middle-income countries

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations. Educational attainment is an important social determinant of maternal, newborn, and child health(1-3). As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting(4-6). The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness(7,8); however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health(9-11). Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but-to our knowledge-no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries(12-14). By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.Peer reviewe