Search for cosmic sources in neutrino telescopes and time calibration in the ANTARES neutrino telescope

Aunque la astronomía de neutrinos es una disciplina muy reciente, está resultando ser muy en un estado estimulante. Los diversos resultados publicados por la colaboración IceCube han mostrado la existencia de un flujo de neutrinos cósmicos de altas energías, del cual se desconoce su origen, y del que no se ha observado una dirección privilegiada. El telescopio de neutrinos ANTARES ha sido capaz de excluir la posibilidad de que algunos de los eventos observados por IceCube se hayan producido por una fuente puntual en la región del centro galáctico. Además, el último análisis de flujos difusos de ANTARES muestra un resultado compatible con el flujo observado por IceCube. Actualmente, existen tres telescopios de neutrinos en funcionamiento: ANTARES, IceCube y Baikal. Asimismo, la colaboración KM3NeT está construyendo la mayor red de telescopios de neutrinos jamás construida. Los análisis realizados en esta tesis se han utilizado con los datos obtenidos por parte de los telescopios ANTARES y IceCube, si bien también se han utilizado simulaciones oficiales de la colaboración KM3NeT. Dos han sido los objetivos principales de este trabajo. El primero ha consistido en la mejora de la actual calibración temporal del telescopio de neutrinos ANTARES para obtener la mejor reconstrucción de los datos. El segundo y principal ha consistido en mejorar nuestro conocimiento sobre la existencia de fuentes puntuales o extensas de neutrinos cósmicos. No ha habido observaciones estadísticamente significativas en las búsquedas realizadas. Además, se ha efectuado una estimación de la sensibilidad de KM3NeT para la búsqueda este tipo de fuentes. Se ha realizado una nueva calibración temporal para la mayoría del periodo de toma de datos de ANTARES. Esta calibración se ha realizado utilizando eventos que provenían de la desintegración de núcleos de K40, para la calibración “intra-storey” (determinación de desplazamientos de tiempo entre ARSs módulos ópticos de un mismo triplete), y utilizando la información de las distribuciones de los residuos obtenidos tras la reconstrucción de las trazas de muones atmosféricos, para las calibraciones “inter-line” (desplazamientos de tiempo entre líneas) y “inter-storey” (entre tripletes dentro de una misma línea). Gracias a esta nueva calibración, el número de eventos bien reconstruidos aumenta un 20%, lo cual indica una mejora en la calibración. En cuanto a la búsqueda de fuentes puntuales y extensas de neutrinos cósmicos, se incluyen los resultados de tres búsquedas. La primera corresponde al primer análisis combinado realizado entre dos colaboraciones diferentes, ANTARES y IceCube, en el cual se utilizaron los datos de ANTARES tomados entre 2007 y 2012, y los datos de IceCube correspondientes a las configuraciones de 40, 59 y 79 líneas (2008 a 2011). Sólo se consideraron eventos de tipo traza provenientes del cielo del hemisferio sur. Este análisis ha demostrado la complementariedad de ambos detectores para este tipo de búsquedas. IceCube presenta una mejor sensibilidad para neutrinos de altas energías debido a su mayor tamaño, pero presenta en el cielo del hemisferio sur una sensibilidad peor para eventos de energías menores de 100 TeV. Esto se debe a la aplicación de un corte en energía que depende de la declinación, el cual se utiliza para disminuir el fondo de muones atmosféricos. El segundo análisis corresponde a la búsqueda de fuentes puntuales y extensas utilizando los datos tomados por ANTARES entre 2007 y 2015. Este es el primer análisis de fuentes puntuales de ANTARES que incluye el uso tanto de eventos de tipo traza como eventos de tipo cascada, permitiendo así una búsqueda para todos los tipos (sabores) de neutrinos. Los eventos de tipo cascada reconstruidos por ANTARES presentan una resolución angular mediana entre 2 a 3 grados, la cual es significativamente mejor que la de IceCube. Aunque la reconstrucción angular de las cascadas es peor que la de los eventos de tipo traza, se observa una mejora de alrededor de un 20% en la sensibilidad cuando se añaden estos eventos. No se han observado acumulaciones significativas en ninguna de las búsquedas anteriores. El último análisis consiste en la estimación de la sensibilidad de KM3NeT para este tipo de búsquedas utilizando únicamente el canal de cascadas, en el que también se ha realizado un estudio detallado para dos fuentes candidatas de neutrinos, SNR RXJ 1713.7-3946 y Vela X.High energy neutrino astronomy is currently at an early yet intriguing stage. The first results observed by the IceCube Collaboration have shown the existence of a high energy neutrino flux of unknown origin with apparently no privileged direction. The ANTARES neutrino telescope has been able to exclude the possibility that some of these IceCube events events had been produced due to a point-source at the Galactic Centre region. Furthermore, the last diffuse-flux ANTARES analysis has shown a result which is compatible with the flux observed by IceCube. Currently, there are three high-energy neutrino telescopes in operation: ANTARES, IceCube and Baikal. Furthermore, the KM3NeT Collaboration is building the largest neutrino telescope network ever built. The analyses explained in this Thesis mostly deal with data taken from ANTARES and IceCube, although prospects of the future KM3NeT are also given. Two have been the main goals of the work presented. The first one has been to improve the current time calibration of the ANTARES neutrino telescope so to have the highest quality data possible. The second one has been to improve our knowledge about the existence of point and extended cosmic neutrino sources. No significant observations of these type of sources have been found in the analysis presented. Furthermore, an estimation of the sensitivity of particular point and extended source searches in the future KM3NeT telescope has been carried out. A 1 ns accuracy level in the time measurements is needed in order to be able to reconstruct events with a median angular resolution of 0.3 degrees for neutrino energies above 10 TeV. A new time calibration procedure has been performed for most of the data taking period of the ANTARES telescope. This calibration has been performed by using events coming from K40 disintegrations for the so-called intra-storey calibration (time offset determination between ARSs in the same storey), and by taking the information of the time residuals obtained after the reconstruction of down-going atmospheric muon events in the inter-line (time offsets between lines) and inter-storey (between storeys) calibrations. This new calibration procedure has shown to increase the number of well-reconstructed down going events, which indicates an improvement of the reconstruction. The results of three different searches of point and extended neutrino sources have been presented. The first one corresponds to the first combined analysis between ANTARES and IceCube, which used ANTARES data taken between 2007 and 2012, and IceCube data from the 40-, 59- and 79-strings configurations (2008 to 2011). Only track events coming from the Southern Sky were considered. This analysis has proven the complementarity of both detectors for these type of searches in the Southern Sky. IceCube presents a better sensitivity for high energy neutrinos due to its larger size, but a worse sensitivity for events with energies under 100 TeV because of the declination-dependent energy cut used to suppress the background of atmospheric muons. The second one is the point and extended source search using ANTARES data between 2007 and 2015, which corresponds to the first published analysis that includes shower events in this type of analysis in ANTARES, allowing an all neutrino flavour search. A better angular resolution in shower-like events is observed in ANTARES compared to Ice- Cube, leading to a value between 2 and 3 degrees for the former. Even if the angular resolution for showers is worse compared to track-like events, an improvement of approximately 20% on the sensitivity is achieved with the addition of these events. No significant clusters have been observed in these searches. The last one corresponds to the performance estimation of the future KM3NeT telescope for these type of searches by using only the cascade channel, in which a detailed study for two candidate galactic neutrino sources, SNR RXJ 1713,7-3946 and PWN Vela X is also performed

Enhanced antitumor efficacy of oncolytic adenovirus-loaded menstrual blood-derived mesenchymal stem cells in combination with peripheral blood mononuclear cells

Several studies have evaluated the efficacy of using human oncolytic adenovirus-loaded mesenchymal stem cells for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5, for treatment of neuroblastoma patients. Results from this clinical trial point out the role of the immune system in the clinical outcome. In this context, a better understanding of the immunophenotypic changes of human mesenchymal stem cells upon adenoviral infection and how these changes affect human autologous or allogeneic peripheral blood mononuclear cells (PBMCs) could guide strategies to improve the antitumor efficacy of infected Mesenchymal Stem Cells (MSCs). In this work, we show how infection by an oncolytic adenovirus (OAdv) induces Toll-like receptor 9 overexpression and activation of the NF-κB pathway in menstrual blood-derived mesenchymal stem cells (MenSCs), leading to a specific cytokine secretion profile. Moreover, a pro-inflammatory environment, mainly mediated by monocyte activation that leads to the activation of both T-cells and natural killer cells (NK cells), is generated when OAdv-loaded MenSCs are co-cultured with allogeneic PBMCs. This combination of allogeneic PBMCs and OAdv-loaded MenSCs enhances antitumor efficacy both in vitro and in vivo, an effect partially mediated monocytes and NK cells. Altogether our results demonstrate not only the importance of the immune system for the oncolytic adenovirus-loaded MSCs antitumor efficacy, but in particular the benefits of using allogeneic MSCs for this therapy

Effect of Linker Distribution in the Photocatalytic Activity of Multivariate Mesoporous Crystals

The use of Metal-Organic Frameworks as crystalline matrices for the synthesis of multiple component or multivariate solids by the combination of different linkers into a single material has emerged as a versatile route to tailor the properties of single-component phases or even access new functions. This approach is particularly relevant for Zr6-MOFs due to the synthetic flexibility of this inorganic node. However, the majority of materials are isolated as polycrystalline solids, which are not ideal to decipher the spatial arrangement of parent and exchanged linkers for the formation of homogeneous structures or heterogeneous domains across the solid. Here we use high-throughput methodologies to optimize the synthesis of single crystals of UiO-68 and UiO-68-TZDC, a photoactive analogue based on a tetrazine dicarboxylic derivative. The analysis of the single linker phases reveals the necessity of combining both linkers to produce multivariate frameworks that combine efficient light sensitization, chemical stability, and porosity, all relevant to photocatalysis. We use solvent-assisted linker exchange reactions to produce a family of UiO-68-TZDC% binary frameworks, which respect the integrity and morphology of the original crystals. Our results suggest that the concentration of TZDC in solution and the reaction time control the distribution of this linker in the sibling crystals for a uniform mixture or the formation of core-shell domains. We also demonstrate how the possibility of generating an asymmetric distribution of both linkers has a negligible effect on the electronic structure and optical band gap of the solids but controls their performance for drastic changes in the photocatalytic activity toward proton or methyl viologen reduction.This work was supported by the EU (ERC Stg Chem-fs-MOF 714122) and Spanish government (CTQ2017-83486-P, RTI2018-098568-A-I00, RYC-2016-1981, CEX2019-000919-M, PID2019-106383GB-C44/AEI/10.13039/501100011033 and RTI2018-098568-A-I00). B.L.-B. thanks the Spanish government for a FPU (FPU16/04162). S.T. thanks the Spanish government for a Ramón y Cajal Fellowship (RYC-2016-60719817). N.M.P. thanks the European Union for a Marie Skłodowska-Curie Global Fellowship (H2020-MSCA-IF-2016-GF-749359-EnanSET). J.G.P. thanks to the SIDIX at Servicios Generales de Apoyo a la Investigación (SEGAI) at La Laguna University. We also thank BSC-RES for computational resources (QS-2020-2-0024) and the University of Valencia for research facilities (Tirant and NANBIOSIS).Peer reviewe

Empresas recuperadas mediante cooperativas de trabajo : Viabilidad de una alternativa

El presente artículo procura una síntesis de la investigación homónima. La misma se propone identificar los elementos que permitan potenciar la viabilidad, crecimiento y autonomía de las cooperativas de trabajo surgidas a partir del cierre o quiebra de empresas capitalistas. Se parte siempre de un enfoque comparativo entre Uruguay y Argentina, tomando en cuenta las especificidades del fenó- meno. El relevamiento de la información se sustenta fundamentalmente en el testimonio de los actores involucrados. Se explora el proceso de recuperación de las empresas, el protagonismo de los trabajadores y las razones de la cooperativización. A través de la constitución de una batería de información actualizada y sistematizada la investigación pretende poner a disposición de los propios protagonistas elementos conceptuales que enriquezcan y potencien su accionar, así como contribuir a la proyección de una intervención eficaz en las mencionadas cooperativas por parte de técnicos y asesores diversos.O presente artigo mostra uma síntese da pesquisa homônima. Propõe-se identificar os elementos que possibilitam ampliar a viabilidade, crescimento e autonomia das cooperativas de trabalho, surgidas a partir do fechamento ou da falência de empresas capitalistas. Parte-se sempre de um enfoque comparativo entre Uruguai e Argentina, levando em consideração as especificidades do fenômeno. A importância da informação está embasada fundamentalmente no testemunho dos atores envolvidos. Explora-se o processo de recupera- ção das empresas, o papel dos trabalhadores e as razões que levam ao cooperativismo. Por meio da composição de uma série de informações atualizadas e sistematizadas, a pesquisa pretende colocar à disposição dos próprios protagonistas elementos conceituais que enriqueçam e potencializem seu funcionamento, bem como contribuir à projeção de uma intervenção eficaz nas cooperativas mencionadas por parte de técnicos e assessores diversos.Facultad de Ciencias Económica

Hydroxamate Titanium−Organic Frameworks and the Effect of Siderophore-Type Linkers over Their Photocatalytic Activity

The chemistry of Metal-Organic Frameworks (MOFs) relies on the controlled linking of organic molecules and inorganic secondary building units to assemble an unlimited number of reticular frameworks. However, the design of porous solids with chemical stability remains still limited to carboxylate or azolate groups. There is a timely opportunity to develop new synthetic platforms that make use of unexplored metal binding groups to produce metal-linker joints with hydrolytical stability. Living organisms use siderophores (iron carriers in greek) to effectively assimilate iron in soluble form. These compounds make use of hard oxodonors as hydroxamate or catecholate groups to coordinate metal Lewis acids like iron, aluminium or titanium to form metal complexes very stable in water. Inspired by the chemistry of these microorganisms, we report the first hydroxamate MOF prepared by direct synthesis. MUV-11 (MUV = Materials of Universidad de Valencia) is a crystalline, porous material (close to 800 m2·g-1) that combines photoactivity with good chemical stability in acid conditions. By using a high-throughput approach, we also demonstrate that this new chemistry is compatible with the formation of single crystalline phases for multiple titanium salts, thus expanding the scope of precursors accessible. Titanium frameworks are regarded as promising materials for photocatalytic applications. Our photoelectrochemical and catalytic tests suggests important differences for MUV-11. Compared to other Ti-MOFs, changes in the photoelectrochemical and photocatalytic activity have been rationalized with computational modelling revealing how the chemistry of siderophores can introduce changes to the electronic structure of the frontier orbitals, relevant to the photocatalytic activity of these solids

Bottom‐Up Fabrication of Semiconductive Metal-Organic Framework Ultrathin Films

Though generally considered insulating, recent progress on the discovery of conductive porous metal-organic frameworks (MOFs) offers new opportunities for their integration as electroactive components in electronic devices. Compared to classical semiconductors, these metal-organic hybrids combine the crystallinity of inorganic materials with easier chemical functionalization and processability. Still, future development depends on the ability to produce high-quality films with fine control over their orientation, crystallinity, homogeneity, and thickness. Here self-assembled monolayer substrate modification and bottom-up techniques are used to produce preferentially oriented, ultrathin, conductive films of Cu-CAT-1. The approach permits to fabricate and study the electrical response of MOF-based devices incorporating the thinnest MOF film reported thus far (10 nm thick)

Empresas recuperadas mediante cooperativas de trabajo : Viabilidad de una alternativa

El presente artículo procura una síntesis de la investigación homónima. La misma se propone identificar los elementos que permitan potenciar la viabilidad, crecimiento y autonomía de las cooperativas de trabajo surgidas a partir del cierre o quiebra de empresas capitalistas. Se parte siempre de un enfoque comparativo entre Uruguay y Argentina, tomando en cuenta las especificidades del fenómeno. El relevamiento de la información se sustenta fundamentalmente en el testimonio de los actores involucrados. Se explora el proceso de recuperación de las empresas, el protagonismo de los trabajadores y las razones de la cooperativización. A través de la constitución de una batería de información actualizada y sistematizada la investigación pretende poner a disposición de los propios protagonistas elementos conceptuales que enriquezcan y potencien su accionar, así como contribuir a la proyección de una intervención eficaz en las mencionadas cooperativas por parte de técnicos y asesores diversos.O presente artigo mostra uma síntese da pesquisa homônima. Propõe-se identificar os elementos que possibilitam ampliar a viabilidade, crescimento e autonomia das cooperativas de trabalho, surgidas a partir do fechamento ou da falência de empresas capitalistas. Parte-se sempre de um enfoque comparativo entre Uruguai e Argentina, levando em consideração as especificidades do fenômeno. A importância da informação está embasada fundamentalmente no testemunho dos atores envolvidos. Explora-se o processo de recupera- ção das empresas, o papel dos trabalhadores e as razões que levam ao cooperativismo. Por meio da composição de uma série de informações atualizadas e sistematizadas, a pesquisa pretende colocar à disposição dos próprios protagonistas elementos conceituais que enriqueçam e potencializem seu funcionamento, bem como contribuir à projeção de uma intervenção eficaz nas cooperativas mencionadas por parte de técnicos e assessores diversos.Facultad de Ciencias Económica

Empresas recuperadas mediante cooperativas de trabajo : Viabilidad de una alternativa

El presente artículo procura una síntesis de la investigación homónima. La misma se propone identificar los elementos que permitan potenciar la viabilidad, crecimiento y autonomía de las cooperativas de trabajo surgidas a partir del cierre o quiebra de empresas capitalistas. Se parte siempre de un enfoque comparativo entre Uruguay y Argentina, tomando en cuenta las especificidades del fenómeno. El relevamiento de la información se sustenta fundamentalmente en el testimonio de los actores involucrados. Se explora el proceso de recuperación de las empresas, el protagonismo de los trabajadores y las razones de la cooperativización. A través de la constitución de una batería de información actualizada y sistematizada la investigación pretende poner a disposición de los propios protagonistas elementos conceptuales que enriquezcan y potencien su accionar, así como contribuir a la proyección de una intervención eficaz en las mencionadas cooperativas por parte de técnicos y asesores diversos.O presente artigo mostra uma síntese da pesquisa homônima. Propõe-se identificar os elementos que possibilitam ampliar a viabilidade, crescimento e autonomia das cooperativas de trabalho, surgidas a partir do fechamento ou da falência de empresas capitalistas. Parte-se sempre de um enfoque comparativo entre Uruguai e Argentina, levando em consideração as especificidades do fenômeno. A importância da informação está embasada fundamentalmente no testemunho dos atores envolvidos. Explora-se o processo de recupera- ção das empresas, o papel dos trabalhadores e as razões que levam ao cooperativismo. Por meio da composição de uma série de informações atualizadas e sistematizadas, a pesquisa pretende colocar à disposição dos próprios protagonistas elementos conceituais que enriqueçam e potencializem seu funcionamento, bem como contribuir à projeção de uma intervenção eficaz nas cooperativas mencionadas por parte de técnicos e assessores diversos.Facultad de Ciencias Económica

Search for Multimessenger Sources of Gravitational Waves and High-energy Neutrinos with Advanced LIGO during Its First Observing Run, ANTARES, and IceCube

Astrophysical sources of gravitational waves, such as binary neutron star and black hole mergers or core-collapse supernovae, can drive relativistic outflows, giving rise to non-thermal high-energy emission. High-energy neutrinos are signatures of such outflows. The detection of gravitational waves and high-energy neutrinos from common sources could help establish the connection between the dynamics of the progenitor and the properties of the outflow. We searched for associated emission of gravitational waves and high-energy neutrinos from astrophysical transients with minimal assumptions using data from Advanced LIGO from its first observing run O1, and data from the Antares and IceCube neutrino observatories from the same time period. We focused on candidate events whose astrophysical origins could not be determined from a single messenger. We found no significant coincident candidate, which we used to constrain the rate density of astrophysical sources dependent on their gravitational-wave and neutrino emission processes

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3