Role of β-adrenergic modulation in myocardial ischemia/reperfusion injury. Mechanisms underlying cardioprotection

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 18-12-2017The β-adrenergic system plays an important role in the regulation of heart function. The early intravenous administration of ß1-adrenergic receptor (ADRB1)-antagonist, metoprolol, in patients with ST-segment elevation acute myocardial infarction (AMI) reduces the extent of infarct size. The prevailing view has been that metoprolol acts mainly on cardiomyocytes function, reducing cardiac output. This work presents evidence that metoprolol reduces ischemia/reperfusion injury by targeting the hematopoietic compartment, specifically by inhibiting neutrophil function through an ADRB1 signallingdependent manner. Metoprolol acts during early phases of neutrophil recruitment, impairing structural and functional rearrangements necessary for effective interactions with circulating platelets to occur. Metoprolol, “stuns” neutrophils that cannot engage the structural conformation necessary to infiltrate tissues, triggering erratic intravascular dynamics and overall blunted inflammation. The in vitro functional assays confirm direct effect on neutrophils through an ADRB1-dependent mechanism. The depletion of circulating neutrophils, the lack of the Adrb1 in hematopoietic cells and the blockade of P-selectin glycoprotein ligand-1, the receptor involved in neutrophil-platelet interactions, result in a complete abrogation of metoprolol´s infarct-limiting effect. Moreover, the association between neutrophil count and microvascular obstruction is abolished in early metoprolol-treated AMI patients. Metoprolol has no direct effect on platelet function, but inhibits neutrophil-platelet interactions in AMI patients by targeting neutrophils directly. Identification of the relevant role of ADRB1 in hematopoietic cells during acute injury and the protective role upon its modulation offers potential for developing new therapeutic strategies.El sistema β-adrenérgico juega un papel importante en la regulación de la función cardíaca. La administración intravenosa y previa a la reperfusión del antagonista ß1-adrenérgico (ADRB1) específico metoprolol, en pacientes con infarto agudo de miocardio con elevación del segmento ST, reduce el tamaño final del infarto. Clásicamente se ha considerado que el metoprolol actúa principalmente sobre los miocardiocitos disminuyendo el gasto cardíaco. Este trabajo presenta por primera vez evidencia de que el metoprolol reduce el daño por isquemia/reperfusión cardiaco actuando directamente sobre el compartimento hematopoyético, inhibiendo de manera específica la cascada de señalización dependiente del ADRB1 en los neutrófilos. El metoprolol actúa durante las primeras etapas del reclutamiento de células inflamatorias al miocardio. Altera la conformación estructural y función neutrofílica, impidiendo que se establezcan interacciones eficientes entre los neutrófilos y las plaquetas circulantes. El metoprolol "aturde" los neutrófilos circulantes, provocando un comportamiento errático que termina abortando su infiltración y por tanto su acción inflamatoria general en los tejidos. Los ensayos funcionales in vitro realizados confirman un efecto directo del metoprolol sobre los neutrófilos dependiente de ADRB1. La depleción de neutrófilos circulantes, la falta de Adrb1 en las células hematopoyéticas y el bloqueo del ligando-1 de la glucoproteína P-selectina, el cual está involucrado en las interacciones de neutrófilos con las plaquetas circulantes, inhiben el efecto limitante sobre el tamaño de infarto del metoprolol. Estos resultados indican que la presencia de ADRB1 en los neutrófilos es indispensable para que el metoprolol ejerza su acción protectora. Además, pacientes con infarto agudo de miocardio (IAM) tratados con metoprolol presentan abrogación de la asociación entre las cuentas de neutrófilos en sangre y la obstrucción microvascular. Por último, el metoprolol no tiene efecto directo sobre la función plaquetaria, e inhibe las interacciones de neutrófilos y plaquetas en pacientes con IAM ejerciendo su efecto directamente sobre los neutrófilos. La identificación del papel de ADRB1 en las células hematopoyéticas durante la lesión aguda y la función protectora de su modulación ofrece el potencial para desarrollar nuevas estrategias terapéuticas

Adaptation of the Electric Machines Learning Process to the European Higher, Education Area

In this paper the basic lines of a complete teaching methodology that has been developed to adaptthe electric machines learning process to the European Higher Education Area (EHEA) arepresented. New teaching materials that are specific to Electric Machines have been created(textbooks, self-learning e-books, guidelines for achieving teamwork research, etc.). Working ingroups has been promoted, as well as problem solving and self-learning exercises, all of which areevaluated in a way that encourages students' participation. Finally, the students' learning process inthe lab has been improved by the development both of a new methodology to follow in the lab andnew workbenches with industrial machines that are easier to use and also enable the labexperiments to be automated. Finally, the first results obtained as a result of applying the proposedmethodology are presented

Scoring coordination patterns in basketball international championships of national teams

The performance of two basketball teams can be analysed by exploring their different scoring dynamics on the basis of the two time series representing the scoring process of each team throughout the game. Existing studies following this approach focused mainly on regular season and playoff games in different basketball leagues. The aim of this study was to conduct this type of analysis on games of National Teams championships, focusing specifically on final round close games, as those in which medals are decided and teams perform in a very similar level. The study considers the final round games (i.e. semi-finals games, third-place game and final game) of the main men's professional basketball International Championships of National Teams (i.e. European Championships, World Championships and Olympic Games) played during the period 2005-2013. Different methods of time series analysis were used (i.e. autocorrelation and cross-correlation functions, double backward moving averages, Hilbert transform). The results revealed an increasing scoring coordination pattern between the teams as the games unfolded, showing extremely high coordinated behaviours in the 3rd and 4th quarters (i.e. similar scoring streaks by the two teams; back-and-forth scoring patterns). This suggests that are the first two quarters of the games those leading to major fluctuations on the scoreboard (i.e. game periods in which one team's scoring performance is very successful whilst the other team's is not). This study may be matter of interest to coaches and performance analysts in the field of basketball, providing practical information for specific games preparations in International Championships of National Teams.El rendimiento de dos equipos de baloncesto se puede analizar mediante la exploración de sus diferentes dinámicas de anotación sobre la base de las dos series temporales que representan el proceso anotador de cada equipo durante todo el partido. Los estudios existentes siguiendo este enfoque se han centrado principalmente en partidos de temporada regular y de playoff en diferentes ligas de baloncesto. El objetivo de este estudio fue llevar a cabo este tipo de análisis en partidos de campeonatos de selecciones nacionales, centrándose específicamente en los partidos ajustados de las rondas finales, como aquellos en los que se deciden las medallas y en los que los equipos desempeñan en un nivel muy similar. El estudio considera los partidos de las rondas finales (semifinales, tercer y cuarto puesto, y final) de los principales campeonatos internacionales de baloncesto de selecciones nacionales en categoría masculina (Campeonatos Europeos, Campeonatos del Mundo y Juegos Olímpicos) disputados durante el período 2005-2013. Se utilizaron diferentes métodos de análisis de series temporales (funciones de autocorrelación y correlación cruzada, doble media móvil, transformada de Hilbert). Los resultados revelaron un patrón creciente de coordinación anotadora entre los equipos a medida que los partidos avanzaban, mostrando patrones de coordinación extremadamente altos en el tercer y último cuarto (rachas de anotación similares para los dos equipos, patrones de anotación de ida y vuelta). Esto sugiere que son los dos primeros cuartos de los partidos aquellos que conducen a mayores fluctuaciones en el marcador (períodos de juego en los que el rendimiento anotador de un equipo es muy exitoso, mientras que el del otro equipo no lo es). Este estudio puede ser de interés para los entrenadores y analistas de rendimiento en baloncesto, proporcionando información práctica para la preparación específica de partidos en los campeonatos internacionales de selecciones nacionales

Efecto de las estelas en los parques eólicos

Para el diseño de parques eólicos es de interés conocer la producción de energía eléctrica de las turbinas eólicas, o aeroturbinas, así como las cargas que pueden sufrir las mismas limitando su vida útil. La producción de energía está ligada a la intensidad del viento incidente, y la vida útil de las aeroturbinas al grado de agitación turbulenta del viento. El grupo de Mecánica de Fluidos Aplicado a la Ingeniería Industrial de la UPM, ha desarrollado programas informáticos para estimar la magnitud del viento y la intensidad de la turbulencia, en función de las características del terreno y de la distribución de las turbinas en el parque eólico, utilizando para ello modelos numéricos que simulan el movimiento turbulento de los fluidos

Efectos topográficos en el recurso eólico.

Para el diseño de parques eólicos es de interés conocer la producción de energía eléctrica de las turbinas eólicas, o aeroturbinas, así como las cargas que pueden sufrir las mismas limitando su vida útil. La producción de energía está ligada a la intensidad del viento incidente, y la vida útil de las aeroturbinas al grado de agitación turbulenta del viento. El grupo de Mecánica de Fluidos Aplicado a la Ingeniería Industrial de la UPM, ha desarrollado programas informáticos para estimar la magnitud del viento y la intensidad de la turbulencia, en función de las características del terreno y de la distribución de las turbinas en el parque eólico, utilizando para ello modelos numéricos que simulan el movimiento turbulento de los fluido

The most accurate determination of the 8B Half-life

Beta decay is a primary source of information of the structure of a nucleus. An accurate measurement of the half-life of a nucleus is essential for the proper determination of the reduced Gammow-Teller transition probability B(GT). In this work, we present an experiment using a compact set-up of Si-telescope detectors to measure the half-life of the B-8 nucleus. Three independent measurements have been analysed, obtaining the values 771.9(17) ms, 773.9(18) ms, and 770.9(27) ms. The value of the half-life obtained as the weighted averaged with the previous published measures is 771.17(94) ms which is a factor 3.2 of improvement in the uncertainty of the half-life

Multi-quasiparticle sub-nanosecond isomers in W-178

We report on the first measurement of the half-lives of K-pi = 11(-) and 12(+) four-quasiparticle states in the even-even nucleus W-178. The sub-nanosecond half-lives were measured by applying the centroid shift method to data taken with LaBr3(Ce) scintillator detectors of the NuBall array at the ALTO facility in Orsay, France. The half-lives of these states only became experimentally accessible by the combination of several experimental techniques - scintillator fast timing, isomer spectroscopy with a pulsed beam, and the event-by-event calorimetry information provided by the NuBall array. The measured half-lives are 476(44)ps and 275(65)ps for the I-pi = 11(-) and 12(+) states, respectively. The decay transitions include weakly hindered E1 and E2 branches directly to the ground-state band, bypassing the two-quasiparticle states. This is the first such observation for an E1 transition. The interpretation of the small hindrance hinges on mixing between the ground-state band and the t-band. (C) 2019 The Author(s). Published by Elsevier B.V

Half-life measurements in Dy-164,Dy-166 using γ−γ fast-timing spectroscopy with the ν-Ball spectrometer

We report on the measurement of lifetimes of excited states in the near-mid-shell nuclei Dy-164,Dy-166 using the gamma-ray coincidence fast-timing method. The nuclei of interest were populated using reactions between an O-18 beam and a gold-backed isotopically enriched Dy-164 target of thickness 6.3 mg/cm(2) at primary beam energies of 71, 76, and 80 MeV from the IPN-Orsay laboratory, France. Excited states were populated in Dy-164, Dy-166, and W-178,W-179 following Coulomb excitation, inelastic nuclear scattering, two-neutron transfer, and fusion-evaporation reaction channels respectively. Gamma rays from excited states were measured using the nu-Ball high-purity germanium (HPGe)-LaBr3 hybrid gamma-ray spectrometer with the excited state lifetimes extracted using the fast-timing coincidence method using HPGe-gated LaBr3-LaBr3 triple coincident events. The lifetime of the first I-pi = 2(+) excited state in Dy-166 was used to determine the transition quadrupole deformation of this neutron-rich nucleus for the first time. The experimental methodology was validated by showing consistency with previously determined excited state lifetimes in Dy-164. The half-lives of the yrast 2(+) states in Dy-164 and Dy-166 were 2.35(6) and 2.3(2) ns, respectively, corresponding to transition quadrupole moment values of Q(0) = 7.58(9) and 7.5(4) eb, respectively. The lifetime of the yrast 2(+) state in Dy-166 is consistent with a quenching of nuclear quadrupole deformation at beta approximate to 0.35 as the N = 104 mid-shell is approached

Evolution induced by dry minor mergers onto fast-rotator S0 galaxies

We analysed collisionless N-body simulations of intermediate and minor dry mergers onto S0s to test whether these mergers can generate S0 galaxies with kinematics intermediate between fast and slow rotators. We find that minor mergers induce a lower decrease of the global rotational support than encounters of lower mass ratios, which results in S0s with properties intermediate between fast and slow rotators. The resulting remnants are intrinsically more triaxial, less flattened, and span the whole range of apparent ellipticities up to $\epsilon_\mathrm{e} \sim 0.8$. They do not show lower apparent ellipticities in random projections than initially; on the contrary, the formation of oval distortions and the disc thickening increase the percentage of projections at $0.4 < \epsilon_\mathrm{e} < 0.7$. In the experiments with S0b progenitor galaxies, minor mergers tend to spin up the bulge and to decrease slightly its intrinsic ellipticity, whereas in the cases of primary S0c galaxies they keep the rotational support of the bulge nearly constant and decrease significantly its intrinsic ellipticity. The remnant bulges remain nearly spherical ($B/A \sim C/A > 0.9$), but exhibit a wide range of triaxialities ($0.20 < T < 1.00$). In the plane of global anisotropy of velocities ($\delta$) vs. intrinsic ellipticity ($\epsilon_\mathrm{e,intr}$), some of our models extend the linear trend found in previous major merger simulations towards higher $\epsilon_\mathrm{e,intr}$ values, while others depart from it. This is consistent with the wide dispersion exhibited by real S0s in this diagram compared with ellipticals, which follow the linear trend drawn by major merger simulations. The different trends exhibited by ellipticals and S0 galaxies in the $\delta$ - $\epsilon_\mathrm{e}$ diagram may be pointing to the different role played by major mergers in the build-up of each morphological type.Comment: Corrected typos. 20 pages, 14 figures. Accepted for publishing in A&

Nature of seniority symmetry breaking in the semimagic nucleus Ru-94

Direct lifetime measurements via gamma -gamma coincidences using a fast timing detector array consisting of LaBr3(Ce) scintillators has been applied to determine the lifetime of low-lying states in the semimagic (N = 50) nucleus Ru-94. The experiment was carried out as the first in a series of "FAIR-0" experiments with the DESPEC experimental setup at the Facility for Antiproton and Ion Research (FAIR). Excited states in Ru-94 were populated primarily via the beta-delayed proton emission of Pd-95 nuclei, produced in the projectile fragmentation of an 850 MeV/nucleon Xe-124 beam impinging on a 4 g/cm(2) Be-9 target. While the deduced E2 strength for the 2(+) -> 0(+) transition in the yrast cascade follows the expected behavior for conserved seniority symmetry, the intermediate 4(+) -> 2(+) transition exhibits a drastic enhancement of transition strength in comparison with pure-seniority model predictions as well as standard shell model predictions in the f pg proton hole space with respect to doubly magic Sn-100. The anomalous behavior is ascribed to a subtle interference between the wave function of the lowest seniority v = 2, I-pi = 4(+) state and that of a close-lying v = 4 state that exhibits partial dynamic symmetry. In addition, the observed strongly prohibitive 6(+) -> 4(+) transition can be attributed to the same mechanism but with a destructive interference. It is noted that such effects may provide stringent tests of the nucleon-nucleon interactions employed in state-of-the-art theoretical model calculations