“Who Lives, Who Dies, Who Tells Your Story?” Lin-Manuel Miranda’s Hamilton: An American Musical

[Abstract] The main aim of this final project will be to analyze and comprehend the relevance and impact of Lin-Manuel Miranda’s Hamilton: An American Musical (2015) on musical theater as well as in society in general. The focus will be put on both the creative process and the critical reception the show has received since its premiere. To do so, I will provide a complete and detailed summary of the plot and the main characters, as well as a close-reading analysis of five specific songs: “My Shot,” “One Last Time,” “Non-Stop,” “Dear Theodosia,” and “The Schuyler Sisters.” The methodology used to achieve these goals will include, firstly, the study of Hamilton: The Revolution by Lin-Manuel Miranda and Jeremy McCarter, which is the main source of information on which this dissertation will be based on and, secondly, a compilation of interviews given by the members of the creative team which include the actors and actresses as well as Miranda himself. The conclusions reached are that Hamilton: An American Musical has marked a before and an after in the history of musical theater and the way in which history is taught. Consequently, it will serve as an inspiration for future works of similar (or greater) importance.Traballo fin de grao (UDC.FIL). Inglés: estudios lingüísticos y literarios. Curso 2021/202

Biomolecule-assisted exfoliation and dispersion of graphene and other two-dimensional materials: a review of recent progress and applications

Direct liquid-phase exfoliation of layered materials by means of ultrasound, shear forces or electrochemical intercalation holds enormous promise as a convenient, cost-effective approach to the mass production of two-dimensional (2D) materials, particularly in the form of colloidal suspensions of high quality and micrometer- and submicrometer-sized flakes. Of special relevance due to environmental and practical reasons is the production of 2D materials in aqueous medium, which generally requires the use of certain additives (surfactants and other types of dispersants) to assist in the exfoliation and colloidal stabilization processes. In this context, biomolecules have received, in recent years, increasing attention as dispersants for 2D materials, as they provide a number of advantages over more conventional, synthetic surfactants. Here, we review research progress in the use of biomolecules as exfoliating and dispersing agents for the production of 2D materials. Although most efforts in this area have focused on graphene, significant advances have also been reported with transition metal dichalcogenides (MoS2, WS2, etc.) or hexagonal boron nitride. Particular emphasis is placed on the specific merits of different types of biomolecules, including proteins and peptides, nucleotides and nucleic acids (RNA, DNA), polysaccharides, plant extracts and bile salts, on their role as efficient colloidal dispersants of 2D materials, as well as on the potential applications that have been explored for such biomolecule-exfoliated materials. These applications are wide-ranging and encompass the fields of biomedicine (photothermal and photodynamic therapy, bioimaging, biosensing, etc.), energy storage (Li- and Na-ion batteries), catalysis (e.g., catalyst supports for the oxygen reduction reaction or electrocatalysts for the hydrogen evolution reaction), or composite materials. As an incipient area of research, a number of knowledge gaps, unresolved issues and novel future directions remain to be addressed for biomolecule-exfoliated 2D materials, which will be discussed in the last part of this review.Financial support from the Spanish MINECO and the European Regional Development Fund (ERDF) through project MAT2015-69844-R as well as from “Plan de Ciencia, Tecnología e Innovación 2013-2017 del Principado de Asturias” and ERDF (project GRUPIN14-056) is gratefully acknowledged.Peer reviewe

In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry

The reduction of sulfur dioxide in wine is a consumer’s demand, considering the allergic effects that may occur in people who are sensitive to it. Stilbenes are candidates of great interest for this purpose because of their antioxidant/antimicrobial activities and health properties, and also because they are naturally found in the grapevine. In the present study, the in vitro toxicity of an extract from grapevine shoots (with a stilbene richness of 45.4%) was assessed in two human cell lines. Significant damage was observed from 30 μg/mL after 24 h, and 40 µg/mL after 48 h of exposure. Similarly, the ultrastructural study revealed a significant impairment of cell growing. The extract was able to protect cells against an induced oxidative stress at all concentrations studied. In view of the promising results, a more exhaustive toxicological assessment of the extract is needed to confirm the safety of its further use as additive in wine.España,Ministerio de Economía, Industria y Competitividad and INIA for the financial support for this project (RTA2015-00005-C02-02

Single cell gel electrophoresis as a tool to assess genetic damage in Heleobia cf. australis (Mollusca: Gastropoda) as sentinel for industrial and domestic pollution in Montevideo bay (Uruguay)

O conhecimento dos danos no DNA em organismos aquáticos de áreas poluídas é uma questão importante, já que a contaminação pode vir a alterar os organismos em níveis subletais. Apesar dos moluscos terem sido amplamente utilizados para monitorar a poluição da água, não há registros de estudos in vivo de genotoxicidade. Heleobia cf. australis é um pequeno gastrópode amplamente distribuído em quase todos os ecossistemas costeiros uruguaios, inclusive em locais altamente poluídos. O ensaio do cometa é um biomarcador genético do dano baseado na migração de fragmentos de DNA com carga negativa produzidas por agentes mutagênicos. Foram coletados indivíduos vivos na Baía de Montevidéu (área impactada) e Laguna Garzón (área controle) para analisar a presença de agentes mutagênicos que ocasionassem dano genético. Células de organismos da área impactada apresentaram níveis significativamente mais elevados de danos genéticos do que os obtidos na área controle. Esse nível de dano foi medido pela porcentagem de DNA na cauda. Embora preliminar, esta abordagem apoia a noção de que H. cf. australispoderia ser usado como sentinela para avaliar a presença de agentes mutagênicos em ambientes estuarinos, alertando sobre o impacto da poluição em estágios iniciais.The knowledge of the extent of DNA damage in aquatic organisms in polluted areas is an important issue because contamination may alter their health at sublethal levels. Although molluscs have been widely used to monitor water pollution, there are no records of in vivo genotoxicity studies. Heleobia cf. australis, is distributed in almost all Uruguayan coastal ecosystems, including highly polluted sites. The comet assay is a damage genetic biomarker based on the migration of negatively charged DNA fragments produced by mutagenic agents in individual cells. Live individuals were collected in the Montevideo Bay (impacted area) and Laguna Garzón (control) to analyze the presence of mutagenic agents in the former site through comet assay. Cells from organisms of the impacted area showed significantly higher levels of genetic damage than those obtained in the control population, measured by percentage of DNA in the tail. Although preliminary, this approach supports the idea that H. cf. australis could be used as a sentinel to evaluate the presence of mutagenic agents in estuarine environments, alerting to the impact of contamination in its early stages

Actualización en la selección y provisión de las Administraciones Públicas

Objetivo general: Realizar un breve análisis de investigación sobre la selección y provisión de las Administraciones Públicas en la actualidad y valorar si es necesaria una actualización del modelo de acceso al empleo público. Objetivos específicos: Reflexionar sobre la planificación de las necesidades y el sistema de selección y provisión de puestos de trabajo. Analizar si es necesaria una reforma en la selección y provisión de puestos de trabajo. Investigar sobre las necesidades y posibilidades de mejora en la selección y provisión de puestos de trabajo. METODOLOGÍA Y PROCEDIMIENTO El planteamiento de nuestro tema de estudio requiere a priori un trabajo extenso de estudio, análisis y conocimiento en la materia de los recursos humanos. Hemos recopilado y analizado fuentes secundarias. Estudiado e interpretado legislación vigente, informes y jurisprudencia. Consultado diferentes artículos publicados por las Administraciones Públicas en su web. Del análisis de toda la información recopilada hemos podido elaborar nuestro trabajo y llegar a una serie de conclusiones. En un primer lugar, estudiaremos los orígenes de la función pública con sus características, avances y normativa diversa. Con posterioridad haremos una visión de la función pública en la actualidad: determinación del personal al servicio de las administraciones públicas, regulación normativa del personal, los elementos instrumentales del empleo público, la adquisición de la relación de empleado público, los derechos individuales, la provisión de puestos de trabajo, super oferta de empleo público y el proyecto de consolidación de interinos. En segundo lugar, analizaremos la situación actual realizando un diagnóstico de los problemas desde el punto de vista de la administración y el opositor, los desajustes existentes entre el sistema educativo y los sistemas de acceso y la transformación digital en la que estamos inmersos. En tercer lugar, analizaremos la planificación de la selección, el proceso selectivo: oposición, concurso-oposición y curso selectivo, y el órgano de selección, con las propuestas de mejora en cada apartado. Por último, realizaremos las conclusiones del presente estudio.Grado en Relaciones Laborales y Recursos Humano

Medidas de protección para una efectiva aplicación de la sentencia en el delito de agresiones de la mujer en el distrito de Lima Norte, período marzo de 2017 a marzo de 2019

El delito de agresiones de la mujer y miembros integrantes de una familia, hoy en día es el delito de más afluencia de denuncias que tramita el Poder Judicial, no solo en el distrito judicial de Lima Norte, sino en otros distritos judiciales. La Ley 30364 para erradicar todo tipo de violencia contra la mujer y los miembros integrantes del grupo familiar, constituye un esfuerzo conjunto del Estado y las instituciones inmersas en la protección de la mujer y el grupo familiar, población que espera una pronta medida que se ajuste a la expectativa sufrida. Es así, que advertida la problemática, la presente investigación con enfoque cuantitativo, trae como propuesta determinar si las medidas de protección para la victima así como las respectivas medidas impuestas al agresor se relacionan con la efectiva aplicación de las sentencias por el delito de agresiones en contra de las mujeres o integrantes del grupo familiar; siendo el diseño de nuestra investigación la teoría fundamentada, para lo cual la muestra de investigación está conformada por 30 encuestas a los representantes de los órganos jurisdiccionales de Lima Norte, emitidos por Jueces Penales en los requerimientos de proceso inmediato, emitidas en marzo de 2017 a marzo de 2019

Medidas de protección para una efectiva aplicación de la sentencia en el delito de agresiones de la mujer en el distrito de Lima Norte, período marzo de 2017 a marzo de 2019

El delito de agresiones de la mujer y miembros integrantes de una familia, hoy en día es el delito de más afluencia de denuncias que tramita el Poder Judicial, no solo en el distrito judicial de Lima Norte, sino en otros distritos judiciales. La Ley 30364 para erradicar todo tipo de violencia contra la mujer y los miembros integrantes del grupo familiar, constituye un esfuerzo conjunto del Estado y las instituciones inmersas en la protección de la mujer y el grupo familiar, población que espera una pronta medida que se ajuste a la expectativa sufrida. Es así, que advertida la problemática, la presente investigación con enfoque cuantitativo, trae como propuesta determinar si las medidas de protección para la victima así como las respectivas medidas impuestas al agresor se relacionan con la efectiva aplicación de las sentencias por el delito de agresiones en contra de las mujeres o integrantes del grupo familiar; siendo el diseño de nuestra investigación la teoría fundamentada, para lo cual la muestra de investigación está conformada por 30 encuestas a los representantes de los órganos jurisdiccionales de Lima Norte, emitidos por Jueces Penales en los requerimientos de proceso inmediato, emitidas en marzo de 2017 a marzo de 2019

The role of subunit interfaces in the function of nicotinic acetylcholine receptor

Nicotinic acetylcholine receptors (nAChR) containing α4 and β2 nAChR subunits are the most prevalent type of nAChR in the brain, where they modulate an assortment of physiological functions such as cognition, mood, reward and analgesia. α4β2 nAChRs have been implicated in a wide range of diseases such as depression, Alzheimer’s, Parkinson’s, Schizophrenia and a type of familial epilepsy. Also, α4β2 nAChRs are necessary and sufficient for the rewarding and reinforcing effects of nicotine. The α4β2 receptors assemble in two functional forms, (α4β2)2α4 and (α4β2)2β2. These two receptors have different pharmacological properties, which is partly accounted for by the presence of an additional agonist site at the signature α4/α4 interface of the (α4β2)2α4 nAChR. The canonical agonist sites of these receptors function asymmetrically, even though they are structurally equivalent. These findings suggested that the fifth subunit (α4 in the (α4β2)2α4 and a β2 in the (α4β2)2β2 may asymmetrically modulate the agonist sites. The impact of the fifth subunit on receptor function was investigated by using concatenated (α4β2)2α4 and (α4β2)2β2 nAChRs expressed heterologously in Xenopus oocytes in combination with mutagenesis and functional analysis. Concatenated receptors permit the expression of only one type of receptor stoichiometry and the mutations can be introduced in defined subunits of the pentamer. The overall aim of this PhD study was to advance our understanding of how the signature β2/β2 and α4/α4 interfaces of (α4β2)2β2 and (α4β2)2α4 nAChRs respectively affect the function of neighbouring α4β2 nAChRs. In (α4β2)2α4 receptors, the presence of an additional site at the α4(+)/α4(-) interface underlies differences in sensitivity to ACh but the interface flanking agonist sites also modulate the function of this site. For the (α4β2)2α4 receptors, this thesis examined the effects of mutations introduced in the fifth subunit or flanking subunits on Zn2+ potentiation of (α4β2)2α4 receptors. Zn2+ potentiation of the agonist responses of the (α4β2)2α4 receptors is mediated by a site located on the fifth subunit (α4). It was found that Zn2+ potentiation is inhibited by alanine substitutions of amino acids linking the fifth subunit to neighbouring agonist sites. For the (α4β2)2β2 receptors, the findings suggest that residues in loop B (W176, T177) and loop E (L146 and F144) of β2(+)/β2(-) interface link to the canonical agonist site anticlockwise to β2(+)/β2(-) to modulate maximal agonist responses. Long-range coupling analysis with the modulator β2(+)/β2(-) residues and a reported mutation in the ion channel, β2L9’T, showed these residues functionally couples, thus suggesting that the modulation of maximal agonist currents likely occur at the gating domain. Overall, it is proposed that the fifth subunit allosterically communicates with adjacent subunits to modulate agonist binding site function. These findings may lead to the development of stoichiometry- or interface-specific α4β2-selective drugs

Actitud Emprendedora Empresarial y Capacidad de Creación de Microempresas en Estudiantes del Instituto de Educación Superior Tecnológico Público San Martín de Pangoa Provincia de Satipo 2016

El trabajo de investigación titulado “Actitud emprendedora empresarial y Capacidad de Creación de Microempresas en Estudiantes del Instituto de Educación Superior Tecnológico Público San Martín de Pangoa Provincia de Satipo 2016” fue desarrollado con el objetivo de determinar la relación que existe entre la actitud emprendedora empresarial y la capacidad de creación de microempresas en estudiantes del Instituto de Educación Superior Tecnológico Público San Martín de Pangoa Provincia de Satipo 2016” dicha investigación es de tipo y nivel descriptivo con diseño correlacional con una población 200 y muestra 140 estudiantes, se utilizó un cuestionario de escala de tipo Likert construido para cada variable con nivel ordinal; luego, en el tratamiento de datos se utilizó el estadístico Tau-b de Kendall llegando al siguiente resultado: Se determinó que existe correlación entre la actitud emprendedora empresarial y la capacidad de creación de microempresas en los estudiantes del Instituto de Educación Superior Tecnológico Público San Martin de Pangoa Provincia de Satipo 2016. Mientras mayor es la actitud emprendedora empresarial es mayor la capacidad de creación de microempresas. Con Tau_b= 0.754. Esto significa que la mayoría de los estudiantes presenta una actitud positiva de emprendedurismo para la creación de microempresas como una concreción de los conocimientos y formación obtenida en la mencionada institución educativa

β-adrenergic-mediated dynamic augmentation of sarcolemmal CaV 1.2 clustering and co-operativity in ventricular myocytes.

Key pointsPrevailing dogma holds that activation of the β-adrenergic receptor/cAMP/protein kinase A signalling pathway leads to enhanced L-type CaV 1.2 channel activity, resulting in increased Ca2+ influx into ventricular myocytes and a positive inotropic response. However, the full mechanistic and molecular details underlying this phenomenon are incompletely understood. CaV 1.2 channel clusters decorate T-tubule sarcolemmas of ventricular myocytes. Within clusters, nanometer proximity between channels permits Ca2+ -dependent co-operative gating behaviour mediated by physical interactions between adjacent channel C-terminal tails. We report that stimulation of cardiomyocytes with isoproterenol, evokes dynamic, protein kinase A-dependent augmentation of CaV 1.2 channel abundance along cardiomyocyte T-tubules, resulting in the appearance of channel 'super-clusters', and enhanced channel co-operativity that amplifies Ca2+ influx. On the basis of these data, we suggest a new model in which a sub-sarcolemmal pool of pre-synthesized CaV 1.2 channels resides in cardiomyocytes and can be mobilized to the membrane in times of high haemodynamic or metabolic demand, to tune excitation-contraction coupling.AbstractVoltage-dependent L-type CaV 1.2 channels play an indispensable role in cardiac excitation-contraction coupling. Activation of the β-adrenergic receptor (βAR)/cAMP/protein kinase A (PKA) signalling pathway leads to enhanced CaV 1.2 activity, resulting in increased Ca2+ influx into ventricular myocytes and a positive inotropic response. CaV 1.2 channels exhibit a clustered distribution along the T-tubule sarcolemma of ventricular myocytes where nanometer proximity between channels permits Ca2+ -dependent co-operative gating behaviour mediated by dynamic, physical, allosteric interactions between adjacent channel C-terminal tails. This amplifies Ca2+ influx and augments myocyte Ca2+ transient and contraction amplitudes. We investigated whether βAR signalling could alter CaV 1.2 channel clustering to facilitate co-operative channel interactions and elevate Ca2+ influx in ventricular myocytes. Bimolecular fluorescence complementation experiments reveal that the βAR agonist, isoproterenol (ISO), promotes enhanced CaV 1.2-CaV 1.2 physical interactions. Super-resolution nanoscopy and dynamic channel tracking indicate that these interactions are expedited by enhanced spatial proximity between channels, resulting in the appearance of CaV 1.2 'super-clusters' along the z-lines of ISO-stimulated cardiomyocytes. The mechanism that leads to super-cluster formation involves rapid, dynamic augmentation of sarcolemmal CaV 1.2 channel abundance after ISO application. Optical and electrophysiological single channel recordings confirm that these newly inserted channels are functional and contribute to overt co-operative gating behaviour of CaV 1.2 channels in ISO stimulated myocytes. The results of the present study reveal a new facet of βAR-mediated regulation of CaV 1.2 channels in the heart and support the novel concept that a pre-synthesized pool of sub-sarcolemmal CaV 1.2 channel-containing vesicles/endosomes resides in cardiomyocytes and can be mobilized to the sarcolemma to tune excitation-contraction coupling to meet metabolic and/or haemodynamic demands