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Transport-mediated antimicrobial interactions and resistance mechanism in Escherichia coli
No full textEsta tesis investiga los mecanismos de resistencia a antibióticos y la interacción entre antibióticos y toxinas en Escherichia coli, enfocándose en el paper del canal de membrana TolC en la expulsión de antibióticos e importación de toxinas. Mediante análisis de las dinámicas de crecimiento, secuenciación genómica, modelado matemático y microscopía de fluorescencia, exploramos la especificidad de TolC como mecanismo de transporte de diversos antibióticos y toxinas, identificando compuestos que usan dicho sistema de forma exclusiva, y estudiando las interacciones que resultan de la competición entre dichos compuestos por este canal de transporte. Entre los hallazgos clave de esta Tesis podemos destacar: (1) la diversidad en la dependencia de mecanismos de exportación por parte de distintos antibióticos; (2) la heterogeneidad en la respuesta de E. coli a la colicina E1, debida en parte a a aparición de mutaciones asociadas a canales de transporte y a regulación metabólica; (3) los efectos sinérgicos entre la colicina E1 y la mitomicina C resultantes de la competición entre ambas toxinas por el uso del canal TolC; y (4) la existencia de patrones complejos de resistencia cruzada y sensibilidad colateral en variantes resistentes a la colicina E1. Estos resultados revelan la adaptabilidad bacteriana al estrés por toxinas, y contribuyen a identificar interacciones inesperadas entre procesos celulares que contribuyen a la resistencia bacteriana. Nuestro trabajo contribuye por tanto a comprender las respuestas al estrés bacteriano, potencialmente informando nuevos enfoques terapéuticos contra infecciones resistentes a antibióticos.This thesis investigates antibiotic resistance mechanisms and the interactions between antibiotics and toxins in Escherichia coli, focusing on the TolC outer membrane channel’s role in antibiotic efflux and toxin import. Using growth dynamics analysis, whole genome sequencing, mathematical modeling, and fluorescence microscopy, we explored the specificity of TolC as a transport mechanism for a variety of antibiotics and toxins, dentified compounds that use the system exclusively, and studied the interactions between them that result from their competition for that transport channel. Key findings include: (1) varied efflux dependencies for different antibiotics; (2) heterogeneous population responses to colicin E1, with resistance conferred by mutations in import and metabolic genes; (3) synergistic effects between colicin E1 and mitomycin C due to TolC channel competition; and (4) complex cross-resistance and collateral sensitivity patterns in colicin-resistant variants. These results reveal the intricate adaptability of bacteria to antimicrobial stresses and identify unexpected interactions between cellular systems in conferring resistance. Our work contributes to understanding bacterial stress responses and adaptation mechanisms, potentially informing novel therapeutic approaches against antibiotic-resistant infections.Programa de Doctorat en Biomedicin
Violència obstètrica a Espanya: una mirada interseccional a una realitat invisibilitzada
No full textTreball de Fi de Grau en Ciències Polítiques i de l'Administració. Curs 2024-2025Tutora: Joana Morrison EsteveAquesta recerca té l’objectiu d’analitzar la violència obstètrica com una manera de violència de gènere i institucional. Aquesta vulnera els drets sexuals i reproductius de les dones durant l’embaràs, el part i el postpart. A través d’una mirada interseccional, s’han recollit testimonis de dones que l'han patida i també s’ha comptat amb l’expertesa d’una llevadora i una advocada especialitzada en aquest tipus de drets. L’objectiu principal és entendre quins són els factors i les causes estructurals que la sustenten i quines conseqüències genera, especialment en els col·lectius més vulnerabilitzats. Els relats mostren pràctiques deshumanitzadores naturalitzades en el sistema sanitari: intervencions no consentides, infantilització, manca d’escolta, patiment emocional i dificultats per establir un vincle amb el nadó. Alhora, es dona espai a les estratègies de resistència i autoprotecció que emergeixen en resposta. Aquesta recerca pretén contribuir al reconeixement d’una problemàtica encara poc visibilitzada i aportar elements per repensar el model actual d’atenció al part des d’una perspectiva de drets humans. Més enllà de la denúncia, obre preguntes sobre com transformar l’atenció obstètrica perquè situï les necessitats i la veu de les dones al centre.This research aims to analyse obstetric violence as a form of gender-based and institutional violence. It violates women’s sexual and reproductive rights during pregnancy, childbirth and the postnatal period. Using an intersectional approach, the study gathers testimonies from women who have experienced such violence, alongside the insights of a midwife and a lawyer specialised in this field. The main objective is to understand the structural causes and factors that sustain it, as well as the consequences it generates, particularly among the most vulnerable groups. The narratives reveal dehumanising practices that have been normalised within the healthcare system: non-consensual interventions, infantilisation, lack of listening, emotional suffering and difficulties in establishing a bond with the baby. At the same time, space is given to the strategies of resistance and self-protection that emerge in response. This research seeks to contribute to the recognition of a still largely invisible issue and to provide elements for rethinking the current model of maternity care from a human rights perspective. Beyond denunciation, it raises questions about how to transform obstetric care in a way that places women’s needs and voices at the centre
Legal practical limits of the UEFA financial sustainibility regulations. Evaluation of the UEFA FSR under EU law ans its capacity to protect competitiveness
No full textFootball is special, inherently different from other industries. That is what UEFA, a private organisation with the regulatory monopoly over European continental football, argues whenever it implements its regulations. One of these regulations are the new UEFA Financial Sustainability Regulations (FSR), the successor of Financial Fair Play, aimed to protect the financial stability and competitive balance within European football. But they also carry various restrictive effects for both clubs and players and might infringe EU competition law as well as certain EU freedoms. Nonetheless, any infringement might be exempted or justified under one of the doctrines developed and/or applied by the ECJ. After establishing the applicability of EU law to sports, this thesis will therefore - as its primary objective - evaluate the compatibility of the UEFA FSR with EU law. During the course of finding this answer, this thesis will also explore the general nature of lex sportiva, the tension between private and public regulation of European football, the special characteristics of sport and the evolution of the ECJ sports case law. Besides the legal evaluation, this thesis will also offer a practical assessment of the effectiveness of the current regulatory approaches with regard to the competitiveness problems that are present in European football - and aims to develop proposals for additional approaches by UEFA and by the EU itself.El fútbol es especial, intrínsecamente diferente de otras industrias. Eso es lo que argumenta la UEFA, una organización privada con el monopolio regulador del fútbol continental europeo, cada vez que aplica sus reglamentos. Uno de estos reglamentos es el nuevo UEFA Financial Sustainability Regulations (FSR), sucesor del Financial Fair Play, cuyo objetivo es proteger la estabilidad financiera y el equilibrio competitivo en el fútbol europeo. Pero también conllevan diversos efectos restrictivos tanto para los clubes como para los jugadores y podrían infringir la legislación de la UE en materia de competencia, así como determinadas libertades de la UE. No obstante, cualquier infracción podría quedar exenta o justificada en virtud de una de las doctrinas desarrolladas y/o aplicadas por el TJCE. Tras establecer la aplicabilidad del Derecho de la UE al deporte, esta tesis evaluará -como objetivo principal- la compatibilidad del FSR de la UEFA con el Derecho de la UE. En el curso de la búsqueda de esta respuesta, esta tesis también explorará la naturaleza general de la lex sportiva, la tensión entre la regulación privada y pública del fútbol europeo, las características especiales del deporte y la evolución de la jurisprudencia deportiva del TJCE. Además de la evaluación jurídica, esta tesis también ofrecerá una evaluación práctica de la eficacia de los enfoques reguladores actuales con respecto a los problemas de competitividad presentes en el fútbol europeo, y aspira a desarrollar propuestas de medidas adicionales por parte de la UEFA y de la propia UE.Programa de Doctorat en Dre
Laderas del Castillo (Callosa de Segura, Alicante) y los inicios de la producción metalúrgica argárica: evidencias y contextos
No full textSe presenta la información arqueológica relativa a los productos metálicos y la producción metalúrgica del yacimiento de Laderas del Castillo, con especial interés en los hallazgos realizados durante las excavaciones llevadas a cabo por el MARQ Museo Arqueológico de Alicante entre los años 2013 y 2021. Aunque no se han documentado áreas de actividad, los restos registrados informan de que en el yacimiento o en sus alrededores se llevaron a cabo procesos de trabajo relacionados con la reducción y fundición de cobre, cuyos desechos posteriormente pasaron a formar parte de rellenos antrópicos para la nivelación de suelos en el interior de diversas edificaciones
European Union-Latin American interregional relations: taking stock and looking ahead
No full textThe European Union (EU) and Latin America and the Caribbean (LAC) have a long and deep-rooted history of economic and political relations, which has shown fluctuations, due to a diverse combination of structural and agential variables. On the EU side, different mechanisms and strategies have been put in place, at different levels, ranging from bilateral dialogues to formal agreements and interregional summits. Moreover, relations revolve around three main agendas, including political dialogue, cooperation, and trade, and involve a wide array of state and nonstate, private and public actors. The literature on EU–LAC relations is vast and widely scattered across fields, but it often remains limited to examining specific dimensions, either a particular policy area, analytical level, or period. This chapter attempts to move forward by proposing a wider perspective on the interregional relations, based on an analytical policy approach. It introduces a novel database, which provides a mapping of the policy instruments that have been employed by the EU to activate such relations, including the agreements governing the relations between the EU and LAC, and the cooperation programs funded by the EU in LAC. Based on this, the chapter will provide an encompassing insight into how interregional relations have evolved, considering their variations across instruments, policy areas, territorial levels, and over time.Andrea C. Bianculli would also like to acknowledge funding support through the project “Rethinking the fundamentals of regions and regionalism. The European Union and Latin America through the lenses of regional regulatory governance” (Reg-EULAC), funded by the Spanish Ministry of Science and Innovation (PID2019-105997GB-I00). Jacint Jordana also acknowledges support from the Institució Catalana de Recerca i Estudis Avançats (ICREA) (2020)
The Role of constraints in coputation exploring optimality through limited resources and intrinsic motivation
No full textWhen interacting with the world, agents take actions they consider optimal, that is, best. Typically, this optimality is evaluated over the entire space of possibilities. However, agents are inherently bounded -- for instance by energy, time, or even lifespan -- resulting in behavior that often deviates from global optimality. In this work, we investigate how introducing constraints reshapes the concept of optimality. First, we explore optimality within the framework of the Breadth-Depth (BD) dilemma, a one-shot allocation of limited resources in large decision trees. Next, we rethink utility and reward within the Maximum Occupancy Principle (MOP): in this intrinsic motivation framework, extrinsic rewards are not the goals per se but means to sustain actions in the world. Finally, we introduce NeuroMOP, showing how intrinsic motivation provides a framework to interpret neural variability. Our results highlight the potential role of constraints in shaping computations in the brain, spanning from neural activity to behavior.Quan interactuen amb el món, els agents prenen les accions que consideren òptimes, és a dir, les millors. Normalment, aquesta òptimització s’avalua en tot l’espai de possibilitats. Tanmateix, els agents estan intrínsecament limitats -- per exemple, per l’energia, el temps o fins i tot l’esperança de vida --, cosa que provoca comportaments que sovint s’allunyen de l’òptim global. En aquest treball, investiguem com la introducció de restriccions redefineix el concepte d’òptimització. Primer, explorem l’òptimització dins el marc del Breadth-Depth (BD) dilema, una assignació única de recursos limitats en grans arbres de decisions. A continuació, replantegem la utilitat i la recompensa dins el Principi de Màxima Ocupació (MOP): en aquest marc de motivació intrínseca, les recompenses extrínseques no són els objectius en si mateixos, sinó els mitjans per sostenir accions en el món. Finalment, introduïm NeuroMOP, mostrant com la motivació intrínseca ofereix un marc per comprendre l’activitat neuronal. Els nostres resultats subratllen el paper potencial de les restriccions en la configuració dels càlculs al cervell, des de l’activitat neuronal fins al comportament.Programa de Doctorat en Tecnologies de la Informació i les Comunicacion
Synergistic and antagonistic activities of IRF8 and FOS enhancer pairs during an immune-cell fate switch
No full textCell fate instructive genes tend to be regulated by large clusters of enhancers. Whether and how individual enhancers within such clusters cooperate in regulating gene expression is poorly understood. We have previously developed a computational method, SEGCOND, which identifies hubs that we termed Putative Transcriptional Condensates (PTCs), consisting of enhancer clusters and associated target genes. Here, we use SEGCOND to identify PTCs in a CEBPA-induced B-cell-to-macrophage transdifferentiation system. We find that PTCs are enriched for highly expressed, lineage-restricted genes and associate with BRD4, a component of transcriptional condensates. Further, we performed single and combinatorial deletions of enhancers within two PTCs active during induced transdifferentiation, harboring IRF8 and FOS. Two enhancers within the IRF8 PTC were found to provide a backup mechanism when combined, safeguarding IRF8 expression and efficient transdifferentiation. Unexpectedly, two individual enhancers within the FOS PTC antagonize each other on day 1 of transdifferentiation, delaying the conversion of B-cells into macrophages and reducing FOS expression, while on day 7, they cooperate to increase FOS levels induced cells. Our results reveal complex, differentiation-stage-specific interactions between individual enhancers within enhancer clusters.This study was supported by CRG internal funds and the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) Plan Estatal 2019 with project reference number PID2019-109354GB-I00
Inequalities in the everyday of care: dimensions of the incorporation of intersectional theory in nursing practice
No full textData de publicació electrònica: 13-02-2025Aim: To offer a practical proposal regarding the implications of integrating intersectional theory into nursing practice, drawing from the experiences and narratives of nurses across diverse professional contexts. Design: Qualitative Grounded theory, following the constructivist approach offered by Kathy Charmaz. Methods: Data collection was conducted between 2022 and 2023 with nursing professionals from Catalonia, Spain. Following Charmaz's approach, thematic analysis was performed after theoretical sampling was saturated through 17 in-depth interviews and 2 focus groups. Results: A total of 26 individuals participated in the study. The analysis identified five dimensions related to considerations for incorporating intersectionality into nursing practice. These dimensions are presented as a conceptual framework, organised from elements most closely related to reflexivity and professional positionality, to those more distally connected to a critique of the structural system within which nursing activities are situated. Conclusion: Although the findings reveal widespread agreement regarding the necessity of adopting a new perspective that challenges the dominance of biomedical knowledge and facilitates alternative approaches to the social and health complexities in our environments, there exists divergence in the methods for achieving this paradigm shift. Intersectional theory provides a theoretical framework conducive to this reassessment. Implications for the profession and/or patient care: The findings outlined in this study hold significant implications for both professional practice and the structuring of nursing education at the university level. Concerning professional practice, we advocate for a theoretical framework that offers lucidity and precision regarding the strategies and skill sets necessary for the integration of an intersectional perspective into nursing practice. This framework may prove beneficial not only to individual practitioners but also to managerial entities seeking to reshape institutional care paradigms. In terms of nursing education, this research provides a foundation for a critical revaluation of curricular structures and their practical execution. Impact (addressing): What problem did the study address? Since health and illness are influenced by social and cultural factors, nursing theories are evolving to address social determinants of health. Strategies are needed to integrate intersectional theory into nursing practice and education. WHAT WERE THE MAIN FINDINGS?: Findings underscore the importance of aligning nursing values with principles of equality, respect, and social justice to address social health inequalities effectively. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: This study provides insights into the ambivalence surrounding the incorporation of intersectional theory in nursing practice, shedding light on its perceived value and feasibility among practitioners. A practical framework is developed which emphasises the significance of understanding power dynamics in healthcare settings and their implications for perpetuating or challenging social inequalities in health. Reporting method: The manuscript is based on the Consolidated Criteria for Reporting Qualitative Research (COREQ). Patient or public contribution: No Patient or Public Contribution
Optimization of transportation services for persons with reduced mobility
No full textAquesta tesi aborda l'optimització dels serveis de transport per a persones amb mobilitat reduïda, centrant-se en el Servei Municipal de Transport Especial de Barcelona. Els sistemes de transport accessibles són essencials per permetre que tots els ciutadans puguin participar plenament en la vida econòmica i social d'una ciutat. Aquesta investigació desenvolupa models matemàtics i algorismes avançats, implementant metaheurístiques i algorismes híbrids per optimitzar tant els serveis de transport regular com l'esporàdic, garantint una planificació de rutes més eficient i introduint estratègies de vehicle compartit. Mitjançant l'anàlisi del comportament dels usuaris i l'ús del servei, aquesta tesi proposa solucions per millorar l'accessibilitat, disminuir l'ús de vehicles, augmentar la qualitat del servei, reduir els costos operatius en un 66% i incrementar la compartició de viatges, amb més del 70% dels viatges compartits. Els models predictius per a la durada dels viatges milloren encara més la fiabilitat del servei. Els models desenvolupats no només milloren el transport per a persones amb mobilitat reduïda a Barcelona, sinó que també són adaptables a entorns similars arreu del món, contribuint a sistemes de mobilitat més inclusius.This thesis addresses the optimization of transportation services for persons with reduced mobility, focusing on Barcelona's Special Municipal Transportation Service. Accessible transportation systems are essential for enabling all citizens to fully engage in a city’s economic and social life. This research develops advanced mathematical models and algorithms, implementing metaheuristics and hybrid approaches to optimize both regular and sporadic transportation services, ensuring more efficient route planning and introducing vehicle-sharing strategies. By analyzing user behavior and service utilization, this thesis proposes solutions to improve accessibility, decrease vehicle usage, enhance service quality, reduce operational costs by 66.6%, and increase trip-sharing, with over 70% of trips being shared.
Predictive models for trip durations further enhance service reliability. The developed models not only improve transportation for persons with reduced mobility in Barcelona but are also adaptable to similar environments globally, contributing to more inclusive mobility systems.Programa de Doctorat en Tecnologies de la Informació i les Comunicacion
La enseñanza de la asignatura de religión en la educación pública: un análisis del caso español desde el derecho comparado
No full textTreball de Fi de Màster: Màster Avançat en Ciències Jurídiques. Curs 2024-2025Tutor: Pablo Cruz Mantilla de los RíosEste trabajo analiza el marco jurídico que regula la enseñanza de la religión en los centros públicos y concertados del sistema educativo español. A través del estudio de la normativa nacional, los acuerdos del Estado con las confesiones religiosas y la jurisprudencia constitucional, se examina cómo se concilian el derecho fundamental a la libertad religiosa y el principio de aconfesionalidad del Estado recogidos en el artículo 16 de la Constitución española. Además, se incluye un análisis comparado con los modelos de otros países europeos, especialmente Italia, y se abordan cuestiones prácticas como la posible segregación del alumnado y el estatus jurídico de los profesores de religión. La investigación concluye que el modelo español presenta tensiones estructurales entre neutralidad institucional y reconocimiento confesional, lo que plantea desafíos jurídicos y sociales no resueltos.This paper analyses the legal framework governing the teaching of religion in public and publicly funded schools in Spain. By examining domestic legislation, the State's agreements with religious communities, and relevant constitutional jurisprudence, it explores how the fundamental right to religious freedom and the principle of State secularism, as established in Article 16 of the Spanish Constitution, are reconciled in the educational context. The study also includes a comparative analysis of other European models—particularly that of Italy—and addresses practical issues such as potential student segregation and the legal status of religion teachers. The research concludes that the Spanish model reveals structural tensions between institutional neutrality and religious recognition, posing unresolved legal and social challenges