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From stress to Amyotrophic Lateral Sclerosis mechanobiology: featuring Piezo1 in Motor Neuron Disease
No full textAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterized in 97% of the cases by the accumulation of TDP-43 in cytoplasmic inclusions. As there is an association between oxidative and mechanical stress and ALS, we aimed this thesis to unveil the interrelationship between these three factors. We proved that the mechanosensitive Piezo1 channel is expressed and can be mechanically activated in murine lower motor neurons. Next, we observed a bidirectional relationship between Piezo1 and oxidative stress. H2O2 increases the activity and expression of Piezo1 through the alteration of its inactivation dynamics and the integrated stress response (ISR), and Piezo1 activation induces ISR activation. We demonstrated that Piezo1 overactivation induces the cytoplasmatic translocation and aggregation of TDP-43 through ISR and nuclear pore complex disruption, two molecular markers of ALS. Finally, using in-silico modelling, we have proposed a list of more than 400 ISR downstream candidates with a high specificity and related them with synaptoplasticity and neurodegeneration pathways. In conclusion, we propose the interrelationship between Piezo1 and ISR as a novel therapeutic target for ALS.La esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa mortal, caracterizada en un 97% de los casos por la acumulación de TDP-43 en inclusiones citoplasmáticas. Como hay una asociación entre los estreses oxidativo y mecánico y la ELA, hemos enfocado esta tesis a desentrañar la interrelación entre estos tres factores. Hemos demostrado que el canal mecanosensible Piezo1 se expresa y se puede activar mecánicamente en motoneuronas inferiores de ratón. Después, observamos una relación bidireccional entre Piezo1 y el estrés oxidativo. El H2O2 incrementa la actividad y expresión de Piezo1 mediante la alteración de sus dinámicas de inactivación y la respuesta integrada al estrés (ISR), y la activación de Piezo1 induce activación de la ISR. Hemos demostrado que la sobreactivación de Piezo1 provoca la translocación citoplasmática y la agregación de TDP-43 mediante la ISR y disrupción del complejo del poro nuclear, dos marcadores moleculares de ELA. Finalmente, usando modelaje in-silico, hemos propuesto una lista de más de 400 candidatos a efectores de ISR con una alta especificidad, y los hemos relacionado con procesos de sinaptoplasticidad y neurodegeneración. En conclusión, proponemos la interrelación entre Piezo1 y la ISR como una nueva diana terapéutica para la ELA.Programa de Doctorat en Biomedicin
L' Obra periodística de Joaquim Maria Puyal i la seva influència en les retransmissions esportives audiovisuals
No full textLa tesi doctoral aborda l’obra periodística de Joaquim Maria Puyal, un referent al camp de la retransmissió radiofònica de partits de futbol en català. S’explora la seva aportació a la ràdio esportiva, el seu model narratiu i la seva contribució al periodisme esportiu. A través d’una anàlisi detallada de les seves transmissions, s’identifiquen elements que l’han convertit en un fenomen de la comunicació esportiva. La investigació fa servir una metodologia qualitativa, incloent entrevistes a 25 professionals de la ràdio i anàlisi d’emissions destacades que han estat transcendents. Els resultats revelen com les transmissions de Puyal han influït en el conjunt de les retransmissions audiovisuals i han contribuït a la normalització de la llengua catalana. La tesi conclou que Joaquim Maria Puyal no només ha transmès per ràdio partits de futbol en català durant 42 anys, sinó que ha construït un model comunicatiu innovador que ha fet escola.The doctoral thesis addresses the journalistic work of Joaquim Maria Puyal, a reference in the field of radio broadcasting of football matches in Catalan. His contribution to sports radio, his narrative model and his contribution to sports journalism are explored. Through a detailed analysis of his transmissions, elements that have made him a phenomenon in sports communication are identified. The research uses a qualitative methodology, including interviews with 25 radio professionals and analysis of notable broadcasts that have been transcendent. The results reveal how Puyal's broadcasts have influenced all audiovisual broadcasts and have contributed to the normalization of the Catalan language. The thesis concludes that Joaquim Maria Puyal has not only broadcast football matches in Catalan on the radio for 42 years but has also built an innovative communication model that has become a school.Programa de Doctorat en Comunicaci
Short assessment for people with human immunodeficiency virus (HIV) aged 50 years or older: essential tests from comprehensive geriatric assessment
No full textBackground: Comprehensive geriatric assessments (CGAs) are necessary to address the needs of people with human immunodeficiency virus infection (PWH) aged ≥ 50 years and ensure that they receive high-quality care. We aimed to identify the most effective tests from an extensive CGA to develop a short CGA. Methods: This observational, cross-sectional, and analytical study was conducted in three phases: (1) describing PWH aged ≥ 50 and matched controls; (2) jointly analyzing data to identify the most effective tests from the original CGA and develop a short version; and (3) applying the short CGA separately to both groups. Results: The most effective tests—the Lawton scale, SPPB, Barber questionnaire, Pittsburgh Sleep Quality Index, and Cognitive Complaints questionnaire—were used to create a short CGA. It identified abnormalities in 77% of PWH flagged by the full CGA, though 65% with the normal short CGA results had at least one abnormal result in the full version. Most false negatives were due to the excluded Hearing-Dependent Activities scale. Conclusions: These findings represent an initial step toward developing a short CGA for an easy and rapid identification of PWH aged ≥ 50, beyond a frailty assessment, who may benefit from early clinical management
Genomic insights into human complex demography: A study of western and eastern European Romani populations
No full textEl poble Romaní, la minoria ètnica transnacional més gran d'Europa, té els seus orígens al sud d'Àsia i ha experimentat complexos canvis demogràfics al llarg de la seva diàspora. Aquesta tesi presenta anàlisis de dades genòmiques i d'ADN-Y que revelen una ascendència comuna entre els grups romanís, així com estructures genètiques distintes arreu d'Europa. Els patrons d'aparellament, com el flux genètic amb biaix de sexe i l'aparellament assortatiu, han modelat de manera significativa el seu perfil genètic. El flux genètic amb poblacions no romanís ha contribuït sovint a compensar la pèrdua de diversitat causada per colls d'ampolla i efectes fundador. Tanmateix, els gitanos espanyols mostren una diferenciació genètica interna molt superior a la dels ibèrics no Romanís, la qual cosa demostra la presència d'estructura interna. L'estudi subratlla la necessitat d'incloure poblacions infrarepresentades en la recerca genètica per captar millor la diversitat humana, i destaca el potencial per a estratègies de salut pública personalitzades, alhora que promou la comprensió social mitjançant l'estudi de grups marginats.The Romani people, Europe's largest transnational ethnic minority, originate from South Asia and have undergone complex demographic shifts during their diaspora. This thesis presents genome-wide and Y-DNA analyses revealing a shared ancestry among Romani groups, alongside distinct genetic structures across Europe. Mating patterns, such as sex-biased gene flow and assortative mating, have significantly shaped their genetic profile. Gene flow with non-Romani populations often offset diversity losses due to bottlenecks and founder effects. However, Spanish Roma show much higher internal genetic differentiation than non-Romani Iberians, demonstrating the presence of a substructure. The study emphasizes the need to include underrepresented populations in genetic research to capture human diversity more fully. It also highlights the potential for tailored public health strategies and promotes social understanding through the study of marginalised groups.Universidad Pompeu Fabra. Doctorado en Biomedicin
Immersive journalism and the Darién Gap: Developing an expert-guided VR prototype on the migrant journey
No full textTreball de fi de Màster en Cultura Digital i Mitjans Emergents (DiCEM)Supervisora: Laura Perez AltableImmersive journalism (IJ) introduces new opportunities for audiences to actively engage with stories through cognitive and physical interaction. Virtual reality (VR) enhances this by offering first-person experiences capable of evoking emotions beyond traditional media’s reach. This practice-based project explores the ongoing migration crisis in the Darién Gap — a perilous region between Panama and Colombia — as a compelling context for socially engaged IJ. It proposes a VR experience placing users in the perspective of a migrant, aiming to evoke empathy and prompt ethical reflection on the systems shaping migration. Using qualitative methods, including semi-structured interviews with immersive media experts and a complementary interview with migrants, the project develops a VR script prototype while addressing ethical, narrative, and practical challenges. Key considerations include audience agency, accessibility, responsible storytelling, and transparent integration of emerging technologies. The project highlights VR’s potential to humanize complex crises while advocating for community-informed, ethically grounded journalism
Integrating public transport in sustainable last-mile delivery: column generation approaches
No full textWe tackle the problem of coordinating a three-echelon last-mile delivery system. In the first echelon, trucks transport parcels from distribution centres outside the city to public transport stops. In the second echelon, the parcels move on public transport and reach the city centre. In the third echelon, zero-emission vehicles pick up the parcels at public transport stops and deliver them to customers. We introduce two extended formulations for this problem. The first has two exponential sets of variables, while the second has one. We propose column generation algorithms and compare several methods to solve the pricing problems on specially constructed graphs. We also devise dual bounds, which we can compute even when the graphs are so large that not a single pricing round completes within the time limit. Compared to previous formulations, our models find 16 new best known solutions out of an existing dataset of 24 instances from the literature.We are extremely grateful to the authors of Pessoa et al. (2023) for sharing with us their VrpSolver implementation of the GVRP. This work was partially funded by the CY Initiative of Excellence (grant "Investissements d'Avenir" ANR-16-IDEX-0008). The work of Alberto Santini has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska Curie grant agreement number 945380. We thank three anonymous reviewers whose comments helped improving a former version of the paper
Turning vulnerability into strength: how independent regulatory agencies enhance accountability and build stakeholder trust
No full textData de publicació electrònica: 30-06-2025Trustable environments are highly appreciated for regulatory performance, but difficult to emerge. A condition for making trust work is to accept vulnerability, and this holds both for stakeholders and agencies in public governance. Trust-related vulnerability can be understood as a dynamic perception of potential harm derived from entering into a desired interaction. While stakeholders increased vulnerability due to voluntary exchanges with public bodies has been widely documented, the conditions under which agencies voluntarily increase their vulnerability remain less explored. Focusing on independent regulatory agencies (IRAs), this paper introduces a conceptual framework where agency vulnerability serves as a strategic tool to enhance IRAs' accountability, ultimately supporting these goals. We argue that IRAs intentionally incorporate vulnerability to make accountability efforts more credible, fostering stakeholder trust and facilitating operations. To achieve this, IRAs disclose sensitive information through accountability mechanisms, including transparency and participation initiatives. While this exposes them to criticism, penalization, or termination, it also strengthens stakeholder support and regulatory effectiveness. However, to manage risks, vulnerability is often selectively applied, prioritizing preferred stakeholders. We empirically apply this framework on Spanish data protection, finance, and food safety regulators. Our findings suggest that while vulnerability increases risks by enabling potential harm to IRAs, it ultimately mitigates accountability challenges and enhances trust among selected stakeholders, making accountability relationships more credible.Previous versions of this paper were presented at “Workshop on Vulnerability” CARR—London School of Economics and Political Sciences (LSE) on September 21, 2023, as well as the “Workshop on Regulation and (Dis)trust: Exploring a Complex Relationship”—European University Institute (EUI) held from January 24 to 26, 2024. This study has received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 870722 (TiGRE project) and the Horizon ERC 2022 Advanced Grant under grant agreement no. 101097835 (RegTrust project)
Factores para aumentar la visibilidad en repositorios digitales: metadatos, interoperabilidad, identificadores persistentes y optimización SEO-GEO
No full textEn el contexto de la ciencia abierta y la comunicación académica, mejorar la visibilidad de los repositorios digitales es esencial para maximizar el alcance, el impacto y la capacidad de descubrimiento del contenido que albergan. Este capítulo de libro explora cinco estrategias clave para mejorar la visibilidad de los repositorios: optimización de la calidad de los metadatos, habilitación de protocolos de interoperabilidad, adopción de identificadores persistentes, implementación de acciones de optimización para motores de búsqueda (SEO) y adopción de la optimización para motores generativos (GEO). A través de un análisis detallado y recomendaciones prácticas, este trabajo destaca cómo los metadatos estandarizados, los vocabularios controlados y los identificadores persistentes, como DOI, Handle y ARK, contribuyen a mejorar la visibilidad. Este capítulo también enfatiza la importancia de alinear los repositorios con las tecnologías web en evolución y los motores impulsados por inteligencia artificial para garantizar que el contenido siga siendo accesible, rastreable e integrado en la experiencia de búsqueda de los usuariosEste trabajo forma parte del proyecto “Parámetros y estrategias para incrementar la relevancia de los medios y la comunicación digital en la sociedad: curación, visualización y visibilidad (CUVICOM)”. Ayuda PID2021-123579OB-I00 financiada por MICIU/AEI/10.13039/501100011033 y por FEDER, UE
Tariffs and technological hegemony
No full textWe provide a theory connecting trade policies to innovation and technological hegemony, based on the notion that high-tech clusters generate technological rents for the countries hosting them. We show that tariffs on high-tech imports may be used to steal technological rents from the rest of the world, by redirecting innovation activities from foreign to domestic firms. This strategy may lead to welfare gains, which however come at the expense of even larger welfare losses in the rest of the world. Tariffs may backfire even for the country imposing them if they are not well designed, or if the rest of the world retaliates