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La independencia judicial y el desafio populista
No full textLa presente tesis doctoral aborda en qué forma el auge del populismo ha socavado la
independencia de los tribunales, un elemento esencial para el Estado de Derecho. A pesar
de su ambigüedad, el populismo ha emergido en la actualidad como un concepto
íntimamente asociado con los procesos de involución democrática.
A partir de un estudio novedoso de derecho comparado donde se analizan los discursos y
los métodos utilizados para aprobar las reformas judiciales, es claro que uno de los
principales objetivos del populismo es debilitar a los tribunales, y así impedirles ser un
contrapeso efectivo a los poderes electos por el pueblo. Ello se aprecia de forma cristalina
cuando se examina la jurisprudencia de los tribunales constitucionales capturados,
convertidos en un actor clave en la legitimación de la agenda iliberal del gobierno.
En este contexto, el análisis de la respuesta ofrecida por los tribunales constitucionales,
los tribunales internacionales y/o supranacionales (TEDH, Corte IDH y TJUE) pone de
manifiesto que una defensa estrictamente judicial del Estado de Derecho puede mitigar
los efectos más perniciosos de las reformas populistas, pero no detenerlas. La
investigación explorará las ventajas de introducir algunas reformas institucionales para
así reforzar la eficacia de la respuesta judicial. Sin embargo, la pervivencia de la
democracia constitucional necesita de la consolidación de una cultura de respeto al Estado
de Derecho compartida y asumida por los poderes políticos y la ciudadanía.This doctoral thesis addresses how the rise of populism has undermined judicial
independence, an essential element of the Rule of Law. Despite populism’s ambiguous
nature, it has emerged today as a concept closely associated with democratic backsliding.
One of the populist main goals is to weaken judicial courts, thereby preventing them from
effectively counterbalancing the political powers as elected by the people. This becomes
clear through this thesis’s comparative law study and its analysis of narratives and
methods used by populist governments to justify judicial reforms. It becomes particularly
evident when analyzing case law of captured constitutional courts, which have become
key actors in legitimizing the illiberal agenda of a populist government.
The responses to the populist threat, as offered by constitutional, international and
supranational courts (ECtHR, IACtHR and the CJEU) reveal that although the judicial
defense of the Rule of Law can mitigate the most harmful effects of populist reforms, it
cannot stop them. While the advantages of introducing some institutional reforms should
be explored, the survival of constitutional democracy as we know it urgently demands the
consolidation of a culture of respect for the Rule of Law, shared and embraced by political
powers and citizens alike.Programa de Doctorat en Dre
El Populismo: Crítica de la teoría demoliberal
No full textLas teorías convencionales del populismo han sido postuladas a partir de las premisas normativas de la democracia liberal. Este trabajo se enfocará en aquellos desarrollos teóricos, poniendo especial atención en la aproximación metodológica que emplean las teorías republicana y liberal con respecto a los fenómenos sociales en general y a los fenómenos políticos en particular. Luego, se harán explícitos los supuestos básicos que subyacen a ambas teorías normativas para visibilizar su marcada distinción en lo que respecta a su entendimiento referido a las categorías políticas de oligarquía y democracia. Esta diferenciación resulta determinante para la descripción y evaluación de toda práctica política, incluidas las prácticas consideradas populistas. Sobre la base de este planteamiento, la tesis persigue dos objetivos: i) reconstruir descriptivamente lo que podría denominarse una teoría demoliberal del populismo y ii) criticar dicha teoría desde la tradición política plebeya, que es inherente al republicanismo democrático, y, por lo tanto, contraria a cualquier expresión política oligárquica.Predominant approaches to populism usually assume the normative tenets of liberal democracy. This thesis will focus on those approaches, subjecting to close scrutiny the way in which republican and liberal theories address, from a methodological standpoint, social phenomena in general, and political phenomena in particular. Then, it will make explicit the basic assumptions underpinning both normative theories, in order to identify how they distinctively conceive of oligarchy and democracy as political categories. This difference determines how political practice is described and assessed, including allegedly populist practices. Building on this framework, the thesis pursues two main goals: i) to offer a descriptive reconstruction of what might be called a demo-liberal account of populism, and ii) to criticize such an account from within the critical plebeian tradition, which is inherent to democratic republicanism, and which denounces all expressions of oligarchic political practice.Programa de Doctorat en Dre
Deep learning segmentation for morphological assessment of optic nerve integrity in optic neuritis
No full textTreball de Fi de Grau en Enginyeria Biomèdica. Curs 2024-2025
Tutors: Dra. Deborah Pareto Onghena, Dr. Jaume Sastre Garriga, Dra. Gemma Piella FenoyStudying the optic nerve in Multiple Sclerosis (MS) patients plays a crucial role in early diagnosis and non-invasive monitoring of disease progression, as Optic Neuritis (ON) is a frequent and often early manifestation of MS. Magnetic Resonance Imaging (MRI) is the technique of choice to assess the integrity of the optic nerve. By examining the presence of lesions in the optic nerve, clinicians can obtain insights
into the progression of the disease and its impact on the central nervous system over time. The goal of this bachelor’s thesis is to generate, from MRI, detailed optic nerve profiles and morphological assessments, allowing for a comparison across different patients. These profiles can help to identify the presence of lesions, track disease progression and predict clinical outcomes. To achieve this, a cohort of subjects with MS, with and without ON, and healthy subjects will be analyzed. Deep learning models will be trained using 3D T1-weighted MRI scans from this dataset to segment the optic nerve. The assessment of optic nerve integrity will be performed by calculating the T1/T2 ratio, enabling precise detection and analysis of ON lesions and allowing for a comparison of these profiles with those of the control patients
Exploring the role of DYRK1 kinases in cell-autonomous and paracrine activities in pancreatic cancer
No full textDual-specificity tyrosine-regulated kinases (DYRKs) are a conserved family of protein kinases regulating critical cellular processes. This study investigates the roles of the paralogues DYRK1A and DYRK1B in pancreatic ductal adenocarcinoma (PDAC) cells and their influence on the tumour microenvironment (TME). Transcriptomic analysis of DYRK1A/B-depleted tumour cells revealed their differential roles in cell cycle regulation, extracellular matrix deposition and cytokines/chemokines expression. Loss of DYRK1s in tumour cells reshapes paracrine interactions with cancer-associated fibroblasts and macrophages. Secretome analysis identified soluble factors differentially regulated by DYRK1A/B that contribute to TME reprogramming. Additionally, the characterization of the interaction between DYRK1s and TROAP showed that TROAP acts as a scaffold for DYRK1s and the microtubule-binding protein EB1, facilitating DYRK1A localization at the spindle. DYRK1s phosphorylate TROAP in vitro, and their loss alters TROAP phosphorylation in vivo. Therefore, DYRK1s may influence microtubule dynamics and mitotic progression through TROAP phosphorylation. In summary, this research provides new insights into the multifaceted roles of DYRK1s in PDAC, illustrating their involvement in intrinsic cellular functions and intercellular communication. Targeting DYRK1s may offer therapeutic potential by impairing tumour cell proliferation while modulating the TME to enhance antitumour immune responses.Las quinasas de doble especificidad reguladas por tirosina (DYRKs) son una familia conservada de proteína quinasas que regulan procesos celulares críticos. Este estudio investiga las actividades de los parálogos DYRK1A y DYRK1B en células tumorales de adenocarcinoma ductal de páncreas y su influencia en el microambiente tumoral. El análisis transcriptómico de células tumorales con depleción de DYRK1A/1B reveló actividades diferenciales en la regulación del ciclo celular, la deposición de matriz extracelular y la expresión de citoquinas/quimioquinas. La pérdida de DYRK1A o DYRK1B en células tumorales remodela las interacciones paracrinas con fibroblastos asociados a cáncer y macrófagos. El análisis del secretoma identificó factores solubles regulados diferencialmente por DYRK1A y DYRK1B en la célula tumoral, que contribuyen a la reprogramación del nicho tumoral. Además, la caracterización de la interacción entre las quinasas DYRK1 y TROAP mostró que TROAP actúa como una plataforma de reclutamiento entre las quinasas DYRK1 y la proteína de unión a microtúbulos EB1, facilitando la localización de DYRK1A en el huso mitótico. Las quinasas DYRK1 fosforilan a TROAP in vitro, y su pérdida en células altera la fosforilación de TROAP in vivo, sugiriendo que las quinasas DYRK1 pueden modular la dinámica de los microtúbulos y la progresión mitótica a través de la fosforilación de TROAP. En resumen, este trabajo proporciona nueva información sobre las actividades multifacéticas de las quinasas DYRK1 en cáncer de páncreas, ilustrando su participación en funciones celulares intrínsecas y en la comunicación entre los componentes celulares del nicho tumoral, sugiriendo además potencial terapéutico al afectar no sólo la proliferación de las células tumorales sino también posibles respuestas inmunitarias antitumorales.Programa de Doctorat en Biomedicin
Herpes simplex virus type 1 reshapes host chromatin architecture via transcription machinery hijacking
No full textHerpes simplex virus type 1 (HSV-1) remodels the host chromatin structure and induces a host-to-virus transcriptional switch during lytic infection. We combine super-resolution imaging and chromosome-capture technologies to identify the mechanism of remodeling. We show that the host chromatin undergoes massive condensation caused by the hijacking of RNA polymerase II (RNAP II) and topoisomerase I (TOP1). In addition, HSV-1 infection results in the rearrangement of topologically associating domains and loops, although the A/B compartments are maintained in the host. The position of viral genomes and their association with RNAP II and cohesin is determined nanometrically. We reveal specific host-HSV-1 genome interactions and enrichment of upregulated human genes in the most contacting regions. Finally, TOP1 inhibition fully blocks HSV-1 infection, suggesting possible antiviral strategies. This viral mechanism of host chromatin rewiring sheds light on the role of transcription in chromatin architecture.We acknowledge support from Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110103001 to M.P.C.); Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology (20200730009 to M.P.C.); National Natural Science Foundation of China (31971177 and 32270577 to M.P.C., 3221101299 to A.C.G.); Science and Technology Program of Guangzhou, China (202002030146 to M.P.C.); Guangdong Foreign Young Talent Program (WGZJXM04 to A.C.G.); Spanish Ministry of Science and Innovation (grant no. PID2020-114080GB I00/AEI/10.13039/501100011033 and grant no. BFU2017-86760-P/AEI/FEDER, UE to M.P.C.) and an AGAUR grant from the Department of Research and Universities of Generalitat de Catalunya (2021-SGR2021-01300 to M.P.C.); Spanish Ministry of Science and Innovation to the European Molecular Biology Laboratory (EMBL) partnership (to M.P.C.); the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN?AEI /10.13039/501100011033); European Social Fund (FI_B00103 to M.F.M.). Funding for open access charge: National Natural Science Foundation of China (NSFC) grant (3221101299 to A.C.G.).; Spanish Ministry of Economy, Industry and Competitiveness (PID2019-108322GB-100 to L.D.C.)
Voice processing ability predicts second-language phoneme learning in early bilingual adults
No full textData de publicació electrònica: 17-01-2025Individuals differ greatly in their ability to learn the sounds of second languages, even when learning starts early in life. Recent research has suggested that the ability to identify the idiosyncratic acoustic variations introduced into the speech stream by the speaker might be relevant for second-language (L2) phoneme learning. However, only a positive correlation between voice recognition and phoneme learning has been shown. In the present study, we investigated whether voice processing ability predicts L2 phoneme learning. We employed a battery of behavioral cognitive ability measures to assess voice processing ability and L2 phoneme learning in 57 early bilingual adults. Confirmatory factor analyses (CFAs) and structural equation modeling (SEM) revealed that voice processing ability predicts L2 phoneme learning. Our findings align with theories of speech perception that attribute a fundamental role to the analysis of voice cues and suggest that the accurate identification of speaker-specific variation is also relevant for phoneme learning.This work was supported by grants from the Ministry of Science and Innovation of the Spanish Government, State Research Agency and European Regional Development Fund (PID2019-106924GA-I00, PID2022-137368NB-I00 and PID2021‐123416NB-I00 funded by MICIN/AEI/10.13039/501100011033/FEDER UE) awarded to BD and NSG. MP was awarded a grant from the Valencian Government (CIAICO/2021/172). NSG was awarded the ICREA Academia Prize by the Catalan Government. GC was supported by a doctoral fellowship from the Universitat Internacional de Catalunya. Two grants financed by the Catalan Generalitat AGAUR (2021 SGR 00911 and 2021 SGR 00625) also supported this work
Therapeutic drug monitoring of amikacin and colistin in patients with multidrug-resistant gram-negative infections using a portable plasmonic biosensor
No full textInnovative diagnostic tools that enhance antibiotic routine monitoring can improve the management of infections caused by antibiotic-resistant bacteria. Therapeutic drug monitoring (TDM) involves measuring drug levels in the patient bloodstream to ensure optimal efficacy and safety, particularly for drugs with a narrow therapeutic index (TI), assisting in dosage control and toxicity risk management. Amikacin (AK) and colistin (CS) are crucial antibiotics for treating multidrug-resistant (MDR) bacteria but they have side effects that require a precise TDM to try to minimize them. Current analytical techniques like immunoassays, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS) are gold standards for the antibiotic analysis, but they may require transferring the human samples to centralized facilities, delaying crucial results and turnaround time. In contrast, plasmonic biosensors offer advantages for clinical diagnostics, enabling real-time drug detection with minimal sample volume and processing, being ideal for point-of-care applications. We have implemented plasmonic biosensors to quantify and rapidly monitor blood levels of amikacin and colistin. The biosensors provide high specificity and sensitivity, with limits of detection (LOD) of 0.92 ng/mL (1.57 nM) for amikacin and 9.11 pg/mL (7.88 pM) for colistin in blood serum. Statistics analyses demonstrated a strong correlation between the biosensor evaluation and the standard analytical methods (Spearman's correlation coefficient of 0.9171 (p-value < 0.001) and 0.7435 (p-value = 0.04) for amikacin and colistin, respectively). Our plasmonic biosensors offer in addition, simplicity, portability, and label-free evaluation, with multiplexed capabilities. The rapid turnaround of results in under 20 min, coupled with minimal sample processing, enhances the feasibility of personalized TDM, supporting tailored treatment strategies that can improve patient outcomes. This work lays the foundation for creating an integrated point-of-care biosensor platform for effectively performing TDM of antibiotics and other drugs in real-time at the patient's bedside in clinical settings.We acknowledge the financial support received for the PHITBAC project (PLEC2021-007739), funded by MCIN/AEI/10.13039/501100011033 and the European Union NextGenerationEU/PRTR. A.A. acknowledges the financial support from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 754397. The ICN2 is supported by the Severo Ochoa Centres of Excellence program, grant CEX2021-001214-S, funded by MCIN/AEI/10.13039.501100011033. The nanoB2A is a consolidated research group (‘Grup de Recerca’) of the Generalitat de Catalunya and is supported by the Departament de Recerca i Universitats de la Generalitat de Catalunya (no. 2021 SGR 00456)
Predicting cellular adaptation proteins dependent on eIF2α regulation under stress conditions: Physiological and pathophysiological implications in neuronal function
No full textUnderstanding the intricate mechanisms governing gene expression regulation is crucial for deciphering neuronal responses to cellular stress at both the physiological (i.e., synaptogenesis) and pathophysiological (i.e., neurodegenerative diseases) levels. These rapid adaptive changes depend on the translation of specific proteins with specialized 5' untranslated regions (5'UTRs), triggered by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), while normal cellular translation remains largely inhibited. This study aims to provide a useful tool to identify mRNAs susceptible to regulation by p-eIF2α. We compiled a database of 5'UTRs using Ensembl canonical transcripts from the GRCh38.p14 genome build. Ensembl IDs were used to extract coding sequences and cDNA via the REST API, and 5'UTR regions were identified. We applied translation efficiency-based filters to existing databases of p-eIF2α-dependent translation to obtain reliable training and testing datasets. A multiple logistic regression (MLR) model-using 5'UTR length, GC content, upstream open reading frames (uORFs), and the features of Atf4 as a reference-predicted scores for p-eIF2α-driven translation. Gene Ontology (GO) enrichment analysis identified significant biological processes, molecular functions, and cellular components involved. An interactome analysis using STRING-db highlighted pathways related to synaptoplasticity (physiological stress) and Alzheimer's disease (pathophysiological stress). In vitro luciferase assays validated SLC30A4 as a novel p-eIF2α-regulated transcript, uncovering the role of eIF2α regulation in zinc homeostasis and neurodegeneration. These findings underscore the importance of translational control mechanisms in memory formation and disease pathogenesis, contributing to the identification of potential therapeutic targets to mitigate pathological outcomes.This work was supported by the Spanish Ministry of Science and Innovation and Agencia Estatal de Investigación plus FEDER Funds through grants PID2023-149767OB-I00 funded by MICIU/AEI/10.13039/501100011033 and by 'ERDF A way of making Europe' (FJM), PID2023-150068OB-I00 funded by MICIU/AEI/10.13039/501100011033 and by ‘ERDF A way of making Europe’ (BO) and PID2022-136511OB-I00 (RV). This work was also funded by the Spanish Institute of Health Carlos III by project reference AC20/00009 -FEDER/UE and ERANET ERA-CVD_JTC2020-015; and, ‘Unidad de Excelencia María de Maeztu’ CEX2024-001431-M, funded by MICIU/AEI/10.13039/501100011033. This project was funded in part by TUBITAK Research GrantNo: 220N252 (AG)
Proposta d’adaptació musical de quatre cançons de la pel·lícula Encanto (2021)
No full textTutora: Aida Franch
Treball de fi de grau en Traducció i InterpretacióElaborar una proposta de traducció pròpia de les cançons d’una banda sonora ens permet entendre quina és l’extensió dels límits per a l’adaptació musical i la traducció audiovisual, a més de posar en pràctica i a prova investigacions anteriors per comprovar-ne que donen bons resultats. Per això, aquest treball neix amb la intenció de crear una proposta pròpia per l’adaptació musical al català de quatre cançons de la pel·lícula Encanto (2021). El nostre objectiu principal és aconseguir traslladar les cançons completament a la llengua catalana, respectant el context de la pel·lícula i la normativa
general de l’adaptació de cançons per doblatge. Durant el procés d’adaptació, abordem reptes lèxics, mètrics i extralingüístics i, en general, obtenim resultats bons i meticulosos, que tenen en compte l’estil de l’autor, centrat en la rima i l’accentuació, i que s’adeqüen al que surt en pantalla. Aquest treball es pot considerar com un primer pas en l’adaptació al català de la pel·lícula sencera.Elaborar una propuesta de traducción propia de las canciones de una banda sonora nos permite entender cuán extensos son los límites de la adaptación musical y de la traducción audiovisual, así como poner en práctica y a prueba investigaciones anteriores para comprobar si dan buenos resultados. Por lo tanto, este trabajo nace con la intención de crear una propuesta propia para la adaptación musical al catalán de cuatro canciones de la película Encanto (2021). Nuestro objetivo principal es conseguir trasladar las canciones
completamente a la lengua catalana respetando el contexto de la película y la normativa general de la adaptación de canciones para doblaje. Durante el proceso de adaptación, abordamos retos léxicos, métricos y extralingüísticos, y, generalmente, conseguimos resultados óptimos y meticulosos, que tienen en cuenta el estilo del autor, centrado en la rima y en la acentuación, y que se adaptan a lo que sale en pantalla. El presente trabajo puede considerarse como un primer paso hacia la adaptación al catalán íntegra de la película.Elaborating a proposal of our own for the translation of the songs of a soundtrack allows us to appreciate the scope of limitations of musical adaptation and audiovisual translation. It also allows as to put previous research into practice and to the test in order to validate weather they give reliable results. Therefore, this assignment is born from the purpose of creating our own proposal for a Catalan musical adaptation of four songs from the film Encanto (2021). Our main goal is to obtain a complete translation of the songs into
Catalan, while respecting the context of the film and the general rules of song adaptation for dubbing. During the adaptation process, we address lexical, metrical and extra-linguistic challenges and often achieve optimal and meticulous results, which consider the author’s style, focusing on rhyme and downbeats, and that are adapted to what is shown on screen. This work may be thought of as a first step towards a Catalan adaptation of the full movie
Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL
No full textIn chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut-off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants <2% VAF from background noise (37 FPs reported by 9 laboratories). The impact of low-VAF variants on time-to-second-treatment (TTST) and overall survival (OS) was investigated in a series of 1092 patients. Among patients not treated with targeted agents, patients with low-VAF TP53 variants had shorter TTST and OS versus wt-TP53 patients, and the relative risk of second-line treatment or death increased continuously with increasing VAF. Targeted therapy in ≥2 line diminished the difference in OS between patients with low-VAF TP53 variants and wt-TP53 patients, while patients with high-VAF TP53 variants had inferior OS compared to wild type-TP53 cases. Altogether, NGS-based approaches are technically capable of detecting low-VAF variants. No strict threshold can be suggested from a technical standpoint, laboratories reporting TP53 mutations should participate in a standardized validation set-up. Finally, whereas low-VAF variants affected outcomes in patients receiving chemoimmunotherapy, their impact on those treated with novel therapies remains undetermined. Our results pave the way for the harmonized and accurate TP53 assessment, which is indispensable for elucidating the role of TP53 mutations in targeted treatment