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L'expressió de la genericitat en llengua de signes catalana
No full textTreball de fi de màster en Lingüística Teòrica i AplicadaDirectores: : Dra. Gemma Barberà AltimiraAquest treball estudia l’expressió de la genericitat en la llengua de signes catalana (LSC). Per fer-ho, es fan servir tres conjunts de dades: dos provenen d’elicitacions amb signants de dues generacions diferents i l’últim és el producte d’aplicar diagnòstics de reeixidesa de diversos tipus de sintagmes nominals en oracions amb lectura genèrica. Dels tres objectius del treball, el primer és comprovar i elaborar sobre les hipòtesis de la recerca prèvia del fenomen en LSC i s’assoleix corroborant-ne algunes, perfilant-ne d’altres i detectant un nou signe relacionat amb la genericitat. El segon és estudiar la possible microdiacronia entre la generació de signants joves i la d’edat avançada i se’n troben indicis tant en l’expressió com en la percepció de la genericitat. Finalment, l’últim objectiu és detallar noves línies de recerca per continuar la recerca, cosa que es fa en base a les troballes d’aquesta investigació.This paper studies the expression of genericity in Catalan Sign Language (LSC). To do so, three datasets are used: two come from elicitation sessions with signers from two different generations, and the third is the results from applying felicity diagnostics to various types of noun phrases in sentences with a generic reading. The study pursues three main objectives. The first is to verify and refine the hypotheses put forward in earlier research on this phenomenon in LSC, and this is achieved by confirming some proposals, sharpening others, and identifying a previously unnoticed sign related to genericity. The second objective is to explore possible micro-diachronic change between the younger and old-aged generations of signers, and evidence is found in both the production and the perception of genericity. Lastly, the final objective is to outline new research avenues based on the paper findings
Garantía de conformidad en la compraventa de bienes de segunda mano entre particulares a través de plataformas colaborativas: aplicación del código civil catalán y el caso de "Wallapop"
No full textTreball de Fi de Grau en Dret. Curs 2024-2025Tutora: Lela MelónEl presente trabajo analiza la garantía de conformidad en los contratos de compraventa civil de bienes muebles de segunda mano celebrados entre particulares, especialmente mediante plataformas digitales como Wallapop, con el objetivo de conocer la protección del comprador. Se parte del régimen jurídico del Libro VI del Código Civil de Cataluña, que extiende la garantía de conformidad a todos los particulares, no solo a consumidores. Para ello, primero se realiza una breve introducción al Código Civil catalán y sobre el contrato de compraventa, para luego profundizar en la garantía de conformidad los remedios disponibles ante el incumplimiento, haciendo especial énfasis en los problemas que plantea la compraventa de bienes usados. Posteriormente, se examina el funcionamiento de plataformas de economía colaborativa, tomando como referencia el caso de Wallapop. Para ello, se analiza su sistema interno de protección al comprador, planteando si es suficiente, y si se le puede exigir responsabilidad en caso de incumplimiento contractual entre sus usuarios. Se concluye que, si bien estas plataformas pueden facilitar la prueba en caso de conflicto, su sistema de resolución de disputas resulta limitado y poco garantista, dada la falta de responsabilidad directa y el escaso margen de actuación otorgado al comprador
A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe
No full textSchizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal. The Psych-STRATA consortium addresses this research gap through a seven-step approach. First, transdiagnostic biosignatures of SCZ, BD and MDD are identified by GWAS and multi-modal omics signatures associated with treatment outcome and TR (steps 1 and 2). In a next step (step 3), a randomized controlled intervention study is conducted to test the efficacy and safety of an early intensified pharmacological treatment. Following this RCT, a combined clinical and omics-based algorithm will be developed to estimate the risk for TR. This algorithm-based tool will be designed for early detection and management of TR (step 4). This algorithm will then be implemented into a framework of shared treatment decision-making with a novel mental health board (step 5). The final focus of the project is based on patient empowerment, dissemination and education (step 6) as well as the development of a software for fast, effective and individualized treatment decisions (step 7). The project has the potential to change the current trial and error treatment approach towards an evidence-based individualized treatment setting that takes TR risk into account at an early stage.The Psych-STRATA project has received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement No 101057454. BTB received funding from the German Federal Ministry of Health (BMG) [2521FSB004_PROMPT, ERAPERMED2020] and La Marato TV3: SLD044/20/000001 (Convocatoria ERAPERMED2020). MD received funding from PROMPT and La Marato TV3: SLD044/20/000001 (Convocatoria ERAPERMED2020) + Amb el suport del Departament de Salut, Fundació La Marató de TV3, 202212-30. AHY independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. For the purposes of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Accepted Author Manuscript version arising from this submission. M-CP was supported with funding from the Investissement d’Avenir (ANR-10-AIHU-06)
ARI0003: Co-transduced CD19/BCMA dual-targeting CAR-T cells for the treatment of non-Hodgkin lymphoma
No full textCD19 CAR-T therapy has achieved remarkable responses in relapsed/refractory non-Hodgkin lymphoma (NHL). However, challenges persist, with refractory responses or relapses after CAR-T administration linked to CD19 loss or downregulation. Given the co-expression of CD19 and BCMA in NHL, we hypothesized that dual targeting could enhance long-term efficacy. We optimized different dual-targeting approaches, including co-transduction of two lentiviral vectors, bicistronic, tandem, and loop and pool strategies, based on our academic anti-CD19 (ARI0001) and anti-BCMA (ARI0002h) CAR-T cells. Comparison with anti-CD19/CD20 or anti-CD19/CD22 dual targeting was also performed. We demonstrate that anti-CD19/BCMA CAR-T cells can be effectively generated through the co-transduction of two lentiviral vectors after optimization to minimize competition for cellular resources. Co-transduced T cells, called ARI0003, effectively targeted NHL tumor cells with high avidity, outperforming anti-CD19 CAR-T cells and other dual-targeting approaches both in vitro and in vivo, particularly in low CD19 antigen density models. ARI0003 maintained effectiveness post-CD19 CAR-T treatment in xenograft models and in spheroids from relapsed CART-treated patients. ARI0003 CAR-T cells were effectively manufactured under Good Manufacturing Practice conditions, with a reduced risk of genotoxicity compared to other dual-targeting approaches. A first-in-human phase 1 clinical trial (CARTD-BG-01; this study was registered at ClinicalTrials.gov [NCT06097455]) has been initiated to evaluate the safety and efficacy of ARI0003 in NHL.This study was supported by research funding from “'la Caixa” Foundation to M.J. (LCF/PR/SP23/52950004); the Spanish Ministry of Science and Innovation under a Ramon y Cajal grant RYC2018-024442-I to S.G. and PID2020-119692RB-C22 to C.F.; the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 116026 to S.G. (this joint undertaking receives support from the European Union’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations), the Spanish Association Against Cancer (INVES222988RODR to A.R.-G.), and the AGAUR_INVESTIGO22 100028TC1 grant, within the framework of the Recovery, Transformation, and Resilience Plan, funded by the European Union’s NextGenerationEU Recovery Mechanism. C.D.-L. was supported by a personal "Formación de personal investigador" fellowship from the Ministry of Economy and competitiveness (PRE2018-083797) associated with the project SAF2017-88275-R to P.P.-G. We also thank the Generalitat de Catalunya for support (AGAUR 2021-SGR-01294) to P.P.-G. M.O.-M. was granted a "Formacion para investigadores en el ámbito de la Investigacin sanitaria" predoctoral training grant (IFI18/00035). B.M.-A. was supported by the Miguel Servet program (grant no. CP21/00111) of the Institute of Health Carlos III. We also acknowledge the support of the CERCA Programme/Generalitat de Catalunya. This work was developed at the Centro Esther Koplowitz, Barcelona, Spain. We thank the Flow Cytometry and Cell Sorting core facility of Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS) for their technical help. We also thank the animal facility of the University of Barcelona
Assessing radiofrequency electromagnetic field exposure in multiple microenvironments across ten European countries with a focus on 5G
No full textTo evaluate the implementation of 5G in Europe, we have systematically measured environmental, auto-induced downlink (DL) and uplink (UL) radiofrequency electromagnetic field (RF-EMF) exposure in more than 800 microenvironments in ten European countries. Outdoor, indoor, and public transport microenvironments were measured in two cities and three villages in each country. Exposure was measured during three mobile-phone user scenarios: flight mode (non-user), inducing maximum DL traffic (max DL) or maximum UL traffic (max UL). The mobile phone was carried in a backpack, placed 30 cm from an ExpoM-RF 4 that continuously measured 35 frequency bands (87.5 MHz-6 GHz). For each user scenario, mean exposure levels were calculated. In the non-user scenario, mean exposure levels ranged from 0.33 to 1.72 mW/m2 per country and were lower in Switzerland, Belgium and Italy. RF-EMF levels were, on average, 80 % lower in villages compared to cities, with DL bands contributing the most in this scenario. During max DL, exposure increased mainly due to the 5G band at 3.5 GHz (mean exposure per country 2.61-11.12 mW/m2). However, the time-division nature of this band prevents distinguishing between DL and UL signals with the ExpoM-RF4. Exposure levels were the highest during max UL, particularly in the Netherlands, Italy and Belgium, with 50 % of the mean levels per country above 16 mW/m2. Exposure was, on average, 35 % higher in villages compared to cities. Environmental exposure levels were below international guideline values. Countries with precautionary limits had lower environmental exposure levels but higher auto-induced uplink exposure during data upload.This project has received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement No 101057262. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. We acknowledge support from the grant CEX2023-0001290-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program. Lea Belácková is part of the ETAIN project that has received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement No. 101057216. Frank de Vocht is partly supported by the National Institute for Health and Care Research Applied Research Collaboration West (NIHR ARC West)
Timing of exercise differentially impacts adipose tissue gain in male adolescent rats
No full textObjective: Circadian rhythms of metabolic, hormonal, and behavioral fluctuations and their alterations can impact health. An important gap in knowledge in the field is whether the time of the day of exercise and the age of onset of exercise exert distinct effects at the level of whole-body adipose tissue and body composition. The goal of the present study was to determine how exercise at different times of the day during adolescence impacts the adipose tissue transcriptome and content in a rodent model. Methods: Rats were subjected to one of four conditions during their adolescence: early active phase control or exercise (EAC or EAE; ZT13), and late active phase control or exercise (LAC or LAE; ZT23). The effects of exercise timing were assessed at the level of subcutaneous and visceral adipose tissue transcriptome, body composition, hypothalamic expression of orexigenic and anorexigenic genes, blood serum markers and 24-hour core body temperature patterns. Results: We found that late active phase exercise (ZT23) greatly upregulated pathways of lipid synthesis, glycolysis and NADH shuttles in LAE rats, compared to LAC or EAE. Conversely, LAE rats showed notably lower content of adipose tissue. In addition, LAE rats showed signs of impaired FGF21-adiponectin axis compared to other groups. Conclusions: Finally, LAE rats showed higher post-exercise core body temperature compared to other groups. Our results thus indicate that our exercise protocol induced an unusual effect characterized by enhanced lipid synthesis but reduced adipose tissue content in late active phase but not early active phase exercise during adolescence
New insights in cell cycle and meiosis regulation in fission yeast
No full textThis thesis is divided into three different sections. The first two sections involve the study of cell cycle and the third section is focused on meiosis. In the first chapter, we have developed a fluorescent-localized cell cycle reporter strain (FLCCR) that enables cell cycle monitoring in life-cell microscopy and have applied it to the study of the role of the MAPK Sty1 in cell cycle. In the second chapter we show how the activity of the G1/S transcription factor MBF is regulated in a cell cycle-dependent manner by the binding and release of the co-repressors Nrm1/Yox1 and driven by CDK phosphorylation and proteasome degradation of Nrm1. Finally, in the third chapter we present data at transcriptomic, proteomic and phosphorylation landscape levels in the regulation of meiosis initiation and progression in fission yeast. Here, we focused on the regulation of protein stability by phosphorylation and identified potential candidates which protein levels may be regulated by phosphorylation.Aquesta tesis està dividida en tres seccions diferents. Les dues primeres es centren en l’estudi de la regulació del cicle cel·lular i la tercera tracta la regulació de la meiosis. En el primer capítol, hem desenvolupat una soca fluorescent, anomenada FLCCR, que permet el seguiment de les fases del cicle cel·lular en microscòpia in vivo i la hem aplicat a l’estudi del paper de la MAPK Sty1 en el cicle cel·lular. En el segon capítol, demostrem que l’activitat de MBF, el factor de transcripció de la transició G1/S, es regula per la unió i alliberament dels co-repressors Nrm1/Yox1.Concretament, Nrm1 es fosforila per CDK en metafase i es degrada pel proteasoma. Finalment, al tercer capítol ensenyem dades a nivell transcripcional, proteòmic i de fosforilació de la regulació de l’inici de la meiosis i la seva progressió en llevats de fissió. En concret, ens centrem en la regulació de l’estabilitat proteínica per fosforilacions i n’identifiquem diferents potencials candidats.Programa de Doctorat en Biomedicin
A founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle cramps
No full textBackground and purpose: Pathogenic variants in the RYR1 gene have been associated with a variety of conditions, ranging from congenital myopathy to adult manifestations. Our aim was to characterize the p.Leu2286Val variant in 17 Basque patients, to accurately determine its correlation with clinical features and to explore the possible founder effect of the variant. Methods: Families harbouring the p.Leu2286 RYR1 variant underwent a detailed clinical evaluation, including muscle magnetic resonance imaging, electromyography and muscle biopsy. Haplotypes were analysed in available patients and their relatives. Results: Individuals carrying the p.Leu2286Val shared a common haplotype, suggesting a founder event in the Basque Country population. The most prevalent features were exertional myalgia, high creatine kinase (CK) levels, cramps and muscle hypertrophy. None of the patients carrying only the p.Leu2286Val showed progression to severe muscle weakness and muscle magnetic resonance imaging showed a heterogeneous muscle involvement. Muscle biopsy revealed non-specific findings in two patients and features associated with central core disease in one patient carrying only the p.Leu2286Val and two patients harbouring an additional RYR1 variant. Three individuals carrying an in trans RYR1 variant presented with an earlier onset and more severe phenotype. Conclusion: Here, it is shown that the dominantly inherited p.Leu2286Val RYR1 founder variant is associated with a milder phenotype of exercise intolerance, myalgia and hyperCKemia.This study was supported by Instituto de Salud Carlos III and FEDER, ‘Una manera de hacer Europa’, with the grants FIS PI18/01585 (LGQ and PG) and PI22/01859 (LGQ), MCIN/AEI/10.13039/501100011033 (PID20220-119780RB-I00, AVI) and Gobierno Vasco (GIU20/057 and 2,022,111,045, AVI). ASC was supported by the Ministerio de Universidades (Spain) with the grant FPU20/06692, and PMM was supported by a PhD fellowship from Fundacion Jesus De Gangoiti Barrera. MYO-SEQ was funded by Sanofi Genzyme, Ultragenyx, LGMD2I Research Fund, CureLGMD2i, LGMD2D Foundation and Kurt+Peter Foundation, Muscular Dystrophy UK and Coalition to Cure Calpain 3 (VS). Analysis was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute and the National Heart, Lung and Blood Institute grant UM1 HG008900, and in part by National Human Genome Research Institute grant R01 HG009141 (VS). FC was supported by Agencia Estatal de Investigación ‘Unidad María de Maeztu’ (CEX2018-000792-M) and Agència de Gestió d'Ajuts Universitaris i de la Recerca (Generalitat de Catalunya, grant 2021SGR00466)
Els professionals de la documentació i la intel·ligència artificial: canvi de rol o canvi competencial?
No full textL’autor es pregunta per l’impacte de la intel·ligèn-cia artificial (IA) generativa en el treball dels professionals de la biblioteconomia-documentació. Argumenta que, en principi, la IA no hauria d’implicar un canvi de rol, sinó canvis profunds en els mètodes de treball, les eines i les competències i habilitats. Centrant el focus en les bibliote-ques universitàries i de centres de recerca, desenvolupa di-verses consideracions al voltant de cadascuna d’aquestes dimensions. Presenta algunes recomanacions concretes en el marc assenyalat, tot destacant la importància clau que les biblioteques han adquirit en el suport i la recerca de les universitats i centres de recerca, on els professionals de la documentació tenen una imatge molt favorable, i són per-cebuts per part dels investigadors com a professionals molt ben preparats. Conclou que la biblioteconomia-documen-tació ja ha demostrat en el passat la seva enorme capacitat d’adaptació i reinvenció, i tot indica que serà igual en el cas del tsunami de la IA