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A scalable and secure transaction attachment algorithm for DAG-based blockchain
No full textBlockchain, as an innovative distributed ledger technology, has attracted considerable attention in recent years from both academic circles and industry sectors. Its applications span a diverse range of domains, including finance and the Internet of Things (IoT). However, the scalability of blockchain technology is still a critical limitation with the increasing volume of data. To address this limitation, a directed acyclic graph (DAG) data structure has been proposed to improve scalability by supporting asynchronous process of transactions. IOTA is a well-known DAG-based blockchain that theoretically offers faster confirmation speeds with an increasing number of transactions. However, in practice, IOTA still faces the challenge of balancing scalability and security. In this article, we propose a scalable and secure transaction attachment algorithm for the DAG-based blockchain IOTA. We determine two critical parameters through our experimental analysis: one for calculating the selection probability and the other for setting the threshold for abnormal transactions. First, we calculate the selection probability of unconfirmed transactions. Then, we select abnormal transactions whose selection probability falls below the predefined threshold to maintain the security. Finally, new transactions attach randomly to former transactions with a time computational complexity O(n) , ensuring the scalability. Through experiments comparing the proposed algorithm to the current transaction attaching algorithm, we demonstrate the scalability and security of our proposed algorithm
The genetic demographic history of the last hunter-gatherer population of the Himalayas
No full textNepal, largely covered by the Himalayan mountains, hosts indigenous populations with distinct linguistic, cultural, and genetic characteristics. Among these populations, the Raute, Nepal's last nomadic hunter-gatherers, offer a unique insight into the genetic and demographic history of Himalayan foragers. Despite strong cultural connections to other regional foragers, the genetic history of this population remains understudied. This study presents newly genotyped genome-wide SNP data of the Raute to explore their genetic isolation, their origins and potential as an older foraging lineage, and their genetic connections to other regional foragers. Our results show that high levels of inbreeding in the Raute indicate recent genetic isolation. Effective population size estimates suggest a dramatic population decline around 50 generations ago. Strong genetic similarity to Nepalese populations of various subsistence styles highlights a dynamic history of genetic interactions prior to isolation, with particular closeness to historical foragers like the Kusunda and Tharu, but excludes an ancient foraging lineage origin. The study underscores the complexity of human population dynamics in the Himalayas, suggesting a history of extensive interaction between foragers and farmers, followed by isolation and demographic decline among the Raute.ABM received funding by a SERI-funded ERC Consolidator Grant (“COLLABORO” Grant MB22.00059 SERI-Uni ZH). ID was funded by the Schultz Foundation (A. H. Schultz-Stiftung zur Förderung primatologischer Forschung am anthropologischen Institut der Universität Zürich), Switzerland; the Graduate Campus, University of Zurich, Switzerland; and the Leakey Foundation. EB is supported by PID2023-147621NB-I00 funded by MICIU/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. We also want to deeply thank the whole Raute community for their participation in this research, the Karnali provincial government of Nepal for their involvement in our research, Lal Bahadur Chetri for his support throughout the entire data collection process, and all other individuals who shared their thoughts in the many discussions around our findings
La responsabilidad penal en la relación materno y paternofilial: una reinterpretación
No full textUna vez demostrada la inconveniencia de los fundamentos ensayados hasta el momento de la responsabilidad penal de las madres y los padres por el cuidado de sus hijos (que no permiten una aplicación equitativa del derecho), esta tesis doctoral reconstruye la estructura de imputación sobre el concepto de autonomía y el paradigma del delito como infracción a competencias jurídico-penales. Se analiza el fundamento normativo de la competencia materno y paternofilial (la sociabilización primaria de los niños) y su legitimación a partir de la idea de autovinculación. Se defiende que, si la autovinculación está ausente (por ejemplo, en caso de violación), no existe una responsabilidad penal maternofilial en sentido estricto. Asimismo, se analiza el contenido propio de esta responsabilidad, presentando la autonomía infantil como su límite intrínseco. Por último, se identifican y examinan las interacciones que tienen lugar en su seno (entre el Estado, la sociedad, los progenitores y los niños).This doctoral thesis reconstructs the structure of imputation of mothers' and fathers' criminal responsibility for their children's care on the concept of autonomy and the paradigm of crime as an infringement of legal duties. To do so, it demonstrates the inappropriateness of the fundamentals expressed by the doctrine so far (which do not allow an equitable application of the law). It also analyzes the normative basis of maternal and paternal-filial duty (the primary socialization of children) and its legitimization based on bonding. In this context, if there is a lack of autonomy upon becoming a mother (for example, in the case of rape), there could be no maternal criminal responsibility in the strict sense. The content of paternal and maternal responsibility is also analyzed, showing child autonomy as its intrinsic limit. Finally, the interactions within it (between the State, society, parents, and children) are identified and examined.Programa de doctorat en Dre
The importance of data transformation in RNA-Seq preprocessing for bladder cancer subtyping
No full textObjective: RNA-Seq provides an accurate quantification of gene expression levels and it is widely used for molecular subtype classification in cancer, with special importance in prognosis. However, the reliability and validity of these analyses can significantly be influenced by how data are processed. In this study we evaluate how RNA-Seq preprocessing methods influence molecular subtype classification in bladder cancer. By benchmarking various aligners, quantifiers and methods of normalization and transformation, we stress the importance of preprocessing choices for accurate and consistent subtype classification. Results: Our findings highlight that log-transformation plays a crucial role in centroid-based classifiers such as consensusMIBC and TCGAclas, while distribution-free algorithms like LundTax offer robustness to preprocessing variations. Non log-transformed data resulted in low classification rates and poor agreement with reference classifications in consensusMIBC and TCGAclas classifiers. Additionally, LundTax consistently demonstrated better separation among subtypes, compared to consensusMIBC and TCGAclas, regardless of preprocessing methods. Nonetheless, the study is limited by the lack of a true reference for objective assessment of the accuracy of the assigned subtypes. Hence, future work will be necessary to determine the robustness and scalability of the obtained results
El Rostro y su ausencia: la supervivencia de la fotogenia en el cine contemporáneo
No full textJean Epstein escribía que, al filmar un rostro de cerca, el cinematógrafo había sido capaz de mostrar el alma humana. Así es como, en el período mudo, se instituyó la teoría de la fotogenia. Esta tesis parte de una voluntad de imaginar la historia del cine desde el punto de vista de los rostros que la han ido poblando y despoblando, apareciendo y desapareciendo del plano. Por un lado, nuestra intención es volver a pensar las ideas de Epstein desde el cine contemporáneo, razón por la cual el relato se abre con el rostro fluorescente de Margarete en Fausto (2011), de Aleksandr Sokurov. Por el otro, se trata de explicar la fotogenia como un lenguaje del tiempo de las imágenes y su manera de funcionar, en consonancia con el vocabulario espectral de Aby Warburg y, en especial, con el concepto de supervivencia, que encierra una doble vocación de memoria y porvenir.Jean Epstein wrote that the cinematographer, by filming a face up close, managed to show the human soul. This is how the theory of the ‘photogénie’ was established during the era of silent films. This thesis starts from an intention to imagine the history of cinema from the point of view of the faces that have filled it and been cleared from it, appearing and disappearing from the shot. One part of this examination is to rethink Epstein’s ideas as regards to contemporary cinema, which is why this story opens with Margarete’s illuminated face in the film Faust (2011), by Aleksandr Sokurov. The other part is about explaining the photogenic quality as a language of the time of images, in accordance with the spectral vocabulary of Aby Warburg and, especially, with the concept of survival, which encompasses both memory of the past and ideas for the future.Programa de doctorat en Comunicaci
Impact of recent protein structure prediction methods on homology, evolutionary and functional inference
No full textRecent advances in deep learning techniques have revolutionised protein structure modelling. Since AlphaFold2’s release, a set of tools have now become available to predict native-like structures at near-experimental accuracy for a large fraction of the proteome. This massive amount of structural data is now powering every kind of biological inference requiring structural information. The work presented here features an exploration of the impact of experimental and predicted protein structural information onto homology, evolutionary and functional inference. The first part addresses the issue of accurate multiple sequence alignment (MSA) computation through a novel large-scale algorithmic approach and the systematic use of predicted structural information. In the second part, I explored the contribution of MSAs and structural information to refine phylogenetic and functional inference. On top of developing generic structure-based phylogeny reconstruction methods, I used RBM10, a well characterised splicing factor, as a showcase for the use of predicted structural information to support the inference of functional and phenotypic predictions, especially in the case of pathogenic mutations. The last part of this thesis presents a best-practice bioinformatics pipeline, nf-core/proteinfold, implemented using the Nextflow workflow management system and following nf-core guidelines. This pipeline was developed as a support for the rest of the projects in order to provide a solution to the need of high throughput structure predictions.Els avenços recents en tècniques de deep learning han revolucionat la modelització d'estructures de proteïnes. Desde el llançament d'AlphaFold2, hi ha disponibles un conjunt d'eines per preveure les estructures de forma nativa amb una precisió gairebé experimental per una gran part del proteoma. A dia d'avui, aquesta gran quantitat de data estructural està alimentant tot tipus de inferència biològica que requereix informació estructural. El treball que es presenta aquí conté una exploració de l'impacte de la informació estructural experimental i predictiva de la proteïna en la inferència de la homologia, l'evolució i la funció. La primera part resolt el problema de la computació precisa d'alineacions de seqüències múltiples (MSA) a través d'un nou enfocament algorítmic de gran escala i l'ús sistemàtic de informació estructural predictiva. En la segona part, exploro la contribució de MSAs i la informació estructural per refinar la inferència filogenètica i funcional. A més a més de desenvolupar mètodes genèrics de reconstrucció filogenètica basada en estructures, he utilitzat RBM10, un factor d'empalmament ben caracteritzat, com un exemple per l'ús d'informació estructural predictiva per recolzar la inferència de prediccions funcional i fenotípica, especialment en el cas de mutacions patogèniques. La última part d'aquesta tesis presenta un pipeline bioinformatic best-practise, nf-core/proteinfold, implementat utilitzant el sistema de gestió de fluxos de treball Nextflow i seguint les directrius de nf-core. Aquest pipeline ha sigut desenvolupat com un suport a la resta de projectes i per proveir una solució a la necessitat de prediccions estructurals de gran escala.Programa de doctorat en Biomedicin
Weak design: Gianni Vattimo and the function of design
No full textTreball de Fi de Màster en Estudis Comparatius de Literatura, Art i Pensament. Curs 2024-2025Tutor: Santiago ZabalaThe thesis proposes the concept of weak design through the lens of Gianni Vattimo’s weak thought. It explores design practices that resist traditionally dominant paradigms of functionalism and universal, solution-oriented production, advocating instead for openness, contingency and interpretative plurality. By engaging deeply with Vattimo’s philosophy and conducting a theoretical analysis of case studies—ranging from postmodern design countercurrents to contemporary design approaches—it identifies a shared gesture: the weakening of deterministic notions of design tied to industrial and techno-rational logics, in order to reconceive design as a hermeneutic act—contextual, interpretative, plural. The thesis argues that weak thought can inform a weak design that cultivates subjectivities, expands imaginaries, and intervenes poetically and politically across the everyday and the yet-to-be
De Barcelona a Valladolid: comparación de actitudes lingüísticas en Cataluña y Valladolid frente a rasgos de del castellano de Cataluña
No full textTreball de fi de màster en Lingüística Teòrica i Aplicada. Director: Dr. Joan Josep Maria Costa CarrerasEn este trabajo se analizan la aceptabilidad de variantes tradicionalmente asociadas al castellano hablado en Cataluña, comparando las percepciones de hablantes catalanes y vallisoletanos, así como los registros a los que se vinculan estas variantes. Se busca determinar si hay variantes que están perdiendo su carácter regional y ampliando su uso, y examinar cómo difieren las actitudes lingüísticas entre catalanes y hablantes de otras zonas, considerando posibles factores sociales, culturales e ideológicos. Para ello, se han utilizado formularios que recogieron datos sobre aceptabilidad y asociación por registros. Los resultados indican que existen variables que influyen en la aceptación de los hablantes, que los catalanes presentan actitudes más prescriptivistas hacia su variedad — posiblemente por la situación sociolingüística de la comunidad— y que algunas variantes están extendiendo su uso más allá de la variedad de castellano hablada en Cataluña
The proteostatic landscape of healthy human oocytes
No full textOocytes, female germ cells that develop into eggs, are among the longest-lived cells in the animal body. Recent studies on mouse oocytes highlight unique adaptations in protein homeostasis (proteostasis) within these cells. However, the mechanisms of proteostasis in human oocytes remain virtually unstudied. We present the first large-scale study of proteostatic activity in human oocytes using over 100 freshly donated oocytes from 21 healthy women aged 19-34 years. We analysed the activity and distribution of lysosomes, proteasomes, and mitochondria in both immature and mature oocytes. Notably, human oocytes exhibit nearly twofold lower proteolytic activity than surrounding somatic cells, with further decreases as oocytes mature. Oocyte maturation is also coupled with lysosomal exocytosis and a decrease in mitochondrial membrane potential. We propose that reduced organelle activity preserves key cellular components critical for early embryonic development during the prolonged maturation of human oocytes. Our findings highlight the distinctive biology of human oocytes and the need to investigate human-specific reproductive biology to address challenges in female fertility.We are grateful to the CRG Advanced Light Microscopy Units for the support and assistance in this work. E.B. acknowledges institutional core funding and the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033) and the Generalitat de Catalunya through the CERCA programme, the Ministerio de Ciencia e Innovación PID2023-146697NB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE and the Vallee Scholar Award (Vallee Foundation Inc)
Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development
No full textBats are the only mammals capable of self-powered flight, an evolutionary innovation based on the transformation of forelimbs into wings. The bat wing is characterized by an extreme elongation of the second to fifth digits with a wing membrane called the chiropatagium connecting them. Here we investigated the developmental and cellular origin of this structure by comparing bat and mouse limbs using omics tools and single-cell analyses. Despite the substantial morphological differences between the species, we observed an overall conservation of cell populations and gene expression patterns including interdigital apoptosis. Single-cell analyses of micro-dissected embryonic chiropatagium identified a specific fibroblast population, independent of apoptosis-associated interdigital cells, as the origin of this tissue. These distal cells express a conserved gene programme including the transcription factors MEIS2 and TBX3, which are commonly known to specify and pattern the early proximal limb. Transgenic ectopic expression of MEIS2 and TBX3 in mouse distal limb cells resulted in the activation of genes expressed during wing development and phenotypic changes related to wing morphology, such as the fusion of digits. Our results elucidate fundamental molecular mechanisms of bat wing development and illustrate how drastic morphological changes can be achieved through repurposing of existing developmental programmes during evolution.We thank A. C. Stiege and U. Fischer for their technical support. We thank the Papiliorama Zoo directorate and staff members for their support during sampling. We thank the people from the transgenic and sequencing units from the Max Planck Institute for Molecular Genetics for their assistance. We thank M. Torres for kindly providing us with the MEIS antibodies. We thank all the members from Mundlos, Lupiáñez and Real groups for their fruitful discussions. C.F. was supported by the EMBO Postdoctoral Fellowship ALT 260-2021. S.M. was supported by a grant (GenRevo) from the European Research Council (ERC) and by the grant MU 880/27-1 from the Deutsche Forschungsgemeinschaft. F.M.R. was supported by grants from the Spanish Research Council (RYC2022-035182-I and PID2023-151163NA-I00/MCIN/AEI/10.13039/501100011033). Research in the Lupiañez lab was funded by the ERC (grant no. 101045439, 3D-REVOLUTION) and by the Spanish ‘Agencia Estatal de Investigación’ (grant no. PID2022-143253NB-I00/AEI/10.13039/501100011033/FEDER, UE). Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the ERC Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. R.H. was supported by the ERC (PREVENT, 101078827). This work was supported by the German Research Foundation (grant HI1423/5-1) and the LOEWE-Centre for Translational Biodiversity Genomics (TBG) funded by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK; LOEWE/1/10/519/03/03.001(0014)/52). M.A.M.-R. acknowledges support from the Spanish Ministry of Science and Innovation (PID2020-115696RB-I00 and PID2023-151484NB-I00) as well as the Catalan government through the AGAUR agency (SGR 01127). A.B. acknowledges support from the Spanish Ministry of Science and Innovation, the State Investigation Agency, and the European Social Fund Plus (PRE2022-101632)