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Massive experimental quantification allows interpretable deep learning of protein aggregation
No full textProtein aggregation is a pathological hallmark of more than 50 human diseases and a major problem for biotechnology. Methods have been proposed to predict aggregation from sequence, but these have been trained and evaluated on small and biased experimental datasets. Here we directly address this data shortage by experimentally quantifying the aggregation of >100,000 protein sequences. This unprecedented dataset reveals the limited performance of existing computational methods and allows us to train CANYA, a convolution-attention hybrid neural network that accurately predicts aggregation from sequence. We adapt genomic neural network interpretability analyses to reveal CANYA's decision-making process and learned grammar. Our results illustrate the power of massive experimental analysis of random sequence-spaces and provide an interpretable and robust neural network model to predict aggregation.This work received support from the following: “La Caixa” Foundation (ID 100010434) under grant agreement LCF/PR/HR21/52410004 (B.L.); European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant agreement 883742 (B.L.); AXA Research Fund AXA Chair in Risk prediction in age-related diseases (B.L.); Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and the European Social Funds 2017 SGR 1322 (B.L.); Bettencourt Schueller Foundation (B.L.); PID2023-146685NB-I00 funded by MCIN/AEI/10.13039/501100011033/ FEDER, UE; Wellcome 220540/Z/20/A, “Wellcome Sanger Institute Quinquennial Review 2021-2026” (B.L.); Spanish Ministry of Science, Innovation and Universities PID2021-127761OB-I00 (B.B.) RYC2020-028861-I funded by MCIN/AEI/ 10.13039/501100011033 “ERDF A way of making Europe” and “ESF Investing in your future” (B.B.); European Union (ERC Consolidator, Glam-MAP, 101125484) (B.B.); EMBO Fellowship ALTF 266-2023 (M.T.); NIH grant R01HG012131 (P.K. and C.R.); and NIH grant R01GM149921 (P.K. and C.R.)
Higher education in welfare state regimes: a literature review
No full textExpansion and the growing role of higher education in determining life outcomes highlight the issue of its provision as a part of state welfare and redistribution policy. This article employs the critical review method and analyzes research on higher education in welfare state regimes. The article addresses research gaps and perspectives in studying higher education addressing the welfare regimes framework. A comparative analysis of access to higher education, educational systems institutional settings, and social stratification provide patterns in higher education redistribution, typical for conservative, liberal and socialdemocratic welfare regimes
The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways
No full textThe folding of the genome in the 3D nuclear space is fundamental for regulating all DNA-related processes. The association of the genome with the nuclear lamina into lamina-associated domains (LADs) represents the earliest feature of nuclear organization during development. Here, we performed a gain-of-function screen in mouse embryos to obtain mechanistic insights. We find that perturbations impacting histone H3 modifications, heterochromatin, and histone content are crucial for the establishment of nuclear architecture in zygotes and/or 2-cell-stage embryos. Notably, some perturbations exerted differential effects on zygotes versus 2-cell-stage embryos. Moreover, embryos with disrupted LADs can rebuild nuclear architecture at the 2-cell stage, indicating that the initial establishment of LADs in zygotes might be dispensable for early development. Our findings provide valuable insights into the functional interplay between chromatin and structural components of the nucleus that guide genome-lamina interactions during the earliest developmental stages.We thank I. de la Rosa Velazquez (Sequencing Facility, Helmholtz Munich), S. Krebs (LAFUGA, Gene Center), and V. Benes (EMBL SOLEXA) for sequencing; N. Battich for manuscript reading; S. Tripathi for helping with illustrations; and R. Grosse, M. Hetzer, P. Percipalle, J. Lammerding, T. Haraguchi, R. Schneider, M.H. Verlhac, and J. Whetstine for plasmids. Work in the M.-E.T.-P. laboratory is funded by the Helmholtz Association, the German Research Foundation (DFG) project-ID 213249687 (SFB1064), and the NIH 4DN program (grant 5U01DK127391-03). M.P., A.H.-G., M.A.M.-R., and M.-E.T.-P. acknowledge support from the EU Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement 813327 “ChromDesign”)
Nation‐building in the wake of empire: identifying patterns of minority policies in the aftermath of soviet collapse
No full textData de publicació electrònica: 31-07-2025The collapse of the USSR forced newly independent states to forge national identities while grappling with imperial legacies. This study investigates nation-building strategies in post-Soviet states during 1990–1999, using the Nation-Building Policies (NBP) dataset from the ETHNICGOODS project, which includes all socially and politically relevant minority groups. Employing cluster analysis, it identifies three typologies of nation-building policies: low, moderate and high inclusion. These typologies reveal varying levels of minority inclusion in language education, citizenship policies and constitutional measures. By examining short-term variations and using the year 2020 as a reference point, this study challenges the simplified view of post-Soviet nation-building as uniformly ‘nationalising’ and highlights significant regional and group-specific differences. Policy shifts reflect dynamic state-minority interactions influenced by geographic, cultural and political factors. The findings enhance understanding of diverse nation-building approaches and provide broader insights into contemporary minority relations in Eastern Europe, Central Asia and the Caucasus, contributing to comparative studies of nation- and state-building.This work was supported by the European Research Council (ERC) under Grant agreement No. 864333 (ETHNICGOODS)
O controlo social sobre a utilização de sistemas de inteligência artificial pela Administração Pública
No full textAo longo deste trabalho analisa-se os princípios reitores da utilização de sistemas de inteligência artificial pela Administração Pública: reserva de humanidade, transparência e explicabilidade. Salienta-se, em especial, que o acesso à informação algorítmica respaldado pela LADA é uma ferramenta essencial para levar a cabo o controlo social sobre a utilização de sistemas de inteligência artificial pela Administração Pública. No entanto, esse acesso à informação algorítmica deve necessariamente fazer-se acompanhar de outra documentação que contenha a descrição dos algoritmos de tal forma que um ser humano os possa compreender
Intergenerational persistence of poverty in five high-income countries
No full textSupplementary materials files: online appendix; replication data.Childhood poverty increases the likelihood of adult poverty. However, past research offers conflicting accounts of cross-national variation in the strength of-and mechanisms underpinning-the intergenerational persistence of poverty. Here the authors investigate differences in intergenerational poverty in the United States, Australia, Denmark, Germany and the United Kingdom using administrative- and survey-based panel datasets. Intergenerational poverty is decomposed into family background effects, mediation effects, tax and transfer insurance effects and a residual poverty penalty. The intergenerational persistence of poverty is 0.43 in the United States (95% confidence interval (CI) = 0.40-0.46; P < 0.001), compared with 0.16 in the United Kingdom (95% CI = 0.07-0.25; P < 0.001) and 0.08 in Denmark (95% CI = 0.08-0.08; P < 0.001). The US disadvantage is not channelled through family background, mediators, neighbourhood effects or racial or ethnic discrimination. Instead, the United States has comparatively weak tax and transfer insurance effects and a more severe residual poverty penalty. If the United States were to adopt the tax and transfer insurance effects of its peer countries, its intergenerational poverty persistence could decrease by more than one-third.We acknowledge funding from the European Union (ERC Starting Grant, ExpPov; agreement number 101039655; to Z.P.)
La Neutralización de la restricción a la libre circulación de capitales en instituciones de inversión colectiva
No full textLa tesis doctoral que se presenta examina el mecanismo de la neutralización de las restricciones a la libre circulación de capitales que se ponen de manifiesto a partir del trato tributario discriminatorio que los Estados miembros pueden otorgar a los no residentes en relación con los residentes.
Dicho mecanismo supone la posibilidad de entender neutralizada, de ahí su nombre, la eventual discriminación a través de la aplicación de los mecanismos previstos en los Convenios para evitar la doble imposición.
La tesis estudia los fundamentos teóricos del tratamiento de la doble imposición y de la distribución del poder financiero internacional, siempre con referencias a la regulación positiva española, para confrontarlos con la doctrina sentada por el Tribunal de Justicia de la Unión Europea en materia de libre circulación de capitales, especialmente en relación con las Instituciones de Inversión Colectiva, donde esta confrontación ofrece unos problemas jurídicos claramente caracterizados y donde el mecanismo de la neutralización está necesitado de mayores precisiones jurídicas.The Doctoral Thesis presented examines the mechanism of neutralization of restrictions on the free movement of capital that derive from the discriminatory tax treatment that Member States can grant to non-residents in relation to residents.
This mechanism implies the possibility of neutralizing, hence its name, the eventual discrimination through the application of the mechanisms provided for in the Double taxation treaties.
The thesis studies the theoretical foundations of the treatment of double taxation and the distribution of international financial power, always with references to Spanish positive regulation, to confront them with the doctrine established by the Court of Justice of the European Union on free movement of capital, especially in relation to Collective Investment Institutions, where this confrontation offers clearly characterized legal problems and where the neutralization mechanism needs greater legal precisions.Programa de Doctorat en Dre
Essays in game theory and mechanism design
No full textThis thesis aims to understand negotiations over the behaviour agents
will take in a game and, separately, robust implementation. Chapter
1 examines the binding agreements that result from a negotiation over
what to play in a strategic game. I propose a negotiation protocol and
characterise the agreement outcomes for a refinement of Subgame Perfect
Equilibrium. This characterisation depends solely on features of
the game and is easily applicable for future work. In Chapter 2, I,
along with Antonio Penta, introduce the concept of Safe Implementation,
which limits the alternatives a mechanism designer can use to
tame agents’ behaviour. We provide necessary and sufficient conditions
and explore various environments where these conditions can be
applied. Finally, Chapter 3 revisits Ray and Vohra’s Coalitional Equilibrium
and shows that a slightly weaker solution concept makes existence
substantially easier. Further, the proof of existence can accommodate
overlapping coalitions.Aquesta tesi pretén comprendre les negociacions sobre el comportament
que els agents tindran en un joc i, per separat, una implementació
robusta. El capítol 1 examina els acords vinculants que resulten d’una
negociació sobre què jugar en un joc, proposant un protocol de negociació i caracteritzant els resultats de l’acord mitjanant un perfeccionament
del concepte Subgame Perfect Equilibrium. Aquesta caracterització depèn únicament de les característiques del joc i és fàcilment
aplicable per a treballs futurs. Al capítol 2, jo, juntament amb Antonio
Penta, introdueixo el concepte d’implementació segura, que limita les
alternatives per a un dissenyador de mecanismes per controlar el comportament
dels agents. Oferim les condicions necessàries i suficients i
explorem diversos entorns on aquestes condicions es poden aplicar. Finalment,
el capítol 3 revisa el concepte Coalitional Equilibrium de Ray
i Vohra i mostra que un concepte de solució una mica més feble facilita
substancialment l’existència. A més, la prova de l’existència pot donar
cabuda a coalicions superposades.Programa de doctorat en Economia, Finances i Empres
QSample: an automated system for rapid monitoring of quality indicators in proteomics samples
No full textMass spectrometry-based proteomics is an essential technique in contemporary biomedicine, offering quantitative, sensitive, and rapid analysis of proteomes. Recent advancements in mass spectrometry have enabled the acquisition of data from increasingly large-scale experiments, often conducted in core facilities and research infrastructures. While automated tools exist to assess instrument performance using predefined control samples, the analysis of experimental samples typically occurs postacquisition, which can delay decision-making and lead to potential data integrity issues. To address these challenges, we developed QSample, an open-source automated system for rapidly monitoring quality indicators in proteomics samples during data collection. QSample enhances the quality control framework by facilitating prompt actions and fast decision-making, ensuring that proteomics core facilities deliver data that adhere to best research practices.We acknowledge support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S grant funded by MCIN/AEI/10.13039/501100011033) and PID2020-115092GB-I00 funded by AEI/10.13039/501100011033 and the Generalitat de Catalunya through the CERCA programme and the Departament de Recerca i Universitats (2021-SGR2021-01225). We also acknowledge financial support from the Core for Life Challenge Projects program, and we specially thank An Staes, Teresa Maia, and Sara Dufour from the VIB Proteomics Core and the rest of the Core for Life Proteomics Working Group for their feedback and fruitful discussion. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech)
