The central banks’ approach to digital currencies : a literature review

Considering the growing relevance of digital currencies and the constant speculation regarding their future, this work aims to analyze the existing literature on the treatment given by central banks to digital currencies. Adopting the form of a systematic literature review, we focus on central bank digital currencies, debating their pros and cons, and elaborating on how they should be designed. We find that the pros seem to outcome the cons, and that there is a clear preference from the authors for a retail digital currency.Considerando a relevância crescente das moedas digitais e a constante especulação relativamente ao seu futuro, este trabalho procura analisar a literatura existente relativa ao tratamento dado pelos bancos centrais a moedas digitais. Através de uma revisão de literatura sistemática, o foco está nas moedas digitais emitidas por bancos centrais, nos seus prós e contras, e no debate relativamente à forma como estas devem ser desenhadas. Assim, conseguimos perceber que há um domínio dos prós relativamente aos contras e que os autores demonstram uma clara preferência por uma moeda digital de retalho disponível para todos os intervenientes

Stem cell-derived retinal pigment epithelium models of lysosomal dysfunction in disease

RESUMO:As doenças degenerativas da retina são as principais responsáveis pela perda de visão, nos países desenvolvidos. Frequentemente, a degeneração dos fotorrecetores ocorre devido à perda de função do Epitélio Pigmentar da Retina (RPE). A Degenerescência Macular relacionada com a idade (DMI) é uma doença degenerativa da área central da retina (mácula) que provoca uma perda progressiva da visão central. Pensa-se que a disfunção do RPE está na origem desta doença. Em particular, pensa-se que a conservação da função lisossomal destas células é de extrema importância no contexto de doença. O RPE é responsável por degradar e reutilizar componentes celulares, como proteínas e lípidos, que resultam do processamento diário dos terminais dos fotorrecetores, necessários ao bom funcionamento celular e ao processo visual. O declínio da função lisossomal tem sido apontado como estando envolvido numa série de doenças crónicas relacionadas com a idade. As células estaminais pluripotentes (hPSc) podem ser usadas como matéria prima para obter modelos de RPE in vitro fiáveis, que permitem ter acesso direto para identificar os mecanismos iniciais de doenças degenerativas da retina. O potencial de proliferação das células estaminais é praticamente ilimitado, pelo que a diferenciação destas células para RPE permite estabelecer uma produção sistemática de linhas humanas de RPE. Isto permite ultrapassar obstáculos existentes com as linhas de RPE disponíveis menos fiáveis ou mais difíceis de obter por culturas primárias. O trabalho aqui apresentado visou o desenvolvimento e a caracterização de um modelo in vitro de RPE derivado de células estaminais pluripotentes, com o objetivo final de estudar os eventos que estão na origem das retinopatias. Este modelo foi usado para explorar a importância da função lisossomal no processamento de material intracelular e, sobretudo, o papel da disfunção lisossomal em doenças do envelhecimento, com particular ênfase na DMI. Assim, foram otimizados protocolos de diferenciação de células estaminais em RPE e as células obtidas (hPSc-RPE) foram caracterizadas em detalhe. Baseado neste modelo celular, a disfunção lisossomal causada pelo processamento dos terminais externos dos fotorrecetores é proposta aqui como ferramenta de estudo, por reproduzir características chave da DMI. Para além disso, foi também implementado e caracterizado um modelo de disfunção lisossomal farmacológico, com base no tratamento de hPSc-RPE com cloroquina. Em iv particular, as células foram submetidas a regimes prolongados de exposição a este fármaco e a função lisossomal foi avaliada em vários períodos de estímulo. Nomeadamente, as células foram sujeitas a tratamentos agudos, continuados ou crónicos e foram demonstradas respostas diferenciadas, consoante os intervalos avaliados. Em primeiro lugar, as doses de cloroquina foram estabelecidas, com base em ensaios de viabilidade, de forma a escolher um regime não letal para as células, durante os tempos de estudo. Posteriormente, foi verificada a translocação nuclear de fatores de transcrição reguladores da função lisossomal. De seguida, as propriedades características dos lisossomas foram avaliadas, incluindo a capacidade de degradação de cargas fagocíticas, endocíticas e provenientes de autofagia, a atividade proteolítica das catepsinas e a acidez luminal. Para além disso, observou-se exocitose de lisossomas após tratamento com cloroquina, e com base na ultraestrutura do RPE, foi proposto que este seja um evento chave no desenvolvimento de doença. Vários dos resultados obtidos com hPSc-RPE foram confirmados em linhas primárias de RPE, humanas e de porco, de forma a reforçar e extrapolar as conclusões do estudo e relacionar com a biologia celular do RPE em geral. Por fim, os modelos celulares de RPE demonstraram reproduzir caraterísticas fundamentais de doenças degenerativas da retina relacionadas com o envelhecimento, nomeadamente com o aparecimento de depósitos subcelulares, tipicamente usados como identificadores de DMI. Adicionalmente, na secção de material suplementar, é apresentado um trabalho complementar, desenvolvido durante o percurso do doutoramento. Este trabalho consiste em estudos sobre o fator de crescimento endotelial vascular (VEGF) e sobre a sua regulação por parte de proteínas Rab do tráfego intracelular do recetor VEGFR2. Globalmente, este estudo abre portas a novas perspetivas para explorar modelos celulares de RPE, de forma a dissecar os mecanismos moleculares de degeneração por detrás das doenças da retina. Para além disso, os modelos aqui desenvolvidos têm o potencial para serem utilizados para estudar novas abordagens terapêuticas, de forma a restaurar a função lisossomal, e abrir caminho para estudos in vivo. Palavras-chave: Epitélio Pigmentar da Retina, diferenciação, células estaminais pluripotentes, modelos celulares de doença, disfunção lisossomal.ABSTRACT: Retinal degenerative disorders are the leading cause of vision impairment in developed countries. In many cases, photoreceptor degeneration occurs as a consequence of Retinal Pigment Epithelium (RPE) dysfunction. This is the case of Age-related Macular Degeneration (AMD) where progressive degeneration typically occurs, stemming from inadequate maintenance of the RPE cells. A crucial feature of this internal preservation is the ability to properly degrade and/or recycle the protein- and lipid- content which result from daily processing of Photoreceptor Outer Segments (POS). Degradation and recycling of cellular components are the main responsibilities attributed to lysosomes and remarkably, many age-related diseases stem from improper lysosomal health. Human Pluripotent Stem cells (hPSc) can be used as starting material to obtain reliable in vitro models of human RPE, providing direct access to identification of the initial events of many retinal degenerative diseases. Stem cell proliferation potential is virtually limitless, therefore hPSc differentiation into RPE paves the way for the standard production of reliable human RPE lines, without the hurdles of available, but unreliable RPE cell lines or the hardships of establishing RPE primary cultures. The present work focuses on the development and characterization of a human RPE in vitro model, derived from pluripotent stem cells, with the ultimate goal of studying retinopathies’ early events. This model was then used to explore the importance of the lysosome in intracellular cargo processing and the role of lysosomal dysfunction in agerelated disorders, in particular in the case of AMD. Accordingly, a stem cell differentiation protocol was optimized and a comprehensive characterization of the obtained hPSc-RPE cells was performed. Based on this cellular model, POS-induced lysosomal dysfunction is proposed as a tool, which can be used to recapitulate AMD disease features. Furthermore, a drug-based model featuring chloroquine-induced hPSc-RPE degeneration through lysosomal dysfunction was establish and characterized. In particular, cells were subjected to extended time-course chloroquine treatments and lysosomal function was thoroughly characterized. Specifically, cells were submitted to acute, continued and chronic treatments and shown to respond differently throughout these time courses. Firstly, chloroquine (CQ) dosage was titrated, based on viability assays, in order to establish under-lethal regimens considering experimental temporal settings. Nuclear translocation of lysosome-regulator transcription factors was verified. Moreover, a thorough characterization featuring relevant lysosomal properties was covered, including i ii their ability to degrade phagocytic, endocytic and autophagy cargoes, their cathepsin proteolytic activity and luminal acidity. Furthermore, lysosomal exocytosis was verified upon CQ treatment and, upon study of the RPE ultrastructure, is suggested as a key disease initiation event. Whenever possible, results obtained with hESc-RPE were repeated using primary RPE cell lines, human and porcine, reinforcing and extrapolating crucial findings to general RPE cell biology. Ultimately, RPE cellular models were shown to recapitulate crucial features of agerelated retinal degeneration, in particular, subcellular deposit formation, which constitutes the defining feature underlying AMD’s early events. Additionally, in the supplementary material, a side-project developed throughout the course of the PhD is presented. Specifically, this study regards VEGF regulation in a mouse RPE line, and in particular VEGF titration by Rab-regulated endocytic trafficking of the VEGFR2. Overall, this study opens new avenues to explore in vitro cellular models of RPE to dissect the molecular mechanisms of degeneration and also to explore new therapeutic approaches aiming to restore lysosomal function and ultimately pave the way for in vivo studies

Experimental study of the human anterolateral abdominal wall : biomechanical properties of Fascia and muscles

Tese de Mestrado Integrado. Bioengenharia (Engenharia Biomédica). Faculdade de Engenharia. Universidade do Porto. 201

The World Exhibitions and the display of science, technology and culture: moving boundaries

From the moment the first World Exhibition was held in London, in 1851, these events have served as “windows” to scientific, technological and industrial progress, allowing the circulation and the disclosure of this change, either directly to visitors or through media publications worldwide. Under the realisation of these world events, which attracted many travellers, exhibitions enabled the parallel organisation of international conferences and congresses of professionals both in science and in industry, engineering and architecture

Tradition and Modernity. The Historiography of The Survey on Regional Architecture

info:eu-repo/semantics/publishedVersio

Nationalism and Rural Modernization. The Spanish Tagus Valley colonization villages in the context of Southern European inner colonization

Between 1945 and 1965, thirty-three new agricultural pueblos de colonización [colonization villages] were built in the Spanish Tagus Valley under the action of the Instituto Nacional de Colonización (INC: 1939-1971). Associated with works of hydraulic infrastructures and soil transformation for an intensive use of irrigated crops, these villages deeply shaped the rural landscape in the scope of an intentional modernization process of the countryside. However, this process also contributes to achieve the agrarian utopia of the authoritarian catholic and conservative policy of Franco’s regime. In addition, the changed status of the settler into a small landowner and the notions imported from more urban context reflected in schemes of rural planning were crucial in order to avoid the exodus towards the city. This paper aims to explore the patterns used in the conception of the pueblos and their relation with national identity building process in the context of similar processes occurred in the Southern Europe. The relation between modernity and traditional references, both in urban shape and architectural design, will be explored, with special attention to the Civic Centre, a mandatory requirement of the pueblo’s programme, functioning as the core of the urban fabric. Its composition and facilities architectonic options will be analyzed, as well as its role in the power rhetoric. The articulation with coeval theoretical debates and external models will be used to understand in which level the Spanish experience contributes to the international architectural culture and the regional processThe presentation of this work was funded by national funds through FCT - Fundação para a Ciência e a Tecnologia, I.P., within the project UID/EAT/04041/2016 and it is based on the research conducted under the project MODSCAPES - Modernist Reinventions of the Rural Landscape (HERA.15.097). This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 649307info:eu-repo/semantics/publishedVersio

Photography and Vernacular Architecture: the Portuguese Approach

At least, from the 1880s, it is possible to identify the presence of popular architecture in surveys, which were formally or informally held in Portugal. However, the most significant survey was the Survey on Portuguese Regional Architecture carried out by the Portuguese Architects’ Union in the second half of the 1950s. This work, published in 1961, used mainly photography as a source of registration of the rural dwellings during the fieldwork. A photography made by architects who have shaped in this work a gaze and an insight that has become decisive in the subsequent architectural production. This work deals with the Survey as photographic record and way to look at vernacular architecture.This work was co-funded with FEDER funds by the Operational Competitiveness Programme – COMPETE and national funds by FCT – Fundação para a Ciência e Tecnologia within the project Photography, Modern Architecture and the “School of Oporto”: Interpretations Around Teófilo Rego Archive (PTDC/ ATP-AQI/4805/2012 - FCOMP-01-0124-FEDER-028054

The 19th century World Exhibitions and their photographic memories. Between historicism, exoticism and innovation in architecture

Peer Reviewe