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We examine how the coronavirus disease 2019 (COVID-19) pandemic has affected trade between Canada and the United States, using a novel dataset on monthly bilateral trade flows between Canadian provinces and US states merged with COVID-19 health data. Our results show that a one-standard-deviation increase in COVID-19 severity (case levels, hospitalizations, deaths) in a Canadian province leads to a 3.1 percent to 4.9 percent fall in exports and a 6.7 percent to 9.1 percent fall in imports. Decomposing our analysis by industry, we determine that trade in the manufacturing industry was most negatively affected by the pandemic, and the agriculture industry had the least disruption to trade flows. Our descriptive evidence suggests that lockdowns may also have reduced Canadian exports and imports. However, although our regression coefficients are consistent with that finding, they are not statistically significant, perhaps because of the lack of variation as a result of similar timing in the imposition of restrictions across provinces.Cet article examine l’incidence de la maladie à coronavirus 2019 (COVID-19) sur le commerce entre le Canada et les États-Unis. La recherche utilise un nouvel ensemble de données sur les échanges commerciaux bilatéraux mensuels entre les provinces canadiennes et les États américains croisées avec les données médicales reliées à la COVID-19. Nos résultats démontrent qu’un accroissement d’un seul écart-type de la sévérité de la COVID 19 (nombre de cas, hospitalisations, décès) dans une province canadienne a causé une chute de 3,1 à 4,9 pour cent des exportations et une chute de 6,7 à 9,1 pour cent des importations. En décomposant notre analyse par industrie, nous constatons que le commerce dans l’industrie manufacturière a été le plus touché négativement par la pandémie, et que le secteur agricole a été le moins perturbé quant aux échanges commerciaux. Nos données descriptives montrent que les périodes de confinement peuvent avoir réduit, à leur tour, les importations et exportations canadiennes. Cependant, même si nos coefficients de régression concordent avec ces résultats, ils ne sont pas pour autant significatifs statistiquement, peut-être en raison du manque de variation découlant des restrictions imposées dans toutes les provinces.

Enquadramento: O presente relatório reporta-se ao estágio de natureza profissional desenvolvido na Unidade de Saúde Familiar no Bombarral. Objetivo: Descrever e refletir sobre o percurso desenvolvido no contexto da prática clínica na aquisição de competências específicas em enfermagem de saúde familiar. Assim como, apresentar uma revisão sistemática de literatura com o título "Intervenção ao casal com filhos, com disfunção sexual, na transição para a parentalidade” desenvolvida em contexto de estágio. Com os objetivos gerais:1) compreender qual a intervenção do enfermeiro especialista em enfermagem de saúde familiar ao casal com filhos, com disfunção sexual na transição para a parentalidade; 2) aprofundar competências e conhecimento técnico, científico e humano acerca da temática da sexualidade e disfuncionalidade sexual, através da RSL com recurso à mnemónica PICO. Metodologia: Revisão sistemática de literatura com metodologia: PICO para dar resposta à questão: Quais as intervenções do enfermeiro especialista em Enfermagem de Saúde Familiar ao casal com filhos, com disfunção sexual, na transição para a parentalidade? Como critérios de inclusão foram definidos estudos de natureza qualitativa ou quantitativa, num horizonte temporal de 5 anos (2017-2022), em língua inglesa ou portuguesa e de outras áreas de conhecimento que não Enfermagem que consigam dar resposta à questão PICO. Os motores de busca consultados foram: EBSCO Host (CINAHL Complete; Medline Complete; Nursing&Allied Health Collection- comprehensive; MedicLatina) Pubmed e B-On. A pesquisa foi efetuada no dia 22 de janeiro de 2022, tendo sido encontrados 158 artigos. Os artigos foram analisados segundo os critérios de inclusão e exclusão estabelecidos e de acordo com o diagrama PRISMA Diagram Flow. (Apêndice VIII) Resultados: Após seleção foram incluídos três artigos específicos para responder à problemática identificada.

Blindness, the complete loss of eyesight is an issue that has affected people all over the world. With time medical, scientific, and technological advancements were made which have caused the cases of blindness throughout the world to steadily decrease, however, there are still many untreatable cases of blindness. According to the World Health Organization, in 2020, there were at least 2.2 billion people with near or distance vision impairment, with at least 1billion of these cases having moderate or severe vision impairment or blindness. For most people in their everyday lives, the majority of information gathered from the surrounding environment is trough visual senses, unfortunately, blind, or severely visually impaired people lack the ability to gather that information reliably. This often causes the navigation of environments to often be unsafe, unpleasant, and even distressing to blind people. This raises the necessity of providing these people with safe, comfortable tools that allow them to explore and navigate environments and train their orientation and mobility skills. This solution for exploration, navigation, and interaction with virtual environments, is an immersive 3D application with gamification elements for VR platforms, that allows the exploration of virtual environments. It provides users with a tool that can benefit their lifestyle by allowing a safe space to train their orientation, mobility, and interaction skills with the surrounding environment. This solution is destined to orientation and mobility trainers, institutions to aid the blind, but also to the end user, since it has the potential to enable the interaction with these virtual spaces to be unsupervised. This solution not only allows the navigation of virtual environments but is also heavily focused on promoting the interaction with virtual objects by the users, unlike other existing solutions which are heavily focused on environment navigation only. A prototype is developed, which consisted in the development of the immersive 3D application for virtual reality, by using a modern all-in-one virtual reality platform which provide head tracking via a headset and hand tracking via two hand controllers, which were used to simulate both a virtual blind cane and a virtual hand which the user controls using his hands. A fully dynamic 3D environment was created that offers the user a safe environment to train, providing him with full audio and haptic feedback allowing him to understand the environment and develop a cognitive mapping of it. The results of the usability tests performed using this solution proved that it is effective, and users were able to accomplish the objective without any visual feedback. At first users performed usability tests after receiving a set of instructions and a goal to accomplish inside the simulation. After completing the simulation users were asked to answer a questionnaire with a series of questions regarding their performance in the simulation and gave additional feedback for future development of the solution. This solution features a virtual environment which allows the users to train their motor skills contributing to the user’s quality of life, it also contributes to the scientific field of VR applied to the visual impaired by allowing the user to explore a living environment simulated in real time where he can interact with objects, identify them and their positions based on different feedback provided. This work also defines a set of evaluation metrics that can be used to characterize and evaluate previous and future work in this scientific field, along with defined requirements and objectives of the solution, contributing this way to the future of this scientific research field.

Background. During atherosclerotic plaque formation smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype We previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium binding protein. Aim. We investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. Results. We found that apelin was highly expressed in R-SMCs compared with S-SMCs. We observed a nuclear expression of apelin in SMCs within experimentally-induced intimal thickening of the porcine coronary artery and rat aorta. Plasmids targeting apelin to the nucleus (N. Ap) and to the secretory vesicles (S. Ap) were transfected into S-SMCs where apelin was barely detectable. Both plasmids induced the SMC transition towards a R-phenotype. Overexpression of N. Ap, and to a lesser degree S. Ap, led to a nuclear localization of S100A4. Stimulation of S-SMCs with platelet-derived growth factor-BB, known to induce the transition toward the R-phenotype, yielded nuclear expression of both apelin and S100A4. Conclusion. Apelin induces a SMC phenotypic transition towards the synthetic phenotype. These results suggest that apelin acts via nuclear re-localization of S100A4, raising the possibility of a new complex pro-atherogenic relationship between apelin and S100A4.

The aim of this Report is to describe the different stages of work that the team representing NOVA University in the 29th edition of the Willem C. Vis Moot Competition of 2022 went through in the past seven months of this project. In this Report, the Team will provide an overview of Willem C. Vis Moot followed by a detailed explanation of each member’s personal experience in the different stages of the competition, namely the process of writing the Memoranda and the preparation for the Pre-Moots and Oral Rounds. The issues raised by this year’s problem will then be analyzed as well as the impact of the competition and the importance it represents in our future paths as young professionals. This Report has been drafted by the four members of the Team as a group, except for the analyses of the relevant issues raised by the Arbitral Tribunal which has been developed individually according to our studies and research throughout the competition.

Funder: UK Regenerative Medicine Platform, Funder: Wellcome Trust, Funder: Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Funder: Chan Zuckerberg Initiative, Production of large quantities of hepatocytes remains a major challenge for a number of clinical applications in the biomedical field. Directed differentiation of human pluripotent stem cells (hPSCs) into hepatocyte-like cells (HLCs) provides an advantageous solution and a number of protocols have been developed for this purpose. However, these methods usually follow different steps of liver development in vitro, which is time consuming and requires complex culture conditions. In addition, HLCs lack the full repertoire of functionalities characterising primary hepatocytes. Here, we explore the interest of forward programming to generate hepatocytes from hPSCs and to bypass these limitations. This approach relies on the overexpression of three hepatocyte nuclear factors (HNF1A, HNF6, and FOXA3) in combination with different nuclear receptors expressed in the adult liver using the OPTi-OX platform. Forward programming allows for the rapid production of hepatocytes (FoP-Heps) with functional characteristics using a simplified process. We also uncovered that the overexpression of nuclear receptors such as RORc can enhance specific functionalities of FoP-Heps thereby validating its role in lipid/glucose metabolism. Together, our results show that forward programming could offer a versatile alternative to direct differentiation for generating hepatocytes in vitro.

Dissertação de Mestrado Integrado em Arquitetura Construção, O Brutalismo foi um movimento arquitetónico que surgiu entre as décadas de 1950 e 1970, no Reino Unido. A sua definição permanece, ao longo dos anos, incerta e ambígua. Contudo, uma primeira abordagem ao tema encaminha-nos para uma definição generalizada, com base numa determinada estética, fruto da narrativa principal do crítico e historiador Reyner Banham e das obras dos Arquitetos Alison e Peter Smithson. Atualmente, a perceção do movimento e as premissas que o constituem revelam-se diferentes das do passado, levando-nos a questionar sobre a então, aparente definição do movimento, perpetuada ao longo do tempo, que será também questionada no trabalho. Neste sentido, é proposto numa primeira fase da dissertação, a análise do Brutalismo enquanto movimento arquitetónico tendo em conta os diferentes pontos de vista de Alison e Peter Smithson e de Reyner Banham. De ressaltar que não é a intenção procurar uma definição ‘correta’ do Brutalismo, mas antes incentivar à discussão dos valores que o integram, permitindo avaliar a sua herança e possível presença num contexto contemporâneo. Como método de abordagem ao tema, são analisados individualmente os pontos de vista em cima mencionados, perante duas linhas cronológicas paralelas: a do casal de Arquitetos Alison e Peter Smithson, numa vertente mais tradicional e humanista, cujo o programa abrangia um conjunto de valores éticos atento às necessidades do usuário; e a de Reyner Banham, numa vertente mais tecnológica e artística, através da qual o autor entende o movimento como associado a uma linguagem formal, relacionada com a arte do pós-guerra, através do seu novo conceito de “Imagem” Esta aproximação ao tema tem, como finalidade, o desenvolvimento de uma posição crítica preparatória da última parte da dissertação. Nesta, que visa precisamente questionar possíveis formas de interpretar o movimento nos dias de hoje, uma vez que, aparentemente, a definição do movimento permanece em aberto, são analisadas quatro obras, e respetivos conceitos, de quatro arquitetos contemporâneos, à luz de premissas observadas no Brutalismo original: Anne Haltrop, Lacaton & Vassal, Peter Märkli e Diébédo Francis Kéré., Brutalism is an architectural movement that emerged between the 1950s and 1970s in the United Kingdom. Its definition remains, over the years, uncertain and ambiguous. In a first attempt to approach to the theme, it leads us to a general definition, based on its aesthetic, consequence of the main narrative between the critic and historian Reyner Banham and the works of the Architects Alison and Peter Smithson, which shows us only one side of the history of Brutalism. Currently, the perception of the movement and the principles of it, reveal themselves to be different from the ones in the past, making us question about the, given as certain, apparent finished designation of the movement, perpetuated over time, and that will be too, questioned in this work. In this sense, it is proposed, in a first phase of this dissertation, the analysis of the Brutalism as an architectural movement, taking into consideration the various and most important points of view and opinions, in this case, the ones of Alison and Peter Smithson and of Reyner Banham. It is relevant to mention that the intention of this work does not seek a definition for the theme, but to encourage a discussion of its values, allowing us to evaluate its heritage and its presence in the contemporary context. As a method of approaching the theme, the points of view mentioned above will be analyzed, as in two parallel chronological lines: the one about the Architects Alison and Peter Smithson, in a more traditional and humanist strand, in which their agenda consisted, entirely, in a unique set of ethical values attentive to the user's needs, breaking the modernist tradition, considered by them to be obsolete; and the one of Reyner Banham, in a more technological and artistic aspect, where the author considers the movement as a formal language, associated with post-war art, through his new concept of “Image”, capable of being reproduced through principles elaborate by him. This approach to the theme aims to elucidate the reader of the events of the movement and its stereotype, allowing them to obtain a critical position, needed for the last part of the work ,which aims, precisely, on questioning the various ways of interpreting the movement nowadays, since, apparently, the definition of it, remains open.

Climate and natural vegetation dynamics are key drivers of global vegetation fire, but anthropogenic burning now prevails over vast areas of the planet. Fire regime classification and mapping may contribute towards improved understanding of relationships between those fire drivers. We used 15 years of daily active fire data from the MODIS fire product (MCD14ML, collection 6) to create global maps of six fire descriptors (incidence, size inequality, season length, interannual variability, intensity, and fire season modality). Using multiple correspondence analysis (MCA) and hierarchical agglomerative clustering, we identified three fire macroregimes: Wild, Tamed, and Domesticated, each of which splitting into prototypical and transitional regimes. Interpretation of the six fire regimes in terms of their main drivers relied on the global maps of anthromes and Köppen climate types. The analysis yielded a two-dimensional space where the principal dimension of variability is primarily defined by interannual variability in fire activity and fire season length, and the secondary axis is based mainly on fire incidence. The Wild fire macroregime occurs mostly in cold wildlands, where burning is sporadic and fire seasons are short. Tamed fires predominate in seasonally dry tropical rangelands and croplands with high fire incidence. Domesticated fires are characteristic of humid, warm temperate and tropical croplands and villages with low fire incidence. The Tamed and Domesticated fire macroregimes, representing managed burning, account for 86% of all active fires in our dataset and for 70% of the global burnable area. Fourteen percent of active fires were found in the cold wildlands, and in the rangelands and forests of steppe and desert climates of the Wild macroregime. These results highlight the extent of human control over global pyrogeography in the Anthropocene.

Made available in DSpace on 2021-06-25T22:23:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-18 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Molybdenum (Mo) is an essential micronutrient involved in several biochemical reactions that influence biological nitrogen fixation (BNF). Plants are known to require less molybdenum. The objective of this study was to evaluate the effect of Mo foliar application on four soybean cultivars (Glycine max [L.] Merrill) and their physiological qualities, crude protein, and lipid content. The experimental design was completely randomized, in a 4 x 3 factorial arrangement, with four replicates. Three Mo application rates (0, 400, and 800 g ha(-1)) were used for the AS 3730 IPRO, Bonus IPRO, Desafio RR, and BMX Potencia RR cultivars during their R3 and R5 reproductive stages. The Mo concentration, nutritional parameters (crude protein [CP] and lipids), and physiological quality (electrical conductivity, vigor, aging seed, and germination) of the seeds were then evaluated. The cultivars x Mo application rate interaction had no significant effect. There was an observed increase in Mo content with molybdic leaf fertilization. The BMX Bonus IPRO and BMX Potencia RR cultivars had the best response, with increased Mo concentration within the seeds. The Mo rates did not influence CP and lipids. However, the soybean cultivar x Mo application rate interaction significantly affected the germination percentage and percentage of accelerated aging seeds. Univ Estadual Londrina, Dept Crop Sci, Londrina, Parana, Brazil Sao Paulo State Univ, Dept Crop Sci, Ilha Solteira, Brazil Embrapa Soja, Dept Soil Fertil & Plant Nutr, Londrina, Parana, Brazil Sao Paulo State Univ, Dept Crop Sci, Ilha Solteira, Brazil

In this paper, I examine the welfare impact of migration in a general equilibrium model with endogenous worker location choice. My framework incorporates labor productivity differences across countries, worker heterogeneity in productivity across skill and nativity types, as well as country-pair specific costs of migration. In a series of experiments, I predict the migration response of workers to an expansion or contraction in the number of European Union (EU) member countries. For the case of the United Kingdom (U.K.) leaving the EU, commonly referred to as Brexit, low skilled native-born U.K. workers suffer a drop-in income, whereas high skilled workers experience an increase. This result is driven, in part, by an increase in high skilled immigration to the U.K. from outside the EU, which helps to dampen the loss in income of low skilled workers.

Resumo: A parte inicial desse trabalho faz uma reflexão sobre o conceito de paradigma e traça uma comparação entre os paradigmas da pesquisa quantitativa em detrimento da pesquisa qualitativa, buscando compreender o contexto de aplicação desses dois tipos de pesquisa e seu histórico. Se objetiva fazer também uma análise dos critérios específicos para aferição da qualidade científica desses tipos de estudos, bem como uma análise do paradigma da pesquisa qualitativa em educação e as formas de garantia da validade e fidelidade dos estudos de natureza interpretativa ou qualitativa.

Resumo: O presente trabalho faz uma reflexão sobre a Epistemologia das Ciências Sociais da Educação. Será realizado uma descrição de como a Sociologia pode contribuir para formação de profissionais da educação. Retrata também o desafio de estabelecer um conceito para educação a partir de uma análide kantiana, e do visionamento de Ken Robinson. Será discutido o conceito de ciência sob a ótica de alguns dos principais epistemólogos da ciência e, por fim a utilização desses conceitos permitira também uma análise da noção de cientificidade aplicada a educação na perspectiva de Anisio Teixeira e de Gilles Gaston Granger.

Resumo: Neste artigo, será desenvolvido um estudo à luz de uma das células do cubo de Bray e Thomas (1995) amplamente citado na literatura associada ao campo da educação comparada. Será feito um recorte na célula do cubo que se relaciona com os termos: países, crenças ou religião e currículo. A opção por essa metodologia se relaciona com os fenômenos educacionais, alvos do interesse desse autor. O objetivo deste artigo é analisar como as crenças epistemológicas em diferentes países do ocidente, interferem no estabelecimento do currículo acerca do que deve ser ensinado sobre a origem e evolução da vida. Apesar de bem estabelecida na literatura científica, a teoria da evolução ainda se apresenta como assunto controverso entre professores e estudantes nas salas de aulas. Essa temática já originou histórias nos tribunais dos Estados Unidos, mas a problemática não se resume a esse país. Pesquisas apontam a dificuldade de professores e estudantes em assimilar esses conceitos em diversas partes do mundo. Esse trabalho está estruturado em três partes: Num primeiro momento fazemos uma reflexão sobre o conceito de currículo e suas aplicações ideológicas. A segunda parte é caracterizada como exploratória, onde se buscou conhecimento sobre o ensino desse assunto em diversos países, principalmente naqueles nomeadamente cristãos. E, finalmente na terceira etapa, percebemos que diferentes correntes de paradigmas moldam o ensino dessa temática, como o cientificismo, a doxologia e a teologia.

A presente dissertação analisa a temática da influência da responsabilidade social no planeamento fiscal nas empresas cotadas na Euronext Lisbon. Embora os estudos científicos sobre a responsabilidade social das empresas e sobre o planeamento fiscal tenham décadas, na verdade, a análise conjunta destas duas temáticas é uma área de investigação em desenvolvimento e que carece de contributos empíricos. Esta linha de investigação é relativamente recente na literatura, uma vez que, a maioria dos estudos empíricos foram realizados apenas na última década. De facto, os estudos científicos existentes dedicam-se ao estudo da responsabilidade social ou ao estudo do planeamento fiscal de modo independente. Porém, é hoje reconhecido que as práticas no âmbito da responsabilidade social realizadas por uma empresa podem ter influência naquelas que são as suas atividades de planeamento fiscal. O estudo é realizado para uma amostra de 30 empresas cotadas na bolsa Euronext Lisbon, para os períodos de 2018 e 2019. Para estudar as hipóteses de investigação foi desenvolvido um modelo de regressão linear múltipla. Os resultados mostram que não existe influência das componentes social, governo das sociedades, ambiental e económica da responsabilidade social no planeamento fiscal. No entanto, evidenciam que a dimensão da empresa tem uma influência negativa no planeamento fiscal, se utilizarmos como variável dependente a Current ETR. Deste modo, esta dissertação tem como valor acrescentado contribuir para uma área de investigação com poucas evidências empíricas tanto para a realidade portuguesas como numa dimensão internacional.

O presente relatório de estágio é redigido no âmbito do estágio curricular inserido no 2.º ano do curso de Mestrado em Solicitadoria de Empresa, lecionado na Escola Superior de Tecnologia e Gestão, do Politécnico de Leiria. O estágio teve a duração de sete meses, e teve como principal objectivo a aquisição de conhecimento e experiência nas áreas do Direito Laboral e Direito da Insolvência e Recuperação Empresas. No decurso dos sete meses foram realizadas diversas actividades como contratos de trabalho de várias modalidades, notas informativas, reestruturações de horários de trabalhadores, cálculo de créditos emergentes de contrato de trabalho, processos de layoff, despedimentos, pedidos de insolvência e reclamações de créditos. Este relatório divide-se em duas secções – principais atividades desenvolvidas e irredutibilidade da retribuição, com a primeira dividida em duas sub-secções – Direito Laboral e Direito da Insolvência.

Direct pulp capping consists of a procedure in which a material is directly placed over the exposed pulp to maintain dental vitality. Although still widely used in clinical practice, previous in vitro studies found that the biomaterial Life® presented high cytotoxicity, leading to cell death. This study aimed to identify the Life® constituents responsible for its cytotoxic effects on odontoblast-like cells (MDPC-23). Aqueous medium conditioned with Life® was subjected to liquid–liquid extraction with ethyl acetate. After solvent removal, cells were treated with residues isolated from the organic and aqueous fractions. MTT and Trypan blue assays were carried out to evaluate the metabolic activity and cell death. The organic phase residue promoted a significant decrease in metabolic activity and increased cell death. On the contrary, no cytotoxic effects were observed with the mixture from the aqueous fraction. Spectroscopic and spectrometric methods allowed the identification of the toxic compounds. A mixture of the regioisomers ortho, para, and meta of N-ethyl-toluenesulfonamide was identified as the agent responsible for the toxicity of biomaterial Life® in MDPC-23 cells. These findings contribute to improving biomaterial research and development.

Exame público realizado em 19 de janeiro de 2023, às 14h30 Dissertação de mestrado em Arquitetura Existem muitos monumentos com valor arquitetónico que se encontram em estado de degradação, o que exige estratégias de intervenção que assegurem a sua preservação. A presente investigação, focada no Mosteiro de Santo André de Rendufe, procura perceber de que forma uma intervenção no património arquitetónico motivada pela alteração funcional e consequente transformação física garante e possibilita a preservação de valores patrimo-niais. O estudo centra-se em como uma transformação num monumento decorrida de qual-quer tipo de intervenção consegue contribuir para a permanência dos valores que o deter-minam como património. Procura-se assim investigar metodologias de reabilitação e os processos de transformação e de redefinição das caraterísticas espaciais e funcionais no património arquitetónico. Para a consolidação do tema, recorre-se ao estudo de referências teóricas e investigam-se três casos de estudo: Torre de Mérola (Carles Enrich Studio); Neues Museum (David Chipperfield); e o Atelier Des Createurs (Nuno Valentim). Estes permitem analisar diferen-tes metodologias e abordagens que garantem a preservação dos valores, não alterando a sua identidade. Formula-se, em conclusão, que a problemática reside em prevenir que o edifício seja esquecido e deixado ao abandono, tentando que o mesmo se prolongue no tempo, ainda que com diferente uso, mas sem perder os seus valores iniciais que o caraterizam. Através de intervenções cuidadas, procura-se dar resposta a novos usos sem comprometer a pree-xistência, aproveitando programas e estruturas que possam acompanhar as novas necessi-dades contemporâneas. Assim, espera-se com este trabalho valorizar o edifício existente e a preservação do património arquitetónico e histórico. There are many monuments with architectural value that are in a state of degradation, which requires intervention strategies to ensure their preservation. The present investiga-tion, focused on the Monastery of Santo André de Rendufe, seeks to understand how an intervention in the architectural heritage motivated by the functional change and conse-quent physical transformation guarantees and enables the preservation of heritage values. The study focuses on how a transformation in a monument resulting from any type of inter-vention can contribute to the permanence of the values that determine it as a heritage. Thus, we seek to investigate rehabilitation methodologies and the processes of transfor-mation and redefinition of spatial and functional characteristics in the architectural herit-age. For consolidation, the study of theoretical references is used and three case studies are investigated: Merola Tower (Carles Enrich Studio); Neues Museum (David Chipperfield); and the Atelier Des Createurs (Nuno Valentim). These examples allow us to analyze differ-ent methodologies and approaches that guarantee the preservation of values, without changing their identity. In conclusion, the goal lies in preventing the building from being forgotten and aban-doned, and therefore trying to extend it over time, albeit with different use, but without los-ing its initial characteristic values. With careful interventions, we seek to provide new uses without compromising pre-existence, taking advantage of programs and structures that can keep up with new contemporary needs. Thus, it is expected with this work to value the existing building and the preservation of the architectural and historical heritage.

En este artículo se evalúan las diferencias en la evolución sectorial y regional de la economía española durante la crisis del COVID-19. Para ello se analiza la heterogeneidad en indicadores sanitarios, las restricciones a la movilidad, la evolución del empleo, del gasto en tarjetas, la actividad y el bienestar entre los distintos sectores y regiones españolas. También se realiza un ejercicio de simulación del contrafactual para cada región de cuál hubiera sido su evolución diferencial respecto a la estructura sectorial de la región española promedio. Los resultados apuntan que, desde el primer trimestre de 2020 hasta el segundo de 2021, el componente sectorial explicaría el 44 % de las diferencias en la evolución del empleo regional respecto al de España, mientras que el componente idiosincrático el 56 % restante.

Dissertação de Mestrado em Construção Metálica e Mista apresentada à Faculdade de Ciências e Tecnologia Na construção de pavilhões industriais, as estruturas metálicas têm vindo a perder competitividade em relação às estruturas em betão armado (pré-fabricado), principalmente, devido à regulamentação prescritiva de segurança contra incêndios (ISO 834) que muitas vezes é adotada, que tem penalizado sistematicamente as soluções em aço. A abordagem com base no desempenho (utilizando o OZone 3 com modelos até duas zonas) recorrendo a modelos de incêndios naturais, tendo em conta várias características do edifício em análise, pode conduzir a soluções mais otimizadas. Uma outra forma de aumentar a competitividade das estruturas em aço, passa por otimizar a proteção passiva, nomeadamente a espessura de tinta intumescente (que representa um peso significativo no custo total da estrutura metálica), sendo feito um balanço entre otimização estrutural (peso) e otimização dessa espessura. Ou seja, se economicamente é mais benéfico ter uma secção mais esbelta, com menos peso mas com maior necessidade de proteção passiva, ou, se por outro lado, uma secção mais pesada mas com menor necessidade de proteção passiva. Nesta dissertação será feito um estudo comparativo entre soluções metálicas (com base na aplicação em pavilhões industriais) considerando diferentes classes de aço, nomeadamente S275, S355 e S460. Por outras palavras, se compensa ter uma estrutura globalmente mais pesada em aço da classe S275, cujo custo unitário é menor, contrapondo com uma solução em aço da classe S355 ou em aço de alta resistência S460, que será mais leve, mas que terá um custo unitário superior. Esta análise irá ter em conta o comportamento estrutural do edifício, contemplando vários parâmetros do dimensionamento como, a deformação, encurvadura, entre outros, em que a mudança de classe de aço poderá já não trazer grandes benefícios no desempenho global da estrutura. Por último, será feita uma avaliação da sustentabilidade da solução em aço comparativamente com a solução em betão, através duma análise de ciclo de vida das soluções estruturais analisadas, já que este requisito será cada vez mais um fator diferenciador na seleção das soluções estruturais, respondendo aos desafios lançados no pacto ecológico europeu. In the construction of industrial buildings, steel structures have been losing competitiveness comparing to reinforced concrete structures (precast), mainly, due to the prescriptive fire safety regulation (ISO 834) that is often adopted, which has systematically penalized steel solutions. The performance-based approach (using OZone 3 with models up to two zones), with models of natural fires, taking into account various characteristics of the building under analysis, may lead to more optimized solutions. Another way to increase the competitiveness of steel structures is to optimize passive protection, particularly the thickness of intumescent paint (which represents a significant weight in the total cost of the metal structure), with a balance being made between structural optimization (weight) and paint thickness optimization. This means, if economically it is more beneficial to have a slender section, with less weight but greater need for passive protection, or, if on the other hand, a heavier section but less need for passive protection. In this thesis a comparative study will also be made between metal solutions (based on application in industrial buildings) considering different grades of steel, namely S275, S355 and S460. In other words, if pays to have an overall heavier structure in grade S275 steel, whose cost per kg is lower, as opposed to a solution in grade S355 steel or high-resistance steel S460, which will be lighter but will have a higher cost per kg. This analysis will take into account the structural behaviour of the building, contemplating several design parameters such as deformation, buckling, among others, in which the change of steel grades may no longer bring great benefits to the overall performance of the structure. Finally, the sustainability of the steel solution will be assessed, through a life cycle analysis of the structural solutions, as this requirement will increasingly be a differentiating factor in the selection of the structural solutions, responding to the challenges launched in the European ecological pact.

Anais do Instituto de Higiene e Medicina Tropical, v. 20 (2021): Suplemento n�� 1 - Perspetivas sobre a educa����o m��dica em Angola

OBJECTIVE This review aims to systematically examine the effectiveness of photodynamic therapy for the treatment of patients with recurrent oral squamous cell carcinoma. INTRODUCTION Oral squamous cell carcinoma is a significant public health problem, and is the seventh most common cancer. Its incidence is mainly due to tobacco use, alcohol consumption, and HPV infection. The survival rates are poor due to diagnosis at advanced stages, with high recurrence rates. Although current evidence does not point to photodynamic therapy as a first-line option, this treatment might be suitable for treating recurrent stages of the cancer where conventional treatments were ineffective. Despite the potential of photodynamic therapy, there is a need to verify the scientific evidence to support its indication for the treatment of recurrent oral squamous cell carcinoma. INCLUSION CRITERIA This review will consider studies on any stage of recurrent oral squamous cell carcinoma treated with photodynamic therapy after receiving first-line conventional treatments. Patients of any age, gender, and geographic location will be included. The primary outcomes will be to evaluate response to treatment, focusing on remission, recurrence, change in size of the lesion, alleviation of symptoms, and survival. Secondary outcomes will be postoperative complications, presence of necrosis, patient quality of life after treatment, and patient satisfaction. METHODS Studies will be searched using a combination of index terms and keywords in MEDLINE, Cochrane Central, Web of Science, Embase, and ClinicalTrials.gov. No date limits will be applied. Articles written in English, French, Spanish, or Portuguese will be considered. Findings will be provided as a narrative synthesis, structured around the photodynamic therapy protocol used. A meta-analysis is planned and subgroup analysis will be conducted if possible. The certainty of findings will be assessed. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO CRD42020141075.

Consumption of lipid-rich foods can increase the blood cholesterol content. b-glucans have hypocholesterolemic effect. However, subtle changes in their molecular branching can influence bioactivity. Therefore, a comparative investigation of the cholesterol-lowering potential of two b-glucans with different branching patterns and a cholesterol-lowering drug, namely simvastatin was undertaken employing the zebrafish (Danio rerio) model of diet-induced hypercholesterolemia. Fish were allocated to 5 dietary treatments; a control group, a high cholesterol group, two b-glucan groups, and a simvastatin group. We investigated plasma total cholesterol, LDL and HDL cholesterol levels, histological changes in the tissues, and explored intestinal transcriptomic changes induced by the experimental diets. Dietary cholesterol likely caused the suppression of endogenous cholesterol biosynthesis, induced dysfunction of endoplasmic reticulum and mitochondria, and altered the histomorphology of the intestine. The two b-glucans and simvastatin significantly abated the rise in plasma cholesterol levels and restored the expression of specific genes to alleviate the endoplasmic reticulum-related effects induced by the dietary cholesterol. Furthermore, the distinct patterns of transcriptomic changes in the intestine elicited by the oat and microalga b-glucans impacted processes such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat and microalgal b-glucans also altered the pattern of lipid deposition in the liver. Our study provides insights into the effectiveness of different b-glucans to alleviate dysfunctions in lipid metabolism caused by dietary cholesterol.

The aim of this paper is to detect evidence of cartel in the application of volatility models in price data of gas dealers in the municipalities of Belém/PA and Santarém/PA. Cartels are coordinated actions between firms in which there are tacit or explicit agreements aimed at price coordination, quantities offered and/or market slices, to maximize profit jointly. For the detection of cartels, arch, GARCH, EGARCH and TGARCH volatility models will be applied. The data used are the average weekly gasoline prices extracted from the official portal of the National Agency for Petroleum, Natural Gas and Biofuels (ANP), in the period from 2004 to 2020. The results of the equation for mean showed no indications of cartel, while the ARCH model for variance detected only in Belém. There were no indications of the presence of asymmetric shocks in the Belém series, with only the occurrence in Santarém. It is concluded that the methodology is useful for the detection of cartels of gasoline dealers. El objetivo de este artículo es detectar evidencias de cártel en la aplicación de modelos de volatilidad en los datos de precios de las estaciones de los distribuidores de gasoline municipios de Belém/PA y Santarém/PA. Los cárteles son acciones coordinadas entre empresas en las que existen acuerdos tácitos o explícitos destinados a la coordinación de precios, cantidades ofrecidas y/o rebanadas de mercado, para maximizar las ganancias juntos. Para la detección de cárteles se aplicarán los modelos de volatilidad arch, GARCH, EGARCH y TGARCH. Los datos utilizados son los precios promedio semanales de la gasolina extraídos del portal oficial de la Agencia Nacional del Petróleo, Gas Natural y Biocombustibles (ANP), de 2004 a 2020. Los resultados de la ecuación para la media no mostraron indicios de cártel, mientras que el modelo ARCH para la varianza se detectó solo en Belém. No hubo indicios de la presencia de choques asimétricos en la serie de Belém, con sólo la ocurrencia en Santarém. Se concluye que la metodología es útil para la detección de cárteles de distribuidores de gasolina. O objetivo deste artigo é detectar indício de cartel na aplicação de modelos de volatilidade em dados de preços de postos revendedores de gasolina dos municípios de Belém/PA e Santarém/PA. Cartéis são ações coordenadas entre firmas nas quais há acordos tácitos ou explícitos objetivando a coordenação de preços, quantidades ofertadas e/ou fatias de mercado, para maximização de lucro conjuntamente. Para detecção dos cartéis, serão aplicados modelos de volatilidade ARCH, GARCH, EGARCH e TGARCH. Os dados utilizados são os preços médios semanais de gasolina extraídos do portal oficial da Agência Nacional do Petróleo, Gás Natural e Biocombustíveis (ANP), no período de 2004 a 2020. Os resultados da equação para média não apontaram indícios de cartel, enquanto o modelo ARCH para variância detectou apenas em Belém. Não houve indícios de presença de choques assimétricos na série de Belém havendo apenas a ocorrência em Santarém. Conclui-se que a metodologia é útil para a detecção de cartéis de revendedores de gasolina.

This study aimed to assess the cytotoxicity of commercially available adhesive strategies—etch-and-rinse (Adper™ Scotchbond™ 1 XT, 3M ESPE, St. Paul, MN, USA, SB1), self-etch (Clearfil™ SE Bond 2, Kuraray Noritake Dental Inc., Tokyo, Japan, CSE), and universal (Scotchbond™ Universal, 3M Deutschland GmbH, Neuss, Germany, SBU). MDPC-23 cells were exposed to adhesives extracts in different concentrations and exposure times. To access cell metabolic activity, viability, types of cell death, and cell cycle, the MTT assay, SRB assay, double labeling with annexin V and propidium iodide, and labeling with propidium iodide/RNAse were performed, respectively. Cultures were stained with May-Grünwald Giemsa for qualitative cytotoxicity assessment. The SB1, CSE, and SBU extracts determined a significant reduction in cell metabolism and viability. This reduction was higher for prolonged exposures, even for less concentrated extracts. CSE extracts significantly reduced the cell’s metabolic activity at higher concentrations (50% and 100%) from 2 h of exposure. After 24 and 96 h, a metabolic activity reduction was verified for all adhesives, even at lower concentrations. These changes were dependent on the adhesive, its concentration, and the incubation time. Regarding cell viability, SBU extracts were the least cytotoxic, and CSE was significantly more cytotoxic than SB1 and SBU. The adhesives determined a reduction in viable cells and an increase in apoptotic, late apoptosis/necrosis, and necrotic cells. Moreover, on cultures exposed to SB1 and CSE extracts, a decrease in the cells in S and G2/M phases and an increase in the cells in G0/G1 phase was observed. Exposure to SBU led to an increase of cells in the S phase. In general, all adhesives determined cytotoxicity. CSE extracts were the most cytotoxic and were classified as having a higher degree of reactivity, leading to more significant inhibition of cell growth and destruction of the cell’s layers.

Despite the significant advances of antibodies as therapeutic agents, there is still much room for improvement concerning the discovery of these macromolecules. Here, we present a new synthetic cell-based strategy that takes advantage of eukaryotic cell biology to produce highly diverse antibody libraries and, simultaneously, link them to a high-throughput selection mechanism, replicating B cell diversification mechanisms. The interference of site-specific recognition by CRISPR/Cas9 with error-prone DNA repair mechanisms was explored for the generation of diversity, in a cell population containing a gene for a light chain antibody fragment. We achieved up to 93% of cells containing a mutated antibody gene after diversification mechanisms, specifically inside one of the antigen-binding sites. This targeted variability strategy was then integrated into an intracellular selection mechanism. By fusing the antibody with a KDEL retention signal, the interaction of antibodies and native membrane antigens occurs inside the endoplasmic reticulum during the process of protein secretion, enabling the detection of high-quality leads for expression and affinity by flow cytometry. We successfully obtained antibody lead candidates against CD3 as proof of concept. In summary, we developed a novel antibody discovery platform against native antigens by endoplasmic synthetic library generation using CRISPR/Cas9, which will contribute to a faster discovery of new biotherapeutic molecules, reducing the time-to-market.

Small interfering RNA (siRNA) application in therapy still faces a major challenge with the lack of an efficient and specific delivery system. Current vehicles are often responsible for poor efficacy, safety concerns, and burden costs of siRNA-based therapeutics. Here, we describe a novel strategy for targeted delivery of siRNA molecules to inhibit human immunodeficiency virus (HIV) infection. Specific membrane translocation of siRNA inhibitor was addressed by an engineered nanobody targeting the HIV co-receptor CXCR4 (NbCXCR4) in fusion with a single-chain variable fragment (4M5.3) that carried the FITC-conjugated siRNA. 4M5.3-NbCXCR4 conjugate (4M5.3X4) efficiently targeted CXCR4+ T lymphocytes, specifically translocating siRNA by receptor-mediated endocytosis. Targeted delivery of siRNA directed to the mRNA of HIV transactivator tat silenced Tat-driven viral transcription and inhibited the replication of distinct virus clades. In summary, we have shown that the engineered nanobody chimera developed in this study constitutes an efficient and specific delivery method of siRNAs through CXCR4 receptor.