Novos mediadores locais da inflamação : proctetinas e resolvinas

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas MonizDiariamente o nosso corpo está sujeito a danos físicos ou infeções por microrganismos exógenos, este responde desencadeando uma resposta inflamatória, que consiste numa reação local e sistémica onde ocorreu a alteração estrutural do tecido, sendo o principal objetivo detetar e eliminar os fatores que interferem com a homeostase do organismo. No início da resposta inflamatória, as células inflamatórias invasivas produzem vários mediadores pró-inflamatórios aumentando o grau da inflamação e basicamente dois mecanismos de defesa: uma resposta inata e uma resposta imune adquirida. Dependendo do momento da resposta inflamatória, os mediadores lipídicos são formados não só com o objetivo de inibir a inflamação, mas também para acelerar a resolução da inflamação. Os mediadores lipídicos de pro-resolução como as lipoxinas, resolvinas, maresinas e proctetinas, são sintetizados a partir do ácido araquidónico e de ácidos gordos essenciais, como o ácido docosahexaenóico e o ácido eicosapentaenóico, durante a fase de resolução da inflamação aguda. Funcionalmente, estes mediadores lipídicos estimulam e aceleram a resolução através de mecanismos multifatoriais ao nível dos tecidos. Estes mediadores lipídicos pró-resolução têm sido considerados como um novo meio para o tratamento de diferentes tipos de doenças inflamatórias

Digital Marketing in Portuguese Religious Organizations

Digital Marketing has changed how organizations communicate with their audiences. The internet has become part of every consumer’s life, as they are increasingly online. Therefore, marketers taken marketing to the digital space through several digital marketing tools. However, Non-profit organizations (NPOs), including religious organizations, have been slow to adapt to this new way of communication. NPOs characteristics cause barriers which justify this delay. Religious organizations have specific characteristics which further difficult digital marketing usage. It is interesting, therefore, to study the adoption of digital marketing in the Portuguese religious context. For the present study, 10 of the main protestant religious organizations were interviewd. This purposive sample was used after a previous analysis of the digital space of religious organizations. However, others were contacted without previous knowledge about their digital presence. The findings showed that, although not every organization prioritizes digital marketing the same way, each organization uses digital marketing tools to some extent, with social media being the main digital marketing tool. The main difference between them is their objective: member maintenance or member acquisition. Overall, this study gives insights into the development of digital marketing in protestant religious organizations in Portugal, their perspectives, the reasons for not using it more intensively, the tools are being used, the objectives they have and the targets they are addressing

The relationships between portuguese banks and their customers in a recessionary context

Financial institutions were in the genesis of the crisis that led to the current recession. This dissertation aims to understand better the relationship Portuguese people have with their banks in a recessionary context, to provide knowledge that may contribute to the Marketing field of research and to the Banking industry. Having that purpose in mind, a quantitative study was conducted using data gathered by questionnaire using a sample of 488 respondents, which was further complemented by the information collected applying Netnography. The overall analysis suggests that the impact of the crisis on the household financial situation throughout the last couple of years influences attitudes towards money and expenses. The way customers’ purchase and consumption behaviors were affected by crisis are, to some extent, positively related to the satisfaction with the main bank. From the Relationship Marketing constructs addressed, only two are important to explain customer loyalty in a recessionary context, implying that marketing researchers and practitioners might need to adapt their conducts according to the economic conjuncture.As instituições financeiras estiveram na génese da crise que conduziu à actual recessão. Esta dissertação pretende entender melhor a relação que os portugueses têm com os seus bancos num contexto de crise, de modo a providenciar conhecimento que possa contribuir para a investigação na área de Marketing e do sector da banca. Com esse objectivo em mente, foi elaborado um estudo quantitativo que tirou partido da informação obtida por intermédio de um questionário feito a 488 inquiridos, tendo sido posteriormente complementado com dados adquiridos através da Netnografia. A análise global indica que o impacto da crise na situação financeira dos agregados familiares nos últimos 2 anos, influencia atitudes em relação ao dinheiro e as despesas. O modo como os comportamentos de consumo e compra dos consumidores foi afectado está, em certa medida, relacionado com a satisfação relativa ao banco principal. Dos construtos do Marketing Relacional abordados, apenas dois são importantes para explicar a fidelidade dos consumidores, implicando uma adaptação das condutas dos investigadores e profissionais de Marketing, de acordo com a conjuntura económica

Social Media Text Processing and Semantic Analysis for Smart Cities

With the rise of Social Media, people obtain and share information almost instantly on a 24/7 basis. Many research areas have tried to gain valuable insights from these large volumes of freely available user generated content. With the goal of extracting knowledge from social media streams that might be useful in the context of intelligent transportation systems and smart cities, we designed and developed a framework that provides functionalities for parallel collection of geo-located tweets from multiple pre-defined bounding boxes (cities or regions), including filtering of non-complying tweets, text pre-processing for Portuguese and English language, topic modeling, and transportation-specific text classifiers, as well as, aggregation and data visualization. We performed an exploratory data analysis of geo-located tweets in 5 different cities: Rio de Janeiro, S\~ao Paulo, New York City, London and Melbourne, comprising a total of more than 43 million tweets in a period of 3 months. Furthermore, we performed a large scale topic modelling comparison between Rio de Janeiro and S\~ao Paulo. Interestingly, most of the topics are shared between both cities which despite being in the same country are considered very different regarding population, economy and lifestyle. We take advantage of recent developments in word embeddings and train such representations from the collections of geo-located tweets. We then use a combination of bag-of-embeddings and traditional bag-of-words to train travel-related classifiers in both Portuguese and English to filter travel-related content from non-related. We created specific gold-standard data to perform empirical evaluation of the resulting classifiers. Results are in line with research work in other application areas by showing the robustness of using word embeddings to learn word similarities that bag-of-words is not able to capture

Cellulose Liquefaction : Optimization of Reaction Parameters

Tese de mestrado, Química Tecnológica, 2021, Universidade de Lisboa, Faculdade de CiênciasNeste trabalho estudou-se a optimização dos parâmetros reacionais da liquefação direta de biomassa lignocelulósica. O solvente usado foi 2-etilhexanol com um liquor ratio de 5:1 (solvente:biomassa), juntamente com o catalisador ácido p-toluenossulfónico (PTSA). Com o objectivo de obter a defnir um modelo experimental, foram efectuadas 17 reacções variando parâmetros como a temperatura, o tempo de reacção e a quantidade de catalisador. As condições ideais foram obtidas a 170 ºC, com 3 horas de reacção e 3% (m/m) de catalisador, resultando num rendimento de 84.8%. Os bio-óleos produzidos foram caracterizados por espectroscopia de infravermelhos e análise elementar tendo-se também determinado a densidade e as viscosidades cinemática e dinâmica. A avaliação dos resultados permitiu confirmar que a temperatura se trata do parâmetro reacional mais influente tendo-se concluído que abaixo dos 170 ºC não se verifica a formação de um grupo carbonilo no espectro FTIR do bio-óleo. O aumento de reacções secundárias com o aumento do tempo de reação também é verificado pela espectroscopia de infravermelhos. As propriedades químicas dos bio-óleos, como a densidade e ambos os tipos de viscosidade, aumentam com a conversão da celulose. A análise elementar permitiu estimar o HHV dos bio-óleos e dos resíduos sólidos tendo sido 30.16 MJ Kg-1 o maior valor obtido, um valor ainda distante dos derivados de combustíveis fósseis. No entanto, o HHV dos resíduos sólidos revelou-se superior ao da celulose pura potenciando a hipótese de aplicar o processo de liquefação ao resíduo sólido de liquefações posteriores.The present work studied the optimization of the reaction parameters in lignocellulosic biomass liquefaction. The solvent used was 2-ethylhexanol with a 5:1 liquor ratio (solvent:biomass) and the used catalyst was p-toluenosulfonic acid (PTSA). To understand the best reaction media for the biomass conversion, 17 reactions were performed varying the reaction temperature, reaction time and catalyst amount. The optimum conditions were 170 ºC, 3 hours and 3 wt%(m/m) of catalyst which produced the highest reported yield – 84.8%. The produced bio-oils were characterized by infrared spectroscopy and elementar analysis with the densities and viscosities, both kinematic and dynamic, also determined. The evaluation of the results confirmed that temperature is the most influential reactional parameter with the FTIR results showing that under 170 ºC no carbonyl groups are formed. The infrared spectroscopy also confirms the increase of secondary reactions with the longer reaction times. Density and viscosity values increased with the conversion of cellulose. The elementar analysis allowed to estimate the high heating value of the bio-oils and solid residues with the highest bio-oil HHV achieved being 30.16 MJ Kg-1 , a distant value from the ones derived from fossil fuels. Although, the solid-residues HHV were superior to pure cellulose’s HHV potentiating the hypothesis of reusing the solid residues for further liquefactions

Estudo metabolómico da reprogramação metabólica induzida por flavonoides em macrófagos humanos

The ability of macrophages to change between pro-inflammatory (M1-like) and anti-inflammatory (M2-like) phenotypes makes their modulation an attractive therapeutic strategy to mitigate excessive and/or chronic inflammation. Bioflavonoids are natural compounds with well documented anti-inflammatory activity. However, little is known about their molecular and metabolic effects on human macrophages. In this thesis, NMR metabolomics has been used to assess how different bioflavonoids (Quercetin, Naringenin and Naringin) modulate the metabolism of human macrophages, with a view to better understand their modes of action. In vitro-cultured macrophages differentiated from human THP-1 monocytes were treated with each flavonoid, both in the uncommitted state (M0) or after pre-polarization with LPS/IFN-γ (M1). Treatment with IL-4/IL-13 (M2) was also carried out for comparison. Cells were solvent-extracted to obtain the polar fractions and subsequently analysed by 1H NMR spectroscopy. Near 50 intracellular metabolites were detected (endometabolome), whereas analysis of cells-conditioned culture medium (exometabolome) was useful to assess consumption and excretion patterns. Multivariate analysis and discrete quantitative assessments of metabolic profiles revealed consistent variations upon macrophage exposure to the different stimuli. The three flavonoids produced pronounced metabolic alterations, with the strongest impact being observed for Quercetin and the mildest for Naringin. The main effects shared by all flavonoids, especially in M1 pre-polarized macrophages, comprised downregulation of glucose uptake and decreased energetic pools (ATP, UTP, phosphocreatine). Other effects were highly flavonoid-specific, namely TCA cycle modulation and amino acid metabolism, antioxidant response and variations in membrane-related metabolites. Overall, this work has shown that, although sharing similar ability to attenuate pro-inflammatory activity of macrophages, the three flavonoids affect macrophage metabolism in distinct ways. Future studies should entail assessment of key metabolic enzymes to further advance current understanding on flavonoid-mediated modulation of macrophage metabolism. This knowledge is expected to support the development of flavonoids as immunomodulatory drugs, especially aimed at attenuating and/or resolving inflammation, for instance, in the context of chronic inflammatory diseases or the rejection of biomaterial implants.A capacidade dos macrófagos alterarem o seu fenótipo entre estados pro-inflamatórios (tipo-M1) e anti-inflamatórios (tipo-M2), faz com que a sua modulação seja uma estratégia promissora para mitigar a inflamação excessiva e/ou crónica. Os bioflavonóides são compostos naturais com atividade anti-inflamatória bem documentada. No entanto, pouco se sabe acerca dos seus efeitos metabólicos em macrófagos humanos. Nesta tese, utilizou-se a metabolómica baseada em RMN para averiguar de que forma diferentes bioflavonóides (Quercetina, Naringenina e Naringina) modulam o metabolismo de macrófagos humanos, com vista a compreender melhor os seus mecanismos de ação. Macrófagos derivados de monócitos humanos THP-1 foram cultivados in vitro e tratados com cada flavonóide, tanto no estado não-polarizado (M0) como após uma pré-polarização com LPS/IFN-γ (M1). A estimulação com IL-4/IL-13 (M2) foi também empregue para comparação. As frações polares das células foram obtidas por extração com solventes orgânicos e subsequentemente analisadas por espetroscopia de RMN-1H. Perto de 50 metabolitos intracelulares foram identificados (endometaboloma), sendo que a análise dos meios de cultura (exometaboloma) foi útil para estudar padrões de consumo e excreção. O estudo dos perfis metabólicos através de análise multivariada e quantitativa revelou variações consistentes perante os diferentes estímulos fornecidos aos macrófagos. Os três flavonóides causaram diferentes alterações metabólicas, sendo que o maior impacto foi observado para a Quercetina e o menor para a Naringina. Os principais efeitos partilhados por todos os flavonóides, especialmente em macrófagos pré-polarizados para M1, incluíram diminuição do consumo de glucose e das reservas energéticas (ATP, UTP, fosfocreatina). Outros efeitos foram muito específicos dependendo do flavonóide, nomeadamente a modulação do ciclo TCA e do metabolismo de aminoácidos, a resposta anti-oxidante e variações em metabolitos associados às membranas. De forma geral, este estudo demonstrou que, apesar de apresentarem capacidade semelhante de atenuar a atividade pró-inflamatória de macrófagos, os três flavonóides afetaram o metabolismo celular de formas distintas. Em estudos futuros, será importante avaliar a expressão/atividade de enzimas metabólicas chave, de modo a incrementar o conhecimento atual sobre a modulação do metabolismo de macrófagos mediada por flavonóides. Este conhecimento deverá pois suportar o desenvolvimento de flavonóides como fármacos imunomodulatórios, especialmente direcionados para a atenuação e/ou resolução da inflamação, por exemplo, no contexto de doenças associadas a inflamação crónica ou da rejeição de biomateriais implantados.Mestrado em Bioquímic

Optimizing rearing and welfare in Senegalese sole (Solea senegalesensis) broodstock: effect of ambient light intensity and handling time on stress response

Broodstock rearing conditions and handling procedures should be optimized in aquaculture species in order to benefit fish welfare and guarantee optimal conditions for spawning. In teleosts, basal cortisol levels display daily rhythms, oscillating along the 24 h of the day. In this sense, handling fish at different moments of the day may lead to different stress responses. The present study aimed at investigating the optimal rearing conditions for Senegalese sole broodstock, considering ambient light intensity and handling time. The optimal light intensity (50, 100 or 200 lx) was investigated by measuring fish cortisol levels and monitoring locomotor activity rhythms under each intensity tested. Results showed a significant increase in cortisol levels of fish exposed to 200 lx, when compared to values obtained under 100 lx, accompanied by changes in locomotor activity rhythms in both tanks under study. These results suggested that 200 lx may be too high as light intensity for this species, whereas 100 lx seems to be more adequate. Also, daily rhythms of stress response were investigated in breeders from different origins (Wild and first generation, G1). Basal cortisol levels and cortisol stress response after an acute stressor (air exposure) were monitored at two distinct moments of the day (Mid-Light and Mid-Dark). Basal levels were higher during the day in the wild group, while G1 fish seemed to have lost the daily fluctuations in basal cortisol plasma levels, as well as their daily rhythms of locomotor activity. Both groups showed lower stress responses during night-time, an indication that this is an adequate period of the day to handle this species. Senegalese sole breeders born in captivity presented more pronounced stress responses when compared to wild fish, reflecting their different life history in terms of stress challenges.FP7/SME/2008/1; UID/Multi/04326/2019; DL 57/2016/CP1361/CT0007; DL 57/2016/CP1361/CT0033info:eu-repo/semantics/publishedVersio

Digital archives : comparative study and interoperability framework

Estágio realizado na ParadigmaXis e orientado pelo Eng.º Filipe CorreiaTese de mestrado integrado. Engenharia Informátca e Computação. Faculdade de Engenharia. Universidade do Porto. 200