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Testing new NRF2 activators in an AMD mouse model
No full textAbstract
Age-related Macular Degeneration (AMD) is a multifactorial and progressive retinal
disease that affects millions of people worldwide and has become the leading cause of
visual impairment in developed countries. This disease can be defined as a disruption of
the retina’s normal homeostatic mechanisms, where ageing coupled with chronic
inflammation, increased lipid and lipoprotein deposition, lysosomal dysfunction, and
oxidative stress contributes to AMD features. The primary cause of AMD pathology appears
to be the retinal pigmented epithelium (RPE) thinning, autofluorescence accumulation
(lipofuscin), and depigmentation, leading to atrophy together with the accumulation of
drusen between the RPE and the choroid.
The main regulator of NRF2 is KEAP1, which, under homeostatic conditions, facilitates its
proteasomal degradation. However, under conditions of stress, KEAP1 becomes oxidized,
preventing NRF2 degradation. This allows newly synthesized NRF2 to translocate into the
nucleus, where it activates genes involved in antioxidant defense, detoxification, and antiinflammatory
responses, as well as those promoting proteasome function and autophagy.
This study aimed to characterize and validate an inducible AMD mice model and select
optimal time points. Alongside analyzing cellular and morphological changes to establish
a screening process to test NRF2 activator compounds on this model.
To accomplish the aim, we have characterized and validated a NaIO3 inducible model
that recapitulates some AMD features in vivo. A single dose of NaIO3 intraperitoneal
injection was given at day 0, followed by retinal thickness (RT) evaluated at day 3, 7, and 14
by Optical Coherence Tomography (OCT). Blue-Light Fundus Autofluorescence (BAF) scan
was done at the same time point to look for lipofuscin-like granules. For a 25mg/kg dose of
NaIO3, we observed a lipofuscin-like phenotype by day 3 and a subsequent increase of this
phenotype over day 7 and 14. RT decreases rapidly from day 3 to day 7 and is followed by a
slowed pace decrease until day 14. Retinal sections were evaluated at these time points for
histological analysis and immunofluorescence assays for detection of cell death (TUNEL
staining) and exploring microglia infiltration (Iba1 staining). The highest number of TUNEL
positive signals were found at day 3, where Iba1 intensity was found significantly higher than the control and reached maximum values at day 7. After extensive analysis, we found the most significant time points in day 3 and 7 to be the most significant time points for evaluating the efficacy of drug compounds.
We then tested an FDA-approved drug dimethyl fumarate (DMF) to explore the potential antioxidative effect by activating the Nrf2 pathway. Unfortunately, at the concentration tested DMF did not show significant cellular and morphological
improvement as compared to the NaIO₃-treated mice, although more optimization is needed. Despite this, the study provided valuable insights into the molecular and cellular markers of inducible AMD mice models and well-tuned workflow plans which will be fruitful for screening other compounds
Exploring the Digital Impact: FOMO, Social Media Influencers, Trust in Voice Assistants and Social Media fatigue
No full textDissertation presented as the partial requirement for obtaining a Master's degree in Data Driven Marketing, specialization in Digital Marketing and AnalyticsThis research explores the contemporary digital landscape's impact on human interaction and
technological engagement, focusing on the interplay between Social Media, Social Media Fatigue,
the Fear of Missing Out (FOMO), and the proliferation of Voice Assistants (VA). Drawing from
scholarly discourse and empirical investigations, this investigation conducts a comprehensive analysis
of the psychological implications of social media, mainly its association with FOMO-induced anxiety.
Additionally, it examines user perceptions and attitudes toward VA, including trust perceptions and
concerns regarding data privacy. The study reveals the detrimental effects of excessive social media
usage on psychological well-being, emphasizing the role of social comparison and the importance of
fostering resilient coping mechanisms. It also highlights a spectrum of trust perceptions regarding
voice assistants, underscoring the need for robust privacy protocols and transparent data
governance frameworks to address user concerns. This study contributes to understanding balanced
digital engagement by advocating for informed consent, digital literacy, and conscientious
technological adoption. It emphasizes the importance of fostering a culture of digital mindfulness
and equitable access to mental health resources to promote individual well-being and societal
flourishing in the digital era
A Edição numa Sociedade de Poetas e Dragões. Relatório de Estágio na The Poets and Dragons Society
No full textEste relatório tem como objetivo descrever a experiência do meu estágio curricular de três meses na The Poets and Dragons Society , refletir sobre o trabalho desenvolvido e sobre o papel das editoras independentes no mercado editorial atual. A The Poets and Dragons Society é uma editora independente, fundada em 2018, que publica livros infantis e livros de adulto, tendo ainda criado o Prémio Literário Ulysses. Sendo uma editora independente num mercado editorial constituído por grandes grupos editoriais, a procura por formas de se destacar sem comprometer a sua visão e qualidade é um trabalho e uma luta constante, e que requer resiliência e dedicação
Otimização e aplicação de um teste de imunofluorescência indireta para o diagnóstico de leptospirose em laboratórios convencionais
No full textRESUMO
A leptospirose é uma zoonose re-emergente com distribuição mundial, com mais de
1.000.000 de casos graves notificados anualmente na população humana. É causada por
espiroquetas patogénicas do género Leptospira. O diagnóstico definitivo da leptospirose,
juntamente com achados clínicos e epidemiológicos compatíveis, baseia-se no Teste de
Aglutinação Microscópica (TAM), um teste sorológico de referência recomendado pela
Organização Mundial da Saúde (OMS) o qual, no entanto, está apenas disponível nos
laboratórios de referência em alguns países nos diversos continentes, com base em cerca
de três dezenas de serovares de Leptospira interrogans sensu lato. (s.l.).
Assim, este estudo visa otimizar um teste de imunofluorescência indireta (Lept-IFA)
alternativo à TAM que possa ser útil para o diagnóstico da referida doença, utilizando
apenas três sorovares patogénicos, reconhecidos em Portugal, pela alta e ubíqua
prevalência.
Utilizaram-se os serovares: Copenhageni, Arborea e Pomona representativos de L
interrogans s.l. e o serovar Patoc de L. biflexa s.l. (espécie saprófita) os quais foram
mantidos em meio de cultura Ellinghaussen, McCullough, Jonhson e Harris (EMJH), até
à sua utilização. A fim de preservar as proteínas leptospíricas de superfície da membrana
externa as espiroquetas foram centrifugadas a baixa velocidade e o lisado obtido colocado
nos diversos poços da lâmina do teste IFA, previamente revestida com lisina e depois
fixada com formalina. Foi testado por Lept-IFA um total (N=50) de amostras de soro
humano, selecionadas do laboratório de leptospirose/BioBanco do IHMT NOVA, com
indicação clínica de possível leptospirose e previamente analisadas por TAM, utilizaramse
também como controlo negativo, soros representativos de população saudável e soros
testados para dois outros espiroquetas (Borrelia burgdorferi s.l. e Treponema sp), agentes
etiológicos da borreliose de Lyme e sífilis, respetivamente.
O teste Lept-IFA confirmou todas as amostras positivas testadas por TAM (19+; 38%),
(6; 12%) das amostras mostraram resultado não conclusivo (NC), tendo o resultado sido
negativo nas restantes amostras (25; 50%). No grupo de soros com resultado não
conclusivo, os soros (controlo) de borreliose de Lyme verificou-se uma reação cruzada
com o serovar Patoc.
Este estudo mostrou que o Lept-IFA pode ser uma ferramenta útil como teste de triagem
de primeira linha para o diagnóstico sorológico da leptospirose em regiões/países cujos
laboratórios não dispõem do teste de referência recomendado pela OMS. No entanto, o
teste Lept-IFA carece de padronização confiável e depende muito da qualificação do
observador.Leptospirosis is a reemerging zoonosis with worldwide distribution, with more than
1,000,000 severe cases notified annually in the human population. It is caused by
pathogenic spirochetes of the genus Leptospira. The definitive diagnosis of leptospirosis,
together with compatible clinical and epidemiological findings, is based on the
Microscopic Agglutination Test (MAT), a reference serological test recommended by the
World Health Organization (WHO), that is based on about three dozen serovars of
Leptospira interrogans sensu lato.(s.1.), however this test is only available in the
reference laboratories in some countries on different continents.
This study aims to optimize an indirect immunofluorescence test (Lept-IFA) alternative
to TAM that may be useful for the diagnosis of leptospirosis, using only three pathogenic
serovars, recognized in Portugal for their high and ubiquitous prevalence.
The serovars Copenhageni, Arborea and Pomona, representative of L interrogans s.l.. and
the serovar Patoc, from L. biflexa s.l. (saprophytic species), were maintained in
Ellinghaussen, McCullough, Johnson and Harris (EMJH) culture medium until use. In
order to preserve the leptospiral proteins on the surface of the outer membrane, the
spirochetes were centrifuged at low speed and the pellet obtained was resuspended in
buffer and placed in each well of the IFA slide, previously coated with lysine, and then
fixed with formalin. Fifty human serum samples (N=50), selected from the leptospirosis
laboratory/BioBank of IHMT NOVA, with clinical indication for leptospirosis and
previously analyzed by TAM, were tested by Lept-IFA. A representative serum from a
healthy population and sera tested for two other spirochetes (Borrelia burgdorferi s.l. and
Treponema sp), etiological agents of Lyme borreliosis and syphilis, respectively, were
used as negative controls.
The Lept-IFA confirmed all positive samples tested by TAM (19+; 38%), 12% (n=6) of
the samples showed inconclusive results (NC), and the remaining 50% were negative
(n=25). In the inconclusive sera group, both Lyme borreliosis sera (controls) crossreacted
with Patoc serovar.
This study has shown that Lept-IFA can be a useful tool as a first-line screening test for
the serological diagnosis of leptospirosis in regions/countries whose laboratories do not
have the reference test recommended by the WHO. However, the Lept-IFA test lacks
reliable standardization and depends heavily on the qualifications of the observer
The Jesuit Procuradoria in Macau: a global agency in the Ming-Qing transition (1620-1680)
No full textA presente dissertação procura analisar a atuação da Procuradoria jesuíta, em Macau, através do estudo da vida e carreira de sete Procuradores da Província do Japão e Vice-Província da China: os Irmãos Manuel de Figueiredo (1589–1663), Belchior Ribeiro (1589–1671), António de Torres (1593–1680), Manuel dos Reis (1635–1669) e Luís de Figueiredo (c. 1622–1705); e os Padres Giovanni Francesco De Ferrariis (1609–1671) e Gonçalo da Fonseca (1618–1662). A historiografia associada à Companhia de Jesus e aos tópicos económico-financeiros tem atribuído muito pouco destaque a estas figuras, pese embora a sua atuação tenha sido vital para a sobrevivência das Missões jesuítas espalhados pelo globo e nos processos de circulação de gente, produtos e conhecimento no período moderno. Este trabalho constitui um contributo para o alargamento do conhecimento sobre o cargo e as suas implicações. Pretende, pois, lançar uma nova luz sobre o papel dos Procuradores, analisando os padrões, as diferenças e as semelhanças que caracterizaram as suas trajetórias; os períodos no ofício e sucessão; as rivalidades e dilemas éticos vividos no Colégio de Macau, bem como as múltiplas redes que, à escala global, estes administradores económico-financeiros foram gerindo, ao colocarem em circulação correspondência, dinheiro, pessoas, bens e conhecimento.This dissertation seeks to analyze the work of the Jesuit Procurator's established in Macau through the study of the lives and careers of seven Procurators of the Province of Japan and Vice-Province of China: Brothers Manuel de Figueiredo (1589–1663), Belchior Ribeiro (1589–1671), António de Torres (1593–1680), Manuel dos Reis (1635-1669) and Luís de Figueiredo (c. 1622–1705); and Fathers Giovanni Francesco De Ferrariis (1609–1671) and Gonçalo da Fonseca (1618–1662). The historiography associated with the Society of Jesus and economic and financial topics has paid little attention to these figures, even though their work was crucial to the survival of the Jesuit missions around the world. This work is a contribution to broadening knowledge about this still largely unexplored position. Aims, therefore, to shed new light on the role of the Procurators, analysing the patterns, differences and similarities that marked their trajectories; the periods in office and succession; the rivalries and ethical dilemmas experienced at the College of Macau, as well as the multiple networks that they managed, on a global scale, through the circulation of correspondence, money, people, goods, and knowledge
A gamified mobile app for food allergens detection
No full textWith adverse food reactions increasing worldwide, more accurate and easy-to-use systems to identify food triggers are needed. Except for severe food allergies, the most common diagnostic method is the self-monitoring of diet and symptoms by the patient, which can be imprecise and burdensome. The shortcomings of this method, alongside technological improvements, have lead to a growing interest in automatic food-tracking. Still, while mHealth apps generally show promise for empowering young adults with chronic conditions, existing food-tracking apps suffer from low engagement, hindering their effectiveness. This project aims to design an interactive prototype for young adults (20-25 yo) that facilitates food trigger identification by correlating meals and symptoms data entered in the app by the user. To overcome the noted engagement issues, this project employs a user-centered design approach for an improved user experience. Furthermore, a literature
review, a comparative analysis, and interviews revealed a number of ways to make the system more engaging to its users, employing techniques such as gamification and voice data recording while offering personalized support throughout the symptoms’ cause identification process. In the end, the system underwent usability tests and a SUS evaluation, obtaining a favorable result
Analysis of business models for privacy and user centered social networks
No full textThis paper addresses the exploitation of user data by social media companies by searching for
alternative business models and social media concepts based on user preferences and online
behavior. A survey was conducted to understand social media to understand user tendencies
towards business models of the social networks and implications emerging from these models.
Based on this survey a freemium model, an integrated app store system and an ad revenue
participation model have been shown to be viable options. For these models and the alternatives
blockchain enabled and federated social networks further research suggestion are given
A consulting lab on how Jkl can rethink its learning and development strategy to contribute to employee flourishing - validating hypothesis and generating relevant recommendations for Jkl
No full textThe goal of this project is to design recommendations for leveraging L&D opportunities to
contribute to employee flourishing. This Work Project intends to assist JKL in rethinking its
Learning & Development strategy to enhance and prepare its workforce for the Future of Work,
ultimately impacting motivation and satisfaction in the workplace. The methodology's main
phases consist of external and internal analysis, including best practices, and concept testing.
The findings are organized around four guiding pillars (awareness, content, format, and
triggers) that led to the recommendation of a personalized Learning Journey. Further research
was suggested to better implement the final recommendations
Intelligent management information systems for Pingo Doce and go Nova Store - agglomerative hierarchical clustering for implementing a shopping mission-driven customer segmentation
No full textThis thesis focuses on Pingo Doce & Go, a retail store within the Jerónimo Martins Group,
operating in Portugal. It provides actionable recommendations to enhance their customers’
experience based on a differentiated customer segmentation and thus, grow sales. It explores the
application of data analytics to create a segmentation based on consumers’ shopping missions, the
reason why they visit the store, which goes beyond traditional demographics and/or a limited
product view. Shopping missions put customers at the center and thus, provide deeper real-time
understanding of their fast-changing needs within the dynamic retail market leveraging on
innovative technology
How can pousadas de Portugal attract a younger target from Portugal, Spain and France to its properties? - Pricing strategy
No full textWith an eighty-year history, Pousadas de Portugal is a unique brand in the hospitality
industry. Historical properties in prime locations and a strong gastronomical offering
contribute to its prestige. To maintain long-term sustainability and strengthen the brand's
presence in the Portuguese, Spanish and French markets, it is essential to rejuvenate the brand
to meet the needs of millennials. As a result of analysing this generation's requirements and
aspirations, it has been possible both to identify untapped opportunities, thus improving and
modernising the current service and proposing a new sub-brand catered to the so-called
experience generation, for which new brand elements were created, assuring its fit into
Pousadas’ new proposed identity. A marketing plan was devised towards delivering true
service excellence, with a special emphasis on segmentation, targeting and positioning,
defining the best service product assortment, pricing, and critical aspects of service-focused
brands such as people strategy, physical evidence and processes. Furthermore, an integrated
marketing communications plan was developed, supporting implementation.
Keywords: Pousadas de Portugal, Marketing Plan, Millennials, Hospitality