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- Efeito da Privação de Sono na Resistência à InsulinaPublication . Pinheiro, Margarida Maria Coelho; Oliveira, Maria Elisa Cairrão RodriguesGrande parte da vida de um ser humano é passada a dormir, e como é sabido, sono adequado tem um papel fundamental para o bem-estar geral e funções cognitivas e fisiológicas. No entanto, numa sociedade cada vez mais focada em produtividade, a problemática da falta de sono torna-se cada vez mais preponderante. Assim, sendo esse um hábito muito adotado por parte da população é importante questionarmo-nos quanto aos seus possíveis impactos. Por outro lado, também se tem observado um aumento da incidência de Diabetes Mellitus, uma patologia crónica que representa elevados custos para os sistemas de saúde, e que está associada a aumento da resistência à insulina. Torna-se por isso pertinente tomar decisões diárias no sentido de contrariar esta tendência e viver anos de vida com mais qualidade, tornando este tema importante no contexto atual. Nesse sentido, com este trabalho pretendo analisar a literatura existente acerca da possível relação existente entre a privação de sono e as suas consequências metabólicas, nomeadamente ao nível do desenvolvimento de resistência à insulina. Para tal, irei realizar uma revisão da literatura nos últimos 10 anos com recurso às bases de dados Pubmed, Scopus e Web of Science com as seguintes associações de palavraschave “sleep deprivation” e “insulin resistance”. Nos estudos analisados registou-se uma diminuição da sensibilidade à insulina em situação de privação de sono, mesmo na presença de variações entre protocolos. Foi possível também verificar a associação entre a privação de sono e o aumento de ácidos gordos não esterificados (AGNE). No entanto, isto não aconteceu para outros parâmetros como cortisol, metanefrinas e normetanefrinas, onde os resultados não foram consensuais entre estudos. Assim, apesar de a hipótese colocada inicialmente se confirmar, isto é que a privação de sono promove a resistência à insulina, os mecanismos através dos quais tal acontece estão ainda pouco esclarecidos. Neste sentido, e tendo em conta as dificuldades que o seu estudo muitas vezes impõe, é importante a realização de mais pesquisa que seja o mais rigorosa possível.
- Anomaly Detection in Microservices Using Ensemble MethodsPublication . Salvado, Nuno Miguel da Silva; Freire, Mário MarquesAnomaly detection represents a critical factor in ensuring the reliability and resilience of microservice-based systems, where failures can rapidly propagate and compromise overall service availability. This dissertation investigates the application of classical Machine Learning (ML) algorithms and ensemble methods for anomaly detection in microservices, using the TraceRCA dataset as a representative benchmark. The work begins with a systematic literature review, which categorizes traditional and ML-based approaches to anomaly detection, identifying key research gaps and datasets. Building on this foundation, a complete experimental pipeline was developed, including preprocessing, feature engineering, and anomaly labeling, followed by the evaluation of multiple baseline classifiers such as Logistic Regression (LogReg), Support Vector Machine (SVM), Decision Tree (DT), K-Nearest Neighbors (KNN), Multilayer Perceptron (MLP), and Gaussian Naïve Bayes (GNB). To enhance predictive performance, ensemble techniques including Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Histogram-based Gradient Boosting (HGBM) were implemented and compared against baselines. The evaluation considered both predictive accuracy and resource efficiency, measuring metrics such as F1-score, precision, recall, accuracy, Receiver Operating Characteristic – Area Under the Curve (ROC-AUC), as well as execution time, Random Access Memory (RAM) consumption, and Central Processing Unit (CPU) utilization. The experimental results demonstrate that ensemble models consistently outperform baselines, with boosting-based methods (XGBoost, LightGBM, HGBM) achieving the highest predictive performance, while RF offered stable results with moderate computational overhead. These findings highlight the trade-offs between accuracy and efficiency, underlining the importance of careful algorithm selection according to deployment constraints. This research contributes by providing a comprehensive benchmark of ML and ensemble methods for anomaly detection in microservices, bridging the gap between predictive performance and practical applicability in real-world environments.
- Development and validation of a method for the determination of cocaine and its metabolites in hair using QuEChERS and GC- MS/MSPublication . Brito, Hugo Bernardo Marques Antunes de; Alba, Maria Eugénia Gallardo; Pires, Bruno Miguel Pinheiro; Rosado, Tiago Alexandre PiresCocaine (COC) is one of the most widely consumed illicit stimulants worldwide, with a high addictive potential and severe toxicological effects. Hair analysis offers unique advantages in forensic toxicology, as it allows the documentation of chronic use and, in some cases, acute exposure. In this study, a miniaturised version of the QuEChERS (Quick, Easy, Cheap, Rugged, and Safe) extraction method was developed for the determination of COC and its major metabolites — anhydroecgonine methyl ester (AEME), ecgonine methyl ester (EME), cocaethylene (COET), benzoylecgonine (BEG), and norcocaine (NCOC) — in hair samples. The procedure involved 3 mL of formic acid (5%) in acetonitrile (ACN) and 625 mg of NH4HCO2 as solvent and partitioning salt, respectively, followed by a dispersive solidphase extraction (d-SPE) step using 175 mg of MgSO4 and 55 mg of primary secondary amine (PSA). Samples were analysed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). Following optimisation through design of experiments (DoE), the method was validated according to the guidelines of the Society of Hair Testing (SOHT). The working range was set at 0.05–5 ng/mg for all analytes, except AEME (0.5–5 ng/mg). Recoveries ranged from 20–29% (AEME), 24–27% (EME), 33–42% (COC), 43–77% (COET), 25– 48% (BEG), and 27–37% (NCOC). The method was successfully applied to authentic hair samples, in which COC was detected in almost all cases, often accompanied by metabolites at concentrations above the lowest limit of quantification (LLOQ). The µ-QuEChERS method proved to be a sustainable, sensitive, and multi-analytical approach for the determination of cocaine and metabolites in hair, with strong potential for application in clinical and forensic toxicology.
- Reverse Logistics: A Mixed-Methods Analysis of Barriers, Strategies, and Key DeterminantsPublication . Soares, Miguel Norberto Mendes; Paço, Arminda Maria Finisterra do; Braga, Alexandra Maria SilvaGrowing concern about the environmental impacts of supply chain activities have stimulated the adoption of more sustainable models, highlighting the transition from a linear paradigm to a circular model. In this context, Reverse Logistics (RL) emerges as a fundamental strategic tool, allowing the recovery, re-use and recycling of products and material at the end of their life-cycle, and contributing to environmental, social and economic sustainability. Despite the recognised importance of RL as a strategic tool to promote the sustainability of supply chains, many companies, especially Small and Medium-Sized Enterprises (SMEs) in the textile and footwear sectors in Portugal, find effective implementation difficult. Therefore, this study aimed to identify and analyse the main barriers hindering adoption of RL in these industries, as well as exploring strategies to implement viable and effective RL networks. To do so, and to increase knowledge about the implementation of RL in textile and footwear SMEs, a mixed methodological approach was adopted, including quantitative and qualitative methods in the five studies making up this thesis. The study began with a Systematic Literature Review (SLR) (first study), following the Denyer and Tranfield (2009) protocol, to map existing scientific knowledge about RL and sustainability. The search carried out in May 2023 on the Web of Science and Scopus databases used the key-words “Reverse Logistics” and “Sustainability. The second study applied the Fuzzy Delphi method to validate and categorize in terms of relevance the barriers to implementing RL. This method allowed validation of a number of barriers with a negative impact on implementation of an efficient reverse flow network. The third study combined Interpretive Structural Modeling (ISM) and Matrices d’Impacts Cross-Multiplication Appliqúe a Classmate (MICMAC) analysis to map hierarchical relations among the barriers. A focus group with eight RL specialists, carried out via Zoom, developed a graphic model of interdependences. The MICMAC analysis classified the barriers in four quadrants (autonomous, dependent, linking and independent), identifying those with the biggest impact. The fourth study focused on SMEs in the textile and footwear sectors, using semistructured interviews with supply chain managers. The intentional sample was formed of participants with practical experience of RL, meaning the themes addressed could be dealt with in depth. The interviews lasted 30 minutes on average and explored specific barriers in the SME context and strategies to overcome them. Finally, the fifth study included the Fuzzy Analytic Hierarchy Process (FAHP) and Fuzzy F-MARCOS to prioritize RL implementation strategies. FAHP attributed weights and criteria based on specialists’ linguistic evaluations, while Fuzzy Measurement of Alternatives and Ranking according to Compromise Solution (F-MARCOS) ordered the strategic alternatives, handling uncertainties inherent to multi-criteria decisions. The main research trends in this area were identified, namely, the development of optimization models, performance assessment, outsourcing activities and the challenges of implementation. The most significant barriers to implementation of RL were found to be categorized in seven groups, highlighting the uncertainty in returning products, high costs and the lack of management commitment as the main factors preventing effective implementation. Analysis of the inter-relations among barriers, using ISM and MICMAC methods, showed that the "lack of an appropriate organisational structure" has the greatest influence, with a direct effect on social responsibility. In the textile and footwear sector, the reasons for adopting RL include environmental sustainability, economic benefits and social responsibility. Nevertheless, companies face challenges such as high operational costs and a lack of collaboration. To overcome these obstacles, this study proposes strategies such as the outsourcing of RL activities and developing strategic partnerships.
- From Hypoxia to Healing: Optimizing Stem Cell Therapy for Neonatal Hypoxic-Ischemic Brain InjuryPublication . Serrenho, Inês Isabel Pires; Baltazar, Graça Maria Fernandes; Manadas, Bruno José Fernandes Oliveira; Grãos, Mário Martins RodriguesNeonatal hypoxic-ischemic encephalopathy (HIE), caused by oxygen and blood flow deprivation to the neonatal brain, is a leading cause of mortality and long-term neurological disabilities in children under five. Its complex pathophysiology— comprising excitotoxicity, inflammation, oxidative stress, and delayed cell death—poses significant therapeutic challenges. Moreover, current management with therapeutic hypothermia (TH) shows limited efficacy, particularly in severe cases, and excludes many neonates due to strict enrollment criteria. To overcome these limitations, preclinical research has explored stem cell therapies (SCT), particularly using stem cells from umbilical cord blood (UCB) and tissue (UC). These therapies show promise in reducing brain injury and improving outcomes, but challenges remain in optimizing doses, delivery methods, and scalability. Building on previous work, this thesis evaluated several approaches to optimize SCT for neonatal HIE. First, administration of UCBCs alone and in combination with TH in a rat model of HIE, reduced brain lesion size and improved functional outcomes more effectively than TH alone, while also reducing glial reactivity—an effect not observed with TH alone. These findings establish UCBCs as a potential therapy, particularly when TH is unavailable or insufficient. Nonetheless, the use of these cells can present disadvantages: autologous use, limited culture and expansion, thus not being possible to manipulate with preconditioning strategies. Thus, we focused on the use of UC-derived MSCs that overcome some of the limitations previously mentioned. Also, since preconditioning strategies are being explored as ways to potentiate MSCs therapeutic effects, we hypothesized that hypoxic preconditioning could enhance UC-MSC efficacy and what explored the potential mechanisms behind neurological recovery. Proteomic analysis revealed that HIE rats treated with hypoxiapreconditioned MSCs had an enrichment of pathways related to synapse function, brain connectivity, and energy metabolism. Moreover, administration of UC-MSCs preconditioned with short hypoxia induced a greater functional recovery in HIE rats than administration of UC-MSCs preconditioned mild hypoxia. Stem cell therapy requires high doses of stem cells, which limits its clinical translatability. To optimize SCT and significantly reduce effective doses of MSCs, we evaluated the impact of two delivery methods and the combination of different strategies on the efficacy of UC-MSCs. Intranasal administration of UC-MSCs was more effective in reducing the infarct volume enhancing motor and cognitive recovery than intravenous administration, restoring myelination in the corpus callosum, and mitigating glial reactivity. Intranasal administration of half the dose of hypoxia-preconditioned UCMSCs reduced neurological deficits associated with neonatal HIE. Strikingly, intranasal administration of secretome from hypoxia-preconditioned MSCs demonstrated similar therapeutic efficacy, offering a promising cell-free alternative. Finally, to address the limitations associated with the expansion of UC-MSCs and donor variability on the therapeutic potency of these cells, we aimed to determine if induced pluripotent stem cell-derived MSCs (iMSCs) could hold the same potential in the neonatal HIE model. Intranasal administration of iMSCs or their secretome improved motor and cognitive recovery, reduced brain lesion size, modulated glial reactivity, and enhanced neurogenesis in the hippocampus of HIE rats. The comparable outcomes between iMSCs and their secretome underscore the critical role of secreted factors, presenting a scalable, cell-free option for clinical application. In summary, this thesis advances the field of regenerative medicine for neonatal HIE by identifying innovative strategies to optimize stem cell therapies. The findings demonstrate the potential of intranasal delivery and hypoxic preconditioning to reduce the required cell doses while maintaining efficacy, making these therapies more feasible for clinical use. Furthermore, secretome-based approaches offer a scalable alternative that addresses logistical challenges. Beyond neonatal HIE, these strategies may have broader implications for other neurodevelopmental and neurological disorders, as well as for veterinary medicine. While significant progress has been made, future research should aim to elucidate the mechanisms underlying MSC and secretome efficacy and advance these approaches toward clinical trials, paving the way for innovations in regenerative medicine.
- Effects of Wing-Fuselage Interface Position on Lift and DragPublication . Bombas, Rodrigo Manuel Cação do Carmo; Gamboa, Pedro VieiraThe interference effect between two aircraft components has become increasingly relevant in the design process, in parallel with the advances in aerodynamic efficiency observed over the last decades. In order to understand how this phenomenon manifests itself in small aircraft operating at low Reynolds numbers, a study was carried out on the influence of wing position relative to the fuselage, as well as the effect of fairings at the interface between the two components and the fuselage cross-section on interference drag. To determine the most favourable wing–fuselage interface positions in terms of drag and lift—considering also two types of fairings and fuselage cross-sections—the aircraft provided by the UBIAT team was modelled in CATIAV5. A simplified model was developed that nonetheless preserved the essential features of the real aircraft. The geometry was then prepared in Ansys Discovery to define the body of influence, the simulation volume, and the boundary conditions. This setup was subsequently imported into Ansys Fluent, where the computational mesh was generated according to a previously conducted mesh-independence study. The CFD simulations were performed using the k − ω SST turbulence model with standard parameters, including corrections for transitional flow and low Reynolds number regimes. Four alternative wing–fuselage interface configurations, in addition to the baseline case, were analysed: two vertical and two horizontal. The vertical configurations were further assessed with fairings and with a circular fuselage cross-section. The results regarding wing–fuselage positioning for both fuselage geometries were consistent with expectations and supported by literature. As for the introduction of fairings, both were found to improve aerodynamic efficiency, although the results did not fully align with published references. The main conclusions drawn from this work are the advantage of a high-wing configuration when interfaced with a square fuselage cross-section, and of a mid-wing configuration when interfaced with a circular fuselage cross-section. The addition of fairings yielded improvements of up to 4.7% in aerodynamic efficiency for the high-wing configuration with a square-section fuselage, while their effect was negligible for the other vertical positions.
- Estudo dos efeitos a nível celular da exposição do Dibutil Ftalato (DBP) em materiais plásticos de uso hospitalarPublication . Quina, Sérgio Miguel Calvelhe; Oliveira, Maria Elisa Cairrão RodriguesCom o avanço incessante da tecnologia, os plásticos tornaram-se uma presença constante no nosso quotidiano, trazendo consigo compostos químicos que representam riscos significativos, uma vez que atuam como perigosos disruptores endócrinos (DEs). Estas substâncias comprometem silenciosamente a nossa qualidade de vida à medida que a industrialização avança. Um dos quais se destaca como particularmente preocupante é o Di-n-butil Ftalato (DBP), um composto sintético classificado como um éster de ácido ftálico de baixo peso molecular. A sua principal utilização consiste em conferir flexibilidade e maleabilidade a polímeros, nomeadamente ao cloreto de polivinilo e látex. Posto isto, o DBP destaca-se em inúmeras aplicações, incluindo produtos de puericultura, artigos de higiene pessoal, produtos cosméticos e em materiais e dispositivos médicos, imprescindíveis nos serviços de saúde. Dado o seu impacto, é urgente reavaliar a sua presença nas vertentes médicas, a fim de eliminar fontes potenciais de exposição a este agente. O DBP está inegavelmente associado a problemas de saúde graves, incluindo alterações metabólicas, dislipidemias, disfunção sexual, efeitos adversos durante a gravidez, bem como consequências negativas para a saúde de lactantes, além de apresentar um risco significativo para os sistemas hepático e urinário. O presente estudo defende a necessidade de reavaliar os danos provocados pelo DBP nos vários sistemas do organismo, com especial ênfase nos seus efeitos sobre a saúde cardiovascular e na sua associação com doenças vasculares, como a aterosclerose. Por conseguinte, desenvolveu-se uma avaliação dos mecanismos de cardiotoxicidade induzidos pelo DBP, destacando o impacto crítico que este composto provoca no desenvolvimento do sistema cardiovascular. Além disso, analisou-se e discutiu-se a acumulação de respostas tóxicas desencadeadas por este composto sintético, que comprometem gravemente a saúde cardíaca, com particular foco em pacientes que permanecem hospitalizados, ou em unidades de cuidados por longos períodos.