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- ARIA-Italy managing allergic rhinitis and asthma in a changing world: The role of the PharmacistPublication . Paoletti, Giovanni; Giua, Corrado; Marti, Alessandro; Baio, Matteo Alberto; Valli, Nicolò; Ridolo, Erminia; Ventura, Maria Teresa; Passalacqua, Giovanni; Puggioni, Francesca; Lourenço, Olga ; Bousquet, Jean; Canonica, Giogio Walter; Heffler, Enrico; Lombardi, CarloAllergic rhinitis (AR) and asthma are common respiratory disorders that often occur together, affecting quality of life and increasing healthcare expenses of patients. These chronic illnesses are often managed without medical supervision, creating distinct challenges. A lack of resources can limit regular follow-up, which in turn promotes disease mismanagement and an increased reliance on self-medication, including the inappropriate use of corticosteroids and nasal decongestants. Community pharmacies could serve as critical primary healthcare providers, facilitating AR and asthma management by promoting therapy adherence, minimizing drug misuse, and improving symptom monitoring using digital tools. The evolving role of pharmacists as vital healthcare team members is highlighted by their involvement in screening, prevention, and patient education, particularly in underserved communities. Strengthening the partnerships between pharmacists, physicians, and patients may lead to more tailored and effective management strategies. This collaborative approach has demonstrated promise in enhancing disease outcomes and reducing healthcare costs.
- Chronotherapy of Brain Diseases: Assessment of the Circadian Rhythms of Efflux Transporters at the Blood-cerebrospinal Fluid BarrierPublication . Furtado, André Filipe Lino ; Paixão, Telma Alexandra Quintela; Santos, Cecília Reis Alves; Gallardo Alba, Maria EugéniaThe choroid plexus (CP) is an integral part of the blood cerebrospinal-fluid barrier (BCSFB). The CP is formed by a monolayer of cuboidal epithelial cells united by tight junctions. On the apical side, these cells present microvilli and are in contact with the cerebrospinal fluid (CSF). On the basal membrane, these cells are surrounded by a vast network of capillary blood vessels. The CP is responsible for several functions that are vital to the homeostasis of the central nervous system (CNS) where we include the production of the CSF, synthesis of several proteins, CNS protection against foreign elements, CSF detoxification from noxious compounds that result from normal cell metabolism and the transport of multiple molecules across the BCSFB. The CP has an essential role on the transport across the BCSFB of therapeutic molecules targeting the CNS. For that, it expresses multiple membrane transporters that have been described in the literature as essential for the transport of therapeutic compounds across CNS biological barriers. Recently, a functional molecular clock was described in the CP. This means that the biological functions of this structure might have a circadian rhythmicity associated. There's the possibility that this circadian clock influences membrane transporters' expression and activity at the CP which would result in circadian changes of the bioavailability of therapeutic compounds in the CNS depending on the time of administration. As such, the main goal of this doctoral thesis was to analyse the influence of circadian rhythms on the expression of multiple membrane transporters on the CP. Additionally, we used therapeutic compounds, namely methotrexate (MTX) and donepezil (DNPZ) to assess the relation between the CP's membrane transporters circadian expression and their drug transport function across the BCSFB. One of the objectives of this project, as mentioned earlier, was to assess the circadian expression of multiple CP’s membrane transporters. For that, CP primary cell cultures of neonate rats were used. We concluded that rSlc9a1 and rSlc1a5 expression was rhythmic during a 24-hour period while rSlc47a1 did not reveal a circadian pattern. This work also aimed at disclosing the influence of sex on the daily expression oscillations of several ABC and SLC membrane transporters expressed by the CP. For this we used CPs from male, female, ovariectomized and sham-operated female rats. The results showed that the membrane transporter rAbcc1 is expressed in a circadian manner in the CP of male rats, while rAbcg2 presented circadian rhythmic expression in the CP of female rats. Both rAbcc4 and rOat3 were rhythmically expressed in the CP of male and female rats. Next, we used an in vitro model of the CP in order to evaluate the relevance of Abcc4’s circadian expression in the transport of MTX across the BCSFB. We demonstrated that MTX transport across the BCSFB was rhythmic. Besides, we also concluded that Abcc4 circadian expression might influence the MTX circadian transport across the BCSFB. Finally, this project also aimed to describe the impact of circadian rhythms on CP Abcg2 expression and also on the circadian transport profile of DNPZ across the BCSFB. Using CP primary cell cultures of neonate rats, we demonstrated the presence of rAbcg2 circadian expression. Next, using primary cell cultures, an in vitro model of the BCSFB was established and we discovered that DNPZ transport across the BCSFB presents circadian rhythmicity. Furthermore, it was also proposed that besides rABCG2, SLC22A4 could also be involved in the DNPZ circadian transport across the BCSFB. The results obtained in this project demonstrate that membrane transporters present circadian expression in the BCSFB. Moreover, the transport of therapeutic compounds, such as MTX and DNPZ, across the BCSFB is also influenced by the circadian rhythm of CP membrane transporters. In the future, it is essential to further exploit the role of circadian rhythms on the expression of membrane transporters at the CP and its influence on the transport of therapeutic compounds across the BCSFB. This information might prove vital in the treatment of CNS diseases. By timing drug administration with the period when they are more prone to reach the target tissue at the CNS, we are ensuring their maximum target tissue concentration, and a reduction in side effects.
- Stand-up Paddle Boarding: Muscle activity, kinematics and performance analysis in recreational athletesPublication . Freitas, João Diogo Rodrigues ; Neiva, Henrique Pereira; Conceição , Ana Teresa SilveiraStand-up paddle (SUP) has become increasingly popular due to its accessibility and physical benefits. Despite its growing popularity, there is limited research focusing on the biomechanical factors influencing SUP performance. This doctoral thesis aims to fill this gap by investigating various determinants of SUP performance through four studies. The general objective of this thesis was to analyze kinematic and neuromuscular factors that influence SUP performance in pratical contexts, in recreational-level athletes. The following steps were undertaken: (i) a literature review focused on performance analysis in SUP; (ii) analysis of muscle activation behavior in SUP, focusing on the activation patterns of adjacent and opposite muscles relative to the paddling side; (iii) classify SUP practitioners based on kinematic and neuromuscular activity variables and identify performance differentiators; iv) to examine how different visual focus conditions affect kinematic and neuromuscular responses during SUP. The main findings demonstrated that: (i) SUP athletes have more muscle mass, less body fat, and use more efficient paddling techniques, resulting in better performance; (ii) there seems to be higher muscle activation on the opposite side of the paddle in SUP, suggesting the importance of alternating the paddling side for muscular balance; (iii) faster performers showed a higher stroke frequency and different neuromuscular activation (i.e., higher triceps brachii activity) during the recovery phase of the stroke; (iv) visual focus significantly impacts kinematic and neuromuscular activity during SUP, with the free choice condition resulting in faster speeds, higher stroke frequencies and higher muscle activation during recovery phases of the stroke. These results demonstrate the importance of kinematic and neuromuscular factors in SUP performance. This thesis provides valuable insights for SUP practitioners and coaches to optimize training and performance through a better understanding of these biomechanical and neuromuscular factors.
- Marketing as a Belief System: a model of consumer behaviourPublication . Oliveira, Patrícia João Rodrigues; Rodrigues, Fernando António de Oliveira Carvalho; Rodrigues, Ricardo José de Ascensão GouveiaUnderstanding consumer behaviour and their decisions is essential in marketing because most marketing campaigns try to influence the consumer’s decision-making process. The term consumer refers not only to the act of purchase itself but also to the entire purchase journey that includes prepurchase activities that consist of increasing awareness of a need or wanting and seeking and evaluating information about products and services or brands that can satisfy it, and post-purchase activities that include evaluation and feedback on the purchased item. Many models have been created to explain and predict consumer behaviour. However, some criticisms have also been presented of the various models, such as the focus on rational reasoning and its lack of focus on subconscious factors, uncertainty and spontaneous choices. This research study explores the Theory of Belief Systems (TBS) and its application in understanding human behaviour, particularly in consumer behaviour, with the aim of developing a model based on TBS to enhance marketing strategies. The primary objective is to propose a model that incorporates uncertainty in predicting consumer behaviour, contributing to evidence-based marketing decisionmaking. Specific objectives include analysing consumer behaviour models in literature, exploring TBS, testing its capabilities in explaining human behaviour, and comparing results with other consumer behaviour theories. The study utilizes mathematical modelling, using the Theory of Belief Functions or Dempster-Shafer Theory (DST), to address gaps in existing consumer behaviour models, focusing on rational reasoning, subconscious factors, and decision-making uncertainty. Two empirical studies were conducted in the Douro region, one utilizing TBS and the other employing Theory of Planned Behaviour (TPB), to analyze and predict consumer behaviour in this specific context. Structural Equation Modelling (SEM) and software tools like R and JASP were employed for data analysis. The findings aim to provide insights for improving marketing activities through a deeper understanding of consumer behaviour. The empirical studies conducted in this research offer practical applications of TBS in real-world scenarios, demonstrating its efficacy in predicting and understanding consumer behaviour. By conducting in-depth investigations into the intricacies of belief systems and their impact on consumer decision-making processes, this research sheds light on the differences between TBS and TPB, elucidating the contexts in which each theory excels and providing valuable insights for researchers and practitioners in the field of marketing.
- Gestão Ótima do Fluxo de Tráfego Aéreo nas Zonas Terminais de Voo com Base em Redes DinâmicasPublication . Simão, Cátia Salomé Azevedo; Bousson, KouamanaO aumento da procura sentido no setor do transporte aéreo refletiu-se no aumento da densidade do fluxo de aeronaves principalmente nas zonas terminais, sendo estas áreas designadas em inglês por Terminal Maneuvering Area (TMA) e fundamentais para a correta realização das aterragens e das descolagens. Esta sobrecarga foi gerida por inúmeros(as) agentes que observaram, controlaram e tomaram as decisões adequadas em cada momento, aliando essas tarefas com o(a) correto(a) tratamento e análise dos dados obtidos através de inúmeras fontes relevantes e dos programas computacionais que têm sido criados, desenvolvidos e implementados nas últimas décadas. Tendo por base esta problemática, pretendeu-se com o presente trabalho de investigação analisar, de forma concreta e crítica, a complexidade da otimização da gestão da capacidade das TMAs e propor medidas corretivas, obtendo uma estimativa preditiva do nível de ocupação das mesmas, em um determinado momento futuro, evitando a ocorrência de congestionamentos. O desejo de garantir e até mesmo de aumentar os níveis da segurança operacional motivaram a constante procura por métodos e metodologias, aliados(as) a programas computacionais. Por esse motivo, a recolha obtida através da revisão bibliográfica permitiu enunciar, descrever e exemplificar as principais medidas utilizadas até aos dias de hoje para gerir o fluxo de tráfego aéreo. Foi possível, dessa forma, evidenciar aspetos que poderão ser analisados, de forma mais detalhada, em trabalhos futuros, proporcionando sugestões de melhoria que beneficiem todos(as) os(as) utilizadores(as) deste setor. Desta forma, e através da modelação realizada com o suporte e a aplicação de redes dinâmicas, foi possível detetar o padrão de funcionamento do fluxo de tráfego aéreo na TMA do Aeroporto Humberto Delgado e sugerir as medidas adequadas que permitirão melhorar a gestão diária do fluxo de tráfego aéreo e que auxiliarão na previsão do mesmo e do nível de ocupação da TMA em análise, com o intuito de implementar essas medidas de forma atempada e segura. A modelação do fluxo de tráfego aéreo efetuada através da aplicação da Teoria das Cadeias de Markov permitiu a criação de um algoritmo cujo principal objetivo incidiu na otimização e na gestão entre a capacidade da TMA e a procura de aeronaves em cada momento, tendo em conta os inúmeros recursos existentes e podendo o mesmo ser extrapolado para outras TMAs. A metodologia selecionada representa um processo de otimização pois tem a capacidade de, através de um procedimento matemático, definir uma solução ótima para a gestão do nível de ocupação da TMA em estudo, maximizando o fluxo de tráfego aéreo com o intuito de satisfazer a procura registada, mas salvaguardando o nível de segurança operacional pretendido a qualquer momento e, simultaneamente, minimizando os atrasos verificados nas operações de tráfego aéreo. Esta otimização é conseguida através da análise da dinâmica verificada no fluxo de tráfego aéreo registado e da identificação de padrões de procura, sendo possível, dessa forma, analisar a variação do congestionamento do fluxo de tráfego aéreo ao longo do tempo. Salienta-se que esta abordagem nunca foi implementada no contexto do presente trabalho de investigação, revelando o seu carácter de originalidade. Através dos modelos criados foi possível identificar o grau de saturação da TMA selecionada e a necessidade de adaptação de medidas e/ou políticas já instauradas, tendo em conta as limitações físicas existentes e que restringem o aumento da procura do fluxo de tráfego aéreo. Desta forma verificou-se o elevado grau de constrangimento vivenciado, durante os períodos analisados, tendo um impacto direto na segurança das operações de tráfego aéreo. Assim sendo, é notória a necessidade da implementação de medidas que consigam minimizar os períodos de saturação, podendo ser tomadas pelas companhias de transporte aéreo através, por exemplo, da disponibilização de diferentes horários de planeamentos de voos e/ou rotas de voo alternativas que, de alguma forma, evitem as situações de constrangimento ou, por outro lado, de medidas tomadas pelas infraestruturas aeroportuárias e pelos(as) agentes que colaboram com o intuito de minimizarem os atrasos verificados nos diferentes voos e, dessa forma, evitando a aglomeração de aeronaves nas TMAs, salvaguardando e garantindo margem para lidarem com situações de emergência e/ou inesperadas. Por fim, mas não menos importante, salienta-se a importante capacidade de previsão obtida a partir dos modelos criados, permitindo dessa forma, e através do conhecimento do comportamento presente de uma determinada rede dinâmica, antever o seu comportamento num momento futuro e auxiliar na otimização da gestão do fluxo de tráfego aéreo. Esta característica é fundamental e de extrema utilidade não só para o conhecimento dos(as) agentes como também para os(as) estudiosos(as) empenhados(as) no desenvolvimento de programas computacionais que pretendem ser instrumentos indispensáveis neste processo.
- Investigação em artes e arquitectura: Natureza, metodologias, validade e impactoPublication . Sequeira, João Manuel Barbosa Meneses deA discussão sobre a Investigação nas artes e na arquitectura, enquanto práticas dotadas de metodologias próprias e com potencial para serem consideradas formas válidas de produção de conhecimento, é central em muitos debates contemporâneos nas humanidades e ciências sociais. Para abordar esta hipótese, podemos dividir a discussão em três áreas principais: Da Natureza: Investigação em Artes e Arquitectura Das Metodologias: Regras Próprias Da Validade e Valor do Conhecimento Produzido
- Improving the Robustness of Demonstration LearningPublication . Correia, André Rosa de Sousa Porfírio; Alexandre, Luís Filipe Barbosa de AlmeidaWith the fast improvement of machine learning, Reinforcement Learning (RL) has been used to automate human tasks in different areas. However, training such agents is difficult and restricted to expert users. Moreover, it is mostly limited to simulation environments due to the high cost and safety concerns of interactions in the real world. Demonstration Learning is a paradigm in which an agent learns to perform a task by imitating the behavior of an expert shown in demonstrations. It is a relatively recent area in machine learning, but it is gaining significant traction due to having tremendous potential for learning complex behaviors from demonstrations. Learning from demonstration accelerates the learning process by improving sample efficiency, while also reducing the effort of the programmer. Due to learning without interacting with the environment, demonstration learning can allow the automation of a wide range of real world applications such as robotics and healthcare. Demonstration learning methods still struggle with a plethora of problems. The estimated policy is reliant on the coverage of the data set which can be difficult to collect. Direct imitation through behavior cloning learns the distribution of the data set. However, this is often not enough and the methods may struggle to generalize to unseen scenarios. If the agent visits out-of-distribution cases, not only will it not know what to do, but the consequences in the real world can be catastrophic. Because of this, offline RL methods try to specifically reduce the distributional shift. In this thesis, we focused on proposing novel methods to tackle some of the open problems in demonstration learning. We start by introducing the fundamental concepts, methodologies, and algorithms that underpin the proposed methods in this thesis. Then, we provide a comprehensive study of the state-of-the-art of Demonstration Learning methods. This study allowed us to understand existing methods and expose the open problems which motivate this thesis. We then developed five methods that push improve upon the state-of-the-art and solve different problems. The first method proposes to tackle the context problem, where policies are restricted to the context in which they were trained. We propose a method to learn context-invariant image representations with contrastive learning, by making use of a multi-view demonstration data set. We show that these representations can be used in lieu of the original images to learn a policy with standard reinforcement learning algorithms. This work also contributed with benchmark environment and a demonstration data set. Next, we tackled the potential of combining reinforcement learning with demonstration learning to cover the weaknesses of both paradigms. Specifically, we developed a method to improve the safety of reinforcement learning agents during their learning process. The proposed method makes use of a demonstration data set with safe and unsafe trajectories. Before each interaction, the method evaluates the trajectory and stops it if deems it unsafe. The method was used to augment state-of-theart reinforcement learning methods, and it reduced the crash rate significantly which also resulted in a slight increase in performance. In the following work, we acknowledged the significant strides made in sequence modelling and their impact in a plethora of machine learning problems. We noticed that these methods had recently been applied to demonstration learning. However, the state-of-the-art method was reliant on task knowledge and user interaction to perform. We proposed a hierarchical method which identifies important states in each demonstration, and uses them to guide the sequence model. The result is a method that is task and user independent but also achieves better performance than the previous state-of-the-art. Next, we made use of the novel Mamba architecture to improve upon the previous sequence modelling method. By replacing the Transformer architecture with the Mamba, we proposed two methods that reduce the complexity, and inference time while also improving the performance. Finally, we apply demonstration learning to under-explored applications. Specifically, we apply demonstration learning to teach an agent to dance to music. We describe the insight of modelling the task of learning to dance as a translation task, where the agent learns to translate from the language of music to the language of dance. We used the previous experience resulted from the two sequence modelling methods to propose two variants: using the Transformer or the Mamba architectures. The method modifies the standard sequence modelling architecture to process sequences of audio features and translate them to dance poses. Results show that the method can translate diverse and unseen music to high-quality dance motions coherent within the genre. Results obtained by the proposed methods advance the state-of-the-art in Demonstration Learning and provide solutions to open problems in the field. All the proposed methods were evaluated against state-of-the-art baselines and evaluated on several tasks and diverse data sets, improving the performance and tackling their respective problems.
- Mitochondrial Gene Therapy: Development of a mitochondrial targeted peptide/plasmid DNA vectorPublication . Faria, Rúben Miguel Ribeiro ; Costa, Diana Rita Barata; Sousa, Ângela Maria Almeida de; Boisguérin, PriscaMitochondria are cellular organelles measuring approximately 1 micron that can be found in large numbers in eukaryotic cells. These small organelles play a crucial role in cellular activity, being essential in intracellular signaling processes, apoptosis mechanisms, and energy production, among others. Mitochondria generate 90% of all energy consumed in cells, through the oxidative phosphorylation system that produces energy in the form of adenosine triphosphate (ATP) molecules. Mitochondria, similar to the nucleus, have their own genome, called mitochondrial DNA (mtDNA). Human mtDNA is composed of double-stranded circular DNA molecules, with each strand having its own composition and encoding different ribonucleic acids (RNA). The guanine-rich strand encodes 14 tRNAs, 2 rRNAs, and 12 polypeptides, while the lighter strand has information to transcribe only 8 tRNAs and one polypeptide. In total, mtDNA consists of just 37 genes that encode 13 mRNA, giving rise to 13 proteins that are part of the electron transport system and the ATPase complex. The oxidative phosphorylation system is composed of 5 complexes (NADH-ubiquinone reductase complex (complex I); succinate dehydrogenase complex (complex II); ubiquinol-cytochrome c oxidoreductase (complex III); cytochrome-C oxidase complex (complex IV) and ATP synthase (complex V)), which form the respiratory chain. mtDNA is much more susceptible to mutations when compared to the nuclear genome. Changes in mtDNA compromise the normal functioning of cells, mainly affecting neuronal and muscle tissues. The higher frequency of mutations in mtDNA can be explained by the fact that it does not have telomeres or introns in its constitution. Mitochondrial dysfunctions lead to the emergence of multisystem diseases, which can affect the normal functioning of the immune response, motor and brain function, and metabolic regulation and lead to aging. The vast majority of pathologies originating from mitochondria are inherited from maternal mtDNA. However, environmental factors such as stress and the consequent presence of reactive oxygen species, also contribute to the emergence of mutations in mtDNA. The most common mitochondrial diseases are Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy, Pearson's syndrome, Parkinson's, Huntington's disease, Alzheimer's, and some types of cancer (breast, kidney, and colorectal). Complex I of the mitochondrial respiratory chain is the main entry point for electrons into the electron transport chain. Due to this fact, this complex is very important in the normal functioning of mitochondria. It is in complex I that the transfer of electrons from Nicotinamide Adenine Dinucleotide + Hydrogen (NADH) to ubiquinone occurs, the transport of protons across the inner mitochondrial membrane and is the main source of reactive oxygen species (ROS). Mutations in mitochondrial genes responsible for structural and assembly proteins of this complex lead to increased ROS production and loss of functions. One of these genes is the mitochondrial gene ND1 (NADH dehydrogenase 1). The mt-ND1 protein plays a crucial role in the structure of complex I. Mutations in mt-ND1 are associated with the emergence of LHON; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); progressive cardiomyopathy, and some types of cancer. Data from 2020 revealed that 1 in every 250 people have mutations in mtDNA and that 1 in every 5,000 have serious pathologies associated with mitochondrial dysfunction. However, currently, the medications available on the market only serve to mitigate the symptoms. No drug approved by the FDA or in development has been able to cure or slow the progression of mitochondrial diseases. Although there are approaches such as the use of antioxidant agents and other drugs to alleviate symptoms, the ineffectiveness of current medications highlights the urgent need for more effective treatments. Mitochondrial gene therapy is a promising approach that can focus its action directly on the cause of mitochondrial diseases and develop therapies tailored to the type of mutation. Gene therapy consists of the application of recombinant DNA techniques in which functional genes are used to replace defective genes and restore their normal functioning. As most mitochondrial diseases originate from mutations in mtDNA, mitochondrial gene therapy appears as a very promising strategy for treating this type of disease. Mitochondrial gene therapy makes it possible to attack the problem at its source and restore normal function to the affected mitochondrial gene. However, this type of therapy needs delivery systems that are effective in protecting and delivering genetic material to target cells/organelles. The greatest difficulty in applying gene therapy has been the development of nanocarriers that can effectively deliver genetic material. For mitochondrial gene therapy, the difficulty has been even greater, as the systems need to cross more barriers and be able to deliver only to that organelle. Thus, the main objective of this thesis is to develop delivery systems that have an affinity for mitochondria and can effectively deliver mitochondrial genes for the treatment of mitochondria-associated pathologies. The work carried out consisted of the development of delivery systems based on peptides (cell-penetrating peptides (CPP)) and polymers (polyethylenimine (PEI)), to deliver the mitochondrially encoded NADH dehydrogenase 1 protein (ND1) gene. To achieve this, these delivery systems were functionalized with ligands that allow specific targeting of mitochondria. The ligands used were triphenylphosphonium (TPP) and dequalinium chloride (DQA) to functionalize PEI and for CPP a mitochondrial targeting sequence (MTS) was used. The first step for the PEI-TPP/pND1 polymeric systems was to evaluate, through an experimental design, the optimal conditions for the formulation of nanoparticles. These systems were then characterized in terms of size, surface charge, and morphology. These delivery systems demonstrated the ability to internalize into cells and, through confocal microscopy, their preferential accumulation in mitochondria was demonstrated. Furthermore, these systems have demonstrated the ability to deliver the ND1 gene to mitochondria and lead to its transcription. The PEI-DQA/pND1 polymeric systems developed also demonstrated excellent physicochemical properties, showing the ability to transfect and internalize into cells. These nanocarriers delivered the ND1 gene directly into the mitochondria, leading to transcription of the gene of interest and production of the ND1 protein. However, the peptide-based systems (MTS-CPP) exhibited superior performance in terms of cellular internalization and targeting to mitochondria. Its greater ability to complex pND1 led to the formulation of nanoparticles with smaller sizes and consequently greater delivery of the gene of interest and protein expression. Showing better in vitro results, the MTS-CPP systems were tested in in vivo models (zebrafish embryos (ZF)). The peptide systems demonstrate the ability to internalize and distribute throughout the ZF organism, without causing any toxicity in these in vivo models. In short, the work carried out during this doctoral thesis sought to find solutions to the lack of effective delivery systems in mitochondrial gene therapy, to make this therapy viable for the treatment of mitochondrial diseases. The results obtained during the thesis demonstrate that the delivery systems developed are very promising for the development of mitochondrial gene therapy protocols. This work contributed to progress and innovation in an area of research that is still little explored, such as mitochondrial gene therapy. In the case of peptide-based systems, these systems have the potential to be considered in future investigations, to evaluate their translation to the clinic. The nanocarriers developed during this thesis were optimized for the delivery of the mitochondrial ND1 gene, however, these systems can be easily adapted for the delivery of any mitochondrial genes that are involved in pathologies associated with mtDNA mutations.
- Teoria critica de apoio pedagógico à unidade curricular de Desenho IPublication . Sequeira, João Manuel Barbosa Meneses deO presente manual insere-se no âmbito da unidade curricular de Desenho I, leccionada no 1.º ano do Mestrado Integrado em Arquitectura da Universidade da Beira Interior. Resulta de uma prática pedagógica continuada que, ao longo dos últimos anos, tem procurado articular a formação técnica do desenho com uma reflexão crítica e sensível sobre o papel da representação na génese do projecto arquitectónico. Embora concebido como instrumento de apoio ao ensino, o seu horizonte ultrapassa o contexto estrito da unidade curricular, visando propor um contributo mais amplo para a pedagogia do desenho em arquitectura.
- Droplet Impact onto Heated Wetted Surfaces: A Fundamental StudyPublication . Rodrigues, Daniel de Almeida Vasconcelos ; Silva, André Resende Rodrigues daThe industrialisation and globalisation of the modern world severely increased the demand for energy production, primarily met by a dependence on fossil fuels. The projected exponential growth of the aviation sector will result in an increase in greenhouse gas and pollutant emissions. Due to this, researching sustainable and cleaner alternative fuels is crucial to neutralise the negative effects of conventional fuels. The physical and chemical processes occurring inside a combustion chamber include fluid dynamics, heat and mass transfer, combustion, among others. Specifically, the phenomena regarding the impact of droplets onto solid surfaces and liquid layers are often encountered in internal combustion engines, heat exchangers and spray cooling. Research on these applications focuses on understanding fluid flow and optimising heat and mass transfer mechanisms. Despite this, single droplets impacting onto liquid films are limited to isothermal conditions, as the influence of temperature on liquid films has been overlooked in the literature. Therefore, the primary objective of this work is researching the phenomena of droplet impact onto heated liquid films. An experimental facility was designed and adapted to account for isothermal and non-isothermal conditions. The key aspects of the experimental facility consist of high-speed imaging and heating systems. Prior to the impact phenomena, the liquid film characterisation is required in terms of temperature fields and evaporation rates. Subsequently, various outcomes from droplet impact are evaluated as a function of the liquid film temperature, including central jets, craters, splashing, and bubbling. Qualitative analysis is conducted on outcome development, while quantitative measurements focus on geometric parameters. Theoretical work is performed regarding the propagation of kinematic discontinuities in liquid layers and time scales for crater and central jet evolution, respectively. The experimental data provides a foundation for the implementation and validation of the numerical model. This model solves the incompressible Navier-Stokes equations coupled with the Volume of fluid (VOF) method under a 2D-axisymmetric assumption. The open-source Computational Fluid Dynamics (CFD) software Basilisk is adopted for the numerical simulations. Overall, the liquid film temperature and correspondent thermophysical properties play a major role in the impact dynamics. Higher values of the dimensionless temperature promote and increase the occurrence and number of secondary droplets, respectively. This is associated with lower values of viscosity and surface tension, contributing to higher Reynolds and Weber numbers. For the onset of boiling, the oscillations induced on the liquid film are not sufficient to affect the impact phenomena. The presence of vapour bubbles in the impact region decreases both the crown diameter and height, with its effect being more pronounced for the latter.