Browsing by resource type "doctoral thesis"
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- A 1- year randomized controlled trial in type 2 diabetes patients : comparing moderate and high-intensity interval training combined with resistance training on health biomarkers /Publication . Magalhães, João Pedro Reis; Sardinha, Luís Fernando Cordeiro BettencourtAs recomendações contemporâneas de atividade física no âmbito da diabetes tipo 2 focam-se no exercício aeróbio contínuo de intensidade moderada. Contudo, existem novas evidências que o exercício intervalado de alta intensidade (TIAI) tem benefícios iguais ou superiores ao treino contínuo moderado, com um volume total da sessão inferior. Intervenções de curto a médio prazo do TIAI demonstraram ter um efeito positivo em várias variáveis relacionadas com a saúde. No entanto, até à data, não há informações sobre os efeitos a longo prazo de intervenções com TIAI em pessoas com diabetes tipo 2. Nota-se ainda que nenhum estudo comparou ainda os efeitos a longo prazo do TIAI combinados com o treino de resistência (TR) e o exercício contínuo moderado (TCM) combinado com o TR, em variáveis relacionadas com a saúde. Esta dissertação apresenta três artigos que são o resultado de um estudo randomizado e controlado de 1 ano desenvolvido para avaliar os efeitos do TIAI combinado com o TR e TCM combinado com o TR, em comparação com um grupo de controlo, num conjunto de bio marcadores relacionados com a saúde, em pessoas com diabetes tipo 2. O primeiro artigo discute os efeitos dos diferentes protocolos de exercício no controlo glicémico, composição corporal, aptidão cardiorrespiratória (APC) e perceção de prazer durante o exercício. Os resultados sugerem que não houve efeito no grupo TCM com TR e do TIAI com TR, no controle glicêmico em pessoas com diabetes tipo 2. No entanto, o grupo de TCM com TR melhorou a composição corporal e APC após 12 meses de intervenção. O segundo artigo analisa o impacto dos dois grupos de exercício nos índices arteriais estruturais e funcionais. Pela primeira vez, após 1 ano de intervenção em pacientes com diabetes tipo 2, mostrou-se que o grupo de TCM com TR e o grupo TIAI com TR reduziram a espessura da camada média-íntima da carótida, enquanto apenas o grupo de TIAI com TR melhorou os índices de rigidez arterial periférica e o coeficiente de distensibilidade. O TIAI com TR pode ser uma ferramenta fundamental na melhoria das complicações cardiovasculares em pessoas com diabetes tipo 2. O estudo 3 examina pela primeira vez o impacto a longo prazo de diferentes intensidades de exercício (i.e., TIAI e TCM) no perfil inflamatório e lipídico de pessoas com diabetes tipo 2. Os resultados sugerem que o TIAI com TR a longo prazo proporciona benefícios superiores no perfil lipídico, quando comparado com o grupo de TCM com RT. No entanto, ambos os grupos de exercício têm XXIII adaptações favoráveis semelhantes no perfil inflamatório em pacientes com diabetes tipo 2. O presente estudo faculta pela primeira vez evidência experimental importante relativamente aos efeitos do TIAI e TCM a longo prazo, quando combinados com TR, no controle glicémico, composição corporal, APC, saúde vascular, lípidos e perfil inflamatório, com informações relevantes para intervenções de saúde pública.
- 1917 – um ano charneira. Relações entre memória e cultura a partir dos relatos de António Manuel TrigoPublication . Honrado, José Alexandre Mendonça de Moraes Sarmento; Furtado, Rodrigo Miguel Correia; Franco, José EduardoTodos os ensaios são um ponto de vista e esta tese, enquanto ensaio, é um ponto de vista sobre Memória, esse repositório de entidades físicas e etéreas, área epistemológica e noção de conhecimento com entrada e difusão algo tardias nas ciências sociais, mas que, ao mesmo tempo, manifesta suma relevância no nosso âmbito de estudo, em todos os momentos em que o desenvolvemos. A importância da Memória na nossa contemporaneidade académica, como aspeto cultural e das culturas, a maior parte das vezes num formato intangível da realidade individual e social, mas sempre matricial, torna-a merecedora de apreensão, descrição, interpretação e representação no âmbito do que estudamos, no nosso percurso de interesse e neste foco de abordagem. Como corpus usámos precisamente um livro de memórias, manuscrito inédito do funchalense António Manuel Trigo. O cidadão António Manuel Trigo, filho de Adelaide Virgínia dos Santos Trigo e de Adriano Augusto Trigo, nascido a 13 de Maio de 1892, na Freguesia de Santa Luzia, concelho e distrito do Funchal, viria a ser oficial do exército, era ainda cadete, em 1917, da Escola de Guerra. Frisamos sempre 1917, porque o escolhemos, por ser um ano seminal, um ano de todas as transformações, nomeadamente culturais, e que nos serviu exemplarmente como motivo de estudo. O elaborarmos raciocínios no âmbito dos estudos de cultura permitiu geminar o tronco comum dos exemplos, e foram muitos que a cultura produziu e cuja síntese trazida a este trabalho nos auxiliou durante toda a nossa formação e nesta etapa de conclusão teórica. Recorremos, por isso, a elementos de cultura que, à margem, acreditamos terem relação com António Manuel Trigo e, observados de perto, em especial na relação direta com o mesmo ano de 1917. Usámos, naturalmente, muitas fontes escritas, na tentativa de esgotar muitas das possibilidades que continham, apoiando-nos, entre outras, numa coleção particular de livros, textos e manuscritos que acumulámos ao longo dos anos, exatamente sobre os temas que considerámos estudar. Acresce, na base em que se construiu o que se segue, os testemunhos orais familiares em que os nossos próprios parentes nos contavam memórias vivas da Primeira República (e amplamente, como memórias vivas, também da Ditadura, do Estado Novo, da Revolução de Abril), sobretudo “coisas de avós” que viram e viveram o País de uma forma tão pessoal que nos legaram memórias ímpares, de cronologias efervescentes (recordações sempre exatas e quase sempre exaltadas), pois chegaram a ser, eles também, nos seus percursos, personagens e protagonistas desta longa narrativa. Conversas com a família de António Manuel Trigo preencheram lacunas geradas pela leitura do seu espólio, o espaço memorial que legou aos vindouros que por ele se interessassem.
- 1961 - Sob o viés da imprensa : os jornais portugueses, britânicos e franceses na conjuntura da eclosão da guerra no império portuguêsPublication . Alves, Tânia; Garcia, José Luís, 1955-Em várias investigações que têm concentrado a sua atenção no chamado colonialismo tardio português, num tempo dominado pela viragem anticolonial do pós-guerra e pela dissolução dos impérios coloniais europeus, é geralmente assumida a importância do novo clima da opinião internacional enquanto fator que terá condicionado a soberania colonial portuguesa. Contudo, as alusões ao que se sugere ser a diferente disposição das opiniões trazida pelos ventos de mudança anticoloniais carecem de fundamentação empírica. A presente pesquisa propõe-se superar o papel marginal muitas vezes consignado aos meios de comunicação e analisar um amplo acervo de artigos de jornais recolhidos da imprensa portuguesa, britânica e francesa sobre a conjuntura de 1961, o annus horribilis do Estado Novo. Através de uma abordagem que combina a sociologia, a história, as ciências da comunicação e os estudos de media procura-se estudar a situação interna e imperial portuguesa nesse período a partir de um ângulo que privilegia as imbricações entre a imprensa – a sua capacidade para construir acontecimentos mediáticos, as suas formas de agendamento, os seus enquadramentos e linguagem, a sua potência propagandística –, o exercício político do governo de Salazar e as dinâmicas internacionais em matéria colonial e imperial. Como é que um conjunto de episódios que levaram o regime a uma situação limite em redor de um vetor fundamental da sua política tomaram forma na imprensa portuguesa, em plena vigência da censura, e na imprensa britânica e francesa, países onde vigorava a liberdade de imprensa e que tinham iniciado os seus processos de descolonização? A pertinência de um estudo comparativo encontra fundamento na hipótese de a conjuntura de 1961 que conduziu ao deflagrar da guerra em Angola e à queda do Estado Português da Índia ter engendrado textos de sentidos certamente muito distintos. As similitudes e divergências nos textos impressos devem ser pensadas como permeáveis a condições diversas de regime político e às transformações que marcaram as diferentes formações imperiais. Mas o “viés da imprensa”, expressão que integra o título da investigação, remete para a faculdade deste medium de modelar os eventos e os conflitos de poder, de condicionar a vida coletiva pelo que torna visível e pelo modo como enforma e deforma informações e conhecimentos, e de constranger diversos atores a algum tipo de acomodação aos seus critérios e ao seu ritmo, quer para tentar usá-los, quer para os controlar. A análise comparativa harmoniza-se com o pressuposto teórico deste estudo: o de que o início do derrube do império português, além de uma história política e militar, é também a história de uma luta do poder político para direcionar o público num âmbito interno e de uma luta obstinada pela opinião internacional.
- 2" a 8" - Do movimento ao objeto corpóreo : como pode o fotográfico dar corpo ao movimentoPublication . Alcântara, Octávio Manuel Rodrigues; Moura, Catarina Isabel Grácio de; Frade, Marta Alexandra da CostaThis PhD Thesis is both theoretical and practical by nature. Putting Photography at its core, as an expanded field, the developed project assumed Bergson’s and Marey’s notions of movement and time, searching in the present time the seminal possibility of creating a new corporeal object. The analysis of the medium’s plastic characteristics, as well of its ability to show the luminous trace through blurred trails, lead to the observation of a continuous movement in an intensive time, where the referent’s shape is lost and replaced by what is unformed and shapeless. This work also implies the contrast between the classic process of threedimensionality’s loss through photography, characterized by the annulment of volumetry and depth, and the possibility to recover a voluminous existence through the image’s virtualization, bringing it closer to the sculptural and therefore allowing the passage of two-dimensionality to three-dimensionality. The theoretical analysis and the practical achievement aimed by this thesis resulted in a project — 2” to 8” — whose primordial goal is to illustrate how the photographic may become sculptural through movement and, with it, through the duration of the present time, generating an interval that materializes and becomes a corporeal object. This project highlights the fertile connection between scientific research and artistic creation, which has been raising more curiosity through the last couple of decades, becoming a natural object of investigation. In this case, the photographic thought, organized as a visual essay, articulates the typical intention and plan of a research project with the reflection resulting from the attention given by the researcher to its own creative process, thus becoming a methodological strategy as well.
- 2D Iterative Image Reconstruction for a Dual Planar Detector for Positron Emission MammographyPublication . Matela, Nuno; Almeida, Pedro Miguel Dinis de, 1968-The Clear-PEM system is a prototype scanner for Positron Emission Mammography (PEM), currently under development. In the scope of this project, we present the implementation of three iterative algorithms for 2D image reconstruction, using linograms: the Algebraic Reconstruction Technique (ART), the Maximum Likelihood Expectation Maximization (ML-EM) and the Ordered Subsets Expectation Maximization (OS-EM) algorithms. To calculate the system matrix required by all algorithms, we have developed three different methods (the pixel-driven, the ray-driven and the tube-driven method). Additionally, we have implemented a method to correct the sensitivity differences between different regions of the field-of-view and to compensate for gaps between the detector elements. The comparison of the algorithms' performance was done with the help of Monte Carlo simulated data, which allowed evaluating image spatial resolution, convergence speed, image uniformity, contrast between lesions and background, signalto- noise ratio and computational speed. The results showed that the OS-EM algorithm produced the best results regarding all evaluated parameters, except the computation time by iteration, in which ML-EM and ART presented better results. Compared to OS-EM, ML-EM presented similar results but at the expense of additional iterations, while ART converged after a similar number of iterations, but produced worse results. Regarding the system matrix, the best results were obtained using the tube-driven method. The results pointed to the need of a precise rebinning method and the importance of the system sensitivity correction. The results indicate that, with these algorithms, we can achieve a spatial resolution of 1,5 mm and detect lesions having 3 mm in diameter. The results also lead to think that 2 mm lesions may be detected with acquisition times higher than the ones simulated for this work. These results compare well with results from other PEM scanners, being better in some of the evaluated parameters. However, these results must be validated with real data during the clinical trials that will be carried on in a near future.
- 3-Hydroxy-quinolin-2(1H)-ones, a useful scaffold : synthesis and biological evaluationPublication . Paterna, Roberta 1985-; Góis, Pedro Miguel Pimenta; Moreira, Rui, 1960-The quinolin-2(1H)-ones ring establish the core structure of many natural and synthetic molecules and a broad spectrum of biological properties like, antimicrobial, enzymatic and neuro protective activities, have been attributed to these molecules. Additionally, 4-hydroxyquinolin-2-ones (4HQs) and 3-hydroxyquinolin-2-ones (3HQs), derivatives of quinolin-2-one, have also been reported with promising biological properties, and have attracted much attention from the medicinal chemist community. The 3HQ core is present in the structure of naturally occurring products viridicatin, viridicatol and 3-O-methyl viridicatin first isolated from the mycelium of Penicillium viridicatum. Although, due to the reduced knowledge about 3HQs, from a synthetic and biological perspective, in the last years, the development of new methodologies for their synthesis has been stimulated and strategies based on condensations, intramolecular cyclization and ring expansions have been applied. Recently reported has nonclassical bioisosteres of α-glycine, 3HQs derivatives are potent inhibitors of the Human D-amino acid oxidase (DAAO) and due to their ability to chelates metal centres, 3HQs are counted as inhibitors of HIV-1 reserve transcriptase associated RNase H activity and as inhibitors of influenza A endonuclease. In view of the present stat-of-the-art, 3HQs new derivatives were synthetized using a new efficient methodology centered on the emergent metal-organo-catalysed (MOC) concept. A one-pot protocol using the MOC system NHCdirhodium( II)/DBU catalyzed Eistert ring expansion reaction of isatins with ethyl diazoacetate to afford the 3-hydroxy-4 ethylesterquinolin-2(1H)-ones core. The reaction provides the final products regioselectively and with yields ranging from good to excellent. Furthermore, DFT calculations were performed on this system and support a mechanism in which the key step is the metallocarbene formation between the 3-hydroxyindole-diazo intermediate and the dirhodium(II) complex. After the above mentioned optimized methodology the second part of this work is dedicated to the biological activity of 3HQ and its derivatives. Various synthetic modifications have been made to introduce specific chemical group keeping the 3HQs core structure. Several compounds with different properties were synthesized and important biological studies were performed on 4-carboxamide-3HQ derivatives showed interesting biological activity as a potential anticancer lead molecule. Additionally, based on the that 3HQs can complex metallic centers and been an isoster of glycine, we hypothesized that 3HQ derivatives could be a useful platform to design new modulators of human phenylalanine hydroxylase (hPAH), the enzyme responsible by the genetic disease phenylketonuria. The new hPAH modulators were simply prepared based on ring-expansion reaction of isatins with NHS-diazoacetate catalysed by di-rhodium(II) complexes yielding 4-Carboxamide-3HQs in good-toexcellent yields. The 7-trifluoromethyl-4-carboxamide-3HQs 134, was identified as the most efficient hPAH modulator, with an apparent binding affinity nearly identical to the natural allosteric activator L-Phenylalanine. Therefore, as 3 hydroxyquinolies have demonstrated to be good scaffolds for the design and development of compounds with activity over phenylalanine hydroxylase and an excellent starting point for the development of novel therapeutics for a phenylketonuria.
- 3-Oxo-β-Sultams and 4-Oxo-β-Lactams as chemical tools for activity-based protein profiling of serine hydrolasesPublication . Carvalho, Luís Miguel Afonso Ramos de; Moreira, Rui Ferreira Alves; Penque, Deborah; Lucas, Susana DiasActivity-based protein profiling (ABPP) is a technique that analyzes the dynamics in enzymatic activity in complex proteomes by using small molecular probes, deemed activity-based probes (ABPs), containing a reactive group to covalently bind enzyme catalytic residues, a tag for detection of labeled targets and a linker as a spacer and also specificity-enhancing. Different reactive groups have been developed to engage a wide range of enzymatic families but there is a constant need to create new chemical tools to expand the pool of engageable targets. In this work we evaluated two 4-membered ring chemotypes as new reactive groups for ABPP of serine hydrolases. The 3-Oxo-β-Sultam was revealed to be a highly reactive chemotype which labels a wide range of proteins with limited target occupancy. A crystallographic analysis of the reaction of 3-Oxo-β-Sultams with elastase enzymes revealed a previously unknown mechanism of inhibition of these enzymes by sulfonylation, suggesting 3-Oxo-β-Sultam compounds could be used to expand the pool of available sulfonylating tools in chemical biology. 4-Oxo-β-Lactams were shown to potently hit a selected group of serine hydrolase with high target occupancy, including human neutrophil elastase (HNE) and members of the ABHD and DPP families of enzymes. A competitive-ABPP approach revealed high potency of a library of 4-Oxo-β-Lactams to target these enzymes. 4-Oxo-β-Lactams were identified as a new chemotype for DPP8 and DPP9 inhibition. Crystallography experiments revealed a new binding mode of these enzymes with 4-Oxo-β-Lactams, highlighting that these compounds could be used to pursue selective DPP8 or DPP9 inhibitors, a highly pursued field in current medicinal chemistry.
- 3D digital breast cancer surgery with augmented realityPublication . Gouveia, Pedro; Almeida, José Crespo Mendes de; Campos, Maria João de Viseu Botelho Cardoso Aires deBreast conservative surgery (BCS) combined with radiotherapy has become the treatment of choice for the majority of early breast cancer patients. With an identical overall survival rate when compared to mastectomy, BCS is usually associated with a better cosmetic outcome. BCS aims to achieve optimal long-term local control, thus performing excisions with free margins. However, the wider the excision, and thus the possibility of attaining free margins, the higher the risk of poor cosmetic outcomes and breast deformity. If a positive margin is obtained, a re-excision may be needed, potentially impacting breast shape and cosmesis. At least 30% of cases still result in fair/poor aesthetic outcomes. These fair/poor results depend on several factors that have been thoroughly studied. Among these, breast volume, tumor size and location are the most important with a major impact on aesthetic outcome in multivariate analysis. But a single, easy and reproducible method to estimate breast volume is not available that could ultimately help in surgical planning for selecting the optimal BCS technique. Moreover, tumor size and location interpretation rely on the treating physician’s cognitive spatial interpretation of radiology images. New tools and methodologies are needed to improve breast cancer surgical planning and oncological outcomes. In this work, a new quantitative and an inexpensive method to accurately calculate breast volume using a three-dimensional (3D) technology was developed and validated with a depth sensor low-cost surface device (Microsoft Kinect®). Standard methods like breast MRI and mastectomy specimen volumes were used as ground truth, but differences between all methods need further developments to reach clinical applicability. Imaging fusion technology was attempted to harmonize anatomic limits and to improve volume delimitation between breast MRI and 3D surface scan methods. Furthermore, a methodology for breast MRI to 3D surface scan fusion was investigated. A patient-specific digital breast model integrating the real breast torso and the tumor location was created and validated with breast MRI to 3D surface scan fusion algorithm in 16 breast cancer patients. This protocol was used to quantify breast shape differences between different modalities and measure the target registration error of several MRI/3D scan fusion algorithm variants. The fusion of single breasts with a free form deformation model of pose transformation had acceptable registration errors and accurate tumor locations. The performance of the fusion algorithm was not affected by breast volume. Breast spatial interpretation and visualization by the treating physician can thus be augmented with a digital 3D breast model that integrates radiological images, allowing immediate image interpretation of breast cancer lesions. Using previous data, a clinical surgical use case was designed and attempted after successfully production of a 3D digital breast with breast MRI to 3D surface scan fusion. An experimental test with a digital non-invasive method for intraoperative breast cancer localization using augmented reality to guide breast conservative surgery was attempted. A successful overlap of the previous standard pre-operative localization technique (carbon tattooing) and tumor visualization inside the patient’s breast with augmented reality was obtained during surgery. Along the pathway and through computer vision as artificial intelligence, various methods were investigated to produce a unified view of a patient-specific 3D digital breast model, with tumor included. A clinical use case was developed to create an innovative methodology and a proof of concept for a digital non-invasive medical device for intraoperative breast cancer localization.
- 3D image reconstruction for a dual plate positron emission tomograph: application to mammographyPublication . Martins, Mónica Vieira, 1975-; Almeida, Pedro Miguel Dinis de, 1968-
- A 3D model-based approach for spatial bat risk assessment at wind farmsPublication . Rodrigues, Sandra Cláudia Matias; Zea Bermudez, Patrícia Cortés deBat collision risk in wind farms remains an issue not adequately addressed in environmental impact assessments (EIA) due to the lack of collision risk models specific for bats. Consequently, risk assessments rely heavily on subjective evaluations and experts opinion. This work's primary objective is to provide a quantitative evaluation through model based analysis for spatial bat risk assessment, integrating data typically collected during EIA (both spatial and temporal) into an unified approach. Additionally, the approach must be economically viable and realistic if to be used in EIA processes. The proposed methodological approach is designed for acoustic spatial and temporal bat data as a proxy for bat exposure to risk. It makes use of data fusion concepts to combine data from two different sources: ground and risk-height level data (i.e. height where bats are at collision risk). The approach comprises a 3-step hierarchical model-based approach with three components: the first component uses spatial point process models combined with distance sampling techniques to determine bat activity at ground level; these second component uses temporal point process models to estimate variations of bat activity at ground and risk-height levels; in the third component the spatial and temporal models are linked to predict the intensity of bat activity at risk-height in space and time (3D approach). This data is used to inform a collision risk model to estimate the number of bat collisions per year either displayed in a map or for each turbine. All models are Bayesian, allowing to correctly account for uncertainty and incorporating previous knowledge from equivalent studies when data is insuficient, a common situation in ecological studies. Furthermore, as more data becomes available the Bayesian framework allows for updating the estimated number of collisions, resembling an adaptive management process, a highly appreciated strategy in environmental consulting industry. Finally, a project in South Africa serves as a real-case application and as proof-of-concept of the approach. Applying this approach in EIA processes is expected to decrease subjectivity, resulting in more informed decisions and, consequently, reduced impacts on bat populations.