Barreiras de radão à base de impermeabilizantes líquidos em pedras naturais

Métodos de construção antigos utilizavam recursos naturais da própria região para construir edifícios, tais como madeiras, argilas e pedras. Segundo os censos de 2011, 189 072 edifícios apresentam estrutura em alvenaria de pedra, sendo que o granito era muito utilizado nas zonas de Trás-os-Montes, Beiras e Douro Litoral. Por questões estéticas muitas dessas paredes de granito são mantidas à vista. O granito é uma rocha rica em rádio e urânio, esta liberta grandes quantidades de radão que se acumulam no interior dos edifícios. O radão é um gás incolor e inodoro, responsável por ser a maior causa de cancro do pulmão a seguir ao tabaco. Atualmente em Portugal, a Portaria nº. 353-A/2013 fixa o limite máximo de concentração em 400 Bq/m3 para edifícios existentes. Procurando manter a beleza do granito à vista e ao mesmo tempo diminuir a concentração de radão no ambiente interior, pretendeu-se estudar neste trabalho a capacidade de alguns revestimentos satisfazerem ambas as situações. A fim de estudar a contribuição de alguns materiais para reduzir a concentração de radão, foram executados dois tipos de ensaio distintos, conhecer a concentração de radão proveniente de amostras de granito e calcular o seu coeficiente de permeabilidade ao oxigénio. Os ensaios foram executados inicialmente para as amostras de granito sem revestimento e posteriormente com revestimento, de forma a comparar as diferenças obtidas com a aplicação dos revestimentos em estudo. Os revestimentos selecionados foram: verniz, hidrofugante e silicone líquido. Estima-se que o verniz reduza a concentração de radão entre 32 e 72%. Após interpretar estatisticamente os resultados, o verniz e o hidrofugante reduziram aproximadamente 40% da concentração de radão, enquanto o silicone líquido aumentou ligeiramente a concentração em 10%. Quanto à permeabilidade ao oxigénio, o silicone apresentou uma redução de 89% do coeficiente de permeabilidade, enquanto o verniz reduziu 79% e o hidrofugante apresentou uma redução de 65%. É necessário efetuar mais estudos referentes à redução de concentração de radão por parte destes materiais, para isso foi projetado um novo modelo de ensaio ao radão. O novo modelo deverá ser utilizado em futuros trabalhos da mesma natureza.Ancient construction methods used the region's own natural resources to construct buildings, such as wood, clay, and rocks. According to the 2011 census, 189 072 buildings have rock masonry structure, since granite was widely used in the Trás-os-Montes, Beiras and littoral Douro regions. Because of aesthetic reasons many of these granite walls are kept in plain sight. Since the granite is a rock with a rich content of radio and uranium, it releases large amounts of radon, which accumulate inside the buildings. The radon is a colorless and odorless gas that is responsible to be the biggest cause of lung cancer after tobacco. Currently in Portugal, the “Portaria” nº. 353-A/2013 sets the maximum concentration limit in 400Bq/m3 for existing buildings. Looking to maintain the granite’s beauty in sight and at the same time to reduce the radon concentration indoors, the current thesis aims to study the capacity of some coatings to satisfy both situations. To understand the contribution of some materials to reduce the radon concentration, two different kinds of test were performed. To know the radon concentration from granite samples and to calculate their oxygen permeability coefficient. The tests were performed initially for the uncoated and then coated granite samples in order to compare the differences obtained after applying the coatings under study. The coatings selected were: varnish, water repellant and liquid silicone. It is estimated that the varnish reduces radon concentration between 32 and 72%. In another statistical interpretation the varnish and the water repellant reduced approximately 40% of the radon concentration, while the liquid silicone slightly increased the concentration by 10%. About oxygen permeability, the silicon showed a reduction of 89% in the permeability coefficient, while the varnish reduced 79% and the water repellant showed a reduction of 65%. It is necessary to carry out further studies concerning the reduction of radon concentration by these materials, for which a new radon test model has been designed. The new model should be used in future works like this

Realidade Aumentada Aplicada a Panoramas Táticos

Com o desenvolvimento tecnológico que se tem vindo a verificar nos últimos anos, uma das tecnologias que mais expetativas tem suscitado, é a Realidade Aumentada (RA): uma forma de estender a perceção humana da realidade. Com o intuito de tornar a Marinha Portuguesa mais consentânea com a evolução a nível tecnológico, a Realidade Aumentada apresenta uma boa solução para uma melhoria sustentável, capacitando variadas áreas de necessidade, impedindo, assim, a estagnação temporal da tecnologia. Uma das missões da Marinha Portuguesa assenta na formação e ensino dos seus elementos. Através do seu método de visualização, a Realidade Aumentada pode tornar a aprendizagem mais gráfica e interativa, usando objetos virtuais em 3D, inserindo-os em ambientes reais, promovendo assim dinamismo ao ministrar formação. Pretende-se com esta dissertação, não só captar a atenção das potencialidades que a Realidade Aumentada pode oferecer, mas também potenciar uma simbiose entre a tecnologia Realidade Aumentada e o ensino/formação ministrado na Escola Naval e na Marinha Portuguesa. Para esse efeito, e após a recolha de informação e dados relativa ao tema proveniente de fontes e autores diversos, auscultou-se a opinião de Aspirantes da E.N., por forma a apurar-se o proveito do uso desta tecnologia, na aprendizagem de operações navais e manobras e evoluções dos navios. Com os dados obtidos, foi desenvolvida uma solução, com o propósito de apresentar diferentes formaturas de navios, através de uma interface digital, onde a visualização é efetuada através de um smartphone. Da análise efetuada à solução foram extraídos dados relevantes, podendo estes ser de suscetível interesse para a Marinha Portuguesa. Este conceito é apenas um exemplo da potencialidade desta tecnologia, abrindo caminho a projetos futuros relacionados com a Realidade Aumentada.With the technological development that has been verified in recent years, one of the technologies that more expectations has raised, is the Augmented Reality (AR): a way to extend the human perception of reality. With the aim of making the Portuguese Navy more in line with developments in technology, the Augmented Reality presents a good solution for a sustainable improvement, enabling a variety of areas of need, thus preventing the temporary stagnation of technology. One of the missions of the Portuguese Navy is based on the training and teaching of its elements. Through its visualization method, Augmented Reality can make learning more graphical and interactive, using 3D virtual objects, inserting them in real environments, thus promoting dynamism in the delivery of training. This dissertation aims not only to capture the attention of the potentialities that the Augmented Reality can offer, but also to foster a symbiosis between the Augmented Reality technology and the teaching / training taught at the Naval School and the Portuguese Navy. To that end, and after collecting information and data related to the theme from various sources and authors, the opinion of Aspirants of the EN was heard, in order to ascertain the use of this technology in learning naval operations and maneuvers and vessel evolutions. With the data obtained, a solution was developed, with the purpose of presenting different sizes of ships, through a digital interface, where the visualization is carried out through a smartphone. From the analysis made to the solution, relevant data were extracted, which could be of interest to the Portuguese Navy. This concept is just one example of the potentiality of this technology, paving the way for future perspectives related to Augmented Reality

Optimizing SUV Analysis: A Multicenter Study on Preclinical FDG-PET/CT Highlights the Impact of Standardization

PURPOSE: Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUV mean and SUV max) of different organs using the same [ 18F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated. PROCEDURES: In total, 12 observers (4 beginners and 8 experts) analyzed identical preclinical [ 18F]FDG-PET-only and PET/CT datasets according to their local default image analysis protocols for multiple organs. Furthermore, a standardized protocol was defined, including detailed information on the respective VOI size and position for multiple organs, and all observers reanalyzed the PET/CT datasets following this protocol. RESULTS: Without standardization, significant differences in the SUV mean and SUV max were found among the observers. Coregistering CT images with PET images improved the comparability to a limited extent. The introduction of a standardized protocol that details the VOI size and position for multiple organs reduced interobserver variability and enhanced comparability. CONCLUSIONS: The protocol offered clear guidelines and was particularly beneficial for beginners, resulting in improved comparability of SUV mean and SUV max values for various organs. The study suggested that incorporating an additional VOI template could further enhance the comparability of the findings in preclinical imaging analyses. </p

Modulation of pro-inflammatory respondes in the retina by neuropeptide Y: the role of NPY Y1 receptor

Dissertação de Mestrado em Farmacologia Aplicada apresentada à Faculdade de Farmácia da Universidade de CoimbraNeuropeptide Y (NPY) is a 36 amino acid peptide that is abundantly distributed in the central nervous system (CNS), including the retina. NPY acts through the activation of several G protein-coupled receptors: Y1R, Y2R, Y4R and Y5R. It has been shown that this peptide has neuromodulatory and neuroprotective roles in the retina, and it has been associated with physiological and pathological conditions. Increasing evidence has shown that NPY is a regulator of inflammatory processes, but its effects depend on cell types and tissues, the type of NPY receptors involved and on factors present in the cellular milieu. However, little is known about its potential inhibitory effects on pro-inflammatory processes in the retina, especially controlling retinal microglia reactivity. Microglia are the innate immune cells of the CNS and are involved in the maintenance of retinal homeostasis. However, in response to retinal injury, activated microglia adopt ameboid morphology, express inducible nitric oxide synthase (iNOS) and release neurotoxic factors such as the pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and reactive oxygen species (ROS), which can lead to neuronal degeneration. The detrimental effects of overactivated microglia are thought to contribute to the pathogenesis retinal degenerative diseases, such as diabetic retinopathy and glaucoma. Since neuroinflammation is described to be involved in the pathogenesis of several retinal degenerative diseases, we investigated the NPY effects, particularly via the Y1R activation, on the modulation of microglia activation and inhibition of pro-inflammatory processes in the retina. To induce an inflammatory response, cultured retinal explants, primary retinal neural mixed cultures and purified cultures of retinal microglial cells were exposed to lipopolysaccharide (LPS), in the absence or presence of NPY or a Y1 receptor agonist ([Leu31, Pro34]-NPY) and/or antagonist (BIBP3226). Additionally, an animal model of retinal degeneration, a retinal ischemia-reperfusion (I/R) injury model, was used. In this case, NPY or [Leu31, Pro34]-NPY (LP-NPY) were injected intravitreally 1 h before ischemia and retinal blood flow was restored for 8 h or 24 h. Several markers and parameters of the retinal inflammatory status were evaluated, including the activation of retinal microglial cells, in terms of changes in morphology and inducible protein expression, as well as the expression and production of pro-inflammatory cytokines in the retina. In cultured retinal explants, NPY was able to inhibit the alterations in retinal microglia morphology, as well as the increase in iNOS expression and ROS production in retinal microglia, triggered by LPS. Moreover, NPY inhibited IL-1β and IL-6 expression and production. Y1R activation mimicked the inhibitory effects of NPY on the LPS-induced alterations in retinal microglia morphology and iNOS expression. In addition, activation of Y1R inhibited the expression and production of all pro-inflammatory cytokines studied (TNF- α, IL-1β and IL-6), indicating that Y1R appears to have a predominant role on the effects mediated by NPY. In the I/R injury model, intravitreal injection of NPY or LP-NPY before ischemia inhibited morphological changes in retinal microglia induced by I/R 24 h after reperfusion. Furthermore, 8 h after reperfusion the upregulation of TNF-α, IL-1β and IL-6, and the production of TNF-α and IL-6, in ischemic retinas, was inhibited by NPY. Altogether, these data provide evidence that NPY and Y1R activation are able to regulate retinal microglia activation and inhibit the expression and production of neurotoxic factors in the retina. Immunohistochemistry data and in vitro studies indicate that retinal microglial cells primarily express iNOS and are the primary sources of ROS production under pro-inflammatory conditions in the retina. These findings could point novel physiological and therapeutic roles of NPY system in neuroinflammation, not only in the retina, but also in the nervous system.O neuropeptídeo Y (NPY) é um peptídeo com 36 aminoácidos que se encontra amplamente distribuído no sistema nervoso central (SNC), incluindo a retina. Os seus efeitos são mediados através da ativação de vários recetores acoplados a proteínas G: Y1R, Y2R, Y4R e Y5R e y6R. Este peptídeo pode atuar como neuromodulador e neuroprotetor na retina, e tem sido associado a diversas doenças e processos fisiológicos. Evidências crescentes têm demonstrado que o NPY é um regulador de processos inflamatórios, dependendo os seus efeitos do tipo de tecidos e células em que atua, do tipo de recetores envolvidos e dos fatores presentes no meio. No entanto, o seu potencial papel antiinflamatório na retina, em particular no controlo da reatividade da microglia, é praticamente desconhecido. As células da microglia são células do sistema imunitário do SNC, e têm um papel na homeostase da retina. No entanto, em resposta a lesões na retina, as células da microglia ficam ativadas, adotando uma morfologia ameboide, expressam a isoforma indutível da sintase do monóxido de azoto (iNOS), libertam substâncias neurotóxicas, como por exemplo as citocinas pró-inflamatórias TNF-, IL-1 e IL-6, e espécies reativas de oxigénio (ROS), o que pode contribuir para a morte neuronal. Pensa-se que os efeitos nocivos da microglia ativada podem contribuir para a patogénese de doenças degenerativas da retina, tais como a retinopatia diabética e o glaucoma. Uma vez que se considera que a neuroinflamação está envolvida na patogénese de várias doenças da retina, neste trabalho investigou-se os efeitos do NPY, e em particular da ativação do recetor Y1 (Y1R), na modulação da ativação da microglia e na inibição da resposta pro-inflamatória na retina. Para induzir uma resposta inflamatória, expuseram-se culturas de explantes de retina, culturas mistas de retina e culturas purificadas de microglia de retina a lipopolissacarídeo (LPS), na ausência ou presença de NPY ou de um agonista ([Leu31, Pro34]-NPY) e/ou antagonista (BIBP3226) do Y1R. Adicionalmente, foi utilizado um modelo animal de isquémiareperfusão (I/R) da retina. Neste caso, o NPY ou o [Leu31, Pro34]-NPY (LP-NPY) foram injetados no vítreo 1 h antes da isquémia, tendo sido utilizados dois tempos de reperfusão, 8 e 24 h. Foram avaliados diversos marcadores e parâmetros indicadores de inflamação na retina, incluindo o estado de ativação das células da microglia, em termos de alterações morfológicas, assim como a expressão e produção de citocinas pro-inflamatórias. Em culturas de explantes de retina, o NPY inibiu as alterações na morfologia das células da microglia, bem como o aumento da expressão de iNOS e a produção de ROS na microglia de retina, desencadeados pela exposição a LPS. Por outro lado, o NPY inibiu a expressão e produção de IL-1β e IL-6. A ativação do Y1R mimetizou os efeitos do NPY na inibição das alterações morfológicas e expressão de iNOS na microglia de retina induzidas pelo LPS. Além disso, a ativação do Y1R inibiu a expressão e produção de todas as citocinas pró-inflamatórias estudadas (TNF-α, IL-1β e IL-6), sugerindo um papel importante para o Y1R nos efeitos mediados pelo NPY. No modelo de I/R, a injeção intravítrea de NPY ou de LP-NPY antes da isquémia inibiu as alterações morfológicas nas células da microglia de retina induzidas pela I/R após 24 h de reperfusão. Além disso, após 8 h de reperfusão, o aumento na expressão de TNF-α, IL-1β e IL-6 e na produção de TNF-α e IL-6 em retinas sujeitas a isquémia foi inibido pelo NPY. No seu conjunto, os dados obtidos revelam que o NPY e a ativação do Y1R são capazes de regular a ativação da microglia de retina e inibir a expressão e produção de fatores neurotóxicos na retina. Estes resultados poderão contribuir para elucidar potenciais efeitos fisiológicos e terapêuticos do NPY em processos neuroinflamatórios não somente na retina, mas também no sistema nervoso

Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body&rsquo;s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8+ T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided

Radionuclide imaging of cytotoxic immune cell responses to anti-cancer immunotherapy

Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body’s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8(+) T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided

Development of antibody immuno-PET/SPECT radiopharmaceuticals for imaging of oncological disorders : an update

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are molecular imaging strategies that typically use radioactively labeled ligands to selectively visualize molecular targets. The nanomolar sensitivity of PET and SPECT combined with the high specificity and affinity of monoclonal antibodies have shown great potential in oncology imaging. Over the past decades a wide range of radio-isotopes have been developed into immuno-SPECT/PET imaging agents, made possible by novel conjugation strategies (e.g., site-specific labeling, click chemistry) and optimization and development of novel radiochemistry procedures. In addition, new strategies such as pretargeting and the use of antibody fragments have entered the field of immuno-PET/SPECT expanding the range of imaging applications. Non-invasive imaging techniques revealing tumor antigen biodistribution, expression and heterogeneity have the potential to contribute to disease diagnosis, therapy selection, patient stratification and therapy response prediction achieving personalized treatments for each patient and therefore assisting in clinical decision making