Macrophages in M1/M2 states and exposed to amyloid-beta: a RNA-seq analysis in human cells

Tese de mestrado em Bioinformática e Biologia Computacional, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, em 2017A Doença de Alzheimer (DA) é uma doença associada à idade e é uma das doenças neurodegenerativas com maior prevalência mundial. Esta doença causa a destruição progressiva de funções cognitivas e memória, levando à eventual morte do indivíduo. Um dos principais achados patológicos, para esta doença, são as placas extracelulares constituídas por beta amilóide (Aβ) que são encontradas frequentemente no cérbero de pacientes com DA. Enquanto que os mecanismos envolvidos na progressão desta doença permanecem desconhecidos, algumas hipóteses foram propostas envolvendo estas placas amilóides. Uma dessas hipótese é conhecida como a hipótese cascata de amiloide, e esta propõe que, através de uma cascata de eventos, a acumulação das placas de Aβ eventualmente resulta em disfunção neuronal e eventual morte celular. Microglia, os macrófagos residentes no cérbero, foram encontrados perto destas placas e já foi provado que eles têm capacidade de fagocitar estas placas. Neste trabalho foi feita uma análise de RNA-seq em dados humanos, com o objectivo de comparar os perfis genéticos e de miRNA de um grupo de controlo, de macrófagos polarizados para os fenótipos M1 e M2a e de macrófagos estimulados com Aβ. Adicionalmente, também se pretendia descobrir novas vias ou genes expressos em macrófagos presentes num ambiente com Aβ. Para tal, uma análise de expressão diferencial foi feita, tanto para os dados relativos ao mRNA como para os dados relativos ao miRNA. Uma análise do enriquecimento funcional foi feita para ajudar na compreensão dos genes diferencialmente expressos no mRNA. Por fim, uma série de testes de correlação foram feitos de modo a perceber o quão influente é a expressão de miRNA sobre o seu mRNA alvo. Através da utilização de marcadores de expressão de mRNA e miRNA, foi possível verificar a polarização dos macrófagos para M1 e M2a. Além disso, foram descobertos alguns miRNA com alta expressão nos estados de polarização, que poderiam ajudar no estudo destes estados de polarização. Relativamente ao teste de correlação, os resultados estavam enviesados para correlações positivas devido a um miRNA em particular. Uma hipótese foi criada para tentar explicar esse resultado, mas nenhuma conclusão sólida foi alcançada neste projecto.Alzheimer’s Disease (AD) is an age-related disease and it is one of the most prevalent neurodegenerative diseases in the world. This disease causes a progressive destruction of cognitive functions and memory, leading to the eventual death of the individual. One of the main pathological findings, for this disease, are the extracellular plaques of amyloid-beta (Aβ) often found in the brain of AD patients. Whilst the mechanisms involved in the progression of AD remain unknown, some hypotheses have been proposed surrounding the amyloid plaques. One such hypothesis is the Amyloid cascade hypothesis, and it purposes that, through a cascade of events, the accumulation of Aβ plaques leads to neuronal dysfunction and eventual cell death. Microglias, brain macrophages, have been found around such plaques, and it has been proven that they can phagocyte said plaques. In this present work, an analysis of human RNA-seq data was done, aiming to compare the genetic and miRNA profiles of a control group, macrophages polarized towards the M1 and M2a phenotype, and of macrophages stimulated with Aβ. Additionally, another aim was to discover of novel pathways or genes expressed in macrophages in an Aβ environment. To do so, a differential expression analysis was done for both the mRNA and miRNA data. Functional enrichment analysis was done to sort the differential expressed genes for the mRNA. Lastly, a series of correlation tests were done in order to access the amount of influence done by the expression of miRNA to their mRNA targets. It was possible to attest for the polarization of the macrophages into M1 and M2a, through the usage of mRNA and miRNA markers. Furthermore, some over-expressed miRNAs were discovered for the polarized states that could provide insight in to the study of this polarization states. For the correlation test, the results were skewed towards a positive correlation due to a single miRNA. While a hypothesis was constructed as to why it may have happened, no solid conclusion was achieved in this project thus far

Aproveitamento da energia da onda de maré no estuário do Tejo

Mestrado em Engenharia FísicaO presente trabalho tem como objectivo a caracterização do potencial de aproveitamento da energia da onda de maré no estuário do Tejo. Esta caracterização é feita com base no estudo de diversas tecnologias já existentes. Esta tese encontra-se dividida em três partes. Na primeira é feita uma avaliação das tecnologias existentes. Seguidamente encontra-se a descrição do local de aplicação, o estuário do Tejo, tendo em conta a localização, batimetria, protecção legal, navegabilidade, ecossistemas e as suas características hidrodinâmicas. Para finalizar, na última parte é feito um estudo da aplicabilidade das diversas tecnologias à região em estudo, bem como o estudo da implementação de um sistema a uma ilha situada no estuário do Tejo.The aim of this work is to describe the tidal energy potential in the Tagus Estuary. This description is made with basis on the technologies that already exist. The thesis is divided into three parts. In the first part, there is a evaluation of all the existent technologies. Afterwards, there is a description of the Tagus Estuary, regarding location, bathymetry, legal protection, navigability, ecosystems and hydrodynamics’ characteristics. In the third and final section, it is crossed the information regarded in the previous parts to obtain all the possible sites for installing the devices and the respective comparison, as well as a case study in a island in the Tagus estuary

A Conceptual Model for Gender-Inclusive Requirements

Gender equality is a fundamental human right. Empowering all women and girls means empowering half of the world’s population, and therefore it is essential to create a peaceful and sustainable future. However, there is still a great deal to be done to achieve full equality of rights and opportunities for everyone. Gender inequality persists and prevents the development and thriving of individuals and societies. Such is the case of girls’ and women’s under-representation in information, communication, and technology, where only 3% of the graduates worldwide are women. Consequently, technology development holds serious problems of inclusion and diversity. As technologies rapidly evolve and revolutionize the way we live, missing diverse perspectives during development produces a gender-biased technology that, instead of advancing gender equality, creates new barriers in achieving it. Technology can play a fundamental role in progressing gender equality and ensuring gender inclusion. Although considered neutral, the software does not equally serve everyone who depends on it. Software systems favor characteristics that are statistically more observed in majorities, ignoring or even attacking certain minorities. Concerning gender, existing systems favor characteristics that are statistically more observed in men over characteristics observed in other genders (e.g., trans, cis women, non-binary). The goal of this dissertation is to create awareness that the problem of non-inclusive software is real and investigate how to develop software that benefits everyone, regardless of their gender. As a first step, we performed a systematic mapping study to gather a comprehensive overview of the state-of-the-art on gender issues in software engineering. This study served as the groundwork for the development of a conceptual model for gender-inclusive requirements. The model aims to support requirements engineers by providing a representation of gender domain knowledge that can be used as a resource for eliciting gender-inclusive requirements. To integrate the conceptual model into the existing practices of requirements engineers, we propose a framework that offers a set of guidelines with concrete goals to ensure a focus on gender inclusion from the earliest phases and throughout the development process. We applied the framework to develop a gender-inclusive prototype tool that supports the process of using the framework. The developed model was empirically evaluated by a group of 31 participants and the results were positive. The conceptual model was published in a CORE A conferenceA igualdade de género é um direito humano fundamental. Empoderar todas asmulheres e raparigas significa empoderar metade da população do mundo, e como tal, é crucial para a criação de um futuro pacífico e sustentável. No entanto, há ainda um longo percurso a percorrer na conquista da total igualdade de direitos e oportunidades. A desigualdade de género ainda persiste, impedindo o desenvolvimento e prosperação de indivíduos e sociedades. Este é o caso da área da informação, comunicação e tecnologia que tem apenas 3% graduadas em todo omundo. Consequentemente, a tecnologia apresenta sérios problemas de inclusão e diversidade, desde o seu desenvolvimento à sua adoção e utilização. A tecnologia, e o software em particular, desempenham um papel cada vez mais central na vida de todos nós. Apesar de considerado neutro, o software não serve da mesma forma todos os que dependem dele. De facto, os sistemas de software privilegiam características estatisticamente mais observadas nas maiorias, ignorando ou mesmo atacando certas minorias. No que diz respeito ao género, os sistemas existentes privilegiam características estatisticamente mais observadas nos homens em detrimento das características observadas noutros géneros (por exemplo, trans, mulheres cis, pessoas não-binárias). O objetivo desta dissertação e tomar consciência que o problema de software nãoinclusivo é real e investigar como desenvolver software que beneficie todos os utilizadores, independentemente do seu género. Como primeiro passo, realizámos um mapeamento sistematico de literatura de modo a construir uma visão integrada sobre o estado da arte em questões de género em engenharia de software. Os resultados deste estudo serviram de base para o desenvolvimento de um modelo conceptual para requisitos inclusivos de genero. Este modelo visa apoiar a elicitacao de informacao inclusiva providenciando uma representacao do conhecimento dominio de genero como recurso para a formulacao de requisitos inclusivos. Para integrar o modelo conceptual nas praticas da engenharia de requisitos, desenvolvemos uma framework que oferece um conjunto de diretrizes com objetivos concretos para garantir um foco na inclusao de genero desde as fases iniciais e ao longo do processo de desenvolvimento. Aplicamos a framework na construcao de um prototipo de uma ferramenta inclusiva de genero que apoia o seu processo de uso. O modelo desenvolvido foi avaliado empiricamente por um grupo de 31 participantes e os resultados foram positivos. O modelo conceptual foi publicado numa conferência CORE A

How are luxury hotels turning the page from opulence to sustainability? : the case of three portuguese hotels

This research aims to contribute to the debate about sustainability in the industry of luxury hospitality, by answering the following research question: how are luxury hotels turning the page from opulence to sustainability? To answer this research question, we used a qualitative approach and conducted a comparative case study on three luxury hotels in Portugal which are committed to deliver a sustainable experience without compromising the guest’s expectations. The findings show that it is possible to combine the two concepts and be successful by implementing five strategies: sourcing locally, favouring sustainable construction, having a biological garden, meeting the luxury standards regarding the hotel’s commodities and being located in the countryside without compromising comfort. Although it requires an investment, the study shows it is worth taking.A presente investigação pretende contribuir para o debate sobre a sustentabilidade na indústria da hotelaria de luxo, respondendo à questão: de que forma é que os hotéis de luxo estão a virar a página da opulência em direção à sustentabilidade? Para responder a esta pergunta de partida, usámos uma abordagem qualitativa e conduzimos um estudo comparativa de três hoteis de luxo em Portugal cujo compromisso passa por ser sustentável sem comprometer a proposta de luxo. As conclusões mostram que é possivel combinar os dois conceitos e ser bem-sucedido através da implementação de cinco estratégias: recorrer a produtores locais, favorecer uma construção sustentável, ter uma horta biológica, preencher os requisitos de um hotel de luxo e estar localizado numa zona rural sem comprometer o conforto. Apesar de requerer um investimento, a presente tese sustém que a sustentabilidade é um investimento essencial para ser competitivo no mercado

Non-destructive assay employing 2D and 3D digital radiographic imaging acquired with thermal neutrons and reactor-produced radioisotopes

The inner structure of some objects can only be visualized by using suitable techniques, when safety reasons or expensive costs preclude the application of invasive procedures. The kind of agent rendering an object partially transparent, unveiling thus its features, depends upon the object size and composition. As a rough rule of thumb, light materials are transparent to gamma and X-rays while the heavy ones are transparent to neutrons. When, after traversing an object, they hit a proper 2-D detector, a radiograph is produced representing a convoluted cross section, called projection, of that object. Taking a large number of such projections for different object attitudes, it is possible to obtain a 3-D tomography of the object as a map of attenuation coefficients. This procedure however, besides a time-consuming task, requires specially tailored equipment and software, not always available or affordable. Yet, in some circumstances it is feasible to replace the 3-D tomography by a stereoscopy, allowing one to visualize the spatial configuration of the object under analysis. In this work, 2-Dand 3-D radiographic images have been acquired using thermal neutrons and reactor-produced radioisotopes and proper imaging plates as detectors. The stereographic vision has been achieved by taking two radiographs of the same object at different angles, from the detector point of view. After a treatment to render them red-white and green-white they were properly merged to yield a single image capable to be watched with red-green glasses. All the image treatment and rendering has been performed with the software ImageJ

Validation of the Portuguese version of community attitudes toward people with mental illness (CAMI) [artigo]

Stigma remains a feature that influences the lifestyle of people with mental illness. Negative attitudes, stereotypes, and discrimination are still prevalent in these people’s life. Stigma is considered a public health problem that occurs unconsciously in society, categorizing people. Portugal is the seventh-worst country concerning stigma in Mental Health. There have been few improvements in reducing stigma over time, and there is a great need to create investigations and validate instruments that measure stigma in the population. This study aims to address the gaps in the level of studies and normative instruments that measure the stigma of the Portuguese population in the face of mental illness. It, therefore, aims to adapt and validate community attitudes toward people with mental illness (CAMI) culturally and examine its psychometric properties. Method: The 27-item version of CAMI was translated and back-translated into English, which was analyzed and evaluated by a panel of experts. A sociodemographic survey and CAMI were applied in an online format, in which participated 427 adults representing the Portuguese population in general. Finally, the reliability and validity of the instrument were analyzed. CAMI showed positive values of reliability and validity but not optimal. The confirmatory factor analysis values satisfactory values that indicate good quality of fit: x2 /df=3.296; comparative fit index = 0.601; goodness of fit index = 0.817; and root mean square error of approximation = 0.073, indicates good quality of fit. Cronbach alpha was different for each factor, but it was positive. Spearman coefficient (r=–0.343) obtained a negative but consistent value. This study contributed to the achievement and validation of new measures to assess the stigma of the general population related to people with mental illness. We must continue to analyze this theme, complete the validation of this instrument, and understand the existing levels of stigma, its predominance in society, and the possible creation and implementation of new measures that support literacy in mental illness and anti-stigma.info:eu-repo/semantics/publishedVersio

Prevalence of celiac disease among first degree relatives of Brazilian celiac patients

Background - Several studies have shown that celiac disease, an autoimmune disorder that occurs in genetically susceptible individuals, is highly prevalent among relatives of celiac patients. Aim - To determine the prevalence of celiac disease in a group of first degree relatives of Brazilian celiac patients. Methods - First degree relatives of celiac patients attending the Brasilia University Hospital Pediatric Gastroenterology Outpatient Clinic or the Celiac Disease Investigation Center, Brasília, DF, Brazil, between March 2001 and November 2004 were invited to undergo serological screening for celiac disease applying the IgA anti-endomysium antibody test (IgA-EMA). All positive IgA-EMA sera underwent a second screening using the IgA anti-tissue transglutaminase antibodies test. Duodenal or small intestinal biopsies were performed in all subjects positive to serological testing. Biopsy samples were classified as type (O) normal, (I) infiltrative, (II) infiltrative hyperplastic, (III) flat destructive, and (IV) atrophic hypoplastic. The final diagnosis was ascertained in subjects showing positive serological tests and a grade I to III small intestinal lesion. Results - Nine new cases of celiac disease were found among the 188 first degree relatives tested (4.8%). Conclusion - The present study confirms the high prevalence of celiac disease among first degree celiac patients’ relatives and reinforces the need of extensive diagnostic screening in this specific group

Performance ao a thermal neutron radiographic system using imaging plates

A performance evaluation of a neutron radiographic system equipped with a thermal neutron sensitive imaging plate has been undertaken. It includes the assessment of spatial resolution, linearity, dynamic range and the response to exposure time, as well as a comparison of these parameters with the equivalent ones for neutron radiography employing conventional films and a gadolinium foil as converter. The evaluation and comparison between the radiographic systems have been performed at the Instituto de Engenharia Nuclear - CNEN, using the Argonauta Reactor as source of thermal neutrons and a commercially available imaging plate reade