Repositório RCAAP

Nowadays, the demand of cosmetics with sustainable and natural origin ingredients is a common practice in the cosmetic industry. Essential oils (EOs) and hydrolates are natural sources of biologically active ingredients because of their chemical composition and broad application. In this study, national producers (mainland Portugal and Azores archipelago) EOs (11) and hydrolates (7) obtained from forest logging and thinning of Eucalyptus globulus, Pinus pinaster, Pinus pinea and Cryptomeria japonica, were chemically evaluated, and their bioactivity and sensorial properties were assessed. EOs and hydrolates volatiles (HVs) were analyzed by gas chromatography and gas chromatography mass spectrometry. 1,8-Cineole was E. globulus EOs and HVs dominant compound, while α- and β-pinene dominated P. pinaster EOs. Limonene and α-pinene were predominant in P. pinea and C. japonica EOs, respectively. P. pinaster and C. japonica HVs were dominated by α-terpineol and terpinene-4-ol, respectively. Antioxidant activity was determined by radical scavenging ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and intracellular ROS measurement. C. japonica EO showed the highest antioxidant activity, whereas one of E. globulus EOs showed the lowest activity. Antimicrobial activity was evaluated by the microdilution plate method determining the minimum inhibitory concentration for Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Bacillus subtilis ATCC 6633, Escherichia coli TCC 8739, Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404. Eucalyptus EOs showed the greatest efficacy against the selected strains while C. japonica EO had no antimicrobial activity against these strains. P. pinea EO had similar efficacy against B. subtilis ATCC 6633 as two of E. globulus EOs. Sensory double-blind evaluation, approved by the local Ethical Committee, was performed in human volunteers. A structured questionnaire was used to collect data about the perception and applicability of different emulsions perfumed with 0.5% of EOs. C. japonica emulsion, which has a fresh and earthy odour, was chosen as the most pleasant by 60% of the volunteers, followed by P. pinea emulsion odour with 53%. C. japonica emulsion was also the one chosen for improving the sense of well-being. Overall, 19% of the volunteers selected C. japonica and P. pinea emulsions as their favorite ones. The studied EOs and Hds showed relevant antioxidant activity and promising antimicrobial activity. Moreover, they address the demand for sustainable and responsibly sourced odour accepted by consumers.

A produção e armazenamento de eletricidade tornaram-se indispensável para o funcionamento da nossa sociedade. Atualmente existe uma grande procura pelo armazenamento de energia, visando a sua utilização num mercado vasto de aplicações, cujas necessidades requerem o fornecimento de eletricidade. Condensadores são conhecidos como um dos primeiros tipos de armazenamento de energia, sendo o seu uso abrangente na maioria dos dispositivos eletrónicos. Os supercondensadores englobamse dentro da categoria de condensadores, sendo que se distinguem pela capacidade de armazenar maiores quantidades de energia em troca de pequenas perdas de potência. Este trabalho visa o estudo e caracterização de elétrodos de carbono ativado aplicados em supercondensadores tratados a laser pulsado, de modo a viabilizar o seu uso comercial, possibilitando novos meios de armazenamento de energia. Este tratamento permite a introdução de novos canais na superfície do elétrodo permitirá aos iões ter acesso a zonas do elétrodo que sejam electroquimicamente inativas ou de difícil acesso e assim aumentar o fluxo iónico na interface elétrodo/eletrólito. Foram preparadas duas amostras de elétrodos à base de carbono ativado. Estas amostras apresentam diferentes quantidade de binder (PVFD) e carbono ativado (CA) variando 10-20% e 80-70% respetivamente, sendo que ambas apresentam a mesma quantidade de carbon black 10%, de modo a obter uma melhor eficiência eletroquímica. Ambas as amostras foram submetidas ao tratamento a laser Nd:YAG, operado em modo pulsado. Desta forma foi possível realizar microperfurações na superfície do elétrodo, com o intuito de aumentar o fluxo iónico da interface elétrodo/eletrólito. Foram testados diferentes níveis de potência, possibilitando o estudo do impacto nos elétrodos. Os estudos destas amostras foram realizados com recurso a técnicas de microscopia, nomeadamente a lupa e o microscópio eletrónico de varrimento (MEV), e posteriormente analisadas com a ferramenta ImageJ ®. Foi elaborado um pequeno protocolo com esta ferramenta de modo a correlacionar as diferentes potências utilizadas com as microperfurações e as áreas dos buracos obtidas das mesmas. Realizou-se uma análise de perfilometria, permitindo obter alguns dados sobre as profundidades e formas dos buracos obtidas. As amostras também foram submetidas a uma pesagem antes e após o tratamento, permitindo uma análise quantitativa mais aprofundada. No seguimento do trabalho experimental obteve-se os resultados desejados das microprefurações, realizando os padrões idealizados e mantendo a coesão da estrutura do elétrodo. A análise mostrou resultados ambiciosos, obtiveram-se algumas conclusões comportamentais sobre a interação do feixe laser e a superficie do elétrodo, e como esta se correlaciona com a intensidade do laser. Assim o trabalho culminou com a realização de elétrodos com as perfurações desejadas, e a colheita de dados sobre os mesmos. Estes dados permitem iniciar um processo iterativo do estudo dos parâmetros laser, de modo a convergir para a melhor solução de tratamento destes elétrodos.

Background: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. Methods: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. Findings: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. Interpretation: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year.

The Monchique alkaline complex (MAC) crops out in southern Portugal with a roughly elliptical shape of about 80 km2 elongated along the ENE-WSW direction. The MAC dates to the Late Cretaceous (69- 72 Ma) and intrudes the Carboniferous Flysh formation of the South Portuguese Zone. At the surface, it comprises two main types of syenites: a central homogeneous nepheline syenite surrounded by a heterogeneous syenite unit, and some less expressive outcrops of mafic rocks (gabbros, hornfels, breccia and basalts). This igneous complex was formed during the Upper Cretaceous West Iberia alkaline magmatic event, which is characterized by alkaline magmatism of sublithospheric origin and was active from approximately 100 Ma to 69 Ma. The Monchique region hosts the most active seismic cluster of mainland Portugal, with low magnitude earthquakes (M < 4) that occur along two lineations with NNE–SSW and WNW–ESE preferred orientations. In this work we study the Monchique region through gravimetric and magnetic methods in order to: 1) better understand how the MAC influences the geomagnetic and gravimetric field in the region; 2) to create new and consistent 2D and 3D models for the intrusion; and 3) to help constrain the origin of the observed seismicity and its possible relationship with the existence of sub cropping magmatic bodies. We process recently acquired data - ground gravity survey (49 points) and drone-borne aeromagnetic survey – and integrate it with existing data. The interpretation of the gravimetric results is complemented by a density analysis of the magmatic and host rocks. We perform 3D magnetic and gravity inversion to model the geometry of gravity and magnetic sources, and 2D magnetic forward modeling along a representative profile. The calculated Bouguer gravity anomaly shows a positive gradient towards the southwest with a negative peak in the center of the Monchique Mountain. However, after applying the terrain correction (complete Bouguer anomaly), this peak vanishes. This is justified by the similar mean density values for the syenite and host rocks, respectively 2560 kg/m3 and 2529 kg/m3. The gravity field shows a significant positive anomaly (both free-air and Bouguer) in the SW part of the study region, close to Ponta de Sagres. This anomaly and its associated gradient, complemented by results from our 3D density inversion model, imply the presence of high density rocks in this region suggesting a decrease in the crustal thickness and consequent shallowing of mantle materials. The new aeromagnetic data allows to map the Monchique magnetic anomaly with unprecedented detail and reveal a 10 km elongated anomaly with 3 km wavelength and maximum 1707 nT amplitude. 3D magnetic susceptibility inversion models show a 15 km long body with maximum depth between 5-10 km, and susceptibility >0.02 SI, in agreement with previous susceptibility analysis of Monchique samples. The highest magnetic anomaly is found at Picota hill (east), but the deepest parts of the intrusion seem to be bellow Fóia hill (west). It is noteworthy that earthquake hypocenters concentrate at depths of 5-20 km, thus mostly below the modeled magmatic intrusion, indicating a fracture zone oriented preferentially ENE-WSW with hydrothermal activity.

Background: Ocular abnormalities have been known to occur in hereditary amyloidotic polyneuropathy since the 1950s. While vitreous opacities and scalloped pupils were described early it has become evident that every component of the eye from the conjunctiva to the retinal vasculature can be involved. Reports from the major centres in Japan, Portugal and Sweden, which primarily treat patients with ATTRV30M, have indicated that with the increased longevity seen in patients treated with liver transplantation the frequency of the more severe eye findings, notably vitreous opacities and subsequent glaucoma, are being detected more frequently. Methods: In an attempt to confirm that the experience was similar in a broader range of locales we performed a survey of ten treatment centres in eight countries to determine the frequency of severe ocular abnormalities (vitreous opacities and glaucoma) in 804 patients with V30M disease and whether there was any relationship to treatment with liver transplantation or the transthyretin stabilizer tafamidis. Results: The data indicate that the frequency of these abnormalities increases with increasing duration of disease. In patients broadly matched for duration of disease the frequency was higher in subjects who had undergone liver transplantation than in those who were untreated. Conclusions: Retrospective surveys are subject to a number of potential biases. In this case, the major potential confounders were defining the time of disease onset and physician bias in choice of therapy, particularly regarding the choice of patients and the time in their course when they should undergo liver transplantation, and when and whether they should receive tafamidis. Nonetheless it appears that the incidence of severe ocular abnormalities in V30M subjects from centres around the world is similar to those found in centres in the areas endemic for this variant protein. The incidence increased with duration of disease regardless of therapy with the highest frequencies seen in patients more than ten years after diagnosis who had undergone liver transplantation.

Background: Cellular metabolism generates reactive oxygen species. The oxidation and deamination of the deoxynucleoside triphosphate (dNTP) pool results in the formation of non-canonical, toxic dNTPs that can cause mutations, genome instability, and cell death. House-cleaning or sanitation enzymes that break down and detoxify non-canonical nucleotides play major protective roles in nucleotide metabolism and constitute key drug targets for cancer and various pathogens. We hypothesized that owing to their protective roles in nucleotide metabolism, these house-cleaning enzymes are key drug targets in the malaria parasite. Methods: Using the rodent malaria parasite Plasmodium berghei we evaluate here, by gene targeting, a group of conserved proteins with a putative function in the detoxification of non-canonical nucleotides as potential antimalarial drug targets: they are inosine triphosphate pyrophosphatase (ITPase), deoxyuridine triphosphate pyrophosphatase (dUTPase) and two NuDiX hydroxylases, the diadenosine tetraphosphate (Ap4A) hydrolase and the nucleoside triphosphate hydrolase (NDH). Results: While all four proteins are expressed constitutively across the intraerythrocytic developmental cycle, neither ITPase nor NDH are required for parasite viability. dutpase and ap4ah null mutants, on the other hand, are not viable suggesting an essential function for these proteins for the malaria parasite. Conclusions: Plasmodium dUTPase and Ap4A could be drug targets in the malaria parasite.

Animal models have for long been pivotal for parasitology research. Over the last few years, techniques such as intravital, optoacoustic and magnetic resonance imaging, optical projection tomography, and selective plane illumination microscopy developed promising potential for gaining insights into host-pathogen interactions by allowing different visualization forms in vivo and ex vivo. Advances including increased resolution, penetration depth, and acquisition speed, together with more complex image analysis methods, facilitate tackling biological problems previously impossible to study and/or quantify. Here we discuss advances and challenges in the in vivo imaging toolbox, which hold promising potential for the field of parasitology.

The aim of this paper is the study of queer zines produced in Madrid in the 1990’s. There were two pioneer groups in queer activism in Spain, La Radical Gai formed by gay men and LSD, formed by lesbians. La radical Gai published six numbers of their zine De un plumazo, plus two dossiers (one about HIV and the other one about a homophobic attack). LSD was created one year later than La Radical Gai; they published four numbers of Non-Grata. Both groups share ideology, but had different aims and agenda because of their specific gender experience: the main theme for gay men was HIV, whereas lesbians mainly focused on visibility. Albeit the groups did not denominate themselves as queer when they were formed (1991 La Radical Gai, 1993 LSD), they were the first to coin this term in the Spanish context (Solá, 2012, p. 267). La Radical Gai named their zine Queerzine in 1993 and LSD use this term in their first zine published in 1994, where they already defined themselves as queer lesbians. This paper will analyze these zines as historical documents, which help us to understand the characteristics and history of the zine production in Spain; as well as, the introduction of Queer Theory in the context of Madrid in the 1990›s. The zines were not only important for the academic group of Queer Theory but also for the activism movement of that period. Produced by university students, some of which continued their careers in academia, these zines promoted and boasted the introduction of Queer Theory in the University.

Diabetes is a chronic metabolic disease characterised by high blood glucose levels. It is a major burden on the national healthcare system as it brings serious problems associated with it over time, such as heart, eye, kidney, nerve and blood vessel problems, and can increase the consumption of healthcare resources. Diabetes greatly disrupts the lives of individuals being associated with poorer quality of life and increased early mortality. Therefore, it is important to characterise the Portuguese diabetic population as well as the comorbidities that most often accompany diabetes. (Organization, 2000). This study is part of a project proposed by EpiDoC Unit at Nova Medical School, where a prospective cohort study entitled Epidemiology in chronic diseases (EpiDoC) was developed in 2011. To this end, this study was designed to be representative of the Portuguese adult population. EpiDoC is a prospective closed cohort study, including a nationally representative sample of adults (older than 18 years) who were not institutionalised and lived in private homes in Mainland Portugal and Islands (Ac¸ores and Madeira). The main objective of this project was to characterise the diabetic population in Portuguese adults using the EpiDoC cohort. Data collected at the three follow-up waves were analysed to assess the impact of diabetes on the loss of quality of life and on the consumption of medical resources, namely the occurrence of hospitalisations and the number of medical appointments. The specific objectives were as follows: • To characterise the population regarding self-reported diabetes among Portuguese adults, taking into account the geographical distribution, socio-demographic characteristics and comorbidities associated with the disease. To this end, a broad exploratory analysis was conducted. • To assess the impact of diabetes on quality of life - measured by the EuroQol Five Dimensional Questionnaire score - at each data collection wave, as well as in a longitudinal perspective, in order to assess the evolution of this measure over time. To answer this question, the Tobit regression model was used. • To assess the impact of diabetes on the occurrence of hospital admissions and the number of medical appointments through longitudinal generalized linear models for binary data and counts, respectively. By the analysis of the prevalences, and analysing the responses of individuals in the first wave, it is concluded that there are more diabetic women than men, yet this difference is not significant. Furthermore, there is a higher prevalence of diabetics of Caucasian ethnicity, aged 66 to 75 years and married. Regarding NUTS II, there is a higher proportion of diabetics in the Norte region. Regarding the level of education, there is a higher proportion of diabetics whose schooling varies between 1 and 4 years. However, age may be considered a confounding factor, since there is a higher probability of low levels of education being associated with individuals with a more advanced age. The fact that most diabetics were retired corroborates the idea of age being a confounding factor. With regard to lifestyle habits, we concluded that most diabetics drink alcohol, do not smoke and do exercise. As expected, most diabetics have a Body Mass Index (BMI) corresponding to the obesity category. Finally, high blood pressure proved to be the most prevalent disease in diabetics. Regarding the quality of life models, it decreases with the presence of diabetes. As regards the occurrence of hospital admissions, a first analysis showed that only 14.5% of diabetic individuals had been hospitalized. Through the analysis of the model, concluded that the chance of an individual being hospitalized increases in diabetic patients. With regard to the number of consultations, it was found that diabetes causes the expected number of medical appointments to increase.

Aim: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry. Results: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities. Conclusion: Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.

A bubonic plague epidemic broke out in the Portuguese city of Oporto in June 1899. Six months later, when it had come to an end, 132 deaths along 320 patients had been recorded. Although it was a city with industrial activity and the precursor of several technological innovations, the hygienic and sanitary conditions of the population of Oporto at that time left a lot to be desired. These features certainly made it easier for the plague to spread, which was detected by unusual deaths in those residing in dilapidated and dirty houses by the river Douro. Ricardo Jorge (1858-1939), the municipal doctor at the time, did not hesitate in stating that the outbreak showed clinical, epidemiological and technological signs of bubonic plague. Civil authorities and the press played down the event for more than a month. Finally, by order of the Government, a wide cordon sanitaire was established around the city, to prevent the spread of the epidemic to the rest of the country. As this resolution was not welcomed by the population, traders, and medical associations, the Government was forced to remove the city siege. Ricardo Jorge, who discovered the cause of the disease and was the main individual promoting the sanitary measures carried out, decided to abandon Oporto and settle in Lisbon after being unfairly misunderstood and subject to persecution.

Fundamento: Plasmodium falciparum (P.f.) cresce a uma taxa variável entre indivíduos, resultando em diferentes parasitemias, cargas parasitárias e graus de gravidade da doença. Além da imunidade, outros fatores parecem influenciar a taxa de crescimento do parasita e o prognóstico da doença, como o grupo sanguíneo ou as hemoglobinopatias, embora os mecanismos ainda não estejam esclarecidos. As culturas in vitro são uma ferramenta essencial para estudar o P.f. e investigar melhores intervenções. É fundamental entender como estas variações afetam o crescimento do parasita em cultura e quais os fatores envolvidos. Objetivos: Este trabalho tem como objetivo investigar possíveis diferenças no crescimento de P.f. em indivíduos não imunes à malária num sistema de cultura in vitro e estudar possíveis associações para as variações observadas. Métodos: Realizaram-se culturas in vitro de P.f. com sangue de 69 indivíduos não imunes à malária. Numa segunda fase, 24 voluntários foram novamente chamados para dar outra amostra de sangue para repetir culturas de P.f. e realizar uma avaliação analítica. Em 14 voluntários, a suplementação a cultura com soro bovino foi substituída por soro humano. Resultados: A média da razão do crescimento do P.f. após 96 horas foi de 10.0, com uma grande variabilidade entre indivíduos (intervalo:3.0–19.3, DP:3.8). Três grupos foram criados. O grupo de “baixo crescimento” é definido por uma razão 1DP abaixo da média (n=12, média:4.7, SD:1.2, intervalo:3.0–6.1). O grupo de “elevado crescimento” é definido por uma razão 1DP acima da média (n=13, média:16.0, DP:1.8, intervalo:13.8–19.3). Os dados sugerem que os indivíduos que apresentam menor crescimento do P.f. estão ligados a países onde a malária é endémica (p=0.03). Além disso, um menor crescimento parece estar relacionado à anemia (p=0.01), apontando para algum problema nos eritrócitos, embora este estudo não tenha permitido encontrar o mecanismo subjacente. A suplementação com soro humano não alterou este padrão de crescimento. Além dos níveis de hemoglobina (p=0.03), nenhum outro parâmetro analítico apresentou diferença significativa.Conclusão: Existem indivíduos cujo sangue permite um crescimento do P.f. consistentemente alto ou baixo. A grande variabilidade do crescimento não é influenciada pelo soro, sugerindo que os eritrócitos parecem ser responsáveis por este padrão. Esta ideia é reforçada pelo facto de que indivíduos com uma história clínica de anemia ou níveis de hemoglobina baixos apresentam menores taxas de crescimento. Assim, a variabilidade no crescimento do parasita pode ser explicada por pequenas variações genéticas ao nível da hemoglobina.

O entretenimento esteve sempre presente nas atividades humanas, satisfazendo necessidades e desempenhando um papel na vida dos indivíduos e das comunidades. Em particular, os filmes e os jogos têm um forte impacto emocional sobre nós; os primeiros com o seu rico conteúdo multimédia e a própria história e os segundos tendem a desafiar-nos e a cativar-nos a enfrentar desafios e, espera-se, alcançar experiências e resultados gratificantes. Nesta dissertação apresentamos uma aplicação web desenvolvida no laboratório de investigação LASIGE (DI-FCUL), concebida e desenvolvida para aceder a filmes com base no impacto emocional, com o foco na anotação emocional de filmes, utilizando diferentes representações emocionais e elementos de gamificação no sentido de incentivar mais os utilizadores nestas tarefas, para além das suas motivações intrínsecas. Estas anotações, com abordagens de Machine Learning, podem ajudar a enriquecer a classificação emocional dos filmes e o seu impacto nos utilizadores, ajudando mais tarde a encontrar filmes baseados nesse impacto. Podem também ser guardadas como notas pessoais, num diário (Personal Journal), onde os utilizadores registam os filmes que mais apreciam, e que podem rever e até mesmo comparar ao longo da sua jornada. Apresentam-se também os dois momentos de avaliação com grupos de participantes, permitindo avaliar e aprender sobre a utilidade, usabilidade e a experiência do utilizador com a aplicação, identificando as características e direções mais promissoras para os futuros melhoramentos e desenvolvimentos.

GalNAc-glycopeptides derived from mucin MUC1 are an important class of tumor-associated antigens. α- O-glycosylation forces the peptide to adopt an extended conformation in solution, which is far from the structure observed in complexes with a model anti-MUC1 antibody. Herein, we propose a new strategy for designing potent antigen mimics based on modulating peptide/carbohydrate interactions by means of O → S/Se replacement at the glycosidic linkage. These minimal chemical modifications bring about two key structural changes to the glycopeptide. They increase the carbohydrate-peptide distance and change the orientation and dynamics of the glycosidic linkage. As a result, the peptide acquires a preorganized and optimal structure suited for antibody binding. Accordingly, these new glycopeptides display improved binding toward a representative anti-MUC1 antibody relative to the native antigens. To prove the potential of these glycopeptides as tumor-associated MUC1 antigen mimics, the derivative bearing the S-glycosidic linkage was conjugated to gold nanoparticles and tested as an immunogenic formulation in mice without any adjuvant, which resulted in a significant humoral immune response. Importantly, the mice antisera recognize cancer cells in biopsies of breast cancer patients with high selectivity. This finding demonstrates that the antibodies elicited against the mimetic antigen indeed recognize the naturally occurring antigen in its physiological context. Clinically, the exploitation of tumor-associated antigen mimics may contribute to the development of cancer vaccines and to the improvement of cancer diagnosis based on anti-MUC1 antibodies. The methodology presented here is of general interest for applications because it may be extended to modulate the affinity of biologically relevant glycopeptides toward their receptors.

Introdução: A reprogramação metabólica consiste na adaptação do fenótipo metabólico das células tumorais às condições do microambiente. Para que possam sobreviver e proliferar, estas células utilizam uma grande variedade de substratos para produzir biomassa e ATP. A reprogramação metabólica é, portanto, um hallmark do cancro. As células tumorais utilizam preferencialmente a glicólise, mesmo em aerobiose, embora esta via lhes permita produzir substancialmente menos ATP (efeito de Warburg). Adicionalmente, nas células tumorais há aumento da taxa de glutaminólise, bem como reprogramação do metabolismo lipídico. Por permitir às células tumorais sobreviver a microambientes adversos, a reprogramação metabólica contribui para a mestastização. Objetivos: Procurámos rever a importância clínica da metabolómica tumoral, bem como avaliar a reprogramação metabólica que ocorre in vitro na linha celular de cancro da mama triplo negativo MDA-MB-231, quando expostas a diferentes concentrações de glicose, glutamina e LDL-colesterol; comparar a reprogramação metabólica que ocorre em células MDA-MB-231 in vivo, em tumores da mama primários e metástases pulmonares, em ratinhos NSG sujeitos a dietas normais, dietas enriquecidas em colesterol e em dietas enriquecidas com colesterol com bloqueio do recetor LDL. Métodos/Resultados: Por PCR quantitativo avaliou-se a expressão dos genes de enzimas chave da fosforilação oxidativa (ND1), glicólise (G6PD, PKM2, LDHA), síntese de novo de ácidos gordos (FASN), transportadores lipídicos (LDLr e CD36) e glutaminólise (GLS2 e IDH2). As células MDA-MB-231 in vitro são dependentes de glicose e glutamina, mesmo quando estão disponíveis outros substratos. In vivo, dietas enriquecidas em colesterol induzem proliferação dos tumores primários da mama após bloqueio do LDLr. As metástases pulmonares sobre expressam transportadores lipídicos comparadas com tumores primários em ambas as dietas. Conclusão: As células MDAMB- 231 apresentam plasticidade metabólica in vivo e in vitro. Dietas ricas em colesterol conferem vantagem às células de cancro da mama, contribuindo para o potencial metastático pulmonar e consistindo num eventual alvo terapêutico.

Coastal marine habitats provide important environmental and socio-economic services, and adjacent coastal areas are very attractive to human populations. Like other coastal marine habitats, rocky reefs are heavily impacted by anthropogenic activity. As these are considered important breeding, nursery and feeding areas for several marine species, their protection is imperative. To improve conservation methods, it is necessary to understand the structure and processes of rocky reef communities. Trophic relationships are one of the ways in which species are connected, with food webs representing the flow of matter and energy from producers to consumers and from prey to predators. Stable isotope analysis (δ13C and δ15N) was used to characterize the food web of the rocky reef of Arrábida Marine Protected Area. The results showed a relatively short food web, most likely due to high abundances of juveniles with consumers with diverse diets and feeding strategies, exploiting different sources of organic matter, of both benthic (macroalgae and benthic POM) and pelagic origin (phytoplankton and pelagic POM). However, the benthic pathway was more important with more than half of the diet of most secondary and tertiary consumers following this route and thus, suggesting a bottom-up control, and hinting at the importance held by macroalgae and benthic production in this ecosystem. There was also a high incidence of omnivores in all trophic groups, which could contribute to the similar trophic redundancy and trophic evenness found between groups. Even so, primary consumers showed greater trophic richness related to basal resources.

Approximately 400 000 children are diagnosed with cancer every year, with the most common types of childhood cancers being leukemia, lymphoma, brain and solid tumors. Moreover, 10-40% of children with solid tumors present lung metastases at the time of diagnosis. Whole lung irradiation (WLI) is a treatment option for pediatric patients with lung metastases that develop from solid tumors like Ewing’s sarcoma (ES), rhabdomyosarcoma, and Wilms’ tumor (WT). However, during treatment delivery, intra and inter-fraction anatomical changes might occur and can greatly affect treatment outcome. These changes can either cause underdosages of the target volume, or overdosage of surrounding organs at risk (OARs). Since growing lung tissue is more sensitive to radiation, avoiding the irradiation of OARs while maintaining target coverage is of utmost importance. Thus, there is the need to ensure that a treatment plan is robust, which is accomplished if the planned and delivery dose distributions agree even in the presence of uncertainties. To evaluate how anatomical changes affect the treatment outcome when delivering WLI to pediatric patients, this thesis comprises a study of robustness of photon dose distributions against intra and inter-fraction anatomical changes. The present study includes treatment plans of 21 pediatric patients that received WLI at University Medical Center Utrecht. The robustness evaluation was performed against intra and inter-fraction anatomical changes. Intra-fraction changes were evaluated by recalculating the original plan on the two extreme breathing phases – maximum inhalation and maximum exhalation. Conversely, inter-fraction changes were evaluated by calculating the fractional dose on the daily cone-beam computed tomography (CBCT) images acquired before treatment and accumulating the resulting dose distributions. The recalculated plans were then compared to the original dose distribution. Overall results of the study demonstrated no clinically relevant differences in terms of mean internal target volume (ITV) coverage of the lungs. However, hot spot values differed significantly for three patients. The differences observed for the V107% were due to diaphragm position shifts (two patients) and electron density (ED) changes within the lung ITV (one patient). Coverage and hot spots of metastases presented clinically relevant differences when considering the extreme breathing phases, as well as the registered-CTs. This was due to differences in ED within the metastases and position variations in relation to surrounding structures (like the heart or ribs). However, these changes were observed for the PTV only, while ITV coverage remained around 100% on all plans. OAR dose values were robust against intra and inter-fraction anatomical changes, with no clinically relevant differences to report. In conclusion, the recalculated WLI plans are considered robust against intra and inter-fraction anatomical changes when taking into consideration average results. However, some clinically relevant differences were identified per patient, which require further attention and improvement in future treatment plans.

Disaster communication guidelines emphasize that journalists should be aware of past major disasters and draw lessons from the coverage of those events. The press is an important source for the evolution of historical disaster and risk research paradigms over time. This study explored the top 10 damaging hydrogeomorphological events in Portugal selected from the disaster database, which includes events that caused human damages (fatalities, injured, missing, evacuated, and displaced) reported over a period of 151 years (1865–2015) by the Portuguese newspaper Diário de Notícias (DN). News analysis was guided by the news protocol. The analysis of the news published in DN enabled us to identify textual marks that present interconnections in the journalistic coverage and produce discursive standards for these disasters. The textual marks were associated with the hazard and risk paradigms. The discursive standards of DN did not clearly reflect the ruptures in the hazard paradigms. As a rule, the journalistic reports contributed to the naturalization of disasters and the gap in public understanding of risks, by presenting an approach focused on relief actions—ignoring social issues, vulnerability, and population resilience—reducing the discourse of preparedness for future disasters.

Retail gentrification is a rising field of research within the wider field of gentrification studies. In this paper we use the old neighbourhood of Marvila in Lisbon as a case study. The information collected from the fieldwork demonstrates the depth of transformations occurring in the commercial fabric of Marvila, which is having a detrimental effect on old stores and the local population. Moreover, it reveals that the current process was triggered by a group of independent investors, whose success is placing them at risk of being displaced. These findings reinforce the existent body of literature on the subject of retail gentrification.

Este trabalho tem como principais objetivos fazer uma análise do desempenho energético de um edifício de serviços, e depois, analisar como torná-lo autossuficiente, ou (se a anterior não for possível) como torná-lo quase autossuficiente, através da integração de sistemas de produção de energia de fonte renovável. As análises devem ser feitas com o recurso a um programa de simulação energética de edifícios. O edifício deste caso de estudo é para ser usado como alojamento que albergue até 30 pessoas construído com materiais com poucos impactos ambientais. Localiza-se em Atalaia de Cima, Sintra em pleno meio rural. É constituído por 4 pisos. Possui um refeitório, uma cozinha, dormitórios (alguns parcialmente enterrados), e uma sala para ser usada para aulas/reuniões. Primeiro foi desenhado o modelo geométrico em Sketchup com a extensão Euclide, versão 0.9.3. De seguida foi simulado com o programa EnergyPlus®, versão 8.7.0 para o período de um ano, e feita uma análise. Mais tarde foi analisado com HOMER Pro® a integração de sistemas de produção renovável: sistemas com painéis fotovoltaicos (PV), e sistemas com turbinas eólicas. Para estimar o custo atual líquido que seria necessário considerou-se que o tempo de vida do projeto é 25 anos. Os resultados mostraram que é melhor a combinação de sistemas eólicos e de PV mas que é impossível só assim tornar Deep retreat autossuficiente. A fração renovável local obtida no melhor cenário, com um tempo de retorno do investimento de cerca de 7 anos, foi 83.7%. Em todos os cenários com turbinas e PV obtidos, a potência instalada de turbinas foi pelo menos 5 vezes superior ao de PV. Salienta-se que Portugal é em geral um país solarengo, e é especialmente ventoso na região deste caso de estudo. Com baterias o software não encontrou soluções devido aos custos destas.