eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development

It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.

Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

Simulação da aplicação da metodologia Balanced Scorecard numa PME: O estudo do caso PME-T.H.

Mestrado em Contabilidade

Monitorization of alveolar deposited surface area of nanoparticles and ultrafine particles in different environments

Nanotechnology is an important emerging industry with a projected annual market of around one trillion dollars by 2015. It involves the control of atoms and molecules to create new materials with a variety of useful functions. Although there are advantages on the utilization of these nano-scale materials, questions related with its impact over the environment and human health must be addressed too, so that potential risks can be limited at early stages of development. At this time, occupational health risks associated with manufacturing and use of nanoparticles are not yet clearly understood. However, workers may be exposed to nanoparticles through inhalation at levels that can greatly exceed ambient concentrations. Current workplace exposure limits are based on particle mass, but this criteria could not be adequate in this case as nanoparticles are characterized by very large surface area, which has been pointed out as the distinctive characteristic that could even turn out an inert substance into another substance exhibiting very different interactions with biological fluids and cells. Therefore, it seems that, when assessing human exposure based on the mass concentration of particles, which is widely adopted for particles over 1 μm, would not work in this particular case. In fact, nanoparticles have far more surface area for the equivalent mass of larger particles, which increases the chance they may react with body tissues. Thus, it has been claimed that surface area should be used for nanoparticle exposure and dosing. As a result, assessing exposure based on the measurement of particle surface area is of increasing interest. It is well known that lung deposition is the most efficient way for airborne particles to enter the body and cause adverse health effects. If nanoparticles can deposit in the lung and remain there, have an active surface chemistry and interact with the body, then, there is potential for exposure. It was showed that surface area plays an important role in the toxicity of nanoparticles and this is the metric that best correlates with particle-induced adverse health effects. The potential for adverse health effects seems to be directly proportional to particle surface area. The objective of the study is to identify and validate methods and tools for measuring nanoparticles during production, manipulation and use of nanomaterials.

Valorização de lamas de tratamento de águas residuais urbanas para utilização agrícola

Trabalho de Dissertação de Natureza Científica para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização em Hidráulica

Development of TNBS-induced colitis: animal model to test new pharmacological approaches

IBD is a gastro-intestinal disorder marked with chronic inflammation of intestinal epithelium, damaging mucosal tissue and manifests into several intestinal and extra-intestinal symptoms. Currently used medical therapy is able to induce and maintain the patient in remission, however no modifies or reverses the underlying pathogenic mechanism. The research of other medical approaches is crucial to the treatment of IBD and, for this, it´s important to use animal models to mimic the characteristics of disease in real life. The aim of the study is to develop an animal model of TNBS-induced colitis to test new pharmacological approaches. TNBS was instilled intracolonic single dose as described by Morris et al. It was administered 2,5% TNBS in 50% ethanol through a catheter carefully inserted into the colon. Mice were kept in a Tredelenburg position to avoid reflux. On day 4 and 7, the animals were sacrificed by cervical dislocation. The induction was confirmed based on clinical symptoms/signs, ALP determination and histopathological analysis. At day 4, TNBS group presented a decreased body weight and an alteration of intestinal motility characterized by diarrhea, severe edema of the anus and moderate morbidity, while in the two control groups weren’t identified any alteration on the clinical symptoms/signs with an increase of the body weight. TNBS group presented the highest concentrations of ALP comparing with control groups. The histopathology analysis revealed severe necrosis of the mucosa with widespread necrosis of the intestinal glands. Severe hemorrhagic and purulent exsudates were observed in the submucosa, muscular and serosa. TNBS group presented clinical symptoms/signs and histopathological features compatible with a correct induction of UC. The peak of manifestations became maximal at day 4 after induction. This study allows concluding that it’s possible to develop a TNBS induced colitis 4 days after instillation.

A fusão de dois mundos: convergência do mundo real e digital nas acções de marketing na rede

No passado, as acções publicitárias eram rotuladas como above the line e below the line, referindo-se à dicotomia de pontos de contacto com os públicos-alvo via Meios de Comunicação Social ou via Ponto de Venda. A esta dicotomia de meios e instrumentos, os anos 90 vieram trazer um terceiro ponto de contacto, crescentemente omnipresente e hegemónico, a world wide web ou rede, a que se acedia via computador. As acções de marketing e comunicação passaram então a rotular-se como online e offline, passando, não já a referir-se aos pontos de contacto, mas aos canais pelos quais circulavam as mensagens e acções das marcas. Desde o início deste século, o poder do digital veio crescendo, em software e hardware, em terminais e tecnologias, assistindo-se a uma transferência de esforços de comunicação, da esfera real para a esfera do digital. O deslumbramento pelo digital conquistou mesmo algumas marcas de dimensão mundial que hoje apostam integralmente o seu orçamento nesta forma de marketing, nas suas múltiplas facetas. Contudo, e porque se tem tornado óbvio que os públicos distribuem os seus favores por múltiplos touch points, para maximizar o impacto, assiste-se agora a um fenómeno único, potenciado por novas tecnologias que surgem todos os dias: em estratégias que se podem denominar de all-line, verifica-se a fusão entre dois mundos, mundo real e mundo digital, em múltiplas actividades de marketing que fazem convergir estas duas realidades em plataformas que vão do computador ao tablet, do smartphone à vending machine interactiva, do facebook ao Google maps, da imprensa tradicional ao pinterest. É esta convergência mundo real - mundo digital que abre agora novas oportunidades à comunicação publicitária, potenciando os ingredientes das marcas de sucesso no futuro: sensações (estímulo dos sentidos), intimidade e mistério, num cocktail suportado por uma nova criatividade.

Implementação em hardware reconfigurável de método de separação de dados hiperespetrais

Relatório do Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia de Electrónica e Telecomunicações

Micro-generation Evaluation of the Zero Emissions Technologies in the Portuguese Market

Micro-generation is the small scale production of heat and/or electricity from a low carbon source and can be a powerful driver for carbon reduction, behavior change, security of supply and economic value. The energy conversion technologies can include photovoltaic panels, micro combined heat and power, micro wind, heat pumps, solar thermal systems, fuel cells and micro hydro schemes. In this paper, a small research of the availability of the conversion apparatus and the prices for the micro wind turbines and photovoltaic systems is made and a comparison between these two technologies is performed in terms of the availability of the resource and costs. An analysis of the new legal framework published in Portugal is done to realize if the incentives to individualspsila investment in sustainable and local energy production is worth for their point of view. An economic evaluation for these alternatives, accounting with the governmentpsilas incentives should lead, in most cases, into attractive return rates for the investment. Apart from the attractiveness of the investment there are though other aspects that should be taken into account and those are the benefits that these choices have to us all. The idea is that micro-generation will not only make a significant direct contribution to carbon reduction targets, it will also trigger a multiplier effect in behavior change by engaging hearts and minds, and providing more efficient use of energy by householders. The diversified profile of power generation by micro-generators, both in terms of location and timing, should reduce the impact of intermittency or plant failures with significant gains for security of supply.

Moradia no centro histórico do Montijo: reabilitação vs construção nova

Dissertação para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização de Edificações

A metáfora e a imagem : estratégias para a transmissão de conteúdos técnicos na aula de Dança Clássica com alunos do 1º ano da Escola de Dança de Ana Luísa Mendonça

Relatório Final de Estágio apresentado à Escola Superior de Dança, com vista à obtenção do grau de Mestre em Ensino de Dança.

Check your biosignals here: a new dataset for off-person ECG biometrics

The Check Your Biosignals Here initiative (CYBHi) was developed as a way of creating a dataset and consistently repeatable acquisition framework, to further extend research in electrocardiographic (ECG) biometrics. In particular, our work targets the novel trend towards off-the-person data acquisition, which opens a broad new set of challenges and opportunities both for research and industry. While datasets with ECG signals collected using medical grade equipment at the chest can be easily found, for off-the-person ECG data the solution is generally for each team to collect their own corpus at considerable expense of resources. In this paper we describe the context, experimental considerations, methods, and preliminary findings of two public datasets created by our team, one for short-term and another for long-term assessment, with ECG data collected at the hand palms and fingers. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution

A novel water soluble organometallic compound, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO3] (TM85, where Cp=eta(5)-cyclopentadienyl, mTPPMS = diphenylphosphane-benzene-3-sulfonate and 2,2'-bipy = 2,2'-bipyridine) is presented herein. Studies of interactions with relevant proteins were performed to understand the behavior and mode of action of this complex in the biological environment. Electrochemical and fluorescence studies showed that TM85 strongly binds to albumin. Studies carried out to study the formation of TM85 which adducts with ubiquitin and cytochrome c were performed by electrospray ionization mass spectrometry (ESI-MS). Antitumor activity was evaluated against a variety of human cancer cell lines, namely A2780, A2780cisR, MCF7, MDAMB231, HT29, PC3 and V79 non-tumorigenic cells and compared with the reference drug cisplatin. TM85 cytotoxic effect was reduced in the presence of endocytosis modulators at low temperatures, suggesting an energy-dependent mechanism consistent with endocytosis. Ultrastructural analysis by transmission electron microscopy (TEM) revealed that TM85 targets the endomembranar system disrupting the Golgi and also affects the mitochondria. Disruption of plasma membrane observed by flow cytometry could lead to cellular damage and cell death. On the whole, the biological activity evaluated herein combined with the water solubility property suggests that complex TM85 could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved.

analytical model and measurements of the target erosion depth profile of balanced and unbalanced planar magnetron cathodes

The erosion depth profile of planar targets in balanced and unbalanced magnetron cathodes with cylindrical symmetry is measured along the target radius. The magnetic fields have rotational symmetry. The horizontal and vertical components of the magnetic field B are measured at points above the cathode target with z = 2 x 10(-3) m. The experimental data reveal that the target erosion depth profile is a function of the angle. made by B with a horizontal line defined by z = 2 x 10(-3) m. To explain this dependence a simplified model of the discharge is developed. In the scope of the model, the pathway lengths of the secondary electrons in the pre-sheath region are calculated by analytical integration of the Lorentz differential equations. Weighting these lengths by using the distribution law of the mean free path of the secondary electrons, we estimate the densities of the ionizing events over the cathode and the relative flux of the sputtered atoms. The expression so deduced correlates for the first time the erosion depth profile of the target with the angle theta. The model shows reasonably good fittings to the experimental target erosion depth profiles confirming that ionization occurs mainly in the pre-sheath zone.

Modulador ressonante em ponte assimétrica para alvo do ISOLDE - CERN

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo de Automação e Electrónica Industrial