680 research outputs found

    How can youlead grow in the Portuguese agency market?

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    This project was developed in collaboration with a portuguese inbound marketing agency, YouLead, and aims to answer the question “How can YouLead grow in terms of service offering” by defining a strategy that enables the company to grow without losing its positioning as an inbound marketing agency. After analysing the agency industry, YouLead’s resources, capabilities, strengths and weaknesses, as well as the external threats and opportunities, growth hypotheses were discussed. As the market is growing and the agency benefits from a good positioning, the proposed strategy is for YouLead to leverage its strengths and take advantage of market opportunities

    The main leachate emissions of uncontrolled landfills

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    Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente, Perfil de Engenharia SanitáriaOne of the biggest current problems is the proper management of solid waste and other waste streams. All types of waste have a potential pollutant affecting soil resources and water resources, mainly in landfills that may not have adequate protection measures and do not know the waste placed in them. Through the study on laboratory scale it is possible to check which potential emissions to the level of leachates of uncontrolled landfills. The leachates can be compared. It is possible to say which ones have more heavy metals and organic fraction emissions. This study analyzed samples of leachate from two landfill waste in North-East Italy, near Verona, two old uncontrolled landfills. The leachate samples come from the simulation of biological reactors, operated in aerobic and anaerobic condition. The leachates were characterized in terms of pH, heavy metals such as Cd, Cr, Cu, Fe, Mn, Ni Pb, Zn, As and Hg and organic fraction (TOC, TKN and NO3). The heavy metal and organic fraction concentrations were found low in order of micrograms, and in the organic fraction in order of milligrams, per litre of leachates. In general, the concentrations in the anaerobic bioreactors were higher than in the aerobic bioreactors. The study showed that pH is a very important factor regarding the mobility of the metals in the leachate. The quality of the leachates in study have little potential for water pollution since they exhibit basic pH values (around 8), even if the residues are saturated, that is, the ability of field reached

    Portuguese transmission grid incidents risk assessment

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    Documento confidencial. Não pode ser disponibilizado para consultaTese de doutoramento. Engenharia Electrotécnica e de Computadores. Faculdade de Engenharia. Universidade do Porto. 201

    The Nested Structure of Emergent Supply Networks

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    Inspired by studies in ecological networks, we look for a nested pattern in a large-scale data set describing the global automotive industry, including more than 18 000 firms, their clients, and products. Two bipartite networks are formed, namely, supplier-product distribution and supplier-manufacturer relations. Both networks are found to be significantly nested. The pattern means that suppliers produce proper subsets of what other suppliers produce and rare products are produced only by those suppliers that already produce high numbers of product types. In addition, the manufacturers that procure from few suppliers procure from those that supply to most other manufacturers in the network. Similarly, suppliers that supply to few supply to those manufacturers that procure from most others. A nested structure is more robust than a nonnested structure as disrupted suppliers can be substituted, but nestedness also means that small suppliers face more competition as their production can be redundant. Our finding is contrary to conventional wisdom that associates large diversified firms with efficiency and small specialist firms with rare products, showing that large-scale complex system analysis can lead to the discovery of important systemic characteristics, which are obscured when viewed from local points of view. We then propose a multiagent model that creates more realistic nested structures to study systemic outcomes influenced by topology

    Unraveling the molecular mechanisms underlying alpha-synuclein oligomerization and cytotoxicity

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    Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2017Neurodegenerative disorders (NDs) are proteinopathies characterized by the accumulation of misfolded and aggregated proteins. Either through loss of normal protein function and the generation of abnormal protein interactions, the protein network deteriorates inside neurons and subsequently along the neuronal networks. Parkinson’s disease (PD) is the second most frequent ND and is associated with the misfolding and aggregation of alpha-Synuclein (aSyn), a pre-synaptic protein whose function is still unclear. Importantly, aSyn dysregulation is also involved in other NDs, as Dementia with Lewy Bodies and Multiple System Atrophy, jointly referred to as Synucleinopathies. Thus, the study of aSyn became crucial for understanding the etiology of those pathologies. There is ample debate as to what the toxic species of aSyn are, although it has been postulated that misfolded oligomeric species of aSyn represent the toxic genus. This thesis aimed to generate new insights into the role of aSyn in health and disease, at a molecular level. To visualize aSyn in the biological orchestra of the cell, we first studied its intracellular dynamics in a cellular model through photoactivation microscopy. Using photoactivatable green fluorescent protein as a reporter, we found that the availability of the aSyn amino-terminus modulates its shuttling into the nucleus. This finding has important implications regarding both the species of aSyn that enter the nucleus and also the function of the protein within that compartment. aSyn was recently suggested to exist naturally as a tetramer. Due to the nuclear pore size, only monomeric or dimeric forms of aSyn can enter the nucleus, and this has been related to a deleterious effect and neurotoxicity, due to transcription deregulation. Interestingly, intracellular dynamics of aSyn was finely modulated by the HSP70 chaperone, PD-associated mutations and by the phosphorylation state of the protein on S129 site. We found that the molecular chaperone HSP70 accelerates the entry of aSyn into the nuclear compartment. Also, A30P and A53T aSyn mutations increased the speed at which the protein moves between the nucleus and cytoplasm, respectively. Finally, specific kinases potentiate the shuttling of aSyn between nucleus and cytoplasm. Importantly, a mutant aSyn form that blocks S129 phosphorylation, S129A, results in the formation of cytoplasmic inclusions, suggesting that phosphorylation modulates aggregation, and thus, alter the normal aSyn intracellular dynamics. To better understand the aggregation process in disease, we focused on the initial steps of aSyn aggregation, thought to be the causative agents of pathology. We used cell-based models of Synucleinopathy to investigate the molecular mechanisms underlying aSyn oligomerization. In particular, we screened, in an unbiased manner, a subset of the human genome-wide collection of lentiviral RNA-interference constructs, targeting genes involved in signal transduction players, to identify modifiers of aSyn oligomerization, using the bimolecular fluorescence complementation assay (BiFC) as readout. Through this approach we identified 9 genetic modifiers of aSyn oligomerization. Interestingly, the hits we identified were functionally related, and associated with neuronal trafficking processes. We then characterized these hits with respect to their effects on aSyn aggregation, toxicity and protein levels. After this first level of general characterization, we further investigated the mechanism of action of the hits by assessing their effects on aSyn secretion, a central aspect in the spreading of aSyn pathology. aSyn is secreted under physiological conditions, via non-classical exocytosis, in association with exosomes, and possibly via other less conventional mechanisms. However, it was demonstrated that pathological and aggregated aSyn species can also be secreted, suggesting that aggregated and misfolded aSyn may be the key agent for propagation of aSyn pathology, possibly in a prion-like manner. Thus, in our study we selected four trafficking hits, based on the literature and on their relevance to secretory pathways. Ras-related Protein in Brain 8b (Rab8b), Rab11a, Rab13 and Synaptotagmin-Like Protein 5 were found to promote the clearance of aSyn inclusions and reduce aSyn toxicity. Moreover, we found that endocytic recycling and secretion of aSyn was enhanced upon expression of Rab11a or Rab13 in cells accumulating aSyn inclusions. Importantly, in cells with inclusions, the trafficking proteins co-localized with aSyn in inclusions. Altogether, our findings suggest specific trafficking steps may prove beneficial as targets for therapeutic intervention in Synucleinopathies, and should be further investigated in other models. Here, we also studied the effects of monoclonal aSyn antibodies on the early stages of aggregation using the BiFC assay. Our results support passive immunization against Synucleinopathies by demonstrating that extracellular administration of monoclonal antibodies can inhibit early steps in the aggregation process of aSyn. As aSyn seems to behave as a prion-like protein, immunization can be a mid-term strategy to delay the progression of Synucleinopathies. The present study uncovered novel aspects about the intracellular dynamics of aSyn and allowed the identification of new genetic players involved in the aggregation, toxicity, secretion and immunization of aSyn, opening novel avenues towards the understanding of the molecular bases of Synucleinopathies.Axa Research Fun

    Cutaneous manifestations associated with SARS CoV-2: an emerging topic in a pandemic era

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    A 70-year-old man was admitted to our COVID-19 ward with thoracalgia, productive mucus cough, fatigue and erythematous–violaceous macules on the inner side of feet and interdigital regions. The patient was started on oxygen and dexamethasone. On the day of discharge, he maintained the skin changes despite the resolution of COVID-19 symptoms. A 57-year-old woman initially presented with diffuse urticarial rash on the cervical and chest region. Oral cetirizine was started, and pruritus improved. Thirty days after the discharge, the patient maintained the rash, but without pruritus. A 49-year old man was admitted with thoracalgia, shortness of breath, dry cough and urticarial rash on the cervical and chest region. The patient was treated with cetirizine. The pruritus improved, and 5 days after discharge, the urticarial areas completely disappearedinfo:eu-repo/semantics/acceptedVersio

    O Profissional de Educação em Contexto Hospitalar

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    O profissional de educação ao exercer as suas funções em contexto hospitalar constrói uma identidade própria, isto porque, o meio influencia a prática pedagógica. No seu percurso de internamento, a criança é influenciada e, é importante conhecer esta realidade. Assim, conhecer o processo de ensino e de aprendizagem, em contexto hospitalar. Para a realizar este estudo optou-se por uma metodologia baseada na abordagem qualitativa. Desta forma, foram utilizadas como técnicas de recolha de dados a entrevista semiestruturada e o inquérito por questionário. Os dados foram tratados e analisados com o objetivo de responder às questões de investigação. O presente estudo revelou que o educador de infância em contexto hospitalar é um elemento relevante para a criança hospitalizada, na medida em que ajuda as crianças no seu desenvolvimento pedagógico e cognitivo e constitui um apoio importante no próprio processo de internamento.The education professional, when performing his / her functions in a hospital context, builds his / her own identity, this because the medium influences the pedagogical practice. In the course of internment, the child is influenced and it is important to know this reality. Thus, to know the process of teaching and learning, in a hospital context. To carry out this study we opted for a methodology based on the qualitative approach. In this way, semi-structured interviews and questionnaire surveys were used as data collection techniques. The data were treated and analyzed in order to answer the research questions. The present study revealed that the childhood educator in a hospital context is a relevant element for the hospitalized child, since it helps the children in their pedagogical and cognitive development and constitutes an important support in the hospitalization process itself
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