28 resultados para COMPARATIVE TOXICITY


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Dissertação para obtenção do Grau Mestre em Engenharia Civil – Perfil de Construção

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous priority pollutants that tend to be trapped in aquatic sediments due to their high hydrophobicity. Nonetheless, the differential toxicological effects and mechanisms between the various classes of PAHs and their mixtures, as they invariably occur in the environment, are scarcely known, especially under ecologically-relevant scenarios. This thesis aimed at establishing a bridge between the study of mechanistic pathways and environmental monitoring of carcinogenic and non-carcinogenic PAHs, by introducing ecological-relevance in the research with model PAHs. A first bioassay conducted in situ with the mussel Mytilus edulis demonstrated that, dredging operations in harbours increase PAH bioavailability, eliciting genotoxicity, and showed that established environmental guidelines underestimate risk. Subsequent ex situ bioassays were performed with the carcinogenic benzo[b]fluoranthene (B[b]F) and non-carcinogenic phenantrene (Phe), selected following preceding results, and revealed that low-moderate concentrations of these PAHs in spiked sediments induce genotoxic effects to the clam Ruditapes decussatus, therefore contradicting the general notion that bivalves are less sensitive to PAHs than vertebrates due to inefficient bioactivation. Also, it was demonstrated that passive samplers permit inferring on PAH bioavailability but not on bioaccumulation or toxic effects. On the other hand, sea basses (Dicentrarchus labrax), yielded a complex pattern of effects and responses, relatively to genotoxicity, oxidative stress and production of specific metabolites, especially when exposed to mixtures of the PAHs which led to additive, if not synergistic, effects. It was shown that Phe may elicit significant genotoxicity especially in presence of B[b]F, even though the low, albeit realistic, exposure concentrations diluted dose- and time-independent relationships. The present work demonstrated that environmental quality guidelines underestimate the effects of PAHs in realistic scenarios and showed that the significant genotoxic and histopathological effects caused by mixed PAHs may not be reflected by oxidative stress- or CYP-related biomarkers. Besides important findings on the metabolism of PAH mixtures, the work calls for the need to re-evaluate the criteria for assessing risk and for the disclosure of more efficient indicators of toxicological hazard.

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Double Degree. A Work Project presented as part of the requirements for the Award of a Master Degree in Management from the NOVA – School of Business and Economics and a Master Degree in Business Engineering from Louvain School of Management

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We examine the drivers behind the establishment mode choice of German multinational enterprises (MNEs) in the sectors of Automotive, Chemicals and Mechanical Engineering in Brazil for the years 1993-2013 using a novel sample of primary data obtained directly from German MNEs. Based on prevalent theories found in the literature, we test the most common hypotheses on our sample. Firms with high R&D activities and firms with prior market knowledge in Brazil in from of previous sales offices are more likely to enter Brazil by a Greenfield investment. We also show that it is the specific private ownership of the German so-called hidden champions that drive those specific SMEs to enter Brazil by Greenfield, a sneaking suspicion that has been made before. Finally, we show that the establishment mode choice between Brazil and the USA only deviates to a low extent, with German MNEs preferring to enter Brazil by Greenfield and the USA by M&A. Thereby, we provide valuable insights for future research in this field.

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The development of human cell models that recapitulate hepatic functionality allows the study of metabolic pathways involved in toxicity and disease. The increased biological relevance, cost-effectiveness and high-throughput of cell models can contribute to increase the efficiency of drug development in the pharmaceutical industry. Recapitulation of liver functionality in vitro requires the development of advanced culture strategies to mimic in vivo complexity, such as 3D culture, co-cultures or biomaterials. However, complex 3D models are typically associated with poor robustness, limited scalability and compatibility with screening methods. In this work, several strategies were used to develop highly functional and reproducible spheroid-based in vitro models of human hepatocytes and HepaRG cells using stirred culture systems. In chapter 2, the isolation of human hepatocytes from resected liver tissue was implemented and a liver tissue perfusion method was optimized towards the improvement of hepatocyte isolation and aggregation efficiency, resulting in an isolation protocol compatible with 3D culture. In chapter 3, human hepatocytes were co-cultivated with mesenchymal stem cells (MSC) and the phenotype of both cell types was characterized, showing that MSC acquire a supportive stromal function and hepatocytes retain differentiated hepatic functions, stability of drug metabolism enzymes and higher viability in co-cultures. In chapter 4, a 3D alginate microencapsulation strategy for the differentiation of HepaRG cells was evaluated and compared with the standard 2D DMSO-dependent differentiation, yielding higher differentiation efficiency, comparable levels of drug metabolism activity and significantly improved biosynthetic activity. The work developed in this thesis provides novel strategies for 3D culture of human hepatic cell models, which are reproducible, scalable and compatible with screening platforms. The phenotypic and functional characterization of the in vitro systems performed contributes to the state of the art of human hepatic cell models and can be applied to the improvement of pre-clinical drug development efficiency of the process, model disease and ultimately, development of cell-based therapeutic strategies for liver failure.

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Strategic alliances represent a key driver for internationalization and growth, being the purpose of this work project to better understand the intertwined relationship between trust and the existence of an alliance management position. Previous research supports the positive impact of such position in stock market returns. However, little attention has been given to the impact of such position on the level of trust in the collaborative arrangement, which is deemed to be a key driver for alliance success. A qualitative comparative case-study of three Portuguese SMEs is used to draw conclusions from the literature to real life business cases and it demonstrates the positive impact of an alliance management position on trust.

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The purpose of the paper is to investigate the effectiveness of supply chain management (SCM) practices to increase a company’s performance based on a cross-border and cross-sector analysis. The paper follows a comparative case study approach which was achieved by interviewing supply chain management experts of three companies operating in different industries and positions in a supply chain. Practices that were mutually applied by the firms and their contribution to achieve quality, economic, cost, and time advantages were analyzed. The paper revealed practices, which contribute the most to increase specific performance areas.

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The capacity to use geologic materials (soil and rock) that are available in the surrounding environment is inherent to the human civilization and has contributed to the evolution of societies throughout the course of history. The use of these materials in the construction of structures such as houses, roads, railways or dams, stirred the improvement of socioeconomic and environmental conditions. Several reports of structural problems on embankments can be found throughout history. A considerable number of those registers can be linked to inadequate compaction, demonstrating the importance of guaranteeing a suitable quality of soil compaction. Various methodologies and specifications of compaction quality control on site of earthworks, based on the fill moisture content and dry unit weight, were developed during the 20th century. Two widely known methodologies are the conventional and nuclear techniques. The conventional methods are based on the use of the field sand cone test (or similar) and sampling of material for laboratory-based testing to evaluate the fill dry unit weight and water content. The nuclear techniques measure both parameters in the field using a nuclear density gauge. A topic under discussion in the geotechnical community, namely in Portugal, is the comparison between the accuracy of the nuclear gauge and sand cone test results for assessing the compaction and density ratio of earth fills, particularly for dams. The main purpose of this dissertation is to compare both of them. The data used were acquired during the compaction quality control operations at the Coutada/Tamujais dam trial embankment and core construction. This is a 25 m high earth dam located in Vila Velha de Rodão, Portugal. To analyse the spatial distribution of the compaction parameters (water content and compaction ratio), a 3D model was also developed. The main results achieved are discussed and finally some considerations are put forward on the suitability of both techniques to ensure fill compaction quality and on additional research to complement the conclusions obtained.

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The paper studies the relationship between four differently rated bank’s financial profile and their standalone credit rating issued by Moody’s. The comparative analysis shows an example that despite their pricing power and geographical coverage, larger banks do not necessarily have better credit ratings. Instead, business model and risk appetite seem to be the defining factors of banks’ vulnerability to shocks, such as the Spanish real estate crisis. The risk-return relationship is also identified in the banks’ fundamentals meaning that while expansionary strategy in riskier asset classes enhances margins, it also potentially distorts the credit risk profile.

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Contemporary painting places, and will continue to place, several questions about its meaning, its chemical nature, its durability and the best way to preserve it. This research aims at putting together comprehensive data on vinyl based paints, including their components, their properties, their aging behavior and their response to selected cleaning products. In this project degradation mechanisms of vinyl binders and formulations used in the 20th and 21st century were studied. Stability over time of selected vinyl polymers was assessed through natural indoor and artificially aging. The objective was to enhance knowledge and understanding of vinyl emulsion formulations and their performance over time. Overall conservation state of pictorial layers namely, adhesion, cohesion and discoloration of selected case studies from the Portuguese artist Julião Sarmento (b.1948) was correlated with the observed molecular level changes studied in laboratory experiments. Sarmento’s paintings were chosen due to conservation concerns (discoloration) on some of his works from the 90’s. Besides, research was carried out to start increasing the knowledge of what can be expected of PVAc based paints in terms of response to conservation treatments namely, surface cleaning. Artificial aging showed that the most recent formulations which are based on a poly(vinyl acetate), poly(vinyl chloride) and polyethylene terpolymer are less stable when compared to some homopolymer formulations. From the four pigments studied, titanium dioxide rutile and a carbon based black proved to be stabilizers for both types of polymer. The mixture lithopone plus calcium carbonate has showed to have a photocatalytic effect on the binders. The studied paintings showed to be in an overall good state of conservation except for the paintings created in the 90’s with white glue and a mixture of white lithoponeand calcium carbonate. Discoloration of this white paint seems to be irreversible and ongoing and is still a major concern. The disapearance of the plasticizer was the only change detected. The current works created by Sarmento are expected to be more stable as they were painted using the rutile titanium dioxide. Immersion/cleaning tests showed that vinyl based paints can be susceptible to water and organic solvents like ethanol as some evidences point to the removal/diffusion of additives from the paint. The observations made point to the need to further proceed in this research field.

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Since the financial crisis, risk based portfolio allocations have gained a great deal in popularity. This increase in popularity is primarily due to the fact that they make no assumptions as to the expected return of the assets in the portfolio. These portfolios implicitly put risk management at the heart of asset allocation and thus their recent appeal. This paper will serve as a comparison of four well-known risk based portfolio allocation methods; minimum variance, maximum diversification, inverse volatility and equally weighted risk contribution. Empirical backtests will be performed throughout rising interest rate periods from 1953 to 2015. Additionally, I will compare these portfolios to more simple allocation methods, such as equally weighted and a 60/40 asset-allocation mix. This paper will help to answer the question if these portfolios can survive in a rising interest rate environment.

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This Work Project aims to discuss the Context Costs and Comparative Advantages of the Telecommunications sector both in Portugal and China. The work was built mostly on primary research by interviews with relevant people (business persons, University Professors and Agencies directors), and by economic data publicly available. A list of context costs and comparative advantages was drawn for each country and possible resolutions suggestions were made in the end. The context costs depend heavily on the economic situation of the countries and it should be taken into account when assessing the degree of magnitude of each cost of context. The competitive advantages of each country were drawn in comparison with one another. Some key results stand out: firstly, Portugal’s costs of context depend mainly on governmental decisions, uncertainties and instability and China’s cost of context depend primarily on cultural norms, mainly the Guanxi; second, the telecommunications sector shares most of its context costs and advantages with other sectors; third, China as an economic power could use the telecommunications sector as a way to further develop and boost its economy.