Internationalization process of Gallo worldwide: Introduction of olive in a non-traditional market - China

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

How reporting and controlling systems can be effectively designed to support the decision-making process: The case of a Software SME

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

A conceptual model to approach the scaling process of social entreprises: The case of Cozinha com Alma

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Winning the war for talent: Does CSR matter in the recruitment process?

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

The internationalization process of born global firms in high-tech and low-tech industries: Is there any difference?

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Development of suberin films driven by an ionic liquid-based depolymerisation process

Dissertation presented to obtain the Ph.D degree in Chemistry

Quality of process modeling using BPMN: a model-driven approach

Dissertação para obtenção do Grau de Doutor em Engenharia Informática

Development of a "green process" for the isolation of natural functional extracts with anti-cancer activity - Application of high-pressure technology

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

Fractionation of hydro-ethanolic extracts from grape pomace through membrane processing: the effect of membrane and extracting media on process performance

The EM3E Master is an Education Programme supported by the European Commission, the European Membrane Society (EMS), the European Membrane House (EMH), and a large international network of industrial companies, research centers and universities

Process Engineering of Stem Cells for Clinical Application

Over the last decade, human embryonic stem cells (hESCs) have garnered a lot of attention owing to their inherent self-renewal ability and pluripotency. These characteristics have opened opportunities for potential stem cell-based regenerative medicines, for development of drug discovery platforms and as unique in vitro models for the study of early human development.(...)

A CMMI-compliant requirements management and development process

Requirements Engineering has been acknowledged an essential discipline for Software Quality. Poorly-defined processes for eliciting, analyzing, specifying and validating requirements can lead to unclear issues or misunderstandings on business needs and project’s scope. These typically result in customers’ non-satisfaction with either the products’ quality or the increase of the project’s budget and duration. Maturity models allow an organization to measure the quality of its processes and improve them according to an evolutionary path based on levels. The Capability Maturity Model Integration (CMMI) addresses the aforementioned Requirements Engineering issues. CMMI defines a set of best practices for process improvement that are divided into several process areas. Requirements Management and Requirements Development are the process areas concerned with Requirements Engineering maturity. Altran Portugal is a consulting company concerned with the quality of its software. In 2012, the Solution Center department has developed and applied successfully a set of processes aligned with CMMI-DEV v1.3, what granted them a Level 2 maturity certification. For 2015, they defined an organizational goal of addressing CMMI-DEV maturity level 3. This MSc dissertation is part of this organization effort. In particular, it is concerned with the required process areas that address the activities of Requirements Engineering. Our main goal is to contribute for the development of Altran’s internal engineering processes to conform to the guidelines of the Requirements Development process area. Throughout this dissertation, we started with an evaluation method based on CMMI and conducted a compliance assessment of Altran’s current processes. This allowed demonstrating their alignment with the CMMI Requirements Management process area and to highlight the improvements needed to conform to the Requirements Development process area. Based on the study of alternative solutions for the gaps found, we proposed a new Requirements Management and Development process that was later validated using three different approaches. The main contribution of this dissertation is the new process developed for Altran Portugal. However, given that studies on these topics are not abundant in the literature, we also expect to contribute with useful evidences to the existing body of knowledge with a survey on CMMI and requirements engineering trends. Most importantly, we hope that the implementation of the proposed processes’ improvements will minimize the risks of mishandled requirements, increasing Altran’s performance and taking them one step further to the desired maturity level.

Melanosome transfer between melanocytes and keratinocytes

RESUMO: A pele é o maior órgão do corpo humano e a sua pigmentação é essencial para a sua coloração e proteção contra os efeitos nocivos da radiação ultravioleta (UV). A pigmentação da pele resulta essencialmente de três processos: a síntese e o armazenamento de melanina pelos melanócitos, em organelos especializados denominados melanossomas; o transporte dos melanossomas dentro dos melanócitos; e finalmente, a transferência dos melanossomas para os queratinócitos adjacentes. Nos queratinócitos, a melanina migra para a região perinuclear apical da célula para formar um escudo protetor,responsável pela proteção do DNA dos danos causados pela radiação UV. Os melanócitos estão localizados na camada basal da epiderme e contactam com 30-40 queratinócitos. Em conjunto, estas células formam a “unidade melano-epidérmica”. Apesar dos processos de síntese e transporte de melanina nos melanócitos estarem bastante bem caracterizados, os mecanismos moleculares subjacentes à transferência inter-celular de melanina são menos conhecidos e ainda controversos. Dados preliminares obtidos pelo nosso grupo, que se basearam na observação de amostras de pele humana por microscopia electrónica, indicam que a forma predominante de transferência de melanina na epiderme consiste na exocitose dos melanossomas pelos melanócitos e subsequente endocitose da melanina por queratinócitos. Para além disso sabe-se que as proteínas Rab, que controlam o tráfego membranar, estão envolvidas em várias etapas de pigmentação da pele, nomeadamente na biogénese e no transporte de melanina. Assim, dado o seu papel fundamental nestes processos, questionámo-nos sobre o seu envolvimento na transferência de melanina. Com este trabalho, propomo-nos a expandir o conhecimento atual sobre a transferência de melanina na pele, através do estudo detalhado dos seus mecanismos moleculares, identificando as proteínas Rab que regulam o processo. Pretendemos também confirmar o modelo de exo/endocitose como sendo o mecanismo principal de transferência de melanina. Primeiro, explorámos a regulação da secreção de melanina pelos melanócitos e analisámos o papel de proteínas Rab neste processo. Os resultados foram obtidos recorrendo a um método in vitro, desenvolvido previamente no laboratório, que avalia a quantidade de melanina segregada para o meio de cultura por espectrofotometria, e ainda por microscopia, contando o número de melanossomas transferidos para os queratinócitos. Através de co-culturas de melanócitos e queratinócitos, verificou-se que os queratinócitos estimulam a libertação de melanina dos melanócitos para o meio extra-celular, bem como a sua transferência para os queratinócitos. Além disso, a proteína Rab11b foi identificada como um regulador da exocitose de melanina e da sua transferência para os queratinócitos. De facto, a diminuição da expressão de Rab11b em melanócitos provocou a redução da secreção de melanina estimulada por queratinócitos, bem como da transferência desta. Em segundo lugar, para complementar o nosso estudo, centrámos a nossa investigação na internalização de melanina por queratinócitos. Especificamente, usando uma biblioteca de siRNA, explorámos o envolvimento de proteínas Rab na captação de melanina por queratinócitos. Como primeira abordagem, usámos esferas fluorescentes como substituto de melanina, avaliando os resultados por citometria de fluxo. No entanto, este método revelou-se ineficaz uma vez que a internalização destas esferas é independente do recetor PAR-2 (recetor 2 ativado por protease), que foi previamente descrito como essencial na captação de melanina por queratinócitos Posteriormente, foi desenvolvido um novo protocolo de endocitose baseado em microscopia, usando melanossomas sem a membrana envolvente (melanocores) purificados do meio de cultura de melanócitos, incluindo um programa informático especialmente desenhado para realizar uma análise semi-automatizada. Após internalização, os melanocores acumulam-se na região perinuclear dos queratinócitos, em estruturas que se assemelham ao escudo supranuclear observado na pele humana. Seguidamente, o envolvimento do recetor PAR-2 na captação de melanocores por queratinócitos foi confirmado, utilizando o novo protocolo de endocitose desenvolvido. Para além disso, a necessidade de quatro proteínas Rab foi identificada na internalização de melanocores por queratinócitos. A redução da expressão de Rab1a ou Rab5b em queratinócitos diminuiu significativamente o nível de internalização de melanocores, enquanto o silenciamento da expressão de Rab2a ou Rab14 aumentou a quantidade de melanocores internalizados por estas células. Em conclusão, os resultados apresentados corroboram as observações anteriores, obtidas em amostras de pele humana, e sugerem que o mecanismo de transferência predominante é a exocitose de melanina pelos melanócitos, induzida por queratinócitos, seguida por endocitose pelos queratinócitos. A pigmentação da pele tem implicações tanto ao nível da cosmética, como ao nível médico, relacionadas com foto-envelhecimento e com doenças pigmentares. Assim sendo, ao esclarecer quais os mecanismos moleculares que regulam a transferência de melanina na pele, este trabalho pode conduzir ao desenvolvimento de novas estratégias para modular a pigmentação da pele.----------------ABSTRACT: Skin pigmentation is achieved through the highly regulated production of the pigment melanin in specialized organelles, termed melanosomes within melanocytes. These are transported from their site of synthesis to the melanocyte periphery before being transferred to keratinocytes where melanin forms a supra-nuclear cap to protect the DNA from UVinduced damage. Together, melanocytes and keratinocytes form a functional complex, termed “epidermal-melanin unit”, that confers color and photoprotective properties to the skin. Skin pigmentation requires three processes: the biogenesis of melanin; its intracelular transport within the melanocyte to the cell periphery; and the melanin transfer to keratinocytes. The first two processes have been extensively characterized. However, despite significant advances that have been made over the past few years, the mechanisms underlying inter-cellular transfer of pigment from melanocytes to keratinocytes remain controversial.Preliminary studies from our group using electron microscopy and human skin samples found evidence for a mechanism of coupled exocytosis-endocytosis. Rab GTPases are master regulators of intracellular trafficking and have already been implicated in several steps of skin pigmentation. Thus, we proposed to explore and characterize the molecular mechanisms of melanin transfer and the role of Rab GTPases in this process. Moreover, we investigated whether the exo/endocytosis model is the main mechanism of melanin transfer. We first focused on melanin exocytosis by melanocytes. Then, we started to investigate the key regulatory Rab proteins involved in this step by establishing an in vitro tissue culture model of melanin secretion. Using co-cultures of melanocytes and keratinocytes, we found that keratinocytes stimulate melanin release and transfer. Moreover, depletion of Rab11b decreases keratinocyte-induced melanin exocytosis by melanocytes. In order to determine whether melanin exocytosis is a predominant mechanism of melanin transfer, the amount of melanin transferred to keratinocytes was then assayed in conditions where melanin exocytosis was inhibited. Indeed, Rab11b depletion resulted in a significant decrease in melanin uptake by keratinocytes. Taken together, these observations suggest that Rab11b mediates melanosome exocytosis from melanocytes and transfer to keratinocytes. To complement and extend our study, we of melanin by keratinocytes. Thus, we aimed to explore the effect of depleting Rab GTPases on melanin uptake and trafficking within keratinocytes. As a first approach, we used fluorescent microspheres as a melanin surrogate. However, the uptake of microspheres was observed to be independent of PAR-2, a receptor that is required for melanin uptakecentred our attention in the internalization of melanin by keratinocytes. Thus, we aimed to explore the effect of depleting Rab GTPases on melanin uptake and trafficking within keratinocytes. As a first approach, we used fluorescent microspheres as a melanin surrogate. However, the uptake of microspheres was observed to be independent of PAR-2, a receptor that is required for melanin uptake.Therefore, we concluded that microspheres were uptaken by keratinocytes through a different pathway than melanin. Subsequently, we developed a microscopy-based endocytosis assay using purified melanocores (melanosomes lacking the limiting membrane) from melanocytes, including a program to perform a semi-automated analysis. Melanocores are taken up by keratinocytes and accumulate in structures in the perinuclear area that resemble the physiological supranuclear cap observed in human skin. We then confirmed the involvement of PAR-2 receptor in the uptake of melanocores by keratinocytes, using the newly developed assay. Furthermore, we identified the role of four Rab GTPases on the uptake of melanocores by keratinocytes. Depletion of Rab1a and Rab5b from keratinocytes significantly reduced the uptake of melanocores, whereas Rab2a, and Rab14 silencing increased the amount the melanocores internalized by XB2 keratinocytes. In conclusion, we present evidence supporting keratinocyte-inducedmelanosome exocytosis from melanocytes, followed by endocytosis of the melanin core by keratinocytes as the predominant mechanism of melanin transfer in skin. Although advances have been made, there is a need for more effective and safer therapies directed at pigmentation disorders and also treatments for cosmetic applications. Hence, the understanding of the above mechanisms of skin pigmentation will lead to a greater appreciation of the molecular machinery underlying human skin pigmentation and could interest the pharmaceutical and cosmetic industries.

Policing and planning child and adolescent neuropsychiatry : the reform process in Bologna 2009-2014

Desde a aprovação do plano de saúde mental regional em Itália ... o Departamento Local de Saúde Mental e Perturbações aditivas em Bolonha, tem desenvolvido um projeto de reforma cujo objectivo é inovar o sistema de saúde mental local. ...ABSTRACT: Since the Regional mental health plan 2009-2011 was approved in Italy the Department of Mental Health and addictions of the Bologna local health trust developed as a laboratory aimed at innovating the mental health systen locally. ...

The effect of key process operational conditions on enhanced biological phosphorus removal from wastewater

Enhanced biological phosphorus removal (EBPR) is the most economic and sustainable option used in wastewater treatment plants (WWTPs) for phosphorus removal. In this process it is important to control the competition between polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs), since EBPR deterioration or failure can be related with the proliferation of GAOs over PAOs. This thesis is focused on the effect of operational conditions (volatile fatty acid (VFA) composition, dissolved oxygen (DO) concentration and organic carbon loading) on PAO and GAO metabolism. The knowledge about the effect of these operational conditions on EBPR metabolism is very important, since they represent key factors that impact WWTPs performance and sustainability. Substrate competition between the anaerobic uptake of acetate and propionate (the main VFAs present in WWTPs) was shown in this work to be a relevant factor affecting PAO metabolism, and a metabolic model was developed that successfully describes this effect. Interestingly, the aerobic metabolism of PAOs was not affected by different VFA compositions, since the aerobic kinetic parameters for phosphorus uptake, polyhydroxyalkanoates (PHAs) degradation and glycogen production were relatively independent of acetate or propionate concentration. This is very relevant for WWTPs, since it will simplify the calibration procedure for metabolic models, facilitating their use for full-scale systems. The DO concentration and aerobic hydraulic retention time (HRT) affected the PAO-GAO competition, where low DO levels or lower aerobic HRT was more favourable for PAOs than GAOs. Indeed, the oxygen affinity coefficient was significantly higher for GAOs than PAOs, showing that PAOs were far superior at scavenging for the often limited oxygen levels in WWTPs. The operation of WWTPs with low aeration is of high importance for full-scale systems, since it decreases the energetic costs and can potentially improve WWTP sustainability. Extended periods of low organic carbon load, which are the most common conditions that exist in full-scale WWTPs, also had an impact on PAO and GAO activity. GAOs exhibited a substantially higher biomass decay rate as compared to PAOs under these conditions, which revealed a higher survival capacity for PAOs, representing an advantage for PAOs in EBPR processes. This superior survival capacity of PAOs under conditions more closely resembling a full-scale environment was linked with their ability to maintain a residual level of PHA reserves for longer than GAOs, providing them with an effective energy source for aerobic maintenance processes. Overall, this work shows that each of these key operational conditions play an important role in the PAO-GAO competition and should be considered in WWTP models in order to improve EBPR processes.

The use of analytical hierarchy process in spatial decision support system for land use management

Geographic information systems give us the possibility to analyze, produce, and edit geographic information. Furthermore, these systems fall short on the analysis and support of complex spatial problems. Therefore, when a spatial problem, like land use management, requires a multi-criteria perspective, multi-criteria decision analysis is placed into spatial decision support systems. The analytic hierarchy process is one of many multi-criteria decision analysis methods that can be used to support these complex problems. Using its capabilities we try to develop a spatial decision support system, to help land use management. Land use management can undertake a broad spectrum of spatial decision problems. The developed decision support system had to accept as input, various formats and types of data, raster or vector format, and the vector could be polygon line or point type. The support system was designed to perform its analysis for the Zambezi river Valley in Mozambique, the study area. The possible solutions for the emerging problems had to cover the entire region. This required the system to process large sets of data, and constantly adjust to new problems’ needs. The developed decision support system, is able to process thousands of alternatives using the analytical hierarchy process, and produce an output suitability map for the problems faced.