An approach to teach Calculus/Mathematical Analysis (for engineering students) using computers and active learning – its conception, development of materials and evaluation

Dissertação para obtenção do Grau de Doutor em Ciências da Educação

Modelling lean and green supply chain

Dissertação para obtenção do Grau de Doutor em Engenharia Industrial

Petri net based development of globally-asynchronous locally-synchronous distributed embedded systems

Dissertação para obtenção do Grau de Doutor em Engenharia Electrotécnica e de Computadores

Res Publica: Citizenship and Political Representation in Portugal, 1820-1926

The term res publica (literally “thing of the people”) was coined by the Romans to translate the Greek word politeia, which, as we know, referred to a political community organised in accordance with certain principles, amongst which the notion of the “good life” (as against exclusively private interests) was paramount. This ideal also came to be known as political virtue. To achieve it, it was necessary to combine the best of each “constitutional” type and avoid their worst aspects (tyranny, oligarchy and ochlocracy). Hence, the term acquired from the Greeks a sense of being a “mixed” and “balanced” system. Anyone that was entitled to citizenship could participate in the governance of the “public thing”. This implied the institutionalization of open debate and confrontation between interested parties as a way of achieving the consensus necessary to ensure that man the political animal, who fought with words and reason, prevailed over his “natural” counterpart. These premises lie at the heart of the project which is now being presented under the title of Res Publica: Citizenship and Political Representation in Portugal, 1820-1926. The fact that it is integrated into the centenary commemorations of the establishment of the Republic in Portugal is significant, as it was the idea of revolution – with its promise of rupture and change – that inspired it. However, it has also sought to explore events that could be considered the precursor of democratization in the history of Portugal, namely the vintista, setembrista and patuleia revolutions. It is true that the republican regime was opposed to the monarchic. However, although the thesis that monarchy would inevitably lead to tyranny had held sway for centuries, it had also been long believed that the monarchic system could be as “politically virtuous” as a republic (in the strict sense of the word) provided that power was not concentrated in the hands of a single individual. Moreover, various historical experiments had shown that republics could also degenerate into Caesarism and different kinds of despotism. Thus, when absolutism began to be overturned in continental Europe in the name of the natural rights of man and the new social pact theories, initiating the difficult process of (written) constitutionalization, the monarchic principle began to be qualified as a “monarchy hedged by republican institutions”, a situation in which not even the king was exempt from isonomy. This context justifies the time frame chosen here, as it captures the various changes and continuities that run through it. Having rejected the imperative mandate and the reinstatement of the model of corporative representation (which did not mean that, in new contexts, this might not be revived, or that the second chamber established by the Constitutional Charter of 1826 might not be given another lease of life), a new power base was convened: national sovereignty, a precept that would be shared by the monarchic constitutions of 1822 and 1838, and by the republican one of 1911. This followed the French example (manifested in the monarchic constitution of 1791 and in the Spanish constitution of 1812), as not even republicans entertained a tradition of republicanism based upon popular sovereignty. This enables us to better understand the rejection of direct democracy and universal suffrage, and also the long incapacitation (concerning voting and standing for office) of the vast body of “passive” citizens, justified by “enlightened”, property- and gender-based criteria. Although the republicans had promised in the propaganda phase to alter this situation, they ultimately failed to do so. Indeed, throughout the whole period under analysis, the realisation of the potential of national sovereignty was mediated above all by the individual citizen through his choice of representatives. However, this representation was indirect and took place at national level, in the hope that action would be motivated not by particular local interests but by the common good, as dictated by reason. This was considered the only way for the law to be virtuous, a requirement that was also manifested in the separation and balance of powers. As sovereignty was postulated as single and indivisible, so would be the nation that gave it soul and the State that embodied it. Although these characteristics were common to foreign paradigms of reference, in Portugal, the constitutionalization process also sought to nationalise the idea of Empire. Indeed, this had been the overriding purpose of the 1822 Constitution, and it persisted, even after the loss of Brazil, until decolonization. Then, the dream of a single nation stretching from the Minho to Timor finally came to an end.

Immunohistochemistry detection of putative miR-200c and miR-203 targets in breast cancer patients

Part of this thesis will be published in the following: Gomes, B.C., Santos, B. 2015. Methods for studying microRNAs expression and their targets in formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues. In Methods in Molecular Biology: Cancer Drug Resistance (Rueff, J. & Rodrigues, A.S. eds), Springer Protocols.

Provide instructions and resources for assessment and training in earth building: the Pirate project

This publication reflects the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein.

Land cover mapping analysis and urban growth modeling using remote sensing techniques

The rapid growth of big cities has been noticed since 1950s when the majority of world population turned to live in urban areas rather than villages, seeking better job opportunities and higher quality of services and lifestyle circumstances. This demographic transition from rural to urban is expected to have a continuous increase. Governments, especially in less developed countries, are going to face more challenges in different sectors, raising the essence of understanding the spatial pattern of the growth for an effective urban planning. The study aimed to detect, analyse and model the urban growth in Greater Cairo Region (GCR) as one of the fast growing mega cities in the world using remote sensing data. Knowing the current and estimated urbanization situation in GCR will help decision makers in Egypt to adjust their plans and develop new ones. These plans should focus on resources reallocation to overcome the problems arising in the future and to achieve a sustainable development of urban areas, especially after the high percentage of illegal settlements which took place in the last decades. The study focused on a period of 30 years; from 1984 to 2014, and the major transitions to urban were modelled to predict the future scenarios in 2025. Three satellite images of different time stamps (1984, 2003 and 2014) were classified using Support Vector Machines (SVM) classifier, then the land cover changes were detected by applying a high level mapping technique. Later the results were analyzed for higher accurate estimations of the urban growth in the future in 2025 using Land Change Modeler (LCM) embedded in IDRISI software. Moreover, the spatial and temporal urban growth patterns were analyzed using statistical metrics developed in FRAGSTATS software. The study resulted in an overall classification accuracy of 96%, 97.3% and 96.3% for 1984, 2003 and 2014’s map, respectively. Between 1984 and 2003, 19 179 hectares of vegetation and 21 417 hectares of desert changed to urban, while from 2003 to 2014, the transitions to urban from both land cover classes were found to be 16 486 and 31 045 hectares, respectively. The model results indicated that 14% of the vegetation and 4% of the desert in 2014 will turn into urban in 2025, representing 16 512 and 24 687 hectares, respectively.

Optimization of export support systems: How to promote exports from Portugal to Germany in the area of information technology and electronics

This work project focuses on developing new approaches which enhance Portuguese exports towards a defined German industry sector within the information technology and electronics fields. Firstly and foremost, information was collected and a set of expert and top managers’ interviews were performed in order to acknowledge the demand of the German market while identifying compatible Portuguese supply capabilities. Among the main findings, Industry 4.0 presents itself as a valuable opportunity in the German market for Portuguese medium sized companies in the embedded systems area of expertise for machinery and equipment companies. In order to achieve the purpose of the work project, an embedded systems platform targeting machinery and equipment companies was suggested as well as it was developed several recommendations on how to implement it. An alternative approach for this platform was also considered within the German market namely the eHealth sector having the purpose of enhancing the current healthcare service provision.

The role of individual ability and structural embeddedness on entrepreneurial success

In the present thesis I analyse the roles of individual ability and structural embeddedness on entrepreneurial success. The results retrieved from a matched employer-employee longitudinal data set show prior worker productivities and environmental embeddedness to have a persistent positive impact on the size and growth rates of new firms. What is more, embeddedness facilitates the impact of ability on start-up performance with outsiders of comparable abilities starting smaller and slower growing firms. Those in higher ability categories are more likely to transfer and also, albeit to a lesser extent, close their ventures, an effect attributed to the higher opportunity costs associated with the group. Firms managed by embedded agents enjoy longer longevities and have better chances of finding a new owner after the departure of the previous one. Finally, higher ability types show evidence of specialisation in serial entrepreneurship.

Historic and potential technology transition paths of grid battery storage: Co-evolution of energy grid, electric mobility and batteries

Scarcity of fuels, changes in environmental policy and in society increased the interest in generating electric energy from renewable energy sources (RES) for a sustainable energy supply in the future. The main problem of RES as solar and wind energy, which represent a main pillar of this transition, is that they cannot supply constant power output. This results inter alia in an increased demand of backup technologies as batteries to assure electricity system safety. The diffusion of energy storage technologies is highly dependent on the energy system and transport transition pathways which might lead to a replacement or reconfiguration of embedded socio-technical practices and regimes (by creating new standards or dominant designs, changing regulations, infrastructure and user patterns). The success of this technology is dependent on hardly predictable future technical advances, actor preferences, development of competing technologies and designs, diverging interests of actors, future cost efficiencies, environmental performance, the evolution of market demand and design and evolution of our society.

Earthen plasters based on illitic soils from Barrocal region of Algarve: contributions for building performance and sustainability

Clayish earth-based mortars can be considered eco-efficient products for indoor plastering since they can contribute to improve important aspects of building performance and sustainability. Apart from being products with low embodied energy when compared to other types of mortars used for interior plastering, mainly due to the use raw clay as natural binder, earth-based plasters may give a significant contribution for health and comfort of inhabitants. Due to high hygroscopicity of clay minerals, earth-based mortars present a high adsorption and desorption capacity, particularly when compared to other type of mortars for interior plastering. This capacity allows earth-based plasters to act as a moisture buffer, balancing the relative humidity of the indoor environment and, simultaneously, acting as a passive removal material, improving air quality. Therefore, earth-based plasters may also passively promote the energy efficiency of buildings, since they may contribute to decreasing the needs of mechanical ventilation and air conditioning. This study is part of an ongoing research regarding earth-based plasters and focuses on mortars specifically formulated with soils extracted from Portuguese ‘Barrocal’ region, in Algarve sedimentary basin. This region presents high potential for interior plastering due to regional geomorphology, that promote the occurrence of illitic soils characterized by a high adsorption capacity and low expansibility. More specifically, this study aims to assess how clayish earth and sand ratio of mortars formulation can influence the physical and mechanical properties of plasters. For this assessment four mortars were formulated with different volumetric proportions of clayish earth and siliceous sand. The results from the physical and mechanical characterization confirmed the significantly low linear shrinkage of all the four mortars, as well as their extraordinary adsorption-desorption capacity. These results presented a positive correlation with mortars´ clayish earth content and are consistent with the mineralogical analysis, that confirmed illite as the prevalent clay mineral in the clayish earth used for this study. Regarding mechanical resistance, although the promising results of the adhesion test, the flexural and compressive strength results suggest that the mechanical resistance of these mortars should be slightly improved. Considering the present results the mortars mechanical resistance improvement may be achieved through the formulation of mortars with higher clayish earth content, or alternatively, through the addition of natural fibers to mortars formulation, very common in this type of mortars. Both those options will be investigated in future research.

Assessing initial embodied energy in building structures using LCA methodology

The considerable amount of energy consumed on Earth is a major cause for not achieving sustainable development. Buildings are responsible for the highest worldwide energy consumption, nearly 40%. Strong efforts have been made in what concerns the reduction of buildings operational energy (heating, hot water, ventilation, electricity), since operational energy is so far the highest energy component in a building life cycle. However, as operational energy is being reduced the embodied energy increases. One of the building elements responsible for higher embodied energy consumption is the building structural system. Therefore, the present work is going to study part of embodied energy (initial embodied energy) in building structures using a life cycle assessment methodology, in order to contribute for a greater understanding of embodied energy in buildings structural systems. Initial embodied energy is estimated for a building structure by varying the span and the structural material type. The results are analysed and compared for different stages, and some conclusions are drawn. At the end of this work it was possible to conclude that the building span does not have considerable influence in embodied energy consumption of building structures. However, the structural material type has influence in the overall energetic performance. In fact, with this research it was possible that building structure that requires more initial embodied energy is the steel structure; then the glued laminated timber structure; and finally the concrete structure.

Analysis of outcome and cancer stem cells status in patients with resectable pancreatic adenocarcinoma

RESUMO: Actualmente, a única possibilidade de cura para doentes com adenocarcinoma do pâncreas (PDAC) é a ressecção cirúrgica, no início deste estudo, perguntamo-nos se os predictores clínico-patológicos clássicos de prognostico poderiam ser validados em uma grande cohort de doentes com cancro do pâncreas ressecável e se outros predictores clínicos poderiam ter um papel na decisão de que doentes beneficiariam de ressecção cirúrgica. No capítulo 2, observamos que até 30% dos doentes morrem no primeiro ano após a ressecção cirúrgica, pelo que o nosso objectivo foi determinar factores pré-operatórios que se correlacionam com mortalidade precoce após ressecação cirúrgica com recurso a um instrumento estatisticamente validado, o Charlson-Age Comorbidity Index (CACI), determinamos que um CACI score superior a 4 foi preditivo de internamentos prolongados (p <0,001), complicações pós-operatórias (p = 0,042), e mortalidade em 1 ano pós- ressecção cirúrgica (p <0,001). Um CACI superior a 6 triplicou a mortalidade no primeiro ano pós-cirurgia e estes doentes têm menos de 50% de probabilidade de estarem vivos um ano após a cirurgia. No capítulo 3, o nosso objectivo foi identificar uma proteína de superfície que se correlacionasse estatisticamente com o prognostico de doentes com adenocarcinoma do pâncreas e permitisse a distinção de subgrupos de doentes de acordo com as suas diferenças moleculares, perguntamo-nos ainda se essa proteína poderia ser um marcador de células-estaminais. No nosso trabalho anterior observamos que as células tumorais na circulação sanguínea apresentavam genes com características bifenotípica epitelial e mesenquimal, enriquecimento para genes de células estaminais (ALDH1A1 / ALDH1A2 e KLF4), e uma super-expressão de genes da matriz extracelular (colagénios, SPARC, e DCN) normalmente identificados no estroma de PDAC. Após a avaliação dos tumores primários com RNA-ISH, muitos dos genes identificados, foram encontrados co-localizando em uma sub-população de células na região basal dos ductos pancreáticos malignos. Além disso, observamos que estas células expressam o marcador SV2A neuroendócrino, e o marcador de células estaminais ALDH1A1/2. Em comparação com tumores negativos para SV2, os doentes com tumores SV2 positivos apresentaram níveis mais baixos de CA 19-9 (69% vs. 52%, p = 0,012), tumores maiores (> 4 cm, 23% vs. 10%, p = 0,0430), menor invasão de gânglios linfáticos (69% vs. 86%, p = 0,005) e tumores mais diferenciados (69% vs. 57%, p = 0,047). A presença de SV2A foi associada com uma sobrevida livre de doença mais longa (HR: 0,49 p = 0,009) bem como melhor sobrevida global (HR: 0,54 p = 0,018). Em conjunto, esta informação aponta para dois subtipos diferentes de adenocarcinoma do pâncreas, e estes subtipos co-relacionam estatisticamente com o prognostico de doentes, sendo este subgrupo definido pela presença do clone celular SV2A / ALDH1A1/2 positivo com características neuroendócrinas. No Capítulo 4, a expressão de SV2A no cancro do pâncreas foi validado em linhas celulares primárias. Demonstramos a heterogeneidade do adenocarcinoma do pâncreas de acordo com características clonais neuroendócrinas. Ao comparar as linhas celulares expressando SV2 com linhas celulares negativas, verificamos que as linhas celulares SV2+ eram mais diferenciadas, diferindo de linhas celulares SV2 negativas no que respeita a mutação KRAS, proliferação e a resposta à quimioterapia. No capítulo 5, perguntamo-nos se o clone celular SV2 positivo poderia explicar a resistência a quimioterapia observada em doentes. Observamos um aumento absoluto de clones celulares expressando SV2A, em múltiplas linhas de evidência - doentes, linhas de células primárias e xenotransplantes. Embora, tenhamos sido capazes de demonstrar que o adenocarcinoma do pâncreas é uma doença heterogénea, consideramos que a caracterização genética destes clones celulares expressando SV2A é de elevada importância. Pretendemos colmatar esta limitação com as seguintes estratégias: Após o tratamento com quimioterapia neoadjuvante na nossa coorte, realizamos microdissecação a laser das amostras primarias em parafina, de forma a analisar mutações genéticas observadas no adenocarcinoma pancreático; em segundo lugar, pretendemos determinar consequências de knockdown da expressão de SV2A em nossas linhas celulares seguindo-se o tratamento com gemicitabina para determinação do papel funcional de SV2A; finalmente, uma vez que os nossos esforços anteriores com um promotor - repórter e SmartFlare ™ falharam, o próximo passo será realizar RNA-ISH PrimeFlow™ seguido de FACS e RNA-seq para caracterização deste clone celular. Em conjunto, conseguimos provar com várias linhas de evidência, que o adenocarcinoma pancreático é uma doença heterogénea, definido por um clone de células que expressam SV2A, com características neuroendócrinas. A presença deste clone no tecido de doentes correlaciona-se estatisticamente com o prognostico da doença, incluindo sobrevida livre de doença e sobrevida global. Juntamente com padrões de proliferação e co-expressão de ALDH1A1/2, este clone parece apresentar um comportamento de células estaminais e está associado a resistência a quimioterapia, uma vez que a sua expressão aumenta após agressão química, quer em doentes, quer em linhas de células primárias.----------------------------- ABSTRACT: Currently, the only chance of cure for patients with pancreatic adenocarcinoma is surgical resection, at the beginning of my thesis studies, we asked if the classical clinicopathologic predictors of outcome could be validated in a large cohort of patients with early stage pancreatic cancer and if other clinical predictors could have a role on deciding which patients would benefit from surgery. In chapter 2, we found that up to 30% of patients die within the first year after curative intent surgery for pancreatic adenocarcinoma. We aimed at determining pre-operative factors that would correlate with early mortality following resection for pancreatic cancer using a statistically validated tool, the Charlson-Age Comorbidity Index (CACI). We found that a CACI score greater than 4 was predictive of increased length of stay (p<0.001), post-operative complications (p=0.042), and mortality within 1-year of pancreatic resection (p<0.001). A CACI score of 6 or greater increased 3-fold the odds of death within the first year. Patients with a high CACI score have less than 50% likelihood of being alive 1 year after surgery. In chapter 3 we aimed at identifying a surface protein that correlates with patient’s outcome and distinguishes sub-groups of patients according to their molecular differences and if this protein could be a cancer stem cell marker. The most abundant class of circulating tumor cells identified in our previous work was found to have biphenotypic features of epithelial to mesenchymal transition, enrichment for stem-cell associated genes (ALDH1A1/ALDH1A2 and KLF4), and an overexpression of extracellular matrix genes (Collagens, SPARC, and DCN) normally found in the stromal microenvironment of PDAC primary tumors. Upon evaluation of matched primary tumors with RNA-ISH, many of the genes identified were found to co-localize in a sub-population of cells at the basal region of malignant pancreatic ducts. In addition, these cells expressed the neuroendocrine marker SV2A, and the stem cell marker ALDH1A1/2. Compared to SV2 negative tumors, patients with SV2 positive tumors were more likely to present with lower CA 19-9 (69% vs. 52%, p = 0.012), bigger tumors (size > 4 cm, 23% vs. 10%, p= 0.0430), less nodal involvement (69% vs. 86%, p = 0.005) and lower histologic grade (69% vs. 57%, p = 0.047). The presence of SV2A expressing cells was associated with an improved disease free survival (HR: 0.49 p=0.009) and overall survival (HR: 0.54 p=0.018) and correlated linearly with ALDH1A2. Together, this information points to two different sub-types of pancreatic adenocarcinoma, and these sub-types correlated with patients’ outcome and were defined by the presence of a SV2A/ ALDH1A1/2 expressing clone with neuroendocrine features. In Chapter 4, SV2A expression in cancer was validated in primary cell lines. We were able to demonstrate pancreatic adenocarcinoma heterogeneity according to neuroendocrine clonal features. When comparing SV2 expressing cell lines with SV2 negative cell lines, we found that SV2+ cell lines were more differentiated and differ from SV2 negative cell lines regarding KRAS mutation, proliferation and response to chemotherapy. In Chapter 5 we aimed at determining if this SV2 positive clone could explain chemoresistance observed in patients. We found an absolute increase in SV2A expressing cells, with multiple lines of evidence, in patients, primary cell lines and xenografts. Although, we have been able to show evidence that pancreatic adenocarcinoma is a heterogeneous disease, our findings warrant further investigation. To further characterize SV2A expressing clones after treatment with neoadjuvant chemotherapy in our cohort, we have performed laser capture microdissection of the paraffin embedded tissue in this study and will analyze the tissue for known genetic mutations in pancreatic adenocarcinoma; secondly, we want to know what will happen after knocking down SV2A expression in our cell lines followed by treatment with gemcitabine to determine if SV2A is functionally important; finally, since our previous efforts with a promoter – reporter and SmartFlare™ have failed, we will utilize a novel PrimeFlow™ RNA-ISH assay followed by FACS and RNA sequencing to further characterize this cellular clone. Overall our data proves, with multiple lines of evidence, that pancreatic adenocarcinoma is a heterogeneous disease, defined by a clone of SV2A expressing cells, with neuroendocrine features. The presence of this clone in patients’ tissue correlates with patient’s disease free survival and overall survival. Together with patterns of proliferation and ALDH1A1/2 co-expression, this clone seems to present a stem-cell-like behavior and is associated with chemoresistance, since it increases after chemotherapy, both in patients and primary cell lines.