Communication middleware for the future mobile internet

A evolução constante em novas tecnologias que providenciam suporte à forma como os nossos dispositivos se ligam, bem como a forma como utilizamos diferentes capacidades e serviços on-line, criou um conjunto sem precedentes de novos desafios que motivam o desenvolvimento de uma recente área de investigação, denominada de Internet Futura. Nesta nova área de investigação, novos aspectos arquiteturais estão ser desenvolvidos, os quais, através da re-estruturação de componentes nucleares subjacentesa que compõem a Internet, progride-a de uma forma capaz de não são fazer face a estes novos desafios, mas também de a preparar para os desafios de amanhã. Aspectos chave pertencendo a este conjunto de desafios são os ambientes de rede heterogéneos compostos por diferentes tipos de redes de acesso, a cada vez maior mudança do tráfego peer-to-peer (P2P) como o tipo de tráfego mais utilizado na Internet, a orquestração de cenários da Internet das Coisas (IoT) que exploram mecanismos de interação Maquinaa-Maquina (M2M), e a utilização de mechanismos centrados na informação (ICN). Esta tese apresenta uma nova arquitetura capaz de simultaneamente fazer face a estes desafios, evoluindo os procedimentos de conectividade e entidades envolvidas, através da adição de uma camada de middleware, que age como um mecanismo de gestão de controlo avançado. Este mecanismo de gestão de controlo aproxima as entidades de alto nível (tais como serviços, aplicações, entidades de gestão de mobilidade, operações de encaminhamento, etc.) com as componentes das camadas de baixo nível (por exemplo, camadas de ligação, sensores e atuadores), permitindo uma otimização conjunta dos procedimentos de ligação subjacentes. Os resultados obtidos não só sublinham a flexibilidade dos mecanismos que compoem a arquitetura, mas também a sua capacidade de providenciar aumentos de performance quando comparados com outras soluÇÕes de funcionamento especÍfico, enquanto permite um maior leque de cenáios e aplicações.

Behavioral modeling optimization and enhancement for high-speed analog mixed-signal I/O interfaces

A integridade do sinal em sistemas digitais interligados de alta velocidade, e avaliada através da simulação de modelos físicos (de nível de transístor) é custosa de ponto vista computacional (por exemplo, em tempo de execução de CPU e armazenamento de memória), e exige a disponibilização de detalhes físicos da estrutura interna do dispositivo. Esse cenário aumenta o interesse pela alternativa de modelação comportamental que descreve as características de operação do equipamento a partir da observação dos sinais eléctrico de entrada/saída (E/S). Os interfaces de E/S em chips de memória, que mais contribuem em carga computacional, desempenham funções complexas e incluem, por isso, um elevado número de pinos. Particularmente, os buffers de saída são obrigados a distorcer os sinais devido à sua dinâmica e não linearidade. Portanto, constituem o ponto crítico nos de circuitos integrados (CI) para a garantia da transmissão confiável em comunicações digitais de alta velocidade. Neste trabalho de doutoramento, os efeitos dinâmicos não-lineares anteriormente negligenciados do buffer de saída são estudados e modulados de forma eficiente para reduzir a complexidade da modelação do tipo caixa-negra paramétrica, melhorando assim o modelo standard IBIS. Isto é conseguido seguindo a abordagem semi-física que combina as características de formulação do modelo caixa-negra, a análise dos sinais eléctricos observados na E/S e propriedades na estrutura física do buffer em condições de operação práticas. Esta abordagem leva a um processo de construção do modelo comportamental fisicamente inspirado que supera os problemas das abordagens anteriores, optimizando os recursos utilizados em diferentes etapas de geração do modelo (ou seja, caracterização, formulação, extracção e implementação) para simular o comportamento dinâmico não-linear do buffer. Em consequência, contributo mais significativo desta tese é o desenvolvimento de um novo modelo comportamental analógico de duas portas adequado à simulação em overclocking que reveste de um particular interesse nas mais recentes usos de interfaces de E/S para memória de elevadas taxas de transmissão. A eficácia e a precisão dos modelos comportamentais desenvolvidos e implementados são qualitativa e quantitativamente avaliados comparando os resultados numéricos de extracção das suas funções e de simulação transitória com o correspondente modelo de referência do estado-da-arte, IBIS.

Synthesis of new Aβ-ligands useful in diagnosis of Alzheimer's disease

Alzheimer’s disease is a chronic progressive neurodegenerative disease and is the most common form of dementia (estimated 50−60% of all cases), associated with loss of memory (in particular episodic memory), cognitive decline, and behavioural and physical disability, ultimately leading to death. Alzheimer’s disease is a complex disease, mostly occurring sporadically with no apparent inheritance and being the age the main risk factor. The production and accumulation of amyloid-beta peptide in the central nervous system is a key event in the development of Alzheimer’s disease. This project is devoted to the synthesis of amyloid-beta ligands, fluorophores and blood brain barrier-transporters for diagnosis and therapy of Alzheimer’s disease. Different amyloid-beta ligands will be synthesized and their ability to interact with amyloid-beta plaques will be studied with nuclear magnetic resonance techniques and a process of lead optimization will be performed. Many natural and synthetic compounds able to interact as amyloid-beta ligands have been identified. Among them, a set of small molecules in which aromatic moieties seem to play a key role to inhibit amyloid-beta aggregation, in particular heteroaromatic polycyclic compounds such as tetracyclines. Nevertheless tetracyclines suffer from chemical instability, low water solubility and possess, in this contest, undesired anti-bacterial activity. In order to overcome these limitations, one of our goals is to synthesize tetracyclines analogues bearing a polycyclic structure with improved chemical stability and water solubility, possibly lacking antibacterial activity but conserving the ability to interact with amyloid-beta peptides. Known tetracyclines have in common a fourth cycle without an aromatic character and with different functionalisations. We aim to synthesize derivatives in which this cycle is represented by a sugar moiety, thus bearing different derivatisable positions or create derivatives in which we will increase or decrease the number of fused rings. In order to generate a potential drug-tool candidate, these molecules should also possess the correct chemical-physical characteristics. The glycidic moiety, not being directly involved in the binding, it assures further possible derivatizations, such as conjugation to others molecular entities (nanoparticles, polymeric supports, etc.), and functionalization with chemical groups able to modulate the hydro/lipophilicity. In order to be useful such compounds should perform their action within the brain, therefore they have to be able to cross the blood brain barrier, and to be somehow detected for diagnostic purposes.

Sinalização celular e a resposta a estrogénios do epitélio mamário

Estrogens, such as 17β-estradiol (E2) are essential for normal growth and differentiation of the mammary gland. There are two estrogen receptors (ERs), ERα and ERβ which are ligand activated transcription factors. ERα stimulates proliferation and is the single most powerful predictor of breast cancer prognosis and since 70% of breast cancers express ERα, strategies to block this receptor are the primary breast cancer treatment. Unlike ERα, the role of ERβ in breast cancer and its potential as alternative therapeutic target remains controversial, mainly due to the lack of correlation between results obtained in vitro and epidemiological studies. The aim of this thesis was to increase our understanding of the molecular and cellular mechanisms of estrogen signaling in normal and cancerous cells, in different cellular contexts and with focus on ERβ. In Paper I we characterized the effect of the flavone PD098059 - which is a commonly used MEK1 inhibitor - on activation of transcription by ERα and ERβ. We found that the estrogenic effect of PD098059 is dose dependent in concentrations ranging from 1 – 10 μM and that activation of transcription by ER is suppressed by the inhibitory effect of PD98059 on MEK1 at concentrations above 50 μM. In agreement with its flavone nature, PD098059 had a much stronger effect on ERβ than on ERα transcriptional activity. Therefore, use of this compound for the study of signalling events in cells expressing ER should be carefully considered. In Paper II we assessed the effect of ERβ agonists in vivo and administered under different conditions in vitro. In basal conditions, ERβ induced apoptosis; however, in vivo ERβ agonists stimulated proliferation and inhibited apoptosis. In vivo effects were reproduced in culture, by activation of MAPK/ERK½ pathway with epidermal growth factor or basement membrane extract. In addition, insulin signalling and PI3-K/AKT activation was necessary for stimulation of proliferation. These results suggest that the cellular context modulates ERβ activity. Manuscript presents preliminary work aimed at the set-up of a methodological strategy to isolate ERs and to identify interacting proteins in different cellular contexts and which could modulate the bi-phased effects of ERβ in cell growth. In conclusion, the studies presented in this thesis contribute to clarify the apparent contradictory information regarding ERβ function in normal and cancerous mammary epithelium and suggest that the cellular context should be considered when ERβ effects are studied.

Challenges in mercury speciation and fractionation in soil and sediment

This investigation focused on the development, test and validation of methodologies for mercury fractionation and speciation in soil and sediment. After an exhaustive review of the literature, several methods were chosen and tested in well characterised soil and sediment samples. Sequential extraction procedures that divide mercury fractions according to their mobility and potential availability in the environment were investigated. The efficiency of different solvents for fractionation of mercury was evaluated, as well as the adequacy of different analytical instruments for quantification of mercury in the extracts. Kinetic experiments to establish the equilibrium time for mercury release from soil or sediment were also performed. It was found that in the studied areas, only a very small percentage of mercury is present as mobile species and that mobility is associated to higher aluminium and manganese contents, and that high contents of organic matter and sulfur result in mercury tightly bound to the matrix. Sandy soils tend to release mercury faster that clayey soils, and therefore, texture of soil or sediment has a strong influence on the mobility of mercury. It was also understood that analytical techniques for quantification of mercury need to be further developed, with lower quantification limits, particularly for mercury quantification of less concentrated fractions: water-soluble e exchangeable. Although the results provided a better understanding of the distribution of mercury in the sample, the complexity of the procedure limits its applicability and robustness. A proficiency-testing scheme targeting total mercury determination in soil, sediment, fish and human hair was organised in order to evaluate the consistency of results obtained by different laboratories, applying their routine methods to the same test samples. Additionally, single extractions by 1 mol L-1 ammonium acetate solution, 0.1 mol L-1 HCl and 0.1 mol L-1 CaCl2, as well as extraction of the organometallic fraction were proposed for soil; the last was also suggested for sediment and fish. This study was important to update the knowledge on analytical techniques that are being used for mercury quantification, the associated problems and sources of error, and to improve and standardize mercury extraction techniques, as well as to implement effective strategies for quality control in mercury determination. A different, “non chemical-like” method for mercury species identification was developed, optimised and validated, based on the thermo-desorption of the different mercury species. Compared to conventional extraction procedures, this method has advantages: it requires little to no sample treatment; a complete identification of species present is obtained in less than two hours; mercury losses are almost neglectable; can be considered “clean”, as no residues are produced; the worldwide comparison of results obtained is easier and reliable, an important step towards the validation of the method. Therefore, the main deliverables of this PhD thesis are an improved knowledge on analytical procedures for identification and quantification of mercury species in soils and sediments, as well as a better understanding of the factors controlling the behaviour of mercury in these matrices.

Metal-organic frameworks based on phosphonate linkers

During the last few decades, Metal-Organic Frameworks (MOFs), also known as Coordination Polymers, have attracted worldwide research attentions due to their incremented fascinating architectures and unique properties. These multidimensional materials have been potential applications in distinct areas: gas storage and separation, ion exchange, catalysis, magnetism, in optical sensors, among several others. The MOF research group at the University of Aveiro has prepared MOFs from the combination of phosphonate organic primary building units (PBUs) with, mainly, lanthanides. This thesis documents the last findings in this area involving the synthesis of multidimensional MOFs based on four di- or tripodal phosphonates ligands. The organic PBUs were designed and prepared by selecting and optimizing the best reaction conditions and synthetic routes. The self-assembly between phosphonate PBUs and rare-earths cations led to the formation of several 1D, 2D and 3D families of isotypical MOFs. The preparation of these materials was achieved by using distinct synthetic approaches: hydro(solvo)thermal, microwave- and ultrasound-assisted, one-pot and ionothermal synthesis. The selection of the organic PBUs showed to have an important role in the final architectures: while flexible phosphonate ligands afforded 1D, 2D and dense 3D structures, a large and rigid organic PBU isolated a porous 3D MOF. The crystal structure of these materials was successfully unveiled by powder or single-crystal X-ray diffraction. All multidimensional MOFs were characterized by standard solid-state techniques (FT-IR, electron microscopy (SEM and EDS), solid-state NMR, elemental and thermogravimetric analysis). Some MOF materials exhibited remarkable thermal stability and robustness up to ca. 400 ºC. The intrinsic properties of some MOFs were investigated. Photoluminescence studies revealed that the selected organic PBUs are suitable sensitizers of Tb3+ leading to the isolation of intense green-emitting materials. The suppression of the O−H quenchers by deuteration or dehydration processes improves substantially the photoluminescence of the optically-active Eu3+-based materials. Some MOF materials exhibited high heterogeneous catalytic activity and excellent regioselectivity in the ring-opening reaction of styrene oxide (PhEtO) with methanol (100% conversion of PhEtO at 55 ºC for 30 min). The porous MOF material was employed in gas separation processes. This compound showed the ability to separate propane over propylene. The ionexchanged form of this material (containing K+ cations into its network) exhibited higher affinity for CO2 being capable to separate acetylene over this environment non-friendly gas.

Optimisation of viscoelastic treatments using genetic algorithms

Viscoelastic treatments are one of the most efficient treatments, as far as passive damping is concerned, particularly in the case of thin and light structures. In this type of treatment, part of the strain energy generated in the viscoelastic material is dissipated to the surroundings, in the form of heat. A layer of viscoelastic material is applied to a structure in an unconstrained or constrained configuration, the latter proving to be the most efficient arrangement. This is due to the fact that the relative movement of both the host and constraining layers cause the viscoelastic material to be subjected to a relatively high strain energy. There are studies, however, that claim that the partial application of the viscoelastic material is just as efficient, in terms of economic costs or any other form of treatment application costs. The application of patches of material in specific and selected areas of the structure, thus minimising the extension of damping material, results in an equally efficient treatment. Since the damping mechanism of a viscoelastic material is based on the dissipation of part of the strain energy, the efficiency of the partial treatment can be correlated to the modal strain energy of the structure. Even though the results obtained with this approach in various studies are considered very satisfactory, an optimisation procedure is deemed necessary. In order to obtain optimum solutions, however, time consuming numerical simulations are required. The optimisation process to use the minimum amount of viscoelastic material is based on an evolutionary geometry re-design and calculation of the modal damping, making this procedure computationally costly. To avert this disadvantage, this study uses adaptive layerwise finite elements and applies Genetic Algorithms in the optimisation process.

Optimization models for a short sea fuel oil distribution problem

O transporte marítimo e o principal meio de transporte de mercadorias em todo o mundo. Combustíveis e produtos petrolíferos representam grande parte das mercadorias transportadas por via marítima. Sendo Cabo Verde um arquipelago o transporte por mar desempenha um papel de grande relevância na economia do país. Consideramos o problema da distribuicao de combustíveis em Cabo Verde, onde uma companhia e responsavel por coordenar a distribuicao de produtos petrolíferos com a gestão dos respetivos níveis armazenados em cada porto, de modo a satisfazer a procura dos varios produtos. O objetivo consiste em determinar políticas de distribuicão de combustíveis que minimizam o custo total de distribuiçao (transporte e operacões) enquanto os n íveis de armazenamento sao mantidos nos n íveis desejados. Por conveniencia, de acordo com o planeamento temporal, o prob¬lema e divido em dois sub-problemas interligados. Um de curto prazo e outro de medio prazo. Para o problema de curto prazo sao discutidos modelos matemáticos de programacao inteira mista, que consideram simultaneamente uma medicao temporal cont ínua e uma discreta de modo a modelar multiplas janelas temporais e taxas de consumo que variam diariamente. Os modelos sao fortalecidos com a inclusão de desigualdades validas. O problema e então resolvido usando um "software" comercial. Para o problema de medio prazo sao inicialmente discutidos e comparados varios modelos de programacao inteira mista para um horizonte temporal curto assumindo agora uma taxa de consumo constante, e sao introduzidas novas desigualdades validas. Com base no modelo escolhido sao compara¬das estrategias heurísticas que combinam três heur ísticas bem conhecidas: "Rolling Horizon", "Feasibility Pump" e "Local Branching", de modo a gerar boas soluçoes admissíveis para planeamentos com horizontes temporais de varios meses. Finalmente, de modo a lidar com situaçoes imprevistas, mas impor¬tantes no transporte marítimo, como as mas condicões meteorológicas e congestionamento dos portos, apresentamos um modelo estocastico para um problema de curto prazo, onde os tempos de viagens e os tempos de espera nos portos sao aleatórios. O problema e formulado como um modelo em duas etapas, onde na primeira etapa sao tomadas as decisões relativas as rotas do navio e quantidades a carregar e descarregar e na segunda etapa (designada por sub-problema) sao consideradas as decisoes (com recurso) relativas ao escalonamento das operacões. O problema e resolvido por um metodo de decomposto que usa um algoritmo eficiente para separar as desigualdades violadas no sub-problema.

Control design for multicast-aware class-based networks

The expectations of citizens from the Information Technologies (ITs) are increasing as the ITs have become integral part of our society, serving all kinds of activities whether professional, leisure, safety-critical applications or business. Hence, the limitations of the traditional network designs to provide innovative and enhanced services and applications motivated a consensus to integrate all services over packet switching infrastructures, using the Internet Protocol, so as to leverage flexible control and economical benefits in the Next Generation Networks (NGNs). However, the Internet is not capable of treating services differently while each service has its own requirements (e.g., Quality of Service - QoS). Therefore, the need for more evolved forms of communications has driven to radical changes of architectural and layering designs which demand appropriate solutions for service admission and network resources control. This Thesis addresses QoS and network control issues, aiming to improve overall control performance in current and future networks which classify services into classes. The Thesis is divided into three parts. In the first part, we propose two resource over-reservation algorithms, a Class-based bandwidth Over-Reservation (COR) and an Enhanced COR (ECOR). The over-reservation means reserving more bandwidth than a Class of Service (CoS) needs, so the QoS reservation signalling rate is reduced. COR and ECOR allow for dynamically defining over-reservation parameters for CoSs based on network interfaces resource conditions; they aim to reduce QoS signalling and related overhead without incurring CoS starvation or waste of bandwidth. ECOR differs from COR by allowing for optimizing control overhead minimization. Further, we propose a centralized control mechanism called Advanced Centralization Architecture (ACA), that uses a single state-full Control Decision Point (CDP) which maintains a good view of its underlying network topology and the related links resource statistics on real-time basis to control the overall network. It is very important to mention that, in this Thesis, we use multicast trees as the basis for session transport, not only for group communication purposes, but mainly to pin packets of a session mapped to a tree to follow the desired tree. Our simulation results prove a drastic reduction of QoS control signalling and the related overhead without QoS violation or waste of resources. Besides, we provide a generic-purpose analytical model to assess the impact of various parameters (e.g., link capacity, session dynamics, etc.) that generally challenge resource overprovisioning control. In the second part of this Thesis, we propose a decentralization control mechanism called Advanced Class-based resource OverpRovisioning (ACOR), that aims to achieve better scalability than the ACA approach. ACOR enables multiple CDPs, distributed at network edge, to cooperate and exchange appropriate control data (e.g., trees and bandwidth usage information) such that each CDP is able to maintain a good knowledge of the network topology and the related links resource statistics on real-time basis. From scalability perspective, ACOR cooperation is selective, meaning that control information is exchanged dynamically among only the CDPs which are concerned (correlated). Moreover, the synchronization is carried out through our proposed concept of Virtual Over-Provisioned Resource (VOPR), which is a share of over-reservations of each interface to each tree that uses the interface. Thus, each CDP can process several session requests over a tree without requiring synchronization between the correlated CDPs as long as the VOPR of the tree is not exhausted. Analytical and simulation results demonstrate that aggregate over-reservation control in decentralized scenarios keep low signalling without QoS violations or waste of resources. We also introduced a control signalling protocol called ACOR Protocol (ACOR-P) to support the centralization and decentralization designs in this Thesis. Further, we propose an Extended ACOR (E-ACOR) which aggregates the VOPR of all trees that originate at the same CDP, and more session requests can be processed without synchronization when compared with ACOR. In addition, E-ACOR introduces a mechanism to efficiently track network congestion information to prevent unnecessary synchronization during congestion time when VOPRs would exhaust upon every session request. The performance evaluation through analytical and simulation results proves the superiority of E-ACOR in minimizing overall control signalling overhead while keeping all advantages of ACOR, that is, without incurring QoS violations or waste of resources. The last part of this Thesis includes the Survivable ACOR (SACOR) proposal to support stable operations of the QoS and network control mechanisms in case of failures and recoveries (e.g., of links and nodes). The performance results show flexible survivability characterized by fast convergence time and differentiation of traffic re-routing under efficient resource utilization i.e. without wasting bandwidth. In summary, the QoS and architectural control mechanisms proposed in this Thesis provide efficient and scalable support for network control key sub-systems (e.g., QoS and resource control, traffic engineering, multicasting, etc.), and thus allow for optimizing network overall control performance.

Estudo dos processos eletroquímicos: eletrooxidação e eletrocoagulação

O tratamento físico-químico de águas residuais, de origem industrial, mais comum é o tratamento baseado na adição de coagulante e floculante a um efluente. No entanto, o tratamento eletroquímico é um tipo de tratamento que tem vindo a ser explorado e estudado com mais ênfase ao longo dos últimos anos. O tratamento eletroquímico é uma tecnologia AOP (Processos de Oxidação Avançada) e divide-se em eletrólise direta (oxidação e redução) e indireta (eletrocoagulação-flotação e eletrooxidação). A eletrocoagulação e eletrooxidação divergem apenas pelo tipo de reações que ocorrem, devido ao material que constitui os elétrodos. São processos complexos com uma multiplicidade de mecanismos que operam sinergicamente para remover poluentes da água. Tendo em conta a sua complexidade e ainda dificuldade de compreensão, existem na literatura diferentes versões acerca de quais os mecanismos chave, assim como diversas configurações geométricas de reatores e elétrodos. Atualmente, este tipo de tratamento tem vindo a evoluir, tornando-se num método economicamente viável para o tratamento de uma grande variedade de águas residuais, nomeadamente, aquelas que possuem compostos recalcitrantes na sua composição. O presente trabalho foi realizado nas instalações da VentilAQUA S.A. e, tendo em conta a sua área de especialidade, o trabalho exposto focou-se no desenvolvimento de soluções técnicas de AOP, nomeadamente na área eletroquímica (eletrocoagulação e eletrooxidação),para estudo dos parâmetros operacionais numa nova configuração geométrica para os elétrodos. Tendo por base os contributos da revisão bibliográfica, o estudo incidiu num reator tubular, com elétrodos de inox dispostos de forma concêntrica, à mesma distância entre si. Com este reator foram executados variados testes, com diferentes efluentes, que permitiram obter resultados operacionais de otimização de funcionamento, tendo em vista a remoção de poluentes. O estudo financeiro associado permitiu concluir que a eletrooxidação é significativamente mais económica que o tratamento físico-químico, nas condições operacionais e para os efluentes tratados. Relativamente ao Acompanhamento e Gestão de ETAR’s (Capítulo 4) foi possível verificar que todos os casos em estudo apresentam uma boa eficiência de remoção de matéria orgânica, permitindo a descarga do seu efluente com uma carga poluente que cumpre com os requisitos legais de descarga em meio hídrico.

Majorantes para a ordem de subgrafos induzidos k-regulares

Muitos dos problemas de otimização em grafos reduzem-se à determinação de um subconjunto de vértices de cardinalidade máxima que induza um subgrafo k-regular. Uma vez que a determinação da ordem de um subgrafo induzido k-regular de maior ordem é, em geral, um problema NP-difícil, são deduzidos novos majorantes, a determinar em tempo polinomial, que em muitos casos constituam boas aproximações das respetivas soluções ótimas. Introduzem-se majorantes espetrais usando uma abordagem baseada em técnicas de programação convexa e estabelecem-se condições necessárias e suficientes para que sejam atingidos. Adicionalmente, introduzem-se majorantes baseados no espetro das matrizes de adjacência, laplaciana e laplaciana sem sinal. É ainda apresentado um algoritmo não polinomial para a determinação de umsubconjunto de vértices de umgrafo que induz umsubgrafo k-regular de ordem máxima para uma classe particular de grafos. Finalmente, faz-se um estudo computacional comparativo com vários majorantes e apresentam-se algumas conclusões.

Network virtualisation from an operator perspective

Network virtualisation is seen as a promising approach to overcome the so-called “Internet impasse” and bring innovation back into the Internet, by allowing easier migration towards novel networking approaches as well as the coexistence of complementary network architectures on a shared infrastructure in a commercial context. Recently, the interest from the operators and mainstream industry in network virtualisation has grown quite significantly, as the potential benefits of virtualisation became clearer, both from an economical and an operational point of view. In the beginning, the concept has been mainly a research topic and has been materialized in small-scale testbeds and research network environments. This PhD Thesis aims to provide the network operator with a set of mechanisms and algorithms capable of managing and controlling virtual networks. To this end, we propose a framework that aims to allocate, monitor and control virtual resources in a centralized and efficient manner. In order to analyse the performance of the framework, we performed the implementation and evaluation on a small-scale testbed. To enable the operator to make an efficient allocation, in real-time, and on-demand, of virtual networks onto the substrate network, it is proposed a heuristic algorithm to perform the virtual network mapping. For the network operator to obtain the highest profit of the physical network, it is also proposed a mathematical formulation that aims to maximize the number of allocated virtual networks onto the physical network. Since the power consumption of the physical network is very significant in the operating costs, it is important to make the allocation of virtual networks in fewer physical resources and onto physical resources already active. To address this challenge, we propose a mathematical formulation that aims to minimize the energy consumption of the physical network without affecting the efficiency of the allocation of virtual networks. To minimize fragmentation of the physical network while increasing the revenue of the operator, it is extended the initial formulation to contemplate the re-optimization of previously mapped virtual networks, so that the operator has a better use of its physical infrastructure. It is also necessary to address the migration of virtual networks, either for reasons of load balancing or for reasons of imminent failure of physical resources, without affecting the proper functioning of the virtual network. To this end, we propose a method based on cloning techniques to perform the migration of virtual networks across the physical infrastructure, transparently, and without affecting the virtual network. In order to assess the resilience of virtual networks to physical network failures, while obtaining the optimal solution for the migration of virtual networks in case of imminent failure of physical resources, the mathematical formulation is extended to minimize the number of nodes migrated and the relocation of virtual links. In comparison with our optimization proposals, we found out that existing heuristics for mapping virtual networks have a poor performance. We also found that it is possible to minimize the energy consumption without penalizing the efficient allocation. By applying the re-optimization on the virtual networks, it has been shown that it is possible to obtain more free resources as well as having the physical resources better balanced. Finally, it was shown that virtual networks are quite resilient to failures on the physical network.

Ressonância magnética em estudos de produção de fala

Estudar os mecanismos subjacentes à produção de fala é uma tarefa complexa e exigente, requerendo a obtenção de dados mediante a utilização de variadas técnicas, onde se incluem algumas modalidades imagiológicas. De entre estas, a Ressonância Magnética (RM) tem ganho algum destaque, nos últimos anos, posicionando-se como uma das mais promissoras no domínio da produção de fala. Um importante contributo deste trabalho prende-se com a otimização e implementação de protocolos (RM) e proposta de estratégias de processamento de imagem ajustados aos requisitos da produção de fala, em geral, e às especificidades dos diferentes sons. Para além disso, motivados pela escassez de dados para o Português Europeu (PE), constitui-se como objetivo a obtenção de dados articulatórios que permitam complementar informação já existente e clarificar algumas questões relativas à produção dos sons do PE (nomeadamente, consoantes laterais e vogais nasais). Assim, para as consoantes laterais foram obtidas imagens RM (2D e 3D), através de produções sustidas, com recurso a uma sequência Eco de Gradiente (EG) rápida (3D VIBE), no plano sagital, englobando todo o trato vocal. O corpus, adquirido por sete falantes, contemplou diferentes posições silábicas e contextos vocálicos. Para as vogais nasais, foram adquiridas, em três falantes, imagens em tempo real com uma sequência EG - Spoiled (TurboFLASH), nos planos sagital e coronal, obtendo-se uma resolução temporal de 72 ms (14 frames/s). Foi efetuada aquisição sincronizada das imagens com o sinal acústico mediante utilização de um microfone ótico. Para o processamento e análise de imagem foram utilizados vários algoritmos semiautomáticos. O tratamento e análise dos dados permitiu efetuar uma descrição articulatória das consoantes laterais, ancorada em dados qualitativos (e.g., visualizações 3D, comparação de contornos) e quantitativos que incluem áreas, funções de área do trato vocal, extensão e área das passagens laterais, avaliação de efeitos contextuais e posicionais, etc. No que respeita à velarização da lateral alveolar /l/, os resultados apontam para um /l/ velarizado independentemente da sua posição silábica. Relativamente ao /L/, em relação ao qual a informação disponível era escassa, foi possível verificar que a sua articulação é bastante mais anteriorizada do que tradicionalmente descrito e também mais extensa do que a da lateral alveolar. A resolução temporal de 72 ms conseguida com as aquisições de RM em tempo real, revelou-se adequada para o estudo das características dinâmicas das vogais nasais, nomeadamente, aspetos como a duração do gesto velar, gesto oral, coordenação entre gestos, etc. complementando e corroborando resultados, já existentes para o PE, obtidos com recurso a outras técnicas instrumentais. Para além disso, foram obtidos novos dados de produção relevantes para melhor compreensão da nasalidade (variação área nasal/oral no tempo, proporção nasal/oral). Neste estudo, fica patente a versatilidade e potencial da RM para o estudo da produção de fala, com contributos claros e importantes para um melhor conhecimento da articulação do Português, para a evolução de modelos de síntese de voz, de base articulatória, e para aplicação futura em áreas mais clínicas (e.g., perturbações da fala).

Brazilian savanna forest : conservation, medicinal reservoir and bioprospecting

This study aimed to analyse the Brazilian savanna forest from a Legal Reserve (LR) area from a perspective of conservation, reservoir of organic carbon and medicinal biomass for a prospective use of native medicinal plants. An ethnobotanical and ethnopharmacological survey was carried out close to a community settled in the rural area in the south of Tocantins, being selected 9 of the most cited species (cajuí- Anacardium othonianum; inharé-Brosimum gaudichaudii; jatobá-Hymenaeae courbaril; jenipapo-Genipa americana, aroeira-Myracrodruon urundeuva; negramina-Siparuna guianensis; barbatimão- Stryphnodendron obovatum; assa peixe-Vernonia brasiliana, embaúba-Cecropia pachystachya). Crude foliar extracts were subjected to a preliminary phytochemical prospection and triage of secondary metabolites with antimicrobial activity of potential interest in health and familiar agriculture. Phenolic compounds, terpenes and flavonoids were detected in the extracts of most species, which suggests the presence of antimicrobial, antioxidant and anti-insect activities. It was evident the need to better know the LR as a reservoir of medicinal biomass in an area under ecological tension where 35% (610ha) of the property is LR and should be protected by law. Therefore, a forest inventory of live woody species was performed using the allometric or indirect method. This identified a rare remnant of Semidecidual Seasonal Forest amidst the largest world savannah, the Cerrado biome. An analysis of the forest average productivity per basal area (m².ha), aerial live biomass (ton.ha-1) and carbon stock was carried out. The forest fragment was considered relatively rich in species and diversity, although showing signs of disturbance and dominance by a few species. Its horizontal structure suggests biotic regeneration conditions. It is an important reservoir of medicinal plants. Of the families (57.5%) presenting medicinal species, 19 from a total of 33 are represented in the area and contain 44% (27) of the total species (61) and 63% (432) of the total individuals catalogued. Medicinal species have ecological importance for the equilibrium of the local flora and represent 80% of the 10 species with higher Importance Value Index (IVI): Tetragastris altissima, Chrysophyllum marginatum, Oenocarpus distichus, Sclerolobium paniculatum, Simarouba versicolor, Alibertia macrophylla, Siparuna guianensis, Maprounea guianensis, Licania parvifolia e Physocalymma scaberrimum. Medicinal productivity was high for this type of phytophysionomy: 183,2 ton. ha-1 of biomass and 91,51 ton. ha-1 of carbon representing 66% of the total biomass and carbon of this Cerrado forest. From this stage S. guianensis (Siparunaceae) was selected for performing bioassays in order to verify its biological activity against microorganisms of health and agricultural relevance. This is a native aromatic medicinal plant recommended as priority for conservation, with local popular medicinal validation and availability of medicinal feedstock (3300 Kg.ha-1), with the foliar fraction giving 38Kg/ha of crude extract and 5L/ha of essential oil. Foliar crude extracts and essential oil were obtained and tested in vitro using a disk diffusion bioassay. Different concentrations of these natural products were tested against gram-positive bacteria (Staphylococcus aureus ATCC 29213), gram-negative bacteria (Escherichia coli ATCC 25922 and ATCC 35218; Pseudomonas aeruginosa ATCC 10145) and fungi (Candida albicans ATCC 6258 e Fusarium oxysporum). The essential oil inhibited the growth of S. aureus in its crude concentration (380μg.mL-1), as well as diluted to half (190μg.mL-1) and a quarter strength (95μg.mL-1). It’s likely that such action is due to sesquiterpenes major components, such as bisabolol and bisabolene (10.35%), measured by gas chromatography (GC-MS, GC-FID). Extracts did not exhibit any antimicrobial activity against the microorganisms tested. The native medicinal plants prospective market is an alternative that favours the conservation of biodiversity while generating benefits for the development of sustainable family productive activities within local ecosystems instead of the current inappropriate uses. This strengthens conservation policies of Legal Reserve in rural settlements and is in agreement with public policy on global warming and climate changes.

Metabolic signature of lung cancer: a metabolomic study of human tissues and biofluids

This thesis reports the application of metabolomics to human tissues and biofluids (blood plasma and urine) to unveil the metabolic signature of primary lung cancer. In Chapter 1, a brief introduction on lung cancer epidemiology and pathogenesis, together with a review of the main metabolic dysregulations known to be associated with cancer, is presented. The metabolomics approach is also described, addressing the analytical and statistical methods employed, as well as the current state of the art on its application to clinical lung cancer studies. Chapter 2 provides the experimental details of this work, in regard to the subjects enrolled, sample collection and analysis, and data processing. In Chapter 3, the metabolic characterization of intact lung tissues (from 56 patients) by proton High Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is described. After careful assessment of acquisition conditions and thorough spectral assignment (over 50 metabolites identified), the metabolic profiles of tumour and adjacent control tissues were compared through multivariate analysis. The two tissue classes could be discriminated with 97% accuracy, with 13 metabolites significantly accounting for this discrimination: glucose and acetate (depleted in tumours), together with lactate, alanine, glutamate, GSH, taurine, creatine, phosphocholine, glycerophosphocholine, phosphoethanolamine, uracil nucleotides and peptides (increased in tumours). Some of these variations corroborated typical features of cancer metabolism (e.g., upregulated glycolysis and glutaminolysis), while others suggested less known pathways (e.g., antioxidant protection, protein degradation) to play important roles. Another major and novel finding described in this chapter was the dependence of this metabolic signature on tumour histological subtype. While main alterations in adenocarcinomas (AdC) related to phospholipid and protein metabolisms, squamous cell carcinomas (SqCC) were found to have stronger glycolytic and glutaminolytic profiles, making it possible to build a valid classification model to discriminate these two subtypes. Chapter 4 reports the NMR metabolomic study of blood plasma from over 100 patients and near 100 healthy controls, the multivariate model built having afforded a classification rate of 87%. The two groups were found to differ significantly in the levels of lactate, pyruvate, acetoacetate, LDL+VLDL lipoproteins and glycoproteins (increased in patients), together with glutamine, histidine, valine, methanol, HDL lipoproteins and two unassigned compounds (decreased in patients). Interestingly, these variations were detected from initial disease stages and the magnitude of some of them depended on the histological type, although not allowing AdC vs. SqCC discrimination. Moreover, it is shown in this chapter that age mismatch between control and cancer groups could not be ruled out as a possible confounding factor, and exploratory external validation afforded a classification rate of 85%. The NMR profiling of urine from lung cancer patients and healthy controls is presented in Chapter 5. Compared to plasma, the classification model built with urinary profiles resulted in a superior classification rate (97%). After careful assessment of possible bias from gender, age and smoking habits, a set of 19 metabolites was proposed to be cancer-related (out of which 3 were unknowns and 6 were partially identified as N-acetylated metabolites). As for plasma, these variations were detected regardless of disease stage and showed some dependency on histological subtype, the AdC vs. SqCC model built showing modest predictive power. In addition, preliminary external validation of the urine-based classification model afforded 100% sensitivity and 90% specificity, which are exciting results in terms of potential for future clinical application. Chapter 6 describes the analysis of urine from a subset of patients by a different profiling technique, namely, Ultra-Performance Liquid Chromatography coupled to Mass Spectrometry (UPLC-MS). Although the identification of discriminant metabolites was very limited, multivariate models showed high classification rate and predictive power, thus reinforcing the value of urine in the context of lung cancer diagnosis. Finally, the main conclusions of this thesis are presented in Chapter 7, highlighting the potential of integrated metabolomics of tissues and biofluids to improve current understanding of lung cancer altered metabolism and to reveal new marker profiles with diagnostic value.