Study of multiferroic materials

The present PhD work aims the research and development of materials that exhibit multiferroic properties, in particular having a significant interaction between ferromagnetism and ferroelectricity; either directly within an intrinsic single phase or by combining extrinsic materials, achieving the coupling of properties through mechanic phenomena of the respective magnetostriction and piezoelectricity. These hybrid properties will allow the cross modification of magnetic and electric polarization states by the application of cross external magnetic and/or electric fields, giving way to a vast area for scientific investigation and potential technological applications in a new generation of electronic devices, such as computer memories, signal processing, transducers, sensors, etc. Initial experimental work consisted in chemical synthesis of nano powders oxides by urea pyrolysis method: A series of ceramic bulk composites with potential multiferroic properties comprised: of LuMnO3 with La0.7Sr0.3MnO3 and BaTiO3 with La0.7Ba0.3MnO3; and a series based on the intrinsic multiferroic LuMn1-zO3 phase modified with of Manganese vacancies. The acquisition of a new magnetron RF sputtering deposition system, in the Physics Department of Aveiro University, contributed to the proposal of an analogous experimental study in multiferroic thin films and multilayer samples. Besides the operational debut of this equipment several technical upgrades were completed like: the design and construction of the heater electrical contacts; specific shutters and supports for the magnetrons and for the substrate holder and; the addition of mass flow controllers, which allowed the introduction of N2 or O2 active atmosphere in the chamber; and the addition of a second RF generator, enabling co-deposition of different targets. Base study of the deposition conditions and resulting thin films characteristics in different substrates was made from an extensive list of targets. Particular attention was given to thin film deposition of magnetic phases La1-xSrxMnO3, La1-xBaxMnO3 and Ni2+x-yMn1-xGa1+y alloy, from the respective targets: La0.7Sr0.3MnO3, La0.7Ba0.3MnO3; and NiGa with NiMn. Main structural characterization of samples was performed by conventional and high resolution X-Ray Diffraction (XRD); chemical composition was determined by Electron Dispersion Spectroscopy (EDS); magnetization measurements recur to a Vibrating Sample Magnetometer (VSM) prototype; and surface probing (SPM) using Magnetic-Force (MFM) and Piezo-Response (PFM) Microscopy. Results clearly show that the composite bulk samples (LuM+LSM and BTO+LBM) feat the intended quality objectives in terms of phase composition and purity, having spurious contents below 0.5 %. SEM images confirm compact grain packaging and size distribution around the 50 nm scale. Electric conductivity, magnetization intensity and magneto impedance spreading response are coherent with the relative amount of magnetic phase in the sample. The existence of coupling between the functional phases is confirmed by the Magnetoelectric effect measurements of the sample “78%LuM+22%LSM” reaching 300% of electric response for 1 T at 100 kHz; while in the “78%BTO+22%LBM” sample the structural transitions of the magnetic phase at ~350 K result in a inversion of ME coefficient the behavior. A functional Magneto-Resistance measurement system was assembled from the concept stage until the, development and operational status; it enabled to test samples from 77 to 350 K, under an applied magnetic field up to 1 Tesla with 360º horizontal rotation; this system was also designed to measure Hall effect and has the potential to be further upgraded. Under collaboration protocols established with national and international institutions, complementary courses and sample characterization studies were performed using Magneto-Resistance (MR), Magneto-Impedance (MZ) and Magneto-Electric (ME) measurements; Raman and X-ray Photoelectron Spectroscopy (XPS); SQUID and VSM magnetization; Scanning Electron Microscopy (SEM) and Rutherford Back Scattering (RBS); Scan Probe Microscopy (SPM) with Band Excitation Probe Spectroscopy (BEPS); Neutron Powder Diffraction (NPD) and Perturbed Angular Correlations (PAC). Additional collaboration in research projects outside the scope of multiferroic materials provided further experience in sample preparation and characterization techniques, namely VSM and XPS measurements were performed in cubane molecular complex compounds and enable to identify the oxidation state of the integrating cluster of Ru ions; also, XRD and EDS/SEM analysis of the acquired targets and substrates implied the devolution of some items not in conformity with the specifications. Direct cooperation with parallel research projects regarding multiferroic materials, enable the assess to supplementary samples, namely a preliminary series of nanopowder Y1-x-yCaxØyMn1O3 and of Eu0.8Y0.2MnO3, a series of micropowder composites of LuMnO3 with La0.625Sr0.375MnO3 and of BaTiO3 with hexagonal ferrites; mono and polycrystalline samples of Pr1-xCaxMnO3, La1-xSrxMnO3 and La1-xCaxMnO3.

Ensino da física em cursos de engenharia: percursos colaborativos no ensino superior

A presente investigação insere-se no domínio científico da Didáctica, em particular no da Didáctica da Física no Ensino Superior. Pretende-se, com este trabalho, contribuir para o desenvolvimento do conhecimento Didáctico, nomeadamente sobre o ensino e a aprendizagem da Física no Ensino Superior e, ainda, sobre o trabalho colaborativo entre investigadores em Didáctica e professores da área das Ciências e Engenharias do Ensino Superior. O estudo empírico desenvolvido neste trabalho é constituído por duas partes, designadas por estudo A e estudo B. No estudo A analisa-se o impacto da implementação, em sala de aula, de estratégias de aprendizagem activa num contexto colaborativo entre investigadora e professora. Fá-lo através de um percurso metodológico de investigação-acção, na qual a investigadora actua como consultora. Utilizaram-se diferentes fontes e instrumentos na recolha de informação, nomeadamente notas de campo da investigadora, questionários e entrevistas a estudantes e entrevista à professora colaboradora. Foram implementadas estratégias identificadas na literatura como promotoras de aprendizagem activa dos estudantes, nomeadamente perguntas conceptuais; folhas de dúvidas; feedback; trabalho de grupo com e sem rotação de tarefas; trabalhos para casa e apresentação oral. Os resultados obtidos evidenciam que os estudantes sentiram interesse pela unidade curricular, pois compreenderam a sua utilidade no âmbito do curso que frequentavam, apreciaram positivamente as estratégias implementadas e, segundo a opinião deles, estas contribuíram para a sua aprendizagem. No estudo B procurou-se compreender a colaboração entre investigadores em Didáctica e professores do Ensino Superior, no contexto da Universidade de Aveiro. Este estudo evidenciou que é possível implementar estratégias inovadoras de ensino através de processos de colaboração entre investigadores em Didáctica e professores. Este estudo, de carácter exploratório, foi realizado através de entrevistas aos investigadores e aos professores que com eles colaboraram, procurando melhorar a qualidade das suas práticas de ensino. Através deste estudo chegou-se à conceptualização de uma proposta de Colaboração Disciplinar, uma colaboração entre investigadores em Didáctica e professores do Ensino Superior, em que os investigadores têm formação base nas unidades curriculares onde irão intervir. Esta proposta procura potenciar uma forma de trabalhar problemas complexos, como por exemplo o processo de ensino e aprendizagem, o desenvolvimento profissional dos professores, a articulação entre a investigação em Didáctica e a prática. As principais vantagens identificadas na Colaboração Disciplinar são: a proximidade disciplinar entre o investigador e o professor; a eficácia nas sugestões proporcionadas; o aumento da segurança do professor na implementação das sugestões; o desenvolvimento profissional contextualizado; a aproximação da investigação à prática. Os contributos deste estudo colocam-se a três níveis: ao nível pessoal e profissional da investigadora e da professora colaboradora; ao nível do desenvolvimento de conhecimento na referida área (no caso do primeiro estudo empírico desenvolvido), na medida em que apesar da especificidade do contexto onde o estudo ocorreu – na unidade curricular Elementos de Física do primeiro ano, primeiro semestre de diferentes cursos de Engenharia da Universidade de Aveiro, nos anos lectivos de 2007/08 e 2008/09 – considera-se que este trouxe ensinamentos que, adaptados a outros contextos, podem influenciar outros estudos e práticas; e ao nível do desenvolvimento de conhecimento sobre como dinamizar e potenciar colaborações entre investigadores da área da Didáctica e professores do Ensino Superior.

Híbridos orgânicos-inorgânicos para aplicações de baixo custo em óptica integrada

O objectivo desta tese é a utilização de materiais híbridos orgânicos-inorgânicos, designados por di-ureiasis modificados pela adição de tetra-propóxido de zircónio (Zr(i-OPr)4) estabilizado com ácido metacrílico (CH2=C(CH3)COOH), obtidos pela via sol-gel, para aplicações em dispositivos ópticos integrados de baixo custo. A estrutura local dos di-ureiasis com diferentes concentrações de propóxido de zircónio (20 a 80 % mol) foi estudada por difracção de raios-X, espalhamento de raios X a baixos ângulos, microscopia de força atómica, ressonância magnética nuclear dos núcleos dos átomos de 29Si e 13C, espectroscopia no infravermelho por transformada de Fourier, espectroscopia de Raman por transformada de Fourier e termogravimetria. A influência dos parâmetros de síntese, concentração de tetra propóxido de zircónio e rácio tetra propóxido de zircónio: ácido metacrilico na estrutura e propriedades das amostras em monólito e filmes finos (depositados pela técnica de deposição por rotação do substrato) foram avaliadas, permitindo obter amostras transparentes, fotopolimerizáveis e estáveis termicamente até aos 100 ºC. Foram determinadas as propriedades dos guias planares em substratos de vidro borosilicato e silício oxidado (1de refracção (1,4774-1,5149 a 1550 nm), espessura (6-10 μm), perdas por propagação (~1,5 dB/cm) e rugosidade (~5,0 nm). Posteriormente o processo de escrita laser directa permitiu a gravação de dispositivos para óptica integrada de que são exemplos: guias de onda em canal com diâmetros modais de 2,5 μm (monomodo) e de 15-20 μm (multimodo) e contraste de valor do índice de refracção de 2x10-3; divisores de potência óptica com geometria em Y com rácios de divisão de ~50:50; filtros ópticos baseados em redes de Bragg com valores de rejeição do sinal óptico de 10 dB (monólitos) e 24 dB (filmes finos); cavidades ópticas do tipo Fabry-Perot com valores de rejeição de ~5 dB e gama espectral livre de 16,5 e 35,5 GHz. A actuação termo-óptica de uma estrutura do tipo Mach-Zhender simétrica conduziu a uma atenuação do sinal óptico de 7,5 dB.

Characterization of water-soluble organic matter from urban aerosols

Water-soluble organic matter (WSOM) from atmospheric particles comprises a complex array of molecular structures that play an important role on the physic-chemical properties of atmospheric particles and, therefore, are linked to several global-relevant atmospheric processes which impact the climate and public health. Due to the large variety of sources and formation processes, adequate knowledge on WSOM composition and its effects on the properties of atmospheric aerosol are still limited. Therefore, this thesis aims at providing new insights on the molecular composition of WSOM from fine atmospheric aerosols typical of an urban area (Aveiro, Portugal). In a first step, adsorption phenomena of semivolatile organic compounds on quartz fibre filters employed in the collection of atmospheric aerosols were assessed. Afterwards, atmospheric aerosol samples were collected during fifteen months, on a weekly basis. A mass balance of aerosol samples was performed in order to set the relative contribution of elemental carbon, WSOM and water-insoluble organic matter to the aerosol mass collected at the urban area of Aveiro, with a special focus on the assessment of the influence of different meteorological conditions. In order to assess the chemical complexity of the WSOM from urban aerosols, their structural characteristics were studied by means of Fourier transform infrared infrared - Attenuated Total Reflectance (FTIR-ATR) and solid-state cross polarization with magic angle spinning 13C nuclear magnetic resonance (CPMAS 13C NMR) spectroscopies, as well as their elemental composition. The structural characterization of aerosol WSOM samples collected in the urban area highlighted a highly complex mixture of functional groups. It was concluded that aliphatic and aromatic structures, hydroxyl groups and carboxyl groups are characteristic to all samples. The semi-quantitative assessment of the CPMAS 13C NMR data showed different distributions of the various functional groups between the aerosol samples collected at different seasons. Moreover, the presence of signals typical of lignin-derived structures in both CPMAS 13C NMR and FTIR-ATR spectra of the WSOM samples from the colder seasons, highlights the major contribution of biomass burning processes in domestic fireplaces, during low temperature conditions, into the bulk chemical properties of WSOM from urban aerosols. A comprehensive two-dimensional liquid chromatography (LC x LC) method, on-line coupled to a diode array, fluorescence, and evaporative light scattering detectors, was employed for resolving the chemical heterogeneity of the aerosol WSOM samples and, simultaneously, to map the hydrophobicity versus the molecular weight distribution of the samples. The LC x LC method employed a mixed-mode hydrophilic interaction column operating under aqueous reversed phase mode in the first dimension, and a size-exclusion column in the second dimension, which was found to be useful for separating the aerosol WSOM samples into various fractions with distinct molecular weight and hydrophobic features. The estimative of the average molecular weight (Mw) distribution of the urban aerosol WSOM samples ranged from 48 to 942 Da and from 45 to 1241 Da in terms of UV absorption and fluorescence detection, respectively. Findings suggest that smaller Mw group fractions seem to be related to a more hydrophobic nature.

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.

Electromechanical properties of engineered lead free potassium sodium niobate based materials

K0.5Na0.5NbO3 (KNN), is the most promising lead free material for substituting lead zirconate titanate (PZT) which is still the market leader used for sensors and actuators. To make KNN a real competitor, it is necessary to understand and to improve its properties. This goal is pursued in the present work via different approaches aiming to study KNN intrinsic properties and then to identify appropriate strategies like doping and texturing for designing better KNN materials for an intended application. Hence, polycrystalline KNN ceramics (undoped, non-stoichiometric; NST and doped), high-quality KNN single crystals and textured KNN based ceramics were successfully synthesized and characterized in this work. Polycrystalline undoped, non-stoichiometric (NST) and Mn doped KNN ceramics were prepared by conventional ceramic processing. Structure, microstructure and electrical properties were measured. It was observed that the window for mono-phasic compositions was very narrow for both NST ceramics and Mn doped ceramics. For NST ceramics the variation of A/B ratio influenced the polarization (P-E) hysteresis loop and better piezoelectric and dielectric responses could be found for small stoichiometry deviations (A/B = 0.97). Regarding Mn doping, as compared to undoped KNN which showed leaky polarization (P-E) hysteresis loops, B-site Mn doped ceramics showed a well saturated, less-leaky hysteresis loop and a significant properties improvement. Impedance spectroscopy was used to assess the role of Mn and a relation between charge transport – defects and ferroelectric response in K0.5Na0.5NbO3 (KNN) and Mn doped KNN ceramics could be established. At room temperature the conduction in KNN which is associated with holes transport is suppressed by Mn doping. Hence Mn addition increases the resistivity of the ceramic, which proved to be very helpful for improving the saturation of the P-E loop. At high temperatures the conduction is dominated by the motion of ionized oxygen vacancies whose concentration increases with Mn doping. Single crystals of potassium sodium niobate (KNN) were grown by a modified high temperature flux method. A boron-modified flux was used to obtain the crystals at a relatively low temperature. XRD, EDS and ICP analysis proved the chemical and crystallographic quality of the crystals. The grown KNN crystals exhibit higher dielectric permittivity (29,100) at the tetragonal-to-cubic phase transition temperature, higher remnant polarization (19.4 μC/cm2) and piezoelectric coefficient (160 pC/N) when compared with the standard KNN ceramics. KNN single crystals domain structure was characterized for the first time by piezoforce response microscopy. It could be observed that <001> - oriented potassium sodium niobate (KNN) single crystals reveal a long range ordered domain pattern of parallel 180° domains with zig-zag 90° domains. From the comparison of KNN Single crystals to ceramics, It is argued that the presence in KNN single crystal (and absence in KNN ceramics) of such a long range order specific domain pattern that is its fingerprint accounts for the improved properties of single crystals. These results have broad implications for the expanded use of KNN materials, by establishing a relation between the domain patterns and the dielectric and ferroelectric response of single crystals and ceramics and by indicating ways of achieving maximised properties in KNN materials. Polarized Raman analysis of ferroelectric potassium sodium niobate (K0.5Na0.5)NbO3 (KNN) single crystals was performed. For the first time, an evidence is provided that supports the assignment of KNN single crystals structure to the monoclinic symmetry at room temperature. Intensities of A′, A″ and mixed A′+A″ phonons have been theoretically calculated and compared with the experimental data in dependence of crystal rotation, which allowed the precise determination of the Raman tensor coefficients for (non-leaking) modes in monoclinic KNN. In relation to the previous literature, this study clarifies that assigning monoclinic phase is more suitable than the orthorhombic one. In addition, this study is the basis for non-destructive assessments of domain distribution by Raman spectroscopy in KNN-based lead-free ferroelectrics with complex structures. Searching a deeper understanding of the electrical behaviour of both KNN single crystal and polycrystalline materials for the sake of designing optimized KNN materials, a comparative study at the level of charge transport and point defects was carried out by impedance spectroscopy. KNN single crystals showed lower conductivity than polycrystals from room temperature up to 200 ºC, but above this temperature polycrystalline KNN displays lower conductivity. The low temperature (T < 200 ºC) behaviour reflects the different processing conditions of both ceramics and single crystals, which account for less defects prone to charge transport in the case of single crystals. As temperature increases (T > 200 ºC) single crystals become more conductive than polycrystalline samples, in which grain boundaries act as barriers to charge transport. For even higher temperatures the conductivity difference between both is increased due to the contribution of ionic conduction in single crystals. Indeed the values of activation energy calculated to the high temperature range (T > 300 ºC) were 1.60 and 0.97 eV, confirming the charge transport due to ionic conduction and ionized oxygen vacancies in single crystals and polycrystalline KNN, respectively. It is suggested that single crystals with low defects content and improved electromechanical properties could be a better choice for room temperature applications, though at high temperatures less conductive ceramics may be the choice, depending on the targeted use. Aiming at engineering the properties of KNN polycrystals towards the performance of single crystals, the preparation and properties study of (001) – oriented (K0.5Na0.5)0.98Li0.02NbO3 (KNNL) ceramics obtained by templated grain growth (TGG) using KNN single crystals as templates was undertaken. The choice of KNN single crystals templates is related with their better properties and to their unique domain structure which were envisaged as a tool for templating better properties in KNN ceramics too. X-ray diffraction analysis revealed for the templated ceramics a monoclinic structure at room temperature and a Lotgering factor (f) of 40% which confirmed texture development. These textured ceramics exhibit a long range ordered domain pattern consisting of 90º and 180º domains, similar to the one observed in the single crystals. Enhanced dielectric (13017 at TC), ferroelectric (2Pr = 42.8 μC/cm2) and piezoelectric (d33 = 280 pC/N) properties are observed for textured KNNL ceramics as compared to the randomly oriented ones. This behaviour is suggested to be due to the long range ordered domain patterns observed in the textured ceramics. The obtained results as compared with the data previously reported on texture KNN based ceramics confirm that superior properties were found due to ordered repeated domain pattern. This study provides an useful approach towards properties improvement of KNN-based piezoelectric ceramics. Overall, the present results bring a significant contribution to the pool of knowledge on the properties of sodium potassium niobate materials: a relation between the domain patterns and di-, ferro-, and piezo-electric response of single crystals and ceramics was demonstrated and ways of engineering maximised properties in KNN materials, for example by texturing were established. This contribution is envisaged to have broad implications for the expanded use of KNN over the alternative lead-based materials.

Evaluation of the matabolic response of osteosarcoma cells to conventional and new anticancer drugs by NMR metabolomics

The main scope of this work was to evaluate the metabolic effects of anticancer agents (three conventional and one new) in osteosarcoma (OS) cells and osteoblasts, by measuring alterations in the metabolic profile of cells by nuclear magnetic resonance (NMR) spectroscopy metabolomics. Chapter 1 gives a theoretical framework of this work, beginning with the main metabolic characteristics that globally describe cancer as well as the families and mechanisms of action of drugs used in chemotherapy. The drugs used nowadays to treat OS are also presented, together with the Palladium(II) complex with spermine, Pd2Spm, potentially active against cancer. Then, the global strategy for cell metabolomics is explained and the state of the art of metabolomic studies that analyze the effect of anticancer agents in cells is presented. In Chapter 2, the fundamentals of the analytical techniques used in this work, namely for biological assays, NMR spectroscopy and multivariate and statistical analysis of the results are described. A detailed description of the experimental procedures adopted throughout this work is given in Chapter 3. The biological and analytical reproducibility of the metabolic profile of MG-63 cells by high resolution magic angle spinning (HRMAS) NMR is evaluated in Chapter 4. The metabolic impact of several factors (cellular integrity, spinning rate, temperature, time and acquisition parameters) on the 1H HRMAS NMR spectral profile and quality is analysed, enabling the definition of the best acquisition parameters for further experiments. The metabolic consequences of increasing number of passages in MG-63 cells as well as the duration of storage are also investigated. Chapter 5 describes the metabolic impact of drugs conventionally used in OS chemotherapy, through NMR metabolomics studies of lysed cells and aqueous extracts analysis. The results show that MG-63 cells treated with cisplatin (cDDP) undergo a strong up-regulation of lipid contents, alterations in phospholipid constituents (choline compounds) and biomarkers of DNA degradation, all associated with cell death by apoptosis. Cells exposed to doxorubicin (DOX) or methotrexate (MTX) showed much slighter metabolic changes, without any relevant alteration in lipid contents. However, metabolic changes associated with altered Krebs cycle, oxidative stress and nucleotides metabolism were detected and were tentatively interpreted at the light of the known mechanisms of action of these drugs. The metabolic impact of the exposure of MG-63 cells and osteoblasts to cDDP and the Pd2Spm complex is described in Chapter 6. Results show that, despite the ability of the two agents to bind DNA, the metabolic consequences that arise from exposure to them are distinct, namely in what concerns to variation in lipid contents (absent for Pd2Spm). Apoptosis detection assays showed that, differently from what was seen for MG-63 cells treated with cDDP, the decreased number of living cells upon exposure to Pd2Spm was not due to cell death by apoptosis or necrosis. Moreover, the latter agent induces more marked alterations in osteoblasts than in cancer cells, while the opposite seemed to occur upon cDDP exposure. Nevertheless, the results from MG-63 cells exposure to combination regimens with cDDP- or Pd2Spm-based cocktails, described in Chapter 7, revealed that, in combination, the two agents induce similar metabolic responses, arising from synergy mechanisms between the tested drugs. Finally, the main conclusions of this thesis are summarized in Chapter 8, and future perspectives in the light of this work are presented.

Characterisation of the cyclic behaviour of reinforced concrete elements with plain bars

Sismos recentes comprovam a elevada vulnerabilidade dos edifícios existentes de betão armado. A resposta das estruturas aos sismos é fortemente condicionada pelas características da aderência aço-betão, que exibe degradação das propriedades iniciais quando sujeitas a carregamentos cíclicos e alternados. Este fenómeno é ainda mais gravoso para elementos com armadura lisa, predominantes na maioria das estruturas construídas até à década de 70 nos países do sul da Europa. A prática corrente de conceção, dimensionamento e pormenorização das estruturas antigas leva a que tenham características de comportamento e níveis de segurança associados não compatíveis com as exigências atuais. Os estudos realizados sobre o comportamento cíclico de elementos estruturais de betão armado com armadura lisa são ainda insuficientes para a completa caracterização deste tipo de elementos. Esta tese visou a caraterização da relação tensão de aderência versus escorregamento para elementos estruturais com armadura lisa e o estudo da resposta cíclica de pilares e nós viga-pilar de betão armado com armadura lisa. Foram realizados dez séries de ensaios de arrancamento (nove monotónicos e um cíclico) em provetes com varões lisos. Os resultados destes ensaios permitiram propor novas expressões empíricas para a estimativa dos parâmetros usados num modelo disponível na literatura para representação da relação tensão de aderência versus escorregamento. É ainda proposto um novo modelo monotónico para a relação tensão de aderência versus escorregamento que representa melhor a resposta após a resistência máxima de aderência. Uma campanha de ensaios unidirecionais em pilares e nós viga-pilar foi também realizada com o objetivo principal de caracterizar o comportamento cíclico deste tipo de elementos. No total foram realizados oito ensaios em pilares, sete ensaios em nós viga-pilar interiores e seis ensaios em nós viga-pilar exteriores representativos de estruturas antigas de betão armado com armadura lisa. Os resultados experimentais permitiram avaliar a influência do escorregamento e estudar o mecanismo de corte em nós e a evolução dos danos para elementos com armadura lisa. Com base nos resultados experimentais foi proposta uma adaptação na expressão do Eurocódigo 8-3 para o cálculo da capacidade última de rotação de elementos com armadura lisa. Foi também desenvolvido um estudo paramétrico, com diferentes estratégias de modelação não linear, para a simulação da resposta de pilares considerando o escorregamento da armadura lisa. Por último, foi proposto um novo modelo simplificado trilinear para o aço que contempla o efeito do escorregamento da armadura lisa.