Calculus of variations on time scales and applications to economics

We consider some problems of the calculus of variations on time scales. On the beginning our attention is paid on two inverse extremal problems on arbitrary time scales. Firstly, using the Euler-Lagrange equation and the strengthened Legendre condition, we derive a general form for a variation functional that attains a local minimum at a given point of the vector space. Furthermore, we prove a necessary condition for a dynamic integro-differential equation to be an Euler-Lagrange equation. New and interesting results for the discrete and quantum calculus are obtained as particular cases. Afterwards, we prove Euler-Lagrange type equations and transversality conditions for generalized infinite horizon problems. Next we investigate the composition of a certain scalar function with delta and nabla integrals of a vector valued field. Euler-Lagrange equations in integral form, transversality conditions, and necessary optimality conditions for isoperimetric problems, on an arbitrary time scale, are proved. In the end, two main issues of application of time scales in economic, with interesting results, are presented. In the former case we consider a firm that wants to program its production and investment policies to reach a given production rate and to maximize its future market competitiveness. The model which describes firm activities is studied in two different ways: using classical discretizations; and applying discrete versions of our result on time scales. In the end we compare the cost functional values obtained from those two approaches. The latter problem is more complex and relates to rate of inflation, p, and rate of unemployment, u, which inflict a social loss. Using known relations between p, u, and the expected rate of inflation π, we rewrite the social loss function as a function of π. We present this model in the time scale framework and find an optimal path π that minimizes the total social loss over a given time interval.

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.

Characterisation of ZG16p, a unique mammalian lectin from pancreatic zymogen granules

The mechanisms of secretory granule biogenesis and regulated secretion of digestive enzymes in pancreatic acinar cells are still not well understood. To shed light on these processes, which are of biological and clinical importance (e.g., pancreatitis), a better molecular understanding of the components of the granule membrane, their functions and interactions is required. The application of proteomics has largely contributed to the identification of novel zymogen granule (ZG) proteins but was not yet accompanied by a better characterization of their functions. In this study we aimed at a) isolation and identification of novel membrane-associated ZG proteins; b) characterization of the biochemical properties and function of the secretory lectin ZG16p, a membrane-associated protein; c) exploring the potential of ZG16p as a new tool to label the endolysosomal compartment. First, we have performed a suborganellar proteomics approach by combining protein analysis by 2D-PAGE and identification by mass spectrometry, which has led to the identification of novel peripheral ZGM proteins with proteoglycan-binding properties (e.g., chymase, PpiB). Then, we have unveiled new molecular properties and (multiple) functions of the secretory lectin ZG16p. ZG16p is a unique mammalian lectin with glycan and proteoglycan binding properties. Here, I revealed for the first time that ZG16p is highly protease resistant by developing an enterokinase-digestion assay. In addition I revealed that ZG16p binds to a high molecular weight complex at the ZGM (which is also protease resistant) and forms highly stable dimers. In light of these findings I suggest that ZG16p is a key component of a predicted submembranous granule matrix attached to the luminal side of the ZGM that fulfils important functions during sorting and packaging of zymogens. ZG16p, may act as a linker between the matrix and aggregated zymogens due to dimer formation. Furthermore, ZG16p protease resistance might be of higher importance after secretion since it is known that ZG16p binds to pathogenic fungi in the gut. I have further investigated the role of ZG16p binding motifs in its targeting to ZG in AR42J cells, a pancreatic model system. Point mutations of the glycan and the proteoglycan binding motifs did not inhibit the targeting of ZG16p to ZG in AR42J cells. I have also demonstrated that when ZG16p is present in the cytoplasm it interacts with and modulates the endo-lysosomal compartment. Since it is known that impaired autophagy due to lysosomal malfunction is involved in the course of pancreatitis, a potential role of ZG16p in pancreatitis is discussed.

Design normal: memória e invisibilidade dos objectos

As últimas décadas têm sido caracterizadas por uma crescente indefinição do design, que refletindo um dia-a-dia cada vez mais complexo, não pode mais ser encarado como actividade fechada no projecto e acabada no produto. O seu universo aumentou e dispersou-se em mercados menores, alargando o seu alcance e sua importância, transformando-o em termo quantitativo e inflacionário. A crescente atenção de que é alvo dramatizou a sua relação com o consumo, o ruído nas prateleiras e a superficialidade da generalização de uma perspectiva do projecto focada nos new media, validando uma abordagem narcisista e de dispensa do diálogo com a indústria, tornaram-no sinónimo de especial. Este trabalho procura confirmar e refletir sobre a existência de um universo de produtos concretos e abordagens que de forma consciente partilham esta noção do contexto actual, em primeiro lugar, sugerindo caminhos alternativos e reacções resultantes da prática e discurso. Em segundo lugar procura analisar se tal reacção pode ser considerada como um movimento. Partindo de uma revisão bibliográfica, e de uma reflexão sobre um universo de produtos do dia-a-dia, procura-se, em terceiro lugar, interpretar e organizar as diversas formas e estratégias de rejeição da noção de design especial. Da procura de abordagens opostas a especial resulta uma ideia base de normal, normal sem ser banal, expressa na exposição Super Normal. Da extensão a um universo maior de produtos, reacções e autores, resulta a ideia de normal como um conceito mais abrangente, mas composto por conceitos menores, mais específicos, mais concretos e fáceis de identificar nos objectos. A organização e interpretação dessas abordagens resulta num triângulo de conceitos que constroem a noção de normal pela procura da evolução por recurso à memória e ao conhecimento, da invisibilidade pela integração e diluição do produto e projecto, e da liberdade como meio de adequação ao contexto actual. O livro resultante reflete uma abordagem definida de uma época, e não todo o panorama. A sistematização do conceito de normal a partir da segmentação em ideias menores, mais concretas e identificáveis nos produtos, procura proporcionar a consulta organizada de reacções ao contexto dominante actual, à ideia de especial, mas mais do que regras, procura fornecer um documento de reflexão a visitar no acto de projectar, seja como um todo, ou em partes.

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.

O interesse socioeducativo (e as dificuldades) de traduzir em português-espanhol

O Projeto que apresentamos insere-se nos estudos do Mestrado em Tradução Especializada dentro da vertente da Saúde e Ciências da Vida; é por isso que, partindo de um texto/suporte que visa promover uma alimentação saudável nas escolas (manual de referência difundido pelos Ministérios da Educação e Ciência e Ministério da Saúde de Portugal), procedemos à tradução (de português para espanhol) de um conteúdo que suscita, nos nossos dias, um grande interesse socioeducativo e cultural. É preciso destacar que o facto de ter nascido e vivido na Venezuela durante doze anos permitiu-me superar com êxito os meus estudos de espanhol na Licenciatura e no referido Mestrado; mas, ao mesmo tempo, tive que me adaptar, enquanto cidadã portuguesa, ao complexo e inacabado processo de ir interiorizando estas duas línguas – português/espanhol – tão próximas e no entanto com sistemas linguísticos bem distintos. Esta evidência encontra a sua maior justificação no grande capítulo dos erros (de forma e de significado) que consegui detetar e analisar graças à ajuda da minha professora orientadora, ao longo deste meu primeiro trabalho académico (texto traduzido para espanhol). Só agora, depois da minha primeira e “ingénua” tradução desse texto/manual, sou capaz de perceber com toda nitidez a dimensão do erro na atividade tradutora, assim como das suas consequências. Além desta importante reflexão, também o facto de elaborar este projeto permitiu-me abordar um aspeto linguístico da língua espanhola que me cativa pessoalmente (no que me diz respeito): o das variantes lexicais do castelhano nos países hispanofalantes. Não duvido em apontar um outro aspeto fundamental: o esforço de ter tido que corrigir minuciosamente e com rigor esta tarefa tradutora (com os seus respetivos comentários tradutológicos) converteu-se numa fonte de múltiplas satisfações pessoais; são aquelas que têm a ver com o cultivo de valores tais como o esforço, o espírito de superação, o exercício da responsabilidade e o (re)conhecimento da honestidade intelectual, entre outros.

Impact of exercise training on cancer-induced cardiac dysfunction

Cachexia is a complex syndrome characterized by severe weight loss frequently observed in cancer patients and associated with poor prognosis. Cancer cachexia is also related to modifications in cardiac muscle structure and metabolism leading to cardiac dysfunction. In order to better understand the cardiac remodeling induced by bladder cancer and the impact of exercise training after diagnosis on its regulation, we used an animal model of bladder cancer induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Healthy animals and previously BBN exposed animals were submitted to a training program in a treadmill at a speed of 20m/min, 60 min/day, 5 days/week during 13 weeks. At the end of the protocol, animals exposed to BBN presented a significant decrease of body weight, in comparison with control groups, supporting the presence of cancer cachexia. Morphological analysis of the cardiac muscle sections revealed the presence of fibrosis and a significant decrease of cardiomyocyte’s cross-sectional area, suggesting the occurrence of cardiac dysfunction associated with bladder cancer. These modifications were accompanied by heart metabolic remodeling characterized by a decreased fatty acid oxidation given by diminished levels of ETFDH and of complex II subunit  from the respiratory chain. Exercise training promoted an increment of connexin 43, a protein involved in cardioprotection, and of c-kit, a protein present in cardiac stem cells. These results suggest an improved heart regenerative capacity induced by exercise training. In conclusion, endurance training seems an attractive non-pharmacological therapeutic option for the management of cardiac dysfunction in cancer cachexia.