Caracterização, evolução e análise de suscetibilidade à ocorrência de instabilidades das arribas do arco Baleal - Bom Sucesso (Peniche-Óbidos)

Tese de mestrado em Geologia Aplicada, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2012A evolução do litoral de arriba é uma das grandes problemáticas no que diz respeito ao ordenamento da orla costeira. Distintos tipos e dimensões de movimentos de massa de vertente ocorrem como processos naturais, sendo mecanismos dinâmicos de elevada perigosidade, muitas das vezes implicando vidas humanas e/ou bens materiais. Com o intuito em determinar a possibilidade de futuras ocorrências, procedeu-se à avaliação da componente espacial dessa perigosidade, a suscetibilidade. Este estudo passa ainda por justificar recorrendo a metodologias numéricas, quais os fatores de predisposição que possuem maior peso na dinâmica destas arribas, quer sejam de natureza geológica (litologia, estrutura, …), geomorfológica (altura, declive, …) ou marítima (potência de onda). As etapas base deste trabalho passaram pela criação de uma cartografia temática de pormenor para os diferentes níveis de informação, obtidos a partir de ortofotomapas, topografia digital de terreno e reconhecimento de campo, além da inventariação dos recuos em arriba ocorridos ao longo dos últimos 60 anos, obtidos por análise comparativa de fotografia aérea. A avaliação de suscetibilidade foi efetuada estatisticamente recorrendo ao método bivariado do Valor Informativo, correlacionando cada classe de cada fator de predisposição com a existência ou não de movimento de vertente. Os modelos foram posteriormente validados através da Curva de Sucesso, justificando face a um modelo ideal qual a performance de cada um ou, conjunto dos fatores de predisposição, através do cálculo da Área Abaixo da Curva (AAC). Para o melhor modelo obtido utilizou-se a Curva Característica de Operação (ROC), determinando a probabilidade de ocorrência de instabilidade numa dada vertente. A avaliação do grau de suscetibilidade é portanto uma parte essencial dos estudos a efetuar em litorais de arriba, uma vez que possibilitará a identificação e delimitação de setores críticos, definindo faixas de risco e contribuindo para um mais eficiente ordenamento do uso e ocupação do território.The evolution of coastal cliffs is one of the greatest problems in coastal planning. Distinct types and sizes of mass movements occur as part of natural processes, and dynamic mechanisms that present high hazard/risk, often involving human life and/or property. In order to determine the possibility of future occurrences, was determined the susceptibility, or spatial hazard component. This work also intends to identify, by using numerical methods, the predisposing factors that have the most contribute to the dynamics of these cliffs, whether they are geological (lithology, structure, ...), geomorphology (high, slope, ...) or maritime (wave power). This work was based on a detailed thematic cartography of different information levels obtained from orthophotomaps, digital terrain topography and field work, besides the inventory of cliff retreats occurred over the last 60 years, obtained by aerial photography analysis. The susceptibility evaluation was performed using the bivariate statistical method, Information Value, correlating each class of each predisposing factor with the existence or non-existence of mass movement. The model was subsequently validated using the Success Curve, in which the performance of each set of predisposing factors was compared with an ideal model, by calculating the Area Under the Curve (AUC). For the best model obtained, the Receiver Operating Characteristic (ROC) was used to determine the probability of an instability occurring on a given cliff section. The susceptibility assessment is essential in the study of cliffed coasts because it is the base of the identification and delimitation of the most critical locations, and aids the definition of hazard areas, that, in turn contribute to a more efficient management of land use

Wine & research

Este trabalho pretende explorar as hipóteses que a tecnologia robótica pode trazer para a indústria da construção. Tendo em conta o uso de elementos robóticos em outras indústrias como a naval, a automóvel e a de componentes informáticos questiona-se aqui como estas tecnologias poderiam ser utilizadas para a indústria da construção e o que mudaria nesta. O trabalho inicia-se por uma alusão a outras indústrias e em como a tecnologia robótica veio alterar o método de produção e os produtos por ela produzidos. Seguidamente tecemos algumas considerações sobre os braço robóticos e sua utilização na Indústria assim como a utilização de drones para fins militares e civis. De modo a extrapolar o impacto destas tecnologias se usadas na construção de edifícios, estudaram-se também algumas técnicas de Fabricação Digital que,nos permitiram observar as alterações que a introdução da tecnologia operou na arquitetura e na construção. Apresentam-se ainda os casos de estudo atuais onde se utilizaram a construção com drones e com braços robóticos. De modo a compreender por um lado as vantagens e por outro a complexidade envolvida no processo de construção que se propõe desenvolveram- se a nível conceptual três experiências, nomeadamente a construção de uma torre com tijolos, de uma parede vertical simples, e de uma parede com uma geometria complexa. Para o desenvolvimento deste trabalho foi de vital importância os testemunhos diretos, através de entrevistas, a alguns dos protagonistas mais relevantes a nível mundial nesta área, os arquitectos Fabio Gramazio e Tobias Bonwetsch da ETH Zurique e o arquiteto José Pedro Sousa da FAUP.This piece is meant to explore the hipothesis of what robotics can bring to the construction industry. Having in mind the usage of robotic elements in other industries such as the naval, cars and of informatic components, the question of how could these technologies be applied to the construction industry, and what it would change, arises. This piece starts itself by alluding to other industries and how it has altered the production method and the products by it produced. Futhermore, a few considerations will be pondered on the robotic arms and its uses in the industry as much as the utilization of drones for military and civil purposes. In order to extrapolate the impact of these technologies if used in the construction of buildings, a few other techniques have been studied in the Digital Making that allowed us to observe the alterations that the introduction of this technology fathered in architecture and construction. A few present study cases where these techniques (robotic arms and drones) are applied, are also presented. In order to comprehend the advantages and complexity involved in the process of building that it is meant to serve, three experiments at conceptual level were developed, mainly the construction of a brick tower, a simple vertical wall, and another with a very intricate and complex geometry. In order to fulfill the development of this work, it was of extreme importance the direct testimonies that were gathered through interviews to a few of the world level protagonists in this area, the architects Fabio Gramazio and Tobias Bonwetsch of ETH Zurique, and the architect José Pedro Sousa from FAUP

Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth

One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype. Carbon monoxide (CO), one of the products of the cytoprotective molecule heme oxygenase-1 (HO-1) in cancer cells, has been implicated in carcinogenesis and therapeutic resistance. However, the functional contributions of CO and HO-1 to these processes are poorly defined. In human prostate cancers, we found that HO-1 was nuclear localized in malignant cells, with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes. Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy, with growth arrest and apoptosis induced in vivo in part throughmitotic catastrophe. CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption, free radical generation, and mitochondrial collapse. Collectively, our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics, ultimately resulting in metabolic exhaustion. ©2013 AACR

Development of new cationic liposome-based systems to promote gene delivery : physicochemical characterization and evaluation of biological activity

Tese de doutoramento em Bioquímica (Tecnologia Bioquímica) apresentada à Fac. de Ciências e Tecnologia da Universidade de Coimbr

DNA pre-condensation with an amino acid-based cationic amphiphile. A viable approach for liposome-based gene delivery

A study related to the development and characterization of a new gene delivery system was performed. The approach consists in both the pre-condensation of plasmid DNA with an arginine-based cationic surfactant, arginine-N-lauroyl amide dihydrochloride (ALA), which was found not to be toxic, and the incorporation of the blood protein transferrin (Tf) into the formulations.Two cationic liposome formulations were used, one composed of a mixture of dioleoyl trimethylammoniopropane and cholesterol (DOTAP:Chol) and the other a pH sensitive formulation constituted of DOTAP, Chol, Dioleoyl phosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS).Particles with different ALA/DNA and cationic lipid/DNA charge ratios were produced and a physicochemical characterization of the systems developed was performed. DNA conformational changes in the presence of ALA were studied by Circular Dichroism (CD) and the ALA binding to DNA was followed by surface tension measurements. Insight into the structure and morphology of the various ALA-complexes (complexes composed of ALA, DNA, Tf and liposomes) was obtained by cryogenic-Transmission Electron Microscopy (cryo-TEM) and the sizes of the ALA-complexes were determined through Photon Correlation Spectroscopy (PCS). We found that the transfection capacity of these systems is directly related with the presence of ALA and the lipidic composition. Complexes based on the pH sensitive liposome formulation present better transfection profiles. The correlation between the inner structure, density and size of the ALA-complexes and their biological activity is discussed. Overall, we demonstrate that the presence of ALA improves the transfection efficiency when conjugated with cationic liposome systems

Physicochemical properties of transferrin-associated lipopolyplexes and their role in biological activity

The combination of polyethylenimine (PEI), as a plasmid DNA pre-condensing agent, and cationic lipids has been reported to result in a synergistic effect on transfection. Recently, we have explored this effect by associating low-molecular weight PEIs with transferrin-associated lipoplexes using different cationic liposome formulations. The resulting lipopolyplexes that have shown to be the most efficient in mediating transfection were those prepared from cationic liposomes composed of DOTAP:Chol (associated or not with transferrin) and from a pH-sensitive liposome formulation (DOTAP:Chol: DOPE:CHEMS). In the present work, the physicochemical properties of these lipopolyplexes were studied aiming at establishing a correlation with their transfection efficiency. For this purpose, the lipopolyplexes were characterized in terms of their morphology by performing ultrastructural Studies using cryo-TEM microscopy, investigating inner DNA Structure using circular dichroism and characterizing particle size by photon correlation spectroscopy. A correlation between efficiency of transfection and more compact inner DNA structure and smaller particle sizes (around 250 nm) was found. In addition, the visualization of liposomes and lipopolyplexes at the ultrastructural level revealed that the particles presenting enhanced transfection efficiencies are associated with higher electron density. Recently, PEI-based lipopolyplexes were reported to gain entry into the cell through the caveolae-mediated pathway. Based on the present finding that DOTAP:Chol liposomes exhibit the ability to form hexagonal structures when prepared at high concentrations, we propose that the lipopolyplexes containing DOTAP:Chol take advantage of such capacity to escape from the endocytotic vesicles, which will contribute to the observed high transfection efficiencies. (C) 2009 Elsevier B.V. All rights reserved

Cationic liposomes for gene delivery

Cationic liposome-DNA complexes (lipoplexes) constitute a potentially viable alternative to viral vectors for the delivery of therapeutic genes. This review will focus on various parameters governing lipoplex biological activity, from their mode of formation to in vivo behaviour. Particular emphasis is given to the mechanism of interaction of lipoplexes with cells, in an attempt to dissect the different barriers that need to be surpassed for efficient gene expression to occur. Aspects related to new trends in the formulation of lipid-based gene delivery systems aiming at overcoming some of their limitations will be covered. Finally, examples illustrating the potential of cationic liposomes in clinical applications will be provided. © 2005 Ashley Publications Ltd

Transferrin-Associated Lipoplexes as Gene Delivery Systems: Relevance of Mode of Preparation and Biophysical Properties

Abstract The successful application of gene therapy depends highly on understanding the properties of gene carriers and their correlation with the ability to mediate transfection. An important parameter that has been described to improve transfection mediated by cationic liposomes involves association of ligands to cationic liposome–DNA complexes (lipoplexes). In this study, ternary complexes composed of 1,2-dioleoyl-3-(trimethylammonium) propane:cholesterol, plasmid DNA and transferrin (Tf, selected as a paradigm of a ligand) were prepared under various conditions, namely, in medium with different ionic strengths (HEPES-buffered saline [HBS] or dextrose), at different lipid/DNA (+/–) charge ratios and using different modes for component addition. We investigated the effect of these formulation parameters on transfection (in the absence and presence of serum), size of the complexes, degree of DNA protection and extent of their association with cells (in terms of both lipid and DNA). Our results show that all the tested parameters influenced to some extent the size of the complexes and their capacity to protect the carried genetic material, as well as the levels of cell association and transfection. The best transfection profile was observed for ternary complexes (Tf-complexes) prepared in high ionic strength solution (HBS), at charge ratios close to neutrality and according to the following order of component addition: cationic liposomes–Tf–DNA. Interestingly, in contrast to what was found for dextrose–Tf-complexes, transfection mediated by HBS-Tf-complexes in the presence of serum was highly enhanced

Generation of Carbon Monoxide Releasing Molecules (CO-RMs) as Drug Candidates for the Treatment of Acute Liver Injury: Targeting of CO-RMs to the Liver

The discovery of the biological effects of carbon monoxide (CO) in recent years strongly suggests that CO could find applications as a therapeutic agent. CO is a highly toxic gas when used at industrial doses, due in part to its binding affinity to hemoglobin. Since hemoglobin binds CO with the highest affinity <i>in vivo</i>, it also constitutes a major barrier to the delivery of CO to tissues in need of therapy. A method of delivering CO that can bypass hemoglobin is the use of pro-drugs or CO carriers, called CO-releasing molecules (CO-RMs) that become activated and release CO in tissues in need of treatment. Organometallic carbonyl complexes are best suited to play the role of CO carriers, and indeed the natural CO carrier molecules hemoglobin and myoglobin belong to this class of chemical compounds. Here we describe the preparation of novel molybdenum CO-RMs of general formula Mo­(CO)₃(CNCR′R″CO₂R‴)₃ (R′, R″ = H, Me, ⁱPr, CH₂Ph, CO₂Li, −CH₂CH₂–, −CH₂(CH₂)₃CH₂–; R‴ = H, Li), which present favorable druglike characteristics, have low toxicity, and demonstrate specific CO delivery to the liver in the treatment of acetaminophen (APAP)-induced acute liver failure in mice

Generation of Carbon Monoxide Releasing Molecules (CO-RMs) as Drug Candidates for the Treatment of Acute Liver Injury: Targeting of CO-RMs to the Liver

The discovery of the biological effects of carbon monoxide (CO) in recent years strongly suggests that CO could find applications as a therapeutic agent. CO is a highly toxic gas when used at industrial doses, due in part to its binding affinity to hemoglobin. Since hemoglobin binds CO with the highest affinity <i>in vivo</i>, it also constitutes a major barrier to the delivery of CO to tissues in need of therapy. A method of delivering CO that can bypass hemoglobin is the use of pro-drugs or CO carriers, called CO-releasing molecules (CO-RMs) that become activated and release CO in tissues in need of treatment. Organometallic carbonyl complexes are best suited to play the role of CO carriers, and indeed the natural CO carrier molecules hemoglobin and myoglobin belong to this class of chemical compounds. Here we describe the preparation of novel molybdenum CO-RMs of general formula Mo­(CO)₃(CNCR′R″CO₂R‴)₃ (R′, R″ = H, Me, ⁱPr, CH₂Ph, CO₂Li, −CH₂CH₂–, −CH₂(CH₂)₃CH₂–; R‴ = H, Li), which present favorable druglike characteristics, have low toxicity, and demonstrate specific CO delivery to the liver in the treatment of acetaminophen (APAP)-induced acute liver failure in mice