Dissertations / Theses on the topic 'Experimental'

No presente trabalho foi estudado o efeito do consumo de soja geneticamente modificada e de sua parental em parâmetros nutricionais e hematológicos em ratos em crescimento. Farinha de soja, desengordurada e autoclavada, foi incorporada em rações experimentais: 12% de proteína para o 1° ensaio e 10% para 2° ensaio. As rações com soja foram suplementadas com aminoácidos essenciais (Ieucina, lisina, metionina e vali na) no 2° ensaio, devido a menor concentração desses aminoácidos nas rações do 1° ensaio quando comparadas ao grupo controle, perfil confirmado pelo aminograma. Ratos Wistar (n=64) foram alimentados, ad libitum, com rações controle (AIN-93G) e rações com a farinha de soja por 28 (1° ensaio) e 32 dias (2° ensaio). Para avaliação do aproveitamento biológico da proteína da dieta e da qualidade protéica, foram realizadas análises de nitrogênio na carcaça dos animais, nas fezes e na urina que foram coletadas ao longo de 2 períodos de balanço de 6 dias cada ensaio. Os parâmetros nutricionais avaliados foram : Coeficiente de eficácia alimentar (CEA), Coeficiente de eficácia protéica (PER), Coeficiente de eficiência líquida da proteína (NPR), Valor biológico da proteína (BV), Coeficiente de utilização líquida da proteína (NPU), digestibilidade protéica e o \"Escore químico corrigido pela digestibilidade real da proteína\". Para avaliação do estado nutricional foram avaliadas as concentrações de albumina, proteínas totais e IGF-1 no plasma. Como parâmetros hematológicos, foram avaliados o hemograma completo, mielograma e esplenograma. Os resultados obtidos demonstraram que animais alimentados com soja GM e sua parental apresentaram desenvolvimento semelhante ao grupo controle (caseína). Os valores de CEP e NPR encontrados nos 2 ensaios mostram que a proteína de soja é nutricionalmente adequada. A oferta protéica de 10% com suplementação com aminoácidos essenciais favoreceu no desenvolvimento dos animais, visto que foi observado aumento de peso em média de 50g, PER e NPR melhores quando comparados com a oferta protéica de 12% sem suplementação. Nos dois ensaios, os valores de digestibilidade dos grupos alimentados com soja foram inferiores aos do grupo controle, resultado evidenciado pela maior dificuldade das enzimas digestivas em digerirem a proteína vegetal, maior perda de aminoácidos endógenos e quantidade de fibra insolúvel presente na soja. O valor de POCAA de 85% demonstra bom aproveitamento dos grupos com soja. Não houve diferença estatística nos parâmetros plasmáticos estudados, bem como nos resultados hematológicos sugerindo que o consumo de soja, convencional ou GM, não altera o estado nutricional dos animais.
In the present work, the effects of genetically modified (GM) soybean and its parental on nutritional and hematological parameters in growing rats were studied. Autoclaved, fat-free soybean flour was added to experimental diets: 12% protein in the first assay and 10% in the second assay. The soybean diets were supplemented with essential amino acids (Ieucine, Iysine, methionine and valine) in the second assay, since such amino acids presented a lower concentration in the diets of the first experiment, as confirmed by the aminogram. Wistar rats (n= 64) were fed a control diet (AIN-93G) and diets supplemented with soybean flour (parental and GM) ad libitum over 28 days (1st experiment) and 32 days (2nd experiment). For evaluating the biological utilization of dietary protein and protein quality, nitrogen analyses were carried out on the animal carcasses, feces and urine. Feces and urine were collected along two 6-day periods within each assay. The following nutritional parameters were evaluated: feed efficiency ratio (FER), protein efficiency ratio (PER), net protein ratio (NPR), biological value (BV), net protein utilization (NPU), protein digestibility and protein digestibility corrected by amino acid (POCM) score. For evaluating the nutritional status, plasma albumin, total proteins and IGF-1 were analysed. Complete hemogram, myelogram and splenogram were used as hematological parameters. The results indicate that animals fed the GM soybean and its parental showed a similar growth rate to the control group (casein). PER and NPR values found in both assays show that soybean protein is nutritionally adequate. A diet containing 10% protein supplemented with essential amino acids favored the growth of the animals in comparison to a diet containing 12% protein without amino acid supplementation. In both assays, the protein digestibility in soybean-fed groups was lower than in the control group, a result evidenced by a greater difficulty of enzymes in digesting vegetal proteins, a greater loss of endogenous amino acids and the presence of insoluble dietary fiber in the soybean. A POCM value of 85% showed a good protein utilization in the soybean-fed groups. No statistically significant differences were observed in the plasmatic and hematological parameters among the groups, suggesting that consumption of soybean (either GM or parental) does not alter the nutritional status of the animals.

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Neste trabalho, foi pesquisada uma forma alternativa de aplicação de experimentos em sala de aula, na qual os alunos foram responsáveis pela confecção deles e não meros expectadores que observaram o professor realizar a atividade experimental. Assim, os estudantes produziram, executaram e tiraram suas conclusões acerca das atividades propostas. Propôs-se, neste trabalho, a aplicação de uma sequência didática para abordar eletrostática utilizando atividades experimentais, como metodologia de aprendizagem significativa, proposta por David Ausubel. Antes da realização dos experimentos, o tema foi contextualizado através de vídeos que mostravam situações intrigantes no cotidiano dos alunos, envolvendo eletrostática. Também foi abordada a história da eletricidade com suas principais descobertas e como os conceitos científicos foram evoluindo ao longo do tempo. Em seguida, utilizando materiais de baixo custo e fáceis de serem encontrados e seguindo roteiros experimentais, os alunos construíram experimentos que permitiram a verificação dos três processos de eletrização: atrito, contato e indução. Também, verificaram a distribuição de cargas em condutores em equilíbrio eletrostático, a blindagem eletrostática e o poder das pontas. O trabalho visou despertar o interesse e motivação dos alunos nas aulas de Física, desenvolvendo suas habilidades em seguir roteiros simples, coletar e analisar dados, além de aplicar os conceitos, abordados em sala, em situações de seu cotidiano.
In this work, an alternative way of applying experiments in the classroom has been investigated, in which the students were responsible by their confections and not mere spectators who observed the teacher to perform an experimental activity. Thus, students produced, performed, and concluded on the proposed activities. It was proposed, in this work, the application of a Didactic Sequence to approach electrostatic using experimental activities, as significant learning methodology, proposed by David Ausubel. Before the experiments, the theme was contextualized through videos that showed intriguing situations in the daily life of students, involving electrostatics. It was also discussed the electricity history with its main discoveries, and how scientific concepts were developed over time. Then, using inexpensive, easy-to-find materials and following experimental script, the students constructed experiments that allowed the verification of the three electrification processes: friction, contact and induction. Also, they verified the charges distribution in conductors in electrostatic equilibrium, the electrostatic shield and the power of the tips. The aim of this work was to arouse student’s interest and motivation in physics classes, developing their skills in following simple scripts, collecting and analyzing data, and applying the concepts, addressed in the classroom, in everyday situations.

A pesar de que la esclerosis múltiple fue descrita por el Dr. Jean-Martin Charcot en el siglo XIX, todavía sigue siendo una enfermedad neurológica desafiante. La etiología de la enfermedad es desconocida, pero se sabe que la degeneración de las vainas de mielina y de las neuronas tiene su origen en la activación aberrante de las células inmunes en las lesiones del sistema nervioso central. Por esta razón, en la presente tesis nosotros proponemos la modulación de la respuesta inflamatoria con el objetivo de disminuir el daño neurológico y la desmielinización en la encefalomielitis autoinmune experimental, un modelo murino de la esclerosis múltiple. Los resultados expuestos en este trabajo muestran que la administración de moléculas antiinflamatorias como el OLT1177 o la IL-37, o mediadores especializados de la resolución de la inflamación, como la Resolvina-D1 o la Maresina-1, tienen efectos terapéuticos en la encefalomielitis autoinmune experimental, incluso cuando el tratamiento es iniciado el primer día que aparecen los signos clínicos de la enfermedad. El OLT1177, la IL-37 y la Maresina-1 sus efectos beneficiosos a través de algunos mecanismos comunes, como la reducción de las citoquinas proinflamatorias y la acumulación de células inmunes en la médula espinal. La IL-37 y la Maresina-1 modulan la respuesta inflamatoria en la periferia y la polarización de linfocitos y macrófagos hacia un fenotipo más antiinflamatorio o regulador. En conjunto, nuestros resultados proporcionan nuevos datos que podrían ayudar al desarrollo de nuestras estrategias terapéuticas más efectivas para tratar la esclerosis múltiple.
Despite multiple sclerosis was described by Dr. Jean-Martin Charcot in the 19th century, it is currently a challenging neurological disorder. The etiology of this pathology is not fully understood but the degeneration that occurs in myelin sheaths and neurons in individual suffering from multiple sclerosis is linked to aberrant presence of immune cells in the lesioned central nervous system. For this reason, in the present thesis we propose to modulate the inflammatory response to ameliorate neurological decline and demyelination in experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. The data shown here reveals that the administration of anti-inflammatory approaches, such as OLT1177 and IL-37, or specialized pro-resolving mediators, such as Resolvin-D1 or Maresin-1, has therapeutic effects in mice with experimental autoimmune encephalomyelitis, even if these treatments are initiated at the onset of the disease. OLT1177, IL-37 and Maresin-1 exerts beneficial effects by reducing some common aspects of inflammation, such as the production pro-inflammatory cytokines and the accumulation of immune cells. IL-37 and Maresin-1 also modulate the inflammatory response in the periphery and alter the polarization of lymphocytes and macrophages towards a more anti-inflammatory or regulatory phenotype. Collectively, the results presented here provide novel data that could pave the way to develop more effective strategies to treat multiple sclerosis.

O interesse pela clorofila vem crescendo recentemente devido a divulgação de dados que atribuem a esta substância muitos efeitos benéficos à saúde, introduzindo a possibilidade desta molécula oferecer proteção contra o desenvolvimento de doenças crônico-degenerativas e cânceres, agindo como um antioxidante e inibindo a mutagênese. Entretanto, as evidências científicas destas ações são ainda controversas. Perguntas estão surgindo a cerca do local de ocorrência de tais propriedades, se no intestino, antes da absorção, ou se devido a uma ação sistêmica, após absorção. O objetivo deste trabalho foi estudar as mudanças químicas da clorofila durante sua passagem pelo trato gastrointestinal, a absorção aparente e a detecção de derivados da clorofila no sangue. O estudo foi realizado durante 10 dias com 12 cães (Canis familiaris) divididos em 2 grupos. O grupo controle recebeu uma dieta comercial atendendo as exigências nutricionais, enquanto que o grupo teste recebeu a mesma dieta adicionada de 0,8% de espinafre liofilizado e 0,35% de óxido do cromo (como um indicador não absorvível). Foi realizada coleta parcial das fezes e após análise, a absorção aparente foi calculada. Em um segundo ensaio, o sangue foi coletado em 0, 15, 30, 45, 60, 90, 120 e 150 minutos após a ingestão da dieta que continha 10% de espinafre liofilizado. Os pigmentos do espinafre, da dieta, das fezes e do sangue foram extraídos com acetona 80%, isolados e quantificados por CLAE. Os resultados mostraram que a feofitinização foi a via predominante. Somente feofitinas a e b foram encontradas nas fezes. A absorção aparente da clorofila variou entre 4 e 6%. Entretanto, não foi possível detectar a presença de clorofila nem de seus derivados no plasma sanguíneo. Estes achados sugerem que os eventuais efeitos benéficos da clorofila devem ocorrer predominantemente no intestino e caso haja alguma passagem para o sangue, esta molécula parece ser rapidamente metabolizada a fim de prevenir efeitos tóxicos relacionados com a atividade fotossintética.
In recent years there has been a growing interest on chlorophyll due to disclosing reports attributing to this substance manifold health benefits, introducing the possibility of this molecule protecting against the development of chronic-degenerative diseases and cancer, acting as an antioxidant and by inhibition of mutagenesis. However, the scientific evidences of these actions are still controversial. Questions have been raised about where these properties take place, if in the gut before absorption or if they are due to a post-absorption systemic action. The purpose of this research was to study the chemical changes of chlorophyll during its passage through the gastrointestinal tract, the apparent absorption and the appearance of any chlorophyll derivative in blood. The study was carried out during 1 O days in twelve dogs (Canis familiaris) divided into 2 groups. The control group received a commercial diet attending their nutritional requirements, while the test group received the same diet to which 0.8% of freeze-dried spinach and 0.35% of chromium oxide (as a non-absorbable indicator) were added. Partial collection and analysis of excreta was carried out and apparent absorption was calculated. ln a second experiment, blood was collected at 0, 15, 30, 45, 60, 90, 120 and 150 min after the intake of the diet, which contained 10% freeze-dried spinach. Pigments in spinach, diet, excreta and blood were extracted with 80% acetone, isolated and quantified by HPLC. The results showed that pheophitinization was the predominant pathway. Only pheophytins a and b were found in excreta. Apparent absorption of chlorophyll ranged from 4 to 6%. However, it was not possible to detect the presence of chlorophyll or any of its metabolites in blood plasma. These findings suggest that eventual beneficial effects of chlorophyll may occur predominantly in the gut and in case that some uptake occurs, the molecule seems to be metabolized fast enough in order to prevent toxic photosynthetic activity related effects.

The diploma thesis deals with analysis of risks in relation to various focus (or types) of economic experiments. On the basis of background research suggests entirely new classification of economic experiments and subsequently examines general structure of economic experiment. Performed analysis then identifies major risks of experimental economics, analyses them and proposes possible countermeasures. Outputs of the work substantially enrich and extend current theory. Their utilization is expected in theory and practice, for purpose of scientific research or specific objectives of companies and institutions.

This essay discusses different opinions about experimental archaeology. To start with literature was examined and a questionnaire was sent out to students and working archaeologists. The possibility for experiments to mediate archaeology to people without an education in archaeology is lifted and is also mentioned in the questionnaire. In the discussion part of the essay the results from the questionnaire and the literature are used to see what opinions are the strongest. The mediating is also discussed and the result is compiled in the conclusion. There are different opinions about experimental archaeology, but no prominent difference between what students and archaeologists answered. It is possible to see different opinions in the literature, but concerning the mediating most of the writers agree that the experimental archaeology is a good method to communicate with the laymen.

Neste estudo pretende caracterizar-se o trabalho experimental realizado no ensino secundário, no âmbito do ensino da Química e estudar qual a influência que a sua realização exerce na motivação dos alunos para o estudo da disciplina. Este estudo foi efectuado com professores que leccionaram a disciplina de Física e Química A, e alunos que frequentaram esta disciplina no 10º e 11º ano, no ano lectivo 2008/2009. Foi alargado a Escolas, públicas e privadas, de várias regiões, com o intuito de obter um maior leque de resultados e de estudar eventuais diferenças. No que respeita ao 10º ano faz-se a comparação entre a opinião dos alunos que tiveram aulas experimentais no 3º Ciclo, e a daqueles que não tiveram, ficando desse modo a conhecer a perspectiva que os próprios alunos têm sobre se esse trabalho foi, ou não, importante no desenvolvimento da sua aprendizagem no âmbito da Química; ABSTRACT:This work intends to characterize the chemical experimental work carried out in Secondary schools, and to study its importance in the motivation of the students in the learning of Chemistry. This study comprises teachers who taught Physics and Chemistry A, and students who attended this subject in their 10th or 11th grade, during the year of 2008/2009. Public and private schools from different regions were included in this study, in order to achieve a wider range of results and have the possibility to analyze the differences. A comparison of opinions was made amongst 10th grade students that had and didn’t have experimental classes in previous grade, and those that had not. Thus, it was possible to know the opinions of students about the importance of experimental work in their Chemistry learning.

A decisão estratégica é tipicamente não estruturada, no sentido de que não existe processo semelhante na memória da organização. Essa estruturação corresponde ao cenário exposto de forma clara, com suas questões, hipóteses e objetivos. A qualidade da decisão estratégica depende principalmente do processo e da competência daqueles que participam dela. Gerar alternativas criativas e viáveis é uma etapa fundamental do processo de tomada de decisão, responsável em grande parte pela qualidade almejada. Entretanto, as pesquisas sobre geração de alternativas têm indicado consistentemente que as pessoas não são eficientes nessa atividade. Buscando-se as explicações para esse fato surgiram lacunas na literatura que serviram de inspiração para o presente estudo. Qual a influência das heurísticas e da isolação entre as etapas convergente e divergente na geração de alternativas? Para explorar essas lacunas e conhecer o desempenho do administrador brasileiro ao gerar alternativas foi realizado um experimento com 174 alunos de cursos MBA, de 4 escolas da Grande São Paulo. O resultado desse experimento propiciou algumas conclusões interessantes como a confirmação do baixo desempenho em geração de alternativas. O desafio para preencher as lacunas observadas permanece e as hipóteses da pesquisa, relacionando as heurísticas e a isolação como fatores que influenciam o desempenho, não foram aceitas. O estudo é uma confluência da pesquisa experimental, oriunda da psicologia cognitiva da decisão, com a visão da ciência da decisão organizacional. Essa linha de pesquisa se mostrou praticamente inexplorada nos estudos em administração desenvolvidos no Brasil.
The strategic decision-making is typically non-structured because there is no similarity process in the memory of the organizations. This structural model would involve a context of elements such as questions, hypotheses and objectives exposed in a quite clear way. The quality of the strategic decision-making depends mainly on its own process and on the competence of the individuals involved. An essential part of the making decision process is to generate creative and viable options that are also responsible for the quality of the process. However, researches on option-generating procedures have consistently suggested that people are not efficient in this kind of task. The present study was inspired by the fact that the current literature lacks studies explaining the reasons why this happen. What is the influence of the heuristics and isolation strategies on the convergent and divergent phases for generating options? In order to investigate this issue and understand the performance of the Brazilian managers for generating options, an experiment was conduct in 174 individuals studying in MBA courses at 4 educational institutions in the urban city area of São Paulo. The results led to some interesting conclusions such as the confirmation of the poor performance for generating options. The challenge and the lack remain mainly because the hypotheses tested, i.e., the heuristic and isolation strategies for generating options, were not effective. The present study is a confluence of two different decision approaches: the experimental research (based on cognitive psychology) and the management science. This line of research hasn’t been explored in the management field in Brazil.

Many problems in science and engineering are solved through experimental investigations. Because experiments can be costly and time consuming, it is important to efficiently design the experiment so that maximum information about the problem can be obtained. It is also important to devise efficient statistical methods to analyze the experimental data so that none of the information is lost. This thesis makes contributions on several aspects in the field of design and analysis of experiments. It consists of two parts. The first part focuses on physical experiments, and the second part on computer experiments. The first part on physical experiments contains three works. The first work develops Bayesian experimental designs for robustness studies, which can be applied in industries for quality improvement. The existing methods rely on modifying effect hierarchy principle to give more importance to control-by-noise interactions, which can violate the true effect order of a system because the order should not depend on the objective of an experiment. The proposed Bayesian approach uses a prior distribution to capture the effect hierarchy property and then uses an optimal design criterion to satisfy the robustness objectives. The second work extends the above Bayesian approach to blocked experimental designs. The third work proposes a new modeling and design strategy for mixture-of-mixtures experiments and applies it in the optimization of Pringles potato crisps. The proposed model substantially reduces the number of parameters in the existing multiple-Scheffé model and thus, helps the engineers to design much smaller experiments. The second part on computer experiments introduces two new methods for analyzing the data. The first is an interpolation method called regression-based inverse distance weighting (RIDW) method, which is shown to overcome some of the computational and numerical problems associated with kriging, particularly in dealing with large data and/or high dimensional problems. In the second work, we introduce a general nonparametric regression method, called kernel sum regression. More importantly, we make an interesting discovery by showing that a particular form of this regression method becomes an interpolation method, which can be used to analyze computer experiments with deterministic outputs.

Neste trabalho apresentamos os principais objetivos dos planejamentos experimentais em modelos de regressão. Na primeira parte do trabalho descrevemos os planejamentos com alavancagem constante, que permitem que todos os pontos amostrais exerçam a mesma influência nas estimativas dos parâmetros do modelo de regressão. Abordamos ainda outros tipos de planejamentos experimentais que obedecem a certos critérios como, por exemplo: G-otimalidade, D-otimalidade e Planejamentos ortogonais. Finalizando o trabalho foi apresentada uma análise prática em que as principais medidas estudadas foram aplicadas a um conjunto de dados reais.
This work presents the main objectives of the sampling plans in regression models. The first part of the study describes the planning with constant leverage, enabling all sampling points exercise the same influence on the estimatives of the parameters of the regression model. We still discussed other types of experimental plans that meet certain criteria, such as G-optimality, D-optimality and Planning orthogonal. Finally the work presented a practical analysis where the main measures were applied to a set of real data.

Orientadores: Nelson Rodrigues Netto Junior, Julia do Prado Franceschi
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O transporte de urina da pelve renal para a bexiga é bem conhecido. Por outro lado, os fatores que alteram o transporte ainda apresentam controvérsias, principalmente quanto ao efeito das catecoIaminas. Foi realizado um estudo experimental com objetivo de verificar os efeitos da enervação (periférica, central e bloqueio ganglionar), a ação das drogas adrenérgicas (noradrenalina e isoproterenol) e medicamentos vasoativos (angio-tensina e nitroprussiato de sódio). Este estudo foi realizado em 43 cães, sendo analizados os resultados encontrados em 28. Os parâmetros estudados foram: peristaltismo ureteral (intervalo interperistáltico, pressão basal e amplitude), pressão arterial e fluxo urinário. A enervação periférica não promoveu alterações no peristaltismo ureteral. Entretanto, a enervação central e o bloqueio ganglionar provocaram diminuição da pressão arterial e do peristaltismo ureteral. A administração de isoproterenol e nitnoprussiato de sódio promoveram diminuição da pressão arterial e do peristaltismo ureteral, enquanto o emprego de noradrenalina e angiotensina promoveram aumento da pressão arterial e do peristaltismo ureteral. Portanto, as variações na pressão sanguínea causaram aumento ou diminuição da filtração glomerular, seguindo-se diminuição ou aumento do fluxo urinário e, por conseguinte, do peristaltismo ureteral. Com o método empregado, a enervação não altera o peristaltismo ureteral. O fato de que as drogas adrenérgicas utilizadas promoveram importantes variações no peristaltismo ureteral, similares às provocadas por medicamentos vasoativos, sugere que, no controle do peristaltismo ureteral as mudanças no fluxo urinário são mais importantes que os efeitos dos medicamentos empregados
Abstract: Urinary transport from the renal pelvis to the bladder is well known. However, the factors which alter the ureteral peristalsis are controvers a 1, especially in relationship as to the effect of catecolamines. An experimental study was done to verify the effects of enervationfperiferic, central and ganglionic blocking), adrenergic drugs (noradrenaline and isoprotere -nol) and vasoative drugs {angiotensin and sodim nitroprussi-de ). The study was carried out in 43 dogs of which the results of 28 were analyzed. The parameters studied were : ureteral peristalsis (interperistaltic interval,basal pressu re and amplitude), blood pressure and urinary flow. The periferic enervation did not show modification of the peristalsis. However, central enervation and ganglionic blocking promoted a fall in blood pressure and ureteral peristalsis. The administration of isoproterenol and sodium nitroprusside promoted a decrease in blood pressure and ureteral peristalsis, while administration of noradrenaline and angiotensin promoted an increase in blood pressure and ureteral peristalsis. The variation in blood pressure caused a decrease or increase in glomerular filtration followed by a diminuation or aumentation of urinary flow and then ureteral peristalsis . With the method utilized, the enervation did not modify the ureteral peristalsis. The fact that the adrener -gic drugs used promoted important variations in the ureteral peristalsis, similar to those caused by the vasoactive drugs suggests that the changes in urinary flow are more important than the effects of the use of drugs themselves in the control of ureteral peristalsis
Doutorado
Doutor em Medicina

Neurologic injuries are major causes of mortality and morbidity after cardiac surgery. This thesis aimed to investigate cerebral metabolism and perfusion abnormalities in pigs during hypothermic circulatory arrest, selective antegrade cerebral perfusion (SACP) and extracorporeal circulation following progressive venous stasis. Hypothermic circulatory arrest induced a metabolic pattern consistent with overt ischaemia, which was absent following SACP. In contrast, metabolism during SACP was influenced by the perfusate temperature, where a colder perfusate (20 °C) preserved cellular metabolism and membrane integrity better than a warmer perfusate (28 °C). The minimum SACP flow required to maintain metabolism during hypothermia at 20 °C was investigated with magnetic resonance imaging, protein S100β, near infrared spectroscopy and microdialysis. The findings suggested an ischaemic threshold close to 6 ml/kg/min in the present models. Furthermore, regional differences in perfusion with a hemispheric distribution were apparent at all flow levels and differed from earlier studies where the differences were uniform and followed a neuranatomical pattern. Venus stasis following superior vena cava congestion produced measurable signs of impaired cerebral perfusion and patterns of cerebral ischaemia were evident in individual animals. As venous pressure increased, the mean arterial pressure stayed more or less unchanged, generating reduced cerebral perfusion pressure and consequently an increased risk of ischaemia, which may impair cerebral perfusion, especially in cases of compromised arterial flow during extracorporeal circulation. In conclusion, cerebral metabolism and perfusion are influenced by temperature, SACP flow levels and venous congestion. In clinical practice, the regional differences in perfusion during SACP may be of pathogenic importance in focal cerebral ischaemia. Furthermore, the reduced superior vena cava cannula flow may pass undetected during bicaval cardiopulmonary bypass if the superior vena cava flow is not specifically monitored.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
A neuropatia motora distal é uma das freqüentes complicações do Diabetes Mellitus , e sua prevalência pode ser considera igual a 100%, se pacientes com alterações de condução nervosa, sem acompanhamento de sinais ou sintomas, são inclusos. Neste contexto, o presente estudo foi desenvolvido com o objetivo de obter informações relacionadas às polineuropatias periféricas em animais com diabetes induzido pela aloxana. Os grupos experimentais foram formados por 50 ratos diabéticos (GD) sem tratamento, da raça Wistar, machos, e 50 ratos não diabéticos (GND) da mesma espécie e idade. As avaliações eletrofisiológicas foram obtidas após 1, 3, 6, 9 e 12 meses de seguimento, respectivamente, nos cinco subgrupos, cada um, com cinco animais. Os exames dos nervos ciático e caudal mostraram: (i) os potenciais de ação muscular composto (CMAPs) apresentaram diminuição da amplitude e aumento da dispersão temporal; (ii) a velocidade de condução nervosa (NCV) foi menor (p < 0,05) no GD, com diferença estatisticamente significante na NCV do nervo caudal nos diferentes intervalos de tempo; (iii) a latência distal (DLAT) foi maior (p < 0,05) no GD, com diferença estatisticamente significante na DLAT do nervo caudal entre os vários subgrupos do GD. Estes resultados demonstram que o modelo experimental proposto pode ser usado para o estudo funcional da neuropatia diabética. Os parâmetros obtidos fornecem subsídios para testes com as terapias convencionais, as cirúrgicas e as de suplementação no tratamento da neuropatia diabética motora distal.
Distal motor neuropathy is one of the most common complications of diabetes mellitus, and its prevalence can be considered as high as 100 percent if patients with abnormalities of nerve conduction without accompanying signs or symptoms are included. In this context, the present study was undertaken to obtain information concerning the peripheral polyneuropathies in alloxan-induced diabetic animals. Experiments were carried out on 50 untreated diabetic control (DG) Wistar male rats, and 50 age-matched nondiabetic controls (NDG). Electrophysiological assessments were obtained after 1, 3, 6, 9, and 12 months of follow-up, respectively, in the five subgroups with 5 animals each. Analysis of the recorded response from the right sciatic and caudal nerves showed: (i) diminished amplitude and increased temporal dispersion of the compound muscle action potentials (CMAPs) in the DG; (ii) nerve conduction velocity (NCV) lower (p< 0.05) in the DG, with statistically significant difference in NCV of the caudal nerve at different time intervals; (iii) distal latency (DLAT) higher (p< 0.05) in the DG, with statistically significant difference in DLAT of the caudal nerve among the several diabetic subgroups. These results demonstrate that the experimental model proposed can be used for a functional study of diabetic neuropathy. The parameters obtained supply assistance for tests with conventional therapies, with surgeries and those with supplementation in treatment of distal motor diabetic neuropathy.

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Sessenta animais da espécie Rattus wistar de ambos os sexos, pesando de 200 a 300 gramas, foram divididos em dois grupos experimentais: G1 ou grupo normal, constituído por dez animais e G2 ou grupo diabético, constituído inicialmente por 50 animais, que foram inoculados com aloxana à 2% por via endovenosa, na dose de 42mg/kg de peso corporal. Desses, dez animais com diabetes experimental grave (glicemia maior que 200mg/dl), sobreviveram durante o seguimento de 12 meses e constituíram o grupo diabético ou G2. Os seguintes parâmetros clínicos e laboratoriais foram estudados em cada grupo experimental: aspecto geral dos animais, peso, ingestão hídrica, ingestão alimentar, diurese e dosagens da glicemia, glicose urinária e proteinúria. As observações, com exceção da proteinúria de 24 horas, foram observadas em três momentos experimentais: inicial ou 14 dias após a indução do diabetes no grupo diabético e 14 dias de observação no grupo normal, 6º e 12º mês de seguimento. A dosagem da proteinúria de 24 horas foi efetuada no 12º mês de seguimento nos dois grupos experimentais. Após o 12º mês de seguimento, os animais foram sacrificados, após anestesia, e o rim direito de quatro animais diabéticos e quatro animais normais, escolhidos ao acaso, foi preparado para o estudo à microscopia eletrônica. As elétron-micrografias obtidas com aumento de 42.000 vezes foram analisadas por morfometria pela utilização de sistema computadorizado Quin Lite 2,5 LEICA, interessando a espessura da MBG, o número de podócitos, o número de slit diaphragme a extensão dos slit diaphragm. Os resultados dos parâmetros clínicos e bioquímicos foram analisados pelo teste de comparações múltiplas de Tukey e pela análise não paramétrica de Mann-Whitney e Kruskal-Wallis, adotando-se o nível de significância de p< 0,05...
Sixty Rattus wistar of both sexes with 200-300 g of body weight, were divided in two experimental groups: normal group (G1 - 10 animals) and diabetic group (G2- 50 animals at the beginning), which were inoculated with a endovenous injection of 2% alloxan in a dose of 42 mg /kg/body weight. From these ten animals with severe experimental diabetics (glicemia > 200 mg%) will survive during 12 months of follow-up, being considered the experimental group (G2). The following clinic and laboratory parameters were studied: clinical aspect, body weight, water and food intake, diuresis, as well fasting glycemia, urinary glucose and proteinuria. The observations, excepting proteinuria (24 hours) were made at three experimental moments as it follows: initial or 14 days after diabetes induction or follow-up (normal controls) and at 6 and 12 months. Proteinuria was measured at the 12th month in boths groups. After 12 months of diabetes induction or follow-up (G1), the animals were sacrificed being the right kidney from four animals of each group processed for Electron Mycroscopy. The electron micrographys were taken with magnification of 42,000 and were analysed according to morphometric techniques by using computer System Quin Lite 2.5 LEICA, being studied the following aspects: glomerular basement membrane thickening, podocytes and slit diaphragm number, and the slit diaphragm extension. The results of the clinical and laboratory parameters were statistically analysed according to Tukey's multiple comparison being used the level of 5% significance. The results of morphometric study were analysed according to Mann-Whitney and Kruskal-Wallis test, using a software Sigma Stat 2,0, being used level of 5% significance. G2 group presented lower body weight, higher water intake and diuresis than G1 group; the general aspect... (Complete abstract click electronic address below)

Most design of experiments assumes predetermined design regions. Design regions with uncertainty are of interest in the first chapter. This chapter proposes optimal designs under a two-part model to handle the uncertainty in the design region. In particular, the logit model in the two-part model is used to assess the uncertainty on the boundary of the design region. The second chapter proposes an efficient and effective multi-layer data collection scheme (Layers of Experiments) for building accurate statistical models to meet tight tolerance requirement commonly encountered in nano-fabrication. "Layers-of-Experiments" (LOE) obtain sub-regions of interest (layer) where the process optimum is expected to lie and collect more data in the sub-regions with concentrated focus. The third chapter contributes a new design criterion combining model-based optimal design and model-free space-filling design in a constraint manner. The proposed design is useful when the fitted statistical model is required to have both characteristics: accuracy in statistical inference and design space exploration. The fourth chapter proposes adaptive combined designs in the layers of experiments. This chapter also develops methods to improve model quality by combining information from various layers and from engineering models. Combined designs are modified to improve its efficiency by incorporate collected field data from several layers of experiments. Updated engineering models are used to build more accurate statistical models.

No presente estudo avaliou-se o potencial quimiopreventivo da goiaba vermelha (GV) e da goiaba branca (GB) quando administradas a ratos Wistar durante as etapas de iniciação e promoção do modelo de hepatocarcinogênese de Ito et al. (1988) (DEN-HP). De acordo com o Protocolo Experimental 3, os animais receberam durante 8 semanas consecutivas, continuamente durante as etapas de iniciação e promoção, água de beber (grupo AG= controle) ou suco com 10% de goiaba vermelha (grupo GV) ou goiaba branca (grupo GB). Um grupo permaneceu no mesmo local e não foi submetido ao modelo (grupo normal). Duas semanas após o início dos tratamentos, os grupos foram submetidos ao modelo de hepatocarcinogênese de lto (Ito et al., 1988) (DEN-HP), exceto pelo grupo normal. Esse modelo consistiu na aplicação intraperitoneal de uma dose do agente iniciante dietilnitrosamina (DEN, 20 mg/100 g de p.c.), seguida, 3 semanas após, de uma hepatectomia parcial (HP) a 70%. Decorridas 6 semanas após a iniciação com DEN, todos os animais foram sacrificados. De acordo com a análise morfométrica das lesões pré-neoplásicas (LPN) hepáticas positivas para a enzima glutationa S-transferase forma placentária (GST-P), não foram constatadas diferenças (p>0,05) entre os grupos controle, GV e GB quanto ao número bem como quanto à área média das LPN GST-P positivas e área agregada do corte ocupada por estas. Com relação ao índice de apoptose, também não foram constatadas diferenças (p>0,05) entre os grupos controle, GV e GB. Houve acúmulo de licopeno hepático por parte de ambos os grupos GV e GB em relação ao grupo AG constatado pela detecção e quantificação por meio da técnica por HPLC. De acordo com os resultados do estudo, quando administradas a ratos Wistar continuamente durante as etapas de iniciação e promoção do modelo de hepatocarcinogênese de Ito (DEN-HP), a GV ou a GB não foram capazes de apresentar atividade quimiopreventiva efetiva, apesar do acúmulo de licopeno hepático nos animais desses grupos.
Lack of chemopreventive activitie of white guava and red guava when administered to Wistar rats submitted to hepatocarcinogenesis model. In the present study, the chemopreventive activity of red guava (RG) and white guava 0NG) was evaluated when administered to Wistar rats during the initiation and promotion phases of Ito\'s hepatocarcinogenesis model (DEN-HP) (Ito et a/., 1988). In the Experimental Protocol 3, animals received during 8 consecutive weeks, continuously during the initiation and promotion phases, drinking water (control group= W) ar 10% red guava juice (group RG) or 10% white guava juice (group WG). A group was kept in the same place as the others and was not submitted to the model (normal group= N). Two weeks after the beginning of the treatments, the groups were submitted to Ito\'s hepatocarcinogenesis model (DEN-HP) (Ito et al., 1988) except by the normal group. Initiation was obtained by administration of a single intraperitoneal dose of diethylnitrosamine (DEN; 20 mg/100 g b.w.) followed, 3 weeks after, by a partial (70%) hepatectomy (PH). Six weeks after DEN initiation, the animals were anesthetized and sacrificed by exsaguination. According to morphometrical analysis of placental form of glutathione S-transferase (GST-P) positive PNL, no differences (p>0,05) were observed among the W, RG, and WG groups regarding the number, average area of GST-P positive PNL, and area of the liver section occupied by these GST-P positive PNL observed. According to apoptosis index, there where also no differences (p >0,05) observed among the W, RG, and WG groups. Lycopene was stored in the livers of animals from both RG and WG groups compared to W, as it was detected and measured using HPLC. According to the results of the study, RG and WG did not present chemopreventive activity when administered to Wistar rats continuously during the initiation and promotion phases of Ito\'s hepatocarcinogenesis model (DEN-HP) (Ito et al., 1988).

Esta tesis se ha desarrollado como parte del proyecto VULCAN (Vulnerabibilty assessment of shrubland ecosystems under climatic changes), un proyecto de investigación llevado a cabo en seis ecosistemas de matorrales europeos (Gales-Reino Unido, Dinamarca, Holanda, Hungría, Cerdaña-Italia y Catalunya-España), distribuidos en un gradiente de temperatura (8.2 - 15.6 ºC) y precipitación (511 - 1427 mm). En ella se han incluido datos recogidos durante el periodo 1999-2005.
El objetivo global de la investigación fue el de aportar conocimientos y reducir incertidumbres acerca del funcionamiento de los matorrales europeos y del rol que pueden desempeñar éstos como fuente o sumidero de carbono bajo la perspectiva del cambio climático.
En las parcelas de los diferentes países se instalaron novedosas manipulaciones experimentales para aumentar la temperatura y para reducir el agua disponible en campo, simulando los efectos del cambio climático previstos para las décadas futuras.
En este trabajo se han estudiado los efectos de los tratamientos en la diversidad vegetal, en la productividad primaria aérea, así como en la fenología del crecimiento y en la elongación de ramas de las especies vegetales dominantes de los ecosistemas arbustivos europeos. Además en las parcelas experimentales de Garraf se investigó la sensibilidad de los procesos relacionados con la captación de carbono por la vegetación a nivel de hoja (fluorescencia, fotosíntesis, conductancia estomática) y se estudió la respuesta de la floración no primaveral de las dos especies arbustivas dominantes, Erica multiflora y Globularia alypum.
Los efectos del cambio climático a nivel de ecosistema fueron complejos debido a la gran variabilidad de respuestas de las plantas a los tratamientos según las variables medidas, las especies, estaciones u años, sitios y periodos de experimentación.
En Garraf, una zona que sufrió un incendio en 1994, encontramos una clara reducción en el número de especies por transecto en las parcelas de sequía respecto a las control, sin embargo no encontramos efectos similares en el resto de Europa lo que sugiere que la riqueza de especies en comunidades en proceso de recuperación después de una perturbación puede ser especialmente sensible al cambio climático respecto a otras comunidades en estadios más maduros. Concretamente, encontramos que los tratamientos de calentamiento y sequía redujeron la habilidad competitiva de Pinus halepensis (germinador obligado) frente a los arbustos rebrotadores y que la estrategia en el uso del agua pudo ayudar a G. alypum a mantener una posición dominante en las parcelas de sequía de Garraf.
En los países con menor aridez las respuestas de la biomasa anual acumulada al calentamiento fueron más positivas sin embargo, el hecho de que también encontremos especies mediterráneas como E. multiflora que respondieron positivamente al calentamiento, junto con el hecho de que fenómenos extremos como la ola de calor Europea en 2003 redujeran la productividad primaria, matizan la hipótesis de que sea en los ecosistemas más fríos en los que el calentamiento global de lugar a una mayor absorción de carbono. Concretamente, la respuesta a los tratamientos de la biomasa a nivel de cubierta en Garraf pudo anularse debido a respuestas opuestas de las especies dominantes.
En este estudio, el gradiente geográfico que dibuja los matorrales estudiados no determinó la sensibilidad de las especies al calentamiento ni la intensidad de la respuesta en lo que a fenología del crecimiento y elongación de ramas se refiere. La fenología del crecimiento de algunas especies mediterráneas fue tan sensible al calentamiento experimental (se avanzó) como algunas especies de distribución más septentrional.
Aunque nuestro estudió mostró que la floración de E. multiflora y G. alypum, que tiene lugar en otoño-invierno, dependió en gran medida de la lluvia acumulada y su distribución durante el periodo primavera-verano, los tratamientos experimentales no afectaron esta variable. Estos resultados se explican en parte por la mayor variación de humedad que hubo entre años respecto a la diferencia de humedad que hubo entre las parcelas de sequía y controles.
This PhD thesis has been developed as part of the VULCAN project (Vulnerabibilty assessment of shrubland ecosystems during climatic changes), a research project conducted in six European shrublands (Wales, United Kingdom, Denmark, Holland, Hungary, Italy-Cerdagne and Catalonia-Spain), distributed in a gradient of temperature (8.2 - 15.6 ° C) and precipitation (511 - 1427 mm). It includes data collected during the 1999-2005 period.
The overall objective of the research was to provide knowledge and reduce uncertainties about the functioning of the shrublands and the role that they can play as a source or sink of carbon under the prospect of climate change.
At each site, novel experimental manipulations were installed to increase the temperature and to reduce the water available in field, simulating the effects of climate change projected for the future decades.
In this work we have studied the effects of treatments on plant diversity, aboveground primary productivity, as well as on the phenology of growth and on the shoot elongation of dominant species. In addition, in Garraf we investigated other processes at leaf level such fluorescence, photosynthesis, stomatal conductance and other at plant level such the response of the non-spring flowering species, Erica multiflora and Globularia alypum.
The effects of climate change at the ecosystem level were complex because of the great variability of plant responses to treatment according to the variables, species, seasons or years, sites and periods of experimentation.
In Garraf, an area which suffered a fire in 1994, we found a clear reduction in the number of species per transect on drought plots, but no similar effects were found in the rest of Europe, suggesting that communities in process of recovery after disturbance can be particularly sensitive to climate change compared to other communities in more mature stages. Specifically, we found that the experimental treatments reduced the competitive ability of the obligate seeder Pinus halepensis against native resprouter shrubs and that the water spender strategy of G. alypum may allow this species to maintain a dominant position in drought plots in Garraf.
In sites with lower aridity, the responses of the annual accumulated biomass to warming were more positive. However, the fact that we found Mediterranean species such as E. multiflora responding positively to global warming, coupled with the fact that extreme events such as the European heat wave in 2003 reduced primary productivity, challenge the assumption that it is in colder ecosystems where global warming will result in a greater carbon sequestration. Specifically, opposite responses of the dominant species could cancel out a clear response of biomass accumulation at canopy level in Garraf.
In this study, the geographical gradient did not determine the susceptibility of the species or the intensity of the response of the phenology of growth and shoot elongation to the warming treatment. The phenology of growth of some Mediterranean species was very responsive to warming treatment (mainly advances) as some species of northernmost distribution.
The study also shows that although flowering of E. multiflora and G. alypum, which takes place in the autumn-winter, depended largely on the accumulated rainfall and its distribution during the spring-summer period, the experimental treatments did not affect this variable. These results are explained in part by the greater range of soil moisture between years than between drought and controls plots.

Orientador: César Tadeu Spadella
Banca: Walkyria de Paula Pimenta
Banca: Luiz Antônio Lima Resende
Banca: Antônio de Castro Rodrigues
Banca: Lauro Bogodar Ruczynski
Resumo: A neuropatia motora distal é uma das freqüentes complicações do Diabetes Mellitus , e sua prevalência pode ser considera igual a 100%, se pacientes com alterações de condução nervosa, sem acompanhamento de sinais ou sintomas, são inclusos. Neste contexto, o presente estudo foi desenvolvido com o objetivo de obter informações relacionadas às polineuropatias periféricas em animais com diabetes induzido pela aloxana. Os grupos experimentais foram formados por 50 ratos diabéticos (GD) sem tratamento, da raça Wistar, machos, e 50 ratos não diabéticos (GND) da mesma espécie e idade. As avaliações eletrofisiológicas foram obtidas após 1, 3, 6, 9 e 12 meses de seguimento, respectivamente, nos cinco subgrupos, cada um, com cinco animais. Os exames dos nervos ciático e caudal mostraram: (i) os potenciais de ação muscular composto (CMAPs) apresentaram diminuição da amplitude e aumento da dispersão temporal; (ii) a velocidade de condução nervosa (NCV) foi menor (p < 0,05) no GD, com diferença estatisticamente significante na NCV do nervo caudal nos diferentes intervalos de tempo; (iii) a latência distal (DLAT) foi maior (p < 0,05) no GD, com diferença estatisticamente significante na DLAT do nervo caudal entre os vários subgrupos do GD. Estes resultados demonstram que o modelo experimental proposto pode ser usado para o estudo funcional da neuropatia diabética. Os parâmetros obtidos fornecem subsídios para testes com as terapias convencionais, as cirúrgicas e as de suplementação no tratamento da neuropatia diabética motora distal.
Abstract: Distal motor neuropathy is one of the most common complications of diabetes mellitus, and its prevalence can be considered as high as 100 percent if patients with abnormalities of nerve conduction without accompanying signs or symptoms are included. In this context, the present study was undertaken to obtain information concerning the peripheral polyneuropathies in alloxan-induced diabetic animals. Experiments were carried out on 50 untreated diabetic control (DG) Wistar male rats, and 50 age-matched nondiabetic controls (NDG). Electrophysiological assessments were obtained after 1, 3, 6, 9, and 12 months of follow-up, respectively, in the five subgroups with 5 animals each. Analysis of the recorded response from the right sciatic and caudal nerves showed: (i) diminished amplitude and increased temporal dispersion of the compound muscle action potentials (CMAPs) in the DG; (ii) nerve conduction velocity (NCV) lower (p< 0.05) in the DG, with statistically significant difference in NCV of the caudal nerve at different time intervals; (iii) distal latency (DLAT) higher (p< 0.05) in the DG, with statistically significant difference in DLAT of the caudal nerve among the several diabetic subgroups. These results demonstrate that the experimental model proposed can be used for a functional study of diabetic neuropathy. The parameters obtained supply assistance for tests with conventional therapies, with surgeries and those with supplementation in treatment of distal motor diabetic neuropathy.
Doutor

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Introdução: A tolerância cutânea à radiação é o principal fator limitante da radioterapia. A escassez de estudos experimentais é imensa, principalmente em animais de médio porte, como os coelhos. Objetivo: Descrever um modelo experimental de radiodermatite em coelhos Métodos: Neste estudo foram utilizados 24 coelhos da raça Nova Zelândia, machos, com 6 meses de idade, peso médio de 2,5 Kg. Os mesmos foram distribuídos em 4 grupos (n=6 para cada grupo), sendo um grupo controle (sem nenhuma intervenção) e os demais submetidos à radioterapia com sessão única de 10, 20 e 30 Gy, respectivamente. Foram realizadas análises fotográficas e histopatológicas das áreas irradiadas. Resultados: Os animais do grupo controle após 30 dias da epilação apresentaram crescimento dos fâneros regularmente. Os animais do grupo 20 Gy e 30 Gy apresentaram alopecia com duração de 60 dias e 90 dias, respectivamente. A partir do dia 30, a área irradiada dos animais do grupo 30 Gy apresentou grau 3 e 4 de radiodermatite, persistindo por 90 dias. A redução progressiva da contagem de anexos, vasos sanguíneos e um aumento da deposição de colágeno foi significante, quando comparado o o grupo controle com o grupo de 30 Gy. Conclusão: A dosagem de 30 Gy é a mais eficaz para este modelo experimental de radiodermatite.
Introduction: The cutaneous tolerance is a limiting factor for this oncologic treatment. The lack of experimental models is enormous, primarily for mid size animals, such as rabbits. Purpose: Describe an experimental model of cutaneous radiation injury in rabbits Methods: On this study 24 six-month-old New Zealand male rabbits, with an average weight of 2.5kg, were used. They were distributed in 4 groups (n=6 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 10, 20 and 30Gy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: After 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 20Gy had a 60-day alopecia and from group 30Gy, a 90-day alopecia. After the 30th day, the 30Gy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was significant, when the control group is compared to the group 30Gy. Conclusion: This study demonstrates the dosage 30Gy is the most effective for this experimental model of cutaneous radiation injury in rabbits.

The normative moral code is considered to be such that it applies universally to all or at least to all who can understand and govern their behavior by it. All or almost all common folk think of and use their own moral codes as them being normative in that for example there simply seem to them to exist “oughts” that apply to all and that there simply, straightforwardly are “things” that are right and wrong, good and bad. Gert Bernard and Gert Joshua have written an article on the topic of defining morality, with the title of “The Definition of Morality”. The authors suggest that the terms ‘normative morality’ refer to a code of conduct that, given some specified conditions, would be put forward by all rational persons. The authors take this formulation as entailing true and important definitional features of what normative morality is, although the authors think of this basic definition, conception as not being complete and that some additional feature hence is lacking but that any such candidate addendum to the definitional basic schema that they surveyed within the article seemed to be controversial, contested. Normative morality seems apt to investigate by creating thought-experiments wherein the participants are for example, envisioned choosing to endorse, put forward or act in accordance with a moral code. Within this large investigative project into normative morality with the help of thought-experiments it seemed to me that there was an under-representation of thought-experiments exhibiting some worthwhile and relevant features and I felt that it was a warranted project to create a thought-experiment which concurrently exhibited these features. Such an experiment could be thought of as an unusual “puzzle-piece” which could be valuable in contributing to furthering the completion of the “puzzle”, i.e. what normative morality is and its moral code. These three features were: i) a high degree of aptness for investigating a major part of or the complete normative moral code and ii) a high degree of freedom pertaining to the participants, e.g. their actions, thoughts etc., as well as iii) a high degree of confidence or warrant concerning what the participants would do, think, feel etc. within the thought-experiment. A thought-experiment, the Normative Moral Codes Workshop (NMCW) was hence created, which was aimed at investigating normative morality and its code and which exhibited these features. It is a thought-experiment mimicking an actual empirical study wherein the participants are given the task to together put forward the moral code for them, that would apply to them and that would cover a major or complete part of what they consider their moral codes to entail. The participants employed within my run of the NMCW thought-experiment were all currently living adult persons who I knew well. The core or main aim of this essay was to investigate whether it would or would not be the case that most or all participants within my run of the thought-experiment the NMCW would decide to put forward the code together with the chosen formulation of the thesis being, that it would not be the case that most or all participants would put forward the code within my run of the NMCW thought-experiment. Part of the core aim was also to elucidate why the thesis was supported or not supported as well as how strong the support was for the outcome of the experiment, i.e. the outcome of a code being put forward or not. The essay also has some minor aims which radiate out from the core aim (see below). As the thought-experimenter, I then reported on the events that I envisioned as happening within my run the NMCW thought-experiment as my selected participants grappled with the task and their decision to put or not put forward the code together that would apply to them. The finding was that the thesis was supported and that the support was robust in that I could identify several reasons the participants had against putting forward the code and I found very little in terms of reasons among the participants for putting forward the code. The essay also had some minor aims to selectively discuss a few further relevant and interesting issues radiating out from the core aim. These minor aims revolved around discussing some selected salient features of the NMCW including how they could relate to the outcome. One such selected salient feature was the feature of the employed participant sample of my run of the NMCW. I for example, discussed the potential extension of it not being the case that most or all participants would decide to put forward the code, if the participant sample would have been modified but still employed currently living5adults and I ended up being of the opinion that pertaining to most potential samples a similar outcome as the one envisioned within my run of the NMCW would be expected. I also wanted to discuss some further selected salient features of the NMCW within the context of addressing whether the NMCW, given its features ought to be considered an unsound, inapt experiment for investigating normative morality, given Gert’s and Gert’s conception of normative morality, since if this was the case the outcome of the experiment ought to be disregarded, given no weight. Although, I did find potential targets for criticism of the NMCW experimental design I did not find any reasons strong enough to disqualify the NMCW experiment as an experiment inapt, unsound for investigating normative morality, given the features of normative morality entailed within the suggested basic definition provided by Gert and Gert. Finally, I also aimed to selectively discuss some aspects of what it could mean pertaining to the conception of normative morality, according to Gert and Gert, that the thesis was supported. For example, given one interpretation the outcome could be taken to provide support for the non-existence of a normative moral code, but given another be taken to mean that addenda has to be identified and added to the basic conception of normative morality and that such addenda would be such that they would disqualify the NMCW (and its outcome) as a sound and apt thought-experiment to be employed in investigating normative morality. I also attempted to briefly illustrate how the NMCW thought-experiment could be used as a substratum facilitating the identification and clarification of such potential addenda to the basic conception of normative morality, suggested by Gert and Gert, and I also suggest some potential candidate features of the NMCW that further potential specifications added to the basic conception of morality ought to be able to disqualify, exclude as acceptable features of experiments aimed at investigating normative morality. In this way, an unusual, under-represented kind of thought-experiment, “puzzle-piece” when it comes to the large investigative project of employing experiments in order to acquire further insight into normative morality, i.e. “the puzzle”, can regardless of whether it seems to fit or does not seem to fit the “puzzle”, still be employed in such a way as to potentially provide further insight into “the puzzle”. This since even when a “puzzle-piece” does not seem to fit the “puzzle”, “seeing” and understanding how and why could provide us with information about the “puzzle”.
Den normativa moraliska koden anses vara sådan att den gäller universellt för alla eller åtminstone för alla som kan förstå den och reglera sitt beteende i enlighet med den. Alla eller nästan alla vanliga människor tänker och använder sig av sina moraliska koder som om dessa koder vore normativa, normerande genom att det t. ex. för dem helt enkelt verkar finnas ”måsten” som gäller alla och att det ”rakt upp och ner” verkar finnas ”saker” som helt enkelt är rätt och fel, gott och ont. Gert Bernard och Gert Joshua har skrivit en artikel kring ämnet hur man kan definiera moralen med titeln “The Definition of Morality” (sv. ”Moralens Definition”). Författarna föreslår att termen ’normativ moral’ (eller den ’normativa moralen’ i bestämd form) gäller en kod som reglerar hur man bör uppföra sig som givet vissa specificerade förhållanden är sådan att alla rationella personer skulle omfamna och förespråka den. Författarna anser att denna formulering innehåller viktiga och sanna egenskaper hos definitionen kring vad normativ moral är, även om författarna anser att denna basala, grundläggande definition, konception inte är fullständig och att därför vissa ytterligare definitions egenskaper, specifikationer saknas men att alla granskade kandidat-tillägg till denna basala definition som undersöktes inom artikeln verkade vara kontroversiella, enligt författarna. Normativ moral verkar lämplig för att undersökas genom att skapa tankeexperiment inom vilka deltagarna tex kan föreställas stödja, lägga fram eller agera i enlighet med en moralisk kod. Inom detta stora undersökande projekt av normativ moral med hjälp av tankeexperiment så verkade det enligt mig som om det fanns en under-representation av tankeexperiment som uppvisade vissa värdefulla och relevanta egenskaper och jag ansåg att det var ett rättfärdigat projekt att skapa ett tankeexperiment som uppvisade dessa värdefulla och relevanta egenskaper. Ett dylikt experiment kunde anses vara en ovanlig ”pusselbit” som kunde vara ett värdefullt bidrag till slutförandet av ”pusslet”, dvs vad normativ moral är och dess kod. De tre under-representerade egenskaperna var i) en hög grad av lämplighet för att undersöka en stor del av den normativa moraliska koden6eller den kompletta koden och ii) en hög grad av deltagarfrihet, exempelvis avseende deltagarnas handlingar, tankar osv samt iii) en hög grad av förtroende eller rättfärdigande avseende vad deltagarna skulle göra, tänka, känna osv inom tankeexperimentet. Tankeexperimentet, den Normativa Moraliska Kods Workshoppen (NMKW) skapades därför med målsättningen att undersöka den normativa moralen, dess kod samt att experimentet då skulle uppvisa de ovan nämnda egenskaperna. Det är ett tankeexperiment som liknar, ”speglar” en riktig empirisk studie inom vilka deltagarna ges uppgiften att tillsammans stödja och lägga fram den moraliska kod som skulle gälla för dem, reglera deras uppförande och som till en stor del eller fullständigt skulle täcka, innehålla det som de ansåg att deras moraliska koder innehöll. Deltagarna som användes inom min körning av tankeexperimentet var alla nu levande vuxna person som jag ansåg att jag kände väl. Kärn- eller huvudmålsättningen med uppsatsen var att undersöka huruvida det skulle eller inte skulle vara fallet att de flesta eller alla deltagare inom min körning av NMKW tankeexperimentet skulle bestämma sig för att tillsammans lägga fram och stödja en kod, med den valda formuleringen för tesen enligt, det skulle inte vara fallet att de flesta eller alla deltagare skulle lägga fram och stödja koden inom min körning av NMKW experimentet. Som en del av kärnmålsättningen var det att utreda varför tesen var eller inte var stödd samt utreda hur starkt stödet var för utfallet av experimentet, dvs utfallet att en kod lades fram eller inte lades fram. Uppsatsen har även mindre eller bi-målsättningar som strålar ut från uppsatsens huvudmålsättning (se nedan). I min roll som tanke-experimenteraren så rapporterade jag sedan kring vilka händelser som jag föreställde mig, som jag ”såg” uppträda inom tanke-experimentet NMKW då mina valda deltagare tog sig an uppgiften som de ombads att utföra, dvs att tillsammans lägga fram och stödja den kod som skulle komma att gälla dom själva, att appliceras på dom själva. Fyndet var att tesen stöddes och att detta stöd var robust eftersom jag kunde identifiera flera skäl hos deltagarna mot att lägga fram koden medan jag fann mycket litet i form av skäl hos deltagarna för att lägga fram koden. Uppsatsen hade även en del mindre målsättningar att selektivt diskutera några ytterligare relevanta och intressanta spörsmål som strålade ut från uppsatsens huvud-målsättning. Dessa mindre målsättningar kretsade kring att diskutera vissa valda tydliga, centrala egenskaper hos NMKW experimentet samt hur dessa kunde tänkas vara relaterade till experimentets utfall. En sådan egenskap vara den specifika deltagargruppen som användes vid min körning av experimentet. Jag diskuterade till exempel, den potentiella extensionen av utfallet att det inte var fallet att de flesta eller alla deltagare valde att lägga fram koden, ifall deltagargruppen modifierades men fortfarande bestod enbart av nu levande vuxna människor och min värdering var att ett liknande utfall, som vid min körningen av NMKW, verkade troligt för de flesta potentiella grupper av deltagare. Jag ville också diskutera vissa valda tydliga, centrala egenskaper hos NMKW experimentet inom kontexten kring huruvida NMKW experimentet givet dessa egenskaper, borde anses vara ett osunt, olämpligt experiment för att undersöka den normativa moralen, givet Gerts och Gerts konception av denna. Detta, eftersom om detta vore fallet så borde utfallet av experimentet förkastas och inte ges någon vikt. Trots att jag hittade potentiella saker att kritisera hos den experimentella designen hos NMKW så hittade jag inte några tillräckligt starka skäl för att diskvalificera NMKW experimentet som ett olämpligt, osunt experiment för att undersöka den normativa moralen, givet den normativa moralens egenskaper beskrivna, täckta inom Gerts och Gerts föreslagna basala, grundläggande definition av denna. Slutligen så ville jag även selektivt diskutera vissa aspekter kring vad det kunde betyda för konceptionen av den normativa moralen, enligt Gert och Gert, att tesen stöddes. Exempelvis, så givet en tolkning så kunde utfallet ses som ett stöd för icke-existensen hos den normativa moraliska koden, medan givet en annan tolkning så kunde utfallet anses betyda att ytterligare addenda till den basala definitionen av den normativa moralen måste identifieras och adderas till definitionen och att dylika addenda skulle komma att vara sådana att de skulle diskvalificera NMKW experimentet och dess utfall som ett sunt och lämpligt experiment att användas för att studera den normativa moralen, nu med dess extenderade specifikation. Jag försökte sedan att illustrera hur NMKW tankeexperimentet kunde användas som ett substrat för att underlätta identifieringen och förtydligandet av dylika potentiella tillägg till den basala konceptionen av den normativa moralen enligt Gerts och Gerts förslag, och jag föreslog även vissa potentiella kandidat egenskaper hos NMKW experimentet som dylika ytterligare tillägg till den basala konceptionen borde kunna diskvalificera, exkludera som acceptabla egenskaper hos experiment designade för att undersöka den7normativa moralen. På detta sätt så kan en ovanlig, underrepresenterad typ av tankeexperiment, ”pusselbit” när det gäller det stora undersökningsprojektet som använder sig av experiment för att erhålla ytterligare insikter inom den normative moralen, dvs ”pusslet”, oberoende om det verkar passa eller inte passa in i ”pusslet”, ändå användas på ett sådant sätt så att det potentiellt kan leda till ytterligare insikter kring ”pusslet”. Detta eftersom även när en ”pusselbit” inte verkar passa in i ”pusslet” så kan ”seendet”, förtydligandet och förståelsen kring hur och varför, ändå potentiellt förse oss med information om ”pusslet”.

Avaliou-se a atividade quimiopreventiva da tributirina (TB), e da vitamina A (VA) administradas em associação ou não, antes, durante e após a iniciação em ratos submetidos a modelo de carcinogênese de cólon. Ratos Wistar receberam VA [1 mg/100 g de p.c (grupo VA)], tributirina [200 mg/100 g de p.c (grupo TB)] ou associação de VA com TB (grupo VA+TB). Ratos tratados com óleo de milho e maltodextrina serviram como controle (GC). Avaliou-se a presença de focos de criptas aberrantes (FCA) e sua localização nos cólons, além de danos e do padrão de metilação global do DNA na mucosa colônica. No cólon total, distal e proximal, o grupo TB apresentou menor (p<0,05) número de FCA com 4 ou mais criptas/cm2, considerados mais agressivos, em relação ao GC. Quanto aos danos no DNA, os grupos VA, TB e VA+TB apresentaram cometas de comprimentos menores (p<0,05) em comparação ao GC. Não houve diferenças estatisticamente significantes quanto ao padrão de metilação global do DNA. Assim, TB consiste em agente quimiopreventivo promissor da carcinogênese de cólon quando administrada isoladamente, mas não em associação com a VA. 15
Chemopreventive activities of tributyrin (TB) and vitamin A (VA) were administered in combination or not, before, during and after the initiation in rats subjected to carcinogenesis model of colon. Wistar rats received VA [1 mg/100 g of b.w (group VA)], tributyrin [200 mg/100 g of b.w (TB group)] or association of VA with BD (group VA + TB). Rats treated with corn oil and maltodextrin were used as control (GC). The presence of aberrant foci crypts (ACF) was evaluated and their location in colon tissue was determined. In addition, DNA damages and the global pattern of DNA methylation in colonic cells was measured. In total colon as in distal and proximal portions, the TB group presented lower (p <0.05) number of ACF with 4 or more crypts/cm2 in comparison to the GC group. The number of ACF with 4 or more crypts /cm2 was used as criteria of aggressiveness. In relation to the damage of DNA, the VA, VA + TB and TB groups exhibits smaller nucleoids lengths (p <0.05) compared to the GC group. There were no statistically significant differences on the global pattern of DNA methylation. So TB is promising chemopreventive agent in carcinogenesis of the colon when administered alone, but not in combination with the VA.

The primary objective of this creative project was to explore and analyze the centuries old technique of animation. The investigation of the material included both text and also visual material such as existing films, videos and interviews.This body of work consisted of a variety of animation techniques combined into one film, a zoetrope with five hand-drawn strips and various forms of merchandise (stickers, bumper stickers and a t-shirt) based on the animation.The goal for this project was to convey the idea that animation is an unlimited field that is always open to new and exciting innovations. The author wanted to express the technique, rather than a plot or some concept to the viewer, with the intent that the viewer will be inspired to also experiment with animation.
Department of Art

In my paper I investigate the experimental nature of my multidisciplinary practice through theory and visual stimulus. I look at the image as a basis for aesthetic, emotional, and philosophical investigation; grounding my research in practice, contemporary photographic theory, ancient philosophy and modern physics. I look at developments in my installational practice in terms of Minimalist and Institutional concerns and performance installation in regards to Relational Aesthetics; this analysis of both the medium and context of the work leading to new strategies in exhibition practice. The grounding of theory in practice has over the course of my Masters project led to a new conception of my work as a series of exercises in medium reflexive practice. This paper outlines medium reflexivity and how this concept has shaped the work I have developed for my final examination as an experimental exhibition.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O Toxoplasma gondii é um protozoário parasita de grande importância no contexto de produção animal e saúde pública, envolvendo alterações fetais e abortos na espécie humana e em animais, sendo ainda importante patógeno oportunista em pacientes imunocomprometidos. A técnica de aglutinação direta modificada (MAT) destaca-se por independer da origem dos anticorpos e permitir diferenciar os estágios da infecção toxoplásmica. Assim, padronizou-se a técnica de sedimentação espontânea, verificando-se que com 60 minutos, a parte líquida da suspensão apresentava predominantemente taquizoítos e raras células pequenas. O antígeno inativado pelo metanol (AM) permitiu a exposição de antígenos de fase aguda somente, enquanto que a formalina (AF) expõe tanto os de fase aguda como crônica. Testou-se o antígeno para três grupos experimentais: G1, ratas infectadas com 104 bradizoítos da cepa BTU10, genótipo I, via oral; G2, ratas infectadas com 104 bradizoítos da cepa BTU10, via oral, e imunodeprimidas com corticóide; G3, grupo controle. A comparação das MATs permitiu a diferenciação dos anticorpos IgG de fase aguda, dos de fase crônica. Gradativamente foi obtida a maturação dos anticorpos, sendo observada pela avidez das mesmas no teste de ELISA. Os anticorpos do grupo experimental se comportaram semelhantemente para as provas sorológicas, até a 13ª semana. A reagudização no G2 foi detectada na bioprova da musculatura antes que no cérebro. Com isso, verificou-se que a MAT-AM e a MAT-AF permitem a diferenciação dos estágios agudo e crônico, e ainda a caracterização da reagudização da infecção em pacientes imunocomprometidos.
Toxoplasma gondii is a parasite protozoan with great importance to animal production and public health, involving foetal alterations and abortions in human and animal species, being an important opportunistic pathogen in immunocompromised patients. Modified agglutination test (MAT) has great importance to independ of the origin of antibody, and to allow differentiating the periods of the Toxoplasma infection. Thus, the protocol of spontaneous sedimentation we standardized, verifying that with 60 minutes, the liquid part of the suspension showed predominantly the presence of tachyzoites and rare small cells. The antigen inactivated with methanol (AM) allowed the exposition of antigens of acute phase only, while formalin (AF) as much the acute as chronic phase. Antigen was tested to three experimental groups: G1, rats infected with 104 bradyzoites of BTU10 strain, genotype I, orally; G2, rats infected with 104 bradyzoites of BTU10 strain, orally, and immunodepressed with corticoid; G3, control group. The comparation of MATs allows the differentiation of IgG from acute phase of the ones from chronic phase. A gradual maturation of immunoglobulins was gotten, being observed through the avidity of the same ones, and surveyed for ELISA. The antibodies of the experimental groups showed similar profile for all serological tests, until the 13th week. Reacutization of the infection in G2 was detected earlier in bioassay of musculature than brain. Thus, we verified that MAT-AM and MAT-AF allow the differentiation of the acute and chronic stages, and still the characterization of the reacutization of the infection in immunocompromised patients.
FAPESP: 2003/08063-0

Orientador: Araí Augusta Bernardez Pécora
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica
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Resumo: Os biocombustíveis têm sido utilizados como uma forma de solucionar os problemas relacionados à geração de energia a partir de combustíveis fósseis, por sua contribuição na redução das emissões de gases de efeito estufa e outros poluentes como SO2. O objetivo desta pesquisa é caracterizar a partícula e estudar o processo de conversão térmica de sementes de tucumã-do-Amazonas (Astrocaryum aculeatum) em óleo combustível através da caracterização dos produtos gerados no processo de pirólise rápida em reator de leito fluidizado borbulhante em escala laboratorial. O efeito da temperatura do processo foi analisado, variando-se a temperatura do reator entre 400 e 600°C, mantendo-se constante a velocidade superficial do gás de fluidização e, portanto o tempo de residência dos gases gerados no processo de pirólise. Em todos os testes, areia com diâmetro médio de 180 m foi o material inerte utilizado. As partículas de biomassa alimentadas no reator possuíam diâmetro inferior a 2 mm e os produtos (sólido, líquido e gás) gerados durante o processo foram quantificados e analisados, obtendo-se seus rendimentos em função da temperatura de operação do reator. Os resultados mostraram que a fração líquida apresentou maior rendimento quando a temperatura do reator foi de 500oC, representando 60% (em massa) dos produtos gerados. Nessa condição, o poder calorífico superior do bio-óleo (livre de umidade) foi de 20,22 MJ/kg, no entanto um valor de 30,48 MJ/kg foi obtido para temperatura do reator igual a 550°C, o que indica ter potencial para ser utilizado como biocombustível. O carvão vegetal produzido apresentou o maior poder calorífico superior a 500°C, com valor médio de aproximadamente 32 MJ/kg. A análise do carvão mostrou que o produto poderia ser aplicado como fonte para melhoria do solo assim como aditivo para fertilizante, devido aos teores obtidos de óxidos de Fe, Mg, Ca, K e Na no material. As análises dos gases produzidos mostraram que houve um crescente aumento no teor de monóxido de carbono com o aumento da temperatura do reator e que os gases gerados tem potencial para posterior queima e utilização como geradores de energia
Abstract: Biofuels have been used as a contribution to solve problems related to power generation from fossil fuels, since they contribute to reduce greenhouse gas emissions and other pollutant materials such as SO2. In addition, the use of biomass and organic wastes as fuel in power plants or small thermochemical processes that generate products with higher added values may encourage the development of remote areas. The purposes of this research were the particle characterization and the study of the thermal conversion process of Amazon-tucumã (Astrocaryum aculeatum) seeds into fuel oil through the process of fast pyrolysis in a laboratory scale bubbling fluidized bed reactor. The effect of process temperature was analyzed with variation of reactor temperature between 400 and 600°C, the gas superficial velocity was kept constant, therefore, the residence time of the gases produced in the process. In all the tests the sand presenting a Sauter mean diameter equal to 180 ?m was used as inert material. The biomass presented particle diameter smaller than 2 mm and the products generated (solid, liquid and gas) during the process were quantified and analyzed, obtaining their yields as a function of the reactor temperature. The results showed that the highest value of the liquid fraction (60%wt) was obtained when the reactor temperature was 500°C. At this condition the high heating value of bio-oil (moisture free) was 20.22 MJ/kg, however a value of 30.48 MJ/kg was obtained for the reactor temperature equal to 550°C, indicating the potential for being utilized as biofuel Regarding the biochar, the highest value for its heating value was roughly 32 MJ/kg (HHV), obtained at 500oC reactor temperature. Analysis of charcoal showed that the product could be used as a fertilizing to improve soil amendment, because of the high contents of Fe, Mg, Ca, K and Na oxides in the material. Analyses of the gases produced showed that there were an increasing in the content of carbon monoxide at higher temperatures and that the gases produced have potential for burning and utilization for energy generation
Mestrado
Termica e Fluidos
Mestre em Engenharia Mecânica

Orientador: Cesár Tadeu Spadella
Resumo: Sessenta animais da espécie "Rattus wistar" de ambos os sexos, pesando de 200 a 300 gramas, foram divididos em dois grupos experimentais: G1 ou grupo normal, constituído por dez animais e G2 ou grupo diabético, constituído inicialmente por 50 animais, que foram inoculados com aloxana à 2% por via endovenosa, na dose de 42mg/kg de peso corporal. Desses, dez animais com diabetes experimental grave (glicemia maior que 200mg/dl), sobreviveram durante o seguimento de 12 meses e constituíram o grupo diabético ou G2. Os seguintes parâmetros clínicos e laboratoriais foram estudados em cada grupo experimental: aspecto geral dos animais, peso, ingestão hídrica, ingestão alimentar, diurese e dosagens da glicemia, glicose urinária e proteinúria. As observações, com exceção da proteinúria de 24 horas, foram observadas em três momentos experimentais: inicial ou 14 dias após a indução do diabetes no grupo diabético e 14 dias de observação no grupo normal, 6º e 12º mês de seguimento. A dosagem da proteinúria de 24 horas foi efetuada no 12º mês de seguimento nos dois grupos experimentais. Após o 12º mês de seguimento, os animais foram sacrificados, após anestesia, e o rim direito de quatro animais diabéticos e quatro animais normais, escolhidos ao acaso, foi preparado para o estudo à microscopia eletrônica. As elétron-micrografias obtidas com aumento de 42.000 vezes foram analisadas por morfometria pela utilização de sistema computadorizado "Quin Lite 2,5 LEICA", interessando a espessura da MBG, o número de podócitos, o número de "slit diaphragm"e a extensão dos "slit diaphragm". Os resultados dos parâmetros clínicos e bioquímicos foram analisados pelo teste de comparações múltiplas de Tukey e pela análise não paramétrica de Mann-Whitney e Kruskal-Wallis, adotando-se o nível de significância de p< 0,05... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Sixty "Rattus wistar" of both sexes with 200-300 g of body weight, were divided in two experimental groups: normal group (G1 - 10 animals) and diabetic group (G2- 50 animals at the beginning), which were inoculated with a endovenous injection of 2% alloxan in a dose of 42 mg /kg/body weight. From these ten animals with severe experimental diabetics (glicemia > 200 mg%) will survive during 12 months of follow-up, being considered the experimental group (G2). The following clinic and laboratory parameters were studied: clinical aspect, body weight, water and food intake, diuresis, as well fasting glycemia, urinary glucose and proteinuria. The observations, excepting proteinuria (24 hours) were made at three experimental moments as it follows: initial or 14 days after diabetes induction or follow-up (normal controls) and at 6 and 12 months. Proteinuria was measured at the 12th month in boths groups. After 12 months of diabetes induction or follow-up (G1), the animals were sacrificed being the right kidney from four animals of each group processed for Electron Mycroscopy. The electron micrographys were taken with magnification of 42,000 and were analysed according to morphometric techniques by using computer System "Quin Lite 2.5 LEICA", being studied the following aspects: glomerular basement membrane thickening, podocytes and slit diaphragm number, and the slit diaphragm extension. The results of the clinical and laboratory parameters were statistically analysed according to Tukey's multiple comparison being used the level of 5% significance. The results of morphometric study were analysed according to Mann-Whitney and Kruskal-Wallis test, using a software "Sigma Stat 2,0", being used level of 5% significance. G2 group presented lower body weight, higher water intake and diuresis than G1 group; the general aspect... (Complete abstract click electronic address below)
Doutor

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system characterized by a coordinated inflammatory attack on the myelin sheaths with ensuing damage to the underlying axons. Using myelin oligodendrocyte glycoprotein (MOG)-induced chronic experimental autoimmune encephalomyelitis (EAE) as a MS model, it has been previously demonstrated that daily administration of the PDE-5 inhibitor sildenafil starting at peak disease rapidly ameliorates clinical symptoms whereas administration at the onset of symptoms prevents disease progression. These beneficial effects involved down-regulation of adaptive and innate immune responses and protection of axons and oligodendrocytes and promotion of remyelination. The aim of this work was confirm the remyelinating potential of sildenafil treatment and investigate mechanisms involved in this effect in CNS cells. Results show that sildenafil induces remyelination in EAE mice even when the administration of the drug starts during the chronic stage of the disease. Sildenafil also stimulates remyelination in cerebellar organotypic cultures demyelinated with lysophosphatidylcholine and this effect is prevented by inhibitors of nitric oxide-dependent guanylyl cyclase (NO-GC), NO synthase type 2 (NOS-2) and cGMP-dependent protein kinase (PKG), indicating the involvement of the endogenous NO-cGMP-PKG pathway. Maturation of oligodendrocytes as a potential mechanism implicated in the remyelinating effect of sildenafil was investigated by immunostaining for transcription factors involved in different stages of oligodendrocyte development. Results in the EAE model show that sildenafil treatment increases oligodendrocyte precursor cells (OPCs; Nkx2.2+ cells) and promotes the final stage of oligodendrocyte maturation (olig2-/MBP+ cells). These later result was confirmed in LPC-demyelinated cerebellar slices treated with cGMP increasing compounds. This work also shows that expression of the neurotrophic factor CNTF, that has been implicated in oligodendrocyte maturation, is increased in astroytes of sildenafil-treated EAE mice spinal cord, as well as in cerebellar slice cultures. Results also show that cGMP-increasing treatments alter expression of inflammatory phenotype markers (COX-2 and Arg-1) in microglia in demyelinated slice cultures. The potential of cGMP-increasing treatments for regulating the inflammatory phenotype of monocytes was confirmed in bone marrow derived macrophages (BMDM). In these cells sildenafil treatment induces arginase activity and potentiates the effect of IL-4 suggesting the promotion of an M2 phenotype. Analysis by flow cytometry of BMDM confirmed that cGMP augments the number of cells expressing an M2 phenotype marker (CD206). This work further demonstrates that sildenafil significantly increases the myelin phagocytic capacity of microglia/macrophages in EAE mice and in BMDM. Taken together these data suggest that promotion of oligodendrocyte maturation, growth factor expression, modulation of the inflammatory process and clearance of myelin debris may be relevant mechanisms involved in sildenafil enhancement of remyelination in demyelinated tissue.

Dissertação(mestrado) - Universidade Federal do Rio Grande, Programa de Pós-Graduação em Engenharia e Ciência de Alimentos, Escola de Química e Alimentos, 2009.
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O interesse na produção de astaxantina por fontes naturais vem aumentando significativamente nos últimos anos, devido a possibilidade de atuar como corante e sua capacidade antioxidante biológica potente. É o carotenóide principal encontrado na levedura Phaffia rhodozyma, sendo esse microrganismo adequado para o uso como fonte do pigmento industrial em razão de seu metabolismo heterotrófico, padrão de crescimento relativamente rápido, qualidade nutricional e seguro como aditivo alimentar. A presente dissertação teve como objetivo principal realizar cultivos utilizando a levedura Phaffia rhodozyma, estudando diferentes meios de cultura, empregando a água de parboilização do arroz como substrato. Inicialmente selecionou-se dentre 3 cepas de P. rhodozyma: NRRL Y-17268, NRRL Y-10921 e NRRL Y-10922, a mais promissora quanto a produção de astaxantina, utilizando glicose e sacarose como fonte de carbono. Os cultivos foram realizados em frascos agitados a 25ºC, 150rpm, por um período de 168h. Através do acompanhamento da bioprodução de astaxantina, a levedura P. rhodozyma NRRL Y-17268 foi selecionada, pois se destacou como boa produtora do carotenóide, alcançando 7,0g.L-1 de biomassa, 350,2μg.g-1 de produção de astaxantina específica e 2,4μg.mL-1 de astaxantina volumétrica, utilizando sacarose. Utilizou-se a metodologia de planejamento experimenta e análise de superfície de resposta para verificar os efeitos das variáveis em estudo e as condições que levaram a melhor bioprodução da astaxantina. Um planejamento experimental fracionário 2IV 6-2 foi realizado para determinar as variáveis que mais influenciavam na produção da astaxantina. As variáveis independentes estudadas foram concentrações de extrato de levedura (1 a 10g.L-1), extrato de malte (1 a 10g.L-1), peptona (1 a 10g.L-1), sacarose (5 a 20g.L-1), efluente da parboilização do arroz (0 a 180g.L-1) e o pH inicial do meio (4 a 6), tendo como resposta a produção de biomassa, produção de astaxantina específica e produção de astaxantina volumétrica. Os valores máximos obtidos foram 8,9g.L-1 de biomassa, 538,4μg.g-1 de astaxantina específica e 3,1μg.mL-1 de astaxantina volumétrica, em diferentes condições de composição de meio de cultivo. O extrato de levedura não apresentou efeito significativo em nenhuma das respostas avaliadas, sendo realizado um teste de Tukey na faixa de 0 a 1g.L-1. A concentração de extrato de levedura não apresentou diferença significativa, sendo retirado do meio de cultivo. No segundo planejamento foram ampliadas as faixas de estudo das variáveis selecionadas: concentrações de extrato de malte (8,75 a 16,25g.L-1), sacarose (15 a 35g.L-1), peptona (8,75 a 16,25g.L-1) e o pH mantido no ponto central 5,0. A partir dos resultados, verificou-se um incremento na concentração máxima de biomassa obtida, alcançando 10,9g.L-1 e na produção de astaxantina específica para 628,8μg.g-1. As melhores condições encontradas através das superfícies de resposta para maximização da produção de astaxantina volumétrica foram: 16,25g.L-1 de extrato de malte, 8,75g.L-1 de peptona, 15g.L-1 de sacarose e 87,5g.L-1 de água de parboilização do arroz, alcançando em torno de 5,4μg.mL-1.
The interest in astaxanthin production by natural sources has increased significantly in the last few years, because of its possibility of acting as corants and its powerfull biological antioxidant capacity. It’s the most important carotenoid found in the yeast Phaffia rhodozyma and this microorganism is appropriate to use in the source of industrial pigment due to its heterotrophic metabolism, relatively rapid growth, nutritional quality and safe as a food additive. The present dissertation had as main objective, through fermentation, using the yeast Phaffia rhodozyma studying different culture medium and the rice parboilization wastewater as a substrate. Firstly, the greatest astaxanthin producer, using glucose and sucrose as carbon source was selected amongst three strains of Phaffia rhodozyma: NRRL Y-17268, NRRL Y-10921 and NRRL Y-10922. The cultivation condition was realized in a rotatory flasks, at 25ºC, 150rpm, for 168h. Through the accompaniment of the bioproduction of astaxanthin, the yeast P. rhodozyma NRRL Y-17268 was selected, because it stood out as a good producer of the carotenoid, 7.0g.L-1 of biomass, 350.2μg.g-1 of specific production of astaxanthin and 2.4μg.mL-1 of volumetric production of astaxanthin, using sucrose. The techniques of experimental design and analysis of response surfaces were used to verify the effects of the studied variables and the condictions wich led to the best production of astaxanthin. A fractional experimental design 2IV 6-2 was used to determine the independents variables that most influenced in the production of astaxanhin. The studied independents variables were yeast extract concentration (1 to 10g.L-1), malt extract (1 to 10g.L-1), peptone (1 to 10g.L-1), sucrose (5 to 20g.L-1), rice parboilization wastewater (0 to 180g.L-1) and the initial pH (4 to 6), having as answer the biomass production, specific production of astaxanthin and volumetric production of astaxanthin. The highest values obtained were 8.9g.L-1 of biomass, 538.4μg.g-1 of specific astaxanthin and 3.1μg.mL-1 of volumetric astaxanthin, in differents conditions of composition of cultivation medium. The yeast extract didn’t show significant effect in any answer, being made a Tukey test in the range of 0 to 1g.L-1. In this test the yeast extract concentration didn’t show significant difference, then it was removed from the cultivation medium. In a second design the range were amplied: malt extract concentration (8.75 to 16.25g.L-1), sucrose (15 to 35g.L-1), peptone (8.75 to 16.25g.L-1) and the pH was maintained in the central point (5.0). From the results, verify an increased in the maximum biomass concentration obtained, reaching 10.9g.L-1 and in a specific production of astaxanthin to 628.8μg.g-1. The better conditions found through of response surface to the maximization of volumetric production of astaxanthin was: 16.25g.L-1 of malt extract, 8.75g.L-1 of peptone, 15g.L-1 of sucrose and 87.5g.L-1 of rice parboilization waste water, reaching around 5.4μg.mL-1.

This dissertation comprises two essays. The unifying theme is the evaluation of non-pecuniary (information or norm based messages) conservation programs. These types of policies are widely applied in developing and developed countries to promote conservation, however, their empirical evidence and their effectiveness are not well documented. Each chapter examines some methodological facets of the heterogeneity of non-pecuniary conservation programs and the reliability of non-experimental methods (program evaluation and econometric techniques) to evaluate treatment effects in the context of non-pecuniary conservation programs.

Two topics related to the experimental design are considered in this thesis. On the one hand, the uniform experimental design (UD), a major kind of space-filling design, is widely used in applications. The majority of UD tables (UDs) with good uniformity are generated under the centralized {dollar}L_2{dollar}-discrepancy (CD) and the wrap-around {dollar}L_2{dollar}-discrepancy (WD). Recently, the mixture {dollar}L_2{dollar}-discrepancy (MD) is proposed and shown to be more reasonable than CD and WD in terms of uniformity. In first part of the thesis we review lower bounds for MD of two-level designs from a different point of view and provide a new lower bound. Following the same idea we obtain a lower bound for MD of three-level designs. Moreover, we construct UDs under the measurement of MD by the threshold accepting (TA) algorithm, and finally we attach two new UD tables with good properties derived from TA under the measurement of MD. On the other hand, the problem of selecting a specific number of representative points (RPs) to maintain as much information as a given distribution has raised attention. Previously, a method has been given to select type-II representative points (RP-II) from normal distribution. These point sets have good properties and minimize the information loss. Whereafter, following similar idea, Fu, 1985 have discussed RP-II for gamma distribution. In second part of the thesis, we improve the discussion of selecting Gamma RP-II and provide more RP-II tables with a number of parameters. Further in statistical simulation, we also evaluate the estimation performance of point sets resampled from Gamma RP-II by making comparison in different situations.

With a rapid development of computing power, computer experiments have gained popularity in various scientific fields, like cosmology, ecology and engineering. However, some computer experiments for complex processes are still computationally demanding. A surrogate model or emulator, is often employed as a fast substitute for the simulator. Meanwhile, a common challenge in computer experiments and related fields is to efficiently explore the input space using a small number of samples, i.e., the experimental design problem. This dissertation focuses on the design problem under Gaussian process surrogates. The first work demonstrates empirically that space-filling designs disappoint when the model hyperparameterization is unknown, and must be estimated from data observed at the chosen design sites. A purely random design is shown to be superior to higher-powered alternatives in many cases. Thereafter, a new family of distance-based designs are proposed and their superior performance is illustrated in both static (one-shot design) and sequential settings. The second contribution is motivated by an agent-based model(ABM) of delta smelt conservation. The ABM is developed to assist in a study of delta smelt life cycles and to understand sensitivities to myriad natural variables and human interventions. However, the input space is high-dimensional, running the simulator is time-consuming, and its outputs change nonlinearly in both mean and variance. A batch sequential design scheme is proposed, generalizing one-at-a-time variance-based active learning, as a means of keeping multi-core cluster nodes fully engaged with expensive runs. The acquisition strategy is carefully engineered to favor selection of replicates which boost statistical and computational efficiencies. Design performance is illustrated on a range of toy examples before embarking on a smelt simulation campaign and downstream high-fidelity input sensitivity analysis.
Doctor of Philosophy
With a rapid development of computing power, computer experiments have gained popularity in various scientific fields, like cosmology, ecology and engineering. However, some computer experiments for complex processes are still computationally demanding. Thus, a statistical model built upon input-output observations, i.e., a so-called surrogate model or emulator, is needed as a fast substitute for the simulator. Design of experiments, i.e., how to select samples from the input space under budget constraints, is also worth studying. This dissertation focuses on the design problem under Gaussian process (GP) surrogates. The first work demonstrates empirically that commonly-used space-filling designs disappoint when the model hyperparameterization is unknown, and must be estimated from data observed at the chosen design sites. Thereafter, a new family of distance-based designs are proposed and their superior performance is illustrated in both static (design points are allocated at one shot) and sequential settings (data are sampled sequentially). The second contribution is motivated by a stochastic computer simulator of delta smelt conservation. This simulator is developed to assist in a study of delta smelt life cycles and to understand sensitivities to myriad natural variables and human interventions. However, the input space is high-dimensional, running the simulator is time-consuming, and its outputs change nonlinearly in both mean and variance. An innovative batch sequential design method is proposed, generalizing one-at-a-time sequential design to one-batch-at-a-time scheme with the goal of parallel computing. The criterion for subsequent data acquisition is carefully engineered to favor selection of replicates which boost statistical and computational efficiencies. The design performance is illustrated on a range of toy examples before embarking on a smelt simulation campaign and downstream input sensitivity analysis.

Rubber material used in seismic isolation systems has a tendency to stiffen in cold climate conditions. Structural responses of rubber based seismic isolation bearings are known to be temperature dependent. The main focus of this research is to investigate the temperature related behavior shifts at a certain type of a rubber based seismic isolation system. This research is a complementary study to a recent experimental study on a newly developed seismic isolator called &ldquo
Ball Rubber Bearing&rdquo
(BRB). BRBs can be easily manufactured as in the case of a standard rubber based bridge bearing and can provide adequate energy dissipation during an earthquake. However, structural response of BRBs at low temperatures has not been examined yet. In this research, behavior of BRBs exposed to different temperatures is examined under combined axial and cyclic lateral load. The performance of the specimens used in this study, &ldquo
Elastomeric Bearing&rdquo
(EB) and &ldquo
Ball Rubber Bearing&rdquo
(BRB) are compared with each other and also with previous researches conducted in this topic. The results indicated that BRBs show better performance at low temperatures in terms of energy dissipation compared to room temperature performance. Big size bearings have higher energy dissipation per cycle compared to small size bearings by reason of size effect. The higher damping percentage is observed at the small size bearings compared to big size bearings due to better confinement of the inner core. As a result of temperature records heat exchange is not detected in the rubber during cyclic loading.

Este proyecto se origina a partir del encargo realizado por el DIE de la U. de Chile. Consiste en el diseño, desarrollo y construcción de una plataforma experimental para el laboratorio de robótica del departamento. Esta plataforma experimental es entendida como un robot de pruebas destinado al ensayo empírico. Es el soporte físico que permite la experimentación y el análisis de errores para el desarrollo de nuevas soluciones de hardware, software y firmware. Estas plataformas deben; por lo tanto, dar la posibilidad de modificar su configuración según el experimento que se desee realizar, estas modificaciones por lo general se basan en el intercambio de componentes o software asociado a la plataforma. Uno de los objetivos fundamentales en el diseño del nuevo robot es abordar lo referido a su apariencia externa, variable que generalmente se deja de lado en la construcción de robots experimentales en el laboratorio, y es por esto que fue tomado como proyecto para optar al título de Diseñador. Además de la apariencia de la plataforma, el proyecto de diseño considera la interfaz operacional de ésta, siendo este ámbito (la interfaz) la esencia del proyecto de diseño, por lo que es a partir de esta interfaz que se desarrolla posteriormente la forma.

Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista
INTRODUCCIÓN: El dolor es una experiencia desagradable asociada a un daño real o potencial que en su forma aguda funciona como un sistema de defensa del organismo, pero al volverse crónico se transforma en un estado patológico que debe ser tratado. El dolor neuropático constituye un tipo de dolor crónico con características propias que inclusive puede llegar a ser inhabilitante para quién lo padece. A nivel orofacial puede expresarse más comúnmente en cuadros de neuralgia trigeminal o neuralgia post-herpética. El manejo de este tipo de dolor en la actualidad no tiene resultados óptimos y se ha comprobado que la terapia de combinación de fármacos tiene mejores resultados que la monoterapia. Al ser los antidepresivos tricíclicos y anticonvulsivantes considerados como el tratamiento de primera línea ante este tipo de dolor, se han incluido en este estudio la nortriptilina y el ácido valproico para evaluar su interacción mediante el Test de la Formalina Orofacial, con el fin de generar bases científicas para futuros ensayos clínicos de analgesia multimodal ante el dolor neuropático a nivel trigeminal. MATERIALES Y MÉTODOS: Se administraron vía intraperitoneal distintas dosis de nortriptilina, ácido valproico y la combinación de ambas a ratones. Se les realizó posteriormente el test de la formalina orofacial al 2% para medir los efectos antinociceptivos de cada fármaco y de la combinación de ambos y compararlo con un grupo control. Finalmente se realizó un estudio isobolográfico para definir la naturaleza de la interacción entre ambos medicamentos. RESULTADOS: La administración de nortriptilina, ácido valproico y la combinación de ambos, producen antinocicepción dosis-dependiente tanto en la fase algésica aguda (fase I) como en la inflamatoria (fase II) del test, siendo mayor para la fase II tanto en el grupo tratado con nortriptilina como en el de ambos fármacos combinados. La interacción producida entre nortriptilina y ácido valproico resultó ser de antinocicepción sinérgica. CONCLUSIONES: La nortriptilina y el ácido valproico producen un efecto de antinocicepción sinérgica administrados intraperitonealmente en ratones y sugiere que esta terapia combinada mejoraría la antinocicepción en casos de dolor neuropático a nivel trigeminal. Se necesitan estudios clínicos de esta combinación para poder extrapolar los resultados a humanos.

Relatively new transducers permit the measurement of dynamic response at many structure locations. Included among such transducers is the scanning laser Doppler vibrometer (LDV). A scanning LDV can measure velocity at many structure locations. An important new technique, Experimental Spatial Dynamics Modeling (ESDM), utilizes such spatially dense velocity data. ESDM models continuous, three-dimensional velocity fields using LDV velocity data. Thus, ESDM is a powerful structural dynamics analysis tool that significantly enhances the usefulness of a scanning LDV. However, heretofore, ESDM has not been experimentally evaluated. The results contained herein partially satisfy this need. Specifically, this research evaluated the ability of ESDM to reconstruct velocity response fields with large in-plane components parallel to a surface in the presence of small out-of-plane components transverse to the surface. To fulfill this objective, a test structure was developed and fabricated; the structure had certain dynamic properties which aided ESDM evaluation. Subsequently, the test structure was harmonically excited at a single frequency such that large in-plane and small out-of-plane velocity components were present on a particular surface. LDV and accelerometer data were then collected. Ultimately, velocity results were obtained from the LDV data via ESDM and the accelerometer data. Velocity results derived from the accelerometer data served as an experimental standard against which ESDM results were compared. Result comparisons clearly indicate that ESDM accurately reconstructs surface velocity fields with large in-plane and small out-of-plane components.
Master of Science

Orientador : Yong Kun Park
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos e Agricola
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Resumo: As propriedades das b-galactosidases da soja e do feijão, purificadas por fracionamento com sulfato de amônio, cromatografia em DEAE-celulose e filtração molecular em Sephadex G-100 foram examinadas.A filtração em Sephadex G-100 produziu duas frações, designadas I e II, com diferentes pesos moleculares. As formas I e II de cada amostra mostraram diferenças em seus valores de pH e temperatura ótima, energia de ativação, Km e Vmax com PNPG, melibiose ou rafinose como substratos. Não se observaram diferenças em suas estabilidades ao calor e à variação de pH.As enzimas apresentaram atividade máxima entre pH 5,0 e 6,0 e foram estáveis na faixa ao redor do pH ótimo; os valores de temperatura ótima ficaram entre 45 e 55ºC e as atividades enzímicas perma-neceram estáveis até 50ºC e todas elas mostraram maior especificidade para o PNPG. Íons metálicos como Ag+ e Hg+2 causaram completa perda de atividade; entretanto, as enzimas não foram sensíveis aos reagentes sul-fidrílicos, sugerindo não haver necessidade de grupos - SH para a atividade catalítica. As enzimas foram inibidas competitivamente por glicose, mais intensamente por galactose e não competitivamente por frutose. As duas formas enzímicas do feijão foram inibidas por al--tas concentrações de PNPG
Abstract: B-Galactosidases from soybean (Glycine max) and feijão (Phaseolus vulgaris) seeds were purified by ammonium sulfate fractionation, chromatography on DEAE-cellulose and gel filtration on Se-phadex G-100, and studied their characteristics. It was found that b-galactosidase was multiple forms, which was consisted of two frac-tions (fraction I and II). Fractions I and II of each sample exhibited differences in their optimal pH and temperature, activation energy, Km and Vmax values with PNPG, melibiose or raffinose as substrates. The properties of the enzymes from these seeds resembled each other with respect to their pH and thermal stabilities. The enzymes showed maximum activity between pH 5.0 and 6.0 and were stable in and around this range. The optimal temperature values were observed between 45 and 55ºC and the enzymes were stable up to 50ºC. All forms were more specific for PNPG. Metal ions such as Ag+ and Hg+2 caused complete loss of activity and sulfhydryl reagents had no effect on the enzyme activities, indicating that the -SH group is not involved in the catalytic site. Glucose and galactose inhibited the enzymic activities competitively, whereas fructose had a non-competitive effect. Two forms of Phaseolus vulgaris b-galactosidase were inhibited by PNPG at high concentrations
Mestrado
Mestre em Ciência de Alimentos

Las emulsiones son dispersiones de dos líquidos inmiscibles que, generalmente están estabilizadas por moléculas tensioactivas. Cuando la fracción en volumen de fase dispersa es superior o igual a 0,74 (valor que corresponde al máximo empaquetamiento de gotas esféricas indeformables y monodispersas) se denominan altamente concentradas. Dichas emulsiones tienen una elevada relación superficie/volumen, además de regiones hidrófilas y lipófilas bien definidas que permiten la incorporación de moléculas de diferente naturaleza. Por todo ello, tienen aplicaciones en el campo farmacéutico, cosmético, alimentario, en síntesis de materiales, etc. En la mayoría de aplicaciones, los procesos de difusión desempeñan un papel importante y por este motivo, se han estudiado los mecanismos de difusión para determinar la influencia de las propiedades de las emulsiones en dichos mecanismos. Sin embargo, no se ha estudiado de forma simultánea la influencia que los factores de composición y formación podrían ejercer sobre los procesos de liberación. Por este motivo, el objetivo principal de esta tesis, ha sido el de modelizar la formulación de emulsiones altamente concentradas de tipo W/O estudiando la relación entre el tamaño de gota, sus propiedades reológicas y la liberación de moléculas activas, incorporadas en la fase dispersa, a soluciones receptoras. Para alcanzar dicho objetivo, se seleccionaron componentes biocompatibles y biodegradables para formar emulsiones altamente concentradas de tipo W/O. De este modo, se seleccionaron tensioactivos derivados de ésteres como el poligliceril-2 diisoestearato (IS-202P), el monoleato de sorbitán (Span80) y un polioxietileno de sorbitano (Tween80), de alcoholes etoxilados (Brij52), del aceite de ricino (CremophorWO7), y dos tensioactivos poliméricos de bloque o copolímeros (SynperonicL2 y PluronicL121). Como componentes oleosos, se seleccionaron hidrocarburos alifáticos (aceite de parafina y escualano), un éster derivado del ácido oleico (decil oleato) y un triglicérido derivado de los ácidos grasos caprílico/cáprico (triglicéridos de cadena media). Se realizaron estudios de formación de emulsiones altamente concentradas, caracterizando las emulsiones formadas, que permitieron seleccionar un sistema modelo (solución acuosa/Span80/aceite de parafina), además del método de adición del componente acuoso a la mezcla del componente oleoso y tensioactivo, como el más apropiado para formar las emulsiones. Asimismo, se seleccionaron tres moléculas activas modelo el metilparabeno, etilparabeno y propilparabeno, ya que se podían incorporar en la fase dispersa de emulsiones altamente concentradas seleccionadas, sin modificar las propiedades de dichas emulsiones. Una vez seleccionados el sistema y las moléculas activas modelo, se aplicaron dos diseños de experimentos. El primero, un diseño central compuesto, permitió relacionar el tamaño de gota y las propiedades reológicas con variables de composición y formación de las emulsiones en ausencia de parabenos. El segundo, un diseño factorial fraccionado permitió la obtención de un modelo empírico para modelizar la formulación de emulsiones altamente concentradas, optimizando su tamaño de gota, sus propiedades reológicas, así como la liberación de las moléculas activas incorporadas. Se realizó un estudio comparativo de la formulación optimizada variando el aceite y el componente tensioactivo, determinando que influía más la estructura del tensioactivo que la polaridad del componente oleoso. También se realizó un estudio preliminar de escalado de la formulación óptima poniendo de manifiesto que, a pesar de la complejidad de los procesos de difusión que tienen lugar en las emulsiones altamente concentradas, en el escalado se obtuvieron resultados de liberación razonablemente similares. Mediante la utilización de diseños de experimentos y seleccionado un sistema modelo de tipo componente acuoso/tensioactivo no iónico/componente oleoso, se ha optimizado la formulación de emulsiones altamente concentradas de tipo W/O, obteniendo un modelo empírico que ha permitido optimizar el tamaño de gota, propiedades reológicas y modular el perfil de liberación de moléculas activas incorporadas en el componente acuoso de dichas emulsiones.
Emulsions are dispersions of two immiscible liquids, generally stabilized with surfactants. When the volume fraction of the disperse phase exceeds 0.74 (the maximum packing of spherical, undistorted and monodisperse droplets), emulsions are classified as highly concentrated emulsions. In most applications of highly concentrated emulsions, diffusion processes have an important role, and as a consequence, diffusion of active molecules incorporated in the disperse phase of emulsions has been studied to find out their relationship with emulsion properties. However, there is still a lack of knowledge on the relationship among composition and formation factors with diffusion processes. The main objective of this thesis has been to model the formulation of highly concentrated W/O emulsions, studying the relationship between droplet size, rheological properties and the release of active molecules, incorporated in the dispersed phase, to receptor solutions. To achieve this objective, the selected surfactants were: sorbitane monooleate (Span80) and polyglyceryl-2 diisostearate (IS-202P). The oil components were aliphatic hydrocarbons (paraffin oil and squalene). Methylparaben, ethylparaben and propylparaben were chosen as model active molecules. Their incorporation in the aqueous phase of emulsions did not modify emulsion properties. An experimental design was performed to optimize the formulation of emulsions in the model aqueous solution/Span80/paraffin oil system. The optimized formulation was compared with other systems by varying oil and surfactant components, concluding that the influence of surfactant structure was more important than the oil polarity. Furthermore, a preliminary scale up study was carried out with the optimized formulation and the results for the two scales considered were reasonably similar. Using design of experiments and selecting a model aqueous/nonionic surfactant/oil system, an empirical model has been obtained that has allowed to optimize emulsion droplet size, their rheological properties and the release of active molecules incorporated in the aqueous phase of these highly concentrated W/O emulsions.

Resumo: Os objetivos do presente estudo foram comparar as populações bacterianas intra-peritoneais e os níveis de bacteremia, em ratos induzidos com peritonite fecal e pneumoperitônio ou laparotomia, com irrigação da cavidade abdominal. Foram utilizados 60 ratos Wistar machos, pesando entre 276 e 290g, divididos em 6 grupos com 10 animais cada. A indução da peritonite foi feita pela inoculação intra-peritoneal de 0,5ml de suspensão fecal humana. O pneumoperitônio foi realizado por 60 minutos, com dióxido de carbono, em pressão constante de 10mmHg. No grupo peritonite e pneumoperitônio (PT+PP) os animais foram submetidos a pneumoperitônio e irrigação da cavidade abdominal com 20ml de solução salina isotônica 12 horas após à indução da peritonite. No grupo peritonite e laparotomia (PT+LAP) procedeu-se laparotomia 12 horas após a indução da peritonite com concomitante irrigação similar da cavidade abdominal. Nos demais grupos realizaram-se: pneumoperitônio e irrigação da cavidade abdominal sem indução prévia de peritonite (PP); indução de peritonite (PT); laparotomia e irrigação da cavidade abdominal sem indução prévia de peritonite (LAP) e o grupo de controle normais (N) no qual se realizou somente coleta de amostras. As amostras de sangue e líquido peritoneal foram coletadas em todos os grupos, 12 horas após a indução da peritonite (T1) e 5 horas após a realização dos procedimentos: laparotomia, pneumoperitônio ou controles (T2). Os resultados obtidos foram: Ocorrência de bacteremia com níveis similares de contagens de bactérias aeróbicas em todos os grupos submetidos à indução de peritonite. O pneumoperitônio e a laparotomia não induziram bacteremia em ratos normais. Os grupos PT+LAP e PT+PP apresentaram redução nos níveis de contaminação peritoneal, quando comparados ao grupo PT (p=0,00004 e p=0,0000006). Os grupos PT+LAP e PT+PP não diferiram entre si, quanto à população bacteriana intra-peritoneal (p=0,8282). No grupo PT+PP os níveis de bacteremia foram significativamente maiores que no grupo PT+LAP (p=0,0035). Concluiu-se nestas condições experimentais, que tanto a laparotomia quanto o pneumoperitönio, ambos, acompanhados de irrigação da cavidade abdominal com Solução Salina Isotônica apresentaram efeitos similares sobre a população bacteriana intra-abdominal em ratos com peritonite induzida; contudo, o pneumoperitonio com dióxido de carbono, durante 60 minutos, sob pressão constante, acompanhados de irrigação da cavidade com SSI, determinou níveis mais elevados de bacteremia que a laparotomia sob as mesmas condições de irrigação da cavidade abdominal.

Bebês precocemente desmamados apresentam maior incidência de infecções, o que sugere que a ausência de ingestão de alguns fatores presentes no leite materno possa modificar processos de defesa. A glutamina (GLN) está presente em concentração significativa no leite materno, sendo o aumento de sua concentração diretamente proporcional ao período de aleitamento. Esse aminoácido é essencial para a funcionalidade de macrófagos, que apresentam aumento da utilização de GLN durante processos inflamatórios e infecciosos. Bebês apresentam necessidade aumentada de GLN, que é suprida pela ingestão do leite materno, enquanto bebês precocemente desmamados dependem da síntese endógena e do fornecimento exógeno de GLN; todavia, a concentração de GLN em fórmulas infantis artificiais é significantemente baixa ou inexistente. Diante desses fatos, o presente projeto avaliou: (i) o efeito do desmame precoce associado à ingestão de ração isenta e suplementada de GLN sobre a funcionalidade de macrófagos peritoniais e o estado nutricional de camundongos; (ii) o efeito da suplementação com GLN in vitro sobre a funcionalidade de macrófagos peritoniais de camundongos desmamados precocemente e alimentados com ração isenta de GLN; e (iii) o efeito da suplementação crônica com GLN in vivo sobre a funcionalidade de macrófagos peritoniais e o estado nutricional de camundongos desmamados precocemente e inoculados com bacilo de Calmette-Guérin (BCG). O desmame precoce associado à ingestão de ração isenta de GLN reduz o crescimento de camundongos e a concentração de proteína presente no fígado, no músculo esquelético e na carcaça, ao mesmo tempo em que diminui as concentrações plasmática e muscular de GLN e prejudica a resposta hematopoiética (leucopenia e linfopenia associada à redução da celularidade na medula óssea) e a funcionalidade de macrófagos peritoniais (redução da capacidade de adesão, espraiamento, fagocítica e fungicida e da síntese de óxido nítrico (NO), peróxido de hidrogênio (H2O2), fator de necrose tumoral (TNF)-α, interleucina (IL)-1β e IL-6). A suplementação com GLN, por meio da ração, reverteu a diminuição da concentração muscular e hepática de proteína, enquanto essa intervenção nutricional reverteu apenas parcialmente as alterações observadas no tocante à funcionalidade de macrófagos (capacidade de espraiamento e síntese de H2O2, NO, TNF-α, IL-1 e IL-6). A suplementação com GLN in vitro, similarmente ao efeito da suplementação in vivo, reverteu apenas parcialmente o prejuízo da função de macrófagos peritoniais de camundongos desmamados precocemente (capacidade de adesão, espraiamento e fagocítica e síntese de H2O2, NO e IL-6). A suplementação crônica com GLN acarreta em aumento da função de macrófagos peritoniais de camundongos previamente inoculados com BCG (capacidade de adesão, espraiamento e fungicida e síntese de H2O2, NO e TNF-α). A partir dos resultados obtidos neste estudo, conclui-se que a GLN modula a função de macrófagos peritoniais de camundongos desmamados precocemente, contudo, a ausência desse aminoácido na dieta é responsável parcialmente pelo prejuízo induzido pelo desmame precoce.
Precociously weaned infants present a higher incidence of infections, which suggests that the absence of ingestion of certain factors present in maternal milk may modify the organism\'s processes of defence. Glutamine (GLN) is present in a significant concentration in maternal milk, this concentration increasing proportionally with the duration of lactation. This amino acid is essential for the correct functioning of macrophages, which increase their demand for GLN during inflammatory and infectious processes. Infants present a high demand for GLN, which is supplied by the ingestion of maternal milk. Precociously weaned infants, on the other hand, depend on the endogenous synthesis and on the exogenous supply of GLN, however, the concentration of GLN in artificial formulations for infants is significantly low or nonexistent. In view of these facts, this study sought to evaluate: (i) the effect in mice of precocious weaning coupled with an ingestion of either a GLN-free or rich diet on the functionality of their peritoneal macrophages and their nutritional state; (ii) the effect of an in vitro supplementation with GLN on the functionality of peritoneal macrophages obtained from precociously weaned mice that were fed a GLN-free diet; and (iii) the effect of a chronic supplementation with GLN in vivo on the functionality of peritoneal macrophages and on the nutritional state of precociouslyt weaned mice that were previously inoculated with BCG. Early weaning coupled with the ingestion of a GLN-free diet slows down growth in mice and decreases the concentration of protein in the liver, in the skeletal muscle and in the carcass, and at the same time decreases the concentration of GLN in the plasma and in the muscle, hindering the haematopoietic response (resulting in leucopoenia and lymphopoenia associated to the decrease in bone marrow cellularity) as well as the functionality of peritoneal macrophages (decrease in their capacity to adhere, spread, phagocyte, kill fungi and synthesise nitric oxide (NO), hydrogen peroxide (H2O2), tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6). The supplementation with GLN through ingestion of ration was able to reverse the fall in muscle and liver concentrations of protein, whereas it only partly reversed the alterations observed as to the functionality of macrophages (adhesion, spreading, and synthesis of H2O2, NO, TNF-α, IL-1 and IL-6). The in vitro supplementation with GLN, like the effect of the supplementation in vivo, was able to only partly reverse the hindering of the functionality of peritoneal macrophage obtained from precociously weaned mice (as to adhesion, spreading, phagocytosis and synthesis of H2O2, NO and IL-6). The chronic supplementation with GLN leads to an increase in the functionality of peritoneal macrophages obtained from mice that were previously inoculated with BCG (as to adhesion, spreading, killing fungi and synthesis of H2O2, NO and TNF-α). We can therefore conclude, from the results obtained in this study that GLN modulates the functionality of peritoneal macrophages obtained from precociously weaned mice and that the absence of GLN in the diet is partly responsible for the damage induced by precocious weaning.

Orientador: Auteliano Antunes dos Santos Junior
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica
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Resumo: O presente trabalho tem como objetivo apresentar e aplicar uma metodologia que possa ser utilizada nos diagnósticos de falhas, a priori, com causas desconhecidas ou diferentes das já conhecidas, por equipes de desenvolvimento de novos produtos. Esse tipo de falha acontece principalmente quando trata-se de produtos inovadores e ocorrem durante o processo de validação e mesmo após o início da produção. A metodologia se baseia na aplicação de Planejamento de Experimentos em conjunto com Árvore de Falhas para a quantificação das importâncias das causas raiz. Como resultado do trabalho é possível identificar quais parâmetros são os principais candidatos a causadores da falha e hierarquizar as causas. É possível ainda verificar as interações entre as causas, se existirem. A combinação entre métodos proposta pode ser inserida em metodologias de projeto consagradas, como o Projeto para Seis Sigma (DFSS), criando uma nova forma de desenvolver projetos inovadores
Abstract: The present work aims to present and apply a methodology that can be used on failures diagnosis, with unknown or different causes from those already known by the development team. This kind of failure happens mainly along the design of innovative products and occurs during the validation process or in the infant life phase. The methodology is based on Design of Experiments, which is applied together with Failure Tree Analysis to quantify the importance of each root cause. From the results of this work it is possible to identify what are the main causes related to the fault and rank them. It is also possible to verify whether there are interactions between the causes or not. The methodology proposed joining both methods can be inserted unusual design methodologies as Design of Six Sigma, creating a new way to develop and improve innovative designs
Mestrado
Mecanica dos Sólidos e Projeto Mecanico
Mestre em Engenharia Mecânica

El treball presentat s'emmarca dins del camp d'actuació propi del Grup de Recerca en Sistemes Intel·ligents: l'aprenentatge artificial. Les grans àrees són la computació evolutiva i el raonament basat en casos, tot dirigint la recerca a problemes de classificació, diagnosi i predicció. En tots aquests camps són objecte d'estudi grans conjunts de dades, pels quals es treballen diferents tècniques que en permeten l'extracció de coneixement i l'aplicació als problemes citats. Els grans avenços en aquestes àrees (sovint en forma de nous algorismes) conviuen amb treballs molt parcials sobre les metodologies adequades per a l'avaluació d'aquestes noves propostes.

En front d'aquesta situació, la tesi que aquí es presenta proposa un nou marc general per a l'avaluació del comportament d'un conjunt d'M algorismes que, per tal de ser analitzats, són assajats sobre N problemes de prova. La tesi sosté que l'anàlisi habitual que es fa d'aquests resultats és clarament insuficient, i que degut a això les conclusions que s'exposen en els treballs publicats són sovint parcials, i en alguns casos fins i tot errònies.

El treball s'inicia amb un estudi introductori sobre les mesures que permeten expressar la bondat d'un algorisme, a través de l'assaig sobre una col·lecció de problemes de prova. En aquest punt, es demostra la necessitat d'un estudi previ de les propietats inherents d'aquests problemes (a partir, per exemple, de les mètriques de complexitat) si es vol assegurar la fiabilitat de les conclusions que s'obtindran.

A continuació, es defineix el marc d'aplicació de tot un conjunt de tècniques d'inferència estadística per les quals, essent aquestes prou ben conegudes, s'analitzen els factors a tenir en compte en la determinació del seu domini d'ús. La tesi proposa un protocol general per a l'estudi, des d'un punt de vista estadístic, del comportament d'un conjunt d'algorismes, incloent uns nous models gràfics que en faciliten l'anàlisi, i l'estudi detallat de les propietats inherents als problemes de prova utilitzats.

Aquest protocol determina el domini d'ús de les metodologies per a la comparació dels resultats obtinguts en cada problema. La tesi demostra, a més, com aquest domini està directament relacionat amb la capacitat d'aquesta metodologia per a determinar diferències significatives, i també amb la seva replicabilitat.

Finalment, es proposen un conjunt de casos sobre resultats ja publicats amb anterioritat, fruit de nous algorismes desenvolupats pel nostre Grup de Recerca, molt en especial en l'aplicació del raonament basat en casos. En tots ells es mostra la correcta aplicació de les metodologies desenvolupades en els capítols anteriors, i es destaquen els errors comesos habitualment, que duen a conclusions no fiables.
El trabajo presentado se enmarca dentro del campo de actuación propio del Grupo de Investigación en Sistemas Inteligentes: el aprendizaje artificial. Las grandes áreas son la computación evolutiva y el razonamiento basado en casos, dirigiendo la investigación a problemas de clasificación, diagnóstico y predicción. En todos estos campos son objeto de estudio grandes conjuntos de datos, para los cuales se trabajan diferentes técnicas que permiten la extracción de conocimiento y la aplicación a los citados problemas. Los grandes avances en estas áreas (muchas veces en forma de nuevos algoritmos) conviven con trabajos muy parciales sobre las metodologías adecuadas para la evaluación de estas nuevas propuestas.

Frente a esta situación, la tesis que aquí se presenta propone un nuevo marco general para la evaluación del comportamiento de un conjunto de M algoritmos que, para poder ser analizados, son ensayados sobre N problemas de prueba. La tesis sostiene que el análisis habitual que se hace de estos resultados es claramente insuficiente, i que debido a esto las conclusiones que se exponen en los trabajos publicados son muchas veces parciales, y en algunos casos hasta erróneas.

El trabajo se inicia con un estudio introductoria sobre las medidas que permiten expresar la bondad de un algoritmo, a través del ensayo sobre una colección de problemas de prueba. En este punto, se demuestra la necesidad de un estudio previo de las propiedades inherentes de estos problemas (a partir, por ejemplo, de las métricas de complejidad) si se quiere asegurar la fiabilidad de las conclusiones que se obtendrán.

A continuación, se define el marco de aplicación de todo un conjunto de técnicas de inferencia estadística para las cuales, siendo éstas bien conocidas, se analizan los factores a tener en cuenta en la determinación de su dominio de uso. La tesis propone un protocolo general para el estudio, desde un punto de vista estadístico, del comportamiento de un conjunto de algoritmos, incluyendo unos nuevos modelos gráficos que facilitan su análisis, y el estudio detallado de las propiedades inherentes a los problemas de prueba utilizados.

Este protocolo determina el dominio de uso de las metodologías para la comparación de resultados obtenidos en cada problema. La tesis demuestra, además, como este dominio está directamente relacionado con la capacidad de esta metodología para determinar diferencias significativas, y también con su replicabilidad.

Finalmente, se proponen un conjunto de casos sobre resultados ya publicados con anterioridad, fruto de nuevos algoritmos desarrollados por nuestro Grupo de Investigación, muy en especial en la aplicación del razonamiento basado en casos. En todos ellos se muestra la correcta aplicación de las metodologías desarrolladas en los capítulos anteriores, y se destacan los errores cometidos habitualmente, que llevan a conclusiones no fiables.
The present work is all part of the work field of the Research Group in Intelligent Systems: the machine learning. The main areas are the evolutive computation and the case based reasoning, the investigation being focused on the classification, diagnosis and prediction issues. In all of these fields, great groups of data are studied, for which different techniques are applied, enabling the knowledge extraction and the application of the aforementioned problems. The big breakthroughs in these areas (many times in ways of algorithms) coexist with very partial works on suitable methodologies for the evaluation of these new proposals.

Before this situation, the thesis herein presented proposes a new general approach for the assessment of a set of M algorithms behaviour which, in order to be analysed, are tested over N datasets. The thesis maintains that the analysis made for these results is clearly insufficient and consequently the conclusions put forward in the works published are very often partial and in some cases even erroneous.

This work begins with an introductory study on the measures allowing to express the performance of an algorithm, through the test over a collection of datasets. At this point it is evidenced that a prior study of the inherent properties of these problems (for instance, based on complexity metrics) is needed, in order to assure the reliability of the conclusions that will be drawn.

Next, the scope of application of a whole set of well known techniques of statistical inference is defined, for which the factors to be taken into account in the determination of their application analysed. The thesis proposes a general protocol for the study, from a statistical point of view, of the behaviour of a set of algorithms, including new graphic patterns which facilitate its analysis, as well as the detailed study of the inherent properties of the test problems used.

This protocol determines the application domains of the methodologies for the comparison of the results obtained in each problem. The thesis demonstrates furthermore how this domain is directly related to the capability of this methodology to determine significant differences, as well as to its replicability.

Finally, a set of cases on results already published are proposed, resulting from new algorithms developed by our Research Group, very specially in the application of the case-based reasoning. In all these cases the application of the methodologies developed in the previous chapters is proved to be correct, and the errors incurred in repeatedly, leading to unreliable conclusions, are highlighted.

Una millor comprensió dels complexos fenòmens que regeixen la dinàmica del fluxos tri-fàsics així com un increment en la capacitat predictiva de la seva dinàmica, són crucials en el disseny i construcció de sistemes fluidics d'interès per a una àmplia gama d'indústries. Aquest treball de recerca presenta el disseny i muntatge de LESLIE, un circuit tancat de baixa pressió destinat a la recerca en la dinàmica de fluxos bifàsics i trifàsics a través de canonades i els seus accessoris. LESLIE està pensat per obtenir mesures de paràmetres clau i caracteritzar fluxos multifàsics amb fases gasoses, líquides i sòlides, tant en canonades horitzontals com verticals. Presentem aquí noves dades experimentals per a règims intermitents en fluxos bifàsics i trifàsics en configuració horitzontal amb aire, aigua i partícules de polipropilè amb mides d'entre 1 i 2 mil·límetres. Visualitzacions del flux, mesures de pressió i fracció de buit s'han obtingut per a diferents condicions d'operació. En aquest treball investiguem l'impacte de la presència de partícules sòlides sobre la caiguda de pressió, el règim de flux i la freqüència del "slug". A més, l'anàlisi del comportament de fluxos bifàsics anulars mitjançant tècniques de processat d'imatges ha permès obtenir resultats sobre la distribució de mida de gotes.
La dinámica de los flujos trifásicos se rige por fenómenos de alta complejidad, tanto conceptual como matemática. Una mejor comprensión así como un incremento en la capacidad de predicción de su dinámica, son cruciales para el diseño y construcción de instalaciones de interés para una amplia gama de industrias. Este trabajo de investigación presenta el diseño y montaje de LESLIE, un circuito cerrado de baja presión destinado a la investigación experimental de la dinámica de flujos bifásicos y trifásicos a través de tuberías y sus accesorios. LESLIE está pensado para obtener medidas de parámetros clave y caracterizar flujos multifásicos con fases gaseosas, líquidas y sólidas, tanto en tuberías horizontales como verticales.Presentamos aquí nuevos datos experimentales para regímenes intermitentes en flujos bifásicos y trifásicos en configuración horizontal usando aire, agua y partículas de polipropileno con tamaños de entre 1 y 2 milímetros. Visualizaciones del flujo, medidas de presión y fracción de vacío se han obtenido para diferentes condiciones de operación de flujos intermitentes. En este trabajo investigamos el impacto de la presencia de partículas sólidas sobre la caída de presión, el régimen de flujo y la frecuencia del "slug". Además, el análisis del comportamiento de flujos bifásicos anulares mediante técnicas de procesado de imágenes ha permitido obtener resultados sobre la distribución de tamaño de partícula, las cuales también se presentan en este trabajo.
The dynamics of three-phase flows involve phenomena of high complexity, whose understanding and an enhanced prediction capacity of fluid dynamics in multiphase flow systems is crucial for the design and construction of facilities meant for a wide range of industries. This research work presents the design and set up of LESLIE, a low pressure multiphase flow loop for the experimental analysis of two and three-phase flows through pipelines and their accessories. It is designed to measure key parameters, so as to characterise the behaviour of multiphase flows involving gas, liquid and solid phases both in horizontal and vertical pipelines. New experimental data is presented in this study for intermittent two and three-phase flows in horizontal pipelines involving air, water and polypropylene pellets of sizes ranging between 1 and 2 millimetres. Flow visualization, pressure and void fraction measurements were performed and are explored in this work for the case of intermittent flows for a variety of settings. The influence of solid particles over the frictional pressure drop, flow regime and slug frequency is reported in this work. Furthermore, the analysis of the dynamics of annular two-phase flows by means of image processing techniques has allowed obtaining droplet size distributions, which are also presented in this study.

This thesis presents three studies which examine the decisions of individuals to pay for clean water and public services. The three impact evaluations, conducted in India and Guatemala, demonstrate that small changes to the way services are provided and presented to individuals can have a large impact on demand for them. The first chapter looks at whether tariffs discourage the use of NGO funded water quality projects in Telengana, India. The estimation strategy takes advantage of panel data from water purification plants where the tariff for 20 litres of water changed. In this setting, a one standard deviation decrease in price is estimated to cause a six percent increase in uptake. The second paper evaluates an adaptation to similar NGO water projects which increased the hours clean drinking water was accessible for, from 4 hours a day to 24. The results from the cluster randomised controlled trial show that the intervention increased demand for clean water by 22 percent. The final chapter presents findings from a nationwide randomised controlled trial in Guatemala that tested various letter reminders to promote tax compliance. The results show that whilst all letters increased the rate of declaration, only two of the letters, which were adapted using behavioural design, were successful at increasing the rate of payment and the average amount paid per letter received. These two letters more than tripled tax receipts compared to the no letter, or the original letter. The best performing letter, if sent to all taxpayers in the sample, would have generated an estimated US$757,837 of extra tax revenue in 11 weeks compared to no letter, over 35 times the cost of sending the letters. Overall, the thesis provides evidence that both economic and behavioural dimensions affect payment for clean water and tax, and so both must be considered when development practitioners and policy makers design 'customer facing' programmes. The methodology used in the three studies highlights that it is possible to rigorously evaluate such programmatic design decisions at low cost using experimental and quasi-experimental methods.