Orientadores: Célia Marina de Alvarenga Freire, Margarita Balester Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-17T07:41:13Z (GMT). No. of bitstreams: 1 Bertocco_BrunoGitti_M.pdf: 1034163 bytes, checksum: 95ccdc8f5c1e575c64c202d4cbd8b5d4 (MD5) Previous issue date: 2010 / Resumo: A fragilização de aços por Hidrogênio é um problema ainda não resolvido nas indústrias petrolíferas e petroquímicas. O Hidrogênio proveniente de reações químicas e eletroquímicas, tais como, corrosão, proteção catódica e reações de processo, é absorvido pelo aço e retido nos defeitos da rede cristalina podendo causar a fragilização do aço e a propagação de trincas e fraturas. O presente trabalho visa analisar o comportamento do aço AISI 4340 na presença de hidrogênio nascente, através de curvas de voltametria cíclica e espectroscopia de impedância eletroquímica. O aço AISI 4340 foi analisado conforme recebido sob duas condições distintas de processamento: fundido em forno elétrico a vácuo, laminado e recozido e fundido e refundido a arco sob vácuo (VAR), laminado e recozido. Os resultados obtidos mostram uma dependência da resposta em relação a processos de adsorção e dessorção do hidrogênio nas superfícies e a microestrutura desses materiais / Abstract: The hydrogen steel embrittlement is a problem not solved in the petroleum and petrochemical industry. The hydrogen resulting from chemical reactions such as corrosion, cathodic processes and process reactions is absorbed and trapped by the net crystal lattice defects which may cause the steel embrittlement, crack propagation and material fracture. The present research analyze the behavior of AISI 4340 steel in relation to the presence of nascent hydrogen, throught cyclic voltametric curves and electrochemical impedance spectroscopy. The AISI 4340 steel was produced under two process conditions: melted in vacuum electric oven, laminate and annealed and melted and remelted under vacuum arc (VAR), laminate and annealed. The results obtained showed a link between the response related to de adsorption and desorption of the hydrogen on the surface and microstructure of these materials / Mestrado / Materiais e Processos de Fabricação / Mestre em Engenharia Mecânica

The physical tumor microenvironment contributes significantly to carcinogenesis, cancer progression and metastatic dissemination. Two main components of the tumor microenvironment, hypoxia and acidosis, are present in nearly every solid tumor and act as powerful selection forces against the tumor. Hypoxia and acidosis promote tumor heterogeneity and contribute to chemotherapy and radiotherapy resistance. This dissertation interrogates methods to target the tumor microenvironment including two novel studies describing mechanisms of buffer therapy resistance and targeting tumor hypoxia with vasodilators to enhance the efficacy of a hypoxia activated prodrug, TH-302. In the first study, mechanisms of buffer therapy resistance were identified and detailed. Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of the buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, I confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. In the second study, improving the efficacy of hypoxia activated prodrug, TH-302, through induction of hypoxia was investigated. Pancreatic ductal adenocarcinomas are desmoplastic and hypoxic tumors, both of which are associated with poor prognosis. Hypoxia activated prodrugs, such as TH-302, are specifically activated in hypoxic environments and are now in a Phase III clinical trial in pancreatic cancer. Using animal models, we show that tumor hypoxia can be exacerbated using a vasodilator, hydralazine, improving TH-302 efficacy. Hydralazine reduces tumor blood flow through the "Steal" phenomenon, where atonal immature tumor vasculature fails to dilate in coordination with normal vasculature. The current study shows that MiaPaCa-2 tumors exhibit a "Steal" effect in response to hydralazine, resulting in decreased tumor blood flow and subsequent tumor pH reduction. The effect is not observed in SU.86.86 tumors with mature tumor vasculature, as measured by CD31 and smooth muscle actin (SMA) immunohistochemistry staining. Combination therapy of hydralazine and TH-302 resulted in a reduction in MiaPaCa-2 tumor volume growth after 18 days of treatment. Further optimization of hypoxia-inducing agents and dosing regimens may lead to increased TH-302 activity, potentially improving clinical outcome. The data presented here demonstrate methods to effectively target the tumor microenvironment for therapeutic benefit. Further investigation into mechanisms of action and biomarkers for therapy response may have important implications on clinical treatment regimens for cancer patients.

Spinodal decomposition is a phenomenon which hinders the usage of ferrite containing steels under certain conditions. With a better understanding and knowledge of spinodal decomposition new ferritic and duplex stainless steels could be designed. The project is divided into two parts, an experimental part and a theoretical part. The aim of the theoretical part was to compare simulated values of the amplitude and wavelength of spinodal decomposition, obtained from solving the Cahn-Hilliard equation with other experimental values. The experimental part is performed as to determine the chemical diffusion coefficient and the mobility of Fe and Cr in the binary Fe-Cr system for lower temperatures using the Boltzmann-Matano method from chemical profiles of different samples. Another purpose with the project is to determine if the methods and the approach which are taken is viable and useful for calculating diffusion coefficients and if it can be used in studies to come. The simulations were in good agreement with other data at higher time intervals, but deviates at lower times. The calculated interdiffusion coefficients were in all cases lower than the expected values and as such the conclusion that is drawn is that the methods which are used could need further development. / Spinodalt sönderfall är ett fenomen som hindrar användningen av stål som innehåller ferrit under vissa förutsättningar. Med en större förståelse och mer kunskap om spinodalt sönderfall så kan nya ferritiska och duplexa rostfria stål utformas. Projektet är uppdelat i två delar, en experimentell del och en teoretisk del. Syftet med den teoretiska delen var att jämföra simulerade värden av amplituden och våglängden för spinodalt sönderfall, vilka erhölls från att lösa Cahn-Hilliard ekvationen med andra experimentella värden. Den experimentella delen utförs för att bestämma kemiska diffusionskoefficienter för Fe och Cr i det binära Fe-Cr system för lägre temperaturer med hjälp av Boltzmann-Matano metod från kemiska profiler av olika prover. Ett annat syfte med projektet är att ta reda på om de metoder och tillvägagångssätt som tas är livskraftiga och användbara för beräkning av diffusionskoefficienter och om den kan användas i studier framöver. Simuleringarna var i god överensstämmelse med annan experimentel data vid högre tidsintervall, men avviker vid lägre tider. De beräknade Interdiffusion koefficienterna var i samtliga fall lägre än de förväntade värdena och som sådan, dras slutsatsen att de metoder som används kan förbättras.

Strachotín is a village on the edge, not just from geological point of view, but in the sense it´s next development too. Currently it´s main problem is, that it does not offer anything specific to become interesting for turists. There are not the best wine, architecture, accomodation, catering or public services. What it does have is undoubtedly the best view of Palava massif. It is not used at all and that was the main reason that led me to think of building at the pier so this attribute could be finally used for further development of this village. For this purpose i chose the object gallery of wine which is missing here and is also welcomed by it´s citizens.

O objetivo deste trabalho é apresentar o teste de esforço com o dinamômetro isocinético na avaliação objetiva da isquemia funcional da doença arterial oclusiva de membros superiores (DAOMS). Reuniu-se 23 pacientes com DAOMS unilateral, no grupo 1. Sete pacientes, sem DAOMS foram selecionados como o grupo controle (grupo 2). Os membros testados sem DAOMS do grupo 1 e do grupo 2 não apresentaram diferença estatística. A comparação de cada membro dos pacientes do grupo 1, com e sem DAOMS mostrou que os membros com DAOMS apresentaram desempenho significativamente menor que os membros sem lesão. Este teste permite a avaliação objetiva da limitação causada pela DAOMS de forma segura e objetiva / The objective of this work is to present the results of a stress test using an isokinetic dynamometer in patients with occlusive arterial disease in upper limbs (OADUL). Group 1 has 23 patients with unilateral subclavian occlusive disease. Seven patients, without OADUL, were included in a control group (group 2). No statistically difference was found in all parameters studied between limbs without OADUL in groups 1 and 2. So, each arm in group 1 (with and without OADUL) were tested. For all these parameters, the SOD limbs presented significantly lower values than the control limbs. This test gives an objective grade of limitation of the muscle function in patients with OADUL

Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging enables non-invasive spatial mapping of changes in cerebral blood flow (CBF). By applying a vasodilatory stimulus (such as inhaled CO2) during BOLD MR imaging, one can measure cerebral vasodilatory capacity. "Cerebrovascular reactivity" (CVR) is defined as the change in CBF per unit of vasodilatory stimulus. Vasodilatory capacity is clinically important as vasodilatation is a mechanism by which the brain maintains constant CBF despite reductions in cerebral perfusion pressure.ii Patients with arterial narrowing commonly demonstrate a paradoxical response: vasodilatory stimulus-induced reduction of BOLD MR signal. BOLD MR depends on CBF but on other factors too. Does a reduction of BOLD MR signal indicate a decrease in flow? Does BOLD MR CVR correlate with CVR measured using arterial spin labeling (ASL) MR? I studied thirty-eight patients with stenosis of brain-supplying arteries and found that the BOLD CVR and ASL CVR results correlate strongly (R=0.83, P<0.0001 for cerebral hemispheric gray matter). The second study aimed to determine whether preoperative CVR predicts the hemodynamic effect of extracranial-intracranial bypass surgery. Whereas prior studies relied on right-left interhemispheric CVR asymmetry indices, this study used “absolute” CVR from each hemisphere. I studied twenty-five patients with intracranial arterial stenosis. I found that the group with normal pre-operative CVR showed no change in CVR following bypass surgery (0.22% ± 0.05% to 0.22% ± 0.01% (mean ± SD)(P=0.881)), the group with reduced pre-operative CVR demonstrated an improvement (0.08% ± 0.05% to 0.21 ± 0.08% (mean ± SD)(P<0.001)), and the group with paradoxical pre-operative CVR demonstrated the greatest improvement (-0.04% ± 0.03% to 0.27% ± 0.03% (P=0.028)). ii Patients with arterial narrowing commonly demonstrate a paradoxical response: vasodilatory stimulus-induced reduction of BOLD MR signal. BOLD MR depends on CBF but on other factors too. Does a reduction of BOLD MR signal indicate a decrease in flow? Does BOLD MR CVR correlate with CVR measured using arterial spin labeling (ASL) MR? I studied thirty-eight patients with stenosis of brain-supplying arteries and found that the BOLD CVR and ASL CVR results correlate strongly (R=0.83, P<0.0001 for cerebral hemispheric gray matter). The second study aimed to determine whether preoperative CVR predicts the hemodynamic effect of extracranial-intracranial bypass surgery. Whereas prior studies relied on right-left interhemispheric CVR asymmetry indices, this study used “absolute” CVR from each hemisphere. I studied twenty-five patients with intracranial arterial stenosis. I found that the group with normal pre-operative CVR showed no change in CVR following bypass surgery (0.22% ± 0.05% to 0.22% ± 0.01% (mean ± SD)(P=0.881)), the group with reduced pre-operative CVR demonstrated an improvement (0.08% ± 0.05% to 0.21 ± 0.08% (mean ± SD)(P<0.001)), and the group with paradoxical pre-operative CVR demonstrated the greatest improvement (-0.04% ± 0.03% to 0.27% ± 0.03% (P=0.028)). The third study arose from an unexpected observation: paradoxical reactivity in the white matter of young healthy subjects. I evaluated healthy subjects using BOLD CVR and ASL CVR, transformed all CVR maps into a common brain space, and generated composite maps of CVR. Composite maps confirmed regions of significant paradoxical iii reactivity in the white matter. These regions may represent the physiological correlate of previously anatomically defined border-zones (watershed zones). The regions match the locations where elderly patients develop white matter rarefaction, so-called leukoaraiosis.

Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging enables non-invasive spatial mapping of changes in cerebral blood flow (CBF). By applying a vasodilatory stimulus (such as inhaled CO2) during BOLD MR imaging, one can measure cerebral vasodilatory capacity. "Cerebrovascular reactivity" (CVR) is defined as the change in CBF per unit of vasodilatory stimulus. Vasodilatory capacity is clinically important as vasodilatation is a mechanism by which the brain maintains constant CBF despite reductions in cerebral perfusion pressure.ii Patients with arterial narrowing commonly demonstrate a paradoxical response: vasodilatory stimulus-induced reduction of BOLD MR signal. BOLD MR depends on CBF but on other factors too. Does a reduction of BOLD MR signal indicate a decrease in flow? Does BOLD MR CVR correlate with CVR measured using arterial spin labeling (ASL) MR? I studied thirty-eight patients with stenosis of brain-supplying arteries and found that the BOLD CVR and ASL CVR results correlate strongly (R=0.83, P<0.0001 for cerebral hemispheric gray matter). The second study aimed to determine whether preoperative CVR predicts the hemodynamic effect of extracranial-intracranial bypass surgery. Whereas prior studies relied on right-left interhemispheric CVR asymmetry indices, this study used “absolute” CVR from each hemisphere. I studied twenty-five patients with intracranial arterial stenosis. I found that the group with normal pre-operative CVR showed no change in CVR following bypass surgery (0.22% ± 0.05% to 0.22% ± 0.01% (mean ± SD)(P=0.881)), the group with reduced pre-operative CVR demonstrated an improvement (0.08% ± 0.05% to 0.21 ± 0.08% (mean ± SD)(P<0.001)), and the group with paradoxical pre-operative CVR demonstrated the greatest improvement (-0.04% ± 0.03% to 0.27% ± 0.03% (P=0.028)). ii Patients with arterial narrowing commonly demonstrate a paradoxical response: vasodilatory stimulus-induced reduction of BOLD MR signal. BOLD MR depends on CBF but on other factors too. Does a reduction of BOLD MR signal indicate a decrease in flow? Does BOLD MR CVR correlate with CVR measured using arterial spin labeling (ASL) MR? I studied thirty-eight patients with stenosis of brain-supplying arteries and found that the BOLD CVR and ASL CVR results correlate strongly (R=0.83, P<0.0001 for cerebral hemispheric gray matter). The second study aimed to determine whether preoperative CVR predicts the hemodynamic effect of extracranial-intracranial bypass surgery. Whereas prior studies relied on right-left interhemispheric CVR asymmetry indices, this study used “absolute” CVR from each hemisphere. I studied twenty-five patients with intracranial arterial stenosis. I found that the group with normal pre-operative CVR showed no change in CVR following bypass surgery (0.22% ± 0.05% to 0.22% ± 0.01% (mean ± SD)(P=0.881)), the group with reduced pre-operative CVR demonstrated an improvement (0.08% ± 0.05% to 0.21 ± 0.08% (mean ± SD)(P<0.001)), and the group with paradoxical pre-operative CVR demonstrated the greatest improvement (-0.04% ± 0.03% to 0.27% ± 0.03% (P=0.028)). The third study arose from an unexpected observation: paradoxical reactivity in the white matter of young healthy subjects. I evaluated healthy subjects using BOLD CVR and ASL CVR, transformed all CVR maps into a common brain space, and generated composite maps of CVR. Composite maps confirmed regions of significant paradoxical iii reactivity in the white matter. These regions may represent the physiological correlate of previously anatomically defined border-zones (watershed zones). The regions match the locations where elderly patients develop white matter rarefaction, so-called leukoaraiosis.

O objetivo deste trabalho é apresentar o teste de esforço com o dinamômetro isocinético na avaliação objetiva da isquemia funcional da doença arterial oclusiva de membros superiores (DAOMS). Reuniu-se 23 pacientes com DAOMS unilateral, no grupo 1. Sete pacientes, sem DAOMS foram selecionados como o grupo controle (grupo 2). Os membros testados sem DAOMS do grupo 1 e do grupo 2 não apresentaram diferença estatística. A comparação de cada membro dos pacientes do grupo 1, com e sem DAOMS mostrou que os membros com DAOMS apresentaram desempenho significativamente menor que os membros sem lesão. Este teste permite a avaliação objetiva da limitação causada pela DAOMS de forma segura e objetiva / The objective of this work is to present the results of a stress test using an isokinetic dynamometer in patients with occlusive arterial disease in upper limbs (OADUL). Group 1 has 23 patients with unilateral subclavian occlusive disease. Seven patients, without OADUL, were included in a control group (group 2). No statistically difference was found in all parameters studied between limbs without OADUL in groups 1 and 2. So, each arm in group 1 (with and without OADUL) were tested. For all these parameters, the SOD limbs presented significantly lower values than the control limbs. This test gives an objective grade of limitation of the muscle function in patients with OADUL

At a Muslim school a group of boys with a reputation for stealing got the opportunity to share stories with communities of concern. Honesty meetings, honesty tests, honesty certificates and honesty celebrations formed part of narrative therapy ways of working together to try and regain reputations for honesty. As an outsider researcher/therapist I was confronted by stories of slavery, racism, unemployment, poverty, crime and violence. Through collaboration with a cultural consultant it became possible to do theology and pastoral care as a Christian in a Muslim community in a respectful and ethical way. The sharing of stories of pain and resistance contributed to the mutual care and community amongst participants from communities separated by racism and apartheid legislation as well as differences of culture and religion. Reflections on this journey mark a migration of identity for me as researcher, therapist, Christian and white South African practical theologian. / Practical Theology / M.Th. (Pastoral Theology)

At a Muslim school a group of boys with a reputation for stealing got the opportunity to share stories with communities of concern. Honesty meetings, honesty tests, honesty certificates and honesty celebrations formed part of narrative therapy ways of working together to try and regain reputations for honesty. As an outsider researcher/therapist I was confronted by stories of slavery, racism, unemployment, poverty, crime and violence. Through collaboration with a cultural consultant it became possible to do theology and pastoral care as a Christian in a Muslim community in a respectful and ethical way. The sharing of stories of pain and resistance contributed to the mutual care and community amongst participants from communities separated by racism and apartheid legislation as well as differences of culture and religion. Reflections on this journey mark a migration of identity for me as researcher, therapist, Christian and white South African practical theologian. / Philosophy, Practical and Systematic Theology / M.Th. (Pastoral Theology)