Medidas de espectroscopia gama de alta resolução têm diversas aplicações. Aplicações envolvendo medidas de radioisótopos de meia-vida curta podem apresentar problemas de baixa precisão nas contagens quando a fonte radioativa está distante do detector e de perda de acurácia por efeitos de tempo morto e empilhamento de pulsos em situação de altas taxas de contagens. Um modo de minimizar esses problemas é alterando a posição da fonte radioativa durante o processo de medição, aproximando-a do detector conforme sua atividade diminui e assim maximizando o número de contagens medidas. Neste trabalho, foi desenvolvido o Movimentador de Amostras Radioativas Automatizado (MARA), um aparato de baixo custo, feito com materiais de baixo número atômico e leve, projetado e construído para auxiliar nas medidas de espectroscopia gama, capaz de controlar a distância entre a fonte e o detector, permitindo inclusive que ocorra alteração dessa distância durante o processo de medição. Por ser automatizado ele otimiza o tempo do operador, que tem total liberdade para criar suas rotinas de medidas no dispositivo, além de evitar que o mesmo tome uma parcela da dose radioativa. Foi também feita uma interface que permite controle do MARA e a programação do sistema de aquisição de dados. Foram realizados testes para otimização da operação do sistema MARA e foi verificada a segurança de operação do MARA, não apresentando nenhuma falha durante seus testes. Foi aplicado o teste de repetitividade, por meio de medições com uma fonte calibrada de 60Co, e verificou-se que o sistema de movimentação de prateleiras automatizado reproduziu os resultados do sistema estático com confiabilidade de 95%. / High resolution gamma spectroscopy measurements have several applications. Those involving short half-life radioisotope measurements may present low precision problems when the radioactive source is far from detector end cup and in the very high activity situations also can present accuracy loss due to dead time and pile-up effects. A way to overcome these problems is changing the source detector distance as the activity is decreasing, and thereby maximizing the statistical counting. In the present study, the Controller of Acquisition and Sample Positioner for Activation (CASPA) was developed. It is a low cost and weight device, made with low atomic number materials designed to assist gamma spectroscopy measurements, which is able to control the distance between the source and the detector, even allowing that there is a change of this distance during the measurement process. Because it is automated it optimizes the time of the operator, who has complete freedom to program their routine measurements in the device besides minimizing the radiation dose in the operator. An interface that allow the user control the CASPA system and to program the acquisition system was created. Tests aiming to optimize the operation of CASPA system were carried out and the safety of the CASPA operation was verified, it was not presented any failure during their tests. It was applied the repeatability tests by the acquisition 60Co standard source and was found that the positioning of automated system has reproduced the results of static system with a 95% of confidence level .

Cystic Fibrosis (CF) is an autosomal recessive genetic disease that leads to severe malfunction in many organs, but particularly the lungs. The primary cause of this malfunction is the decrease of the airway surface liquid layer on the lung epithelium. The lack of hydration leads to mucus build up on the epithelial lining, leading to blockage of airways. The underlying cause of CF is the dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), which results from mutations in the protein. Almost 90% of CF patients are caused by the deletion of the phenylalanine at position 508 of CFTR, which is believed to affect the folding and stability of CFTR. The misfolded ΔF508-CFTR undergoes ER associated degradation (ERAD), causing the failure of ΔF508-CFTR trafficking to the cell surface. Small molecule correctors yield moderate improvements in the trafficking of ΔF508-CFTR to the plasma membrane. It is currently not known if correctors increase trafficking through improved cargo loading of transport vesicles or through direct binding to CFTR. In this dissertation, real-time measurements of trafficking were utilized to identify the mechanistic details of chemical, biochemical, and thermal factors that impact CFTR correction, using the corrector molecule VX-809, a secondary mutation (I539T), and low temperature conditions. Each individually improved trafficking of ΔF508-CFTR to approximately 10% of wild-type levels. The combination of VX-809 with either low temperature or the I539T mutation increased the amount of CFTR on the plasma membrane to nearly 40%, indicating synergistic activity. The number of vesicles reaching the surface was significantly altered; however the amount of channel in each vesicle remained the same. Therefore, a 2 step therapeutic approach might be an ideal treatment for CF. The first step would be composed of a compound that mimics the mechanism of stabilization provided by low temperature or the I539T mutation, while the second step would be VX-809 or a similar corrector compound. These studies suggest that understanding how low temperature and second site suppressors alter ΔF508-CFTR could be key to the development of future therapeutics for the effective treatment of CF. The precise pathophysiology of cystic fibrosis is not well studied. The involvement of another transport protein, epithelial sodium channel (ENaC), makes the situation more complicated. ENaC and CFTR are colocalized on the apical surface of epithelia cells. With our fluorescence microscopy techniques, we explored the effects of CFTR on the residence time of ENaC on the cell membrane. A reliable approach measuring the half-life of protein on the cell membrane is required for this study. We present a new approach to quantify the half-life of membrane proteins on the cell surface, through tagging the protein with the photoconvertible fluorescent protein, Dendra2. Total internal reflection fluorescence microscopy (TIRF) is applied to limit visualization of fluorescence to proteins located on the plasma membrane. Photoconversion of Dendra2 works as a pulse chase experiment by monitoring only the population of protein that has been photoconverted. As the protein is endocytosed the red emission decreases due to the protein leaving the TIRF field of view. The half-life of the protein on the plasma membrane was calculated upon imaging over time and quantifying the change in red fluorescence. Our method provides a unique opportunity to observe real-time protein turnover at the single cell level without addition of protein synthesis inhibitors. This technique will be valuable for the future protein half-life study.

<p>The tumor vasculature is poor and heterogeneous which may result in inadequate oxygenation and changed energy status. In addition the balance between cell proliferation and the rate of cell death is disturbed, which results in tumor growth. </p><p>The aims of this study were 1) to gain more insight into the relation between tumor vascularity, hypoxia, and proliferation in solid tumors, and 2) to study the changes and dynamics of tumor oxygenation in relation to the vascular architecture within individual tumors. For this purpose a double hypoxic marker method was developed, which was subsequently used to 3) determine the turnover rate of hypoxic cells in three different tumor models and 4) to study the effect of cytotoxic drugs on tumor hypoxia and cell death.</p><p>Solid tumor models grown in mice were used. The tumor microenvironment was investigated with exogenous cell markers for hypoxia (pimonidazole and CCI-103F), cell proliferation (BrdUrd) and blood perfusion (Hoechst 33342). The vasculature and the exogenous cell markers were visualized with immunohistochemical techniques. The tumor sections were scanned and quantified with an image analysis systemconsisting of a fluorescence microscope, CCD camera and image analysis software.</p><p>The spatial organization of hypoxia, proliferation, and tumor vasculature was analyzed in several xenograft lines. The study revealed two main hypoxic patterns that seemed to be the consequence of complex relations between vasculature, oxygen delivery, proliferation, and cell loss. The novel double hypoxic cell marker method, with sequential injection of two hypoxic markers, was developed to study dynamic changes of the tumor oxygenation. Based on varying injection intervals between the markers the hypoxic cell half-life was determined in three tumor lines, and ranged from 17 to 49 hours. Intra-tumoral changes in oxygenation status upon oxygen modifying treatments were measured with the double hypoxic marker method. Both decreased levels of tumor hypoxia after carbogen breathing (95%O2 and 5% CO2) and increased levels of tumor hypoxia, as a result of reduced tumor perfusion after hydralazine treatment was detected. Finally the double hypoxic marker assay was used to analyze the effects of the hypoxic cytotoxin tirapazamine in relation to the hypoxic cell population, which caused a reversible decrease of the hypoxic fraction.</p><p>The results presented in this thesis now form the basis for further studies to identify subpopulations of cells that represent specific targets for therapy, and to investigate the effects of different treatment modalities.</p>

The tumor vasculature is poor and heterogeneous which may result in inadequate oxygenation and changed energy status. In addition the balance between cell proliferation and the rate of cell death is disturbed, which results in tumor growth. The aims of this study were 1) to gain more insight into the relation between tumor vascularity, hypoxia, and proliferation in solid tumors, and 2) to study the changes and dynamics of tumor oxygenation in relation to the vascular architecture within individual tumors. For this purpose a double hypoxic marker method was developed, which was subsequently used to 3) determine the turnover rate of hypoxic cells in three different tumor models and 4) to study the effect of cytotoxic drugs on tumor hypoxia and cell death. Solid tumor models grown in mice were used. The tumor microenvironment was investigated with exogenous cell markers for hypoxia (pimonidazole and CCI-103F), cell proliferation (BrdUrd) and blood perfusion (Hoechst 33342). The vasculature and the exogenous cell markers were visualized with immunohistochemical techniques. The tumor sections were scanned and quantified with an image analysis systemconsisting of a fluorescence microscope, CCD camera and image analysis software. The spatial organization of hypoxia, proliferation, and tumor vasculature was analyzed in several xenograft lines. The study revealed two main hypoxic patterns that seemed to be the consequence of complex relations between vasculature, oxygen delivery, proliferation, and cell loss. The novel double hypoxic cell marker method, with sequential injection of two hypoxic markers, was developed to study dynamic changes of the tumor oxygenation. Based on varying injection intervals between the markers the hypoxic cell half-life was determined in three tumor lines, and ranged from 17 to 49 hours. Intra-tumoral changes in oxygenation status upon oxygen modifying treatments were measured with the double hypoxic marker method. Both decreased levels of tumor hypoxia after carbogen breathing (95%O2 and 5% CO2) and increased levels of tumor hypoxia, as a result of reduced tumor perfusion after hydralazine treatment was detected. Finally the double hypoxic marker assay was used to analyze the effects of the hypoxic cytotoxin tirapazamine in relation to the hypoxic cell population, which caused a reversible decrease of the hypoxic fraction. The results presented in this thesis now form the basis for further studies to identify subpopulations of cells that represent specific targets for therapy, and to investigate the effects of different treatment modalities.

As a part of our program to test the unitarity of the Cabibbo-Kobayashi-Maskawa matrix, the decay of the superallowed 0⁺ --> 0⁺ beta emitters ³⁸Ca and ⁴⁶V has been studied in this dissertation. For ³⁸Ca, the half-life, 443.88(36) ms, and superallowed branching ratio, 0.7738(41), have been measured. In our half-life experiment, pure sources of ³⁸Ca were produced and the decay positrons detected in a high-efficiency 4[pi] proportional gas counter. Since the beta⁺ decay of ³⁸Ca feeds ³⁸K^m, which is itself a superallowed beta⁺ emitter, the data were analyzed as a linked parent-daughter decay. Our result for the half-life of ³⁸Ca, with a precision of 0.08%, is a factor of five improvement on the best previous result. The branching-ratio of ³⁸Ca depended on beta-delayed gamma-ray intensities being measured with a high-purity germanium detector calibrated for absolute efficiency to 0.2% precision. This branching-ratio result represents our first step in bringing the ft value for the superallowed ³⁸Ca transition into the desired range of 0.1%. With our half-life and superallowed branching ratio results for ³⁸Ca, we obtain the Ft to be 3072(17) s, in good agreement with the conserved vector current expectation. The half-life of ⁴⁶V has been measured to be 422.66(6) ms, a factor of two more precise than the best previous measurement. Our present result determines the corresponding Ft value to be 3074.5(26) s, which is consistent with the average $\overline{\mathcal{F}t}$ value of 3072.08(79) s established from the 13 best-known superallowed transitions. This demonstrates that previously accepted half-lives of ⁴⁶V were correct in their contribution to a precision test of the conserved vector current hypothesis.

An increase in environmental awareness and energy concerns had recently prompted efforts to make pavement construction cheaper and more environmentally friendly. Warm mix asphalt (WMA) is an asphalt mixture production technology that promises to reduce production costs and greenhouse gas emissions. Foamed asphalt binder is increasingly being used to produce WMA. This dissertation addresses several issues related to the use of foamed asphalt binder for WMA applications. The first objective of the research presented in this dissertation is to develop a method and metrics to precisely quantify the characteristics of asphalt binder foams. Laboratory measurements were obtained using the newly developed method to evaluate the extent and stability of foams produced using different asphalt binders at different water contents and laboratory foaming devices. Results demonstrate that the method developed is promising in terms of its ability to provide a detailed history of the behavior of foamed asphalt binder as the foam collapses. In addition, results indicate that the method is sensitive to distinguish between foaming characteristics of different asphalt binders as well as different water contents and foaming devices. The second objective of this study was to relate intrinsic properties of the asphalt binder to its foaming characteristics. A physical model was developed for expansion of asphalt binder foam based on foam physics and fluid mechanics of micro-droplets. The model relates foamant water and asphalt binder mixing efficiency with the surface tension of the asphalt binder. The model can be used to predict which binder can be effectively foamed and used, and whether any chemical modification to the binder is necessary to achieve the same. Results indicate that only a small percentage of water is effective in foaming the asphalt binder. The last objective of this research was to evaluate the influence of foaming on asphalt binder residues and mixture workability and coatability. The influence of foaming process on the rheological properties of asphalt binder residue was investigated. In addition, the significance of foamed asphalt binder characteristics on mixture workability and coatability was evaluated. Results from this last part of the study can be used to optimize binder foaming such that the resulting mixture is coated and compacted without compromising performance. / text

In the field of product development, many organizations struggle to create a value proposition that can overcome the headwinds of technology change, regulatory requirements, and intense competition, in an effort to satisfy the long-term goals of sustainability. Today, organizations are realizing that they have lost portfolio value due to poor reliability, early product retirement, and abandoned design platforms. Beyond Lean and Green Manufacturing, shareholder value can be enhanced by taking a broader perspective, and integrating sustainability innovation elements into product designs in order to improve the delivery process and extend the life of product platforms. This research is divided into two parts that lead to closing the loop towards Sustainable Value Creation in product development. The first section presents a framework for achieving Sustainable Lifetime Value through a toolset that bridges the gap between financial success and sustainable product design. Focus is placed on the analysis of the sustainable value proposition between producers, consumers, society, and the environment and the half-life of product platforms. The Half-Life Return Model is presented, designed to provide feedback to producers in the pursuit of improving the return on investment for the primary stakeholders. The second part applies the driving aspects of the framework with the development of an Adaptive Genetic Search Algorithm. The algorithm is designed to improve fault detection and mitigation during the product delivery process. A computer simulation is used to study the effectiveness of primary aspects introduced in the search algorithm, in order to attempt to improve the reliability growth of the system during the development life-cycle. The results of the analysis draw attention to the sensitivity of the driving aspects identified in the product development lifecycle, which affect the long term goals of sustainable product development. With the use of the techniques identified in this research, cost effective test case generation can be improved without a major degradation in the diversity of the search patterns required to insure a high level of fault detection. This in turn can lead to improvements in the driving aspects of the Half-Life Return Model, and ultimately the goal of designing sustainable products and processes.

The half-life of two-neutrino double beta decay of 150 Nd has been measured with data taken by the NEMO-3 experiment at the Modane Underground Laboratory. Using 1918.5 days of data recorded with 36.55 g of 150 Nd the half-life of this process is measured to be T2ν 1/2 = (8.99 ± 0.18 (stat.) ± 0.71 (syst.)) × 1018 y. SuperNEMO is the successor to NEMO-3 and will be one of the next generation of 0νββ experiments. It aims to measure 82 Se with an half-life sensitivity of 1026 yr corresponding to ⟨mββ⟩ < 50 - 100 meV. In order to achieve this target, a testing apparatus for the scintillator characterization has been developed and 140 scintillator blocks were characterized for the calorimeter of the SuperNEMO. It was determined that none of the blocks violate defined criteria of uniformity (± 3% for the energy resolution at 1 MeV) nor the criteria of energy resolution (< 16% at 1 MeV). The average uniformity of the blocks was found to be 0.7% and the average energy resolution of these blocks is 12% at 1 MeV. However, it was discovered during the visual tests that 23 out of 140 blocks contain more than 20 visible dust specks, thus alarming the possible contamination of these blocks with the natural radioactive isotopes.

Made available in DSpace on 2014-06-11T19:33:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-13Bitstream added on 2014-06-13T19:04:51Z : No. of bitstreams: 1 rocha_rjs_dr_jabo.pdf: 825439 bytes, checksum: 2af7dcdaa1a7cdb8311729451dfa2d74 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O nitrogênio é nutriente absorvido em maiores quantidades na cultura do milho e o que proporciona maiores produtividades de grãos, sendo seu uso no sistema solo-planta alterado pelo sistema de cultivo utilizado. Com o objetivo de avaliar o efeito de sistemas de cultivo e doses de nitrogênio na produção de matéria seca, nitrogênio na planta, nitrogênio foliar, produtividade de grãos e eficiência do nitrogênio no milho, foi implantado experimento de campo nos anos de 2008 e 2009, em um Argissolo Vermelho-Amarelo, distrófico, sob irrigação. Utilizou-se o delineamento experimental em parcelas subdivididas, com oito repetições. As parcelas foram constituídas pela semeadura direta (SD) e plantio convencional (PC). Nas subparcelas, foram aplicadas seis doses de N (0; 40; 80; 120; 160 e 200 kg ha-1) na forma de uréia. Em 2009 a fim de avaliar a velocidade de decomposição e liberação do nitrogênio do feijão utilizado como cobertura morta, esses resíduos foram acondicionados em sacolas de náilon, as quais foram dispostas sobre o solo nas parcelas correspondente a SD e o seu conteúdo analisado em intervalos de 25 dias, até 100 dias após sua instalação. A adubação nitrogenada aumentou significativamente as variáveis relacionadas com a produtividade, sendo que a SD proporcionou a maior produção de matéria seca da parte aérea, matéria seca do grão, nitrogênio na parte aérea, nitrogênio do grão, produtividade de grãos, eficiência de absorção e uso do nitrogênio. A faixa de suficiência de nitrogênio na folha variou de 25,7 a 28,4 g kg-1. As doses máximas econômicas em 2008 e 2009 foram respectivamente de 125 e 160 kg ha-1 N / Nitrogen is the nutrient absorbed in largest quantities in maize which provides more grain yields, and its use in soil-plant system is modified by the tillage system utilized. Aiming to evaluate the effect of cropping systems and nitrogen rates on dry matter production, nitrogen in the plant, leaf nitrogen, grain yield and nitrogen efficiency in maize, field experiment was established in 2008 and 2009 in a dystrophic red-yellow Argisoil under irrigation. The split-plot experimental design were used with eight replications. The plots were established by no-tillage (NT) and conventional tillage (CT). Subplots were set in six levels of N(0, 40, 80, 120, 160 and 200 kg ha-1) as urea. In 2009, in order to assess the speed of decomposition and nitrogen release from the bean plant used as cover crop, plant residues were packaged in nylon bags, which were arranged on the ground in the plots corresponding to NT and its contents examined at intervals of 25 days until 100 days after its installation. The nitrogen fertilization increased significantly the variables related to productivity, being that no-tillage provided the highest dry matter yield on shoot, dry matter of grain, nitrogen on shoot, grain nitrogen, grain yield, nitrogen uptake efficiency and nitrogen use efficiency. The sufficiency range of leaf nitrogen ranged from 25.7 to 28.4 g kg-1. The maximum economic rates in 2008 and 2009 season were respectively 125 and 160 kg ha-1N

Medidas de espectroscopia gama de alta resolução têm diversas aplicações. Aplicações envolvendo medidas de radioisótopos de meia-vida curta podem apresentar problemas de baixa precisão nas contagens quando a fonte radioativa está distante do detector e de perda de acurácia por efeitos de tempo morto e empilhamento de pulsos em situação de altas taxas de contagens. Um modo de minimizar esses problemas é alterando a posição da fonte radioativa durante o processo de medição, aproximando-a do detector conforme sua atividade diminui e assim maximizando o número de contagens medidas. Neste trabalho, foi desenvolvido o Movimentador de Amostras Radioativas Automatizado (MARA), um aparato de baixo custo, feito com materiais de baixo número atômico e leve, projetado e construído para auxiliar nas medidas de espectroscopia gama, capaz de controlar a distância entre a fonte e o detector, permitindo inclusive que ocorra alteração dessa distância durante o processo de medição. Por ser automatizado ele otimiza o tempo do operador, que tem total liberdade para criar suas rotinas de medidas no dispositivo, além de evitar que o mesmo tome uma parcela da dose radioativa. Foi também feita uma interface que permite controle do MARA e a programação do sistema de aquisição de dados. Foram realizados testes para otimização da operação do sistema MARA e foi verificada a segurança de operação do MARA, não apresentando nenhuma falha durante seus testes. Foi aplicado o teste de repetitividade, por meio de medições com uma fonte calibrada de 60Co, e verificou-se que o sistema de movimentação de prateleiras automatizado reproduziu os resultados do sistema estático com confiabilidade de 95%. / High resolution gamma spectroscopy measurements have several applications. Those involving short half-life radioisotope measurements may present low precision problems when the radioactive source is far from detector end cup and in the very high activity situations also can present accuracy loss due to dead time and pile-up effects. A way to overcome these problems is changing the source detector distance as the activity is decreasing, and thereby maximizing the statistical counting. In the present study, the Controller of Acquisition and Sample Positioner for Activation (CASPA) was developed. It is a low cost and weight device, made with low atomic number materials designed to assist gamma spectroscopy measurements, which is able to control the distance between the source and the detector, even allowing that there is a change of this distance during the measurement process. Because it is automated it optimizes the time of the operator, who has complete freedom to program their routine measurements in the device besides minimizing the radiation dose in the operator. An interface that allow the user control the CASPA system and to program the acquisition system was created. Tests aiming to optimize the operation of CASPA system were carried out and the safety of the CASPA operation was verified, it was not presented any failure during their tests. It was applied the repeatability tests by the acquisition 60Co standard source and was found that the positioning of automated system has reproduced the results of static system with a 95% of confidence level .