Os venenos das serpentes são compostos protéicos complexos com extensas atividades biológicas. Estas moléculas abrangem até 95% do peso seco do veneno, e compreendem enzimas, toxinas não enzimáticas e proteínas atóxicas. Dentre as complicações fisiológicas, a Insuficiência Renal Aguda - IRA é bem comum nos acidentes crotálicos, onde as concentrações renais do veneno se apresentam até 50% maiores do que na concentração plasmática. A fração tóxica responsável por essa complicação é a crotoxina. O veneno das serpentes, quando irradiado com raios gama de 60Co, tem a sua toxicidade diminuída, entretanto, são mantidas as suas propriedades imunológicas. Nossa hipótese é que a utilização de veneno irradiado em substituição ao nativo pode reduzir a taxa de lesões renais em animais de grande porte durante a produção de soros antiofídicos, propiciando melhor qualidade de vida e bem estar desses animais. No presente estudo realizou-se o isolamento da crotoxina por técnicas cromatográficas, a partir do veneno da serpente Crotalus durissus terrificus. Parte da toxina isolada foi reservada e denominada crotoxina nativa (CTXN) enquanto que outra parte foi irradiada com 2 kGy de raios gama oriundos de uma fonte de 60Co e denominada crotoxina irradiada (CTXI). Diferentes grupos de camundongos Balb/c receberam a toxina nativa ou irradiada e tiveram seus rins removidos em diferentes tempos pós-injeção da crotoxina. Realizou-se a nefrectomia dos animais e foi feito o preparo dos cortes histológicos em Hematoxilina-Eosina (HE) e cortes de imunohistoquímica com anticorpo policlonal de coelho anticrotoxina. As alterações histopatológicas encontradas nas amostras foram glomerulonefrite (GN), congestão capilar (CC) e necrose tubular aguda (NTA). Verificou-se que a GN teve maior ocorrência no grupo CTXN que no grupo CTXI. A NTA foi dominante no grupo CTXN em relação ao grupo CTXI. A CC foi predominante no grupo CTXI que no grupo CTXN. Entretanto esta diferença não é estatisticamente significante segundo o teste t Student de amostras independentes. O tratamento imunohistoquímico revelou que a concentração de antígeno marcado com o anticorpo é decrescente segundo os intervalos de tempo de eutanásia dos animais do grupo inoculado com CTXI, pois a crotoxina quando irradiada tem a sua excreção renal facilitada. Conclui-se que as alterações histopatológicas GN e a NTA foram significativamente menos frequentes em rins de animais inoculados com CTXI. Diferentemente da crotoxina nativa, a crotoxina irradiada é detectada pelo anticorpo anticrotoxina apenas nos tempos intermediários pós-inoculação e em baixa concentração, indicando que a radiação gama promoveu mudanças na forma de ligação da toxina ao tecido renal, facilitando sua eliminação e diminuindo, portanto, as chances de lesão. Esses resultados reforçam as evidências de que o uso de veneno irradiado no processo de imunização garante uma melhor qualidade de vida e bem estar aos animais soroprodutores. / Snake venoms are complex mixtures of proteins and peptides with a wide spectrum of physiological targets such as the blood coagulation and cardiovascular systems and the motor end plate among others. Acute renal failure is a common complication in accidents with the South American rattlesnake. The toxin involved in this pathology is crotoxin, a major component of the venom in terms of concentration and toxicity. Snake venoms, when irradiated with 60Co gamma rays present a significant decrease in toxicity while the immunogenic properties of its components are preserved. The use of irradiated rattlesnake venom is an attractive alternative for antisera production since it might reduce the appearance of renal lesions improving the welfare and lifespan of animals employed for antivenom production. In the present work, we have isolated crotoxin from crude venom of C. d. terrificus and irradiates part of it with 2 kGy of gamma rays from 60Co and compared the effects of native (CTXN) and irradiated (CTXI) crotoxin on the mice renal function. We conducted nephrectomy of animals and preparation of histological sections with hematoxylin-eosin (HE) and immunohistochemistry with polyclonal rabbit anticrotoxin for analysis in optical microscopy. Histopatological changes found in the samples were glomerulonephritis (GN), capillary congestion (CC) acute kidney tubular necrosis (NTA). Immunohistochemistry indicates that the concentration of bound antibody labelled antigen decreases in a time dependent manner. The GN ante NTA were significantly less frequent in kidneys of animals inoculated with irradiated toxin. The capillary congestion was evidenced in all animals treated with irradiated or native crotoxin. Concluding, ionizing radiation appears to mitigate the nephrotoxic effects of crotoxin and may represent an alternative for antivenin production, improving welfare for seroproductor animal.

Medidas das secções de choque de fotonêutrons do 9Be, 13C e 17O foram obtidas no intervalo de energia entre 1,6 e 10,8 MeV, utilizando radiação gama de alta resolução em energia (3 a 21 eV) produzida na captura de nêutrons térmicos por 21 materiais alvo, quando posicionados no interior de um canal tangencial, junto ao núcleo do reator de pesquisa IEAR1 (5 MW) do IPEN/CNEN-SP. As amostras foram irradiadas no interior de um sistema detector de nêutrons “Long Counter”, de geometria 4π, a 520,5 cm de distância do alvo de captura. O fluxo de raios gama foi determinado por meio da análise do espectro gama obtido fazendo uso de um detector de estado sólido do tipo Ge(Li) (EG&G ORTEC, 25 cm3, 5%), previamente calibrado com raios gama de captura produzidos por uma amostra padrão de nitrogênio (Melamina). A secção de choque de fotonêutron foi medida para o espectro de raios gama de captura de cada alvo (secção de choque composta). Uma metodologia de inversão de matrizes para a resolução de problemas inverso discretos foi utilizada para a deconvolução do conjunto de valores experimentais da secção de choque composta, com a finalidade de obter a secção de choque em valores específicos de energia de excitação (energia das linhas gama principais dos alvos de captura). As secções de choque obtidas, nas energias das linhas gama principais de todos os alvos, foram comparadas com as medidas realizadas por outros autores utilizando diferentes fontes de radiação gama. Uma boa concordância foi observada entre os resultados experimentais deste trabalho com as relatados na literatura. / Photoneutron cross sections measurements of 9Be, 13C e 17O have been obtained in the energy interval between 1,6 and 10,8 MeV, using neutron capture gamma-rays with high resolution in energy (3 a 21 eV), produced by 21 target materials, placed inside a tangential beam port, near the core of the IPEN/CNEN-SP IEA-R1 (5 MW) research reactor. The samples have been irradiated inside a 4π geometry neutron detector system “Long Counter”, 520,5 cm away from the capture target. The capture gamma-ray flux was determined by means of the analysis of the gamma spectrum obtained by using a Ge(Li) solid-state detector(EG&G ORTEC, 25 cm3, 5%), previously calibrated with capture gamma-rays from a standard target of Nitrogen (Melamine). The neutron photoproduction cross section has been measured for each target capture gamma-ray spectrum (compound cross section). A inversion matrix methodology to solve inversion problems for unfolding the set of experimental compound cross sections, was used in order to obtain the cross sections at specific excitation energy values (principal gamma line energies of the capture targets). The cross sections obtained at the energy values of the principal gamma lines were compared with experimental data reported by other authors, with have employed different gamma-ray sources. A good agreement was observed among the experimental data in this work with reported in the literature.

Extensas lesões na pele expõem o organismo a uma série de agentes agressores, dificultando a reparação espontânea da pele e muitas vezes levando o paciente a óbito. Nesse caso, se não houver áreas doadoras de autoenxertos, pode se utilizar aloenxertos. Neste tipo de enxerto, os tecidos são processados em Bancos de Tecidos, onde se pode empregar a radiação ionizante como método de esterilização. De acordo com estudos in vitro, a radiação gama, em doses acima de 25 kGy, provoca desestruturação das fibrilas de colágeno I da derme conservada em glicerol na concentração de 85%, reduzindo significativamente a resistência à tração dos tecidos irradiados. Observações clínicas sugerem, ainda, integração mais rápida da derme humana, conservada em glicerol e submetida à radiação ionizante, com os tecidos do receptor, quando comparada à derme somente conservada em glicerol. Para verificar se essas alterações relatadas in vitro, comprometeriam o emprego in vivo, de amostras de pele humana, submetidas à radiação gama, foram realizados transplantes de peles humanas, irradiadas ou não, em camundongos Nude. A pele dos camundongos foi submetida à análise macroscópica, imagens de tomografia de coerência óptica, histologia e ensaios biomecânicos. Foi possível concluir que os enxertos irradiados a 25 kGy promoveram uma contração inicial maior, mas essa alteração não interferiu na dimensão da área final de reparação, ainda, os animais que receberam esses enxertos apresentaram mais rápido fechamento da ferida em comparação com os demais, além disso o emprego de enxertos irradiados (25 e 50 kGy) promoveu a formação de um processo de reparação mais organizado e sem efeitos significantes nas propriedades biomecânicas. / Extensive skin lesions expose the body to damaging agents, which makes spontaneous regeneration difficult and, in many cases, leads patient to death. In such cases, if there are no donating areas for autograft, allografts can be used. In this type of graft, tissue is processed in tissue banks, where it can be subjected to radiosterilization. According to in vitro studies, gamma radiation, in doses higher than 25 kGy, induces alterations in skin preserved in glycerol at 85%, reducing the tensile strength of irradiated tissue. Clinical observation also suggests faster integration of such graft with the receptors tissue. In order to assess if the alterations observed in vitro, would compromise in vivo use, transplants of human tissue, irradiated or not, were performed in Nude mice. The skin of the mice was subjected to macroscopic analysis, optical coherence tomography imaging, histological and biomechanical assays. It was possible to conclude that grafts irradiated with 25 kGy promoted greater initial contraction, without alteration of the final dimensions of the repair area, also displaying a faster closing of the wound. Moreover, the use of irradiated grafts (25 and 50 kGy) enabled the formation of a more organized healing process without significant effects on biomechanical properties.

No description available.

Bayesian approaches to prediction and the assessment of predictive uncertainty in generalized linear models are often based on averaging predictions over different models, and this requires methods for accounting for model uncertainty. In this thesis we describe computational methods for Bayesian inference and model selection for generalized linear models, which improve on existing techniques. These methods are applied to the building of flexible models for gamma ray count data (data measuring the natural radioactivity of rocks) at the Castlereagh Waste Management Centre, which served as a hazardous waste disposal facility for the Sydney region between March 1978 and August 1998. Bayesian model selection methods for generalized linear models enable us to approach problems of smoothing, change point detection and spatial prediction for these data within a common methodological and computational framework, by considering appropriate basis expansions of a mean function. The data at Castlereagh were collected in the following way. A number of boreholes were drilled at the site, and for each borehole a gamma ray detector recorded gamma ray emissions at different depths as the detector was raised gradually from the bottom of the borehole to ground level. The profile of intensity of gamma counts can be informative about the geology at each location, and estimation of intensity profiles raises problems of smoothing and change point detection for count data. The gamma count profiles can also be modelled spatially, to inform the geological profile across the site. Understanding the geological structure of the site is important for modelling the transport of chemical contaminants beneath the waste disposal area. The structure of the thesis is as follows. Chapter 1 describes the Castlereagh hazardous waste site and the geophysical data, which motivated the methodology developed in this research. We summarise the principles of Gamma Ray (GR) logging, a method routinely employed by geophysicists and environmental engineers in the detailed evaluation of hazardous site geology, and detail the use of the Castlereagh data in this research. In Chapter 2 we review some fundamental ideas of Bayesian inference and computation and discuss them in the context of generalised linear models. Chapter 3 details the theoretical basis of our work. Here we give a new Markov chain Monte Carlo sampling scheme for Bayesian variable selection in generalized linear models, which is analogous to the well-known Swendsen-Wang algorithm for the Ising model. Special cases of this sampling scheme are used throughout the rest of the thesis. In Chapter 4 we discuss the use of methods for Bayesian model selection in generalized linear models in two specific applications, which we implement on the Castlereagh data. First, we consider smoothing problems where we flexibly estimate the dependence of a response variable on one or more predictors, and we apply these ideas to locally adaptive smoothing of gamma ray count data. Second, we discuss how the problem of multiple change point detection can be cast as one of model selection in a generalized linear model, and consider application to change point detection for gamma ray count data. In Chapter 5 we consider spatial models based on partitioning a spatial region of interest into cells via a Voronoi tessellation, where the number of cells and the positions of their centres is unknown, and show how these models can be formulated in the framework of established methods for Bayesian model selection in generalized linear models. We implement the spatial partition modelling approach to the spatial analysis of gamma ray data, showing how the posterior distribution of the number of cells, cell centres and cell means provides us with an estimate of the mean response function describing spatial variability across the site. Chapter 6 presents some conclusions and suggests directions for future research. A paper based on the work of Chapter 3 has been accepted for publication in the Journal of Computational and Graphical Statistics, and a paper based on the work in Chapter 4 has been accepted for publication in Mathematical Geology. A paper based on the spatial modelling of Chapter 5 is in preparation and will be submitted for publication shortly. The work in this thesis was collaborative, to a smaller or larger extent in its various components. I authored Chapters 1 and 2 entirely, including definition of the problem in the context of the CWMC site, data gathering and preparation for analysis, review of the literature on computational methods for Bayesian inference and model selection for generalized linear models. I also authored Chapters 4 and 5 and benefited from some of Dr Nott's assistance in developing the algorithms. In Chapter 3, Dr Nott led the development of sampling scheme B (corresponding to having non-zero interaction parameters in our Swendsen-Wang type algorithm). I developed the algorithm for sampling scheme A (corresponding to setting all algorithm interaction parameters to zero in our Swendsen-Wang type algorithm), and performed the comparison of the performance of the two sampling schemes. The final discussion in Chapter 6 and the direction for further research in the case study context is also my work.

Bibliography: p. 106.

Observations of gamma-rays have been made from celestial sources such as active galaxies, gamma-ray bursts and supernova remnants as well as the Galactic ridge. The study of gamma rays can provide information about production mechanisms and cosmic-ray acceleration. In the high-energy regime, one of the dominant mechanisms for gamma-ray production is the decay of neutral pions produced in interactions of ultra-relativistic cosmic-ray nuclei and interstellar matter. Presented here is a parametric model for calculations of inclusive cross sections and transverse momentum distributions for secondary particles - gamma rays, elecrons, positrons, electron neutrinos, electron antineutrinos, muon neutrinos and muon antineutrinos - produced in proton-proton interactions. This parametric model is derived on the proton-proton interaction model proposed by Kamae et al.; it includes the diffraction dissociation process, Feynman-scaling violation and the logarithmically rising inelastic proton-proton cross section. To improve fidelity to experimental data for lower energies, two baryon resonance excitation processes were added; one representing the Delta(1232) and the other multiple resonances with masses around 1600 MeV/c^2. The model predicts the power-law spectral index for all secondary particles to be about 0.05 lower in absolute value than that of the incident proton and their inclusive cross sections to be larger than those predicted by previous models based on the Feynman-scaling hypothesis. The applications of the presented model in astrophysics are plentiful. It has been implemented into the Galprop code to calculate the contribution due to pion decays in the Galactic plane. The model has also been used to estimate the cosmic-ray flux in the Large Magellanic Cloud based on HI, CO and gamma-ray observations. The transverse momentum distributions enable calculations when the proton distribution is anisotropic. It is shown that the gamma-ray spectrum and flux due to a pencil beam of protons varies drastically with viewing angle. A fanned proton jet with a Gaussian intensity profile impinging on surrounding material is given as a more realistic example. As the observer is moved off the jet axis, the peak of the spectrum is moved to lower energies. / QC 20100803

The quest for the first detection of a galaxy cluster in the high energy gamma-ray regime is ongoing, and even though clusters are observed in several other wave-bands, there is still no firm detection in gamma-rays. To complement the observational efforts we estimate the gamma-ray contributions from both annihilating dark matter and cosmic-ray (CR) proton as well as CR electron induced emission. Using high-resolution simulations of galaxy clusters, we find a universal concave shaped CR proton spectrum independent of the simulated galaxy cluster. Specifically, the gamma-ray spectra from decaying neutral pions, which are produced by CR protons, dominate the cluster emission. Furthermore, based on our derived flux and luminosity functions, we identify the galaxy clusters with the brightest galaxy clusters in gamma-rays. While this emission is challenging to detect using the Fermi satellite, major observations with Cherenkov telescopes in the near future may put important constraints on the CR physics in clusters. To extend these predictions, we use a dark matter model that fits the recent electron and positron data from Fermi, PAMELA, and H.E.S.S. with remarkable precision, and make predictions about the expected gamma-ray flux from nearby clusters. In order to remain consistent with the EGRET upper limit on the gamma-ray emission from Virgo, we constrain the minimum mass of substructures for cold dark matter halos. In addition, we find comparable levels of gamma-ray emission from CR interactions and dark matter annihilations without Sommerfeld enhancement. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted.

A new generation of medical grade Cf-252 sources was developed in 2002 at the Oak Ridge National Laboratory (ORNL). The combination of small size and large activity of these Cf-252 sources makes them suitable to be used with the conventional high-dose-rate (HDR) remote afterloading systems for interstitial brachytherapy. A recent in-water calibration experiment showed that the measured gamma dose rates near the new source are slightly greater than the neutron dose rates; contradicting the well established neutron-to-gamma dose ratio of approximately 2:1 at locations near a Cf-252 brachytherapy source. Specifically, the MCNP-predicted gamma dose rate is a factor of two higher than the measured gamma dose rate at the distance of 1 cm, and the differences between the two results gradually diminish at distances farther away from the source. To resolve this discrepancy, we updated the source gamma spectrum by including in the ORIGEN-S data library the experimentally measured Cf-252 prompt gamma spectrum as well as the true Cf-252 spontaneous fission yield data to explicitly model delayed gamma emissions from fission products. We also investigated the bremsstrahlung x-rays produced by the beta particles emitted from fission-product decays. The results show that the discrepancy of gamma dose rates is mainly caused by the omission of the bremsstrahlung x-rays in the MCNP runs. By including the bremsstrahlung x-rays, the MCNP results show that the gamma dose rates near a new Cf-252 source agree well with the measured results and that the gamma dose rates are indeed greater than the neutron dose rates. The calibration experiment also showed discrepancies between the experimental and computational neutron dose profiles obtained. Specifically the MCNP-predicted neutron dose rates were ~25% higher than the measured neutron dose rates at all distances. In attempting to resolve this discrepancy the neutron emission rate was verified by the National Institute of Standards and Technology (NIST) and an experiment was performed to explore the effects of bias voltage on ion chamber charge collection. So far the discrepancies between the computational and experimental neutron dose profiles have not been resolved. Further study is needed to completely resolve this issue and some suggestions on how to move forward are given.

published_or_final_version / Radioisotope / Master / Master of Philosophy