No description available.

Ziel der vorliegenden Arbeit war es einerseits zu untersuchen, ob unter den Bedingungen eines regulären Schlachtbetriebs die stumpfe Schuss-Schlagbetäubung eine den tierschutzrechtlichen Anforderungen entsprechende Alternative zur Bolzenschussbetäubung darstellt. Andererseits sollte überprüft werden, ob es zu einer nachweisbaren Embolisierung von ZNS-Gewebe in die Lungengefäße, das Herzlumen oder das Herzspitzengewebe kommt.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19770号 / 農博第2166号 / 新制||農||1040(附属図書館) / 学位論文||H28||N4986(農学部図書室) / 32806 / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 河田 照雄, 教授 保川 清, 教授 橋本 渉 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Ein Ziel dieser Arbeit war die Entwicklung eines differentialdiagnostischen Tests (FLI-Test), der die Abgrenzung einer BSE- von einer Scrapieinfektion durch die direkte Untersuchung des Hirnstammmaterials ermöglicht. Bei einem Teil der dabei untersuchten deutschen klassi-schen Scrapiefälle wurde diese Charakterisierung zusätzlich im bis dahin zur Differenzierung verwendeten klassischen Mausbioassay durchgeführt, um die Ergebnisse aus dem FLI-Test zu verifizieren und um die vorhandenen Scrapieisolate weitergehend zu charakterisieren. Im zweiten Teil dieser Arbeit wurden die biochemischen Eigenschaften atypischer deutscher Scrapieisolate analysiert und ihre Infektiosität anhand von Übertragungsversuchen auf drei Wildtypmauslinien und eine transgene Mauslinie beurteilt. Darüber hinaus wurden diese Isolate dem klassischen BSE-Isolat gegenüber gestellt.

No description available.

This dissertation consists of three essays examining the impacts of Sanitary and Phytosanitary (SPS) Measures on agricultural trade. The first essay estimates the impact of the 2003 Bovine Spongiform Encephalopathy (BSE) outbreak in the US on Japanese beef imports. I develop a source-differentiated demand system of fresh/chilled and frozen beef imports augmented with endogenous smooth transition functions. Results suggest that over one-half of the estimated income, own-price, and cross-price elasticities reached a new regime in the post-BSE period of Japanese beef imports where the competitive relationship and substitutability between US and Australian beef exports changed significantly. The second essay develops a product-line structural gravity model to estimate the trade flow effects of SPS measures that have been flagged as specific trade concerns in the World Trade Organization's (WTO's) SPS Committee meetings for the top 30 agricultural trading countries covering four major product sectors. Our findings are striking and call attention to the need for a deeper understanding of the impacts of SPS measures on WTO members' agricultural trade. Results show that the trade effects of SPS trade concern measures reduce exporters' agricultural trade by 67%, on average, during periods in which concerns were active. Significant heterogeneity in the trade effect of SPS measures exists with average estimated ad valorem equivalent tariffs ranging from 33% to 106%. The AVE effect of SPS concern measures maintained by the US is estimated at 42%, less than a half (a third) of the AVE effects of SPS concern measures imposed by the European Union (China). China's restrictions on Avian Influenza and ractopamine restrictions in pork exports are estimated to be the most prohibitive, causing an AVE effect of 120.3% and 88.9%, respectively. The third essay develops a discrete-time duration model to examine the extent to which these SPS concern measures affect the hazard rate of US agri-food exports during the 1995-2016 period. Results show that SPS concern measures raise the hazard rate of US agri-food exports by a range of 2.1%~15.3%, causing the predicted hazard rate to increase from 21.8% to a range of 23.6%~27.9%. This effect is heterogeneous across different agricultural sectors, with the most substantial effects occurring in US exports of meat, fruits, and vegetables. / Doctor of Philosophy / This dissertation consists of three essays on the examination of Sanitary and Phytosanitary (SPS) Measures and their impacts on agricultural trade. The first essay estimates the impact of the US 2003 Bovine Spongiform Encephalopathy (BSE) outbreaks on Japanese beef imports. Using a source-differentiated demand system of fresh/chilled and frozen beef imports embedded with endogenous smooth transition functions, we find that over one-half of the estimated income, own-price, and cross-price elasticities have changed remarkably, causing the Japanese beef import market to reach a new regime in the post-BSE period where the substitution and/or competition relationships between the US and Australia have changed. The second essay develops a product-line structural gravity model to estimate the trade effects of SPS measures flagged as concerns in the WTO's SPS Committee meetings for the top 30 agricultural trading countries covering four major product sectors. Results show that the trade effects of SPS concern measures are negative and significant, with the average estimated AVE tariffs ranging 33%~106%. The AVE effect of SPS concern measures maintained by the US is estimated to be 42%, less than a half (a third) of the AVE effects of SPS concern measures imposed by the European Union (China). China's restrictions on Avian Influenza and various ractopamine restrictions in the production and export of pork products are estimated to be the most prohibitive, causing an AVE effect of 120.3% and 88.9%, respectively. The third essay applies a discrete-time duration model to examine the extent to which SPS concern measures affect the hazard rate of US agri-food exports in 1995-2016. Results show that SPS concern measures raise the hazard rate of US agri-food exports by a range of 2.1%~15.3%, causing the predicted hazard rate to increase from 21.8% to a range of 23.6%~27.9%. This effect is heterogeneous across different agricultural sectors, with the most substantial effects occurring in US exports of meat, fruits, and vegetables.

No description available.

Príons são patógenos infecciosos que causam um grupo de doenças neurodegenerativas fatais. A proteína normal, PrP celular, denominada PrPC, é convertida em PrPSc, isoforma anormal e patogênica de PrP, através de um processo no qual uma porção de -hélice da estrutura é reenovelada em folhas . A conversão de PrPC em PrPSc ocorre por um mecanismo auto-catalítico. Para um melhor entendimento do mecanismo de propagação dos príons, têm sido propostos vários modelos matemáticos. Nesse trabalho, estudamos o tempo de incubação de algumas doenças causadas por príons: Encefalopatia Espongiforme Bovina (BSE), ou mal da vaca louca; doença variante de Creutzfeldt-Jakob (vCJD), que afeta humanos, através da exposição ao agente de BSE; e Scrapie murina, uma infecção priônica experimental em camundongos. A distribuição de probabilidades da duração do período de incubação foi suposta ser lognormal, modelo este extensamente aceito em doenças infecciosas. Os objetivos desse trabalho foram esclarecer aspectos obscuros sobre a cinética de replicação priônica e o mecanismo de toxicidade das doenças priônicas, através de comparação dos resultados de simulações computacionais com os perfis de distribuição de tempos de incubação de BSE, vCJD e Scrapie murina. Foram realizadas simulações computacionais, utilizando o Método Monte Carlo Dinâmico (MCD) e o modelo Difusão Limitada à Agregação. Primeiramente, estudamos o modelo de Eigen (1996), através de simulações computacionais usando o MCD, para verificar quais termos são importantes para a cinética priônica. De posse desse resultado, partimos então para o estudo sobre a toxicidade das doenças priônicas, usando o modelo DLA e o método MCD: considerando que PrPC se converte em PrPSc quando existe contato (auto-catálise); e PrPCs são livres e podem se movimentar por uma rede, enquanto PrPScs, ou agregados de PrPScs são fixos. Confirmamos a suspeita de Eigen de que o termo mais importante nas equações de cinética priônica é o termo de Michaelis-Menten, ou termo auto-catalítico. Os resultados obtidos através das simulações MCD e modelo DLA foram comparados com os perfis de distribuições de tempos dessas doenças (BSE, vCJD e Scrapie murina). Conseguimos o ajuste de diferentes perfis de distribuição de tempos de incubação para algumas doenças priônicas, lognormal para BSE e vCJD, e lognormal com segundo pico para Scrapie murina. A auto-catálise é o mecanismo mais importante na cinética priônica, a conversão espontânea de PrPC em PrPSc pode ser negligenciada. A partir do modelo DLA, fica reforçada a hipótese de que para BSE e vCJD, doenças priônicas de ocorrência natural, a toxicidade é causada, principalmente, pela formação das placas amilóides. Para Scrapie murina, uma infecção experimentalmente induzida, a toxicidade é, possivelmente, causada por dois mecanismos: formação das placas amilóides e depleção de PrPC. Apenas com a mudança dos parâmetros iniciais e finais, conseguimos ajustar as distribuições de tempos de incubação das três doenças priônicas estudadas, apesar de o modelo ser bastante simples. A lognormalidade, de acordo com o modelo, é resultado do processo difusivo. As concentrações de PrPC devem ser baixas, menores que 1% e o número de PrPScs deve ser menor que 10 para que a lognormalidade ocorra sem a depleção de PrPC. / Prions are infectious agents responsible for a group of fatal neurodegenerative disorders. A pathogenic isoform of the prion protein (PrPSc) generated by a posttranslational process involving the conversion of alpha helices into beta sheets of the normal cellular prion protein (PrPC) is believed to be the main component of these infectious agents. The conversion of a normal PrPC into an abnormal isoform PrPSc, kinetically follows through an autocatalytic process. For better understanding of this kind of abnormal protein propagation, many analytical models have been proposed. Thus, we studied, using the Monte Carlo method, the distribution of the incubation periods in some of these neurodegenerative disorders, such as: bovine spongiform encephalopathy well known as mad cow disease (BSE), Variant Creutzfeldt Jakob disease (vCJD) and murine scrapie, an experimental murine prionic disease. The distribution of the incubation times of these diseases were considered lognormal. The aim of this study was to investigate some aspects of toxicity and replication of the prionic diseases, by comparing the results of computational simulations with the incubation times of BSE, vCJD and murine scrapie, previously established. Computational simulations, using a Dynamical Monte Carlo method (DMC) and the diffusion limited aggregation model (DLA), were worked out. At first, we evaluate the Eigen model through computational simulations using the DMC to verify the essential parameters in the kinetic of the prionic diseases. Following the results, we studied the toxicity of the prionic diseases using the DMC and the DLA model; by considering that PrPC converting in PrPSc just when exists contact (autocatalysis) and free PrPCs are allowed to diffuse randomly to their nearest neighbour sites in a square lattice, while isolated PrPScs or aggregate of PrPScs are fixed. Confirming the Eigen suspicion, the most important parameter in the equation of the prionic kinetic is the Michaelis Menten term (or the autocatalytic term). The results obtained through simulations using DMC and DLA model were compared with the time distribution profiles of the prionic diseases already established (BSE, vCJD and murine Scrapie). We get the fitting in different profiles of the distribution of the incubation periods (lognormal to BSE and vCJD and lognormal with a second peak to murine scrapie). It is concluded that autocatalysis is an essential mechanism for the prionic kinetics and the spontaneous conversion of PrPC in PrPSc can be neglected. Starting from the DLA model, is reinforced that the hypothesis for BSE and vCJD, prionic diseases of natural occurrence, the toxicity is caused, mainly, by the formation of amyloid plaques. For Scrapie murina, an experimentally induced infection, the toxicity is, possibly, caused by two mechanisms: formation of amyloid plaques and depletion of PrPC. Just with the change of the initial and final parameters, we fitted all studied prionic diseases, in spite of the model to be quite simple. The lognormality from the model, is resulting of a diffusive process. Concentrations of PrPC should be low, smaller than 1% and the number of PrPScs should be smaller than 10 for the lognormality take place without the depletion of PrPC.

Príons são patógenos infecciosos que causam um grupo de doenças neurodegenerativas fatais. A proteína normal, PrP celular, denominada PrPC, é convertida em PrPSc, isoforma anormal e patogênica de PrP, através de um processo no qual uma porção de -hélice da estrutura é reenovelada em folhas . A conversão de PrPC em PrPSc ocorre por um mecanismo auto-catalítico. Para um melhor entendimento do mecanismo de propagação dos príons, têm sido propostos vários modelos matemáticos. Nesse trabalho, estudamos o tempo de incubação de algumas doenças causadas por príons: Encefalopatia Espongiforme Bovina (BSE), ou mal da vaca louca; doença variante de Creutzfeldt-Jakob (vCJD), que afeta humanos, através da exposição ao agente de BSE; e Scrapie murina, uma infecção priônica experimental em camundongos. A distribuição de probabilidades da duração do período de incubação foi suposta ser lognormal, modelo este extensamente aceito em doenças infecciosas. Os objetivos desse trabalho foram esclarecer aspectos obscuros sobre a cinética de replicação priônica e o mecanismo de toxicidade das doenças priônicas, através de comparação dos resultados de simulações computacionais com os perfis de distribuição de tempos de incubação de BSE, vCJD e Scrapie murina. Foram realizadas simulações computacionais, utilizando o Método Monte Carlo Dinâmico (MCD) e o modelo Difusão Limitada à Agregação. Primeiramente, estudamos o modelo de Eigen (1996), através de simulações computacionais usando o MCD, para verificar quais termos são importantes para a cinética priônica. De posse desse resultado, partimos então para o estudo sobre a toxicidade das doenças priônicas, usando o modelo DLA e o método MCD: considerando que PrPC se converte em PrPSc quando existe contato (auto-catálise); e PrPCs são livres e podem se movimentar por uma rede, enquanto PrPScs, ou agregados de PrPScs são fixos. Confirmamos a suspeita de Eigen de que o termo mais importante nas equações de cinética priônica é o termo de Michaelis-Menten, ou termo auto-catalítico. Os resultados obtidos através das simulações MCD e modelo DLA foram comparados com os perfis de distribuições de tempos dessas doenças (BSE, vCJD e Scrapie murina). Conseguimos o ajuste de diferentes perfis de distribuição de tempos de incubação para algumas doenças priônicas, lognormal para BSE e vCJD, e lognormal com segundo pico para Scrapie murina. A auto-catálise é o mecanismo mais importante na cinética priônica, a conversão espontânea de PrPC em PrPSc pode ser negligenciada. A partir do modelo DLA, fica reforçada a hipótese de que para BSE e vCJD, doenças priônicas de ocorrência natural, a toxicidade é causada, principalmente, pela formação das placas amilóides. Para Scrapie murina, uma infecção experimentalmente induzida, a toxicidade é, possivelmente, causada por dois mecanismos: formação das placas amilóides e depleção de PrPC. Apenas com a mudança dos parâmetros iniciais e finais, conseguimos ajustar as distribuições de tempos de incubação das três doenças priônicas estudadas, apesar de o modelo ser bastante simples. A lognormalidade, de acordo com o modelo, é resultado do processo difusivo. As concentrações de PrPC devem ser baixas, menores que 1% e o número de PrPScs deve ser menor que 10 para que a lognormalidade ocorra sem a depleção de PrPC. / Prions are infectious agents responsible for a group of fatal neurodegenerative disorders. A pathogenic isoform of the prion protein (PrPSc) generated by a posttranslational process involving the conversion of alpha helices into beta sheets of the normal cellular prion protein (PrPC) is believed to be the main component of these infectious agents. The conversion of a normal PrPC into an abnormal isoform PrPSc, kinetically follows through an autocatalytic process. For better understanding of this kind of abnormal protein propagation, many analytical models have been proposed. Thus, we studied, using the Monte Carlo method, the distribution of the incubation periods in some of these neurodegenerative disorders, such as: bovine spongiform encephalopathy well known as mad cow disease (BSE), Variant Creutzfeldt Jakob disease (vCJD) and murine scrapie, an experimental murine prionic disease. The distribution of the incubation times of these diseases were considered lognormal. The aim of this study was to investigate some aspects of toxicity and replication of the prionic diseases, by comparing the results of computational simulations with the incubation times of BSE, vCJD and murine scrapie, previously established. Computational simulations, using a Dynamical Monte Carlo method (DMC) and the diffusion limited aggregation model (DLA), were worked out. At first, we evaluate the Eigen model through computational simulations using the DMC to verify the essential parameters in the kinetic of the prionic diseases. Following the results, we studied the toxicity of the prionic diseases using the DMC and the DLA model; by considering that PrPC converting in PrPSc just when exists contact (autocatalysis) and free PrPCs are allowed to diffuse randomly to their nearest neighbour sites in a square lattice, while isolated PrPScs or aggregate of PrPScs are fixed. Confirming the Eigen suspicion, the most important parameter in the equation of the prionic kinetic is the Michaelis Menten term (or the autocatalytic term). The results obtained through simulations using DMC and DLA model were compared with the time distribution profiles of the prionic diseases already established (BSE, vCJD and murine Scrapie). We get the fitting in different profiles of the distribution of the incubation periods (lognormal to BSE and vCJD and lognormal with a second peak to murine scrapie). It is concluded that autocatalysis is an essential mechanism for the prionic kinetics and the spontaneous conversion of PrPC in PrPSc can be neglected. Starting from the DLA model, is reinforced that the hypothesis for BSE and vCJD, prionic diseases of natural occurrence, the toxicity is caused, mainly, by the formation of amyloid plaques. For Scrapie murina, an experimentally induced infection, the toxicity is, possibly, caused by two mechanisms: formation of amyloid plaques and depletion of PrPC. Just with the change of the initial and final parameters, we fitted all studied prionic diseases, in spite of the model to be quite simple. The lognormality from the model, is resulting of a diffusive process. Concentrations of PrPC should be low, smaller than 1% and the number of PrPScs should be smaller than 10 for the lognormality take place without the depletion of PrPC.

This dissertation documents the results of two related efforts. Firstly, a model of nucleon-nucleon (NN) interactions is developed based on scalar field theory. Secondly, the relativistic 2-body Bethe-Salpeter equation (BSE) is generalized to handle inelastic processes in the ladder approximation. Scalar field theory describes the behavior of scalar particles, particles with spin 0. In the present work scalar field theory is used to describe NN interactions mediated by pion exchange. The scalar theory is applied to nucleons despite the fact that nucleons are fermions, spin 1/2 particles best described by fourcomponent Dirac spinor fields. Nevertheless, the scalar theory is shown to give a good fit to experiment for the total cross sections for several reactions [1]. The results are consistent with more elaborate spinor models involving one boson exchange (OBE). The results indicate that the spin and isospin of nucleons can to some extent be ignored under certain conditions. Being able to ignore spin and isospin greatly reduces the complexity of the model. A limitation of the scalar theory is that it does not distinguish between particle and anti-particle. Consequently one must decide how to interpret the s-channel diagrams generated by the theory, diagrams which involve particle creation and annihilation. The issue is resolved by extending the scalar theory to include electric charge, and formulating NN interactions in terms of complex scalar fields, which are able to describe both particles and anti-particles. A generalized Bethe-Salpeter equation (GBSE) is developed to handle inelastic processes in the ladder approximation. The GBSE, formulated using the scalar theory, is new, and introduces a systematic method for analyzing families of coupled reactions. A formalism is developed centered around the amplitude matrix M' defined for a given Lagrangian. M' gives the amplitudes of a family of reactions that arise from the Lagrangian. The formalism demonstrates how these amplitudes, to 2nd order, segregate into independent groups of coupled BSE's. The GBSE formalism is applied to the coupled BSE (CBSE) of Faassen and Tjon (FT) [2] for the reaction N+N->N+Delta, showing that the CBSE is missing a coupling channel, and in the expansion, under counts ladder diagrams. A proof is given of the equivalence of the series of ladder diagrams generated by M' and the S-matrix. A section on future work discusses several projects for further development and application of the GBSE.