In phylogenetic analysis, an important issue is to construct the confidence region for gene trees from DNA sequences. Usually estimation of the trees is the initial step. Maximum likelihood methods are widely applied but few tests are based on distance methods. In this thesis, we propose a new test based on balanced minimum evolution. We first examine the normality assumption of pairwise distance estimates under various model misspeci cations and also examine their variances, MSEs and squared biases. Then we compare the BME method with the WLS method in true tree reconstruction under different variance structures and model pairs. Finally, we develop a new test for finding a confidence region for the tree based on the BME method and demonstrate its effectiveness through simulation.

В работе изучаются три нелинейных модели, предложенных Альбертом Голдбетером для описания ферментативной реакции в живой клетке. Математически эти нелинейные модели интересны своей быстро-медленной динамикой, автоколебаниями канардового типа, крайней неоднородностью детерминированных фазовых портретов, большой вариабельностью и сосуществованием динамических режимов. В этих условиях даже небольшие случайные возмущения существенно изменяют динамику системы и индуцируют такие феномены, как стохастическая возбудимость, мультимодальность, фантомный аттрактор и переходы от порядка к хаосу. Проведенное исследование данных моделей дает понимание основных механизмов этих явлений с помощью методов численного и статистического анализа, а также теоретического подхода, основанного на функции стохастической чувствительности и методе доверительных областей. / The work examines three nonlinear models proposed by Albert Goldbeter to describe the enzymatic reaction in a living cell. Mathematically, these nonlinear models are interesting for their slow-fast dynamics, canard-type self-oscillations, extreme inhomogeneity of deterministic phase portraits, great variability and coexistence of dynamic modes. Under these conditions, even small random perturbations significantly change the dynamics of the system and induce such phenomena as stochastic excitability, multimodality, phantom attractor, and transitions from order to chaos. The study of these models provides an understanding of the main mechanisms of these phenomena using methods of numerical and statistical analysis, as well as a theoretical approach based on the stochastic sensitivity function and the method of confidence domains.

No description available.

The central theme of this thesis is the construction of simultaneous confidence regions (SCR) corresponding to stepwise multiple comparison procedures (MCP). The first chapter is devoted to the theory of multiple comparisons, including the class of closed testing procedures which contains every MCP that strongly con- trols the familywise error rate. The second chapter is concerned with the gene- ral principle of construction of SCR corresponding to closed testing procedures. These general results are used in the third and the forth chapter for deriving the SCR corresponding to a subclass of closed testing procedures which are based on weighted Bonferroni tests. The SCR corresponding to the Holm, the Holm(W), the fixed-sequence and the fallback MCP are derived explicitly. The theoretical results are numerically illustrated on a bioequivalence study. In the fifth chapter we briefly discuss the SCR corresponding to the Hommel, the Hochberg and the step-down Dunnett MCP.

The aim of this thesis is a comprehensive description of the properties of a nonlinear least squares estimator for a nonlinear regression model with normally distributed errors and thorough development of various methods for constructing confidence regions and confidence intervals for the parameters of the nonlinear model. Due to the fact that, unlike the case of linear models, there is no easy way to construct an exact confidence region for the parameters, most of these methods are only approximate. A short simulation study comparing observed coverage of various confidence regions and confidence intervals for models with different curvatures and sample sizes is also included. In case of negligible intrinsic curvature the use of likelihood-ratio confidence regions seems the most appropriate.

Experimentos nos quais uma ou mais variáveis respostas são influênciadas por diversos fatores quantitativos são bastante comuns nas áreas agrícola, química, biológica, dentre outras. Nesse caso, o problema de pesquisa consiste em se estudar essa relação, sendo de grande utilidade o uso da metodologia de superfícies de resposta (MSR). Nesse contexto, a determinação dos níveis dos fatores que otimizam a resposta consiste inicialmente na obtenção das coordenadas do ponto estacionário do modelo ajustado. No entanto, como o modelo verdadeiro é desconhecido, é interessante obter uma região de confiança das coordenadas verdadeiras de modo a avaliar a precisão da estimativa obtida. Foram abordados aqui os procedimentos para construção de regiões de confiança para as coordenadas do ponto estacionário em diferentes situações considerando-se a forma das superfícies analisadas e a distribuição e magnitude da variância dos erros do modelo. Foram utilizadas a metodologia de Box e Hunter (1954) (BH), "bootstrap" e "bootstrap" Bayesiano aliados ao cálculo da distância de Mahalanobis entre as coordenadas do ponto estacionários da amostra observada e aquelas obtidas por meio das estimativas "bootstrap"(BM e BBM), e métodos "bootstrap" e "bootstrap" Bayesiano aliados a métodos não paramétricos de estimação de funções densidade de probabilidade (BNP e BBNP). A avaliaçãoda metodologia foi realizada por meio de simulação e foi aplicada a um conjunto de dados de produção de amendoim. No estudo de simulação, a metodologia BH, baseada na distribuição normal dos erros, apresentou um bom desempenho em todas as situações analisadas, havendo concordância entre as regiões de confiança nominais e reais, mesmo naquelas em que essa distribuição é bastante assimétrica. Este mesmo comportamento foi observado para os métodos BM e BBM. No entanto, os métodos BNP e BBNP não apresentaram um desempenho satisfatório, resultando em um nível de significância real menor que o nominal para os autovalores com menor valor absoluto, gerando regiões de confiança maiores. No caso de autovalores com maior valor absoluto observou-se situação inversa. No caso da análise do conjunto de dados de amendoim os métodos BH, BM e BNP apresentaram regiões de confiança mais amplas comparativamente aos métodos BBM e BBNP. No entanto, os valores das estimativas do "bootstrap" Bayesiano são mais próximas das estimativas de mínimos quadrados e apresentam menor dispersão o que explica a menor área da região de confiança. / Experiments in which one or more response variables are influenced by several quantitative factors are very common in agricultural, chemistry, biology and other areas. In this case, the research question consists in studying this relation, being of great utility the use of response surface methodology (RSM). In this context determining the level of the factors that optimize the response consists finding the coordinates of the stationary point of the model. However, as the true model is unknown, it is of interest to obtain a confidence region of the true coordinates to analyze the precision of the obtained estimate. The procedures for the construction of confidence regions for the coordinates of the stationary point were studied in diferent situations, considering the shape of the surfaces analyzed and the distribution and magnitude of the variance errors. The methodology of Box and Hunter (1954) (BH), bootstrap and Bayesian bootstrap with Mahalanobis distance among the coordinates of the stationary point of the observed sample and those obtained using bootstrap estimates(BM and BBM) and bootstrap and Bayesian bootstrap with non-parametric methods for density estimation (BNP and BBNP) were compared. The methodology evaluation was realized by means of simulation and applied to a peanut yields data set. In simulation study the BH methodology, which is based in normal distribution of errors, presented a good performance in all of the analyzed situations, having concordance among the nominal and real confidence regions, even in those which this distribution is fairly asymmetric. This behavior was also observed in BM and BBM methods. The BNP and BBNP methods did not presented a satisfactory performance, resulting in a real significance level lower than the nominal for the eigenvalue with lower absolute value, generating bigger confidence regions. The inverse was observed using eigenvalue with higher absolute value. In the analysis of the peanut yields data set the BH, BM and BNP methods presented confidence regions larger than the BBM and BBNP methods. The Bayesian bootstrap estimate values are closer of the minimum square estimates and present less dispersion what explain the confidence region lower area.

Experimentos nos quais uma ou mais variáveis respostas são influênciadas por diversos fatores quantitativos são bastante comuns nas áreas agrícola, química, biológica, dentre outras. Nesse caso, o problema de pesquisa consiste em se estudar essa relação, sendo de grande utilidade o uso da metodologia de superfícies de resposta (MSR). Nesse contexto, a determinação dos níveis dos fatores que otimizam a resposta consiste inicialmente na obtenção das coordenadas do ponto estacionário do modelo ajustado. No entanto, como o modelo verdadeiro é desconhecido, é interessante obter uma região de confiança das coordenadas verdadeiras de modo a avaliar a precisão da estimativa obtida. Foram abordados aqui os procedimentos para construção de regiões de confiança para as coordenadas do ponto estacionário em diferentes situações considerando-se a forma das superfícies analisadas e a distribuição e magnitude da variância dos erros do modelo. Foram utilizadas a metodologia de Box e Hunter (1954) (BH), "bootstrap" e "bootstrap" Bayesiano aliados ao cálculo da distância de Mahalanobis entre as coordenadas do ponto estacionários da amostra observada e aquelas obtidas por meio das estimativas "bootstrap"(BM e BBM), e métodos "bootstrap" e "bootstrap" Bayesiano aliados a métodos não paramétricos de estimação de funções densidade de probabilidade (BNP e BBNP). A avaliaçãoda metodologia foi realizada por meio de simulação e foi aplicada a um conjunto de dados de produção de amendoim. No estudo de simulação, a metodologia BH, baseada na distribuição normal dos erros, apresentou um bom desempenho em todas as situações analisadas, havendo concordância entre as regiões de confiança nominais e reais, mesmo naquelas em que essa distribuição é bastante assimétrica. Este mesmo comportamento foi observado para os métodos BM e BBM. No entanto, os métodos BNP e BBNP não apresentaram um desempenho satisfatório, resultando em um nível de significância real menor que o nominal para os autovalores com menor valor absoluto, gerando regiões de confiança maiores. No caso de autovalores com maior valor absoluto observou-se situação inversa. No caso da análise do conjunto de dados de amendoim os métodos BH, BM e BNP apresentaram regiões de confiança mais amplas comparativamente aos métodos BBM e BBNP. No entanto, os valores das estimativas do "bootstrap" Bayesiano são mais próximas das estimativas de mínimos quadrados e apresentam menor dispersão o que explica a menor área da região de confiança. / Experiments in which one or more response variables are influenced by several quantitative factors are very common in agricultural, chemistry, biology and other areas. In this case, the research question consists in studying this relation, being of great utility the use of response surface methodology (RSM). In this context determining the level of the factors that optimize the response consists finding the coordinates of the stationary point of the model. However, as the true model is unknown, it is of interest to obtain a confidence region of the true coordinates to analyze the precision of the obtained estimate. The procedures for the construction of confidence regions for the coordinates of the stationary point were studied in diferent situations, considering the shape of the surfaces analyzed and the distribution and magnitude of the variance errors. The methodology of Box and Hunter (1954) (BH), bootstrap and Bayesian bootstrap with Mahalanobis distance among the coordinates of the stationary point of the observed sample and those obtained using bootstrap estimates(BM and BBM) and bootstrap and Bayesian bootstrap with non-parametric methods for density estimation (BNP and BBNP) were compared. The methodology evaluation was realized by means of simulation and applied to a peanut yields data set. In simulation study the BH methodology, which is based in normal distribution of errors, presented a good performance in all of the analyzed situations, having concordance among the nominal and real confidence regions, even in those which this distribution is fairly asymmetric. This behavior was also observed in BM and BBM methods. The BNP and BBNP methods did not presented a satisfactory performance, resulting in a real significance level lower than the nominal for the eigenvalue with lower absolute value, generating bigger confidence regions. The inverse was observed using eigenvalue with higher absolute value. In the analysis of the peanut yields data set the BH, BM and BNP methods presented confidence regions larger than the BBM and BBNP methods. The Bayesian bootstrap estimate values are closer of the minimum square estimates and present less dispersion what explain the confidence region lower area.

В данной магистерской диссертации рассматривается нелинейная модель взаимодействия иммунных и опухолевых клеток под воздействием химиотерапии. Данная модель является модификацией уже известной модели Кузнецова, в которой отсутствует лечение. В работе был проведен бифуркационный анализ в зависимости от коэффициента интенсивности лечения. В ходе анализа было выявлено три характерных состояния системы: "активная опухоль", "спящая опухоль" и "нулевая опухоль". Для равновесных и автоколебательных режимов найдены параметрические зоны сосуществования и определены сепаратисты, разделяющие бассейны соответствующих аттракторов. Найдены оценки параметра интенсивности химиотерапии, при котором возможно как удержание системы в режиме «спящей̆» опухоли, так и ее полное подавление. Для стохастической̆ модели описаны сценарии результатов воздействия случайных возмущений на режимы динамического взаимодействия иммунных и опухолевых клеток. Исследованы условия, при которых индуцированные шумом переходы играют позитивную роль, приводя к резкому сокращению опухолевых клеток. / We study a two-dimensional model of the dynamical interaction of immune and tumor cells under chemotherapy. This model is a modification of the well-known model which was studied by Kuznetsov but without treatment. A bifurcation analysis of the deterministic model was carried out depending on the parameter of the intensity of chemotherapy. It has been shown that the system admits three characteristic states: "active", "dormant", and "zero" tumor. For this multistable system, a description of the equilibrium and self-oscillating modes is given, and the basins of coexisting attractors are determined. We have found estimates of the doses of chemotherapy to keep tumor in the "dormant" regime or to suppress it completely. For the stochastic model, parametric estimates of the probability of transitions between the "active" and "dormant" or "zero" tumor modes were obtained, as well as the conditions under which random disturbances play a positive role, leading to a sharp reduction in the population of tumor cells.

No description available.

Fischer-Tropsch Synthesis (FTS) is a promising technology for the production of ultra-clean fuels and chemical feedstocks from biomass, coal, or natural gas. Iron catalysts are ideal for conversion of coal and biomass. However, precipitated iron catalysts used in slurry-bubble column reactors suffer from high attrition resulting in difficulty separating catalysts from product and increased slurry viscosity. Thus, development of an active and selective-supported iron catalyst to manage attrition is needed. This thesis focuses on the development of a supported iron catalyst and kinetic models of FTS on the catalyst using advanced statistical methods for experimental design and analysis. A high surface area alumina, modified by the addition of approximately 2 wt% lanthanum, was impregnated with approximately 20 wt% Fe and 1% Pt in a two step procedure. Approximately 10 wt% Fe and 0.5 wt% Pt was added in each step. The catalyst had a CO uptake of 702 μmol/g, extent of reduction of 69%, and was reduced at 450°C. The catalyst was stable over H2 partial pressures of 4-10 atm, CO partial pressures of 1-4 atm, and temperatures of 220-260°C. Weisz modulus values were less than 0.15. A Langmuir-Hinshelwood type rate expression, derived from a proposed FTS mechanism, was used with D-optimal criterion to develop experiments sequentially at 220°C and 239°C. Joint likelihood confidence regions for the rate expression parameters with respect to run number indicate rapid convergence to precise-parameter estimates. Difficulty controlling the process at the designed conditions and steep gradients around the D-optimal criterion resulted in consecutive runs having the same optimal condition. In these situations another process condition was chosen to avoid consecutive replication of the same process condition. A kinetic model which incorporated temperature effects was also regressed. Likelihood and bootstrap confidence intervals suggested that the model parameters were precise. Histograms and skewness statistics calculated from Bootstrap resampling show parameter-effect nonlinearities were small.