Techn. Univ., Diss. u.d.T.: Modell und Mimesis--Wien, 1994, zum Problem der Dimension in der Architektur am Beispiel von Fritz Langs Metropolis. / Literaturverz. S. 203 - 208.

Determining which genes are essential for growth of a bacterial organism is an important question to answer as it is useful for the discovery of drugs that inhibit critical biological functions of a pathogen. To evaluate essentiality, biologists often use transposon mutagenesis to disrupt genomic regions within an organism, revealing which genes are able to withstand disruption and are therefore not required for growth. The development of next-generation sequencing technology augments transposon mutagenesis by providing high-resolution sequence data that identifies the exact location of transposon insertions in the genome. Although this high-resolution information has already been used to assess essentiality at a genome-wide scale, no formal statistical model has been developed capable of quantifying significance. This thesis presents a formal Bayesian framework for analyzing sequence information obtained from transposon mutagenesis experiments. Our method assesses the statistical significance of gaps in transposon coverage that are indicative of essential regions through a Gumbel distribution, and utilizes a Metropolis-Hastings sampling procedure to obtain posterior estimates of the probability of essentiality for each gene. We apply our method to libraries of M. tuberculosis transposon mutants, to identify genes essential for growth in vitro, and show concordance with previous essentiality results based on hybridization. Furthermore, we show how our method is capable of identifying essential domains within genes, by detecting significant sub-regions of open-reading frames unable to withstand disruption. We show that several genes involved in PG biosynthesis have essential domains.

Dans la plupart des études, le nombre de variables peut prendre des valeurs élevées ce qui rend leur analyse et leur visualisation assez difficile. Cependant, plusieurs méthodes statistiques ont été conçues pour réduire la complexité de ces données et permettant ainsi une meilleure compréhension des connaissances disponibles dans ces données. Dans cette thèse, notre objectif est de proposer deux nouvelles méthodes d’analyse des données multivariées intitulées en anglais : " Multidimensional Fitting" et "Projection under pairwise distance control". La première méthode est une dérivée de la méthode de positionnement multidimensionnelle dont l’application nécessite la disponibilité des deux matrices décrivant la même population : une matrice de coordonnées et une matrice de distances et l’objective est de modifier la matrice des coordonnées de telle sorte que les distances calculées sur cette matrice soient les plus proches possible des distances observées sur la matrice de distances. Nous avons élargi deux extensions de cette méthode : la première en pénalisant les vecteurs de modification des coordonnées et la deuxième en prenant en compte les effets aléatoires qui peuvent intervenir lors de la modification. La deuxième méthode est une nouvelle méthode de réduction de dimension basée sur la projection non linéaire des données dans un espace de dimension réduite et qui tient en compte la qualité de chaque point projeté pris individuellement dans l’espace réduit. La projection des points s’effectue en introduisant des variables supplémentaires, qui s’appellent "rayons", et indiquent dans quelle mesure la projection d’un point donné est précise. / In various studies the number of variables can take high values which makes their analysis and visualization quite difficult. However, several statistical methods have been developed to reduce the complexity of these data, allowing a better comprehension of the knowledge available in these data. In this thesis, our aim is to propose two new methods of multivariate data analysis called: " Multidimensional Fitting" and "Projection under pairwise distance control". The first method is a derivative of multidimensional scaling method (MDS) whose the application requires the availability of two matrices describing the same population: a coordinate matrix and a distance matrix and the objective is to modify the coordinate matrix such that the distances calculated on the modified matrix are as close as possible to the distances observed on the distance matrix. Two extensions of this method have been extended: the first by penalizing the modification vectors of the coordinates and the second by taking into account the random effects that may occur during the modification. The second method is a new method of dimensionality reduction techniques based on the non-linearly projection of the points in a reduced space by taking into account the projection quality of each projected point taken individually in the reduced space. The projection of the points is done by introducing additional variables, called "radii", and indicate to which extent the projection of each point is accurate.

This thesis was prompted by three major concerns. Firstly there is need for a structure of centres providing a wider range of facilities closer to home. Secondly, the Wynberg centre is slowly changing to become almost exclusively a shopping centre, and thirdly, the quality of the environment of the centre is also declining. The first aspect of the analysis was the establishment of what those qualities are that make a centre. Having examined the existing Wynberg centre structure and operation;and · the plans, mainly road schemes, presently proposed by the local authority it became apparent that with these influences the centre of Wynberg would definitely not develop into the centre which was needed. A further six alternatives were prepared to determine the possible future for Wynberg. In the first four alternatives, the involvement presently practiced by the local authority was considered to be a fix and the alternatives were mainly achieved by keeping or omitting one or both of the two road schemes to be built through Wynberg viz. the Wynberg ByPass and the Widening of the Main Road. The second set of alternatives was based on the premise that the Local Authority would become actively involved in the development of the centre, able to use economic and legal techniques to induce development in the direction of the goals. An economic and analysis was undertaken to give quantitive values to the alternatives.

Accra Metropolis is the major recipient of agricultural produce in Ghana, with almost the entire population depending on rural agricultural activities for subsistence. To increase agricultural produce, various forms of pesticides are normally used in fruits and vegetable farming. The consequence is that several cases of pesticide poisoning have been observed. In this preliminary study, a field survey was carried out to assess the knowledge, attitudes, and peoples' perception concerning the use of pesticides by farmers in fruit production. The residual concentrations of selected pesticides in pawpaw, imported apples and tomato samples and the potential health risks associated with the exposure to these pesticides were also assessed. The field survey data indicated that more than 70% of the participants reported one or more poisoning upon fruits consumption resulting in pesticide-related illnesses. Pesticide residues in the various environmental samples were determined by gas chromatography with electron capture detector (GC-ECD). The results showed that, the levels of pesticide residues varied from <0.01 μg/g to as high as 0.11 μg/g depending on the pesticide monitored. The analysis of health risk estimates revealed heptachlor, heptachlor epoxide, endrin aldehyde, and endrin ketone levels exceeded the reference dose, suggesting a great potential for systemic toxicity in children considered the most vulnerable population subgroup. Lastly, the public is in the know of pesticide residues in fruits and calls for the curtailing of pesticide use on fruits and vegetable production via educational programmes for farmers on control and safer use of pesticides.

As interações moleculares, em especial as de caráter não-covalente, são processos-chave em vários aspectos da biologia celular e molecular, desde a comunicação entre as células ou da velocidade e especificidade das reações enzimáticas. Portanto, há a necessidade de estudar e criar métodos preditivos para calcular a afinidade entre moléculas nos processos de interação, os quais encontram uma gama de aplicações, incluindo a descoberta de novos fármacos. No geral, entre esses valores de afinidade, o mais importante é a energia livre de ligação, que normalmente é determinada por modos computacionalmente rápidos, porém sem uma forte base teórica, ou por cálculos muito complexos, utilizando dinâmica molecular, onde mesmo com um grande poder de determinação da afinidade, é muito custoso computacionalmente. O objetivo deste trabalho é avaliar um modelo menos custoso computacionalmente e que promova um aprofundamento na avaliação de resultados obtidos a partir de simulações de docking molecular. Para esta finalidade, o método de Monte Carlo é empregado para a amostragem de orientações e conformações do ligante do sítio ativo macromolecular. A avaliação desta metodologia demonstrou que é possível calcular grandezas entrópicas e entálpicas e analisar a capacidade interativa entre complexos proteína-ligante de forma satisfatória para o complexo lisozima do bacteriófago T4. / The molecular interactions, especially the ones with a non-covalent nature, are key processes in general aspects of cellular and molecular biology, including cellular communication and velocity and specificity of enzymatic reactions. So, there is a strong need for studies and development of methods for the calculation of the affinity on interaction processes, since these have a wide range of applications like rational drug design. The free energy of binding is the most important measure among the affinity measurements. It can be calculated by quick computational means, but lacking on strong theoretical basis or by complex calculations using molecular dynamics, where one can compute accurate results but at the price of an increased computer power. The aim of this project is to evaluate a computationally inexpensive model which can improve the results from molecular docking simulations. For this end, the Monte Carlo method is implemented to sample different ligand configurations inside the macromolecular binding site. The evaluation of this methodology showed that is possible to calculate entropy and enthalpy, along analyzing the interactive capacity between receptor-ligands complexes in a satisfactory way for the bacteriophage T4.

Neste trabalho são apresentados dois modelos de sobrevivência com fração de cura e efeitos aleatórios, um baseado no modelo de Chen-Ibrahim-Sinha para fração de cura e o outro, no modelo de mistura. São estudadas abordagens clássica e bayesiana. Na inferência clássica são utilizados estimadores REML. Para a bayesiana foi utilizado Metropolis-Hastings. Estudos de simulação são feitos para avaliar a acurácia das estimativas dos parâmetros e seus respectivos desvios-padrão. O uso dos modelos é ilustrado com uma análise de dados de câncer na orofaringe. / In this work, it is shown two survival models with long term survivors and random effects, one based on Chen-Ibrahim-Sinha model for models with surviving fraction and the other, on mixture model. We present bayesian and classical approaches. In the first one, we use Metropolis-Hastings. For the second one, we use the REML estimators. A simulation study is done to evaluate the accuracy of the applied techniques for the estimatives and their standard deviations. An example on orofaringe cancer is used to illustrate the models considered in the study.

This work considers black-box Bayesian inference over high-dimensional parameter spaces. The well-known and widely respected adaptive Metropolis (AM) algorithm is extended herein to asymptotically scale uniformly with respect to the underlying parameter dimension, by respecting the variance, for Gaussian targets. The result- ing algorithm, referred to as the dimension-independent adaptive Metropolis (DIAM) algorithm, also shows improved performance with respect to adaptive Metropolis on non-Gaussian targets. This algorithm is further improved, and the possibility of probing high-dimensional targets is enabled, via GPU-accelerated numerical libraries and periodically synchronized concurrent chains (justified a posteriori). Asymptoti- cally in dimension, this massively parallel dimension-independent adaptive Metropolis (MPDIAM) GPU implementation exhibits a factor of four improvement versus the CPU-based Intel MKL version alone, which is itself already a factor of three improve- ment versus the serial version. The scaling to multiple CPUs and GPUs exhibits a form of strong scaling in terms of the time necessary to reach a certain convergence criterion, through a combination of longer time per sample batch (weak scaling) and yet fewer necessary samples to convergence. This is illustrated by e ciently sampling from several Gaussian and non-Gaussian targets for dimension d 1000.

[pt] O objetivo deste trabalho é desenvolver uma estratégia Metropolis-Hastings para inferência Bayesiana, usando a estrutura ARCH multivatriada com representação BEKK.Em problemas complexos, como a generalização ARCH/GARCH univariadas para estruturas multivariadas, o processo de inferência é dificultado por causa do número de parâmetros envolvidos e das restrições a que eles estão sujeitos. Neste trabalho desenvolvemos uma estratégia Metropolis- Hastings para inferência Bayesiana, usando uma estrutura ARCH multivariada com representação BEKK. / [en] The objective of this work is to develop Metropolis-Hasting for strategy Bayesian Inference, based on a Multivariate ARCH model with BEKK representation. In complex problems, such as the multivariate generalization of ARCH/GARCH structures, the inference process in complicated, due to the large number of parameters involved and to the restrictions they must satisfy. We propose Metropolis- Hastings structure to provide inference, in a Bayesian framework, for a multivariate ARCH model with BEKK representation. / [es] EL objetivo de este trabajo es desarrollar una estrategia Metropolis-Hastings para inferencia Bayesiana, usando La extructura ARCH multivatriada con representación BEKK.En problemas complejos, como la generalización ARCH/GARCH univariadas para extructuras multivariadas, el proceso de inferencia se hace dificil por causa del número de parámetros involucrados y de las restricciones a que ellos están sujetos. En este trabajo desarrollamos una estrategia Metropolis- Hastings para inferencia Bayesiana, usando una extructura ARCH multivariada con representación BEKK.

Made available in DSpace on 2015-03-03T15:15:29Z (GMT). No. of bitstreams: 1 FranciscoBLJ_DISSERT.pdf: 1340368 bytes, checksum: 23cf640d31d17bdd88ad96134433ceb1 (MD5) Previous issue date: 2013-11-29 / We studied the Ising model ferromagnetic as spin-1/2 and the Blume-Capel model as spin-1, > 0 on small world network, using computer simulation through the Metropolis algorithm. We calculated macroscopic quantities of the system, such as internal energy, magnetization, specific heat, magnetic susceptibility and Binder cumulant. We found for the Ising model the same result obtained by Koreans H. Hong, Beom Jun Kim and M. Y. Choi [6] and critical behavior similar Blume-Capel model / ?Neste trabalho estudamos o modelo de Ising ferromagn?tico com spin-1/2 e o modelo Blume-Capel com spin-1, ? > 0 em rede mundo pequeno, usando simula??o computacional atrav?s do algoritmo de Metropolis. Calculamos grandezas macrosc?picas do sistema, tais como a energia interna, a magnetiza??o, o calor espec?fico, a susceptibilidade magn?tica e o cumulante de Binder. Encontramos para o modelo de Ising o mesmo resultado obtido pelos Coreanos H. Hong, Beom Jun Kim e M. Y. Choi [6] e um comportamento cr?tico similar o modelo Blume-Capel.