Frankfurt (Main), Universiẗat, Diss., 2002.

Darmstadt, Techn. Universiẗat, Diss., 2002. / Dateien im PDF-Format.

Introduction The present study evaluated reported methodological characteristics of GWAS, investigating relationships between reported methodological characteristics and outcomes observed. Methods GWAS were identified from NHGRI’s catalogue of GWAS (2005 to 2009). Multivariate meta-regression models (random effects) were produced to identify the impact of reported study characteristics and the strength of relationships between the variables and outcomes. Results The summary odds ratios for replication components of GWAS in cancer was 1.34 (95% CI 1.25, 1.43) and neuropsychiatric disorders was 1.43 (95% CI 1.30, 1.57). Heterogeneity was accounted for by nature of the control group, relationship between case/control groups, whether cases/controls were drawn from the same population, if data was a primary collection or a build on pre-existing data, if quality assurance was reported, and if the study reported power/sample size. Conclusion Evidence supports the existence of variability in reporting, with index components demonstrating less variability than replication components in the GWAS.

Acute myeloid leukemia (AML) is a highly fatal blood cancer that is characterized by disruption of healthy differentiation of stem cells into functional blood cells in the bone marrow. Most patients with AML consequently die from infections due to the lack of immune cells. For decades, the standard method of remission induction for AML has been chemotherapy using an antineoplastic drug known as AraC. However, even after successful remission induction, aggressive, refractory relapse occurs in the majority of patients within 3 years with dismal survival rates. Here, we sought to develop a genome-wide screening approach to determine the causative genes in AML relapse. In the developed procedure, protein-coding genes of the human genome are screened using a leading-edge technology known as CRISPR (clustered regularly interspaced short palindromic repeats) activation screening. This involves usage of a pooled guide RNA library that upregulates a unique gene for each individual AML cell. By treating these cells with AraC in a mouse xenograft model, the bone marrow will gradually be enriched with cells that carry a guide RNA for a relapse-conducive gene. By harvesting and sequencing all enriched guide RNAs at relapse, the causative genes in AML relapse can be determined. All parameters of the in vivo CRISPR-activation screen have been optimized, and the workflow from preparation to the end of screening has been detailed. Follow-up studies that will validate the results of the screen have also been described. The long-term goal of this developed screen is to elucidate the mechanisms of AML relapse and find ways to clinically target these pathways in conjunction with standard the AraC-based chemotherapy. / Thesis / Master of Science (MSc)

No description available.

O presente trabalho propõe uma nova análise de negócio para avaliar a importância de classes de consumidores para o modelo de negócio de aplicações de negócio eletrônico para a WWW. Esta avaliação é feita através do agrupamento dos consumidores em classes e da medição da receita gerada e do consumo de recursos de cada uma das classes. Este trabalho também propõe a modelagem e a implementação de uma ferramenta para a medição do consumo de recursos computacionais de cada uma das classes de consumidores. Para medir o consumo de recursos foi criada uma nova técnica baseada na proposta por Menasce et al. (1999).que permite a medição do consumo de recursos de servidores WWW através da monitoração de uma aplicação de negócio eletrônica durante a operação ou através da extração dos dados necessários para medir o consumo de recursos de arquivos de log. Para realizar a medição do consumo e para validar a técnica proposta foi projetada e construída uma ferramenta que, uma vez passada a forma de identificação de classes de consumidores e a navegação desses consumidores em arquivos de logs ou em banco de dados, permite contabilizar os recursos computacionais consumidos pelos mesmos. A ferramenta e o seu correto funcionamento foram validados através da aplicação da ferramenta sobre dados de navegação simulados para grupos pré-definidos de consumidores cujo resultado obtido foi comparado ao resultado esperado. / This work describes a new business analysis to evaluate the importance of individual customer classes to the business model of a web-based electronic business application. This can be accomplished by breaking the customer base into classes and measuring the monetary income and the resource consumption for each class. This work also proposes a software tool modeling to measure the computer resource consumption for each customer class and each individual application module. To measure the resource consumption, a new technique based on the one proposed by Menasce et al. (1999) was created to allow the proper breakdown of the resource consumption by the customers in a WWW server through monitoring the business software application during its operation or through the extraction of the data needed to measure the resource consumption from the log files generated by the WWW servers hosting the application. To perform the measurement and to validate the proposed technique, it was designed and built a software tool that is able to evaluate the resource consumption of a customer group when it receives the way to identify the group of a customer and the navigation of these customers in the form of a navigation database or in a log file. This software tool was validated by applying it over some simulated customer navigating data based on the expected behavior of some predefined customer groups and comparing the data obtained with the expected result.

O presente trabalho propõe uma nova análise de negócio para avaliar a importância de classes de consumidores para o modelo de negócio de aplicações de negócio eletrônico para a WWW. Esta avaliação é feita através do agrupamento dos consumidores em classes e da medição da receita gerada e do consumo de recursos de cada uma das classes. Este trabalho também propõe a modelagem e a implementação de uma ferramenta para a medição do consumo de recursos computacionais de cada uma das classes de consumidores. Para medir o consumo de recursos foi criada uma nova técnica baseada na proposta por Menasce et al. (1999).que permite a medição do consumo de recursos de servidores WWW através da monitoração de uma aplicação de negócio eletrônica durante a operação ou através da extração dos dados necessários para medir o consumo de recursos de arquivos de log. Para realizar a medição do consumo e para validar a técnica proposta foi projetada e construída uma ferramenta que, uma vez passada a forma de identificação de classes de consumidores e a navegação desses consumidores em arquivos de logs ou em banco de dados, permite contabilizar os recursos computacionais consumidos pelos mesmos. A ferramenta e o seu correto funcionamento foram validados através da aplicação da ferramenta sobre dados de navegação simulados para grupos pré-definidos de consumidores cujo resultado obtido foi comparado ao resultado esperado. / This work describes a new business analysis to evaluate the importance of individual customer classes to the business model of a web-based electronic business application. This can be accomplished by breaking the customer base into classes and measuring the monetary income and the resource consumption for each class. This work also proposes a software tool modeling to measure the computer resource consumption for each customer class and each individual application module. To measure the resource consumption, a new technique based on the one proposed by Menasce et al. (1999) was created to allow the proper breakdown of the resource consumption by the customers in a WWW server through monitoring the business software application during its operation or through the extraction of the data needed to measure the resource consumption from the log files generated by the WWW servers hosting the application. To perform the measurement and to validate the proposed technique, it was designed and built a software tool that is able to evaluate the resource consumption of a customer group when it receives the way to identify the group of a customer and the navigation of these customers in the form of a navigation database or in a log file. This software tool was validated by applying it over some simulated customer navigating data based on the expected behavior of some predefined customer groups and comparing the data obtained with the expected result.

ETH, Diss.--Zürich, 2007.

Zugl.: Wien, WirtschaftsUniversiẗat, Diplomarbeit, 2008.

Thesis (Ph. D.)--University of Texas at Austin, 1998. / Vita. Includes bibliographical references (leaves 162-172). Available also in a digital version from Dissertation Abstracts.