Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (M.S.)--University of Michigan, 1947.

Thesis (M.S.)--University of Michigan, 1958.

Zugl.: München, Univ., Diss., 2009

University, Diss., 2002--Mainz.

Le principal défi des techniques de transfert de gènes est de garantir l’expression du gène d’intérêt tout en assurant l’innocuité des cellules génétiquement modifiées. La plupart des systèmes d’intégration, dérivés des transposons, assurent une intégration aléatoire au sein du génome de la cellule. L’enjeu de ce travail est de développer des outils permettant de cibler l’intégration du transgène au niveau d’un locus choisi dans le but d’améliorer la biosécurité. L’étude s’est portée sur l’utilisation des protéines à ZFD (Zinc Finger Domain) pour leur aptitude à être conçues à façon, in silico, en utilisant les nombreuses ressources disponibles sur Internet. Pour comparer, les propriétés de deux domaines de liaison, NterR2P, provenant de deux rétrotransposons R2 de type non-LTR, ont été étudiées pour leur capacité naturelle à reconnaître spécifiquement une région de 100 pb située dans l’ADN ribosomique 28S. Les résultats obtenus ont montré que les domaines NterR2P reconnaissent spécifiquement leur ADN cible avec une forte affinité de liaison. Deux protéines de fusion, utilisant le domaine NterR2P, ont ensuite été synthétisées dans le but d’intégrer le transgène au niveau de l’ADNr en utilisant le transposon Sleeping Beauty. L’idée originale de ce travail est de réaliser l’intégration du transgène via le ciblage indirect du transposon, ou de la transposase sans que celle-ci ne soit modifiée. L’impact de ces systèmes de ciblage sur les cellules nécessite de réexaminer une telle stratégie. / The main challenge of gene transfer technologies is to maintain and to sustain transgene expression and to confer innocuity on the genetically-modified cells. Most integration systems, derived from transposons, integrate randomly within the genome of cells. The issue of this work is to develop tools to target transgene integrations in a selected locus in order to improve biosecurity. This study consists in using ZFD (Zinc Finger Domain) proteins for their capability to be in silico synthesize, in using many bioinformatic sites. For compare, the properties of two DNA binding domains (DBD), NterR2P, originating from the endonucleases encoded by R2 non-LTR retrotransposons, are able to bind specifically within a 100-bp region of the 28S rRNA genes. The results show that NterR2P DBDs specifically recognize their DNA target with high affinity. Two fusion proteins, using NterR2P DBD, are synthesized in order to integrate the transgene within rDNA, using Sleeping Beauty transposon. The original idea of this work is to realize transgene integration via indirect targeting of transposon, or transposase without its modification. The use of such a targeting system will have to be extensively studied to determine its impacts on cells before it can be considered as safe for use.

Hand and finger force data are used in many settings, including industrial design and indicating progress during rehabilitation. The application of appropriate work design principles, during the design of tools and workstations that involve the use of the hand and fingers, may minimize upper extremity injuries within the workplace. Determination and integration of force capabilities and requirements is an essential component of this process. Available data in the literature has focused primarily on whole-hand or multi-digit pinch exertions. The present study compiled and examined maximal forces exerted by the fingers in a variety of couplings to both enhance and supplement available data. This data was used to determine whether finger strength could be predicted from other strength measures and anthropometry. In addition, this study examined whether exerted finger forces could be estimated using surface electromyography obtained from standardized forearm locations. Such processes are of utility when designing and evaluating hand tools and human-machine interfaces involving finger intensive tasks, since the integration of finger force capabilities and task requirements are necessary to reduce the risk of injury to the upper limbs. Forces were measured using strain gauge transducers, and a modification of standard protocols was followed to obtain consistent and applicable data. Correlations within and among maximum finger forces, whole-hand grip force, and anthropometric measures were examined. Multiple regression models were developed to determine the feasibility of predicting of finger strength in various finger couplings from more accessible measures. After examining a wide variety of such mathematical models, the results suggest that finger strength can be predicted from easily obtained measures with only moderate accuracy (R²-adj: 0.45 - 0.64; standard error: 11.95N - 18.88N). Such models, however, begin to overcome the limitations of direct finger strength measurements of individuals. Surface electrodes were used to record electromyographic signals collected from three standardized electrode sites on the forearm. Multiple linear regression models were generated to predict finger force levels with the three normalized electromographic measures as predictor variables. The results suggest that standardized procedures for obtaining EMG data and simple linear models can be used to accurately predict finger forces (R²-adj: 0.77 - 0.88; standard error: 9.21N - 12.42N) during controlled maximal exertions. However, further work is needed to determine if the models can be generalized to more complex tasks. / Master of Science

No description available.

No description available.

The nucleosome remodeling factor (NURF) is a mutli-protein complex that plays a role in the regulation of gene expression through its ability to remodel nucleosomes. The largest subunit of this complex, Bptf (Bromodomain PHD Finger Transcription Factor) is important for many cellular processes as a transcriptional regulator and improper function results in disease or malignancy. To further understand the genome-wide recruitment of the NURF complex, the interaction partner for the N-terminal PHD finger domain of Bptf was investigated through pull down assays followed by mass spectrometry. It was determined that this domain does not recognize histones; instead it recognizes a nonhistone protein, Thoc4 or Hmgb1. The expression of a cDNA corresponding to Bptf was also tested for expression in mouse ES cells after the addition of two exons found to be missing in the original cDNA. Addition of this sequence did not allow for exogenous Bptf expression in ES cells.