Thesis (Ph. D.)--Oregon Graduate Center, 1980.

Thesis (Ph. D.)--Lehigh University, 2001. / Includes vita. Includes bibliographical references (leaves 200-206).

published_or_final_version / Physics / Master / Master of Philosophy

No description available.

Eukaryotic genomes must be folded and compacted to fit within the restricted volume of the nucleus. This folding, and the subsequent organization of the genome, reflects both the transcription profile of the cell and of the specific cell type. A dispersed, mesh-like chromatin configuration, for example, is characteristic of a pluripotent stem cell. Here we show that the acquisition of the pluripotent state during somatic cell reprogramming is coincident with the disruption of compact heterochromatin domains. Using Electron Spectroscopic Imaging (ESI), I made the surprising observation that the heterochromatin domains of the induced pluripotent and of the parental somatic cell contained 10 nm chromatin fibres. Since ESI generates projection images, the precise three-dimensional organization of all chromatin fibres within these domains could not be elucidated. To circumvent this limitation, I developed an electron microscopy technique that combines ESI with tomography. Using this approach, I found that both heterochromatin domains and the surrounding euchromatin of murine pluripotent cells, fibroblasts, and somatic tissues are in fact organized entirely as 10 nm chromatin fibres. This challenges the current paradigm that most, if not all, of the genome exists as 30 nm and higher-order chromatin fibre assemblies. Rather than transitions between 10 nm and 30 nm fibres, I propose that the organization and thus the regulation of the genome is achieved by the bending and folding of 10 nm chromatin fibres into discrete domains in a cell type-specific manner.

Eukaryotic genomes must be folded and compacted to fit within the restricted volume of the nucleus. This folding, and the subsequent organization of the genome, reflects both the transcription profile of the cell and of the specific cell type. A dispersed, mesh-like chromatin configuration, for example, is characteristic of a pluripotent stem cell. Here we show that the acquisition of the pluripotent state during somatic cell reprogramming is coincident with the disruption of compact heterochromatin domains. Using Electron Spectroscopic Imaging (ESI), I made the surprising observation that the heterochromatin domains of the induced pluripotent and of the parental somatic cell contained 10 nm chromatin fibres. Since ESI generates projection images, the precise three-dimensional organization of all chromatin fibres within these domains could not be elucidated. To circumvent this limitation, I developed an electron microscopy technique that combines ESI with tomography. Using this approach, I found that both heterochromatin domains and the surrounding euchromatin of murine pluripotent cells, fibroblasts, and somatic tissues are in fact organized entirely as 10 nm chromatin fibres. This challenges the current paradigm that most, if not all, of the genome exists as 30 nm and higher-order chromatin fibre assemblies. Rather than transitions between 10 nm and 30 nm fibres, I propose that the organization and thus the regulation of the genome is achieved by the bending and folding of 10 nm chromatin fibres into discrete domains in a cell type-specific manner.

Thesis (Ph. D.)--Lehigh University, 1999. / Includes vita. Bibliography: leaves 145-153.

Thesis (M.S.)--Virginia Polytechnic Institute. 1950. / Abstract. Includes bibliographical references (leaves 128-149). Also available via the Internet.

Thesis (Ph. D.)--Lehigh University, 2004. / Includes vita. Includes bibliographical references (leaves 184-195).

This dissertation focuses on an electron microscopy investigation of the microstructure of SiC layers in TRISO coated particles deposited by chemical vapour deposition under different experimental conditions, which include temperature, concentration of gases and deposition time. The polycrystalline β-SiC was deposited from the decomposition of methyl trichlorosilane MTS in the presence of hydrogen (H2) as carrier gas. Scanning electron microscopy (SEM), using the backscattered electron (BSE) mode, was used to image the microstructure of and defects in the SiC layers of TRISO particles. Electron backscatter diffraction (EBSD) in the SEM was used to determine the SiC grain sizes and distribution thereof in TRISO particles deposited under different conditions. For samples with a poor EBSD indexing rate, transmission Kikuchi diffraction and transmission electron microscopy (TEM) investigations were also carried out. From the results, the effects of growth temperature on the SiC microstructure, specifically on the grain size and shape and the porosity were determined. The effects of cooling or non-cooling of the gas inlet nozzle on the SiC microstructure were also investigated. TEM and scanning TEM (STEM) analyses of the SiC layers in TRISO particles were performed to image the defects and reveal the crystallinity of SiC layers. The microstructure and composition of SiC tubes fabricated by reaction bonding (RB) was also investigated by using electron microscopy and Raman spectroscopy. SEM-BSE imaging of RBSiC samples allowed the identification of impurities and free silicon in the RBSiC. Finally, the penetration of the metallic fission product, palladium, in reaction bonded SiC at a temperature of a 1000ºC is determined. A brief comment on the suitability of RBSiC as candidate for fuel cladding in a PWR is made. A short discussion of the suitability of the characterisation techniques used is included at the end.