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.

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Self-consistent Monte Carlo simulation studies of n-channel Si/SiGe modulation doped field effect transistors (MODFETs) and silicon-on-insulator lateral bipolar junction transistors (SOI- LBJTs) are reported in this thesis. As a preliminary to the device studies Monte Carlo simulations of electron transport in bulk Si strained as if grown on Si(_0.77)Ge(_0.23) and Si(_0.55)Ge(_0.45) substrates have been carried out at 300 K, for field strengths varied from 10(^4) to 2 x 10(^7) Vm(^-1). The calculations indicate an enhancement of the average electron drift velocity when Si is tensilely strained in the growth plane. The enhancement of electron velocity is more marked at low and intermediate electric fields, while at very high fields the velocity saturates at about the same value as unstrained Si. In addition the ensemble Monte Carlo method has been used to study the transient response to a stepped electric field of electrons in strained and unstrained Si. The calculations suggest that significant velocity overshoots occurs in strained material. Simulations of n-channel Si/Si(_1=z)Ge(_z) MODFETs with Ge fractions of 0.23, 0.25, and 0.45 have been performed. Five depletion mode devices with x = 0.23 and 0.25 were studied. The simulations provide information on the microscopic details of carrier behaviour, including carrier velocity, kinetic energy and carrier density, as a function of position in the device. Detailed time-dependent voltage signal analysis has been carried out to test device response and derive the frequency bandwidth. The simulations predict a current gain cut-off frequency of 60 ± 10 GHz for a device with a gate length of 0.07 /nm and a channel length of 0.25 um. Similar studies of depletion and enhancement mode n-channel Si/Sio.55Geo.45 MODFETs with a gate length of 0.18 /im have been carried out. Cut-off frequencies of 60 ±10 GHz and 90± 10 GHz are predicted for the depletion and enhancement mode devices respectively. A Monte Carlo model has also been devised and used to simulate steady state and transient electron and hole transport in SOI-LBJTs. Four devices have been studied and the effects of junction depth and silicon layer thickness have been investigated. The advantage of the silicon-on-insulator technology SOI device is apparent in terms of higher collector current, current gain, and cut-off frequency obtained in comparison with an all-silicon structure. The simulations suggest that the common-emitter current gain of the most promising SOI-LBJT structure considered could have a cut-off frequency approaching 35 ± 5 GHz.

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Using electron beam evaporation for the production of polycrystalline silicon (pc-Si) thin-film solar cells is an attractive alternative to PECVD deposition. Due to its faster deposition rate, using evaporation technology could significantly reduce module production costs. Other advantages are lower running costs, and the fact that no toxic gases are involved. However, currently no on-shelf equipment is available, and research in this field often relies on in-house designed systems. These can have various problems with reliability, deposition uniformity, and due to their custom design require frequent maintenance. In this work, a newly purchased electron beam evaporation system was upgraded and redesigned to be capable of depositing amorphous Si diodes for the fabrication of pc-Si thin-film solar cells. The main goal of the upgrade was to provide a safe and reliable tool which allows for the deposition of high purity semiconductor material. Reliable and safe operation was accomplished by designing the entire electrical supply circuit and incorporating various safety interlocks. Source cross-contamination issues were addressed by installing a specially designed shroud (source housing). To provide uniform substrate temperatures up to 600??C, a heater was specially designed, fabricated, installed and tested. Accurate design of all mechanical system components was realised by using 3D product design software (ProEngineer). The new evaporator was commissioned, which included testing and calibration of all the system components required for depositing on substrate sizes of up to 10x10cm2. Over this area a Si film thickness uniformity of +/-2%, performed with a maximum deposition rate of 7nm/s was achieved. Initial experiments using solid phase crystallisation and rapid thermal annealing revealed a sheet resistance uniformity of +/-4% for the Phosphorus and +/-7% for the Boron dopant effusion cell. Experimentation via Raman spectrometry and X-ray diffraction has revealed good crystalline properties, of the crystallised Si films, which is comparable to those of existing evaporation systems. Although the system was upgraded to achieve deposition pressures below 3x10-7 mbar, experiments have shown that this quality of vacuum may not be necessary for the fabrication of low impurity films. The system is now ready for further research in the field of thin-film photovoltaics, and the first functioning devices have been fabricated.