Newts, such as Notophthalmus viridescens, can regenerate many structures after amputation or injury and have also shown a refractory response to the formation of cancer in tissues that have regenerative capabilities. The mechanisms behind this latter ability have surprisingly not been studied. In the current study, N. viridescens were exposed to a variety of carcinogens in tissue that cannot regenerate with the intention of inducing tumour formation. After testing multiple carcinogens, multiple sites of injection, and two different modes of delivery, no tumours were generated. Consequently, in vitro assays were developed in order to better understand this ability of newt cells to evade transformation. Mouse and newt muscle cells were exposed to DNA damaging agents, such as irradiation and carcinogens, in culture and their response was monitored with respect to the DNA damage response proteins γ-H2AX, p53, and phospho-p53. These proteins are important as they help prevent mutations in the genome from being passed on to daughter cells and potentially generating cells that proliferate uncontrollably, a hallmark of cancer. Preliminary results suggest that after irradiation, γ-H2AX is present in newt cells for a considerably longer period of time in comparison to mouse cells. p53, as well as phospho-p53, appear to be present at a basal level before and after irradiation in newt cells, whereas mouse cells have a distinct increase upon damage and decrease upon repair. The carcinogen treatments also suggest that newt cells have basal levels of expression of these proteins prior to treatment. These studies suggest that newt cells may have a unique profile of these DNA damage response proteins and may be “primed” to repair any future damage. This is a good first step in understanding what is likely a very complicated explanation for newts’ refractory response to cancer formation.

The response of mammalian cells to ionizing radiation has been extensively studied with single cells exposed to acute doses. Little information is, however, available for cells growing in tissues, especially for cells subjected to multiple exposures. Our aim in this thesis was therefore to use a more complex in vitro system, three dimensional spheroids grown from V79-171b Chinese hamster lung cells, to determine the role of repair, redistribution and repopulation during multifraction irradiation. Repair and redistribution effects were isolated by using spheroids under normal culture conditions of 37°C, or at 22°C where repair occurs but cell proliferation is markedly inhibited. As expected, we found that cells surviving an initial 8 Gy dose showed cell cycle dependent fluctuations in radiosensitivity when allowed to progress at 37°C before exposure to a second 8 Gy dose. Sublethal radiation damage was repaired more rapidly at 37°C than at 22°C, and was also affected by proliferation. Due, however, to the small proliferating population in the spheroid system, a large initial dose was required to produce a population with enough synchrony for the expected split dose survival fluctuations throughout the cell cycle to be observed. When two doses of 6 Gy separated by 4 hours were administered to spheroids, the subsequent cellular radiosensitivity to a third dose remained quite constant for at least 10 hours, indicating a more extended mitotic delay than observed in the two dose experiments. Mitotic delay consequently was not linear with dose, a result apparently dependent upon the fractionation scheme used, and the complexity of the multicell system. In multifraction schedules where doses of 6 Gy or 8 Gy were administered daily for 6 days, we found, as expected, that repair, redistribution and repopulation all affected cell viability. However, each effect dominated at different times throughout the experiments. The overall cytotoxicity for each 6 Gy fraction decreased with increasing fraction number, while the 8 Gy fraction survival remained fairly constant. A novel feature of our experimental design, administering each 6 Gy or 8 Gy fraction in 1-2 Gy increments, also allowed evaluation of successive responses to the clinically relevant dose of 2 Gy. Cell survival at that level fluctuated greatly due to a decreasing repair capacity, 'and an increasing effect of repopulation with fraction number. Using two radioactive Iridium sources of different activities, high dose rate fractionated exposure was compared to continuous low dose rate irradiation. Also, the linear quadratic model was used to predict the equivalent doses. We found that the model did not provide a good prediction; more repair of radiation induced damage was observed at the lower dose rates than the higher dose rates, an effect which could not be incorporated into this theoretical model. We conclude that, with fractionated radiation exposures to the spheroid system, repair, redistribution, repopulation and cell killing all contribute to the multifraction responses. Each has varying significance on each fraction. An equal effect per fraction, often implicit in radiotherapy regimens, is therefore only achieved in the fortuitous situation where repair, redistribution, repopulation and cell killing combine in different proportions to result in the same overall survival. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

No description available.

Pages 154 and 155 were not included in the thesis. / <p> The post-irradiation annealing of highly converted styrene-polystyrene systems was explored. Experimental conditions necessary for the entrapment of high concentrations of free radicals in such systems were investigated. They were found to bear a relation to the glass transition temperature of the system.</p> <p> The concentration of free radicals formed by subjecting the polymer-monomer systems to Gamma rays, at room temperature, was measured, and the subsequent GM and GP values were calculated. The structure of the formed radical was found to be in agreement with that suggested by previous investigators. The free radicals decay was examined at varied temperatures above and below Tgs, and was found to follow a second order mechanism. The activation energy of decay was found to increase by raising the temperature above Tgs.</p> <p> When irradiation was executed at temperatures below Tgs, post-irradiation annealing led to high rates of polymerization when carried out at temperatures above Tgs. </p> <p> The number average molecular weight was practically unchanged during the polymerization of the last few percent monomer.</p> / Thesis / Master of Engineering (MEngr)

<p> The products and mechanism of the photolytic rearrangement of the equilibrium mixture of triphenylmethylcyclopentadienes have been studied. Direct irradiation of the equilibrium mixture of triphenylmethylcyclopentadienes yields 5,6,6-triphenylbicyclo{3.1.0}hex-2-ene. Photolysis with a triplet sensitizer yields dimeric products in addition to 5,6,6-triphenylbicyclo{3.1.0}hex-2-ene. Thermolytic isomerization of 5,6,6-triphenylbicyclo{3.1.0}hex-2-ene is reported. The predominant isomer in the equilibrium mixture of triphenylmethylcyclopentadiene has been established as 2-triphenylmethylcyclopentadiene.</p> / Thesis / Master of Science (MSc)

The effects of space irradiation on the cardiovascular systems remain a great mystery. After conducting studies on survivors of the atomic bomb, radiotherapy as a treatment for cancer and other diseases, and health data of astronauts who have participated in short and long duration space missions, the overall conclusion is that ionizing irradiation of any type results in cardiovascular damage. Problems manifest decades after irradiation exposure and the accumulating health complications have led to fatalities. However, little is known about space irradiation and how it affects our bodies. Predictive models that were developed to date were created based on events that have occurred on earth. National Aeronautics and Space Administration (NASA) plans for manned missions to the Moon and Mars in the near future. There is a great need for ground-based studies about the effects of cosmic irradiation on the human body. We examined molecular pathways in the heart tissue of adult 7-9 months old mice, an equivalent of middle-age for astronauts (35-55), after receiving a single low dose full body of either 56Fe (iron) or 1H (proton) irradiation + aging of 1, 3, and 10 months. We also investigated mice after 56Fe or 1H irradiation + aging of 1, 3, and 10 months, and 3 days after an induced acute myocardial infarct (AMI). Western blot analyses were performed for proteins involved in cardiac function and cardiac recovery. Results indicated that 56Fe irradiation impaired cardiac function significantly during aging and continued to worsen with age. AMI results were less straightforward. The younger, 56Fe irradiated mice revealed a significant decrease in the expression of proteins associated with survival of cardiac tissue. The older, 1H irradiated mice group revealed a significantly decreased expression of proteins associated with survival of cardiac tissue. The 10 month 56Fe irradiated mice did not show compensatory mechanisms and the cardiac protein expression levels were attributed to aging. While the 10 month 1H irradiated mice compensated and required less repair activation.

The present PhD project was carried out as part of an EPSRC Leadership Fellowship for the study of irradiation damage in zirconium alloys. The National Nuclear Laboratory (NNL) directly supported the project in terms of additional funding and insightful discussions regarding irradiation damage in zirconium alloys. The research carried out within the project aims to gain a better understanding of both a- and c-loops, formed during irradiation damage in zirconium alloys. A range of techniques have been utilised to assess the morphology and density of the dislocation loops after proton-irradiations. These techniques include transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS) and line profile analysis (LPA) using synchrotron X-ray diffraction (SXRD) profiles and analysing the data utilizing the extended convolutional multiple whole profile (CMWP) analysis software. The effect of experimental conditions on dislocation loop formation and stability of a-loops during post-irradiation annealing have also been investigated. Proton-irradiations were carried out on the commercial alloys Zircaloy-2, Optimized ZIRLOTM and also on binary Zr-0.1Fe and Zr-0.6Fe alloys. A mechanism has been proposed as to the effect of Fe redistribution on dislocation loop formation. By comparing proton-irradiated Zr-0.1Fe and Zircaloy-2 alloys it was possible to investigate the effect of increased amount of Fe redistribution, which occurs from secondary phase particle (SSP) dissolution, on the microstructural features that develop during irradiation. Zircaloy-2 has a higher density of SPPs and these are more homogenously distributed throughout the matrix in comparison to the Zr3Fe SPPs found in the Zr-0.1Fe alloy. It was found that Fe redistribution facilitates the formation of Fe-rich nano-precipitation. Bright-field STEM imaging has been used to image a- and c-loops and it was found that Zircaloy-2 had a lower dislocation line density compared to Zr-0.1Fe for both types of loops at similar damage levels. Therefore it has been proposed that Fe redistributed from SPPs precipitates in the matrix and the subsequent irradiation-induced precipitates act as annihilation sites for point defects; therefore preventing the formation of new dislocation loops and the growth of existing loops. In order to assess the effect of proton-irradiation temperature on a-loops, Zircaloy-2 and Optimized ZIRLOTM were proton irradiated to 2.3 dpa at 280°C, 350°C and 450°C. It was found that the a-loop density dropped in both alloys as irradiation temperature was increased and the a-loop diameter decreased. The changes in the density and size were more dramatic in Zircaloy-2 and this was explained by the presence of fine irradiation induced clustering of Nb seen in Optimized ZIRLOTM. These trends were calculated from both STEM imaging and CMWP, highlighting the suitability of using CMWP to investigate irradiation-induced dislocations. Finally the stability of the a-loops in proton-irradiated Zr-Fe binary alloys were investigated using novel in-situ SXRD and TEM annealing experiments. From CMWP analysis of the profiles generated during the in-situ annealing of a Zr-0.6Fe 3 dpa sample it was shown that the majority of the annealing takes place between 300°C-400°C. This was highlighted by a period of no change in the dislocation density up to 300°C, after which the density drops dramatically. In-situ annealing of a 1.5 dpa Zr-0.1Fe sample in the TEM allowed for the observation of a-loop gliding along prismatic planes enabling the annealing process taking place between 280°C-450°C, i.e. a similar temperature range at which SXRD analysis indicates the greatest level of annealing.

Yes / Osmium nanocrystals can be fabricated by electron (3–50 nm, formed by atom migration), 785–815 nm laser (20–50 nm, in micelle islands), and microwave (ca. 1 nm in arrays, >100 mg scale) irradiation of a polymer-encapsulated OsII carborane; microfocus X-ray absorption studies at the Os LIII-edge show differences between the three preparation methods, suggesting that the electron-beam irradiated materials have a significant support interaction and/or surface oxidation, while the laser and microwave samples are more like metallic osmium. / Royal Society (University Research Fellowship No. UF150295 to NPEB), the Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the ERC (Grant No. 247450 to PJS), EPSRC (Grant No. EP/F034210/1 to PJS and EP/ J007153/1 to VGS), Diamond Light Source (Beam-time grant number SP11314).

published_or_final_version / Physics / Doctoral / Doctor of Philosophy

published_or_final_version / Physics / Doctoral / Doctor of Philosophy