Thesis (MS)--Montana State University--Bozeman, 2010. / Typescript. Chairperson, Graduate Committee: Brock LaMeres. Includes bibliographical references (leaves 59-63).

Thesis (PhD)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: The factors which control radiosensitivity are of vital importance for the understanding of cell inactivation and for cancer therapy. Cell cycle blocks, total induced DNA damage, DNA repair, apoptosis and chromatin structure are likely to playa role in the responses leading to cell death. I have examined aspects of irradiation-induced G2/M blocks in DNA damage and repair. In HT29, L132 and ATs4 cells the total amount of induced DNA damage by isodoses of 4.5 Gy, 5 Gy and 2 Gy was found to be 14 %, 14 % and 12 % respectively. Most of the DNA repair was completed before the G2/M maximum and only 3 % of DNA damage remains to be restored in the G2/M block. The radiosensitivity in eleven cell lines was found to range from SF2 of 0.02 to 0.61. By FADU assay the undamaged DNA at 5 Gy was found to range from 56% to 93%. The initial DNA damage and radiosensitivity were highly correlated (r2=0. 81). After 5 Gy irradiation and 12 hours repair two groups of cell lines emerged. The group 1 cell lines restored undamaged DNA to a level ranging from 94 % to 98 %. The group 2 cell lines restored the undamaged DNA to a level ranging from 77 % to 82 %. No correlation was seen between residual DNA damage remaining after 12 hours repair and radiosensitivity. In CHO-K1 cells chromatin condensation induced by Nocodazole was found to marginally increase the radiosensitivity as shown by the change of the mean inactivation dose (D) from 4.446 to 4.376 Gy. Nocodazole also increased the initial DNA damage, induced by 5 Gy, from 7 % to 13 %. In xrs1 cells these conditions increased the radiosensitivity from D of 1.209 to 0.7836 Gy and the initial DNA damage from 43 % to 57 %. Disruption of chromatin structure with a hypertonic medium was found to increase radiosensitivity in CHO-K1 cells from D of 4.446 to 3.092 Gy and the initial DNA damage from 7 % to 15 %. In xrs1 cells these conditions caused radiosensitivity to decrease from D of 1.209 to 1.609 Gy and the initial DNA damage from 43 % to 36 %. Repair inhibition by Wortmannin increased the radiosensitivity in CHO-K1 from a D of 5.914 Gy in DMSO controls to a D 3.043 Gy. In xrs1 cells repair inhibition had no effect on radiosensitivity. Significant inhibition of repair was seen in CHO-K1 at 2 hours (p<0.0001) and at 20 hours (p=0.0095). No inhibition of repair was seen in xrs1 cells at 2 hours (p=0.6082) or 20 hours (p=0.6069). While DNA repair must be allocated to the post-irradiation period, the G2/M block seen in p53 mutants reaches a maximum only 12 hours post-irradiation when most of the repair is completed. As the G2/M block resolves and cells reenter cycle 28 hours after the G2 maximum it appears that repair processes cannot be the only reason for the G2IM cell cycle arrest. At low doses of irradiation initial DNA damage correlates with radiosensitivity. This suggests that the initial DNA damage is a determinant for radiosensitivity. Repair of DNA double-strand breaks by the non-homologous end joining (NHEJ) mechanism, identified by inhibition with Wortmannin, was shown to influence residual DNA damage and cell survival. Both the initial DNA damage and DNA repair were found to be influenced by chromatin structure. Chromatin structure was modulated by high salt and by Nocodazole, and has heen identified as a parameter which influences radiosensitivity. / AFRIKAANSE OPSOMMING: Die faktore wat betrokke is in die meganisme van stralings-sensitisering is van hoogs belang vir die begrip van sel inaktiveering en kanker terapie. Sel siklus blokke, totale geïnduseerde DNS skade, DNS herstel, apoptose en chromatien struktuur is moontlike rol vertolkers in die sellulêre response wat ly tot seldood. Ek het die aspekte van stralings-geïnduseerde G2/M blokke in DNS skade en DNS herstelondersoek. Die hoeveelheid geïnduseerde DNS skade, deur ooreenstemmende stralings-dosisse, in HT29, L132 en ATs4 selle is 14 %, 14 % en 12 %. Meeste van die DNS herstel is klaar voordat die G2/M maksimum beryk word en net 3 % DNS skade blyoor om herstel te word in die G2/M blok. Die stralings-sensitiwiteit in elf sel lyne varieer tussen 'n SF2 van 0.02 en 0.61. Deur die gebruik van die FADU metode is gevind dat die onbeskadigde DNS na 5 Gy bestraling varieer tussen 56 % en 93 %. Die totale geïnduseerde DNS skade en stralings-sensitiwiteit was hoogs gekorreleer (r2=0.81). Na 5 Gy bestraling en 12 ure herstel kan die sel lyne in twee groepe gegroepeer word. Die groep 1 sellyne herstel die onbeskadigde DNS terug na 'n vlak wat varieer tussen 94 % en 98 %. Die groep 2 sel lyne herstel die onbeskadigde DNS terug tot op 'n vlak wat varieer tussen 77 % en 82 %. Geen korrelasie is gesien tussen oorblywende DNS skade en stralings-sensitiwiteit na 12 ure herstel nie. In die CHO-K1 sel lyn, chromatien kompaksie geïnduseer deur Nocodazole, vererger die stralings- sensitiwiteit soos gesien deur die gemiddelde inaktiveerings dosis (D) wat verlaag het van 4.446 tot 4.376. Nocodazole het ook die totale DNS skade verhoog van 7 % tot 13 %. Onder dieselfde kondisies, in die xrs1 sel lyn, is 'n verergering van stralings-sensitiwiteit (D) gesien van 1.209 tot 0.7836 en verhoog ONS skade van 43 % tot 57 %. Die ontwrigting van die chromatien struktuur deur die gebruik van hipertoniese medium het die stralings-sensitiwiteit (D) vererger in CHO-K1 selle van 4.446 tot 3.092. Die totale ONS skade is verhoog van 7 % tot 15 %. Onder dieselfde kondisies, in die xrs1 sellyn, verbeter die stralings-sensitiwiteit (D) van 1.209 tot 1.609 en die totale ONS skade verminder van 43 % tot 36 %. ONS herstel inaktiveering in die teenwoordigheid van Wortmannin het die stralings-sensitiwiteit (D) in CHO-K1 selle vererger van 5.914 in DMSO verwysings kondisies tot 3.043. Die ONS herstel inaktiveering in xrs1 selle het geen uitwerking gehaat op stralingssensitiwiteit nie. Noemenswaardige inaktiveering van ONS herstel is gesien in CHO-K1 selle na 2 ure (p<0.0001) en na 20 ure (p=0.0095). Geen inaktiveering is gesien in xrs1 selle na 2 ure (p=0.6082) of na 20 ure (p=0.6069) nie. TerwylONS herstel moet plaasvind na die bestralings periode, beryk die G2/M blok in p53 gemuteerde selle sy maksimum 12 ure na bestraling terwyl meeste van die ONS herstel alreeds voltooi is. Aangesien die G2/M blok eers 28 ure later begin sirkuleer moet die G2/M blok nog 'n funksie vervul anders as ONS herstel. By lae dosisse van bestraling korreleer die totale geïnduseerde ONS skade met stralings-sensitiwiteit. Dit dui daarop dat die totale ONS skade 'n bepalende faktor moet wees in stralings-sensitiwiteit. Die herstel van ONS skade deur die nie-homoloë eindpunt samevoeging (NHES) meganisme, geïdentifiseer deur inaktiveering deur Wortmann in, het 'n invloed op oorblywende ONS skade en sellulêre oorlewing. Beide die totale ONS skade en ONS herstel was beïnvloed deur die chromatien struktuur. Chromatien struktuur was gemoduleer deur hoë sout konsentrasies en deur Nocodazole, en is geïdentifiseer as a belangrike parameter wat stralings-sensitiwiteit beïnvloed.

It is increasingly recognised that individual risk of cancer may be related to genetically determined differences in the ability of cells to identify and repair DNA damage. Cell cycle based assays of chromosomal radiosensitivity provide the greatest power for discriminating differences in response to DNA damage and it has been suggested that individuals who are genetically susceptible to cancer show increased chromosomal radiosensitivity. The relationship between chromosomal radiosensitivity and early onset cancer was investigated in a population of Danish survivors of childhood and adolescent cancer and a control group comprising of their partners using the G₂ assay of chromosomal radiosensitivity. Heritability was also examined in the offspring. No significant differences in radiosensitivity profiles were found between partner controls and either the cancer survivors or offspring. However, when compared to the Westlakes Research Institute control population, significant differences were observed with the cancer survivors (P = 0.002) and offspring (P < 0.001), supporting an association of chromosomal radiosensitivity with cancer predisposition. Heritability studies suggested the majority of phenotypic variance of chromosomal radiosensitivity was attributable to a putative major gene locus with dominant effect. Since G2 chromosomal radiosensitivity indirectly measures the ability of cells to repair DNA damage induced by ionising radiation exposure, variants in DNA repair genes may explain inter-individual variation observed. Sixteen polymorphisms in nine genes from four DNA repair pathways were investigated. Genotype frequencies at the Asp148Glu polymorphism were associated with childhood cancer in survivors. Analysis of variance and FBAT analysis suggested significant associations at both the Thr241Met and Ser326Cys polymorphism sites with G₂ radiosensitivity, but neither remained significant after multiple-test adjustment. This study invites further exploration of the predictive capacity of G₂ chromosomal radiosensitivity in cancer predisposition. Clearly, further work is needed to correlate radiosensitivity with genetic polymorphisms, which may underlie cancer susceptibility and variation in radiosensitivity.

In the next decade, technology trends--smaller dimension, lower voltage, higher operating frequency--introduce new technical considerations and challenges for radiation effects in integrated circuits. Semiconductor based circuits and traditional dynamic random-access memories will malfunction when exposed to extreme environments, such as space and nuclear reactor. The mechanisms for radiation effect are mainly attributed to the radiation-induced charging of the oxide in a CMOS device. Spintronics is an emerging area of nanoscale electronics involving the detection and manipulation of electron spin. The magnetic tunnel junctions (MTJs), based on the intrinsic spin of the electron, can be used as the storage elements in non-volatile magnetoresistive random-access memories (MRAMs). In this effort, we study radiation tolerance of MTJs by exposing the devices in gamma and neutron radiation environment. Theoretical model for the radiation-induced defects is analyzed in this work. Experiments of the MgO-based MTJs under the conditions of pre- and post-radiation are concluded. MTJs were irradiated with gamma ray to a total dose of 10 Mrad. During the neutron irradiation, total epithermal neutron fluence up to 2.9��10�����/cm�� was obtained. The experimental results show that neither the electrical nor the magnetic properties of MTJs are affected by the radiation. / Graduation date: 2013 / Access restricted to OSU community at author's request from Sept. 11, 2012 - Sept. 11, 2014

The purpose of this study is to investigate the role of strain in the accumulation of crystalline defects created by ion irradiation. Previous studies state that strained Si1xGex is more easily amorphized by ion irradiation than unstrained, bulk Si in a periodic superlattice structure; however, the reason for preferential amorphization of the strained Si1xGex layer in the periodic structure of strained and unstrained layers is not well understood. In this study, various ion irradiations will be carried out on SiGe strained layer superlattices grown on (100)-orientation bulk Si by low temperature molecular beam epitaxy. The samples under investigation are 50 nm surface Si0:8Ge0:2/bulk Si and 50 nm surface Si/60 nm Si0:8Ge0:2/bulk Si. Defects will be created in both surface and buried SiGe strained layers by medium and high energy light ion irradiation. The amount of permanently displaced atoms will be quantified by channeling Rutherford backscattering spectrometry. The amorphization model, the path to permanent damage creation, of bulk Si and surface strained SiGe will be investigated. The strain in surface and buried Si0:8Ge0:2 layers will be measured by comparison to bulk Si with Rutherford backscattering spectrometry by a novel technique, channeling analysis by multi-axial Rutherford backscatter- ing spectrometry, and the limitations of measuring strain by this technique will be explored. Results of this study indicated that the amorphization model, the number of ion collision cascades that must overlap to cause permanent damage, of strained Si0:8Ge0:2 is similar to that of bulk Si, suggesting that point defect recombination is less efficient in strained Si0:8Ge0:2. Additionally, a surface strained Si0:8Ge0:2 is less stable under ion irradiation than buried strained Si0:8Ge0:2. Repeated analysis by multi-axial channeling Rutherford backscattering spectrometry, which requires high fluence of 2 MeV He ions, proved destructive to the surface strained Si0:8Ge0:2 layer.

The objective of this research is to understand the design and performance of state-of-the-art silicon-germanium (SiGe) BiCMOS high-frequency circuits for phased- array radar and wireless communication systems operating in extreme environment conditions. This work investigates the performance of RF circuits over a wide- temperature and exposure to a radiation intensive environment. The design and characterization of a fully integrated transmit/receive (T/R) module and integra- tion onto a multi-element antenna array is presented. In addition, individual circuit blocks are characterized in these extreme environments.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.