This dissertation describes the approach taken in measuring two neutrino double beta decay of Cd-116 to the ground state of Sn-116 and in searching for the effective Majorana neutrino mass by placing a lower limit on the half-life for neutrinoless double beta decay of Cd-116 using the powerful technique of a combined tracking chamber and calorimeter with the NEMO-3 detector. The description of the detector, its natural background contamination, and the tools used to perform the analysis are discussed. The single electron channel was used to identify source foil contamination from [beta]-emitters and the electron-gamma channel was used to confirm the previous measurements of Tl-208 and Bi-214 contaminations in the source foil. Using these backgrounds, the two neutrino double beta decay half-life of Cd-116 was measured for the single states dominance hypothesis and the higher states dominance hypothesis. The final data set was defined to be data from Phrase One and Phase Two for the medium and low activity regions. Using 1471 days of data, the values of the half-life for the single data dominance hypothesis and the higher states dominance hypothesis were found. / text

Stuttgart, Univ., Diss., 2002.

No description available.

Master of Science / Department of Anatomy and Physiology / Lei Wang / Jishu Shi / Transforming growth factor beta (TGF-β) and interleukin-1β (IL-1β) are both up-regulated in high grade gliomas and their elevated activities have been associated with prognosis in glioma patients. It is known that TGF-β is involved in proliferation and maintenance of glioma stem cells. In this study, I evaluated whether IL-1β also plays an important role in glioma stem cell development. Glioma stem cells are usually identified by using a sphere assay where glioma stem cells proliferate as neurospheres in serum free medium (SFM) in the presence of two growth factors: EGF and bFGF. However, LN229, a human glioblastoma cell line does not form neurospheres in SFM, suggesting that LN229 cells contain very few stem cells. I found that combination of IL-1β and TGF-β, but not IL-1β or TGF-β alone induced LN229 cells to grow as neurospheres in SFM. Furthermore, quantitative RT-PCR analyses show that the expression of stem cell markers (Nestin, Bmi1, Notch2, and LIF), cytokines (IL-1β, IL-6 and IL-8) and invasive genes (SIP1, β-integrin and N-Cadherin) are significantly enhanced in IL-1β /TGF-β induced spheres compared to the control. Using an invasion assay, drug resistance test, and colony assay, I found that LN229 sphere cells induced by IL-1β and TGF-β are more invasive, have increased drug resistant ability, and are more oncogenic in comparison to the control. Together, these results suggest that IL-1β cooperates with TGF-β to induce glioma stem-like cell phenotype.

Call number: LD2668 .T4 1952 K7 / Master of Science

Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Reported claims of a solar neutrino influence on radioactive β - -decay rates prompted a series of three long term measurements that were carried out at the Koeberg nuclear power plant North of Cape Town to investigate the mirror reaction of reactor antineutrinos with a β + - source. The β + -emitter 22Na was exposed to a changing reactor antineutrino flux of the order of ~1012 cm-2 s -1 through the various phases of reactor operation, from off to on or vice versa, to investigate the antineutrino effect on its decay rate. 22Na sources were placed on the face of or inside a scintillation detector while γ-ray energy spectra were measured at source-toreactor-core distances of 17 m and 23 m for reactor unit #1 and unit #2 respectively. The analytical method employed uses ratios of the net-peak count rates of the photopeaks in the γ- ray energy spectra while the antineutrino flux changes during the various phases of reactor operation. These ratios reduce some potential systematic factors such as dead time, but should also remain constant during all phases of reactor operation and be independent of antineutrino flux if antineutrinos have no significant effect on the decay rate of 22Na. Measurement series 1 employed a LaBr3(Ce) detector. Results indicated an effect between reactor-off and –on corresponding to an antineutrino interaction cross section upper limit of the order of barns, assuming that antineutrinos are indeed the cause. Subsequently, two confirmation measurements were performed using a normal (cylindrical) NaI(Tl) detector as well as a NaI(Tl) well-counter. Results of these two measurements did not indicate any correlation with the reactor status. Measurements series 3 proved to be the most sensitive measurement for detecting changes in the decay rate of 22Na and an upper limit of ~10-25 cm 2 was estimated for the cross section of antineutrinos interacting with 22Na. This upper limit is one order of magnitude smaller compared to measurements series 1 and two orders of magnitude smaller compared to measurement series 2. It is also one of magnitude smaller than the effect reported by Jenkins et al. and two orders of magnitude smaller than observed by de Meijer et al. at the Delft reactor. Considering the systematic effects encountered during each measurement series we find no significant evidence for antineutrinos affecting β + -decay in 22Na. / AFRIKAANSE OPSOMMING: Berigte bewerings van son-afkomstige neutrinos se invloed op β - -verval het gelei tot drie lang termyn metings wat uitgevoer is by die Koeberg kernkrag stasie Noord van Kaapstad om die spieëldbeeld reaksie van antineutrinos met ‘n β + -bron te ondersoek. Die 22Na β + -bron is blootgestel aan ‘n veranderende reaktor antineutrino vloed van die order ~1012 cm -2 s -1 soos die reaktor deur verskeie fases van operasie gaan, vanaf afgeskakel na aangeskakel of omgekeerd, om die effek van antineutrinos op die bron se vervaltempo te ondersoek. 22Na bronne was teen die voorkant of binne ‘n sintillator detektor geplaas terwyl γ-straal energie spektra gemeet was by bron-tot-reaktor kern afstande van 17 m en 23 m vir reaktor eenheid #1 en #2 afsonderlik. Die analitiese metode gebruik verhoudings van die netto-piek teltempos van die fotopieke in die γ-straal energie spektra terwyl die antineutrino vloed verander tydens verskeie fases van reaktor operasie. Hierdie verhoudings verminder sekere potensiële systematiese effekte soos dooietyd en moet konstant bly tydens alle fases van reaktor operasie en moet ook onafhanklik wees van die antineutrino vloed indien antineutrinos geen effek het op die vervaltempo van 22Na nie. Die eerste reeks metings het gebruik gemaak van ‘n LaBr3(Ce) detektor. Resultate het ‘n effek getoon tussen reaktor-af en reaktor-aan wat ooreenstem met ‘n boonste limiet vir die interaksie kansvlak van antineutrinos met grootteorde van barns, indien antineutrinos wel die oorsaak is. Twee reekse van opvolgende metings is uitgevoer wat gebruik gemaak het van ‘n gewone (silindriese) NaI(Tl) detektor asook ‘n NaI(Tl) put detektor. Resultate van hierdie metings het geen korrelasie met die reaktor status gewys nie. Die derde reeks metings was die sensitiefste om veranderinge in die verval tempo van 22Na te wys en ‘n boonste limiet vir die interaksie kansvlak van antineutrinos op 22Na was beraam as ~10-25 cm 2 . Hierdie boonste limiet is een grootteorde kleiner in vergelyking met reeks 1 en twee grootteordes kleiner as reeks 2. Dit is ook een grootteorde kleiner as die waarde van Jenkins et al. en twee grootteordes kleiner as wat de Meijer et al. berig het by die Delft reaktor. In agneming van die systematise probleme wat ondervind was tydens die drie reeks metings vind ons geen beduidende effek van antineutrinos op die vervaltempo van 22Na nie.

Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia, with an incidence of up to 50% in western populations over the age of 85 and a high heritability (up to 80%). The identification of risk factors for the development of LOAD is imperative for improving our understanding of this disease and for identifying therapeutic targets for treatment or prevention. Currently, the major known risk factors for the development of LOAD are age and the ApoE ε4 genotype. Previous studies have implicated plasma levels of the amyloid beta (Aß) peptide as a LOAD-associated quantitative trait and identification of loci influencing this trait could provide new insights into LOAD. In this thesis, plasma levels of the Aß peptides Aß40 and Aß42 have been measured in two isolated populations and genome-wide linkage and association analyses were performed. The genome-wide association analyses identified a number of promising quantitative trait loci; highlighting both novel and previously reported LOAD genes for further study, whilst also providing an excellent resource for genetic convergence studies with other LOAD related traits. Several studies have reported an association between levels of oxidative stress and levels of Aß such that increasing levels of Aß appear to increase markers for oxidative stress and vice versa. The role of oxidative stress in LOAD and aging was therefore also investigated through analysis of mitochondrial mutational burden and DNA damage respectively, using DNA isolated from both blood and the brain and by carrying out a candidate gene association study of loci involved in mitochondrial function in LOAD cases and controls. Approaches to the investigation of mitochondrial genetics for the study of LOAD are comprehensively reviewed, adapted and tested and the results indicate a need for additional research in this aspect of the disease. This thesis therefore presents a focus on two aspects of genetic research into LOAD, a complex disease with multiple environmental and genetic influences which aims to advance our understanding of the disease and bring us closer to treatment and prevention strategies.

Type 2 diabetes (T2D) is a growing health-care and economic burden. Obesity is a risk factor for developing T2D, but the underlying molecular mechanisms are not well understood. However, mechanisms such as lipotoxicity, endoplasmic reticulum stress and inflammation are becoming increasingly well-recognised in obesity, and may underlie the development and progression of T2D. A central player in these mechanisms is Protein Kinase R (PKR), proposed to have a role within nutrient- and pathogen-sensing pathways, and is activated by ER stress and lipotoxicity. A small molecule inhibitor Compound-16, adenoviral vectors and RNAi techniques in BRIN-BD11 rodent pancreatic β-cells, were used to demonstrate that PKR knockdown affords significant protection against palmitate-induced cell death. Furthermore, PKR knockdown potentiates palmitoleate cytoprotection during lipotoxicity, suggesting the cytotoxic and cytoprotective actions of long-chain fatty acid species may function via the PKR signalling pathway. The use of a novel 1.1B4 human pancreatic β-cell line has shown that important differences exist between human and rodent cell responses to fatty acids in vitro. In 1.1B4 cells, long-chain saturated and monounsaturated fatty acids do not provide increasing protection as their chain-length increases, in contrast to rodent cell models. Furthermore, methyl-saturated fatty acid species are well tolerated, and methyl-monounsaturated fatty acids are cytoprotective to 1.1B4 β-cells. TXNIP overexpression in an INS-TXNIP β-cell model has a proapoptotic role in conditions of glucotoxicity, but not glucolipotoxicity. Furthermore, in this cell model, succinate is cytoprotective against glucotoxicity, but not glucolipotoxicity. By contrast in 1.1B4 β-cells, succinate significantly protects against apoptosis induced by both glucotoxic and glucolipotoxic conditions. Chronic inflammation has been implicated in the development and progression of T2D. At the centre of this response is the pro-inflammatory cytokine IL-1β. The cellular origin of IL-1β is unclear, but IL-1β secretion has been linked to activation of the NLRP3 inflammasome, recently implicated in pancreatic β-cell death in T2D. Results suggest that IL-1β is secreted by INS-TXNIP and 1.1B4 pancreatic β-cells under lipotoxic conditions, thus offering a potential role for targeted IL-1β therapy in T2D.

No description available.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy