Thesis (Ph. D.)--University of Oregon, 2006. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 174-183). Also available for download via the World Wide Web; free to University of Oregon users.

Background: Hypothalamic kisspeptin and neurokinin B (NKB) are central regulators of GnRH and thus gonadotropin (LH and FSH) secretion. Men and women with loss-of-function mutations in NKB-kisspeptin pathway show hypogonadotropic pubertal delay with reduced GnRH/LH pulsatility. Studies in patients with defects in NKB signalling suggest that kisspeptin is functionally downstream of NKB, although there are very limited data on the relevance of the NKB pathway in normal men or women, and no hierarchical data on this. The studies described in this thesis have investigated the interaction between these neuropeptides in the control of human reproduction in conditions of varying sex-steroid environment, and in states of fast and slow LH secretion (men, menopause, various stages across the menstrual cycle). Overall hypothesis: Pharmacological blockade of NKB signalling will decrease LH secretion by modulating GnRH/LH pulsatility, indicating the involvement of the NKB pathway in normal human reproductive function. It is also hypothesised that this will not abrogate the stimulatory kisspeptin response, revealing a functional hierarchy whereby NKB signalling is upstream of kisspeptin. Research strategy: A specific neurokinin-3 receptor antagonist (NK3R antagonist, AZD4901) was administered 40 mg twice daily orally for 7 days with and without kisspeptin-10 (KP-10) challenge. Response of reproductive hormones (serum and urinary where applicable) was measured. LH was sampled every 10 minutes for 8 hours to assess LH pulsatility by blinded deconvolution. Results: Role of neurokinin B and kisspeptin in healthy men Six healthy men underwent LH pulsatility study pre-treatment and on day 7 of NK3R antagonist administration with iv KP-10 bolus (0.3 μg/kg) at 6 hours. NK3R antagonist reduced LH and testosterone secretion, whilst stimulatory LH response to KP-10 was unaffected. LH pulse frequency was unchanged by the NK3R antagonist but basal (nonpulsatile) and pulsatile LH secretion was markedly reduced. Role of neurokinin B and kisspeptin in postmenopausal women Eleven postmenopausal women underwent LH pulsatility study pre-treatment and on day 7 of NK3R antagonist administration with iv KP-10 bolus (0.3 μg/kg) at 6 hours. NK3R antagonist decreased LH secretion. Basal (nonpulsatile) LH secretion also fell and while LH pulse frequency did not change in a group as a whole, it did fall in the 8 of 11 postmenopausal womenwith hot flushes. These women reported a reduction in hot flush frequency (3.4±1.2 vs 1.0± 0.6 flushes/day with NK3Ra, p=0.008) and severity whilst on NK3R antagonist. LH response to KP-10 was minimal and unaffected by the NK3R antagonist. Role of neurokinin B across different phases of menstrual cycle The effect of NK3R antagonist on ovarian function was compared in early follicular (n=13), late follicular (n=6) and luteal phase (n=6) to no treatment control cycle. Early follicular: NK3R antagonist was commenced from cycle day 5-6. The diameter of the leading follicle was smaller than in controls at the end of treatment (9.3±0.4 vs 15.1±0.9 mm, p < 0.0001). Serum estradiol was also reduced and the endometrium was thinner. Although NK3R antagonist had no effect on LH pulse frequency, basal (nonpulsatile) LH secretion was decreased, suggesting that NKB modulates GnRH secretion. After stopping treatment, follicle development resumed and estradiol secretion increased thereby delaying the LH surge in 11/13 women (LH surge cycle day 22±1 vs 15±1, p=0.0006). The delayed LH surge and ovulation were confirmed by a similarly delayed rise in urinary progesterone and prolonged cycle length. NK3R antagonist did not affect luteal function. Late follicular: NK3R antagonist was administered from the emergence of a dominant follicle (≥12mm). Whilst there was an LH surge in all treated cycles, estrogen feedback was perturbed by the NK3R antagonist, as there was increased variation in the timing of LH surge compared to control cycle. NK3R antagonist had no effect on the growth of a dominant follicle and luteal function was unaffected. Luteal: NK3R antagonist was administered from day +2-3 of the disappearance of the dominant follicle. NK3R antagonist reduced the variation in the timing of peak estradiol secretion. Estradiol and progesterone concentrations remained unchanged, suggesting that luteal function was overall unaffected by this treatment. No difference in mean LH was observed, although LH pulsatility was not assessed. Role of neurokinin B and kisspeptin in the mid-cycle LH surge A model of follicular phase (cycle day 9-11) administration of estradiol (200μg/day) to induce LH secretion at 48 hours was used in twenty women, mimicking LH surge. In this model, KP-10 infusion (4μg/kg/hr for 7 hours) enhanced LH secretion, the response of which was directly correlated with estrogen concentration, indicating a role of kisspeptin in estrogen feedback. Pre-treatment with NK3R antagonist decreased LH pulse frequency and whilst the immediate LH response to KP-10 was unaffected, it blunted the duration of this response and abolished the relationship between estradiol and kisspeptin-induced LH secretion. Conclusions: These data indicate the role of NKB-KP pathway in regulating human reproductive function and that this is via the modulation of pulsatile GnRH secretion. Whilst NKB is predominantly proximal to kisspeptin, the hierarchy is more complex than simply linear in the control of human HPG axis. Manipulation of NKB-KP signalling has therapeutic potential in regulating GnRH/LH secretion in wide range of clinical settings, including contraception, sex-steroid dependent disorders and in the treatment of hot flushes.

Philosophiae Doctor - PhD / The major result of this thesis is the development of a framework for the application of pair-mixtures of copulas to model asymmetric dependencies in bivariate data. The main motivation is the inadequacy of mixtures of bivariate Gaussian models which are commonly fitted to data. Mixtures of rotated single parameter Archimedean and Gaussian copulas are fitted to real data sets. The method of maximum likelihood is used for parameter estimation. Goodness-of-fit tests performed on the models giving the highest log-likelihood values show that the models fit the data well. We use mixtures of univariate Gaussian models and mixtures of regression models to investigate the existence of bimodality in the distribution of the widths of autocorrelation functions in a sample of 119 gamma-ray bursts. Contrary to previous findings, our results do not reveal any evidence of bimodality. We extend a study by Genest et al. (2012) of the power and significance levels of tests of copula symmetry, to two copula models which have not been considered previously. Our results confirm that for small sample sizes, these tests fail to maintain their 5% significance level and that the Cramer-von Mises-type statistics are the most powerful.

The Clemson GRB Follow-Up program utilizes the SARA 0.9-m telescope to observe optical afterglows of Gamma Ray Bursts. SARA is not yet robotic; it operates under direct and Target-of-Opportunity (ToO) interrupt modes. To facilitate rapid response and timely reporting of data analysis results, we developed a software suite that operates in two phases: first, to notify observers of a burst and assist in data collection, and second, to quickly analyze the images.

No description available.

A dissertation submitted to the Geophysics Department, School of Geosciences, Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Masters of Science. Johannesburg, February 2012 / Impala Platinum Mine (Impala), situated north of the town of Rustenburg in the North West Province of South Africa, has experienced an increase in seismicity from ~841 seismic events in the year 2005 to ~1588 seismic events in 2008. The seismologists and rock engineers need to understand the underlying mechanisms and driving forces responsible for seismicity to develop and design mining layouts and support strategies to lessen the risks posed by rockburts. However, most previous studies of seismicity conducted on Impala and other Bushveld Complex mines in the Rustenburg area provided limited information regarding the source parameters and mechanism due to insufficient data. The study is designed to investigate the seismic hazard on Impala Platinum Mine by means of two approaches: an investigation of seismic source parameters and the mechanism of potentially damaging seismic events, and mapping of the weathered layer of the near surface within the Impala mine lease area. A number of detailed investigations of rockbursts were conducted whereby damage was mapped and photographed. The investigations includes reviews of the seismic history, short-, medium- and long-term seismic hazard assessment methods, and an analysis of the source parameters of the seismic event and associated ground motions. The study has revealed that most of the seismic events occur close to the reef plane, and are the result of the failure of a volume of rock that includes the pillar and the host rock that forms the foundation of the pillar.

A review of coal bumps. their nature. causes. prediction. prevention. and mitigation is presented. The design and construction of a borehole stressmeter is discussed. Laboratory testing. which yielded promising results of the stressmeter (inclusion) is presented along with preliminary field test results. Laboratory testing involved comparison with the results of a two-dimensional finite element model of the physical laboratory test with those of the physical test itself. Results correlated well. The results of the field test indicate the need for further research into the practical application of the solid inclusion method in the field. / Master of Science

Nesta dissertação estudamos como os efeitos das inomogeneidades da matéria (escura e bariônica) modificam as distâncias e afetam a determinação dos parâmetros cosmológicos. As inomogeneidades são fenomenologicamente descritas pelo parâmetro de aglomeramento alpha e quantificadas pela equação da distância proposta por ZeldovichKantowskiDyer Roeder (ZKDR). Além disso, utilizando amostras de Supernovas e Gamma-Ray Bursts, aplicamos um teste chi quadrado para vincular os parâmetros de dois modelos cosmológicos distintos, a saber: o modelo LambdaCDM plano e o modelo com criação de matéria escura fria. Para o modelo LambdaCDM plano, vinculamos os parâmetros alpha e ­OmegaM considerando um prior gaussiano para a constante de Hubble. Realizamos também uma análise detalhada envolvendo duas calibrações distintas associadas aos dados de Gamma-Ray Bursts: uma calibração para o modelo LambdaCDM plano e outra para o modelo cardassiano. Verificamos que os resultados são fracamente dependentes da calibração adotada. Uma análise conjunta envolvendo Supernovas e Gamma-Ray Bursts permitiu quebrar a degenerescência entre o parâmetro de aglomeramento alpha e o parâmetro de densidade da matéria ­OmegaM. Considerando a calibração dos Gamma-Ray Bursts para o modelo LambdaCDM plano, o melhor ajuste obtido foi alpha = 1.0 e ­OmegaM = 0.30, com os parâmetros restritos ao intervalos 0.78 < alpha < · 1.0 e 0.26 < ­OmegaM < 0.36 (2sigma). Para o modelo com criação de matéria escura consideramos também um prior gaussiano para a constante de Hubble e as amostras de Supernovas e Gamma-Ray Bursts (calibrados para o modelo LambdaCDM plano). A degenerescência entre o parâmetro alpha e o parâmetro de criação gamma foi novamente quebrada através de uma análise conjunta das 2 amostras de dados. Para o melhor ajuste obtivemos alpha = 1.0 e gamma = 0.61, com os parâmetros restritos aos intervalos 0.85 < alpha < 1.0 e 0.56 < gamma < 0.66 (2sigma). / In this dissertation we study how the effects of matter (baryonic and dark) inhomogeneities modify the distances thereby affecting the determination of cosmological parameters. The inhomogeneities are phenomenologically described by the clumpiness parameter alpha and quantified through the equation distance proposed by ZeldovichKantowskiDyer Roeder (ZKDR). Further, by using Supernovae and Gamma-Ray Bursts separately, a chi-squared analysis was performed to constrain the parameter space for two distinct cosmological models, namely: the flat LambdaCDM model and the cold dark matter creation model. For the flat LambdaCDM model we have constrained the parameters alpha and ­OmegaM by considering a Gaussian prior for the Hubble parameter. A detailed analysis was also performed involving two different calibrations associated to the Gamma-Ray Bursts data: a calibration for the flat LambdaCDM model as well as for the cardassian model. We have verified that the results are weakly dependent on the adopted calibration. A joint analysis involving Supernovae and Gamma-Ray Bursts allowed us to break the degenerescence between the clumpiness parameter alpha and the matter density parameter ­OmegaM. By considering the calibration for the flat LambdaCDM model, the best fits obtained were equal to alpha = 1.0 and ­OmegaM = 0.30 with the parameters restricted on the intervals 0.78 < alpha < 1.0 and 0.26 < ­OmegaM < 0.36 (2sigma). For the dark matter creation model we have also adopted a Gaussian prior for the Hubble constant and the Supernovae and Gamma-Ray Bursts (calibrated for the flat LambdaCDM model) samples. The degenerescence between the clumpiness parameter alpha and the creation parameter gamma was again broken trough a joint analysis of the two data sample. For the best fits we have obtained alpha = 1.0 and gamma = 0.61 with the parameters restricted on the intervals 0.85 < alpha < 1.0 and 0.56 < gamma < 0.66 (2sigma).

Nesta dissertação estudamos como os efeitos das inomogeneidades da matéria (escura e bariônica) modificam as distâncias e afetam a determinação dos parâmetros cosmológicos. As inomogeneidades são fenomenologicamente descritas pelo parâmetro de aglomeramento alpha e quantificadas pela equação da distância proposta por ZeldovichKantowskiDyer Roeder (ZKDR). Além disso, utilizando amostras de Supernovas e Gamma-Ray Bursts, aplicamos um teste chi quadrado para vincular os parâmetros de dois modelos cosmológicos distintos, a saber: o modelo LambdaCDM plano e o modelo com criação de matéria escura fria. Para o modelo LambdaCDM plano, vinculamos os parâmetros alpha e ­OmegaM considerando um prior gaussiano para a constante de Hubble. Realizamos também uma análise detalhada envolvendo duas calibrações distintas associadas aos dados de Gamma-Ray Bursts: uma calibração para o modelo LambdaCDM plano e outra para o modelo cardassiano. Verificamos que os resultados são fracamente dependentes da calibração adotada. Uma análise conjunta envolvendo Supernovas e Gamma-Ray Bursts permitiu quebrar a degenerescência entre o parâmetro de aglomeramento alpha e o parâmetro de densidade da matéria ­OmegaM. Considerando a calibração dos Gamma-Ray Bursts para o modelo LambdaCDM plano, o melhor ajuste obtido foi alpha = 1.0 e ­OmegaM = 0.30, com os parâmetros restritos ao intervalos 0.78 < alpha < · 1.0 e 0.26 < ­OmegaM < 0.36 (2sigma). Para o modelo com criação de matéria escura consideramos também um prior gaussiano para a constante de Hubble e as amostras de Supernovas e Gamma-Ray Bursts (calibrados para o modelo LambdaCDM plano). A degenerescência entre o parâmetro alpha e o parâmetro de criação gamma foi novamente quebrada através de uma análise conjunta das 2 amostras de dados. Para o melhor ajuste obtivemos alpha = 1.0 e gamma = 0.61, com os parâmetros restritos aos intervalos 0.85 < alpha < 1.0 e 0.56 < gamma < 0.66 (2sigma). / In this dissertation we study how the effects of matter (baryonic and dark) inhomogeneities modify the distances thereby affecting the determination of cosmological parameters. The inhomogeneities are phenomenologically described by the clumpiness parameter alpha and quantified through the equation distance proposed by ZeldovichKantowskiDyer Roeder (ZKDR). Further, by using Supernovae and Gamma-Ray Bursts separately, a chi-squared analysis was performed to constrain the parameter space for two distinct cosmological models, namely: the flat LambdaCDM model and the cold dark matter creation model. For the flat LambdaCDM model we have constrained the parameters alpha and ­OmegaM by considering a Gaussian prior for the Hubble parameter. A detailed analysis was also performed involving two different calibrations associated to the Gamma-Ray Bursts data: a calibration for the flat LambdaCDM model as well as for the cardassian model. We have verified that the results are weakly dependent on the adopted calibration. A joint analysis involving Supernovae and Gamma-Ray Bursts allowed us to break the degenerescence between the clumpiness parameter alpha and the matter density parameter ­OmegaM. By considering the calibration for the flat LambdaCDM model, the best fits obtained were equal to alpha = 1.0 and ­OmegaM = 0.30 with the parameters restricted on the intervals 0.78 < alpha < 1.0 and 0.26 < ­OmegaM < 0.36 (2sigma). For the dark matter creation model we have also adopted a Gaussian prior for the Hubble constant and the Supernovae and Gamma-Ray Bursts (calibrated for the flat LambdaCDM model) samples. The degenerescence between the clumpiness parameter alpha and the creation parameter gamma was again broken trough a joint analysis of the two data sample. For the best fits we have obtained alpha = 1.0 and gamma = 0.61 with the parameters restricted on the intervals 0.85 < alpha < 1.0 and 0.56 < gamma < 0.66 (2sigma).

Während seiner normalen Funktion generiert das Gehirn starke elektrische Signale, die technisch gemessen werden können. Das schon seit über einem Jahrhundert bekannte Phänomen ermöglicht es die Signalverarbeitung im Gehirn räumlich und zeitlich zu beobachten. Heute versteht man die zellulären Prozesse die zur Generierung der elektrischen Signale in einzelnen Neuronen führen. Jedoch rekrutieren die meisten neuronalen Ereignisse große Populationen von Zellen, dessen Aktivität zeitlich und räumlich koordiniert ist. Diese Koordinierung führt dazu, dass ihre elektrische Aktivität auch weit von den Quellen gemessen werden kann, sodass die Beobachtung des Gehirns auch nicht invasiv auf der Schädeloberfläche mittels dem sogenannten Elektroenzephalogramm (EEG) möglich ist. Der zeitliche Verlauf des Signals hängt nicht nur von den Eigenschaften einzelner Zellen ab sondern auch von ihrer Wechselwirkung mit anderen Neuronen, die oft komplex oder gar nicht bekannt ist. Diese Komplexität verhindert die Auswertung der gemessen Signale im Bezug auf die Anzahl von aktiven Neuronen, die Art der Antwort (Inhibition, Exzitation), die Synchronisationsstärke und den Einfluss anderer aktiver Prozesse (wie zum Beispiel: Lernen, Aufmerksamkeit usw.). In dieser Arbeit werden die Zusammenhänge zwischen diesen mikroskopischen Parametern (einzelne Neurone) und ihrer makroskopischen Wirkung (EEG) experimentell, datenanalytisch und theoretisch untersucht. / During its normal function the brain generates strong and measurable electric signals. This phenomenon, which has been known for more than a century, makes it possible to investigate the signal processing in the brain. Nowadays the cellular processes taking part in the generation of the electric signals are well understood. However, most of the neuronal events recruit large populations of cells, whose activities are coordinated spatially and temporally. This coordination allows for summation of activities generated by many neurons leading to extracellular electric signals that can be recorded non-invasively from the scalp by means of electroencephalography (EEG). The temporal structure of the EEG signal does not depend only on the properties of single neurons, but also on their interactions that may be very complex. The complexity hinders the evaluation of the recoded signal with respect to the number of active neurons, the type of response, the degree of synchronisation and the contribution of other processes (such as, learning and attention). In the thesis, the relations between the microscopic (single-neuron) and their macroscopic (EEG) properties will be investigated by means of experimental, data-analytic and theoretical approaches.