Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 186-210). Also available on the Internet.

Darbe pateiki žvilgsnio ir rankos(sekant vienu metu) taškinio taikinio sekimo parametrai, taikiniui judant (5 10 20 laipnsių per sekundę greičiu). Pateikti gauti sekimo parametrai: paklaidų standartinis nuokrypis, paklaidų standartinis nuokrypis po vėlinimo, vėlinimo laikas. Palyginimui pateikiami sekimo tik žvilgsniu parametrai. / In this work gaze and hand(working together) smooth pursuit target-dot, target-dot mowed by three velocities (5 10 20 degree/second). Obtained the smooth pursuit parameters: errors standart deviation, errors standart deviation after eliminated latency, latency time. For comparison the smooth pursuit was perform only gaze.

Thesis (Ph. D.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains xxiii, 251 p. : ill. Vita. Includes abstract. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Missouri--Columbia, 2004. / Typescript. Vita. Includes bibliographical references (leaves 166-179). Also issued on the Internet.

Thesis (Ph. D.)--University of Virginia, 2007. / Title from title page. Includes bibliographical references. Also available online through Digital Dissertations.

[pt] Desde o século XVI, já existia a idéia de que o poder de compra deveria influenciar no valor de cada moeda. A fim de se entender as relações entre câmbio e inflação, modelos autoregressivos lineares sempre apresentaram dificuldades para superar o passeio aleatório. Possíveis fricções em operações cambiais podem dificultar a arbitragem próxima do câmbio de equilíbrio considerado pelos agentes financeiros. À medida em que se distancia do valor considerado justo, a convergência se torna mais intensa, pois os custos já não seriam uma parcela tão relevante para o lucro potencial da operação. No modelo não-linear proposto, há dois regimes diferentes: um próximo do equilíbrio (comportamento de passeio aleatório) e um comportamento longe dele ocorrendo simultaneamente, mas com pesos variáveis. A depender do nível do câmbio em relação ao equilíbrio, um regime ganha mais peso e outro perde relevância. Essa tese tem o objetivo de avaliar o caráter preditivo do movimento cambiais. O modelo não-linear ESTAR é usado para montar cestas de moedas a serem compradas e vendidas e o retorno advindo de oscilações cambiais é computado. Por fim, incorporamos os efeitos de juros ao modelo para montar portfólios de moedas a fim de simular o retorno de um investimento usando essa estratégia. Para as cestas de moedas, o modelo gerou bons retornos e baixos riscos, tanto em termos de desvio padrão quanto em termos de drawdown. Tal característica foi observada no modelo in-sample e no out-of-sample o que indica um forte caráter preditivo. Levando em conta o efeito dos juros, os portfólios com menos moedas apresentaram retornos positivos, porém essa vantagem é perdida ao se aumentar a quantidade de moedas. / [en] Since the sixteenth century, there was already the idea that purchasing power should influence the value of each currency. In order to understand the relationship between exchange rate and inflation, linear autoregressive models always presented difficulties to beat the random walk. Possible frictions in foreign exchange operations may hinder arbitrage close to the equilibrium exchange rate considered by financial agents. As the exchange rate distances itself from the value considered fair, the convergence becomes more intense, because the costs would no longer be so relevant to the potential profit of the operation. In the proposed nonlinear model, there are two different regimes: one near equilibrium (random walk behavior) and one behavior away from it occurring simultaneously, but with variable weights. For different levels of the exchange rate relative to the equilibrium, one regime gains more weight and the other loses relevance. This thesis aims to evaluate the predictive nature of the exchange rate movement. The nonlinear model ESTAR is used to create baskets of currencies to be bought and sold and the aggregate return based on exchange rate movements is computed. Finally, we consider the interest rate effects on the model to set up currencies portfolios in order to simulate the return on an investment using this strategy. For the baskets of currencies, the model generated good returns and low risks, based on both standard deviation and drawdown. This characteristic was observed in the in-sample model and in the out-of-sample model, which indicates a strong predictive power. Considering the interest effect, portfolios with fewer currencies showed positive returns, but this advantage is lost by increasing the number of currencies.

Indiana University-Purdue University Indianapolis (IUPUI) / Coronary artery disease (CAD) is a leading cause of death among Americans and is fueled by underlying metabolic syndrome (MetS). The prevalence and lethality of CAD necessitates rigorous investigations into its underlying mechanisms and to facilitate the development of effective treatment options. Coronary smooth muscle (CSM) phenotypic modulation from quiescent to synthetic, proliferative, and osteogenic phenotypes is a key area of investigation, with underlying mechanisms that remain poorly understood. Using a well-established pre-clinical model of CAD and MetS, the Ossabaw miniature swine, we established for the first time the time course of Ca2+ dysregulation during MetS-induced CAD progression. In particular, we used the fluorescent Ca2+ dye, fura-2, to examine alterations in CSM intracellular Ca2+ regulation during CAD progression, as perturbations in intracellular Ca2+ regulation are implicated in several cellular processes associated with CAD pathology, including CSM contractile responses and proliferative pathways. These studies revealed that the function of several CSM Ca2+ handling proteins is elevated in early CAD, followed by loss of function in severe atherosclerotic plaques. Decreased intracellular Ca2+ regulation occurred concurrently with reductions in CSM proliferation, measured with Ki-67 staining. In particular, alterations in sarcoplasmic reticulum (SR) Ca2+ store together with altered function of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) were associated with induction of proliferation. Organ culture of coronary arterial segments revealed that culture-induced medial thickening was prevented by SERCA inhibition with cyclopiazonic acid (CPA). Activation of SERCA with the small molecule activator, CDN1163, increased CSM proliferation, which was attenuated by treatment with CPA, thus establishing upregulated SERCA function as a proximal inducer of CSM proliferation. Further, we demonstrated that in vitro treatment of CSM from lean Ossabaw swine with the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, increased SERCA function. However, in vivo treatment of Ossabaw swine with MetS with the GLP-1 receptor agonist, AC3174, had no effect on CAD progression and in vitro examination revealed resistance of SERCA to GLP-1 receptor agonism in MetS. These findings further implicate SERCA in CAD progression. Collectively, these are the first data directly linking SERCA dysfunction to CSM proliferation and CAD progression, providing a key mechanistic step in CAD progression.

Indiana University-Purdue University Indianapolis (IUPUI) / Cardiovascular disease is the number one cause of death for Americans. New treatments are needed for serious conditions like atherosclerosis, as it can lead to stroke and heart attack. Many types of cells contribute to the progression of cardiovascular disease, including smooth muscle cells that comprise the middle layers of arteries. Inappropriate growth and migration of smooth muscle cells into the lumen of arteries has been implicated in vascular diseases. Death associated protein kinase (DAPK) is a protein that has been found to regulate the survival and migration of cancer cells, but has not been well characterized in vascular cells. The objective of this work was to determine the signaling pathways that DAPK regulates in smooth muscle cells. These studies have focused on smooth muscle cells isolated from human coronary arteries (HCASM cells). We have determined that HCASM cells depleted of DAPK exhibit more rapid migration, showing that DAPK negatively regulates migration of vascular cells. Results from a focused RT-PCR array identified matrix metalloproteinase 9 (MMP9) as a gene that is increased in cells depleted of DAPK. MMP9 is an important enzyme that degrades collagen, a component of the extracellular matrix through which smooth muscle cells migrate during atherosclerosis. We found that DAPK regulates phosphorylation of the NF-kappa B transcription factor p65 at serine 536, a modification previously found to correlate with increased nuclear levels and activity of p65. In DAPK-depleted HCASM cells, there was more phosphorylation of p65, which causes increased MMP9 promoter activity. Additional experiments were conducted using transgenic mice in which the DAPK gene has been deleted. By studying these mice, we have determined that under some circumstances DAPK augments maximal MMP9 levels in mouse carotid arteries which have been injured by ligation surgery via other signaling pathways. MMP9 has been previously implicated as a protein that promotes vascular diseases such as atherosclerosis. Our research in identifying DAPK as a regulator of MMP9 expression identifies a new target for treatment of vascular diseases like atherosclerosis.

OBJECTIVE:Vascular smooth muscle cell (VSMC) hypertrophy and proliferation occur in response to strain-induced local and systemic inflammatory cytokines and growth factors which may contribute to hypertension, atherosclerosis, and restenosis. We hypothesize VSMC strain, modeling normotensive arterial pressure waveforms in vitro, results in attenuated proliferative and increased hypertrophic responses 48 hrs post-strain.METHODS:Using Flexcell Bioflex Systems we determined the morphological, hyperplastic and hypertrophic responses of non-strained and biomechanically strained cultured rat A7R5 VSMC. We measured secretion of nitric oxide, key cytokine/growth factors and intracellular mediators involved in VSMC proliferation via fluorescence spectroscopy and protein microarrays. We also investigated the potential roles of VEGF on VSMC strain-induced proliferation.RESULTS:Protein microarrays revealed significant increases in VEGF secretion in response to 18 hours mechanical strain, a result that ELISA data corroborated. Apoptosis-inducing nitric oxide (NO) levels also increased 43% 48 hrs post-strain. Non-strained cells incubated with exogenous VEGF did not reproduce the antimitogenic effect. However, anti-VEGF reversed the antimitogenic effect of mechanical strain. Antibody microarrays of strained VSMC lysates revealed MEK1, MEK2, phospo-MEK1T385, T291, T298, phospho-Erk1/2T202+Y204/T185+T187, and PKC isoforms expression were universally increased, suggesting a proliferative/inflammatory signaling state. Conversely, VSMC strain decreased expression levels of Cdk1, Cdk2, Cdk4, and Cdk6 by 25-50% suggesting a partially inhibited proliferative signaling cascade.CONCLUSIONS:Subjecting VSMC to cyclic biomechanical strain in vitro promotes cell hypertrophy while attenuating cellular proliferation. We also report an upregulation of MEK and ERK activation suggestive of a proliferative phenotype. Hhowever, the proliferative response appears to be aborogated by enhanced antimitogenic cytokine VEGF, NO secretion and downregulation of Cdk expression. Although exogenous VEGF alone is not sufficient to promote the quiescent VSMC phenotype, we provide evidence suggesting that strain is a necessary component to induce VSMC response to the antimitogenic effects of VEGF. Taken together these data indicate that VEGF plays a critical role in mechanical strain-induced VSMC proliferation and vessel wall remodeling. Whether VEGF and/or NO inhibit signaling distal to Erk 1/2 is currently under investigation.