No description available.

No description available.

No description available.

No description available.

This thesis addresses the problem of quality degradation in speech produced by parameter-based speech synthesis, within the framework of an articulatory-acoustic forward mapping. I first investigate current problems in speech parameterisation, and point out the fact that conventional parameterisation inaccurately extracts the vocal tract response due to interference from the harmonic structure of voiced speech. To overcome this problem, I introduce a method for estimating filter responses more precisely from periodic signals. The method achieves such estimation in the frequency domain by approximating all the harmonics observed in several frames based on a least squares criterion. It is shown that the proposed method is capable of estimating the response more accurately than widely-used frame-by-frame parameterisation, for simulations using synthetic speech and for an articulatory-acoustic mapping using actual speech. I also deal with the source-filter separation problem and independent control of the voice source characteristic during speech synthesis. I propose a statistical approach to separating out the vocal-tract filter response from the voice source characteristic using a large articulatory database. The approach realises such separation for voiced speech using an iterative approximation procedure under the assumption that the speech production process is a linear system composed of a voice source and a vocal-tract filter, and that each of the components is controlled independently by different sets of factors. Experimental results show that controlling the source characteristic greatly improves the accuracy of the articulatory-acoustic mapping, and that the spectral variation of the source characteristic is evidently influenced by the fundamental frequency or the power of speech. The thesis provides more accurate acoustical approximation of the vocal tract response, which will be beneficial in a wide range of speech technologies, and lays the groundwork in speech science for a new type of corpus-based statistical solution to the source-filter separation problem.

No description available.

No description available.

The Estrogen Receptor alpha (ER alpha) is a multi-domain transcription factor that has been extensively studied due to its known involvement in breast cancer treatment and progression. Subsequent studies have shown coregulators are extensively involved in modulating the transcriptional activation of ER alpha and many of these proteins possess enzymatic functions. Coregulators are divided into two categories, coactivators which enhance transcriptional output and corepressors which decrease transcriptional output. One protein responsible for Angelman syndrome, E6-associated protein (E6-AP) was found to be a coactivator of ER alpha and possessed ubiquitin ligase activity; however, the ubiquitin ligase activity has been shown not to be essential to E6-AP coactivation ability. The current work was undertaken to explore the role of E6-AP in the regulation of ER alpha. E6-AP was found to play a role in a unique ligand-independent degradation pathway. Because the degradation effect was ligand-independent, it was proposed that the degradation signal mediating the event occurred through phosphorylation of E6-AP. In silico analysis of E6-AP indicated several potential phosphorylation sites on the E6-AP protein. Numerous phosphorylation sites of E6-AP were confirmed by western blot and mass spec indicating a possible phosphorylation signal mediating E6-AP/ER alpha interaction. Because it has been shown that the ligase function of E6-AP is not required for its coactivation, we then examined E6-AP coactivation of ERα in the presence of ligand. One well studied gene TFF-1 (pS2) was examined as a model ERα target gene. Estrogen-mediated transcription from TFF-1 was decreased with knockdown of E6-AP in both MCF-7 and T47D cell lines. Furthermore, under E6-AP knockdown conditions, ChIP of p300, a known histone acetyl transferase (HAT), indicated a reduced recruitment to the TFF-1 promoter in both cell lines. Interestingly, the reduced recruitment of p300 had a cell specific effect on phosphorylated RNA polymerase II (pRNA pol II) recruitment indicating cell specific functions of E6-AP. Further investigation also found a gene specific effect for E6-AP on pRNA pol II recruitment. The current work provides a new role for E6-AP as a coactivator of ER alpha in the form of a scaffold allowing creation of fully functional transcription complexes in a gene and cell specific manner.

In this dissertation, the problem of using accelerated degradation testing data for reliability estimation is studied and demonstrated. Simulation and analytical approaches have been investigated. By simulation which generates a large number of degradation paths, the reliability estimate of the product can be estimated using an empirical formation. This approach is general and has a great flexibility in estimating the reliability of a product regardless of the functional form of the degradation paths. However, it is time-consuming and sometimes can not provide efficient and accurate reliability estimates. Alternatively, the analytical approach may provide the closed-form expressions for reliability estimates for specific degradation process models. If the model fits, this approach is more accurate and efficient than the simulation approach. More importantly, when the closed-form solution exists, the optimal design of testing plans can be formulated and solved with the objective of either improving the accuracy of the reliability estimate or the accuracy of the economic loss. In addition to the statistical study of the reliability estimation, the optimal design of Accelerated Degradation Testing (ADT) plans has been investigated extensively. The objectives considered include minimizing the variance of single reliability estimate for the maintenance requirement, minimizing the weighted variances of multiple reliability estimates and minimizing the weighted economic loss associated with the reliability estimates considering multiple maintenance requirements. In the literature, this work is the first study regarding the optimal design of testing plans that considers maintenance requirements. By determining the optimal setting of decision variables such as the stress levels in the ADT experiments, the improvements in these objectives have been demonstrated using numerical examples. It can be seen that the novel methodology developed in this dissertation can significantly reduce the uncertainty of certain indices associated with the reliability estimates. This work is important in the area of reliability engineering as it indicates an efficient way of conducting accelerate degradation testing to verify the product's reliability and make management decisions under limited testing resources. / Thesis (Ph.D.)--Wichita State University, College of Engineering, Dept. of Industrial and Manufacturing Engineering. / "December 2006." / Includes bibliographic references (leaves 126-132)

No description available.