Interferon (IFN)-mediated innate immune response is the first line of defense against viral infections. And interferon regulatory factor 7 (IRF7) is a potent transcription factor of type I IFNs and IFN stimulated genes (ISGs) and is known as the master regulator of type I IFN-dependent immune responses. To overcome the effects of IFN responses, viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), have evolved various strategies to interfere with the IRF7 functions. We previously found that KSHV ORF45 blocks virus-induced phosphorylation and nuclear translocation of IRF7. In chapter two, I further demonstrated the underlying mechanisms by which ORF45 inhibits the phosphorylation of IRF7 by IKKe and TBK1 and found ORF45 itself is robust phosphorylated by these two kinases and inhibits IRF7 phosphorylation competitively as a decoy substrate. So that the IFN responses do not become so excessive as to harm the host, IRF7 itself is delicately regulated at the transcriptional, translational, and posttranslational levels by cellular factors. In chapter three and chapter four, I identified two novel cellular binding partners of IRF7, activating transcription factor 4 (ATF4) and tripartite motif-containing protein 28 (TRIM28). ATF4 is the critical regulator for integrated stress responses. Viral infections trigger both innate immune responses and integrated stress responses, however the link between these two pathways is less understood. I determined that ATF4 blocks IRF7 activation by inhibiting its transcription and phosphorylation, and IRF7 increases the expression and activity of ATF4 in return. This regulatory circuit between ATF4 and IRF7 suggests the cross-regulation between innate immune response and integrate stress response. Posttranslational modifications, such as phosphorylation, ubiquitination, ans SUMOylation, are critical for delicate regulation of IRF7 activation and activity. Modification of IRF7 by small ubiquitin-related modifiers (SUMO)s has been shown to regulate IFN expression and antiviral responses negatively, but the specific E3 ligase needed for IRF7 SUMOylation has remained unknown. In chapter four, I identified TRIM28 as a binding partner of IRF7. I have demonstrated that TRIM28 also interacts with the SUMO E2 enzyme and increases SUMOylation of IRF7 both in vivo and in vitro, suggesting it acts as a SUMO E3 ligase of IRF7. Unlike the common SUMO E3 ligase PIAS1, the E3 activity of TRIM28 is specific to IRF7, because it had little effect on IRF7's close relative IRF3. Therefore, so far as we know, TRIM28 is the first IRF7-specific SUMO E3 to be reported. TRIM28-mediated SUMOylation of IRF7 is increased during viral infection. SUMOylation of transcription factors usually results in transcriptional repression. Consequently, overexpression of TRIM28 inhibits IRF7 transactivation activity, whereas knockdown of TRIM28 has the opposite effect and potentiates IFN production and antiviral responses. In summary, our results suggest that TRIM28 is a specific SUMO E3 ligase and negative regulator of IRF7. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester, 2011. / November 1, 2011. / ATF4, innate immunity, interferon, IRF7, KSHV ORF45, TRIM28 / Includes bibliographical references. / Fanxiu Zhu, Professor Directing Dissertation; Wei Yang, University Representative; Kenneth Roux, Committee Member; Thomas C. S. Keller, III, Committee Member; Hengli Tang, Committee Member.

A lot of attention has been paid to the stochastic volatility model where the volatility is randomly fluctuating driven by an additional Brownian motion. In our work, we change the mean level in the mean-reverting process from a constant to a function of the underlying process. We apply our models to the pricing of both equity and interest rate derivatives. Throughout the thesis, a singular perturbation method is employed to derive closed-form formulas up to first order asymptotic solutions. We also implement multiplicative noise to arithmetic Ornstein-Uhlenbeck process to produce a wider variety of effects. Calibration and Monte Carlo simulation results show that the proposed model outperform Fouque's original stochastic volatility model during some particular window in history. A more efficient numerical scheme, the heterogeneous multi-scale method (HMM), is introduced to simulate the multi-scale differential equations discussed over the chapters. / A Dissertation submitted to the Department of Mathematics in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester, 2012. / February 9, 2012. / asymptotic approach, equity derivative, interest rate derivative, Monte Carlo simulation, multi-scale, stochastic volatility / Includes bibliographical references. / Alec N. Kercheval, Professor Co-Directing Dissertation; Xiaoming Wang, Professor Co-Directing Dissertation; Liu, Guosheng, University Representative; Brian Ewald, Committee Member; Warren D. Nichols, Committee Member.

This dissertation examines strategies of regional integration from the perspective of second order centers (SOCs). These sites are defined in socio-political terms as the second tier within an administrative hierarchy of a regional system. The goals of this study are to develop an archaeological definition of SOCs and to use this information to model processes of regional integration. This work links our theoretical knowledge about the roles of SOCs in state-level societies to actual archaeological data, putting archaeological theory into practice. To evaluate regional integration from the perspective of these sites, it is necessary to formulate an archaeological definition of SOCs. The data collected for this study are used to develop and enhance this definition and to model processes of regional integration. This first goal of this study is achieved by performing an evaluation of potential second order centers in the Mycenaean regions of Pylos and Mycenae. The definition states that a SOC is (1) a settlement that (2) shares architectural forms, construction methods, and/or construction materials with a primary center, has (3) administrative control over economic activities (craft production), and (4) participates within a regional network as a node of trade. Several sites in each region meet the criteria set out by the SOC archaeological definition. In total, nine probable or possible SOCs were found in the Pylos region and seven in the Mycenae region. This research develops a model of regional integration, the Composite Model of Regional Integration, that is dynamic and consists of two strategies. The competition strategy is built on the idea that increasingly intensive rivalries between sites that are at similar sociopolitical levels leads to a situation in which the sites become linked together. Emergent elites at each site rely on the competitive system for their high statuses and as a conduit for prestige goods from intra- and inter-regional trade networks. In this way, competition between sites leads to a regional system of interconnected sites and elites that are reliant on the system and each other to maintain their positions. The imposition strategy follows a more conflict driven perspective, in which primary centers forcibly incorporate sites to act as regional subcenters. This study finds that both strategies were used in each Mycenaean region, and that there is a temporal component to their utilization. In general, the competition strategy is more clear in the Mycenae region, while the imposition strategy is more clear in the Pylos region. This research has implications for archaeological research in multiple areas of the world. In order to create viable social, political, and economic models it is important to focus on the various elements of a polity. SOCs represent a critical part of overall administrative and economic systems within state-level societies. A detailed study of SOCs contributes to our knowledge of this particular class of settlements as well as to our understanding of state development. / A Dissertation submitted to the Department of Anthropology in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester, 2012. / December 2, 2011. / competition, imposition, Mycenaean, regional integration, second order center, state development / Includes bibliographical references. / Lynne A. Schepartz, Professor Directing Dissertation; Daniel J. Pullen, University Representative; Glen H. Doran, Committee Member; Rochelle A. Marrinan, Committee Member.

First, we present two novel semiparametric survival models with log-linear median regression functions for right censored survival data. These models are useful alternatives to the popular Cox (1972) model and linear transformation models (Cheng et al., 1995). Compared to existing semiparametric models, our models have many important practical advantages, including interpretation of the regression parameters via the median and the ability to address heteroscedasticity. We demonstrate that our modeling techniques facilitate the ease of prior elicitation and computation for both parametric and semiparametric Bayesian analysis of survival data. We illustrate the advantages of our modeling, as well as model diagnostics, via reanalysis of a small-cell lung cancer study. Results of our simulation study provide further guidance regarding appropriate modelling in practice. Our second goal is to develop the methods of analysis and associated theoretical properties for interval censored and current status survival data. These new regression models use log-linear regression function for the median. We present frequentist and Bayesian procedures for estimation of the regression parameters. Our model is a useful and practical alternative to the popular semiparametric models which focus on modeling the hazard function. We illustrate the advantages and properties of our proposed methods via reanalyzing a breast cancer study. Our other aim is to develop a model which is able to account for the heteroscedasticity of response, together with robust parameter estimation and outlier detection using sparsity penalization. Some preliminary simulation studies have been conducted to compare the performance of proposed model and existing median lasso regression model. Considering the estimation bias, mean squared error and other identication benchmark measures, our proposed model performs better than the competing frequentist estimator. / A Dissertation submitted to the Department of Statistics in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester, 2012. / March 26, 2012. / Bayesian Analysis, Median regression, Semiparametric, Survival Analysis, Transform-Both-Sides / Includes bibliographical references. / Debajyoti Sinha, Professor Directing Thesis; Yi Zhou, University Representative; Stuart Lipsitz, Committee Member; Dan McGee, Committee Member; Xu-Feng Niu, Committee Member; Yiyuan She, Committee Member.

The purpose of this study was to determine the effect, if any, receiving music therapy services has on the satisfaction level and consumer behavior of clients at pediatric interdisciplinary clinics. Pediatric interdisciplinary clinic was defined as a clinic primarily serving clients under the age of 18 and offering at least two of the following allied health services: physical therapy, occupational therapy, speech-language pathology, behavior therapy, music therapy, art therapy, feeding therapy, or tutoring/academic support. Parents and guardians of clients receiving services at three clinics located in the states of Florida, Georgia, and Texas were surveyed using a combination of printed and online questionnaires (N = 42). Participants were divided into two groups: those who receive music therapy services and those who do not. Satisfaction levels and consumer behavior predictors were compared between the two groups. A two sample t-test for independent samples was used to analyze the results. On two of the survey items, music therapy significantly reduced satisfaction levels of clients at pediatric interdisciplinary clinics. Music therapy did not significantly improve satisfaction levels on any survey item. Though not significant, music therapy clients reported higher levels of satisfaction with four clinic services (billing services, art therapy, behavior therapy, and academic instruction/tutoring), the price paid for services at the clinic, the cleanliness and organization of the clinic space, as well as consumer behavior survey items (likelihood to continue services, likelihood to recommend services to others). Despite these findings, mean scores for all groups on all survey items indicate high levels of satisfaction. Implications of these results are discussed, as well as suggested future research. / A Thesis submitted to the College of Music in partial fulfillment of the requirements for the degree of Master of Music. / Summer Semester, 2012. / June 15, 2012. / Allied healthcare, Music Therapy, Occupational Therapy, Pediatric, Physical Therapy, Speech Language Pathology / Includes bibliographical references. / Jayne M. Standley, Professor Directing Thesis; Clifford Madsen, Committee Member; Alice-Ann Darrow, Committee Member.

We propose a Riemannian framework for shape analysis of annotated curves, curves that have certain attributes defined along them, in addition to their geometries.These attributes may be in form of vector-valued functions, discrete landmarks, or symbolic labels, and provide auxiliary information along the curves. The resulting shape analysis, that is comparing, matching, and deforming, is naturally influenced by the auxiliary functions. Our idea is to construct curves in higher dimensions using both geometric and auxiliary coordinates, and analyze shapes of these curves. The difficulty comes from the need for removing different groups from different components: the shape is invariant to rigid-motion, global scale and re-parameterization while the auxiliary component is usually invariant only to the re-parameterization. Thus, the removal of some transformations (rigid motion and global scale) is restricted only to the geometric coordinates, while the re-parameterization group is removed for all coordinates. We demonstrate this framework using a number of experiments. / A Dissertation submitted to the Department of Statistics in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester, 2011. / August 15, 2011. / Annotated curve, Riemannian, Shape analysis / Includes bibliographical references. / Anuj Srivastava, Professor Directing Dissertation; Jinfeng Zhang, Professor Co-Directing Dissertation; Eric P. Klassen, University Representative; Fred Huffer, Committee Member.

Many marine species are typified by a pelagic stage during which tiny larvae develop in the open ocean, where they are subject to high mortality and transport via ocean currents. For organisms with this life history, the study of their population dynamics is challenging because individuals are not directly traceable. Challenges to the study of population dynamics include the determination of source and sink populations, of connectivity among populations, of the mechanisms that drive the abundance and relatedness of recruits, and of how life-history characteristics mitigate or exacerbate the uncertainty of the ocean environment. My dissertation addressed these challenges in the Pacific black rockfish, Sebastes melanops, using a combination of standardized field sampling, population genetics, and mathematical modeling. Like other members of the rockfish genus, black rockfish are long-lived fishes that suffered severe declines in the 1980's due to overfishing. I collected adults from Oregon to British Columbia, and genotyped them at 8 microsatellite markers. I used isolation by distance theory to estimate the width of the dispersal kernel, as well as compared coalescent-migration matrices with Bayes factors. My results illustrated that over several generations, gene flow in the population occurred from south-to-north (a bearing in agreement with the direction of currents during the pelagic phase) and the mean dispersal distance (< 50 km) was smaller than might be expected based on an extensive pelagic phase of 60--80 days. This analysis was extended to examine the source populations for rockfish recruits that were collected between 2005 and 2009 from Barkley Sound (British Columbia), and my results suggested that substantial local recruitment occurred during downwelling regimes that favored the retention of larvae. However, the number of source populations for larvae was not correlated with the genetic diversity of recruits. I used cross-correlations to examine the relationships between oceanographic conditions, the abundance of recruits, and the genetic diversity of those recruits. I found that although there was a strong positive relationship between upwelling and the abundance of recruits, the effective number of breeders that contributed to each cohort was positively correlated with temperature. Finally, I utilized computer simulations to examine the conflicting predictions for multiple paternity for the effective size of a population (Ne). For long-lived species like rockfish, there were small differences in Ne between populations with multiple paternity and a monandrous mating systems, indicating that multiple paternity had little effect on the genetic patterns observed in this study. The results of my research can be applied to the conservation and management of this species across the US-Canada border, and may be useful in predicting how this species will respond to climate change. / A Dissertation submitted to the Department of Biology in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester, 2011. / October 14, 2011. / Connectivity, Dispersal, Larval Growth, Multiple Paternity, Pacific Rockfish, Sweepstakes / Includes bibliographical references. / Don Levitan, Professor Directing Dissertation; Jeffery Chanton, University Representative; Alice Winn, Committee Member; Peter Beerli, Committee Member; Brian Inouye, Committee Member.

Groundwater systems are open and complex, rendering them prone to multiple conceptual interpretations and mathematical descriptions. When multiple models are acceptable based on available knowledge and data, model uncertainty arises. One way to assess the model uncertainty is postulating several alternative hydrologic models for a site and using model selection criteria to (1) rank these models, (2) eliminate some of them, and/or (3) weight and average predictions statistics generated by multiple models based on their model probabilities. This multimodel analysis has led to some debate among hydrogeologists about the merits and demerits of common model selection criteria such as AIC, AICc, BIC, and KIC. This dissertation contributes to the discussion by comparing the abilities of the two common Bayesian criteria (BIC and KIC) theoretically and numerically. The comparison results indicate that, using MCMC results as a reference, KIC yields more accurate approximations of model probability than does BIC. Although KIC reduces asymptotically to BIC, KIC provides consistently more reliable indications of model quality for a range of sample sizes. In the multimodel analysis, the model averaging predictive uncertainty is a weighted average of predictive uncertainties of individual models. So it is important to properly quantify individual model's predictive uncertainty. Confidence intervals based on regression theories and credible intervals based on Bayesian theories are conceptually different ways to quantify predictive uncertainties, and both are widely used in groundwater modeling. This dissertation explores their differences and similarities theoretically and numerically. The comparison results indicate that given Gaussian distributed observation errors, for linear or linearized nonlinear models, linear confidence and credible intervals are numerically identical when consistent prior parameter information is used. For nonlinear models, nonlinear confidence and credible intervals can be numerically identical if parameter confidence and credible regions based on approximate likelihood method are used and intrinsic model nonlinearity is small; but they differ in practice due to numerical difficulties in calculating both confidence and credible intervals. Model error is a more vital issue than differences between confidence and credible intervals for individual models, suggesting the importance of considering alternative models. Model calibration results are the basis for the model selection criteria to discriminate between models. However, how to incorporate calibration data errors into the calibration process is an unsettled problem. It has been seen that due to the improper use of the error probability structure in the calibration, the model selection criteria lead to an unrealistic situation in which one model receives overwhelmingly high averaging weight (even 100%), which cannot be justified by available data and knowledge. This dissertation finds that the errors reflected in the calibration should include two parts, measurement errors and model errors. To consider the probability structure of the total errors, I propose an iterative calibration method with two stages of parameter estimation. The multimodel analysis based on the estimation results leads to more reasonable averaging weights and better averaging predictive performance, compared to those with considering only measurement errors. Traditionally, data-worth analyses have relied on a single conceptual-mathematical model with prescribed parameters. Yet this renders model predictions prone to statistical bias and underestimation of uncertainty and thus affects the groundwater management decision. This dissertation proposes a multimodel approach to optimum data-worth analyses that is based on model averaging within a Bayesian framework. The developed multimodel Bayesian approach to data-worth analysis works well in a real geostatistical problem. In particular, the selection of target for additional data collection based on the approach is validated against actual data collected. The last part of the dissertation presents an efficient method of Bayesian uncertainty analysis. While Bayesian analysis is vital to quantify predictive uncertainty in groundwater modeling, its application has been hindered in multimodel uncertainty analysis because of computational cost of numerous models executions and the difficulty in sampling from the complicated posterior probability density functions of model parameters. This dissertation develops a new method to improve computational efficiency of Bayesian uncertainty analysis using sparse-grid method. The developed sparse-grid-based method for Bayesian uncertainty analysis demonstrates its superior accuracy and efficiency to classic importance sampling and MCMC sampler when applied to a groundwater flow model. / A Dissertation submitted to the Department of Scientific Computing in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester, 2012. / March 29, 2012. / Bayesian model averaging, Data worth, Model selection criteria, Multimodel analysis, Uncertainty measure / Includes bibliographical references. / Ming Ye, Professor Directing Dissertation; Xufeng Niu, University Representative; Peter Beerli, Committee Member; Gary Curtis, Committee Member; Michael Navon, Committee Member; Tomasz Plewa, Committee Member.

Legal mandates, educational reform, and professional policy changes, have emphasized the need to promote the integration of services for students with communication impairments within the general education curriculum. However, speech-language pathologists (SLPs) continue to report the provision of primarily pull-out services with intervention content separate from the general education curriculum. SLPs report minimal use of collaboration required for evidenced-based models of service delivery--like response to intervention (RTI). Graduate training programs are challenged to provide coursework targeting competencies consistent with educational reform and professional policy efforts. Graduate students in the School of Communication Science and Disorders (SCSD) distance education master's degree program received instruction infused with experiential learning opportunities related to evidence-based practice, collaboration, problem solving models such as response to intervention, and embedding social communicative intervention in the curriculum to measure change in content knowledge and application. This study documented changes in content knowledge related to the preceding content areas, practical application of content knowledge through an action research project, and practices and perceptions related to collaboration and service delivery through questionnaires completed by graduate students and school personnel (e.g. collaborating teachers, graduate supervisors, and principals). The course led to gains in content knowledge and offered meaningful practical experiences to apply through implementation of a social communicative intervention in an elementary or secondary general education classroom. Significant change did not occur in practices related to collaboration and service delivery as supported by questionnaire results; however, some positive changes were noted in perceptions. Common themes emerged and informed results related to the selection of service delivery models and obstacles to collaboration. Overall results indicate sustained efforts may be needed to change actual behaviors in practice as future SLPs will continue to be challenged to use service delivery options compatible with including students with disabilities in general education settings. / A Dissertation submitted to the School of Communication Science and Disorders in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester, 2012. / March 13, 2012. / classroom-based services, collaboration, distance education, personnel preparation, response to intervention, speech and language therapy / Includes bibliographical references. / Juliann J. Woods, Professor Directing Dissertation; Michelle M. Kazmer, University Representative; Carol M. Connor, Committee Member; Julie A. G. Stierwalt, Committee Member.

Radie Britain (1899-1994) was a successful American composer by almost any measure. Despite her long and productive career, Britain remains on the periphery of scholarly literature. In part this could be a result of Britain's compositional style, which is reminiscent of an older romantic style in terms of its thematic development, orchestration, and harmonic palette; but it could also be a reflection of a more general absence of women composers in the musicological literature. My thesis hopes to address this situation as it regards one woman. The thesis provides a biographical sketch of the composer based on her autobiography and the composer's archive. It also discusses three pieces by Radie Britain that were inspired by American heroes: "Heroic Poem" a tribute to Charles Lindbergh, "Epic Poem" also known as "Musical Portrait of Thomas Jefferson" and "Light" dedicated to Thomas Edison. Written between 1927 and 1934, Radie Britain's compositions were performed numerous times by orchestras throughout the years of the Great Depression. These works show Britain to be a composer of her time, and a musician deserving our attention today. / A Thesis submitted to the College of Music in partial fulfillment of the requirements for the degree of Master of Music. / Summer Semester, 2012. / May 7, 2012. / American Music, Federal Music Project, Gender, Patriotism, Radie Britain, Works Progress Administration / Includes bibliographical references. / Denise Von Glahn, Professor Directing Thesis; Michael Broyles, Committee Member; Suzanne Sinke, Committee Member.