The finite element method (FEM) has been widely applied to various medical imaging applications over the past two decades. The remarkable progress in high-resolution imaging techniques has allowed FEM to draw great research interests in computing trabecular bone (TB) stiffness from three-dimensional volumetric imaging. However, only a few results are available in literature on applying FEM to multi-row detector CT (MDCT) imaging due to the challenges posed by limited spatial resolution. The research presented here develops new methods to preserve TB structure connectivity and to generate high-quality mesh representation for FEM from relatively low resolution images available at MDCT imaging. Specifically, it introduced a space-variant hysteresis algorithm to threshold local trabecular structure that preserves structure connectivity. Also, mesh generation algorithms was applied to represent TB micro-architecture and mesh quality was compared with that generated by traditional methods. TB stiffness was computed using FEM simulation on micro-CT (µ-CT) and MDCT images of twenty two cadaveric specimens of distal tibia. Actual stiffness of those specimens were experimentally determined by mechanical testing and its correlation with computed stiffness was analyzed. The observed values of linear correlation (r2) between actual bone stiffness and computed stiffness from µ-CT and MDCT imaging were 0.95 and 0.88, respectively. Also, reproducibility of the FEM-based computed bone stiffness was determined from repeat MDCT scans of cadaveric specimens and the observed intra-class correlation coefficient was a high value of 0.98. Experimental results demonstrate the feasibility of application of FEM with high sensitivity and reproducibility on MDCT imaging of TB at distal tibia under in vivo condition.

Cystic Fibrosis (CF) is a lethal autosomal recessive genetic disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR transports anions at the apical surface of epithelial membranes and functions in many areas of the body. However in CF, loss of CFTR function in the lungs is the major source of morbidity and mortality. Replacing the defective CFTR in the lungs through gene therapy has the potential to cure the disease. Recombinant adeno-associated virus (AAV) is an effective gene transfer vector and has been used extensively to deliver genes to cells in culture. A number of clinical trials using AAV have been attempted for a variety of diseases, including CF, albeit with limited success. Poor vector transduction efficiency prevents effective gene therapy. We have previously used a technique to greatly increase the transduction efficiency of AAV in human lung tissues by selecting from a library of AAVs using a directed evolution technique. However, this evolution was performed in cultured cells and did not fully represent the in vivo environment in which the AAV would be used. In 2008, a CF pig model was developed to develop a further understanding of the mechanisms of CF and CFTR function. We hypothesized that we could use directed evolution to select for a vector in vivo using the pig, allowing gene therapy studies to be conducted in a physiologically relevant model of CF. We selected a novel AAV variant, called AAV2H22, which is closely related to AAV2 but with greatly increased transduction efficiency in pig airway epithelia. AAV2H22 displayed specific tropism for pig airway epithelia and saturated cell surface receptors, indicating specific binding in those cells. We found that AAV2H22-mediated gene transfer corrected chloride and bicarbonate transport defects both in vitro and in vivo. Importantly, bicarbonate transport was sufficient to normalize pH in the airway surface liquid, resulting in increased bacterial killing likely due to increased activity of antimicrobial peptides. To investigate the mechanics of the increased transduction of AAV2H22, capsid mutants were assayed for transduction efficiency. Two of the five amino acid differences between AAV2 and AAV2H22 lie at the surface and are predicted to alter capsid binding. This is consistent with the results showing specific binding in cultured airway epithelia. This research has important implications for gene therapy and investigations using AAV2H22 will increase our understanding of the biology needed to successfully treat CF.

The primary objective of this thesis is to develop hydrologic and hydraulic models for the Soap Creek Watershed, IA for the evaluation of alternative flood mitigation strategies and the analysis of the differences between hydrologic and hydraulic routing methods. In 2008, the state of Iowa suffered a disastrous flood that caused extensive damage to homes, agricultural lands, commercial property, and public infrastructures. To reduce the flood damage across Iowa, the U.S. Department of Housing and Urban Development (HUD) awarded funds to the Iowa Flood Center and IIHR-Hydroscience &Engineering at the University of Iowa to conduct the Iowa Watersheds Project. The Soap Creek Watershed was selected as one of the study areas because this region has suffered frequent severe floods over the past century and because local landowners have organized to construct over 130 flood detention ponds within it since 1985. As part of the Iowa Watersheds Project, we developed a hydrologic model using the U.S. Army Corps of Engineers’ (USACE) Hydrologic Center’s hydrologic Modeling System (HEC-HMS). We used the hydrologic model to evaluate the effectiveness of the existing flood mitigation structures with respect to discharge and to identify the high runoff potential areas. We also investigated the potential impact of two additional flood mitigation practices within the Soap Creek Watershed by utilizing the hydrologic model, which includes changing the land use and improving the soil quality. The HEC-HMS model simulated 24-hour design storms with different return periods, including 10, 25, 50, and 100 year. The results from modeling four design storms revealed that all three practices can reduce the peak discharge at different levels. The existing detention ponds were shown to reduce the peak discharge by 28% to 40% depending on the choice of observed locations and design storms. However, changing the land use can reduce the peak discharge by an average of only 1.0 %, whereas improving the soil quality can result in an average of 15 % reduction. Additionally, we designed a hydraulic model using the United States Army Corps of Engineers’ (USACE) Hydrologic Engineering Center’s River Analysis System (HEC- RAS) to perform a comparative evaluation of hydrologic and hydraulic routing methods. The hydrologic routing method employed in this study is the Muskingum Routing method. We compare the historical and design storms between HEC-HMS, HEC-RAS, and observed stage hydrographs and take the hydrograph timing, shape, and magnitude into account. Our results indicate that the hydraulic routing method simulates the hydrograph shape more effectively in this case.

Using both quantitative and qualitative methods of inquiry, this dissertation study undertakes an exploration of the dynamics of the social interaction in discourse co-constructed by pairs of college students in telecollaborative tandem exchanges. Two groups of participants, Mexican learners of English as a foreign language and American learners of Spanish as a foreign language, participated in video-based telecollaborative tandem exchanges where they worked in pairs to discuss topics assigned by their instructors, communicating half the time in Spanish and half in English. According to the principle of reciprocity in tandem learning, the participants switch between the roles of native speaker (NS) expert and non-native speaker (NNS) learner as they invest equal time, effort, and interest in each language part of the chats. Grounded in sociocultural theory (SCT) for second language acquisition (SLA), this study addresses research questions pertaining to (1) the distribution of talk between the members of each pair and between the language parts of the exchange, (2) the distribution of interactional resources deployed by the members of each pair to establish and maintain intersubjectivity and build a relationship, and (3) the individual experiences of participants regarding their positioning in and perspectives of the exchange. Addressing the three research questions allowed the researcher to look at the telecollaborative tandem exchanges from the perspectives of language production, social aspects of interaction, and individual experiences and perspectives to gather a deeper understanding of the tandem context. The analysis of three data sources—survey responses, chat transcripts from one chat of the semester-long telecollaborative tandem project, and post-project participant interviews—shows that the principle of reciprocity posited by tandem theorists as equal time, effort, and interest in each language part underestimates the complexity of the construct as it was created by the participants in the telecollaborative tandem interactions examined in this dissertation study. A mixed methods approach allowed the researcher to deconstruct and reconsider the construct of reciprocity in telecollaborative tandem learning. The telecollaborative tandem exchanges examined in this study were not reciprocal between language parts of the exchange in terms of language production, use of interactional resources, or tandem participant positioning. Instead, they presented complex pair relationships that used language differently in each language part to establish and maintain intersubjectivity, as well as the strong desire of the participants to position themselves and their partners as peers rather than take on the roles assumed to characterize the tandem context; that is, NS as expert and NNS as learner. In accordance with these findings, telecollaborative tandem learning should be approached with an open understanding of the concept of reciprocity in which the participants co-construct their relationship through meaningful social dialogue as peers, rather than through the roles of NS expert and NNS learner. Based on the findings of this study, the expert–learner model of reciprocity may be too rigid and too static for the dynamic context of telecollaborative tandem learning.

Recent advancements in instructional technology and interactive learning space designs have transformed how undergraduate classrooms are envisioned and conducted today. Large number of research studies have documented the impact of instructional technology and interactive learning spaces on elevated student learning gains, positive attitudes, and increased student engagement in undergraduate classrooms across nation. These research findings combined with the movement towards student-centered instructional strategies have motivated college professors to explore the unfamiliar territories of instructional technology and interactive learning spaces. Only a limited number of research studies that explored college professors’ perspective on instructional technology and interactive learning space use in undergraduate classrooms exist in the education research literature. Since college professors are an essential factor in undergraduate students’ academic success, investigating how college professors perceive and utilize instructional technology and interactive learning environments can provide insights into designing effective professional development programs for college professors across undergraduate institutions. Therefore, the purpose of this study was to investigate college professors’ pedagogical reasoning behind incorporating different types of instructional technologies and teaching strategies to foster student learning in technology-infused interactive learning environments. Furthermore, this study explored the extent to which college professors’ instructional decisions and practices are affected by teaching in an interactive learning space along with their overall perception of instructional technology and interactive learning spaces. Four college professors from a large public Midwestern university who taught undergraduate science courses in a classroom based on the ‘SCALE-UP model’ participated in this study. Major data sources included classroom observations, interviews and questionnaires. An enumerative approach and the constant comparative method were utilized to analyze the data. According to the results obtained, all the participating college professors of this study employed a variety of instructional technologies and learning space features to actively engage their students in classroom activities. Participants were largely influenced by the instructional technology and the learning space features at lesson planning and execution stages whereas this influence was less notable at the student assessment stage. Overall, college professors perceive technology-infused interactive learning environments to be advantageous in terms of enabling flexibility and creativity along with easy facilitation of classroom activities. However, they felt challenged when designing effective classroom activities and preferred continuous professional development support. Overall, college professors’ pedagogical decision making process, their perceived benefits and challenges seemed to be interrelated and centered on the learners and the learning process. Primary implication of this study is to implement effective professional development programs for college professors which enable them to familiarize themselves with student-centered pedagogy and effective classroom activity design along with the novel trends in learning space design and instructional technologies. Furthermore, higher education institutions need to devise incentives and recognition measures to appreciate college professors’ contributions to advance scholarship of teaching and learning.

The Rising Above the Gathering Storm report (National Academy of Sciences, 2007) emphasizes a need for improved science education in United States schools. Instruction, informed by assessment, has been repeatedly demonstrated to be effective for increasing students' performance. In particular, the use of curriculum-based measurement (CBM) to assist with making screening decisions has been shown to increase the likeliness of students meeting meaningful outcomes. While CBM tools for assisting with making screening decisions in reading, mathematics, and written language have been well examined, tools for use in content areas (e.g., science and social studies) remain in the beginning stages of research. In this study, two alternate forms of a new CBM tool, Statement Verification for Science (SV-S), for assisting with making screening decisions regarding students' science content knowledge is examined for technical adequacy. A total of 1,545 students across Grades 7 (N = 799) and 8 (N = 746) completed Forms A and B of SV-S the week prior to, and within two weeks after, a statewide high-stakes test of accountability including Science, Reading, and Mathematics. Obtained data were used in order to examine internal consistency, test-retest with alternate forms reliability, and evidence of criterion- and construct-related validity. Promising results were found for reliability, in particular internal consistency, while results related to evidence of criterion- and construct-related validity were less than desired. Such results, along with additional exploratory analyses, provide support for future research of SV-S as a CBM tool to assist teachers and other educators with making screening decisions.

Drug instability in solid dosage forms includes chemical or physical processes involving covalent or polymorphic transformations wherein different polymorphs possess crystal structure differences. Gabapentin chemically degrades by intramolecular cyclization to gabapentin-lactam (lactam) in the solid-state. Additionally, gabapentin undergoes polymorphic solid-state transformations. A kinetic model was developed to describe the environmental and excipient effects on chemical and physical instability associated with milling induced stress and subsequent storage under controlled temperature and humidity conditions. Reaction mixtures were generated by co-milling gabapentin Form II with various excipients. The effects of environmental conditions were studied by storing reaction mixtures at 40-60 ºC and 5-50 %RH. The chemical and polymorphic compositions of the reaction mixtures were measured as a function of time using a combination of chromatographic method, 13C ssNMR and XRPD. Degradation models that describe the relationship between polymorphs and degradation product in a series of sequential or parallel steps were devised based on analysis of the resultant concentration time profiles. Model parameters were estimated using non-linear regression and Bayesian methods and evaluated in terms of their quantitative relationship to compositional and conditional variations. In reaction mixtures composed of co-milled gabapentin and excipients, gabapentin was found to exist in three forms: anhydrous polymorph II and III and gabapentin-lactam. A fourth form (II*) was observed based on initial degradation kinetics and was hypothesized to be a crystal-disordered form generated by mechanical stress. The effect of environment moisture was to decrease the net rate of lactam formation by facilitating polymorphic transformation kinetics and crystal annealing. However, excipient blocked the catalytic moisture effect on polymorphic transformations. The key features of our model are first-order physical state transitions of II* and III to II, first-order degradation of II* to lactam and autocatalytic lactamization of II and III. For chemical transitions, no humidity effect was present but the catalytic effects of excipients on the conversion of II and III → lactam were observed. For physical transitions, excipient primarily influenced the physical state transitions of II*and III → II through its ability to interact with humidity and the degree of contact between excipient and substrate.

This dissertation presents muon charge asymmetry, fiducial differential cross section and CMS single muon trigger efficiency measurements as a function of muon pseudorapidity for inclusive W→μν events produced in proton-proton collisions at the LHC. The data were recorded by the CMS detector at a center-of-mass energy of 8 TeV and correspond to an integrated luminosity of 18.8 fb-1. Several comparisons are performed to cross-check the experimental results. Muon efficiency measurements are compared to estimated values from Monte Carlo simulations and reference values recommended by CMS physics object groups. The differential cross section and the charge asymmetry measurements are compared to theoretical predictions based on next-to-leading order and next-to-next-to-leading order QCD calculations with different PDF models. Inputs from the charge asymmetry and the differential cross section measurements for the determination of the next generation of PDF sets are expected to bring different predictions closer together and aid in reducing PDF uncertainties. The impact of the charge asymmetry on PDFs has been investigated by putting the asymmetry results into a QCD analysis at next-to-leading order and next-to-next-leading order with inclusive deep-inelastic scattering data from HERA. Significant improvement of the accuracy on the valence-quark distributions is observed. This measurement is recommended for more accurate constraints in future PDF determinations. More precise measurements of PDFs will improve LHC predictions.

This thesis consists of three chapters and investigates the issues related to liquidity risk, credit market contagion, and corporate cash holdings. The first chapter is coauthored work with Professor Jay Sa-Aadu and Associate Professor Ashish Tiwari and is titled ‘Market Liquidity, Funding Liquidity, and Hedge Fund Performance.’ The second chapter is sole-authored and is titled ‘Credit Market Contagion and Liquidity Shocks.’ The third chapter is coauthored with Steven Savoy and titled ‘Ambiguity Aversion and Corporate Cash Holdings.’ The first chapter examines the interaction between hedge funds’ performance and their market liquidity risk and funding liquidity risk. Using a 2-state Markov regime switching model we identify regimes with low and high market-wide liquidity. While funds with high market liquidity risk exposures earn a premium in the high liquidity regime, this premium vanishes in the low liquidity states. Moreover, funding liquidity risk, measured by the sensitivity of a hedge fund’s return to the Treasury-Eurodollar (TED) spread, is an important determinant of fund performance. Hedge funds with high loadings on the TED spread underperform low-loading funds by about 0.49% (10.98%) annually in the high (low) liquidity regime, during 1994-2012. The second chapter provides evidence on credit market contagion using CDS index data and identifies the channels through which contagion propagates in credit markets. The results show that funding liquidity and market liquidity are significant channels of contagion during periods with widening credit spreads and adverse liquidity shocks. These results provide support for the theoretical model proposed by Brunnermeier and Pedersen (2009) according to which negative liquidity spirals can lead to contagion across various asset classes. Furthermore, during periods with tightening credit spreads and positive liquidity shocks, the results indicate that a prime broker index and a bank index are important channels contributing to co-movement in credit spreads. This suggests that financial intermediaries play an important role in spreading market rallies across credit markets. The third chapter investigates the link between investors’ ambiguity aversion and precautionary corporate cash holdings. Investors’ ambiguity aversion is measured by the proportion of individual investors in a firm’s investor base who are hypothesized to be more ambiguity averse compared to institutional investors. We show that the value of cash holdings is negatively associated with the extent of ambiguity aversion in a firm’s shareholder base for firms that are financially constrained. Our results also show that financially constrained firms with a higher proportion of ambiguity averse investors hold less cash. These results provide support for models in which ambiguity averse investors dislike the cash holdings of firms, that are held for precautionary reasons to fund long term projects, given that the returns on long term projects are ambiguous.

In the year 589 Reccared, king of the Visigoths, called together leaders of the Catholic Church and the Visigothic nobility to meet at the Third Council of Toledo. That council marked a dramatic change in the Visigothic Kingdom and began a collaboration between the Catholic Church and the Visigothic royal government that would come to define the kingdom, and has forever colored our view of the history of Spain. This dissertation will attempt to place the events that occurred at the Third Council of Toledo into the larger context of the sixth century and will show that the union between the Catholic Church and the Visigothic royal government that occurred at Toledo III was the result of a connection between two longstanding forces in society: the efforts of a small number of provincial bishops to purify society through strict, orthodox Catholicism and the efforts of a few Visigoth monarchs to centralize the kingdom and create a political entity that would be the natural heir to official Roman legitimacy in the west as well as offer a counterbalance to the Eastern Roman Empire. Further, it will draw some connections between the work of the Catholic Church in the Suevic Kingdom, the other Germanic Kingdom that existed on the Iberian Peninsula during the sixth century, and the the Third Council of Toledo. Finally, it will show that in the immediate aftermath of the Third Council of Toledo the bishops were disappointed to find that the introduction of coercive power as a tool of instruction for bishops proved largely unworkable in the short term which led them to abandon some of their new found powers.