Doctoral Dissertations (before 2014 -- partial holdings)

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The Office of Graduate & Professional Education deposits all master's theses from a given semester after the official graduation date.

For the time being, this particular UDSpace collection of doctoral dissertations from before 2014 is of limited scope. However, doctoral dissertations from 1948 to present are also available online at ProQuest/UMI through Dissertations & Theses @ University of Delaware. Check DELCAT Discovery to locate print or microform copies of dissertations that are not available online.

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Investigation of chemical ubiquitination of PCNA and mechanism, inhibition of USP1/UAF1 & the molecular recognition of RNA by the pseudouridine synthase RluA
(University of Delaware, 2011) Chen, Junjun
Chapter 1: Pseudouridine synthases (Ψ synthases) catalyze the isomerization of uridine to pseudouridine (Ψ) and are present in all domains of life. The Ψ synthases fall into six families based on sequence similarity, and crystal structure of members of each family show that they share the same core fold and have one universally conserved aspartic acid residue in motif II. The cocrystal structures of the E. coli Ψ synthase RluA bound to an RNA oligomer corresponding to the anticodon stem-loop (ASL) of E. coli tRNAPhe has been determined. This structure is only the second of a Ψ synthase bound to an RNA substrate. In the RluA•RNA cocrystal, the RNA has undergone significant conformational changes from its unbound form. The isomerized uridine U32, is everted in the active site of RluA. This conformation is stabilized by the reverse-Hoogsteen base pair formed by U33 and A36 and the hydrogen bond formed between A36 and Pro 36 on RluA. To test the importance of particular interactions in the RluA•RNA cocrystal structure, kinetic studies were undertaken. RNA containing 5-fluorouridine, F5U, has been used as a mechanistic probe to distinguish the two proposed Ψ synthases’ mechanisms. RluA forms heat-sensitive and apparently covalent adduct with [F5U]RNA. Upon heating, hydrated F5U products are also formed by the collapse of the adduct of RluA. Thus, the reactivity between RluA and two altered [F5U]ASLs (A36C and U33C) was investigated. ☐ Chapter 2 to Chapter 4: The non-proteolytic function of ubiquitination has attracted increasing attention in recent years, including protein trafficking, immune response, transcription regulation and DNA damage response. Monoubiquitination of proliferating cell nuclear antigen (PCNA) plays an important role in eukaryotic translesion synthesis (TLS), a mechanism utilized by cells to synthesize past DNA lesion. One obstacle in studying eukaryotic TLS resides in the difficulty of preparing sufficient amount of ubiquitinated PCNA for in-depth biochemical and biophysical investigation. In Chapter 2, we developed a chemical approach that combines the power of intein chemistry and the facile disulfide exchange chemistry for efficient protein ubiquitination and SUMOylation. The chemically ubiquitinated PCNA is functionally equivalent to the native ubiquitinated PCNA in effecting polymerase switch between the replicative and the specialized DNA polymerases. We also demonstrated the strict requirement of PCNA ubiquitination for polymerase switch. Moreover, we probed the effect of the site of ubiquitination by preparing chemically ubiquitinated PCNAs that differ only in the position of modification. Our study revealed a surprising degree of flexibility of ubiquitin modification. ☐ Deubiquitinating enzymes (DUBs) cleave the ubiquitin moiety from mono- and poly-ubiquitinated proteins. Close to 100 DUBs have been identified in the human proteome. Abnormal cellular expression of DUBs or the loss of function due to mutation in certain DUB genes have been linked to various human diseases, including cancer and neurodegenerative diseases. Ubiquitin-specific proteases (USPs) constitute the largest DUB family. There is growing evidence suggesting that the activity of DUBs, in particular USPs, is stringently regulated through their interaction with many other protein partners. A recent global proteomic analysis of human DUBs identified 774 interacting proteins for the 75 DUBs studied. Remarkably, 34 human USPs were found to be associated with WD40-repeat proteins that adopt a β-propeller structure comprising up to eight blades. Given its widespread occurrence, the interaction between WD40-repeat proteins and USPs likely represents a fundamentally important way of regulating USP activity. Based on the reported kinetic data for USP1/UAF1 complex and USP1 alone, we hypothesize that the interaction between UAF1 and USP1 may reorganize the catalytic triad into a more productive conformation. To probe the active site conformation, in Chapter 3, cysteine-reactive small organic molecules (H2O2 or iodoacetamide) were used to determine the reactivity of the catalytic sulfhydryl group in USP1/UAF1 complex or USP1 alone. ☐ DUBs are promising targets for pharmacological intervention. The advantage of inhibiting DUB lies in the specificity of therapeutic intervention that can lead to better efficacy and eliminate nonspecific side effects seen in proteasome inhibitors. In Chapter 4, we identified small-molecule inhibitors against the USP1/UAF1 complex through high throughput screening. Two highly selective inhibitors, pimozide and GW7647, inhibit USP1/UAF1 noncompetitively with a Ki of 0.50 and 0.75 μM, respectively. We demonstrated that both compounds are reversible inhibitors that bind the USP1/UAF1 complex at a site different from the active site. Because USP1/UAF1 is involved in DNA damage response through deubiquitinating PCNA and FANCD2 in translesion synthesis and Fanconi anemia pathways, we tested USP1/UAF1 inhibitors as a sensitizer of cancer cells to DNA damaging agent, cisplatin. Our results indicated that the USP1/UAF1 inhibitors act synergistically with cisplatin in inhibiting the proliferation of cancer cells.
The effect of gait retraining on external loading and associated bony loading in runners
(University of Delaware, 2011) Fellin, Rebecca Elizabeth
In the United States alone, approximately 16.4 million people participate in running activities. Unfortunately, up to 79% of these runners are injured each year. One more serious type of injury runners sustain is a tibial stress fracture, which is an injury that requires 6-8 weeks of rest. These injuries also have an alarmingly high 36% re-injury rate. Excessive vertical loading, such as load rates and tibial shock, has been linked to an increased risk of tibial stress fractures. Many runners exhibit excessive vertical loading bilaterally. Furthermore, torsional loading, quantified by the free moment, has been also implicated in tibial stress fracture development. Although both of these risk factors involve external loading, stress fractures occur due to loading at the bony level. Gait retraining to decrease vertical loading has been effective at decreasing these loads on the trained limb that received feedback. However, the impact of gait retraining on other risk factors such as free moment, contralateral limb loading, and the bony loading along the entire region where stress fractures are most common is unknown. Therefore, this dissertation consisted of three aims to examine changes following gait retraining with respect to each of these areas. ☐ The purpose of Aim 1 was to identify if runners who have high vertical and torsional loads can decrease those torsional loads through gait retraining to decrease vertical loading. We hypothesized that runners would decrease those loads following gait retraining. We further hypothesized that the decrease in torsional loading would be less than the decrease in vertical loading as the subjects were not receiving feedback on torsional loads. We collected data on twenty runners both pre and post gait retraining during overground running at 3.7 m/s. The gait retraining protocol consisted of eight sessions of real-time visual feedback during treadmill running at a self-selected speed. This feedback was from an accelerometer attached to the anterior-medial aspect of the subject's tibia on their limb with higher loads. The results revealed that runners with high peak adduction free moments reduce this peak following gait retraining. The decrease in free moment was moderately correlated to the decrease in vertical loading. Furthermore, the subjects decreased their free moment to a lesser degree than their vertical loading. ☐ The purpose of Aim 2 was to identify if reductions in vertical loading on the trained limb transfer to the contralateral, untrained limb. We hypothesized that runners would decrease vertical load rates and tibial shock on their trained and untrained, contralateral limb following gait retraining. We collected data on ten runners both pre and post gait retraining during treadmill running at 3.35 m/s and a self-selected speed. The gait retraining protocol consisted of eight sessions of real-time visual feedback during treadmill running at a self-selected speed. This feedback was from an accelerometer attached to the anterior-medial aspect of the subject's tibia on their limb with higher loads. Runners significantly decreased vertical load rates and tibial shock following gait retraining on both limbs and both running speeds. ☐ The purpose of Aim 3 was to identify if runners with high vertical loading decrease tibial strain rates from the midshaft to distal third following gait retraining. We hypothesized that runners would decrease tibial strain rates following gait retraining. Furthermore, we hypothesized that these tibial strain rate decreases would be proportional to the subject's external, vertical loading decreases. We collected data on five runners both pre and post gait retraining during overground running at 3.7 m/s. The gait retraining protocol consisted of eight sessions of real-time visual feedback during treadmill running at a self-selected speed. This feedback was from an accelerometer attached to the anterior-medial aspect of the subject's tibia on their limb with higher loads. The results were mixed as only 4/5 subjects demonstrated decreased tibial strain rates following gait retraining. These external loading decreases were similar in magnitude to the strain rate decreases for 2/5 subjects. Additional subjects should be studied to further validate these findings.
Improving the spatial, angular, and temporal resolution in light field imaging
(University of Delaware, 2013) Yu, Zhan
A light field captures a dense set of rays as scene descriptions in place of geometry. Recent advances on computational imaging have enabled novel and efficient light field acquisition devices. For example, the new Lytro and Raytrix cameras are able to capture light fields in a single shot. However, the effective spatial resolution is reduced by the number of microlenses. For example, in Lytro, the resulting image at a desired focal plane has a resolution of 1080x1080, which is too low for photographic uses or in computer vision tasks. The acquired light field also has a low angular resolution, usually less than 10x10 for each spatial sample. This results in aliasing artifacts when synthesizing dynamic Depth-of-Field (DoF). Finally, the data size of each captured light field can easily reach 20 MB, prohibiting live streaming and processing at interactive frame rates. ☐ In this dissertation, I develop a new class of image processing algorithms and camera designs that can significantly improve the spatial, angular, and temporal resolution in light field imaging. ☐ Spatial Resolution: We develop a simple but effective technique by maneuvering the demosaicing process. We first show that traditional solutions that demosaic each individual microlense image and then blend them for DoF synthesis is suboptimal. We instead propose to demosaic the synthesized view at the rendering stage by first mapping the rays onto the refocusing plane and then conduct resampling. Our approach can significantly improve the spatial resolution while reducing the aliasing artifacts. ☐ Angular Resolution: We introduce a light field triangulation scheme to improve the angular resolution. Our triangulation technique aims to fill in the ray space with continuous and non-overlapping simplices anchored at sampled points (rays). Such a triangulation provides a piecewise-linear interpolant useful for angular super-resolution. We develop a novel triangulation algorithm that uses the depths and structures of 3D lines as constraints for producing high quality triangulations. For robust depth estimation, we further present two light field stereo matching algorithms that greatly outperform the state-of-the-art. ☐ Spatial-Angular Resolution: We further present a unified framework to simultaneously enhance the spatial and angular resolutions by stitching multiple light fields. We first estimate the warping function between two light fields and then stitch them by finding an optimal cut through the overlapping region. We further accelerate the graph-cut algorithm via a coarse-to-fine scheme. We demonstrate various stitching applications to improve the field-of-view as well as translational and rotational parallaxes of the light fields. ☐ Temporal Resolution: Finally, we construct a hybrid-resolution stereo camera system for acquiring and rendering dynamic light fields. Our system couples a high-res/low-res camera pair to replace the bulky camera array system. From the input stereo pair, we recover a low-resolution disparity map and upsample it via fast cross bilateral filters. We subsequently use the recovered high-resolution disparity map and its corresponding video frame to synthesize a light field using GPU-based disparity warping. Our system can produce racking and tracking focus effects at a resolution of 640x480 at 15 fps.
Integrating perspectives on social vulnerability to disasters and emergency management in Puerto Rico
(University of Delaware, 2013) Santos-Hernández, Jenniffer Marie
As economic losses associated to disasters continue on the rise, the study of disasters continues to show that the causes of these events are fundamentally social. In a macrocosm, this dissertation explores how the practice of emergency management may impact, address, or fail to address social vulnerability to disasters at the community level. This research explored how the emergency management organization evolved, how it functions, and how their services are delivered. In addition, it presents a case study of the 2009 explosion at a fuel storage facility in Cataño, Puerto Rico. This case study moves beyond inventories of indicators of social vulnerability to explore the interaction between the emergency management organization and community units during crisis and non-crisis times. Max Weber's ideal type of bureaucracy was used as a conceptual tool to guide the analysis and to explore management changes. The findings provide insights that could assist practitioners and researchers working in the areas of development, emergency management, bureaucratic change, decision-making, and policy making.
A life less valuable? Adjudication and sentencing outcomes for perpetrators of child homicide.
(University of Delaware, 2013) Poteyeva, Margarita
Killing a child almost universally galvanizes great outrage among the public. Despite this condemnation, little is known about how and if this abhorrence of killing a child translates into criminal justice practices. The purpose of this dissertation is to advance our understanding about the imposition of the law in cases of child homicide using a mixed-method design. The two general research objectives of the current study are: (1) to explore whether there are any differentials in the application of the law (e.g. decisions to prosecute, probability of conviction for offenders, and sentences received) for those who kill children compared to those who kill older victims; (2) to gain insight into the moral gradation of child homicide by exploring whether certain types of child homicide or certain perpetrators of the crime are treated more harshly than others. ☐ Quantitative analysis of a nationally representative data collected from prosecutors' offices in 33 large urban counties revealed that while killing a child did not have any effect on the probability of conviction, those who killed children received significantly shorter sentences than those who killed older victims. Being a mother-offender exuded a significant influence over the sentencing decision of the courts. ☐ Thematic and qualitative content analyses of data from the State of Maryland showed that the majority of death eligible cases with child victims either originated in a romantic conflict or involved a sexual assault on the child. No definitive conclusions could be drawn about the criteria that state attorneys in Maryland considered in determining whether or not to seek capital punishment in a particular child homicide case. In fact, there were several instances where legally similar crimes and offenders received different treatment. No female defendant in the Maryland sample was tried capitally, including the two women who were mothers to their victims. Contrasting these cases with female child homicide perpetrators who were sentenced to the death penalty in other states, however, suggests that prosecutors need to overcome a number of challenges to successfully portray female defendants as death-worthy.
Reading matter: animals, vegetables, and media in Renaissance England
(University of Delaware, 2012) Calhoun, Joshua
Reading Matter explores the poetic interplay of words and matter in sixteenth- and seventeenth- century English texts. Made of recycled clothes, slaughtered animals, and felled trees, books in Renaissance England were filled with visible traces of ecological matter. Reading Matter demonstrates that the flora and fauna from which a text was made were legible, significant elements of its poetic form. Attending to the ecologies of writing and reading in sixteenth- and seventeenth-century England, this dissertation seeks to first recover and then to read those organic elements of Renaissance texts that both inflect meaning and indicate much about the intertwined acts of poesis and textual production in Renaissance England. I consider how plant fibers in the pages of printed and written texts were legible to Renaissance readers, how animals became illegible or invisible in paper even as their boiled down body parts allowed readers to make themselves legible in the margins of their printed books, how blots on a page make legible that which one might wish to obliterate, and how trees might be read, misread, and ventriloquized on the stage of the wooden Globe theater. ☐ More broadly, by studying the negotiations between poetics and ecology in Renaissance texts and by drawing on critical approaches such as material culture studies, book history, and historical formalism, Reading Matter seeks to outline a scholarly reading strategy that attends to the natural history of books, to both the function and the form of the organic matter used to mediate human ideas. Though focused on Renaissance texts, the project offers a methodology by which others might interrogate the textual ecologies of millennia-old Eastern palm leaf books, eighteenth-century Japanese texts, post-colonial Caribbean texts, or the latest iPad.
Not so obscure a challenge: battered female migrants and public policies in the United States and Greece
(University of Delaware, 2011) Wasileski, Gabriela
Immigration is becoming an increasingly important policy concern both in the U.S. and Greece, and also in many other nations. Importantly, there is an ever-growing number of women who migrate, many of whom are undocumented. Violence against immigrant women is nearly impossible to estimate. However, immigrant women who are abused face multiple barriers to seeking legal protection from the abuse as a result of their migration status. In many cases, immigrant women are unaware of the protection afforded to noncitizens, or the legal protection is limited so they may fear deportation from being exposed as noncitizens or fear the loss of custody of their children. Those immigrants who entered the country through a family reunion program are awarded derivative immigration status, so they can join their spouses in the United States. Consequently, a battered immigrant's ability to obtain or maintain lawful immigration status may depend on her relationship to her United States citizen or lawful permanent resident spouse and his willingness to file an immigrant relative petition on her behalf. ☐ Despite the increase in female migration, there is a paucity of research on gender issues within regularization and family programs. This study sheds light on how the migration status of battered immigrant women affects their options for seeking a remedy from interpersonal violence. Moreover, this research highlights how migration policies in Greece and the United States interfere with social and legal protection of undocumented immigrant battered women.
Pathogenomic approaches to characterizing the avian host innate immune response to microbial infection
(University of Delaware, 2012) Maughan, Michele Nancy
The avian innate immune response is activated within hours of infection. While it is difficult to prevent infection by a pathogen, clinical signs of disease can be ameliorated once the host-pathogen interactions are elucidated. Host-pathogen interaction research has predominantly focused on the adaptive immune response and cell signaling events later in infection; recently however, the innate immune response and early signaling events have garnered increased attention as another area worthy of investigation and intervention. Cells of innate immunity serve as the first-responders to infection, their signaling and antigen presentation is critical to the development of a protective adaptive immune response, and the cellular products of their activity (cytokines, reactive oxygen species, complement, etc.) are responsible for many of the clinical signs associated with disease. ☐ Avian immunology research is expanding quickly due to the growing knowledge base of the chicken cytokines, Toll-Like Receptors (TLRs) and their immune signaling pathways. Our aim was characterize the avian innate immune response to microbial infection by utilizing a pathogenomics approach. By performing microarray experiments using our Avian Innate Immune Microarray (AIIM), we were able to measure the transcriptional host immune response to several important avian pathogens. Furthermore, by performing immunotherapeutic interventions using TLR agonists prior to challenge with highly pathogenic avian influenza virus, we were able to extend survival time of treated birds by 14% (p<0.01). This project has led to the characterization of the avian innate immune in different avian species, to different pathogens, at early time points throughout infection, and with and without the aid of a pre-treatment.
Metabolic flux analysis of mammalian cell metabolism using multiple isotopic tracers and mass spectrometry
(University of Delaware, 2012) Ahn, Woo Suk
Metabolic flux analysis (MFA) is a powerful technology to characterize intracellular metabolism in living cells using isotopic tracers and mass spectrometry. Therefore, in the past two decades, MFA techniques have been developed to study biological systems. However, the applications of MFA for mammalian cells have been limited due to the complexity of cellular metabolism even though mammalian cells are key platforms for biopharmaceutical production and biomedical research. Here, we present two applications for glycolysis and gluconeogenesis systems. First, we describe the analysis of metabolic fluxes in CHO metabolism at fed-batch mode. We established two metabolic models of CHO cells for non-stationary and stationary 13C-MFA. It was found that cellular metabolism in CHO cells were significantly rewired from exponential growth to stationary phases during culture. The results provide a solid foundation for applications such as cell line development and medium optimization. Second, we describe gluconeogenesis metabolism of Fao rat hepatoma cells perturbed by transcription factors. Using multiple isotopic tracers and combined 13C-MFA, we observed the regulations of metabolic fluxes by transcriptional activators and inhibitors for gluconeogenesis metabolism. The discovery and the applied MFA techniques can allow us to evaluate the pharmaceutical drug for metabolic disease, e.g. Type II diabetes. And finally, we provide the comprehensible procedures to be considered for 13C-MFA technique: isotopic and metabolic stationarity, isotopic tracer design, key measurements, multiple isotopic tracers and model validation.
Monstrous creators: the female artist in nineteenth-century women's gothic
(University of Delaware, 2012) Miller, Kathleen A.
Using archival research, as well as literary, cultural, and media criticism and the theoretical frameworks of women's studies and disability studies, this dissertation creates a new understanding of the "Female Gothic," as it demonstrates that the presence of the artistic heroine is the genre's true defining feature and that the issue of women's art is its much-contested focus. The work analyzes distinctions among nineteenth, twentieth, and twenty-first-century figurations of the female artist in Gothic texts by women across a variety of media, from Jane Austen's novel Northanger Abbey through Sandra Goldbacher's Neo-Victorian film, The Governess. It illuminates how and why anxieties regarding women's economic and social independence, gender norms, sexuality, ethnic and racial difference, physical disability, and questions of representation have been and continued to be filtered through a Gothic lens.
Tuning material properties via peptide design and photopolymerization of self-assembled peptide based hydrogels
(University of Delaware, 2009) Rughani, Ronak
Self-assembly of de novo designed peptides is a promising approach towards fabrication of functional materials. Hydrogels are one such class of materials, which are highly hydrated and mechanically rigid, and show potential as scaffolds for tissue engineering and drug delivery applications. Schneider and Pochan labs have developed a strategy to fabricate three-dimensional scaffolds for biomedical applications employing self-assembling beta-hairpin peptides. These 20 amino acid peptides can be triggered to fold and self-assemble in response to environmental cues such as pH and ionic strength, which then leads to formation of a physically crosslinked mechanically rigid hydrogel. A hallmark of these hydrogels is that they can be syringe delivered to a target site with spatial and temporal resolution. This property has been investigated towards development of injectable hydrogels for therapeutic and cellular delivery. ☐ An important criterion for development of scaffolds for tissue engineering applications is that the mechanical properties of the engineered scaffold should be similar to the mechanical properties of the native tissue to restore normal function. A limitation of many physically crosslinked hydrogels is that they are mechanically weak. A potential approach to enhancing the mechanical properties of these hydrogels includes formation of covalent crosslinks through chemical modification of the peptide sequence. This thesis specifically focuses on molecular level design of stimuli responsive self-assembling peptides to fabricate hydrogels with enhanced mechanical properties. In particular, two avenues were investigated to construct mechanically rigid hydrogels. First, the beta-hairpin peptides were covalently modified with photopolymerizable groups at specific positions to allow covalent crosslinking of the hydrogel network. In addition, peptide-polymer hydrogel constructs were prepared using self-assembling peptides and bifunctional polymers to create interpenetrating network hydrogels with enhanced mechanical properties. The material rigidity of the interpenetrating networks could be modulated depending upon the method of its preparation. Second, self-assembling, three-stranded antiparallel beta-sheets were designed. These peptides exhibited faster kinetics of self-assembly and formed mechanically more rigid hydrogels than their beta-hairpin counterpart. The mechanical properties of the gels formed by the three-stranded peptides were further modulated by varying the hydrophobicity of the turn region residues. ☐ The results described in this thesis demonstrate that peptide-based hydrogel scaffolds with tailored mechanical properties can be constructed through molecular level design. These hydrogel materials show potential for use as load bearing substitutes for tissue engineering applications.
Streamlining internationalization strategies for the Department of Education at a Mid-Atlantic State University: context and recommendations
(University of Delaware, 2002) Tigan, Anna
This Educational Leadership Portfolio (ELP) provides recommendations on internationalization strategies for the Department of Education (DoE) at a Mid-Atlantic State University (MASU). These recommendations are based on the premises that most U.S. institutions of higher education are responding to global challenges and pressures to internationalize their programs, curricula, and degree offerings. Findings of this portfolio demonstrate that a given DoE has the capacity to build on internationalization practices parallel to university-wide strategies while adhering to its own specific goals. ☐ Artifacts illustrate the efforts I made to develop these recommendations. Efforts began with conducting literature and policy reviews on the topic. I also conducted an organizational review of a sponsoring agency as an illustrative example of how international partners might differ from U.S. higher education institutions in their approach of considering what constitutes a reliable institution for international students. Understanding these nuances will save U.S. higher education institutions time and money because principles of customer service and stakeholder engagement are a priori present in the U.S. higher education system (Lapovsky, 2019). Similarly, when U.S. higher education institutions engage with international sponsors, they need to understand that successful partnerships are a result of accepting and understanding the norms and principles of operation as seen by the sponsors. Sometimes (as discussed in Appendix D) international institutional partners have different management mechanisms than U.S. counterparts. ☐ Next, I developed a program evaluation plan for an international professional development program currently administered by MASU. Although conducting a longitudinal study for programs like this will be a challenge, recommendations provided in the artifact can be considered in the context of similar customized programs that the Department of Education can initiate with other global partners. I then conducted a comparative analysis of written strategic institutional plans of MASU’s comparator institutions or Schools/ Departments of Education to analyze how internationalization is articulated in those plans and what specific initiatives serve as a sign of success for those institutions. Finally, through conducting a faculty survey I was able to identify the perceptions of the DoE faculty towards different aspects of internationalization and identify the areas of interest for further internationalization. ☐ As a result, I developed four recommendations that the Department of Education at MASU can consider to potentially streamline efforts in internationalization. These recommendations include forming a faculty task force; expanding on communication and interaction with institutional partners and volunteer ambassadors to expand on domestic internship opportunities in international education; conducting educational seminars for faculty and staff to explain the benefits of internationalization; and capitalizing on the Department’s domestic and international reputation by promoting its programs to international students and scholars. These recommendations, if implemented in whole or in part, can serve as a solid ground for continuous internationalization of the Department of Education at MASU. The University already demonstrated strong commitment to internationalization by incorporating internationalization strategies and initiatives in the Strategic Plan and participation in the American Council on Education (ACE) Internationalization Laboratory for the 2019-2020 cycle. Because ACE Internationalization Lab focuses on strategies developed for institutions rather than individual departments, recommendations of this ELP focus on the DoE’s capacity and articulated interest in internationalization and how those fit with institutional mandate for internationalization.
Incorporating groups, collective behavior, and information visualization in agent-based models of evacuation
(University of Delaware, 2013) Best, Eric
This dissertation is intended to advance research in building evacuation modeling through the introduction of detailed social groups, collective behavior, and improvements in information visualization. The model built as a part of this dissertation makes significant original contributions to both input and output of building evacuation models. ☐ Regarding inputs, this work prototypes new ways to catalog social groups, leadership, and the concept of supra force - a combination of high density, contraflows of crowds, and environment. The central difference between this model and previous efforts is the role of group affiliations. The effort resulting from this dissertation, SocEvac, creates a three-layer decision tree for most agents, who have to balance individual and group responsibilities while attempting to avoid supra force. This interaction of individually optimal exit paths and social responsibilities creates significantly more contraflow situations as agents attempt to locate and evacuate with their loved ones. These contraflows impede efficient evacuation, helping to explain scenarios such as the Station nightclub evacuation; where there were significantly more fatalities then would have been expected based on population and number of exits. ☐ On the output side, this work creates new methods to examine simulation models in real-time, and suggests new methods of measurement to determine what makes an accurate model. The real-time visualization methods allow for researchers to quickly understand what is happening while a model is running. These visualizations allow for users of a simulation to control what features they want to highlight in a model in real-time. The new methods of output measurement center around tracking agents as individuals, cataloging outcomes of agents each modeling a real-world counterpart complete with demographics and relationships. By transitioning away from aggregate population tracking and focusing on individuals, it is now possible to compare models to an entire evacuation narrative instead of only attempting to recreate end results. ☐ These improved inputs and outputs result in the most descriptive model to date of population movements during the Station nightclub fire in 2003. More than ten years after the fire, I believe the SocEvac model can finally begin to explain the complex events that led to the high fatalities and unconventional exit paths of the evacuation. ☐ While this dissertation focuses on one scenario, the underlying program can be used to model almost any building evacuation. This platform is designed to inspire other model builders to consider adding group social behaviors to models.
Understanding the flavoenzyme human augmenter of liver regeneration: biochemical and structural perspectives
(University of Delaware, 2013) Ramadan, Stephanie Aron
Augmenter of liver regeneration (ALR) is a multifaceted protein with biological roles including, but not limited to, disulfide bond formation, mitochondrial fission and fusion, spermatogenesis and activation of the MAP kinase pathway. This dissertation explores kinetic, thermodynamic and structural aspects of this protein. The first three Chapters provide background information on disulfide bond formation, the ERV/ALR family of proteins and biological roles of ALR, respectively. In Chapter 4, we determine the rate-limiting step of this flavin-dependent enzyme during the oxidation of the model substrate dithiothreitol by molecular oxygen. We also determined the redox potential of the redox-active disulfide proximal to the FAD cofactor and gained new insight into the formation and stabilization of the charge-transfer intermediate. Chapters 5 and 6 investigate the structural and functional consequence of replacing sulfur with selenium in both a random (Chapter 5) and specific (Chapter 6) manner. The final Chapter briefly describes the structure of two active site mutants of ALR, C142S and C142A. The C142S mutation crystallized with the charge-transfer interaction intact while the C142A construct was susceptible to oxidation that resulted in a cysteine sulfinic acid at position 145.
A bail of two cities: Atlanta vs. Philadelphia, the first criminal court phase
(University of Delaware, 2012) Starks, Brian Chad
This study examines bail operational procedures in Atlanta and Philadelphia. These two urban cities were chosen to provide a comparative analysis of bail systems based on geographical location (northeast and south). The comparison with an agency in the South is being done to examine the thesis in the criminal justice literature that the South has different criminal justice practices than most other locations. Specifically, race/ethnic disparities in arrest rates, trial outcomes and sentencing practices provide support for this thesis. Conducting an organizational analysis of the bail system will help structure the methodology for the project. The objective is to investigate the individuals‟ roles, the group process and the structure of the organization of bail in order to provide clarity on how the system(s) actually work. The social organization of both locales offers more insight to how the administration of bail produces disparate outcomes. This dissertation offered a more holistic view of operational bail procedures.
Lord Byron and the cosmopolitan imagination, 1795-1824
(University of Delaware, 2011) Steier, Michael P.
Following George Gordon, Lord Byron across Britain, Europe, and the Eastern Mediterranean, "Lord Byron and the Cosmopolitan Imagination, 1795-1824" traces Byron's cosmopolitanism to its foundations in Greek Cynical philosophy and to its founder, Diogenes, Byron's self-confessed mentor. The Cynics are commonly regarded as the first cosmopolitans; yet the cosmopolitanism they practiced is quite different from the cosmopolitanism we value today. Instead of stressing a need for social progress and global interconnectedness, the Cynics chose to live outside of society, challenging its conventions and declaring themselves to be citizens of the cosmos. I argue that Byron followed Cynical ideas closely and, as a Cynical cosmopolitan, rejected the theories of cultural unity and social progress that had become popular during the Enlightenment. My first two chapters, which focus on Byron and Anglo-Scottish relations, chart the development of Byron's internationalism in English Bards and Scotch Reviewers and Hints from Horace, two early neoclassical satires rarely studied as cosmopolitan texts. The next two chapters, which focus on Byron's travels in Europe and the Eastern Mediterranean, explore the limits of universal cosmopolitanism in Childe Harold's Pilgrimage, Byron's first poem explicitly to adopt a Cynical philosophy. My last chapter focuses on Byron's later years when he internalized the principles of Cynical philosophy in Don Juan and The Age of Bronze. The conclusion brings the full scope of Byron's cosmopolitan into focus by examining the urbane rhetoric of the prose writings he prepared in defense of Alexander Pope in 1820 and 1821.
"I've lost my city": law, community, and immigration under colorblind neoliberalism
(University of Delaware, 2011) Longazel, Jamie G.
This research is centered around Hazleton, Pennsylvania's Illegal Immigration Relief Act (IIRA). Passed in 2006 and subsequently ruled unconstitutional (i.e., Lozano et al. v. Hazleton), the IIRA sought to punish landlords and sanction businesses who rented to or hired undocumented immigrants and to make English the official language of the city. Taking a constitutive approach to the study of law and society and using a variety of ethnographic and qualitative methods (e.g., archival analysis, in-depth interviews, focus groups, participant observation, and media analysis), this research explores how and to what effect white working class residents, politicians, and activists have made sense of social, demographic, and economic change in Hazleton. Set in the context of the neoliberal political economic climate and a post-Civil Rights era characterized by colorblind racial discourse, this dissertation argues that we can understand the IIRA as a reassertion of local collective identity made in the face of change and constructed along racial rather than class lines. I proceed in two parts. First, I explore how Hazleton residents came to misinterpret their city's economic struggles as an undocumented immigrant "invasion." In this regard I explore how local elites (e.g., developers, politicians) injected hegemonic "pro-growth" and "tough on crime" narratives with sentiments that appealed to residents' nostalgia and sense of community solidarity. Second, I explore the activism that followed the passage of the IIRA. Here I describe how a vision of rights emerged that coincided with community imaginings, leaving Hazleton's newcomers and their advocates in a tenuous position despite the legal victory in Lozano. Taken together, this dissertation illuminates how social upheaval mobilizes discourses of `community' and `rights.' Ultimately, however, neither community nor rights are realized on the ground. In contrast, local hierarchies are strengthened and attention is diverted away from core economic troubles to the detriment of white working class residents and Latino/a immigrants alike.
Characterization of surface plasmon resonance (SPR) active nanohole array sensing platforms: development and application of novel instrumentation and methodology
(University of Delaware, 2013) Kegel, Laurel L.
Surface plasmon resonance (SPR) active nanohole array substrates offer a diverse biosensing platform with high sensitivity and unique characteristics. This dissertation investigates the sensitivity and fundamental SP features of various nanohole array substrates and demonstrates higher sensitivity than conventional continuous gold platforms, tunability to specific analytes, and great enhancement of the local field intensity. Novel instrumentation and analytical techniques are developed and utilized to assess the nanohole array SPR sensing substrates in the near infrared as well as with interaction of other nanostructures. The nanohole array substrates are evaluated throughout the near-infrared (NIR) region by novel SPR instrumentation and methodology that extends the working SPR wavelength range and measurement reliability. Development of a robust NIR-SPR instrument allows access to higher wavelength ranges where sensitivity is improved and novel SP modes and plasmonic materials may be investigated. Different aspects of the NIR-SPR instrument, including temporal stability, mechanical resilience and sensitivity, are evaluated and presented. Furthermore, a method is developed for improving precision and accuracy of empirically determined SP penetration depth, a merit of SPR spectroscopy sensitivity. The technique incorporates an adsorbate-metal bonding effect which improves the consistency in the penetration depth value calculated at different adsorbate thicknesses from 41-1089% relative deviation (without bonding effect) to 2-11% relative deviation (with bonding effect). It also improves the experimental agreement with theory, increases the accuracy of assessing novel plasmonic materials and nanostructures, and increases the precision in adsorbate parameters calculated from the penetration depth value, such as thickness, binding affinity, and surface coverage. Utilizing this NIR-SPR instrument and improved technique for calculation of penetration depth, the sensitivity and various SP modes of the nanohole arrays throughout the NIR range are evaluated, and an improvement in sensitivity compared to conventional continuous gold is observed. Both the Bragg SPs arising from diffraction by the periodic holes and the traditional propagating SPs are characterized with emphasis on sensing capability of the propagating SPs. There are numerous studies on the transmission spectroscopy of nanohole arrays; however this dissertation presents one of the few studies in Kretschmann mode, and the first in the near infrared, where greater surface sensitivity is observed. The sensitivity profile of various nanohole array parameters (periodicity, diameter, excitation wavelength) and SP modes is also presented. Further control and enhancement of the SP field is pursued by interaction between nanohole array substrate and nanoparticles to exploit field intensification between plasmonic structures, i.e. gap mode enhancement. Under specific conditions, the SPs couple together and the electric field between the structures is amplified and localized, which may be exploited for sensing purposes and surface enhanced techniques, including tip enhanced Raman spectroscopy (TERS) or surface enhanced Raman spectroscopy (SERS). A technique for observing nanohole array-nanoparticle distance dependent SP interaction is developed and utilized to demonstrate SP interaction. Scanning probe microscopy controls the position of a single nanoparticle (SNP) affixed to an atomic force microscope probe, and the location specific interaction of the SNP-nanohole array surface plasmons is measured by darkfield surface plasmon resonance spectroscopy. Coupling of the nanoparticle to the nanohole array exhibits a maximum when the SNP resides within a nanohole, which resulted in a maximum SPR wavelength shift of 17 nm and an increase in scatter intensity. This dissertation presents the first empirical observations of SPM controlled gap mode enhancement of more complex nanostructures and allows for optimization of positioning prior to use in sensing.
Acoustic characterization of ultrasound contrast microbubbles and echogenic liposomes: applications to imaging and drug-delivery
(University of Delaware, 2013) Paul, Shirshendu
Micron- to nanometer - sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes, are being actively developed for possible clinical implementations in diagnostic imaging and ultrasound mediated drug/gene delivery. Contrast microbubbles (1-10 micron in diameter) contain a low solubility gaseous core stabilized by an encapsulation made of lipids/proteins/polymers/surfactants. Echogenic liposomes (ELIPs), which combine the advantages of liposomes such as biocompatibility and ability to encapsulate both hydrophobic and hydrophilic drugs with a strong reflection of ultrasound, are also excellent candidates for concurrent ultrasound imaging and drug delivery applications. The primary objective of this thesis is to characterize the acoustic behavior and the ultrasound-mediated content release of these contrast agents for developing multi-functional ultrasound contrast agents. The first part of this thesis reports the investigation of encapsulated microbubbles utilized as ultrasound contrast agents, whereas the second part reports the experimental characterizations of echogenic liposomes (ELIPs) and echogenic polymersomes. Contrast microbubbles are nonlinear systems capable of generating a subharmonic response i.e., response at half the excitation frequency, which can improve image quality by providing a higher signal to noise ratio. However, design and development of contrast microbubbles with favorable subharmonic behavior requires accurate mathematical models capable of predicting their nonlinear dynamics. To this goal, ‘strainsoftening’ viscoelastic interfacial models of the encapsulation were developed and subsequently utilized to formulate a modified form of the Rayleigh-Plesset equation to model the nonlinear dynamics of these encapsulated microbubbles. A hierarchical twopronged approach of modeling — a model is applied to one set of experimental data to obtain the model parameters (material characterization), and then the model isvalidated against a second independent experiment — is demonstrated in this thesis for two lipid coated (Sonazoid™ and Definity®) and a few polymer (polylactide) encapsulated microbubbles. We performed in vitro acoustic characterization with these contrast microbubbles, i.e., determined the material properties of their encapsulations and compared model predictions with experimental observations. The nonlinear elastic models developed were successful in predicting several experimentally observed behaviors e.g., low subharmonic thresholds and “compression-only” radial oscillations. Results indicate that neglecting the polydisperse size distribution of contrast agent suspensions, a common practice in the literature, can lead to inaccurate predictions and unsatisfactory results. Recent numerical investigations of the nonlinear dynamics of encapsulated microbubbles from our group contradicted previously published experimental results on the dependence of subharmonic behaviors on ambient pressure. We wanted to investigate this issue through new in vitro acoustic experiments by designing a modified experimental setup. Preliminary results indicate that the previously published conclusion that subharmonic response from contrast microbubbles linearly decreases with increasing ambient pressure might not be correct under all excitation conditions; it may both increase or decrease under appropriate excitations in conformity with the results of numerical investigations. Experimental characterization of the ELIPs and polymersomes was performed with the goal of demonstrating their potential as ultrasound agents with simultaneous imaging and drug/gene delivery applications — ‘dual-purpose’ contrast agents. Carefully performed experiments conclusively demonstrate the ultrasound reflectivity (echogenicity) of the liposomes prepared using an established protocol. Although, no subharmonic response from these ELIPs was observed, altering the constituents of the lipid bilayer and polymerizing it generated a subharmonic response indicating that the echogenic properties of ELIPs can be controlled by altering the preparation protocol. Our results indicate that the freeze-thaw cycle and lyophilization in presence of mannitol followed by reconstitution in a buffer was critical for generating echogenic response from these liposomes. A finite amount of mannitol (above 100 mM) proved critical for echogenicity, but increasing the mannitol concentration above that amount did not change the echogenicity. Lyophilized powders create a polydisperse suspension of liposomes upon reconstitution, which in turn results in a response without a distinct resonance peak. We believe that the echogenicity of the liposomes results from the larger diameter liposomes present in this polydisperse suspension. In spite of the conclusive experimental evidence of echogenicity, the underlying mechanisms are not completely understood primarily due to the uncertainty regarding the exact location of the gas pockets. An accurate knowledge of the locations and dimensions of the gas pockets is critical for developing improved mathematical models of their acoustic behaviors. For the experimental validation of the concept of ‘dual-purpose’ contrast agents, four novel formulations were investigated—a lipopeptide conjugated ELIP formulation that can be triggered by the extracellular enzyme matrix metalloproteinase-9 (MMP- 9), a polymer coated redox triggered ELIP formulation for cytosolic drug delivery, pH sensitive liposomes with tunable echogenicity capable of drug-release in mildly acidic micro-environment and redox sensitive echogenic polymersomes. Both in vitro acoustic studies and ultrasound imaging (the latter performed in NDSU by our collaborators) demonstrated the echogenicity of each of these formulations. Although, ultrasound excitation (< 5 MHz) alone was incapable of causing optimal release of contents, a dualtriggering strategy proved successful. Application of ultrasound in conjunction of other triggers (e.g., enzyme, pH, redox) showed significant enhancements (10-20%), which resulted in a total release of up to 80-90%. Considering these experimental results, it can be concluded that these novel formulations have the potentials for simultaneous imaging and therapeutic applications. These contrast agents hold the potential of providing powerful treatment strategies for many diseases, including cardiovascular ones and various cancers.
Solid-state NMR studies of structure and dynamics of HIV-1 capsid (CA) protein assemblies
(University of Delaware, 2013) Han, Yun
There are around 34 million people in the world living with HIV-1, which is a causative agent of acquired immunodeficiency syndrome (AIDS). AIDS has become the ninth leading cause for death of people ages 25-34 in the US. Even though highly active antiretroviral therapy (HAART) showed effectiveness in suppressing the virus replication and significantly prolonged the patients lives, AIDS still remains an uncured disease. To develop new therapies, atomic-level understanding of the mechanism of HIV-1 lifecycle, including the structures of the various protein assemblies, is needed. The Gag polyprotein and its component capsid (CA) protein are essential constituents of the HIV-1 life cycle, and have recently attracted attention as targets for drug development. However, the atomic resolution structure and the dynamics of Gag and CA protein assemblies and their complexes with small-molecule inhibitors are not available because these assemblies are not amenable for characterization by traditional structural biology methods, X-ray diffraction and solution NMR spectroscopy. Solid-state NMR spectroscopy has the unique capability of providing atomic-level structural and dynamics information in large protein assemblies. The focus of this dissertation is establishing solid-state NMR spectroscopy as an atomic-level probe of structure and dynamics in HIV-1 protein assemblies. This effort required first establishing sample conditions for formation of HIV-1 protein assemblies that give rise to high-resolution solid-state NMR spectra for subsequent structural studies. In my Ph.D. work, I have optimized protocols to prepare homogeneous HIV-1 CA protein assemblies in vitro, developed confocal imaging method to characterize the morphologies of the resulting assemblies. With the suitable samples in hand, I have acquired solid-state NMR spectra on assemblies of CA protein and the maturation intermediate, CA-SP1, for structural analysis. Using these solid-state NMR data, I and my colleagues have obtained novel insights into the following aspects of HIV-1 structural biology: i) conformation of CA protein in conical assemblies; ii) the role of conformational dynamics of the hinge region in the structural polymorphism of CA in conical assemblies; iii) conformation of spacer peptide SP1 in tubular CA-SP1 assemblies; iv) conformation and dynamics of CA in tubular assemblies. In this thesis, I will first discuss the preparation and characterization of HIV-1 CA and CA-SP1 protein assemblies (Chapter 2 and 3). I will then describe the resonance assignments and secondary structure analysis of conical assemblies of HIV-1 CA protein (Chapter 4). Next, in Chapter 5, I will present the dynamics studies of conical assemblies of HIV-1 CA protein assemblies. In Chapter 6, I will discuss the resonance assignments and conformational analysis of tubular assemblies of HIV-1 CA and CA-SP1 proteins. The long-term goal of this research is developing comprehensive understanding of the mechanism of capsid assembly and disassembly, HIV-1 maturation, through the structural and dynamics analysis of the CA and Gag assemblies. The work discussed here represents the first step toward this goal and lays out the methodological and intellectual foundations enabling the solid-state NMR analysis of HIV-1 protein assemblies.

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