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Title: Patient-specific prediction of abdominal aortic aneurysm expansion using efficient physics-based machine learning approaches
Creator: Jiang, Zhenxiang
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Computational vascular Growth and Remodeling (G&R) models have been developed to capture key physiological and morphological features during the arterial disease progression and have shown promise for aiding clinical diagnosis, prognosis prediction, and staging classification. However, the translation of computational G&R models into their applications has yet to wait for clinical practice. Partly, due to the high complexity of the arterial adaptation mechanism, high-fidelity arterial G&R...
Show moreComputational vascular Growth and Remodeling (G&R) models have been developed to capture key physiological and morphological features during the arterial disease progression and have shown promise for aiding clinical diagnosis, prognosis prediction, and staging classification. However, the translation of computational G&R models into their applications has yet to wait for clinical practice. Partly, due to the high complexity of the arterial adaptation mechanism, high-fidelity arterial G&R simulations typically require hours or even days, which hinders its time-consuming applications such as patient-specific parameter estimation, disease prediction, verification, validation, and sensitivity analysis. Furthermore, the typical Finite Element Method (FEM) based computational G&R model should be extended to provide the uncertainty quantification associated with simulation and prediction results. Therefore, to enhance practicality of the G&R modeling, we develop a novel and computationally efficient simulation framework that comprehensively combines physics-based G&R simulations and data-driven machine learning methods using a Multi-Fidelity Surrogate (MFS) approach. This greatly enhances the computational efficiency of arterial G&R simulations, enabling more time-consuming applications such as personalized parameter estimation. The proposed framework is then tested for a specific disease, Abdominal Aortic Aneurysms (AAAs), by estimating G&R model parameters from follow-up CT images in 21 patients.
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Title: IT’S LIKE LOOKING IN A MIRROR, ONLY NOT : THE INFLUENCE OF ACQUIRER-TARGET SIMILARITY ON CORPORATE ACQUISITIONS
Creator: Wuorinen, Stefan
Date: 2022
Collection: Electronic Theses & Dissertations
Description: With the recent explosion of behavioral acquisition research, the collective knowledge in respect to acquisition behavior and outcomes has advanced tremendously. Despite these advancements, due to the rapid growth in this literature, various shortcomings have also developed. One such shortcoming is that the vast majority of this literature has examined acquisition influences emanating from the acquirer or the target but has rarely investigated the joint effects of these two entities. As such,...
Show moreWith the recent explosion of behavioral acquisition research, the collective knowledge in respect to acquisition behavior and outcomes has advanced tremendously. Despite these advancements, due to the rapid growth in this literature, various shortcomings have also developed. One such shortcoming is that the vast majority of this literature has examined acquisition influences emanating from the acquirer or the target but has rarely investigated the joint effects of these two entities. As such, in an attempt to contribute to the growing wealth of acquisition knowledge, the aim of this dissertation is to extend this research by examining how the degree of similarity between the acquirer and target can contribute to the outcomes of acquisition decisions. Specifically, this dissertation first investigates the implications for post-acquisition innovation due to pre-acquisition authority structure similarity, while also introducing and testing the arguments of Structural Adaptation Theory to the macro-organizational level and acquisition literature. Second, the influence of CEO regulatory fit between acquirer and target executives and the degree to which their respective orientations align with each manager’s negotiation roles within an acquisition are argued to influence acquisition premium and market reactions. Collectively, these studies begin to illuminate the joint affects that acquirers and targets have on distinct acquisition outcomes.
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Title: EXPERIMENTAL INVESTIGATIONS OF Al-BASED INITIATIOR FOR (CO)POLYMERIZATION OF EPOXIDES AND EPISULFIDE AND APPLICATION TOWARD MEMBRANE SYNTHESIS
Creator: Safaie Ashtiani, Niloofar
Date: 2022
Collection: Electronic Theses & Dissertations
Description: We developed a novel aluminum-based initiator for epoxide polymerization which facilitated polymerization of various epoxides (epichlorohydrin, propylene oxide, etc.) and episulfide up to molecular weights of 100 kg/mol while maintaining relatively narrow polydispersity (Ð < 1.3). The initiator was simply synthesized through the reaction of a thiol ligand and trialkyl aluminum, with the thiol ligand choice enabling polymer end group control. Copolymerization of epichlorohydrin and propylene...
Show moreWe developed a novel aluminum-based initiator for epoxide polymerization which facilitated polymerization of various epoxides (epichlorohydrin, propylene oxide, etc.) and episulfide up to molecular weights of 100 kg/mol while maintaining relatively narrow polydispersity (Ð < 1.3). The initiator was simply synthesized through the reaction of a thiol ligand and trialkyl aluminum, with the thiol ligand choice enabling polymer end group control. Copolymerization of epichlorohydrin and propylene oxide and copolymerization of different epoxides with episulfide demonstrated the ability of this method to control polymer architecture. We further investigated the effect of catalyst concentration and initiator structure on the kinetics of epoxide polymerizations through 1H NMR spectroscopy. Finally, we combined our method of polymerization with another facile method, reversible addition fragmentation with chain transfer (RAFT) polymerization, to synthesize block-co-polymers made from vinyl and epoxide monomers. To do this, we made a macroinitiator from polystyrene (PS) and poly(methyl methacrylate) (PMMA), synthesized by RAFT polymerization, and further polymerized epoxide from it. Therefore, this new synthetic tool allows for the facile and controlled polymerization of epoxides into well-defined, functional, polyether materials. Furthermore, the introduced innovative and reliable methodology for the synthesis of SAl initiators enabled us to tune the polymer architecture to readily access more complex structure of polyepisulifides. We synthesized di-functional (d-H) and tetra-functional (t-H) SAl initiators to produce ABA and star-(co)polymers consisting of propylene sulfide and PO or ECH. Finally, polyethylene glycol (PEG) was used as a macroinitiator to create PEG-b-PPS block copolymers and characterized by 1H, 13C NMR spectroscopy, DOSY, DSC, and SEC. Motivated by the result, we prepared the star shape cross linked membrane from t-H initiator. The composition was controlled through the monomer feed ratio of propylene oxide (PO) and epichlorohydrin (ECH) for synthesis of PPO-PECH membrane in the presence of poly(ethylene oxide)-diglycidyl ether as a cross linker and the most optimized PPO-PECH with the ratio of 90:10 resulted optically clear and flexible film. We further modified the membrane with a range of amines like trimethylamine (TEA), dimethylamine (DMA), triethylamine (TEA), and diethylamine (DEA) by membrane dipping method. The chemical, physical, and mechanical properties of resultant secondary amine grafted and quartenized membranes were characterized as a candidate for CO2 transport. Moreover, we designed the facilitated transport membranes of crosslinked ether-based PPO-PECH membranes with the range of hindered and unhindered primary amines using previously reported mono(μ-alkoxo)- bis(alkylaluminum) (MOB). The physical and chemical properties of the membranes investigated by FT-IR spectroscopy, DSC, TGA, and rheology. This method demonstrated a simple and robust strategy to prepare copolymers cross linked membranes containing amines for CO2 transport. This enables us to compare the effect of different amines in the structure of facilitated transport membranes. In this thesis research we seek to develop a SAl initiator as a platform that is both simple to use and can synthesize new polymeric materials. This methodology is simple and tunable to produce robust crosslinked membranes for molecu
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Title: UNDERSTANDING THE IMPACT OF SEXUAL ASSAULT RELATED SOCIAL MEDIA CONTENT ON SURVIVORS : AN EXPLORATORY SEQUENTIAL MIXED METHODS STUDY
Creator: PettyJohn, Morgan E.
Date: 2022
Collection: Electronic Theses & Dissertations
Description: In recent years, hashtag activism movements (i.e., using a common message or phrase to unite user voices to address injustice; Yang & Kaun, 2016) have unfolded across social media (SM) platforms to bring attention to the prevalence and impacts of sexual assault. Specifically, the online #MeToo Movement went viral around the world in 2017, resulting in increased news coverage and public discourse surrounding this topic (Anderson & Toor, 2018). Indeed, nearly half (44%) of women in the United...
Show moreIn recent years, hashtag activism movements (i.e., using a common message or phrase to unite user voices to address injustice; Yang & Kaun, 2016) have unfolded across social media (SM) platforms to bring attention to the prevalence and impacts of sexual assault. Specifically, the online #MeToo Movement went viral around the world in 2017, resulting in increased news coverage and public discourse surrounding this topic (Anderson & Toor, 2018). Indeed, nearly half (44%) of women in the United States experience unwanted sexual contact in their lifetime (Smith et al., 2018) and these violations are associated with increased risk for negative mental health outcomes, including depression, anxiety, and posttraumatic stress disorder (PTSD; Mason & Lodrick, 2013). After experiencing interpersonal violence, reminders of the trauma (e.g., words, images) can trigger psychophysiological reactions for survivors, such as emotional dysregulation, physical symptoms (e.g., heart racing), and increases in adverse mental health symptomatology (Mchugo et al., 2001; Moser et al., 2015). Given the popularity of SM among women in the U.S. (78% report usage; Pew Research Center, 2019), survivors of sexual assault are presumably being exposed to trauma related content connected to popular hashtag activism movements while spending time online. However, little is known about how exposure to sexual assault narratives and related discourse in this context could impact the mental health and relationships of survivors.The present study aims to address this gap in the literature by using an exploratory sequential mixed methods design to better understand survivors’ online experiences during this unique cultural moment. The qualitative strand of the study utilized thematic analysis of semi-structured interviews (n = 12) to explore the lived experiences of young women survivors (18-34 years old) using SM since initiation of the #MeToo Movement. Survivors described adverse changes in their mental health during periods of intense media coverage relating to sexual assault stories (e.g., Dr. Christine Blasey Ford’s Senate testimony). Some survivors also reported negative changes in their personal relationships with people in their life based on how they discussed sexual assault on these platforms. Findings from the qualitative strand were used to inform development of an online, cross-sectional quantitative survey, facilitated through CloudResearch’s MTurk toolkit. Multiple regression analyses found general SM use, exposure to sexual assault content, and exposure to unsupportive attitudes (i.e., victim blaming or perpetrator supporting) to be significantly predictive of depression, anxiety, and PTSD symptomatology among young women, both survivors (n = 312) and non-victims (n = 171). Survivors reported noticing people from their support systems (e.g., family, friends, co-workers) posting unsupportive attitudes about other victims’ stories at significantly higher rates than non-victims. Findings from the present study implore clinicians to assess SM use and level of exposure to sexual assault related content among clients, particularly those who have experienced sexual assault. Further, clinicians should stay informed about viral news stories and hashtag activism movements addressing sexual assault and provide space for clients to process this content during times of high saturation on SM platforms.
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Title: THE ROLE OF ARID1A IN ENDOMETRIOSIS-RELATED INFERTILITY
Creator: Marquardt, Ryan Michael
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The inner lining of the uterus, the endometrium, is composed of a luminal epithelial cell layer supported by an underlying stroma which contains epithelial gland structures. These distinct cell types coordinate with complex and dynamic molecular crosstalk tightly controlled by ovarian steroid hormones to regulate a healthy menstrual cycle and support the initiation and maintenance of a healthy pregnancy. Endometriosis occurs when endometrium-like tissue forms lesions outside the uterine...
Show moreThe inner lining of the uterus, the endometrium, is composed of a luminal epithelial cell layer supported by an underlying stroma which contains epithelial gland structures. These distinct cell types coordinate with complex and dynamic molecular crosstalk tightly controlled by ovarian steroid hormones to regulate a healthy menstrual cycle and support the initiation and maintenance of a healthy pregnancy. Endometriosis occurs when endometrium-like tissue forms lesions outside the uterine cavity, and this painful disease afflicts about 10% of reproductive-age women, an estimated 176 million worldwide. Up to 50% of these individuals also experience infertility, and many cases cannot be explained by morphological or ovarian defects, which implicates a uterine environment that is non-receptive to embryo implantation. The molecular basis for the correlation between endometriotic lesion presence and a non-receptive endometrium is unclear, but available evidence suggests that dysregulation of epigenetic regulators may play a role. Expression of AT-rich interaction domain 1A (ARID1A), a chromatin remodeling factor, is lost in some endometriotic lesions and markedly reduced in endometrial biopsies from infertile women with endometriosis, but it is essential in the uterus for fertility. This dissertation evaluates the overarching hypothesis that ARID1A loss connects endometriosis and infertility by causing increased lesion development and a non-receptive endometrium. Chapter 1 provides a review of the current literature on the topics of normal ovarian steroid hormone regulation of endometrial function, the dysregulation that occurs in endometriosis with its clinical implications and therapeutic options, and the specific involvement of ARID1A in endometrial pathophysiology. Chapter 2 delineates a critical role for endometrial epithelial ARID1A in uterine gland function for fertility. Chapter 3 reports the need for endometrial epithelial ARID1A to maintain uterine immune homeostasis during early pregnancy. Chapter 4 explores the involvement of endometrial ARID1A loss in a mouse model of endometriosis-related infertility. Chapter 5 describes a method for in vivo photoacoustic imaging of this endometriosis mouse model through the application of nanoparticle labeling. Finally, Chapter 6 summarizes the findings, discusses conclusions from the synthesized data in the context of the current literature, and provides ideas for future studies of related topics. Together, the studies herein make the case that endometrial ARID1A loss contributes to endometriosis-related infertility by exacerbating endometriotic lesion formation and compromising the ability of the endometrium to maintain the gland function and immune homeostasis necessary for the establishment and maintenance of pregnancy. Continued investigation through studies like these is key to understanding endometrial pathophysiology at the molecular level in order to enable development of targeted treatment options for women suffering the devastating effects of endometriosis and related infertility.
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Title: When is "Tough Love" Too Much? An Exploratory Study of Tough Love Coaching in Sport
Creator: Saxton, Sarah
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Tough love is often discussed in sport, but there is not a clear understanding of what tough love is, which tough love behaviors are commonly used by coaches and how effective they are, or which factors may influence the effectiveness of tough love strategies. Additionally, tough love may cross over into abuse or maltreatment if approached incorrectly. The purpose of this study was to propose a definition of tough love coaching, identify effective tough love strategies, determine whether...
Show moreTough love is often discussed in sport, but there is not a clear understanding of what tough love is, which tough love behaviors are commonly used by coaches and how effective they are, or which factors may influence the effectiveness of tough love strategies. Additionally, tough love may cross over into abuse or maltreatment if approached incorrectly. The purpose of this study was to propose a definition of tough love coaching, identify effective tough love strategies, determine whether tough love coaching can be inappropriate or harmful to the athlete, and identify individual factors that influence the way in which tough love is received by athletes. This study adopted a basic interpretive approach to qualitative research by using semi-structured interviews to investigate athletes’ experiences with and feelings toward tough love in sport. Specifically, in-depth interviews were conducted with 12 current and former athletes (three males, nine females) ranging in age from 18 to 27 who had or were participating in a variety of sports. Thematic analysis was conducted on the transcribed interviews to identify relevant themes, subthemes and categories in the data. Four major results were found. First, a definition of tough love coaching was proposed. Second, examples of effective, ineffective, and harmful tough love strategies were provided. Third, factors perceved to influence tough love’s effectiveness were identified, including the coach-athlete relationship, coach demographics, athlete characteristics, sport demographics, encouragement and support, clear feedback, frequency of use, motivational climate, and privacy. Fourth, the “line” between tough love and harmful or abusive coaching was identified. Results are discussed relative to the coaching feedback and approaches as well as maltreatment in sport reseach literature.
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Title: DIVERSIFYING AGRICULTURAL LANDSCAPES FOR BIODIVERSITY AND ECOSYSTEM SERVICES
Creator: Kemmerling, Lindsey Renee
Date: 2022
Collection: Electronic Theses & Dissertations
Description: This dissertation focuses on strategies to restore biodiversity and ecosystem services in agricultural landscapes through diversifying the plant community at the landscape level. Biodiversity and ecosystem services are declining globally, and a leading cause of this decline is large-scale row crop agriculture which results in habitat loss and pollution. Simultaneously, the human population is growing, as are human demands for resources produced by agriculture. Diversifying agricultural...
Show moreThis dissertation focuses on strategies to restore biodiversity and ecosystem services in agricultural landscapes through diversifying the plant community at the landscape level. Biodiversity and ecosystem services are declining globally, and a leading cause of this decline is large-scale row crop agriculture which results in habitat loss and pollution. Simultaneously, the human population is growing, as are human demands for resources produced by agriculture. Diversifying agricultural landscapes is one method to both mitigate the loss biodiversity while providing essential human resources. I conducted three studies that test if diversifying cropping systems can increase biodiversity and ecosystem services and maintain or even increase agricultural yield. In Chapter 1, I tested the ability of multiple native, perennial bioenergy crops (alternatives to annual bioenergy crops) to provide both crop yield and conserve pollinators. I measured pollinator abundance and species richness, flower abundance and species richness, and crop yield across four native perennial biofuel crop varieties: successional land (unmanaged), restored prairie, a mix of native grasses, and seeded switchgrass. Successional land had the most diverse community of pollinators but the lowest crop yield, native grasses had the highest yield but the least diverse pollinator community, and switchgrass and restored prairie were intermediate. If both pollinator conservation and crop yield are valued similarly, restored prairie was the optimal biofuel crop. Chapter 2 tested the effects of crop management practices in row crop agriculture, including the establishment of a conservation practice called “prairie strips” on biodiversity and ecosystem services. Prairie strips are strips of farmland retired from production and actively restored with native prairie plant species. I synthesized the tradeoffs and synergies of a suite of biodiversity and ecosystem service measures across a land use intensity gradient, as well as their spillover from prairie strips into cropland. The lowest land use intensity consistently had the highest levels of biodiversity and ecosystem services other than crop yield. Treatments with prairie strips had higher pollination services and a higher abundance of butterflies and spiders than other row crop treatments. Crop yield in a treatment with low land use intensity and prairie strips remained as highest land use intensity treatment, even when including the area taken out of production for prairie strips. Biodiversity and ecosystem services decreased with increasing distance from prairie strips and this effect was more pronounced in the second year of the prairie strips than the first for several measures. These results show that, even in early establishment, prairie strips can contribute to the conservation of biodiversity and ecosystem services without a disproportionate loss of crop yield. Chapter 3 further investigated one of the measures addressed in Chapter 2: butterfly biodiversity. I measured butterfly and plant species richness and abundance across three years in the same land use intensity gradient. Butterfly abundance and richness increased as land use intensity decreased. Prairie strips harbored unique butterfly communities and had a higher abundance of butterflies than other row crop treatments, including conservation land. Across the 1 ha plot of which 5% was prairie strip, butterfly abundance was higher in row crops with prairie strips than in row crops without prairie strips, likely as a result of prairie strips and other crop management practices in treatments with prairie strips, such as reduced pesticides. Altogether, this work presents evidence that restoring habitat within farms can support biodiversity and ecosystem services without disproportionately impacting crop yields. Furthermore, when strategically placed, these conservation strategies can prevent unnecessary greenhouse gas emissions, and potentially increase crop yield.
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Title: DO INFORMATION ACQUISITION COSTS MATTER? THE EFFECT OF SEC EDGAR ON STOCK ANOMALIES
Creator: Kim, Yong-Hyuck
Date: 2022
Collection: Electronic Theses & Dissertations
Description: I estimate the costs of information acquisition and the extent to which they explain stock anomaly returns. The SEC’s staggered implementation of EDGAR from 1993 to 1996 greatly lowered the costs of acquiring accounting information. I study how this quasi-exogenous and staggered shock affects the profitability of 126 accounting and 108 non-accounting anomalies. The EDGAR introduction lowers the average alphas for the accounting anomalies by 4.0% per year, explaining more than half of the pre...
Show moreI estimate the costs of information acquisition and the extent to which they explain stock anomaly returns. The SEC’s staggered implementation of EDGAR from 1993 to 1996 greatly lowered the costs of acquiring accounting information. I study how this quasi-exogenous and staggered shock affects the profitability of 126 accounting and 108 non-accounting anomalies. The EDGAR introduction lowers the average alphas for the accounting anomalies by 4.0% per year, explaining more than half of the pre-EDGAR alphas. The attenuation is stronger for the accounting anomaly portfolios that require more up-to-date accounting information and those consisting of EDGAR filer stocks with less information available in the pre-EDGAR period. By contrast, alphas for the non-accounting anomalies remain unaffected. These results imply that the information acquisition costs, which are usually neglected, can be as important as the transaction or short sale costs.
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Title: COVID-19 information sharing on social media : Channels and Motives from the Kazakhstani people's perspective
Creator: Moldagaliyeva, Moldir
Date: 2022
Collection: Electronic Theses & Dissertations
Description: COVID-19 pandemic news has become popular and topical content for the last couple of years. And the wide usage of social media across the globe makes it easy to share information, including misinformation, about COVID-19. Although sharing news on social media has been actively studied in most western countries, little attempt has been made to look into the issue from the perspectives of developing countries where the amount of social media use has been increasing enormously over the last...
Show moreCOVID-19 pandemic news has become popular and topical content for the last couple of years. And the wide usage of social media across the globe makes it easy to share information, including misinformation, about COVID-19. Although sharing news on social media has been actively studied in most western countries, little attempt has been made to look into the issue from the perspectives of developing countries where the amount of social media use has been increasing enormously over the last years. Besides, almost nothing is known about the social media users’ choice of a particular platform when they decide to share information and misinformation, especially within the context of the COVID-19 pandemic. Therefore, this master’s thesis explored how motivation factors Kazakhstani people follow when sharing COVID-19 news shape their decision to share COVID-19 news on specific social media platforms and their COVID-19 misinformation sharing patterns.The study used a quantitative research method approach, surveying 288 people from Kazakhstan over 18 years old.
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Title: NUMERICAL SIMULATIONS OF PERMEABLE-WALL TURBULENCE WITH APPLICATIONS IN HYPORHEIC EXCHANGE
Creator: SHEN, GUANGCHEN
Date: 2022
Collection: Electronic Theses & Dissertations
Description: In aquatic environments such as rivers, the exchange of solutes across the interface between the sediment and the overlying water plays a signifcant role in controlling biogeochemical processes, which are important for an array of topics from nutrient transport and cycling to release of greenhouse gases such as nitrous oxide. Most previous studies on characterizing this exchange are focused on flows with sediment bedforms much larger than individual sediment grains. The physics at the pore or...
Show moreIn aquatic environments such as rivers, the exchange of solutes across the interface between the sediment and the overlying water plays a signifcant role in controlling biogeochemical processes, which are important for an array of topics from nutrient transport and cycling to release of greenhouse gases such as nitrous oxide. Most previous studies on characterizing this exchange are focused on flows with sediment bedforms much larger than individual sediment grains. The physics at the pore or grain scale were typically not resolved. The effects of grain roughness on the sedimentbed surface on the transport across the sediment-water interface (SWI), isolated from those of bed permeability and bedforms, are not well understood. In this work, direct numerical simulations (DNS) of the connected system of turbulent open-channel flow and pore-resolved sediment flow are carried out, with different arrangements of grains at the sediment surface.First, the statistics and structure of the mean flow and turbulence are characterized in flows with a friction Reynolds number of 395 and a permeability Reynolds number of 2.6 over sediments with either regular or random grain packing on a macroscopically flat bed. It is shown that, even in the absence of any bedform, the subtle details of grain roughness alone can signifcantly affect the dynamics of turbulence and the time-mean flow. Such effects translate to large differences in penetration depths, apparent permeabilities, vertical mass fluxes and subsurface flow paths. The less organized distribution of mean recirculation regions near the interface with a random packing leads to a more isotropic form-induced stress tensor, which plays a signifcant role in increasing mixing and wall-normal exchange of mass and momentum.Next, the mass exchange is characterized in detail for macroscopically flat river beds, focusing on the transit time—the time spent by a fluid particle in the sediment—which determines the role of hyporheic zones in transforming the chemical signature of stream water. Results show that bedroughness leads to interfacial pressure variations, which induces deep subsurface flow paths that yield a transit time distribution with a heavy tail. Furthermore, the addition of molecular diffusionis accounted for and is shown to increase transit times regardless of roughness texture. The results demonstrate that particle roughness on a macroscopically flat sediment bed can induce signifcant hyporheic exchange that is fundamentally similar to that induced by bedforms.Lastly, to identify possible interaction between the effect of grain roughness and that of a bedform, DNSs of open channels with a friction Reynolds number of 1580 on a porous dune with two different roughnesses are conducted. Results show that the roughness modifes the wall friction, shear penetration depth and pressure distribution along the interface. Unlike the case on a macroscopically flat bed where the random roughness induces more intense roughness-scale pressure variation than the regular roughness, over a bedform the random roughness reduces the macroscopic pressure distribution at the interface instead due to its higher hydrodynamic drag. The weaker pressure variation in turn weakens the pumping and shortens transit times. The results highlight the nonlinear interaction between the effects of bed morphological features of different scales. Pore-resolved simulations such as the ones herein can be used in the future in direct characterization of pore-scale dynamics to provide insights for pore-unresolved modeling of biogeochemical processes.
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Title: Contextual Support, Resilience, Allostatic Load, and Mental Health in Transgender and Gender Diverse Individuals
Creator: Kimball, Devon Mary
Date: 2022
Collection: Electronic Theses & Dissertations
Description: A growing body of literature suggests that how much support TGD individuals experience in the places they live, including their present context and context of origin, can influence their wellbeing. Other research about physical health has found exposure to stressors has physiological effects on sexual and gender minority people, which can be measured through allostatic load (a selection of multiple physiological indicators that reflects “wear and tear” on the body; AL). Research on mental...
Show moreA growing body of literature suggests that how much support TGD individuals experience in the places they live, including their present context and context of origin, can influence their wellbeing. Other research about physical health has found exposure to stressors has physiological effects on sexual and gender minority people, which can be measured through allostatic load (a selection of multiple physiological indicators that reflects “wear and tear” on the body; AL). Research on mental health has also indicated that TGD individuals are at higher risk of depression and anxiety. TGD populations also have unique resilience factors that are important to consider, such as pride and community connectedness, which may influence health outcomes. This study used latent class analysis to examine how individuals clustered based on current and past levels of contextual support, and then examined the relationship between these classes and AL, depression, and anxiety, including whether pride and community connectedness moderated these relationships. Contextual support across the lifetime was also examined as a continuous variable. Participants either had lived consistently in contexts with high levels of support (High Support class), had moved from contexts with low levels of support to high levels of support (Low to High Support class), or had consistently lived in contexts with low levels of support (Low Support class). Individuals in the Low Support class had lower levels of AL compared to their peers in the High Support class. There were no associations between class and depression and anxiety, and there were no moderating effects of community connectedness or pride. This study suggests that contextual support may not influence depression and anxiety among TGD people, but that lower levels of support may actually correlate with decreased AL.
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Title: WHAT HAPPENS DURING AND AFTER MULTITASKING? CONCURRENT AND CARRY-OVER EFFECTS OF MEDIA MULTITASKING AND SELF-REGULATION ON TASK PERFORMANCE
Creator: Baek, Jong-Hwan
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Much research has suggested that multitasking impairs cognitive outcomes and task performance. Given its negative role in information processing, the vast majority of work has focused on concurrent effects during multitasking (e.g., recall, recognition). However, prior research in the multitasking literature has rarely examined short-term or lingering effects on subsequent tasks. One of the theories concerning this after-effect is ego depletion, a state of reduced self-regulatory resources.To...
Show moreMuch research has suggested that multitasking impairs cognitive outcomes and task performance. Given its negative role in information processing, the vast majority of work has focused on concurrent effects during multitasking (e.g., recall, recognition). However, prior research in the multitasking literature has rarely examined short-term or lingering effects on subsequent tasks. One of the theories concerning this after-effect is ego depletion, a state of reduced self-regulatory resources.To this end, the present study examined concurrent and carry-over effects of multitasking and self-regulation on task performance. Specifically, the current study examined whether the effects of media multitasking with different attentional demands vary by self-regulation (i.e., single-task, multitask with divided attention, multitask with selective attention, multitask with flexible attention) and how such effects occur during and after multitasking. Consistent with predictions, media multitasking decreased performance on subsequent self-control and cognitive tasks. Also, participants in the multitasking condition with flexible attention watched a subsequent movie longer, and they perceived it as more enjoyable than those in the single-task condition. Additionally, findings showed how exerting self-regulation could lead to better performance on both primary and secondary tasks. Findings and implications for research on media multitasking are further discussed.
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Title: Tunable Fluorescent Organic Salts for Imaging and Therapy
Creator: Broadwater, Deanna May
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Cancer remains a leading cause of death worldwide and many treatments still rely on non-targeted chemotherapy, which has inadequate efficacy and is plagued by toxic side effects. A promising solution is photodynamic therapy (PDT), a noninvasive clinical cancer treatment that combines a light activated photosensitizer (PS) with excitatory light to generate toxic reactive oxygen species (ROS). These photoactive agents can also produce detectable wavelengths of light upon photoactivation, which...
Show moreCancer remains a leading cause of death worldwide and many treatments still rely on non-targeted chemotherapy, which has inadequate efficacy and is plagued by toxic side effects. A promising solution is photodynamic therapy (PDT), a noninvasive clinical cancer treatment that combines a light activated photosensitizer (PS) with excitatory light to generate toxic reactive oxygen species (ROS). These photoactive agents can also produce detectable wavelengths of light upon photoactivation, which has been used clinically to image tumors in cancer diagnostics and image-guided surgery. Having uses as both diagnostic and therapeutic agents, these molecules are known as theranostics. However, current light-activated theranostics are limited by low brightness, poor tissue penetration, and nonspecific cytotoxicity independent of light excitation. Due to these obstacles, PDT is currently limited to precancerous lesions, superficial neoplastic tissue, or palliative care. Therefore, improved theranostic agents are needed. Prevailing efforts to improve existing photoactive agents focus on chemical modifications that cannot independently control electronic properties (which dictate toxicity) from optical properties. To overcome these limitations, work in this dissertation develops a novel counterion pairing platform to modulate the toxicity of organic salts composed of a photoactive cationic heptamethine cyanine (Cy+) and a non-photoactive anion. These counterion-tuned fluorescent organic salts can be designed to be either nontoxic for imaging, or phototoxic for PDT. Organic salts self-organize into nanoparticles with shifted frontier molecular orbital levels dependent on the counterion while the bandgap remains the same. This allows for tuning of electronic properties without affecting optical properties. Improvements in these areas could expand light-activated theranostics into a wider range of cancers and improve patient outcomes. This dissertation will begin with a review of current photoactive agents used in cancer therapy and ongoing challenges to the adoption of PDT as a frontline therapy. Modern PDT regimens and potential combinatorial therapies will be appraised, and recent advances in rational PS design will be highlighted. Initial in vitro studies investigated the optoelectronic tuning capabilities of counterion pairing in human lung carcinoma (A549) and melanoma (WM1158) cell lines. Viability assays establish that pairings with weakly coordinating bulky anions could generate organic salts that are non-cytotoxic and selectively phototoxic, while pairing with standard hard anions yield cytotoxic organic salts. These studies demonstrate that anion pairing can be exploited to shift energy levels and influence ROS generation to either enhance photokilling of cancer cells or improve cell imaging. Organic salts were further investigated in a metastatic breast cancer mouse model to characterize biodistribution, antitumor efficacy within a complex tumor microenvironment, and off-site toxicity. In vivo experiments confirm that counterion tuning can generate a selectively phototoxic antitumor PS which abolishes tumor growth and reduces metastasis without systemic toxicity in a breast cancer mouse model. Overall, this work demonstrates the utility of using counterion tuning to control phototoxicity, and further demonstrates the untapped potential of photoactive theranostic agents for clinical cancer therapy.
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Title: ENHANCING CORPORATE CRIME ENFORCEMENT WITH MACHINE LEARNING—A MULTIDISCIPLINARY RISK FACTOR APPROACH
Creator: Chan, Fiona
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Despite its severe and lasting social and financial ramifications, corporate financial crime remains one of the most understudied crime types, as it is often hindered by two challenges. First, its multidisciplinary nature requires both financial and criminological expertise among others to conduct proper investigations. Second, corporate crime data is fraught with constraints such as high dimensionality, complex interactions, and nonlinear functional forms that are ill-suited for classical...
Show moreDespite its severe and lasting social and financial ramifications, corporate financial crime remains one of the most understudied crime types, as it is often hindered by two challenges. First, its multidisciplinary nature requires both financial and criminological expertise among others to conduct proper investigations. Second, corporate crime data is fraught with constraints such as high dimensionality, complex interactions, and nonlinear functional forms that are ill-suited for classical statistical modeling. The lack of research coupled with the limited resources in corporate crime enforcement represent a great impediment to the advancement of fraud interventions. This dissertation seeks to overcome these specific challenges by unifying cross-disciplinary financial fraud research under a risk factor framework, and by leveraging recent advancements in artificial intelligence. The goal is to examine whether two machine learning algorithms—random forest and neural network—can be used to enhance corporate fraud risk detection/prediction beyond more commonly employed analytical techniques. Findings from the analysis showed that the random forest algorithm outperformed logistic regression and a naïve classifier in a 1:1 matched sample. The neural network performed better than a naïve classifier but slightly worse than logistic regression. Feature selection improved the algorithms’ predictive accuracy and ability to distinguish between classes even further. Despite promising results from the 1:1 matched sample, both machine learning algorithms struggled with a heavily imbalanced 1: many dataset, which represents a more realistic setting. With the implementation of an oversampling strategy and feature selection, the algorithms improved substantially in identifying the rare fraud cases, and showed promise of improvement with further research on imbalanced classification. Feature importance from the random forest classifier identified risk factors that are consistent with findings from prior studies. Measures of financial distress ranked lower in importance than measures of financial health, suggesting future research can build on prior findings on corporate strain to examine specific mechanisms. The analysis also identified auditor independence as a key concept of guardianship and opportunity structure that warrants further study. Findings from this research also have important methodological implications for corporate crime studies—namely, the need to improve measurements of organizational-level fraud risk factors.
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Title: SUBJECTIVE AND OBJECTIVE STRESS RESPONSES AMONG YOUNG AUTISTIC ADULTS
Creator: Peña, Jarhed Macarubbo
Date: 2022
Collection: Electronic Theses & Dissertations
Description: This study was conducted to examine the subjective (psychological) and objective (physiological) stress responses of autistic individuals guided by the Transactional Theory of Stress and Coping by Lazarus and Folkman (1984). Subjective stress responses were measured through a Visual Analog Scale (VAS) rating by the participants on their stress perception and objective stress responses were measured through heart rate variability (HRV) using a heart rate monitor as participants underwent a...
Show moreThis study was conducted to examine the subjective (psychological) and objective (physiological) stress responses of autistic individuals guided by the Transactional Theory of Stress and Coping by Lazarus and Folkman (1984). Subjective stress responses were measured through a Visual Analog Scale (VAS) rating by the participants on their stress perception and objective stress responses were measured through heart rate variability (HRV) using a heart rate monitor as participants underwent a standardized online Trier Online Stress Test (TSST; Kirschbaum et al., 1993) protocol to stimulate a social evaluative stress protocol. A systematic and qualitative interview was followed to investigate the appraisal of participants’ perception on the TSST. Literature suggests lack of insight and poor reporting of stressful experiences among autistic individuals. Participants consisted of 12 young adults with autism spectrum disorder (ASD) and 24 typically developing young adults currently attending college. Both subjective and objective stress quantitative analyses resulted in non-significant findings. However, findings suggested some between-group differences in subjective stress responses and objective stress responses for each phase of the stress stimulation (i.e., Baseline, Stress Task, Recovery). Particularly, higher observed stress perception and HRV were noted during Baseline and Recovery and lower observed stress perception and HRV were noted during the Stress Task in the ASD group. Further exploration of qualitative data findings revealed that both groups were able to have insight and self-report physical stress response such as increased heart rate and sweating, further supporting the importance of the appraisal of the stressful experience. Clinical, education, and research implications are also addressed. In terms of clinical implications, the current study highlighted young adults are susceptible to stress and can benefit from stress management intervention regardless of ASD diagnosis. Early intervention to teach autistic individuals stress management skills may also be beneficial. Furthermore, the use of objective measures can raise the awareness of one’s stress response, and that the appraisal of one’s subjective perception of stress is equally important in understanding individual differences in the stress experience. In terms of education implications, educators should train health professionals such as rehabilitation counselors in understanding diverse ways of stress manifestation and coping. They should also be trained to teach stress coping skills when working with clients, including autistic individuals. In terms of research implications, the unique methodology to combine psychological data with physiological data, as well as appraisal process to obtain cognitive information to gain a more holistic perspective on the stress experiences of participants. Future research recommends increasing sample size and diverse demographic participants, matching participants with ASD with those without, re-examining different methods to characterize potential similarities and differences among ASD, typically developing and other clinical groups, further examining not only the stress phase but also the baseline and recovery phases of the stress stimulation, improving the ASD screening to verify autism diagnosis, recruiting participants who have not received stress management intervention or training, examining the impact of in person and online TSST, and investigating the impact of comorbid conditions on stress responses in the ASD population.
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Title: Topological Approaches for Quantifying the Shape of Time Series Data
Creator: Tymochko, Sarah
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Topological data analysis (TDA) is field that started only two decades ago and has already shown promise both in theory and in applications. The goal of TDA is to quantify the shape of data in a manner that is concise and robust using concepts from algebraic topology. Persistent homology, arguably the most popular tool from TDA, studies the shape of a filtered space by watching how its homology changes. The output of persistent homology is a persistence diagram, which encodes information...
Show moreTopological data analysis (TDA) is field that started only two decades ago and has already shown promise both in theory and in applications. The goal of TDA is to quantify the shape of data in a manner that is concise and robust using concepts from algebraic topology. Persistent homology, arguably the most popular tool from TDA, studies the shape of a filtered space by watching how its homology changes. The output of persistent homology is a persistence diagram, which encodes information about the changing homology.Persistent homology has shown success in various application areas; one ever growing area of study in this field is time series analysis. Nonlinear time series analysis is a research field in and of itself that aims to capture structure in time series data, however, it lacks theoretically justified tools to analyze the resulting structure. Persistent homology comes with a solid theoretical framework, is robust to noise, and quantifies the same type of structure as appears in time series data. Thus combining tools from time series analysis and TDA provides a new approach to analyze and quantify behavior in time series data.One field where time series are prevalent is dynamical systems, since a time series arises from a projection of a solution to a system. Specifically, given a time series, Takens' theorem can be leveraged to embed the time series as a point cloud in a higher dimensional space, where this point cloud is a sampling of the full state space. Then for each time series, persistent homology can be computed on the embedding. The result is a persistence diagram for each time series. The question then becomes how do we analyze this collection of persistence diagrams to learn something about the original time series data? Many people have developed methods to answer this question, through methods such as machine learning or statistics. This dissertation provides several new methods leveraging tools from both TDA and nonlinear time series analysis to study time varying data.
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Title: Robust Maxwell Solvers for Large Scale Particle-in-Cell Simulations
Creator: Crawford, Zane Daniel
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The design of modern devices is impacted heavily by the use and availability of robust, accurate, and efficient computational tools. This includes modeling devices that exploit plasma physics like particle accelerators, klystrons, ion thrusters, and micro-plasma generators among many other applications. While there are a number of current and emerging applications, the common thread between all is the need to accurately and efficiently capture all the relevant physics in geometrically...
Show moreThe design of modern devices is impacted heavily by the use and availability of robust, accurate, and efficient computational tools. This includes modeling devices that exploit plasma physics like particle accelerators, klystrons, ion thrusters, and micro-plasma generators among many other applications. While there are a number of current and emerging applications, the common thread between all is the need to accurately and efficiently capture all the relevant physics in geometrically intricate structures. The holy grail is to enable topology optimization to explore the design space. But all this requires rigorous translation from the continuous to the discrete world, while capturing all the underlying physics and not adding spurious artifacts due to discretization.A common computational model to perform this analysis is the particle-in-cell (PIC) method. It provides a straightforward paradigm to self-consistently solve for the distribution of the plasma as a collection of particles. The prevailing approach to solve for the fields in PIC is the finite difference time domain method (FDTD), or EM-FDTDPIC. But this effort leaves much to be desired, given the leaps that have been made in the finite element method; indeed, the latter is the method of choice for most commercial tools that that have become the de-facto workhorse in RF design industry. As a result, in the past decade, considerable effort has been expended in developing finite element (FEM) based PIC schemes, EM-FEMPIC. But we are still not there. One major concern of utilizing EM-FEMPIC over EM-FDTDPIC is the computational cost of FEM, which is greater than FDTD, despite the advantages of field and geometry accuracy FEM affords.This dissertation seeks to develop (i) a theoretically rigorous means to translate from the continuous to the discrete world while ensuring that there are no spurious artifacts, (ii) develops a higher order accurate method in both space and time, and (iii) overcomes cost complexity by introducing a linear scaling domain decomposition scheme. In all of these, the methods developed ensure that the necessary conservation properties are satisfied to machine precision. Numerous examples developed demonstrate these claims.
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Title: Machine Learning on Drug Discovery : Algorithms and Applications
Creator: Sun, Mengying
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Drug development is an expensive and time-consuming process where thousands of chemical compounds are being tested and experiments being conducted in order to find out drugs that are safe and effective. Modern drug development aims to speed up the intermediate steps and reduce cost by leveraging machine learning techniques, typically at drug discovery and preclinical research stages. Better identification of promising candidates can significantly reduce the load of later processes, e.g.,...
Show moreDrug development is an expensive and time-consuming process where thousands of chemical compounds are being tested and experiments being conducted in order to find out drugs that are safe and effective. Modern drug development aims to speed up the intermediate steps and reduce cost by leveraging machine learning techniques, typically at drug discovery and preclinical research stages. Better identification of promising candidates can significantly reduce the load of later processes, e.g., clinical trials, saving tons of resources as well as time.In this dissertation, we explored and proposed novel machine learning algorithms for drug discovery from the aspects of robustness, knowledge transfer, molecular generation and optimization. First of all, labels from high-throughput experiments (e.g., biological profiling and chemical screening) often contain inevitable noise due to technical and biological variations. We proposed a method that leverages both disagreement and agreement among deep neural networks to mitigate the negative effect brought by noisy labels and better predict drug responses. Secondly, graph neural networks (GNNs) has become popular for modeling graph-structured data (e.g., molecules). Graph contrastive learning, by maximizing the mutual information between paired graph augmentations, has been shown to be an effective strategy for pretraining GNNs. However, the existing graph contrastive learning methods have intrinsic limitations when adopted for molecular tasks. Therefore, we proposed a method that utilizes domain knowledge at both local- and global-level to assist representation learning. The local-level domain knowledge guides the augmentation process such that variation is introduced without changing graph semantics. The global-level knowledge encodes the similarity information between graphs in the entire dataset and helps to learn representations with richer semantics. Last but not least, we proposed a search-based approach for multi-objective molecular generation and optimization. We show that given proper design and sufficient information, search-based methods can achieve performance comparable or even better than deep learning methods while being computationally efficient. Specifically, the proposed method starts with existing molecules and uses a two-stage search strategy to gradually modify them into new ones, based on transformation rules derived from large compound libraries. We demonstrate all the proposed methods with extensive experiments.
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Title: Toward a Virulent Community Literacy : Constellating the Science, Technology, and Medicine of Queer Sexual Health
Creator: Flores, Wilfredo Antonio
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Toward a Virulent Community Literacy: Constellating the Science, Technology, and Medicine of Queer Sexual Health is a qualitative study (informed by Indigenous and decolonial methodologies) of how queer and trans people of color generate and share knowledge about their sexual health on Twitter with regards to HIV/AIDS. With a Twitter archive of 15,000 discrete tweets built with the keywords “Truvada,” PrEP,” and “HIV,” three datasets were derived comprising general utterances from queer users...
Show moreToward a Virulent Community Literacy: Constellating the Science, Technology, and Medicine of Queer Sexual Health is a qualitative study (informed by Indigenous and decolonial methodologies) of how queer and trans people of color generate and share knowledge about their sexual health on Twitter with regards to HIV/AIDS. With a Twitter archive of 15,000 discrete tweets built with the keywords “Truvada,” PrEP,” and “HIV,” three datasets were derived comprising general utterances from queer users of color, public health officials using social media for outreach, and organizations sharing research findings. Focusing on the data subset comprising 300 discrete users of color and relevant media (i.e., news articles, public health advertisements, other emergent artifacts from the data), this dissertation recounts three case studies focusing on: the rollout of HIV prevention advertisements within queer-centered media; the patent breaking of Truvada, a once-daily medication for preventing HIV; and the use of social media to take to task bad actors and misinformed healthcare providers. The data are used as part of an argument that the manner by which medicine and public health interface with queer and trans people of color hinges on ongoing colonization via the medical and outreach practices derived from colonial practices. Moreover, using a theoretical argument derived from Black and Native technology studies (as well as Black Feminist Thought, Anishinaabe cosmology, settler colonial studies, and digital rhetorical theory), the data was reviewed through a protocol for understanding identity construction amid technology use. The results revealed three rhetorical strategies: 1) continuing community-born public health practices created during the HIV/AIDS crisis of the 1980s and 90s by deploying descriptive hashtags to challenge stigma; 2) creating emergent whisper networks for sharing information about dealing with healthcare providers, navigating insurance networks, and communicating the symptoms of taking the medication; and 3) recognizing and countering the complex systems of late capitalist biomedicalization that prioritize profit over life. To contribute to ongoing commitments within writing and rhetoric studies to create equitable healthcare experiences, an HIV/AIDS health literacy framework follows the data results, which allows for outreach in non-clinical settings through relational design, or a participatory communication design process that incorporates community voices via an attunement to social media such as Twitter. This dissertation contributes to ongoing incursions within technical and professional communication, as well as the rhetoric of health and medicine, to upcycle disciplinary savvy into building better public health and clinical experiences for queer and trans people of color.
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Title: ECOPHYSIOLOGY OF (PERI)ORAL BACTERIA AND IMPACT OF OTIC COLONIZATION
Creator: Jacob, Kristin Marie
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The middle ear is typically assumed to be sterile in health due to its secluded location, closed off from external forces by the tympanic membrane (ear drum) and from the naso/oropharynx by a collapsed Eustachian tube. However, the periodic opening of the Eustachian tube to the naso/oropharyngeal space, which releases pressure across the eardrum and drains otic fluids, could introduce bacteria. Previous studies have tested for the presence of bacteria in the uninfected otic cavity using...
Show moreThe middle ear is typically assumed to be sterile in health due to its secluded location, closed off from external forces by the tympanic membrane (ear drum) and from the naso/oropharynx by a collapsed Eustachian tube. However, the periodic opening of the Eustachian tube to the naso/oropharyngeal space, which releases pressure across the eardrum and drains otic fluids, could introduce bacteria. Previous studies have tested for the presence of bacteria in the uninfected otic cavity using samples collected via invasive surgeries (through or around the eardrum). Findings from these studies are controversial due to contradictory results between studies, lack of critical experimental controls, and sampling of participants with underlying ailments (i.e., cochlear implant surgery) that could impact the microbiology of the otic mucosa. The studies reported herein bypass these limitations by using samples of otic secretions collectively non-invasively (through the mouth) in a cohort of healthy young adults. This dissertation describes cultivation-dependent methods to investigate the microbiology of the middle ear in health. The study used an IRB-approved protocol (#17-502) to collect otic secretions in order to 1) sequence their microbiome (contribution by Dr. Joo-Young Lee) and 2) recover in pure culture otic bacteria for further characterization (my contribution). As controls, we also collected buccal (top palate and inside of cheeks) and oropharyngeal swabs from each participant. Of the collected secretions, samples from 19 individuals were used for culture independent studies, while samples from the remaining 3 participants were subjected to culture dependent studies. 16S rRNA-V4 sequencing detected a diverse and distinct microbiome in otic secretions comprised primarily of strictly anaerobic bacteria belonging to the phyla Bacteroidetes, Firmicutes and Fusobacteria, and to a lesser extent facultative anaerobes (Streptococcus). I recovered from the otic, oropharyngeal, and buccal secretions 39 isolates of predominantly facultative anaerobes belonging to Firmicutes (Streptococcus and Staphylococcus), Actinobacteria (Micrococcus and Corynebacterium), and Proteobacteria (Neisseria) phyla, and used partial 16S rRNA amplicon sequences to demonstrate the distinct phylogenetic placement of otic streptococci compared to the oral ancestors (Chapter 2). This finding is consistent with the ecological diversification of oral streptococci once in the middle ear microenvironment. The recovery of streptococci and transient migrants (Staphylococcus, Neisseria, Micrococcus and Corynebacterium) from otic secretions prompted us to study the adaptive responses that give the streptococcal migrants a competitive advantage during the colonization of the middle ear (Chapter 3). For these studies, I sequenced and partially assembled the genomes of the otic isolates and used the full length 16S rRNA sequences for taxonomic demarcation at the species levels. Phylogenetic analyses demonstrated the oral ancestry of the otic streptococci, which retained from the otic adaptive traits critical for growth and reproduction in the middle ear mucosa (biofilm formation, mucolytic and proteolytic activity, robust growth under redox fluctuations, and fermentative production of lactate, a key metabolic intermediate in the otic trophic webs). These adaptive traits give oral streptococci a colonization advantage over competing (peri)oral migrants such as Staphylococcus. Furthermore, the otic streptococci inhibited the growth of otopathogens, including Staphylococcus aureus. These antagonistic interactions give streptococci a competitive advantage during the colonization of the middle ear and suggest a role for these commensals in promoting mucosal health. The ability of staphylococcal migrants to breach the middle ear mucosal barrier and cause infections prompted us to study the environmental factors that facilitate the spreading of staphylococci from the nasal to the middle ear mucosa. Allergies, respiratory maladies (cold, flu), or (peri)oral bacterial infections (sinus, adenoids, tonsils, etc.) lead to inflammation of the Eustachian tube and changes in the rheological properties of the otic mucus that increase the risk of infections. Thus, we examined the spreading of staphylococci on mucus-like viscous surfaces (semisolid agar plates). In Chapter 4, I show that mucins, the mucosal glycoproteins that control the viscosity and wettability of the mucus layer, induce the rapid spreading and dendritic expansion of clinical isolates closely related to S. aureus and Staphylococcus epidermidis but not of Staphylococcus hominis. Mucin glycosylation controlled the hydration of the mucoid surface and the ability of the cells to spread rapidly, in a process that was dependent on the secretion of surfactant-active, phenol-soluble modulins via the agr-quorum sensing two-component system. These results provide a plausible explanation for the rapid spreading of staphylococcal otopathogens from the nasopharynx to the middle ear through a swollen, and mucin-rich Eustachian tube. The work described in this dissertation provides much needed understanding of the adaptive responses that allow (peri)oral bacteria to colonize the middle ear. The studies add to the accumulating evidence that the middle ear mucosa is not sterile but rather harbors a commensal microbiota in health. These commensal community shares many metabolic similarities with ancestors in oral biofilms and retain adaptive traits critical for growth in the otic mucosa and inhibition of otopathogens. Additionally, this work identifies environmental factors that could contribute to staphylococcal virulence, broadening the understanding of newly identified motility phenotypes in the genus that could provide novel pharmaceutical targets.
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