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Title: Competition in the long-distance market : a comparative study of the United States and Canada
Creator: Jaffery, Naqi Abbas
Date: 1991
Collection: Electronic Theses & Dissertations

Title: Black reaction to "Bird of the Iron Feather"
Creator: Hardy, Thomas Andrew
Date: 1972
Collection: Electronic Theses & Dissertations

Title: THE IMPACT OF ERAP1 FUNCTIONS ON INNATE AND ADAPTIVE IMMUNITY IN HUMAN DISEASE MODELS
Creator: Blake, Maja Kristin K.
Date: 2022
Collection: Electronic Theses & Dissertations
Description: ERAP1 has long been appreciated for its role in antigen presentation during the adaptive immune response. It is a peptidase in the endoplasmic reticulum that trims peptide antigens prior to their loading onto awaiting MHC-1. However, ERAP1 has also been shown to play an important role in innate immune responses, although the mechanisms underlying these associations have been unclear. The ERAP1 gene has also been linked to a number of autoimmune diseases including, but not limited to Multiple...
Show moreERAP1 has long been appreciated for its role in antigen presentation during the adaptive immune response. It is a peptidase in the endoplasmic reticulum that trims peptide antigens prior to their loading onto awaiting MHC-1. However, ERAP1 has also been shown to play an important role in innate immune responses, although the mechanisms underlying these associations have been unclear. The ERAP1 gene has also been linked to a number of autoimmune diseases including, but not limited to Multiple Sclerosis, Ankylosing Spondylitis, and Ulcerative Colitis. In addition, it is known to be altered in various tumor types as a means of immune evasion, and inhibitors for ERAP1 have shown promising results against tumors in vitro. Therefore, ERAP1’s significance in the susceptibility to diverse diseases is vast, and further study into how this protein participates in both innate and adaptive immune response mechanisms is justified. Our lab has previously published that immune cells and animals deficient in ERAP1 display proinflammatory phenotypes. In this dissertation, the mechanism as to how disruptions in normal ERAP1 function leads to proinflammatory phenotypes is studied. First, proinflammatory mechanisms within a critical innate immune cell, macrophages, are discerned using both ex vivo models and an in vivo inducible colitis mouse model. ERAP1 deficiency in the setting of a murine model of autoimmunity is also evaluated, revealing both disturbances in B cell development and function as dependent on normal ERAP1 activity, and that these disturbances can lead to exaggerated neuroinflammation in several murine models of MS. ERAP1 dependent proinflammatory mechanisms within B cells are further studied ex vivo using global RNA sequencing technology along with flow cytometry-based methods. Together, the results of these studies reveal that loss of ERAP1 function causes enhanced ER stress within the cell, leading to UPR activation, increased inflammasome activity, and evidence of increased pyroptosis. Given the broad spectrum of ERAP1 functions on immune cell functions, we capitalized on these insights to determine how ERAP1 inhibition might impact diseases such as cancer. Specifically, our results confirmed that that ERAP1 inhibition promoted NK cell directed tumor killing, a modality that had never been attempted until now. In conclusion, this dissertation capitalizes upon insights gained from human genetic studies associating ERAP1 with a variety of human disease susceptibilities, identifying the molecular mechanisms underlying these associations, and also illuminates possible new therapies for human diseases derived from study of ERAP1.
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Title: Electrical Weed Control in Integrated Weed Management : Impacts on Vegetable Production, Weed Seed Germination, and Soil Microbial Communities
Creator: Galbraith, Christopher G.
Date: 2023
Collection: Electronic Theses & Dissertations
Description: Electrical weeding is an emerging practice for late-season weed control that is being adopted in numerous cropping systems and agricultural industries, including Michigan vegetable production. However, little scientific research has been conducted directly evaluating the performance of electrical weeding and its effects on the agroecosystem. The objectives of the research program were to investigate electrical weeding in terms of 1) weed control, 2) crop injury, 3) economic viability, as well...
Show moreElectrical weeding is an emerging practice for late-season weed control that is being adopted in numerous cropping systems and agricultural industries, including Michigan vegetable production. However, little scientific research has been conducted directly evaluating the performance of electrical weeding and its effects on the agroecosystem. The objectives of the research program were to investigate electrical weeding in terms of 1) weed control, 2) crop injury, 3) economic viability, as well as its effects on 4) weed seed germinability and 5) rhizosphere microbial communities. Field trials at Hart, MI in 2021 and 2022 investigated these research objectives in conventional carrot and organic green bean production systems. Late-season weed control methods including one hand-weeding event (HW), one electrical weeder pass (1P), two electrical weeder passes performed consecutively [2P(ST)], one pass followed by one pass after a 14-day interval [2P(14d)], two passes followed by one pass after a 14-day interval (3P), and no late-season control (NLC) were evaluated in both carrot and green beans. Early-season weed control methods [low, medium, and intensive herbicide programs, weed-free, and no early-season control (NEC)] were also included in the carrot trials in order to produce different weed densities within which to assess the performance of the late-season weed control methods. In carrot, use of the intensive herbicide program typically led to lower densities of above-canopy redroot pigweed compared to NEC or the low herbicide program. There was no difference reported in redroot pigweed control with respect to early-season weed control methods after performing the various late-season weed control methods in 2021. However, in 2022, redroot pigweed control tended to be higher for treatments that caused initially lower weed densities (weed-free and intensive herbicide program). Increasing passes above 2P(ST) did not provide any higher control of redroot pigweed in carrot, while 3P did have higher weed control in green beans. Foliar injury did not exceed 10% in carrot and 20% for green beans. Electrical weeding did not cause any internal damage to carrot root tissue or have any effect on carrot root length. Hand weeding was correlated with a yield increase in 2022, whereas none of the electrical treatments led to any difference in yield in either year that was not related to natural variation in weed pressure. For green beans, neither electrical weeding nor hand weeding led to a yield difference in both years. Hand weeding had a significantly higher cost acre-1 than all electrical treatments in both years (19.6 and 28.4 times higher than 1P in carrot and green bean, respectively) due to the greater amount of time required. The range of time and cost acre-1 observed relates to the differences in weed pressure, where fields with higher weed competition requiring longer hand and electrical weeding times. Electrical weed control was found to significantly reduce redroot pigweed seed germination in 2021 (10 to 14%) but not in 2022. However, germination did not differ between early- or late season weed control methods in either year. Electrical weeding did not generally lead to differences in NH4+ or NO3- that would indicate changes in N mineralization in the rhizosphere. Microbial biomass C was higher after 1P than NLC in 2021. Apart from this, there were no differences in microbial biomass C or N reported with respect to early-season or late-season weed control methods in either year. Informed by the experimental results, growers can make more pragmatic decisions around investing in electrical weeding equipment based on its weed control performance, risk of crop injury, and economic feasibility compared with alternative late-season control practices. As well, electrical weeding has the potential to be an effective integrated weed management solution in vegetable production for control of the weed seedbank with little to no significant impacts on rhizosphere microbial communities.
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Title: IDENTIFYING LEVERAGE POINTS TO CREATE RESILIENCE TO CLIMATE SHOCKS IN DRYLAND SOCIAL-ECOLOGICAL SYSTEMS
Creator: Sharma, Shubhechchha
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Drylands cover approximately 40 percent of the earth’s land area and support more than a billion people, most of whom live in Sub-Saharan Africa (SSA), where agro-pastoralism is the major food system. Climate-related shocks such as drought, water-scarcity, diseases and pests, and food price spikes have profoundly impacted household food security among dryland agro-pastoralists, especially in Tanzania. Thus, there is a need to investigate mechanisms to ensure the future resilience of...
Show moreDrylands cover approximately 40 percent of the earth’s land area and support more than a billion people, most of whom live in Sub-Saharan Africa (SSA), where agro-pastoralism is the major food system. Climate-related shocks such as drought, water-scarcity, diseases and pests, and food price spikes have profoundly impacted household food security among dryland agro-pastoralists, especially in Tanzania. Thus, there is a need to investigate mechanisms to ensure the future resilience of livelihoods and food systems in these regions. The goal of this dissertation is to use resilience thinking approaches to identify points of intervention in dryland SES, to manage both present and future climate risks. Resilience assessment is guided by three major questions: “resilience of what, to what, and for whom”.Paper-I explores “resilience of what, to what, for whom” through the use of systems archetypes for a Maasai dryland agro-pastoralist food system in Northern Tanzania. The paper identified three system archetypes— Escalation, Limits to Growth, and Shifting the Burden—to (1) pinpoint the elements, patterns, and relationships that make up agro-pastoralist food systems; and (2) find leverage points to address the archetypical patterns limiting food security. The paper suggests a need for institutional strengthening and polycentricity to deal with food insecurity among agro-pastoralists. Paper-II explores what shocks Tanzanian food systems are responding to and how, i.e., “resilience of what, to what”. The paper used randomly sampled household data collected at national level through secondary sources to understand how different adaptive capacities influence their ability to deal with climate shocks, particularly with respect to ensuring food security, measured in terms of dietary diversity and household consumption expenditure. Through Structural Equation Modeling (SEM), the paper drew a path model that indicated investment in wealth and income diversification and investment in infrastructure were able to mediate the impact of shocks on food security. Paper-III similarly explores “resilience of what, to what” but using System Dynamics Modeling (SDM). The model allowed the exploration of feedback mechanisms and interactions between the population, livestock, and crop sub-sectors with food security in agro-pastoralist food systems in Naitolia village in Tanzania. The goal of the model was also to evaluate effectiveness of multiple policy scenarios required for food security. Out of four simulated scenarios, the model identified enhancing mechanisms for food production, along with reducing post-harvest losses and livestock predation, as most likely to result in a food sufficient scenario in the future. In creating these analyses and findings, the dissertation recommends four major leverage points to support food security through both present and future climate shocks : (1) maintaining diversity and redundancy in income and assets that provide insurance against failures; (2) fostering connectivity between multiple actors across networks for promoting bridging social capital; (3) ensuring polycentric governance so that the right well-connected institutions at the right time can deal with both agro-pastoralist rights to food and respond to disturbance and uncertainty. The dissertation also creates methodological advancement in the understanding of food security in complex systems under climate shocks, by utilizing a variety of approaches that support system thinking - systems archetypes, statistical modeling, and simulation through a system dynamics model.
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Title: When the War Raged On : Montana Territory, the Politics of Authority, and National Reconstruction
Creator: Andrella, Jennifer
Date: 2022
Collection: Electronic Theses & Dissertations
Description: In July 1861, the US House Committee on Territories drafted the first Reconstruction bill to detail a procedure for readmitting Southern states into the Union. Expecting a quick end to the Civil War, the earliest framers of Reconstruction recommended that rebellious states be assigned into an unorganized status as territories. It was a pragmatic solution that placed the South firmly in the control of a Republican Congress; a plan that complemented the Committee on Territories’ simultaneous...
Show moreIn July 1861, the US House Committee on Territories drafted the first Reconstruction bill to detail a procedure for readmitting Southern states into the Union. Expecting a quick end to the Civil War, the earliest framers of Reconstruction recommended that rebellious states be assigned into an unorganized status as territories. It was a pragmatic solution that placed the South firmly in the control of a Republican Congress; a plan that complemented the Committee on Territories’ simultaneous pursuit of territorial expansion in the trans-Mississippi West. Indeed, between 1861 and 1868 Congress incorporated seven Western territories to consolidate federal power in a growing domain. From the onset of the war, federal actors envisioned Reconstruction as a national process. Yet, the reality on the ground seldom matched their strategic plans. This dissertation analyzes Reconstruction from the vantage point of the Northwestern Great Plains. Using Montana Territory as a case study, I examine how relations between and among Native American nations, settlers, and government officials defined Reconstruction at both local and federal levels. The federal government had enduring political and economic interests in the Northwestern Plains prior to the outbreak of the war. Between 1828 and 1865, the region emerged as the last US stronghold of the global fur trade, cycled through several mining booms, and showed a promising future for homesteading and ranching. The Northwestern Plains were and are the homelands to a mosaic of Native American nations who asserted their rights to sovereignty by demanding federal recognition of their territorial, political, economic, and cultural autonomy. As these lands became contested under the pressure of US settlement, Native actors continued to press for visibility against local and federal modes of authority. The lived experiences of Native actors unveil some of the critical limitations of Reconstruction; that the expansion of citizenship, suffrage, and labor protections coincided with land dispossession, colonization, and erasure. By the time this study concludes in 1883, it becomes apparent that the dissolution of Reconstruction rested in the program’s failure to resolve the nation’s most fundamental questions over belonging, space, and power.I argue that Reconstruction was a process that experimented with federal and local forms of authority, settler colonialism, and state formation which came under stress after the onset of war in 1861. Republican governance throughout the Civil War and Reconstruction introduced new federal economic and political imperatives, destabilized local patterns of power among settlers, and opened new threats to Indigenous sovereignty. Using cartography, personal and mass communication, artwork, literature, and government records, this study portrays a version of Reconstruction that was fluid, chaotic, and often violent as western civil institutions either broke down or competed for primacy. By integrating the historiographies of Reconstruction, Western history, and Native American ethnohistory this study challenges the notion that federal state formation in the West (and state restoration in the South) were linear processes ushered by a collective of federal actors. Moreover, the existing literature on both Reconstruction and Western territorial expansion has overstated the ability of the federal government to produce communal order through efforts like military occupation, property laws, and multitiered administrative systems such as the Bureau of Indian Affairs. By essentializing the scale of local forces that stacked against federal administration in distant, contested spaces like Montana, the ambitious designs to restore and expand the Union ultimately produced a more exclusionary, unstable, and violent nation.
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Title: Synthesis of HIV-1 GP41 Including FP and MPER by Native Chemical Ligation with Applications to SSNMR. Expression, Solubilization, and Purification of SARS-CoV-2 Spike Protein Subunit 2
Creator: Wolfe, Robert John
Date: 2022
Collection: Electronic Theses & Dissertations
Description: AbstractSynthesis of HIV-1 GP41 Including FP and MPER by Native Chemical Ligation with Applications to SSNMR. Expression, Solubilization, and Purification of SARS-CoV-2 Spike Protein Subunit 2 By Rob Wolfe Human immunodeficiency virus type 1 (HIV-1) and Coronavirus 2019 (Covid-19) have caused substantial risk to public health worldwide. Both HIV-1 and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are membrane enveloped viruses which cause acquired immune deficiency...
Show moreAbstractSynthesis of HIV-1 GP41 Including FP and MPER by Native Chemical Ligation with Applications to SSNMR. Expression, Solubilization, and Purification of SARS-CoV-2 Spike Protein Subunit 2 By Rob Wolfe Human immunodeficiency virus type 1 (HIV-1) and Coronavirus 2019 (Covid-19) have caused substantial risk to public health worldwide. Both HIV-1 and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are membrane enveloped viruses which cause acquired immune deficiency syndrome (AIDS) and COVID-19 in humans, respectively. The process by which these viruses initiate the infection by membrane fusion of the viral and host cells is similar. However, they differ in which membrane protein is responsible for the fusion process. The HIV-1 glycoprotein 41 (Gp41) is a single-pass integral viral membrane protein containing a ~170-residue ectodomain that is important for membrane fusion between virus and host cells. The ectodomain includes the fusion peptide (FP), N-helical region (NHR), loop, C-helical region (CHR) and viral membrane-proximal external region (MPER). The ectodomain mediates joining (fusion) of the HIV-1 and host cell membranes, which is in an initial step in infection. The ectodomain also adopts different structures, including a final hyper thermostable state. Some data supports a fusion role for this final state. Like HIV-1, SARS2-CoV-2 is enveloped by a membrane that is obtained during budding from an infected host cell. Infection of a new cell requires fusion of the virus membrane with a membrane of the target cell and subsequent deposition of the viral nucleocapsid in the cytoplasm. This process is catalyzed by the Spike (S) protein subunit 2 (S2). My research has focused on the production and characterization of several protein constructs (with or without FP) and the characterization of S2_816-1273, a large S2 protein construct containing all regions including the FP, transmembrane (TM) and the cytoplasmic tail (CT). The expression vector used is pET-24a(+). Biophysical characterization comparisons between S2_816-1273 and shorter constructs including S2_903-998SGGRGG1153-1207 and S2_903-998SGGRGG1163-1207 were performed. Biophysical characterization techniques such as circular dichroism (CD) spectroscopy, size exclusion chromatography (SEC), mass spectrometry (MS), and vesicle fusion assays were used in this study. In addition, this work also describes development and application of native chemical ligation (NCL) methods to produce most of the HIV glycoprotein-41 (gp41) ectodomain. NCL with yields up to 45% were achieved between the chemically synthesized N-terminal FP (gp41512-534) and bacterially synthesized hairpin with MPER (HM) (gp41535-581/SGGRGG/628-683) segments. The hairpin is the NHR-loop-CHR region. These high yields were achieved by solubilizing the HM segment in guanidinium chloride and imidazole which worked together to fully denature the reactants, facilitating the NCL reaction via exposure of the reactant termini. HM was produced with fractional 13C or 2H-labelings that were respectively in the 14-82% and 18% to 54% ranges. The synthesized FP included a non-native N-terminal H6G6D4K tag, which allowed for the binding of FP-HM to a metal-affinity column at the Nterminus to facilitate the separation of unreacted HM. FP-HM was then released from the column by enterokinase-catalyzed cleavage. My work will help future scientists synthesize site-specific 13C and 2H labeled large protein constructs since this is the first time that large Gp41 constructs including full MPER have been synthesized in mg quantities using a combination of bacterial expression system and solid phase peptide synthesis. Furthermore, this methodology is applicable to many proteins that cannot be easily characterized by other methods inside of the lipid bilayer, such as crystallography.
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Title: DATA-DRIVEN COMPUTATIONAL APPROACHES TO UNRAVEL AGE/SEX BIASES & CROSS-SPECIES ANALOGS OF COMPLEX TRAITS AND DISEASES
Creator: Johnson, Kayla A.
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Cellular mechanisms and genetic underpinnings of most complex diseases and traits are not well understood. Most diseases also vary in their incidence and presentation in people of different ages and sexes, yet it is still largely unclear how age and sex influence normal tissue physiology and disease at the molecular level. Additionally, while we need research organisms to experimentally study many aspects of human disease etiology, choosing the best genes and conditions in a model organism...
Show moreCellular mechanisms and genetic underpinnings of most complex diseases and traits are not well understood. Most diseases also vary in their incidence and presentation in people of different ages and sexes, yet it is still largely unclear how age and sex influence normal tissue physiology and disease at the molecular level. Additionally, while we need research organisms to experimentally study many aspects of human disease etiology, choosing the best genes and conditions in a model organism for such studies is difficult due to our incomplete knowledge of functional and phenotypic conservation across species. The goal of my research is to address these challenges towards gaining a systematic understanding of the genetic etiology of complex diseases and traits. I have worked towards this goal by developing computational frameworks capable of leveraging massive amounts of publicly-available genomic data with prior knowledge using network analysis and machine learning. These approaches have shed light on the genomic signatures, pathways, and interactions that characterize the age/sex biases and cross-species analogs of complex diseases and traits. I make all the code to reproduce these approaches available by github and have provided tools to make the results searchable by scientists investigating these important biological factors. Collectively, this research will help build infrastructure for advancing biomedical research into the era of precision medicine.
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Title: 3D Printed Fluidic Devices for Biomedical Applications
Creator: Redman, Nathan Abraham
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Antimicrobial resistance represents an imminent and growing threat to global health. It is estimated that antimicrobial resistance will cause 10 million deaths a year by 2050. The testing of clinical infections for susceptibility to antimicrobial drugs is therefore critical. However, current methods of susceptibility testing are prohibitively slow, and they require pathogen isolation and culture. This inability to rapidly screen infections causes serious problems including patient mortality...
Show moreAntimicrobial resistance represents an imminent and growing threat to global health. It is estimated that antimicrobial resistance will cause 10 million deaths a year by 2050. The testing of clinical infections for susceptibility to antimicrobial drugs is therefore critical. However, current methods of susceptibility testing are prohibitively slow, and they require pathogen isolation and culture. This inability to rapidly screen infections causes serious problems including patient mortality by sepsis, over-prescription of broad-spectrum antibiotics, and the accelerated spread of antimicrobial resistance in human pathogens. Faster susceptibility testing is required to more effectively treat sepsis and prevent the unnecessary selection for resistant pathogenic strains more effectively. Quantifying drug susceptibility at the single-cell level on a multiphase chip platform will eliminate the need for culture and enable drug susceptibility screening within minutes. Antibiotics often alter extracellular levels of adenosine triphosphate (ATP) in susceptible microbial cells, while leaving resistant cells mostly unaffected. An individual microbial cell will contain ~1-5 attomoles of ATP, which is only detectable if confined to extremely small reaction volumes. Here we propose a multiphase (immiscible aqueous and ether) microfluidics platform combined with a microcapillary system (Chapters 2,3). This system will confine individual pathogens and challenge drugs inside droplets of nanoliter-scale volume to enable detection of drug-induced alteration of ATP release from susceptible cells. This system will enable more informed and specific prescription of drugs to both improve patient outcomes and relieve unnecessary selective pressure for the spread of antimicrobial resistance.The same 3D printing tools that apply well to multiphase fluidic devices are also leveraged to address biomedical challenges in tangent fields. Progress in the fields of organoid modeling and regenerative tissue printing are discussed (Chapter 4).
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Title: Unraveling Galaxy Evolution Using Numerical Simulations
Creator: Kopenhafer, Claire
Date: 2022
Collection: Electronic Theses & Dissertations
Description: One of the primary concerns in galaxy evolution is how galaxies form their stars: what keeps thatstar formation going over cosmic time, and what causes it to stop in a processes called “quenching”. Galaxies with mass similar to our own Milky Way occupy a sweet spot between abundance and brightness that makes them easy to find in the sky, and such galaxies also populate a transitionary regime in behavior that make them interesting for studying galaxy evolution. Numerical modeling— from semi...
Show moreOne of the primary concerns in galaxy evolution is how galaxies form their stars: what keeps thatstar formation going over cosmic time, and what causes it to stop in a processes called “quenching”. Galaxies with mass similar to our own Milky Way occupy a sweet spot between abundance and brightness that makes them easy to find in the sky, and such galaxies also populate a transitionary regime in behavior that make them interesting for studying galaxy evolution. Numerical modeling— from semi-analytic models to numerical simulations—are valuable tools for understanding the multiple intersecting physical processes that drive galaxy evolution. These processes act both within and around individual galaxies such that numerical models must necessarily encompass a range of spatial and temporal scales. Multiple approaches are commonly used in order for this modeling to be physically insightful. In this dissertation I will present my efforts to unravel the mechanisms of galaxy evolution affect Milky Way-like galaxies using a variety of numerical models.Addressing the issue of what causes galaxies to stop forming stars, I first investigate an unusualpopulation of galaxies called the “breakBRDs” (Tuttle and Tonnesen 2020). Within the dominant framework for galaxy quenching, galaxies first stop forming stars in their centers and later in their outskirts. This is the “inside-out” quenching paradigm. The breakBRD galaxies possess observa- tional markers that run counter to this narrative. We used the IllustrisTNG cosmological simulation (Pillepich et al. 2018b) to find a set of simulated galaxies that are analogous to the observed breakBRDs in order to better understand their evolution. We found that the breakBRD analogues are galaxies that ultimately become fully quenched, but found no clear cause for the “outside-in” modality. This is not the dominant channel for quenching in the IllustrisTNG simulation, but roughly 10% of quiescent galaxies with 10 < log10 (?∗/M⊙) < 11 had centrally-concentrated star formation similar to the breakBRD analogues.As to what keeps galaxies forming their stars, I used a set of idealized simulations of MilkyWay-like galaxies to study the interactions of the circumgalactic medium (CGM) and its host galaxy. The CGM is an extended volume of gas that accounts for about half of the baryonic matter in a galaxy’s dark matter halo. This gas is also “multiphase,” containing gas at a wide range of densities and temperatures. It may therefore function as a reservoir from which gas may cool, condense, and accrete onto the host galaxy where it can eventually drive star formation and stellar feedback primarily via Type II supernovae. This cycle of condensation and feedback may self-regulate the overall star formation rate of a galaxy. Our idealized simulations include both the CGM and explicit formation of stars but find that stellar feedback can drive outflows that disrupt the CGM with large, hot, low-density cavities. This is true even after we adjust the stellar feedback efficiency to accommodate the “settling” of the initial conditions. We therefore conclude that the picture of star formation self-regulation in Milky Way-like galaxies is missing physical processes at the edge of the galaxy halo that work in tandem with accretion of CGM gas and stellar feedback.The CGM is typically observed via absorption spectra that contain features from numerousmetal ions. In order to better compare the simulated CGM with observations, most simulations need to be post-processed to derive similar information as that extracted from spectra. Therefore, I also present preliminary work quantifying the uncertainties inherent to this post-processing. The results herein focus on the assumption that metals in the CGM follow the abundance pattern of our Sun, which is not physically well-reasoned. We derive plausible alternative abundance patterns using chemical evolution modeling and apply these to a post-processing of the FOGGIE cosmological zoom simulations (Peebles 2020; Simons et al. 2020). We find that adopting a non-Solar abundance affects the column density of CGM absorbers of about ±1 dex.Finally, I present future research directions for all the projects described herein. These includeinvestigating the CGM of the breakBRD analogues from IllustrisTNG, outlining additions to our idealized galaxy simulations that may address the issue of disruptive outflows, and both scaling up our existing uncertainty quantification project as well as including the additional source of uncertainty, ionizing radiation.
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Title: ANALYSIS OF EJECTOR-STYLE MICROBUBBLE GENERATORS : MASS-TRANSFER PROPERTIES, MATHEMATICAL MODELING, AND DESIGN ALGORITHM
Creator: Wang, Ziwei
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Gas-to-liquid mass transfer is a rate-limiting step for many commercial-scale operations in the chemical, biochemical, pharmaceutical, and wastewater-treatment industries. The use of microbubbles with a diameter on the100 μm scale has been shown to provide high volumetric mass-transfer rates due to its high gas contact area per volume. However, the use of microbubbles in commercial processes has been hampered by the lack of design algorithms with which to fabricate high-performance,...
Show moreGas-to-liquid mass transfer is a rate-limiting step for many commercial-scale operations in the chemical, biochemical, pharmaceutical, and wastewater-treatment industries. The use of microbubbles with a diameter on the100 μm scale has been shown to provide high volumetric mass-transfer rates due to its high gas contact area per volume. However, the use of microbubbles in commercial processes has been hampered by the lack of design algorithms with which to fabricate high-performance, microbubble-sparged gas-liquid contacting equipment. The goals of this study were to identify the type of microbubble generator best suited to provide high volumetric mass transfer rates in commercial-scale equipment, characterize the mass-transfer properties, develop models able to predict the mass-transfer rate as a function of the key independent variables, and use the models to develop a design algorithm suitable to use microbubble sparging in industrial processes. The study began with a literature review of microbubble generators that considered factors including the mechanism, safety, cost, and scalability, with the goal of identifying generators suited to cost-effectively provide extremely high mass transfer in commercial-scale equipment. Microbubble generators that used liquid turbulence were found to have the best combination of properties for such applications. In collaboration with the Michigan Biotechnology Institute, a 300-L bioreactor was customized for use with either a RiverForest microbubble ejector and a conventional ring sparger. E.coli batch growth experiments were conducted to compare the growth rates using the two aeration methods. The E.coli growth rate observed during microbubble aeration was about twice that observed with the traditional ring sparger. Mathematical models describing the performance properties of both a microbubble ejector and a Modified Jameson Cell were developed. The models included energy requirements, mass transfer rates, gas and liquid flow patterns, and clearance of spent bubbles. The models predicted that the ejector would be more energy-efficient for applications requiring higher mass-transfer rates and lower gas volume fractions, whereas the Modified Jameson Cell would be more energy-efficient for applications requiring lower mass-transfer rates and higher gas void fractions. Moreover, the ejector generator was considered to have operational advantages over the modified Jameson Cell in terms of surfactant requirement and scalability. Based on these advantages, ejector generators were used for subsequent studies. A novel flow system was developed to measure the mass-transfer rate of microbubble produced by an ejector generator. A mathematical model was developed to reproduce experimental trends and estimate the effective microbubble diameter generated as a function of the gas and liquid flow rates. New axial mixing and two-phase friction factor correlations were developed for the model fidelity. The mathematical model was used to determine the effective microbubble diameter that best reproduced the dissolved oxygen profile for various combinations of gas and liquid velocities. The results were used to develop a correlation to predict the effective microbubble size as a function of system properties. The predictive power of this correlation has utility for industrial process design and scale-up applications. The friction factor and microbubble diameter correlations developed in this study were used to develop additional models to simulate the microbubble mass-transfer in large reactors that are sparged with arrays of microbubble ejectors. The models simulated flow from each ejector using an entrainment model for jet cones. They also simulated arrangement of ejectors into triangular arrays to estimate insufficiently aerated volume and optimize ejector spacing. Collectively, the models developed in this study provide powerful new design tools that enable rational design, optimization, and scale-up of ejector microbubble sparger arrays for commercial-scale reactors that require extremely high volumetric mass-transfer rates.
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Title: SEX DIFFERENCES IN HYPERTENSION AND THE ROLE OF ENDOTHELIAL TRPV4 CHANNELS IN CEREBROVASCULAR AND COGNITIVE FUNCTION
Creator: Chambers, Laura Christine
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Vascular cognitive impairment and dementia (VCID) describes a spectrum of cognitive disorders that have a cerebrovascular origin. VCID can range from mild cognitive impairment to frank vascular dementia. The mechanisms behind VCID development are not fully understood and there are no effective treatments available. VCID arises from functional impairment in the small arteries and arterioles in the brain. Hypertension, which affects nearly half of all American adults, is the leading modifiable...
Show moreVascular cognitive impairment and dementia (VCID) describes a spectrum of cognitive disorders that have a cerebrovascular origin. VCID can range from mild cognitive impairment to frank vascular dementia. The mechanisms behind VCID development are not fully understood and there are no effective treatments available. VCID arises from functional impairment in the small arteries and arterioles in the brain. Hypertension, which affects nearly half of all American adults, is the leading modifiable risk factor for VCID. Hypertension impairs cerebrovascular function that can starve neurons of necessary nutrients, increasing risk of cognitive impairment. My studies focus on cerebral parenchymal arterioles (PAs), which direct blood flow from the pial circulation to the capillaries. Because they lack collateral connections, PAs are considered the weak link in the cerebral perfusion. The occlusion of a single PA creates a discrete column of ischemic tissue that can produce cognitive impairment. PAs are dependent on TRPV4 channels for endothelium-dependent dilation, and there is a strong link between TRPV4 and cognitive function. Previous studies in male rodents showed that hypertension impairs TRPV4-mediated dilation in PAs, and this was associated with memory impairments. When mineralocorticoid receptor (MR) antagonists are administered alongside developing hypertension, these impairments are prevented. However, it is thus far unknown whether MR antagonist treatment can reverse cerebrovascular and cognitive impairments after they have developed. My first aim tests the hypothesis that rats with established hypertension will have impaired TRPV4 function in PAs that is associated with cognitive impairment, and that treatment with the MR antagonist eplerenone can reverse this damage after its development. My second aim focuses on sex differences in hypertension, as this is a major gap in the literature. Thus far, all studies linking TRPV4 function to cognition have been conducted in male mice. Given that estrogen is vasoprotective in other vascular beds, I hypothesize that hypertensive female mice would be protected against impaired TRPV4 function in PAs, and from the associated cognitive deficits observed in male mice. Lastly, my third aim addresses the importance of TRPV4 channels specifically in the endothelium. There is a consistent link between TRPV4 impairment and cognitive dysfunction, but due to the channel’s ubiquitous expression, its role in endothelial cells is unknown. Here, I test the hypothesis that male and female mice with endothelial TRPV4 channel deletion will have cognitive impairment. My studies show that MR antagonism reverses cerebrovascular and cognitive damage in hypertension, and that female sex protects against the development of these impairments. Further, I show that endothelial TRPV4 channel deletion results in cognitive dysfunction and increased inflammation in both male and female mice. My studies show for the first time that young female mice have preserved TRPV4 channel function in PAs that is associated with preserved cognitive function. Further, my data suggest the MR is a promising therapeutic target in hypertensive patients because it not only protects against neurovascular damage but can reverse it after it has developed.
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Title: ANTI-DEFICIT FRAMING TYC TRANSFER STUDENTS’ SELF-EFFICACY AS CONTEXTUALLY IMPACTED BY EDUCATION ENVIRONMENTS
Creator: Wood, Laura
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The work in this dissertation aims to support a more equitable science education culture that better supports students who have historically and continue to be inequitably pushed out of science. Our equity-oriented and anti-deficit research agenda led us to study community college and transfer students as well as their self-efficacy and self-efficacy experiences. This dissertation opens by overviewing the state of STEM education and explaining how research approaches often frame students in...
Show moreThe work in this dissertation aims to support a more equitable science education culture that better supports students who have historically and continue to be inequitably pushed out of science. Our equity-oriented and anti-deficit research agenda led us to study community college and transfer students as well as their self-efficacy and self-efficacy experiences. This dissertation opens by overviewing the state of STEM education and explaining how research approaches often frame students in deficit ways. Chapter 1 introduces the author's researcher positionality and relevant literature to her research approaches. The author's research agenda prioritizes supporting marginalized students in STEM through studying the construct of self-efficacy. After reviewing the research framing, Chapter 2 introduces relevant literature about self-efficacy and two-year college (TYC) transfer student experiences. Chapter 2 ends by addressing how the author's research positionality aligns with and impacts the ways she researches self-efficacy and TYC transfer students. Afterwards, each body chapter (Chapters 3, 4, and 5) opens with a transition situating it in the broader story of the dissertation. Chapter 3 opens by reminding readers of the reasons for our qualitative approach to studying self-efficacy. Then, it describes the development of a qualitative codebook for self-efficacy. Chapter 4 opens by explaining our shift to a narrative analysis case study of a single transfer student. This chapter ultimately diverged from self-efficacy, and Chapter 4 will discuss the reasons and the results of that narrative analysis, stating that supporting characters were instrumental in a transfer student’s success story. The chapter ends with implications for universities to learn from TYCs. The dissertation transitions to Chapter 5 by broadening out from a single student’s case study to a positively impactful course experience at a TYC for STEM students intending to transfer. This chapter describes design considerations learned from the course as well as opportunities the course provided for student self-efficacy experiences. Chapter 6 discusses the story across all three body chapters as situated in the research framing and concludes the dissertation.
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Title: NEAR INFRARED (NIR) SURFACE-ENHANCED RAMAN SPECTROSCOPY AND FLUORESCENCE MICROSCOPY FOR MOLECULAR-GUIDED SURGERY
Creator: Yao, Cheng-You
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Molecular imaging has become an emerging technology to assess tumor margins. As the imaging contrast agents are functionalized with multiple ligands that can bind to different biomarkers – multiplexed molecular imaging, this technique can achieve high sensitivity and specificity for tumor margin detection. Optical-based molecular imaging modalities provide non-hazardous optical radiation, multiplexing wavelengths, and higher spatial resolution than ionizing radiation tomography techniques....
Show moreMolecular imaging has become an emerging technology to assess tumor margins. As the imaging contrast agents are functionalized with multiple ligands that can bind to different biomarkers – multiplexed molecular imaging, this technique can achieve high sensitivity and specificity for tumor margin detection. Optical-based molecular imaging modalities provide non-hazardous optical radiation, multiplexing wavelengths, and higher spatial resolution than ionizing radiation tomography techniques. Two categories of optical contrast agents, fluorescent dyes and Surface-Enhanced Raman Spectroscopy (SERS) nanoparticles are introduced and mainly applied in this dissertation. However, because of the tissue-photon interactions, the imaging contrast and penetration depths are limited by the visible wavelengths. The light in the NIR regime (700~1700 nm) has shown a deeper imaging penetration and better contrast with lower autofluorescence background. Thus, in this dissertation, NIR fluorescent dyes and SERS NPs excited by 785 nm are used for ex vivo and in vivo imaging for biological studies.This work aims to develop a variety of optical instruments for NIR ex vivo and in vivo biomedical imaging applications with deeper penetration, better contrast, and higher sensitivity. The optical instruments include a spectrometric system for SERS Raman detection, a VO2 MEMS scanner for SERS imaging, portable confocal microscopes, and a PZT MEMS scanner-based macroscope for wide-field fluorescence imaging. Chapter 1 briefly introduced the research background, pros and cons of existing techniques, and motivations of this study. In Chapter 2, the spectrometric SERS Raman system and ratiometric analysis have been applied to the detection of Alzheimer's Disease biomarkers and breast cancer image-guided surgery, using different SERS NPs conjugated with ligands. The Raman results were confirmed with histological analysis. In Chapter 3, a VO2 MEMS scanner has been designed, fabricated, and characterized for the Lissajous scanning SERS imaging application. In Chapter 4, two variants of the portable confocal microscopes, the point-scan and line-scan systems were designed with reflective parabolic mirrors for broadband wavelengths from the visible to NIR ranges. Ex vivo and in vivo confocal imaging results have been demonstrated using tumor-bearing mouse tissues. In Chapter 5, a thin-film PZT MEMS scanner has been reported, characterized, and integrated into a wide-field macroscope for fluorescence imaging. In Chapter 6, a novel photodetector - SNSPD has been integrated into the point-scan portable confocal microscope and PZT MEMS scanner-based wide-field macroscope to increase the efficiency and contrast of fluorescent imaging in the NIR range. In the last chapter, the future applications of the advanced VO2 MEMS scanners and fluorescence lifetime imaging microscopy using SNSPD were discussed in detail.
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Title: Perinatal HIV Exposure and Infection and its Association with Caregiver Depression Symptoms and Child Executive Function
Creator: Brewer, Sarah Kathleen
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Survival is possible for children perinatally exposed to or infected by Human Immunodeficiency Virus (HIV) in the post-combined antiretroviral therapy era, but the long-term effects of HIV exposure on children and their caregivers are still being explored. Identifying factors affecting children’s ability to thrive within an HIV context has great public health significance, particularly within a sub-Saharan context where the burden of HIV is felt disproportionately by women and children....
Show moreSurvival is possible for children perinatally exposed to or infected by Human Immunodeficiency Virus (HIV) in the post-combined antiretroviral therapy era, but the long-term effects of HIV exposure on children and their caregivers are still being explored. Identifying factors affecting children’s ability to thrive within an HIV context has great public health significance, particularly within a sub-Saharan context where the burden of HIV is felt disproportionately by women and children. Additionally, caregiver mental health is an important focus given its bidirectional relationship with child behavior. Previous studies on these topics have not included a full complement of HIV exposure or infection groups, considered how caregivers’ mental health may depend on child serostatus, and or are investigated in HIV endemic areas. The three aims presented in this dissertation will explore how perinatal HIV infection and exposure can affect caregivers and school-aged children. In Aim one, we compare depressive symptoms among caregivers of 3 groups of 6-10 year old children in Uganda with known HIV exposure status: children HIV-infected perinatally (CPHIV, n=102), children born to HIV-infected mothers, but HIV negative (CPHEU, n=101), and HIV-unexposed, uninfected community controls (CHUU, n=103). Caregiver depression symptoms were assessed using the Hopkins Symptom Checklist. In Aims two and three, child executive functioning (EF) assessed by caregiver report was compared across the three HIV exposure groups; effect modification of these associations by social support and wealth was also explored. We used random effects general linear models to estimate mean differences among the three HIV exposure groups. Adjusted models included caregiver age, education, social support, lifetime trauma, and wealth as covariates. In aim one, we observed that perinatal HIV exposure status was associated with mean caregiver depression symptoms. Specifically, in unadjusted analyses, depression symptoms were higher among CPHEU compared to CPHIV caregivers (unstandardized beta coefficient [B]=-3.5, 95% confidence interval [CI] -5.3, -1.8). We also observed that caregiver social support modified the findings above (p < 0.10) with CPHEU caregivers with lower social support and lower wealth reporting higher caregiver depressive symptoms compared to CPHIV caregivers. We repeated all analyses within the subsample of biological mothers to examine whether their own diagnostic status drove any findings we observed; our pattern of results remained unchanged. For Aim two, in our unadjusted analyses, perinatal HIV exposure was not associated with the Global Executive Composite (GEC) and Metacognition Index (MCI) scores of EF. However, for the Behavioral Regulation Index (BRI), the CPHIV group had lower levels of problems relative to the CHUU and CPHEU groups (B= -0.40, 95% CI -0.77, -0.03, B=-0.40, 95%CI -0.76, -0.02 respectively). For Aim three, we observed that the child’s sex and caregiver depression symptoms modified the association between HIV status and specific subscales of EF. Future directions for this work should include investigation into what drives the difference in caregiver depression symptoms between exposure groups. Additionally, collecting longitudinal measures of child EF and caregiver depression would help further interrogate time order between caregiver and child functioning among families affected by HIV. Lastly, continued investigation on how our findings relate to outcomes linked to EF such as academic achievement and behavioral problems would help to establish the importance of EF as a potential intervention target to improve school readiness.
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Title: Understanding Student Experiences in Informal Physics Programs Using the Communities of Practice Framework
Creator: Prefontaine, Brean Elizabeth
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Studies on physics identity have shown that it is one of the main factors that can predict a person’s persistence in the field; therefore, studying physics identity is critical to increase diversity within the field of physics and to understand what changes can allow more women and people of color to identify with the field. Informal physics spaces are not only made up of youth participants, but also facilitators who can be undergraduate or graduate student volunteers. In this work, the...
Show moreStudies on physics identity have shown that it is one of the main factors that can predict a person’s persistence in the field; therefore, studying physics identity is critical to increase diversity within the field of physics and to understand what changes can allow more women and people of color to identify with the field. Informal physics spaces are not only made up of youth participants, but also facilitators who can be undergraduate or graduate student volunteers. In this work, the experiences of facilitators within informal physics programs are investigated as spaces for physics identity development. Thus, the driving question for all of this work is: In what ways can participating as a facilitator within an informal physics program affect identity development? The data for these studies were collected through observations, written artifacts, and semi-structured interviews with those who facilitated the informal physics programs. In order to understand more about the experiences of the facilitators, the informal physics programs were viewed as Communities of Practice (CoP), and the CoP framework was operationalized within the context of these spaces. First, stories from two physics graduate students out of the interview sample are presented to provide a context for testing the feasibility of the extended framework and to identify how experiences within an informal physics program can shape physics identity development. Then, the operationalized CoP framework is used to study three distinct informal physics programs to understand the structures that support physics identity development. Finally, informal programs that combine physics and music/art are examined with the operationalized CoP framework to understand how these blended spaces can form communities of practice and support identity development. Analysis showed that the CoP framework is an effective tool for analyzing informal physics programs and highlights the structures that lead to identity development. These findings indicate that informal physics programs that operate with a CoP structure can provide valuable experiences to undergraduate and graduate facilitators that lead to physics identity growth.
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Title: The Construct Development and Measurement of Contributive Justice
Creator: Scott, William Campbell
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Organizational justice has long since been considered multi-dimensional. However, the dimensionality of organizational justice has been stagnant in recent years, consisting primarily of distributive, procedural, interpersonal, and informational justice. When further examining the meaning of justice and fairness in organizations, it becomes apparent that these organizational justice dimensions are not capturing an important element of justice, that being the equality of opportunity. This is an...
Show moreOrganizational justice has long since been considered multi-dimensional. However, the dimensionality of organizational justice has been stagnant in recent years, consisting primarily of distributive, procedural, interpersonal, and informational justice. When further examining the meaning of justice and fairness in organizations, it becomes apparent that these organizational justice dimensions are not capturing an important element of justice, that being the equality of opportunity. This is an important absence because the opportunity to contribute in organizations will likely affect both organizational outcomes and personal outcomes outside of work. Therefore, building upon previous work, the construct of contributive justice in organizations was introduced and defined as the fairness of opportunities to contribute to core work processes. Contributive justice consists of two dimensions, the equal opportunity to engage in complex labor, and the equal opportunity to participate in decision-making processes. A measure was constructed to capture these dimensions, along with specific subdimensions. In a sample of 534 full-time employees, the results suggested that the contributive justice measure was a reliable two-factor measure that was discriminable from the other organizational justice dimensions and was positively correlated with other variables such as meaningful work, instrumental voice, inclusion, empowerment, and self-esteem. Contributive justice was also found to have incremental validity over the other organizational justice dimensions. These results suggest the importance of contributive justice as an aspect of organizational fairness and employee well-being.
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Title: MACHINE LEARNING APPROACHES FOR PROCESSING AND DECODING ATTENTION MODULATION OF SENSORY REPRESENTATIONS FROM EEG
Creator: saba-sadiya, sari
Date: 2023
Collection: Electronic Theses & Dissertations
Description: This thesis presents novel machine learning algorithms that achieve state-of-the-art performance on a variety of electroencephalography (EEG) tasks, including decoding, classification, and unsupervised / semi-supervised artifact detection and correction. These algorithms are then used within the scope of an EEG experiment that explores how attention to multiple items modulates sensory representations. Using a signal detection paradigm, we demonstrate that attending to multiple items impacts...
Show moreThis thesis presents novel machine learning algorithms that achieve state-of-the-art performance on a variety of electroencephalography (EEG) tasks, including decoding, classification, and unsupervised / semi-supervised artifact detection and correction. These algorithms are then used within the scope of an EEG experiment that explores how attention to multiple items modulates sensory representations. Using a signal detection paradigm, we demonstrate that attending to multiple items impacts the sensitivity of our participants, causing a sharp increase in false-alarm rates and only slightly decreasing hit-rate. We conclude that our behavioral and EEG decoding results contradict simultaneous attention guidance by multiple items (the multiple item template hypothesis).
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Title: DEVELOPMENT OF 3D BIOACTIVE AND ANTIBACTERIAL SILICATE-BASED SCAFFOLDS FOR BONE TISSUE REGENERATION IN LOAD-BEARING APPLICATIONS
Creator: Marsh, Adam Christoph
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Current gold-standard approaches to addressing the needs of bone defects in load-bearing applications entail the use of either autographs or allographs. Both solutions, however, are imperfect as both autographs and allographs carry the risk of additional trauma, threat of disease transmission, and potential donor rejection respectively. Porous 3D scaffolds are attractive alternatives, illuminating a potential path towards achieving the ideal scaffold for targeting bone tissue regeneration in...
Show moreCurrent gold-standard approaches to addressing the needs of bone defects in load-bearing applications entail the use of either autographs or allographs. Both solutions, however, are imperfect as both autographs and allographs carry the risk of additional trauma, threat of disease transmission, and potential donor rejection respectively. Porous 3D scaffolds are attractive alternatives, illuminating a potential path towards achieving the ideal scaffold for targeting bone tissue regeneration in load-bearing applications, usurping autographs to become the new gold-standard. To unlock the full healing potential of 3D scaffolds, such scaffolds must be multifunctional such that (1) their mechanical performance meets the requisite requirements as dictated by the mechanical performance characteristics of interest for native bone tissue, (2) they stimulate the necessary biological responses for bone tissue regeneration, and (3) they exhibit antibacterial characteristics to combat the threat of infection. To date, no reports document 3D scaffolds exhibiting all three performance characteristics. The aim of this dissertation, therefore, is to deliver 3D scaffolds that are mechanically competent, possess and exhibit inherent and advanced antibacterial characteristics, and are successful at providing the needed biological characteristics for bone tissue regeneration. To achieve this, this dissertation implements a multidisciplinary approach, utilizing comprehensive structural characterization across a wide range of scales to elucidate process – performance relationships to execute scientifically driven modifications to engineer and deliver a 3D scaffold to successfully target bone tissue regeneration in load-bearing applications. A silver-doped bioactive glass-ceramic (Ag-BG) composition was selected as the material for scaffold synthesis due to its inherent and attractive antibacterial and biological performance characteristics. Two fundamentally different processing approaches were utilized for synthesizing Ag-BG scaffolds: the polymer foam replication technique and fused filament fabrication (FFF). The Ag-BG scaffolds studied herein were found to exhibit advanced antibacterial performance characteristics against methicillin-resistant Staphylococcus aureus (MRSA), a common pathogen implicated in osteomyelitis development, able to combat MRSA both in planktonic and biofilm forms. Ag-BG scaffolds demonstrated the ability to form an apatite-like layer when immersed in simulated body fluid (SBF), an indicator that Ag-BG scaffolds will induce the necessary mineralization for bone tissue regeneration, in addition to exhibiting attractive cell viability, proliferation, and differentiation characteristics when studied in vitro. The mechanical performance of Ag-BG scaffolds reported herein saw progressive improvements in each iteration of Ag-BG scaffold synthesis, achieving desirable mechanical competency and reliability as a result of the multidisciplinary approach formulated. In addition to the exploration of developing 3D antibacterial and biological silicate-based scaffolds capable of targeting bone tissue regeneration in load-bearing applications, foundational work towards the development of class II hybrid scaffolds comprised of gelatin methacryloyl (GelMA) and Ag-BG for targeting softer tissue regeneration. The novel syntheses applied to the successful molecular coupling of GelMA and Ag-BG presents an attractive class II hydrogel showing great promise as a compatible ink for 3D bioprinting cell-laden scaffolds capable of targeting tissue regeneration of more sophisticated systems.
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Title: Molecular epidemiology, pangenomic diversity, and comparative genomics of Campylobacter jejuni
Creator: Rodrigues, Jose Alexandre
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Campylobacter jejuni, the leading cause of bacterial gastroenteritis in the United States, is often resistant to commonly used antibiotics and has been classified as a serious threat to public health. Through this work, we sought to evaluate infection trends, quantify resistance frequencies, identify epidemiological factors associated with infection, and use whole-genome sequencing (WGS) as well as comparative phylogenomic and pangenomic approaches to understand circulating C. jejuni...
Show moreCampylobacter jejuni, the leading cause of bacterial gastroenteritis in the United States, is often resistant to commonly used antibiotics and has been classified as a serious threat to public health. Through this work, we sought to evaluate infection trends, quantify resistance frequencies, identify epidemiological factors associated with infection, and use whole-genome sequencing (WGS) as well as comparative phylogenomic and pangenomic approaches to understand circulating C. jejuni populations in Michigan. C. jejuni isolates (n=214) were collected from patients via an active surveillance system at four metropolitan hospitals in Michigan between 2011 and 2014. Among the 214 C. jejuni isolates, 135 (63.1%) were resistant to at least one antibiotic. Resistance was observed for all nine antibiotics tested yielding 11 distinct resistance phenotypes. Tetracycline resistance predominated (n=120; 56.1%) followed by resistance to ciprofloxacin (n= 49; 22.9%), which increased from 15.6% in 2011 to 25.0% in 2014. Notably, patients with ciprofloxacin resistant infections were more likely to report traveling in the past month (Odds Ratio (OR): 3.0; 95% confidence interval (CI): 1.37, 6.68) and international travel (OR: 9.8; 95% CI: 3.69, 26.09). To further characterize these strains, we used WGS to examine the pangenome and investigate the genomic epidemiology of this set of C. jejuni strains recovered from Michigan patients. Among the 214 strains evaluated, 83 unique multilocus sequence types (STs) were identified that were classified as belonging to 19 previously defined clonal complexes (CCs). Core-gene phylogenetic reconstruction based on 615 genes identified three clades, with Clade I comprising six subclades (IA-IF) and predominating (83.2%) among the strains. Because specific cattle-associated STs, such as ST-982, predominated among strains from Michigan patients, we also examined a collection of 72 C. jejuni strains from cattle recovered during an overlapping time period by WGS. Several phylogenetic analyses demonstrated that most cattle strains clustered separately within the phylogeny, but a subset clustered together with human strains. Hence, we used high quality single nucleotide polymorphism (hqSNP) profiling to more comprehensively examine those cattle and human strains that clustered together to evaluate the likelihood of interspecies transmission. Notably, this method distinguished highly related strains and identified clusters comprising strains from both humans and cattle. For instance, 88 SNPs separated a cattle and human strain that were previously classified as ST-8, while the human and cattle derived ST-982 strains differed by >200 SNP differences. These findings demonstrate that highly similar strains were circulating among Michigan patients and cattle during the same time period and highlight the potential for interspecies transmission and diversification within each host. In all, the data presented illustrate that WGS and pangenomic analyses are important tools for enhancing our understanding of the distribution, dissemination, and evolution of specific pathogen populations. Combined with more traditional phenotypic and genotypic approaches, these tools can guide the development of public health prevention and mitigation strategies for C. jejuni and other foodborne pathogens.
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