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Title: INVESTIGATING THE IMPACT OF ANTIOXIDANT SUPPLEMENTATION ON MUSCLE ANTIOXIDANT STATUS AND THE SKELETAL MUSCLE PROTEOME IN THOROUGHBRED RACEHORSES
Creator: Henry, Marisa LeeAnn
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Glutathione (GSH) and Coenzyme Q10 (CoQ10) are potent cellular antioxidants that work to mitigate oxidative stress arising from reactive oxygen species (ROS) production. GSH is not well absorbed because it is broken down into individual amino acids in the small intestines. Cysteine is the rate limiting amino acid in GSH synthesis but is not well absorbed and is instead largely produced from methionine intracellularly. N-acetyl cysteine (NAC) supplementation has been studied as an alternative...
Show moreGlutathione (GSH) and Coenzyme Q10 (CoQ10) are potent cellular antioxidants that work to mitigate oxidative stress arising from reactive oxygen species (ROS) production. GSH is not well absorbed because it is broken down into individual amino acids in the small intestines. Cysteine is the rate limiting amino acid in GSH synthesis but is not well absorbed and is instead largely produced from methionine intracellularly. N-acetyl cysteine (NAC) supplementation has been studied as an alternative to cysteine or GSH supplements and has been shown to increase the amount of circulating cysteine and increase transport activity for this reduced form in humans. GSH concentrations in skeletal muscle have been measured in only a few studies in other species. Neither GSH nor NAC have been previously studied in the skeletal muscle of horses. CoQ10 is an electron transporter in the mitochondrial electron transport chain (ETC) where it transfers electrons either from complex I or complex II to complex III. Within the ETC, complex I has been shown to be the primary source of ROS during exercise in comparison to the other complexes. Due to its location and function, CoQ10 can also function as a potent membrane bound antioxidant and mitigate ROS produced through the ETC. CoQ10’s function as an antioxidant and electron transporter has not been studied in great depth in horses. Branched chain amino acid (BCAA) supplements are three essential amino acids that have been shown to have positive effects on protein synthesis through the mammalian target of rapamycin pathway (mTOR). BCAA can serve as an energy source in skeletal muscle where they are directly metabolized in the tricarboxylic acid cycle. There are a limited number of studies of the impact of BCAA supplementation on equine skeletal muscle and none have looked at BCAA combined with antioxidant supplements. The overarching objective of this dissertation was to evaluate the impact of antioxidant supplementation on fit, healthy Thoroughbred horses. The first study supplemented NAC and CoQ10 to maximally exercising Thoroughbreds to determine its effect on the redox equilibrium and skeletal muscle proteome. We determine that NACQ increases muscle GSH concentrations post exercise while increasing TCA cycle enzymes and enhancing capacity for cellular NADPH production. The second study measured the effect of a single dose of differing amounts and formulations of CoQ10 on plasma CoQ10 concentrations. We determined that individual horses have different absorption responses, with 50% showing no response. The third study analyzed chronic CoQ10 supplementation’s effect on plasma CoQ10 concentrations, concentrations or activities of skeletal muscle antioxidants, mitochondrial respiration, and the skeletal muscle proteome. Results supported CoQ10’s function as an antioxidant and ability to alter the contribution of complex I and complex II to electron transfer without increasing mitochondrial volume density. The final study of this dissertation analyzed the impact of NAC and BCAA supplementation on sub-maximally exercising Thoroughbreds by measuring antioxidant status and alterations to the skeletal muscle proteome before and after exercise. This study identified no changes in skeletal muscle GSH concentrations and ROS before or after exercise but did find differentially expressed proteins within the ETC, redox reactions, and glycolysis after submaximal exercise. All supplements warrant further investigation in horses with myopathies.
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Title: An exploratory analysis of next of kin data in COVID-19 deaths
Creator: Rukat, Caitlin
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Objective: This thesis aims to: 1) conduct a formative evaluation of the next of kin (NOK) interview data collected during the Michigan COVID-19 Death Investigation (MiCOVDI);2) investigate the prevalence of proxy-reported health care discrimination experienced by those that died from COVID-19 in Michigan during March 3-July 26, 2020. Methods: Decedents were eligible for inclusion in the mortality review if COVID-19 was listed as an underlying or related cause of death on the death...
Show moreObjective: This thesis aims to: 1) conduct a formative evaluation of the next of kin (NOK) interview data collected during the Michigan COVID-19 Death Investigation (MiCOVDI);2) investigate the prevalence of proxy-reported health care discrimination experienced by those that died from COVID-19 in Michigan during March 3-July 26, 2020. Methods: Decedents were eligible for inclusion in the mortality review if COVID-19 was listed as an underlying or related cause of death on the death certificate. A stratified random sample of deaths was taken and NOK interviews were conducted via telephone. The completeness of the dataset was assessed to evaluate feasibility and validity. NOK-reported discrimination in decedent’s COVID-19 testing and care was described and compared by attributes of the decedent and NOK using univariate statistics. Qualitative interview responses were used to elaborate on the NOK’s understanding of the decedent’s experience. Results: The overall prevalence of NOK-reported health care discrimination experienced by the decedent was 28% with no strong associations with decedent or NOK attributes. The majority of reported discrimination was age- (20%) or comorbidity-based (27%). The prevalence estimates of situation-specific discrimination were: doctor’s office (2%), urgent care (12%), COVID-19 testing (13%), being hospitalized (14%), and at an emergency room (18%). The overall completeness of the MiCOVDI survey was 59%. Completeness did not differ by race. Conclusion: Mortality reviews shed light on systematic issues experienced by those that passed away from COVID-19 and may inform targets that improve health equity. Examining the completeness of these data can provide insight to improve future endeavors.
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Title: PRE-SERVICE SCIENCE TEACHERS’ ARTICULATION AND REVISION OF FRAMEWORKS OF SCIENCE TEACHING IN A JUSTICE-ORIENTED METHODS CLASS
Creator: Brien, Sinéad Carroll
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The reasons particular people enjoy science, pursue science, and see themselves as science people, or not, are diverse and complex (Brickhouse, et al., 2000). The ways that teachers present science and value particular ways of knowing and doing in the classroom can influence which students see themselves as science people (Carlone et al, 2011). When teachers treat one particular cultural way of knowing in science as the superior way of knowing, specifically Eurocentric ethnoscience with its...
Show moreThe reasons particular people enjoy science, pursue science, and see themselves as science people, or not, are diverse and complex (Brickhouse, et al., 2000). The ways that teachers present science and value particular ways of knowing and doing in the classroom can influence which students see themselves as science people (Carlone et al, 2011). When teachers treat one particular cultural way of knowing in science as the superior way of knowing, specifically Eurocentric ethnoscience with its grounding in whiteness, heteropatriarchy, Protestantism, and settler colonialism, they create/maintain a hierarchy of knowledge that limits how all students can participate and see themselves in science, in particular girls, Black students, Indigenous students, and students of Color (Archer et al., 2010; Bang et al., 2012; Mutegi, 2013). Especially as Eurocentric ethnoscience is often presented as neutral, objective and universal (Harding, 2006), science teachers may not realize that there are multiple ways to know and do in science. In this study I draw from Gee’s (2016) conception of Framework Discourse Analysis to posit that pre-service science teachers (PSTs) can be supported to articulate, question, and revise their socially-derived ideas/expectations of science and teaching (i.e., their “frameworks” of science and teaching) through participation in my two-semester long Science Teaching Methods Class focused on justice-oriented science teaching. Through a case study of three PSTs’ select artifacts from the class and interviews the summer after the class, I identified each PST’s frameworks of science and teaching, how PSTs questioned and revised these across Methods Class, and which types of Methods Class activities supported this articulation, questioning, and revising of frameworks. I found that all PSTs clearly articulated their frameworks of science and teaching and that a pluralist/contextual framework of science was important in developing justice-oriented science teaching frameworks. In addition, the types of Methods Class activities that supported clearer articulation of science and teaching frameworks were those focused on connecting science and culture, expanding notions of what it meant to be a “successful” science student, and methods to recognize and address the sociopolitical in science and teaching in the classroom. These findings have implications for the use of Gee’s (2016) Framework Discourse Analysis as a guide for raising critical consciousness and recognizing value in multiple ways of knowing and doing. In addition, they raise questions about criteria for recruiting pre-service science teachers and assessing their readiness to enter the field of teaching as justice-oriented science teachers.
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Title: INVESTIGATIONS INTO THE VIRUS-LIKE PARTICLE BACTERIOPHAGE Qβ AS A CARRIER PLATFORM IN CONJUGATE VACCINES AGAINST CANCER AND ALZHEIMER’S DISEASE
Creator: McFall-Boegeman, Hunter Sean
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Traditional vaccines are made of either killed or live-attenuated viruses. Killed virus vaccines may suffer from weak immune responses and live attenuation is an inexact science that can take years. There has been an interest in developing alternative vaccine technologies. One class of vaccine technology that has shown promise is the subunit conjugate vaccine. In such vaccines only antigenically relevant portions of infectious agents are conjugated to a carrier capable of stimulating a...
Show moreTraditional vaccines are made of either killed or live-attenuated viruses. Killed virus vaccines may suffer from weak immune responses and live attenuation is an inexact science that can take years. There has been an interest in developing alternative vaccine technologies. One class of vaccine technology that has shown promise is the subunit conjugate vaccine. In such vaccines only antigenically relevant portions of infectious agents are conjugated to a carrier capable of stimulating a stronger immune response. The use of virus-like particles as carriers in conjugate vaccines has shown promise, allowing for the targeting on non-traditional vaccine targets. In this dissertation we report on the use of the virus-like particle Qβ as a carrier in conjugate vaccines targeting cancer and Alzheimer’s disease. Cancer’s ability to escape the immune response requires a total immune response ensure that cancer does not mutate and return resistant to previously used immunotherapies. Previous use of Qβ-based conjugate vaccines against cancer have focused eliciting humoral responses. Herein we report lessons learned from the attempts to functionalize Qβ to elicit cellular immune response in a manner that would minimize the effect on a potential humoral response. Alzheimer’s disease is one of the most common causes of dementia and is hallmarked by the aggregation of tau. A Qβ-based conjugate vaccine targeting the tau-tau binding sites was synthesized and evaluated. Immunization generated a strong humoral immune response superior to a KLH-based conjugate vaccine targeting the same epitope. Generated antibodies were able to preferentially recognize disease associate forms of tau and stain tau in human tissue.
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Title: SEMI-ANALYTICAL METHOD FOR THE ANALYSIS AND DESIGN OF CYLINDERS WITH CONTROLLABLE ELASTIC POST-BUCKLING RESPONSE
Creator: Imani Azad, Ali
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Research over the past ten years has generated an increased interest in studying elastic structural instabilities as a useful response for smart applications rather than a failure. Buckling under axial compression is a type of structural instability that can be used for rapid geometric transformations (switching) and energy harvesting applications, if the deformations arising from buckling are properly controlled. Controlling transverse deformations due to buckling in slender elements usually...
Show moreResearch over the past ten years has generated an increased interest in studying elastic structural instabilities as a useful response for smart applications rather than a failure. Buckling under axial compression is a type of structural instability that can be used for rapid geometric transformations (switching) and energy harvesting applications, if the deformations arising from buckling are properly controlled. Controlling transverse deformations due to buckling in slender elements usually needs external constraints/boundaries. Short thin-walled cylinders can experience several elastic buckling events under axial compression without additional constraints. However, predicting the post-buckling response in cylinders is very challenging, particularly far in the post-buckling regime since they are highly sensitivity to initial imperfections.The concept of cylinders with non-uniform stiffness distribution (NSD) was recently proposed to localize a cylinder’s buckling events in targeted zones. This notion has been proven effective for controlling the number of elastic buckling events, the sequence at which they occur, and the regions experiencing buckling. However, this information is not enough to design NSD cylinders for smart applications, which requires being able to predict the actual applied force for each buckling event, the end shortening of the cylinder for the buckling event, the drop in force, the drop in strain energy, and the post-buckling stiffness of the cylinder. Here, a semi-analytical model has been developed to predict the elastic post-buckling response of NSD cylinders under compression. The developed semi-analytical model is based on three general steps: • Separate the NSD cylinder into parallel segments, • Simplify and predict the response of each segment, and • Integrate the response of individual segments. The first step in predicting the elastic post-buckling response of a cylindrical segment was to simplify its geometry into a cylindrical panel with uniform thickness. Linear springs are connected to the top and bottom of the uniform cylinder to match the stiffness of the simplified segment to the actual one. Based on classical shell theory, the elastic post-buckling response of a cylindrical panel is solved as a boundary value differential equation using the pseudo-arclength method. Comparing the post-buckling response of four cylinders from the proposed semi-analytical model with the response of the same cylinders from the experiment and finite element analysis showed the effectiveness of the proposed model. Results from the proposed model predict well the axial deformation and force level corresponding to buckling events more accurately than the post-buckling stiffness. The response of cylindrical panels for a large variety of dimensions is needed to design NSD cylinders for targeted post-buckling behavior. Thus, the classic differential equation of the cylindrical panels under axial compression was solved independently of the material's cylinder radius and elastic modulus. These results allowed the development of design maps for several post-buckling responses such as axial strain and stresses corresponding to the first buckling event, force, and energy drops from the buckling event, the secondary (or post-buckling) stiffness of the panel, the radial deformation at the panel center, and the maximum von Mises stress in the panel. By using genetic programming, predictive equations were developed for each design parameter to relate it to the geometry of the panels. Three cylinders were designed using the developed design maps to validate the proposed approach. One NSD cylinder was designed to undergo several buckling events under compression at pre-defined end shortenings. A second NSD cylinder was designed to feature a post-buckling force-deformation response that plateaus at a constant force level. The third cylinder was designed to experience the same force drop at each buckling event and in identical axial end shortenings after the first event. Finite element analyses of the designed cylinders verified that using the proposed design procedure using the developed design maps provides NSD cylinders with a post-buckling response that is very close to the desired one, and the ultimate design goal can be achieved by slight modifications to the geometry of the cylinder. This study advances the knowledge on the elastic buckling and post-buckling response of slender cylindrical shells under axial compression and provides an approach to analyze and design them for a desired far post-buckling response. The proposed framework, which combines the notion of decomposing NSD cylindrical segments into linear and nonlinear springs in series, a semi-analytical model for NSD equivalent panels, and design maps for several nonlinear responses provides insight for designing these elements for smart devices and structures relying on structural instabilities. This work expands the harnessing of elastic instabilities to the area of thin-shell buckling under compression, which has received less attention in comparison to other forms of structural instability.
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Title: The Storyteller’s Granddaughtxr : (Re)Envisioning Methodologies for Healing and Liberation
Creator: Furman, Olivia Ann
Date: 2022
Collection: Electronic Theses & Dissertations
Description: My dissertation is an arts-based embodiment, in the form of an exhibition in the LookOut Gallery of Snyder-Phillips Hall at Michigan State University (MSU). This exhibition is the culmination of my interdisciplinary auto-ethnographic dissertation study, within which I utilize Black feminist-womanist storytelling methodology (Baker-Bell, 2017) and Black womxn's literacies of critical self-reflection, art-making, and Afrofuturist dreaming to articulate my own Black womxn's standpoint (Collins,...
Show moreMy dissertation is an arts-based embodiment, in the form of an exhibition in the LookOut Gallery of Snyder-Phillips Hall at Michigan State University (MSU). This exhibition is the culmination of my interdisciplinary auto-ethnographic dissertation study, within which I utilize Black feminist-womanist storytelling methodology (Baker-Bell, 2017) and Black womxn's literacies of critical self-reflection, art-making, and Afrofuturist dreaming to articulate my own Black womxn's standpoint (Collins, 2002). This collection is an inquiry, a piecing together of quilting, collage, speculative fiction, my story, and the intergenerational stories of other Black womxn and femmes to consider the ways our ancestors, identities, and embodied knowledges inform our method(ologie)s of sustainability, healing, and liberation.*Keywords: womanist, Black feminist, storytelling, interdisciplinary, auto-ethnography*Throughout my work, I use an “x” in words such as womxn, mothxrs & othermothxrs to disrupt binary conceptualizations of gendered identities, and to be inclusive of the diverse range of queer and gendered identities and experiences.
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Title: ENERGY TRENDS IN IRRIGATION : A METHOD FOR ESTIMATING LOCAL AND LARGE-SCALE ENERGY USE IN AGRICULTURE
Creator: McCarthy, Benjamin Michael
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Agricultural Intensification has presented various opportunities for study in the field of water use, crop trends and energy consumption. In the United States alone, 70% of water consumed is used for the agricultural sector. Whether sources from surface bodies or groundwater, the energy required to irrigate fields has changed over the last three decades. The advent of efficient irrigation systems has created new avenues for farmers to grow crops, through new planting practices, increased...
Show moreAgricultural Intensification has presented various opportunities for study in the field of water use, crop trends and energy consumption. In the United States alone, 70% of water consumed is used for the agricultural sector. Whether sources from surface bodies or groundwater, the energy required to irrigate fields has changed over the last three decades. The advent of efficient irrigation systems has created new avenues for farmers to grow crops, through new planting practices, increased water extractions and varied on-farm practices. In this thesis, I evaluate the impact that shifting technologies have had on the FEW nexus, with a strong emphasis on the Energy consumption from irrigation. In Chapter 1, I developed an energy model for Kansas, one of the states with the highest data availability for farm practices. I used a combination of state and federal datasets to estimate the impact of shifting irrigation technologies on energy consumption. The results of this study are then investigated by energy source and a life cycle assessment model is applied to understand the role of shifting energy sources on the agricultural system. For Chapter 2, I expanded my energy model to encompass the continental United States. I estimate county level aggregates of direct energy consumed for irrigation. The results are then leveraged by agricultural region, and the crop types are evaluated spatially. Understanding how energy consumption in the agricultural sector is distributed both spatially and temporally can become a key asset when determining how to improve water practices, which regions need further study, and develop spatial relationships.
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Title: LIFETIME MEASUREMENTS OF THE NEUTRON-RICH 36,38SI ISOTOPES
Creator: Grinder, Mara Mikelah
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The shell structure of nuclei far from stability evolves from the standard shell modelpicture that accurately describes stable nuclei. Experimental evidence has been given by changes in structural properties of nuclei such as the shell closures. The evolution of shell structure is gradual and must be studied by looking systematically at isotopic or isotonic nuclear chains. Studies of these chains can deepen the understanding of shell structures, magic numbers and the collective natures of...
Show moreThe shell structure of nuclei far from stability evolves from the standard shell modelpicture that accurately describes stable nuclei. Experimental evidence has been given by changes in structural properties of nuclei such as the shell closures. The evolution of shell structure is gradual and must be studied by looking systematically at isotopic or isotonic nuclear chains. Studies of these chains can deepen the understanding of shell structures, magic numbers and the collective natures of nuclei far from stability. The neutron rich silicon isotopes display evidence of shell evolution seen in the ratio of the low-lying excitation energies. 34Si has a closed shell nature with a proton bubble structure which evolves along the isotopic chain to the absence of the N=28 shell closure expected in 42Si. Another complementary way to probe these changes is by studying the reduced transition rates of the first 2+ and 4+ states. The ratio of the reduced transition rates has characteristic values for different collective modes. However, these values are not known for isotopes that are more neutron rich than 30Si. The reduced transition rates can be compared to various theoretical models to understand the changes taking place in this neutron-rich region. This work discusses an experiment that studied 36Si and 38Si to determine the lifetimes of their excited states and to determine the reduced transition rates of the first 2+ and 4+ states in both nuclei. From these B(E2) values, the ratio is calculated and compared to the collective models and shell model calculations. The recoil distance measurement was con- ducted at the National Superconducting Cyclotron Laboratory using the S800 Spectrograph, the GRETINA array, and the TRIPLEX plunger. The experiment successfully measured the lifetimes of the 2+1 and 4+1 states in 38Si and the 4+1 and 6+1 states in 36Si. Results from the measurement included the confirmation of the 2383-keV state in 38Si that had only been seen once before. The B(E2) values determined from the experiment indicate the reduced collectivity for the first 4+ states of 36,38Si indicating the persistence of the N=20 magic number through 36Si and 38Si.
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Title: DESIGNING OUR FREEDOM : A NARRATIVE INQUIRY AND VISUAL RHETORICAL ANALYSIS OF BLACK WOMEN ENTREPRENEURS DIGITAL CONTENT STRATEGY ON SOCIAL NETWORKING SITES
Creator: Wourman, Ja'La Janice
Date: 2022
Collection: Electronic Theses & Dissertations
Description: This study explores the role of race and identity in Black women entrepreneurship and how each of these play a part when developing content for online audiences. The purpose of this study was to better understand how our intersecting identities are important to draw upon or consider, when conducting research in work-place studies or entrepreneurship for technical and professional communication scholars. And with the rise of digital platforms, I wanted to better understand if the...
Show moreThis study explores the role of race and identity in Black women entrepreneurship and how each of these play a part when developing content for online audiences. The purpose of this study was to better understand how our intersecting identities are important to draw upon or consider, when conducting research in work-place studies or entrepreneurship for technical and professional communication scholars. And with the rise of digital platforms, I wanted to better understand if the entrepreneurial journey factors into the design process of developing content for online audiences. To answer these questions, I used a narrative inquiry approach to conduct 5 separate interviews for each of my participants. The purpose of the interviews was to amplify the voices of each of my participants drawing from Patricia Hill Collins and the Combahee River Collective’s Black feminist theory. I then conducted a content analysis of 3 images from each of my participants business Instagram profiles, to demonstrate how design and cultural background can play a role in developing content. The results from this study revealed 3 major outcomes from each of the interviews and 4 emerging themes in the images used for all 5 participants content analysis of Instagram. Together, the themes and outcomes show a direct correction of race, culture, and design in content strategy. Using this data, I was able to develop tenets to help scholars and practitioners imagine a culturally centered design framework for developing content for diverse audiences and situations.
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Title: AGGRESSION AND THE GUT-BRAIN AXIS
Creator: Kwiatkowski, Christine Carole
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Violence is a widespread public health and justice system problem with far-reaching consequences for victims, offenders, and their communities. Aggression, the cognitive and behavioral antecedent to violent action, is mainly understood in terms of the psychosocial risk factors that increase the likelihood of aggressive behavioral strategies. Neighborhood context is a principal risk factor for violent crime perpetration, but the mechanisms that mediate the effect of the environment on...
Show moreViolence is a widespread public health and justice system problem with far-reaching consequences for victims, offenders, and their communities. Aggression, the cognitive and behavioral antecedent to violent action, is mainly understood in terms of the psychosocial risk factors that increase the likelihood of aggressive behavioral strategies. Neighborhood context is a principal risk factor for violent crime perpetration, but the mechanisms that mediate the effect of the environment on individual-level aggression behavior are poorly understood, especially the biological factors that may contribute to our understanding of violent behavior. In order to gain a better understanding of mechanisms that precipitate violence in specific geographic contexts, this dissertation explores the relationship between aggression behavior and the gut microbiome, a spatially determined physiological system that affects human health and behavior. Preclinical experiments elucidate the role of the gut microbiome in territorial, reactive aggression behavior in mice. Results show significant differences in gut microbiome composition across the spectrum of murine aggression behavior. Moreover, manipulation of the gut microbiome via administration of short-term antibiotics and sodium butyrate, a short-chain fatty acid byproduct of microbial fermentation, increases aggression behavior. The overall goal of this research is to use basic science findings in mice to better understand how environmental exposures could influence human health and behavior, thus revealing how community health affects individuals and supplying a potential target for future intervention.
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Title: CIRCADIAN RHYTHMS IN LATE PREGNANCY : A ROLE IN THE REPRODUCTIVE AXIS, UTERINE CONTRACTIONS AND PRETERM LABOR
Creator: Duong, Thu Van Quynh
Date: 2022
Collection: Electronic Theses & Dissertations
Description: What drives labor onset remains largely unknown. Understanding the molecular mechanisms defining pregnancy duration and preparing the uterus for labor onset can help improve current treatment strategies to promote or halt labor. Biological processes with a ~24-hour cycle called circadian rhythms are generated by endogenous “clock” transcription factors referred to as the molecular clock, which drives daily changes in cellular functions. To understand the role of circadian rhythms in pregnancy...
Show moreWhat drives labor onset remains largely unknown. Understanding the molecular mechanisms defining pregnancy duration and preparing the uterus for labor onset can help improve current treatment strategies to promote or halt labor. Biological processes with a ~24-hour cycle called circadian rhythms are generated by endogenous “clock” transcription factors referred to as the molecular clock, which drives daily changes in cellular functions. To understand the role of circadian rhythms in pregnancy, we first characterized how the molecular clock of the reproductive axis adapts to pregnancy and found the molecular clock is upregulated. Next, to understand if the molecular clock helps define pregnancy duration, we analyzed gene expression data from pregnant women. We found that low maternal levels of two clock genes increased the risk of preterm birth 5 fold. As preterm birth is driven by a premature increase in uterine contractions, we then asked how time of day impacted uterine contractile response to oxytocin, a hormone that increases uterine contractions and is widely used to induce labor. As model for human pregnancy, mice presented with daily time windows of increased uterine sensitivity to oxytocin. To determine if the molecular clock drives this daily change in sensitivity to oxytocin, we used conditional knockout mice which had the molecular clock ablated in uterine smooth muscle. These mice lost the daily change in sensitivity to oxytocin-induced contractions and presented stronger spontaneous uterine contractions than controls. In conclusion, we show that circadian rhythms have an important role in regulating pregnancy duration and uterine function, where the uterine molecular clock defines daily time windows of enhanced uterine sensitivity to oxytocin.
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Title: Metamodeling in Evolutionary Multi-Objective Optimization for constrained and unconstrained Problems
Creator: Hussein, Rayan
Date: 2022
Collection: Electronic Theses & Dissertations
Description: One of the main difficulties in applying an optimization algorithm to a practical problem is that the evaluation of objectives and constraints often involve computationally expensive procedures. To handle such problems, a metamodel (or surrogate model, or response surface approximations) is first formed from a few exact (high-fidelity) solution evaluations, and then optimized by an algorithm in a progressive manner. However, there has been lukewarm interest in finding multiple trade-off...
Show moreOne of the main difficulties in applying an optimization algorithm to a practical problem is that the evaluation of objectives and constraints often involve computationally expensive procedures. To handle such problems, a metamodel (or surrogate model, or response surface approximations) is first formed from a few exact (high-fidelity) solution evaluations, and then optimized by an algorithm in a progressive manner. However, there has been lukewarm interest in finding multiple trade-off solutions for multi-objective optimization problems using surrogate models. The literature on surrogate modeling for constrained optimization problems is also rare. The difficulty lies in the requirement ofbuilding and solving multiple surrogate models, one for each Pareto-optimal solution. In this study, we propose a taxonomy of different possible metamodeling frameworks for multi-objective optimization and provide a comparative study by discussing advantages and disadvantages of each framework. Also, we argue that it is more efficient to use different metamodeling frameworks at different stages of the optimization process. Thereafter, we propose a novel adaptive method for switching among different metamodeling frameworks. Moreover, we observe the convergence behavior of the proposed approaches is better with a trust regions method applied within the metamodeling frameworks. The results presented in this study are obtained using the well-known Kriging metamodeling approach. Based on our extensive simulation studies on proposed frameworks, we report new and interesting observations about the behavior of each metamodeling framework, which may provide salient guidelines for further studies in this emerging area within evolutionary multi-objective optimization. Results of this study clearly show the efficacy and efficiency of the proposed adaptive switching approach compared to three recently-proposed other metamodeling algorithms on challenging multi-objective optimization problems using a limited budget of high-fidelity evaluations.
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Title: INDIGENOUS MENTAL HEALTH : EXAMINING POPULATIONS IN TRIBAL AREAS AND NON-TRIBAL AREAS
Creator: Nash, Madeline
Date: 2022
Collection: Electronic Theses & Dissertations
Description: In this paper, I hypothesize that Indigenous populations in tribal areas fare better than those populations residing outside of tribal areas because of stronger social ties due to higher levels of integration and regulation. I review some of the studies that have been undertaken to measure mental health outcomes and suicide rates for the Indigenous populations in the US and Canada, paying close attention to the studies that describe differences between populations residing in tribal areas...
Show moreIn this paper, I hypothesize that Indigenous populations in tribal areas fare better than those populations residing outside of tribal areas because of stronger social ties due to higher levels of integration and regulation. I review some of the studies that have been undertaken to measure mental health outcomes and suicide rates for the Indigenous populations in the US and Canada, paying close attention to the studies that describe differences between populations residing in tribal areas compared to those who do not. I then use a panethnicity/race as a fundamental cause approach to explain why Indigenous populations have disparate mental health outcomes compared to the rest of the population, utilizing structural genocide to explain diminished integration and regulation. Pooling data from the National Drug Use and Health Survey (NSDUH), 2014-2017, I test this hypothesis controlling for sociodemographic variables. The results are mixed. On measures of serious psychological distress (SPD), my results are consistent with Park-Lees et al (2018). findings that there is no significant difference between these populations. However, there is a significant difference in serious thoughts of suicide. This contradicts Park-Lee et al. findings that though people residing in tribal areas had a lower rate than those who resided outside of tribal areas—the difference was not statistically significant using a T-test (2018). I found in my regression that after controlling for gender, age, marital status, education and income that living in tribal areas lowered one’s odd of having serious thought of suicide by over 30%.
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Title: WRITING ASSESSMENT IN MIDDLE SCHOOL STUDENTS : ANALYZING SPELLING WITHIN A MULTIDIMENSIONAL LANGUAGE FRAMEWORK
Creator: Sweet, Lake Eiseler
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Although producing quality written expression is a vital skill, many students in the United States struggle to produce proficient written language. There are many academic and career outcomes related to the ability to produce written expression, yet many schools lack formalized writing assessment and instruction. As such, many questions remain related to individual differences in writing ability and best practices in assessment and instruction. To answer these questions, it is necessary to...
Show moreAlthough producing quality written expression is a vital skill, many students in the United States struggle to produce proficient written language. There are many academic and career outcomes related to the ability to produce written expression, yet many schools lack formalized writing assessment and instruction. As such, many questions remain related to individual differences in writing ability and best practices in assessment and instruction. To answer these questions, it is necessary to establish a model of written expression and what specific variables exist within the model to be used to assess written language. Modern writing assessment theory uses levels of language as a framework with commonly assessed dimensions of accuracy, complexity and productivity. This framework has yet to be firmly established in the literature, and the variables included in each level are just beginning to be explored. One salient variable in writing research, assessment and instruction is spelling ability, and how this ability may influence the production of written language. This study furthers the work by Wilson et al. (2017), Troia and colleagues (2019) and many others (e.g., Berninger et al., 2006; Flower & Hayes, 1981) with the ultimate goal of developing a model of written language to guide assessment and instruction in schools. Specifically, data were drawn from Truckenmiller and colleagues (2020) study piloting a writing assessment tool, Writing Architect, which sampled 526 students from third to eight grades; this study used sixth, seventh and eighth grades with a resulting sample size of 290 students. Results indicated spelling was a significant predictor of writing quality, in that better spelling indicated better writing quality. The same was true for text. For the sentence-level variable, a higher score indicated worse writing quality in a significant way. The word variable did not significantly predict writing quality in the model. The significant interaction between spelling and text variables suggests that the effect of text on writing quality is even higher when spelling ability is also high. Findings highlight the importance of writing and spelling instruction in school. The findings for this age group help identify how writing abilities may change over the trajectory of development and vary individually. Additionally, this analysis echoes the call for further research to establish variables for automated writing assessment.
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Title: DEVELOPMENT OF NOVEL FLUORESCENT PROTEIN TAGS FOR NO-WASH LIVE-CELL IMAGING WITH MINIMUM FLUORESCENT BACKGROUND
Creator: Esmatpour Salmani, Rahele
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Recent fluorescence microscopy technologies have revolutionized many areasof biomedical research. Nonetheless, high brightness, far-red/near infra-red emission, deep tissue penetration, and selective fluorescent imaging with the minimum background are among the most desired novel fluorescent labeling. One of our primary goals is to develop flexible fluorescent protein tags capable of being tailored ad infinitum. We successfully demonstrated the ability to fine-tune the absorption and emission...
Show moreRecent fluorescence microscopy technologies have revolutionized many areasof biomedical research. Nonetheless, high brightness, far-red/near infra-red emission, deep tissue penetration, and selective fluorescent imaging with the minimum background are among the most desired novel fluorescent labeling. One of our primary goals is to develop flexible fluorescent protein tags capable of being tailored ad infinitum. We successfully demonstrated the ability to fine-tune the absorption and emission spectra of protein-bound chromophores over an unprecedented wide range (~200 nm). In contrast to intrinsically fluorescent proteins that are always “ON” in our systems, fluorescent is activated upon covalent binding of ligand and the target protein leading to temporal control of fluorescence. However, the fluorescence background from unbound free chromophore and non-specific binding has always been a deep concern in fluorescent labeling. This Ph.D. research aimed to develop novel proteinbased fluorescent tags emitting in the far-red/NIR region of the spectrum for no-wash background-free live-cell imaging applications. This was accomplished by coupling novel synthetic fluorogenic chromophores with hCRBPII mutants. Unbound free aldehyde ThioPhenol and CyThioPhenol are non-emissive dyes that become highly iii fluorescent upon imine formation with an active site lysine residue engineered deep in the hCRBPII cavity. We created a hydrogen-bonding network around the ThioPhenol hydroxyl group through rational protein engineering that facilitates its deprotonation upon photoexcitation. On the other hand, engineering the target protein to maintain a high iminium pKa resulted in Protonated Schiff Base (PSB) formation. The resultant complex experiences a strong intramolecular charge transfer (ICT), leading to fluorescence and a large bathochromic shift in the emission (~700 nm). The designed protein-based photoacid provides an unprecedented spatiotemporal control for nowash bright NIR imaging. Our most recent report demonstrated that hCRBPII/chromophore complexes could be developed as a photobase where the imine is converted to an iminium upon photoexcitation. In the course of optimizing hCRBPII to promote ESPT of the hydroxyl group, we discovered that ThioPhenol is capable of acting as both a photoacid and a photobase upon a single photoirradiation. When bound as a Schiff base (SB) to protein mutants that maintain a low iminium pKa (~5), engineered to deprotonate the hydroxyl group, a dual ESPT process leads to protonation of the imino to iminium (the photobase) and deprotonation of the hydroxyl to alkoxide (the photoacid). This double ESPT feature is recapitulated in a proteinligand micro-environment, yielding bright protein-dye complexes with unapparelled large pseudo-Stokes shifts (~250 nm). Additionally, the double ESPT ThioPhenol/hCRBPII complexes show fast binding rates (half-life of <3 min) that were successfully used to visualize whole-cell and the nucleus as a fluorogenic tag without any washing steps. Currently, further modifications are in progress to optimize the double ESPT systems with CyThioPhenol and further in-vivo applications.
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Title: Memory-efficient emulation of physical tabular data using quadtree decomposition
Creator: Carlson, Jared
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Computationally expensive functions are sometimes replaced in simulations with an emulator that approximates the true function (e.g., equations of state, wavelength-dependent opacity, or composition-dependent materials properties). For functions that have a constrained domain of interest, this can be done by discretizing the domain and performing a local interpolation on the tabulated function values of each local domain. For these so-called tabular data methods, the method of discretizing...
Show moreComputationally expensive functions are sometimes replaced in simulations with an emulator that approximates the true function (e.g., equations of state, wavelength-dependent opacity, or composition-dependent materials properties). For functions that have a constrained domain of interest, this can be done by discretizing the domain and performing a local interpolation on the tabulated function values of each local domain. For these so-called tabular data methods, the method of discretizing the domain and mapping the input space to each subdomain can drastically influence the memory and computational costs of the emulator. This is especially true for functions that vary drastically in different regions. We present a method for domain discretization and mapping that utilizes quadtrees, which results in significant reductions in the size of the emulator with minimal increases to computational costs or loss of global accuracy. We apply our method to the electron-positron Helmholtz free energy equation of state and show over an order of magnitude reduction in memory costs for reasonable levels of numerical accuracy.
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Title: Design and Evaluation of End Effectors and an Indoor Simulated Orchard Environment for Robotic Apple Harvesting
Creator: Dickinson, Nathan
Date: 2022
Collection: Electronic Theses & Dissertations
Description: A recently developed vacuum-based harvesting robot has shown promise in picking fruit from clusters, providing better access to tree canopies and minimizing fruit bruising. One of the main technical issues for this harvesting robot is the design of an end effector that can effectively grip the fruit for detachment. Field fruit picking studies using manual straight pull and twisting picking methods were first conducted for three varieties of apple. The critical pulling force and torque needed...
Show moreA recently developed vacuum-based harvesting robot has shown promise in picking fruit from clusters, providing better access to tree canopies and minimizing fruit bruising. One of the main technical issues for this harvesting robot is the design of an end effector that can effectively grip the fruit for detachment. Field fruit picking studies using manual straight pull and twisting picking methods were first conducted for three varieties of apple. The critical pulling force and torque needed to detach 95% of apples were determined to be 28.3 N and 0.257 N-m (equivalent suction force of 21.0 N for the current robot’s vacuum tube). Three new conformable silicone end effectors with different configurations (i.e., “Straight”, “Bellow”, and “Curved”) were designed and fabricated to provide more effective air sealing, and thus lower vacuum pressure for increased gripping force to effectively detach fruit compared to the robot’s original end effector. Laboratory and field picking performance studies with the harvesting robot showed that all three new end effectors performed significantly better than the original, non-conformable end effector. The straight end effector achieved 87% picking success rate; performing consistently better than the other two new end effectors based on multiple performance metrics, and hence should be used in further development of the robotic harvesting system. To enhance robotic harvest research, an indoor simulated orchard environment was constructed, which allows to mimic real fruit picking processes by using artificial trees embedded with specially designed tree branches and magnetic artificial stems for use with real fruit and a unique light system that can simulate different natural lighting conditions for different times of day.
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Title: MUTANT ANALYSIS OF A POLYOL MONOSACCHARIDE TRANSPORTER IN ARABIDOPSIS INVOLVED IN LIGNIFICATION
Creator: Tran, John Dang Khoa
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Monolignols have important roles in plant development and primarily serve as monomers for lignin polymerization in secondary cell walls. Monolignols are synthesized in the plant cytoplasm prior to entering the apoplast where oxidation occurs. Upon oxidation, monolignols are incorporated into the cell wall. Several mechanisms have been suggested to explain how monolignols cross the plasma membrane, including endocytosis, diffusion, and active transport. However, evidence for those models...
Show moreMonolignols have important roles in plant development and primarily serve as monomers for lignin polymerization in secondary cell walls. Monolignols are synthesized in the plant cytoplasm prior to entering the apoplast where oxidation occurs. Upon oxidation, monolignols are incorporated into the cell wall. Several mechanisms have been suggested to explain how monolignols cross the plasma membrane, including endocytosis, diffusion, and active transport. However, evidence for those models relied on theoretical calculations or produced results using in vitro approaches. Further, only one active transporter protein has been characterized to date. Yet, of the three monolignols tested, the transporter was only demonstrably shown to transport p-coumaryl alcohol, the least abundant monolignol present in Arabidopsis.Here we show that AtPMT4 is likely a monolignol transporter, particularly for the more abundant monolignols: coniferyl alcohol and sinapyl alcohol. Gene expression analysis performed on AtPMT4 in dicots and monocots shows coexpression with lignin biosynthetic genes. Cell-specific expression analysis of the inflorescence stem, a tissue that undergoes intense lignification to provide plant structural support, shows that AtPMT4 is expressed higher in cell types that lignify. We demonstrate that Arabidopsis Col-0 plants transformed with a CRISPR-Cas9 construct targeted near the TSS of AtPMT4, a member of the POLYOL/ MONOSACCHARIDE TRANSPORTER family, which is a subfamily of the MONOSACCHARIDE TRANSPORTER-LIKE family, displayed altered lignin phenotypes. We quantified the total lignin, free monomer subunits, and digestibility of the inflorescence stem in pmt4. Our studies show lower amounts of lignin and increased digestibility when AtPMT4 is mutated. Further, we show that pmt4 is sensitive to monolignols when grown in the presence of coniferyl alcohol. pmt4 displayed shorter root length compared to Col-0 at low concentrations of coniferyl alcohol. In conclusion, we provide evidence for an understanding of monolignol translocation and lignification by which transporters are likely involved in a proton-coupled manner.
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Title: THE NUCLEO-CYTOPLASMIC FUNCTION OF ACTIN AND ACTIN DEPOLYMERIZATION FACTORS IN PLANT IMMUNITY
Creator: Li, Pai
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The plant immune system is a multi-phase complex network that involves the collaboration of multiple subcellular structures. In the past two decades, the core signaling pathways of the immune process, including pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and systemic acquired resistance (SAR), as well as the behavior of organelles, have been revealed to a level of clarity that is able to describe a general and well-covered process of the immune response. However,...
Show moreThe plant immune system is a multi-phase complex network that involves the collaboration of multiple subcellular structures. In the past two decades, the core signaling pathways of the immune process, including pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and systemic acquired resistance (SAR), as well as the behavior of organelles, have been revealed to a level of clarity that is able to describe a general and well-covered process of the immune response. However, there are still many events during the immune response that remain mysterious. For instance, while higher plants live a sessile lifestyle, there are countless intracellular motions mediated by the cytoskeleton (including its associated proteins) in response to the external triggers, such as the invasion of pathogens. As our knowledge of plant immunity accumulates, the deficiency in knowledge on how immune signaling regulates the behavior of the cytoskeleton as a critical aspect of defense response, howbeit, becomes more evident. Therefore, this is a field of research that calls for powerful toolboxes to facilitate the analysis of the cytoskeleton in the context of immunity, as well as instructive biological model(s) that guide the direction of the multifarious studies. In this dissertation, I focus on the summary and prospective discussion on the immune function of the actin cytoskeleton and, more importantly, describe my original studies on two major aspects of this topic. First, a prerequisite to functional study of the actin cytoskeleton in the cytoplasm is the ability to accurately describe the status of the cytoskeleton. To achieve this goal, I developed an algorithm, namely implicit Laplacian of enhanced edge (ILEE), to accurately identify and analyze the biological status of the cytoskeleton from confocal image samples. This method significantly improves the accuracy, stability, and robustness of cytoskeleton segmentation, solves other technical hindrances, and enables abundant information to be extracted from images for biological interpretation (see Chapter 2). The ILEE algorithm will further help me to explore the phenotypes of actin architecture in response to immune signaling, which was not previously available due to the lack of the toolbox. Also, the ILEE has been packaged as a library released publicly to benefit the community with a powerful cytoskeleton analysis platform.For the second project of my total research, I focused on the immune function of the actin cytoskeleton in the nucleus. Previously, some Arabidopsis actin depolymerization factors were reported to genetically contribute to plant immunity by unknown mechanism(s), and my story began with a novel activity identified among Arabidopsis actin depolymerization factors – to interact with WRKYs, the stress-responsive transcription factors. During my research, I proved that certain ADFs can form a complex with WRKYs that binds to targeted promoters, hence regulating the activity of WRKYs and playing a positive role in the immune response. The knowledge obtained through this study, in combination with previous research (Lu et al., 2020; Porter et al., 2012a) of my lab, can be summarized into a biological model, in which ADF mediates a nuclear-cytoplasmic immune regulation that systemically facilitates both cytoskeleton dynamics and pro-immune transcriptome reprogramming. In general, this study reveals a novel yet general pattern of cytoskeleton mediated transcriptional regulation, as ADF and perhaps other components of the actin cytoskeleton can shuttle between the cytoplasm and nucleus to form a network with a higher level of complexity. As a potential broader impact, the application range of this model includes but is not necessarily limited to plant immunity.
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Title: HERD- LEVEL VARIABLES ASSOCIATED WITH ANTIMICROBIAL USE IN THE DAIRY HERDS
Creator: Said, Fuaad
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The aim of this study was to identify variables associated with antimicrobial drug use for bovine mastitis. Intramammary tubes used for lactating cows, discarded by farm personnel, were collected in dedicated trash bins for 12 months on each of 104 herds (Michigan n = 49, Pennsylvania n = 55). Antimicrobial use was quantified using two metrics: arithmetic (number of discarded tubes) and defined daily dose (DDD) per 1,000 cow-days. Mastitis control practices, attitudes, and behaviors were also...
Show moreThe aim of this study was to identify variables associated with antimicrobial drug use for bovine mastitis. Intramammary tubes used for lactating cows, discarded by farm personnel, were collected in dedicated trash bins for 12 months on each of 104 herds (Michigan n = 49, Pennsylvania n = 55). Antimicrobial use was quantified using two metrics: arithmetic (number of discarded tubes) and defined daily dose (DDD) per 1,000 cow-days. Mastitis control practices, attitudes, and behaviors were also collected using a survey of herd owners and managers conducted during herd visits. Additionally, a human resources questionnaire survey about dairy producers/manager’s beliefs and practices regarding employee communications, training, and education was also collected for each herd. Across all herds, intramammary tube use based on arithmetic count was 4.43 tubes per1,000 cow-days and 3.52 per 1,000 cow-days based on DDD. A higher trend of antimicrobial use (5.22 tubes per 1,000 cow-days and DDD of 4.1 per 1,000 cow-days) was found in Pennsylvania than in Michigan (3.61 tubes per1000 cow-days and the DDD 2.91 per 1,000/ cow-days). Ranking of antimicrobial use showed that ceftiofur was the most frequently used antimicrobial in the study, followed by cephapirin, pirlimycin, amoxicillin, hetacillin, and cloxacillin. A majority of producers believed that they had sufficient knowledge of mastitis treatment and control, but only 23% of them had a written treatment protocol, and less than half of them (44%) reviewed animal health? History before treating infected cows. Moreover, 80% disagreed that culture of milk samples is needed to make mastitis treatment or management decisions. Multivariate models had similar results, regardless of the metric used to determine intramammary drug use; there was a positive correlation between drug use and the new subclinical mastitis rate (based on monthly DHI SCC testing) and the producer’s willingness to improve the image of the dairy products. Use of natural remedies for mastitis treatment was negatively correlated with intramammary drug use. Our results indicate that there continues to be a gap between producer practices and beliefs and best practices to reduce antimicrobial use on dairy farms. Also, intramammary drug use is highly associated with the dynamics of subclinical mastitis as measured in individual cows, and a herd average level.
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