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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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Title: I. Determination of Absolute Configuration of Chiral 1,2-Diols. II. Progress Towards the Total Synthesis of Napyradiomycin A1.
Creator: Torabi Kohlbouni, Saeedeh
Date: 2022
Collection: Electronic Theses & Dissertations
Description: This dissertation focuses on two parts. The first part introduces an operationally simple and microscale method for the absolute stereochemical determination of 1,2-diols. In situ derivatization of 1,2-diols with dinaphthyl borinic acid generates the induced helicity of the two naphthyl groups, which leads to an observable ECCD spectrum. The observed P or M helicity follows a predictable trend for S and R chiral 1,2-diols, respectively.The Second chapter is the progress towards the asymmetric...
Show moreThis dissertation focuses on two parts. The first part introduces an operationally simple and microscale method for the absolute stereochemical determination of 1,2-diols. In situ derivatization of 1,2-diols with dinaphthyl borinic acid generates the induced helicity of the two naphthyl groups, which leads to an observable ECCD spectrum. The observed P or M helicity follows a predictable trend for S and R chiral 1,2-diols, respectively.The Second chapter is the progress towards the asymmetric catalytic synthesis of napyardiomycin A1. The chapter is divided to three sections. The first section is installation of chlorine chiral center at C3. This goal is achieved using cinchona chiral catalyst, and DCDMH as chloronium source. The second section is the synthesis of the -lapachone core of napyradiomycin A1, was accomplished using Diels-Alder/aromatization cascade reaction. The last section shows our effort toward the attachment of geranyl side chain.
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Title: DEVELOPING LIGNIN-BASED EPOXY AND POLYURETHANE RESINS
Creator: Nikafshar, Saeid
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Lignin, the most abundant natural aromatic polymer, is currently produced as by-product during biorefinery and chemical pulping processes. Lignin is rich in hydroxyl functional groups (both phenolic and aliphatic OH), making it an excellent raw material for synthesizing epoxy and polyurethane resins. However, there are several challenges in utilizing unmodified lignins as feedstock for product development, including high polydispersity/heterogeneity, low reactivity, poor accessibility of...
Show moreLignin, the most abundant natural aromatic polymer, is currently produced as by-product during biorefinery and chemical pulping processes. Lignin is rich in hydroxyl functional groups (both phenolic and aliphatic OH), making it an excellent raw material for synthesizing epoxy and polyurethane resins. However, there are several challenges in utilizing unmodified lignins as feedstock for product development, including high polydispersity/heterogeneity, low reactivity, poor accessibility of hydroxyl groups for reaction with co-monomers low solubility in common organic solvents, and dark color. There are significant variations in lignin characteristics, depending on the source of biomass and isolation methods. Therefore, in-depth lignin characterization is needed to provide the basic knowledge of the structural, chemical, and thermal properties to facilitate lignin valorization.This study was focused on lignin characterization and development of lignin-based epoxy and polyurethane resins. First, a wide range of lignin samples was fully characterized by measuring their ash contents, elemental analyses, hydroxyl contents, chemical structures, molar mass distributions, and thermal properties. Next, a novel method was developed to measure the reactivity of thirteen different unmodified lignins toward biobased epichlorohydrin (ECH). A partial least square regression (PLS-R) model (with 92 % fitting accuracy and 90 % prediction ability) was created to study the correlation between lignin properties and epoxy content. The results showed that lignins with higher phenolic hydroxyl contents and lower molecular weights were more suitable for replacing 100 % of toxic bisphenol A (BPA) in the formulation of resin precursors. Additionally, two epoxidized lignin samples (with the highest epoxy contents) were cured using a biobased hardener (Cardolite from cashew nutshell), showed comparable thermomechanical performances and thermal stabilities to a petroleum-based epoxy system. Biobased waterborne polyurethane resins (PUDs) were also developed by entirely replacing the petroleum-based polyol and the internal emulsifier with either alkaline pre-extraction lignins or enzymatic hydrolysis lignins as well as tartaric acid (a biobased diacid). The formulated resins had zero VOC (volatile organic compound), which was achieved by replacing toxic n-methyl-2-pyrrolidone (NMP) with cyrene (a biobased solvent). To further improve the mechanical properties of our biobased PUD resins, 20 wt.% of lignin was substituted with low hydroxyl value soy-polyol, which increased their tensile strength and elongation at break to 87% and 68% of a commercial PUD resin. The results of this study demonstrated that it is imperative to fully characterize lignin and choose the right lignin for each specific application. This approach enabled us to entirely replace petroleum-based raw materials (BPA and polyol) with lignin and formulate biobased epoxy and polyurethane resins.
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Title: Development and application of hierarchical models for monitoring avian soundscapes, populations, and communities
Creator: Doser, Jeffrey W.
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Climate change, land use change, and other anthropogenic pressures are increasing species extinctions, phenology shifts, and drastic population declines. Avian populations and communities are particularly vulnerable to global change given their mobile and migratory life history strategies. Avian abundance has drastically declined throughout North America over several decades, which is compounded by phenological shifts in breeding periods and migratory patterns. Informed management and...
Show moreClimate change, land use change, and other anthropogenic pressures are increasing species extinctions, phenology shifts, and drastic population declines. Avian populations and communities are particularly vulnerable to global change given their mobile and migratory life history strategies. Avian abundance has drastically declined throughout North America over several decades, which is compounded by phenological shifts in breeding periods and migratory patterns. Informed management and conservation of avian populations and communities requires large-scale monitoring programs, as well as associated inferential tools to provide statistically robust inference using multiple data sources. In this dissertation, I develop a suite of hierarchical modeling approaches to understand avian soundscapes, populations, and communities. I leverage a hierarchical Bayesian modeling framework, which is ideally suited for complex wildlife data with numerous types of observation error and dependencies among data points. In Chapter 1, I provide a brief overview of avian monitoring approaches and their associated statistical analysis frameworks. In Chapters 2 and 3, I develop hierarchical models for the analysis of complex avian soundscape data, and apply these approaches to two case studies. In Chapter 2, I apply a two-stage hierarchical beta regression model to quantify the relationship between anthropogenic and biological sounds in avian soundscapes in western New York. In Chapter 3, I use a multivariate linear mixed model to assess disturbance impacts of a shelterwood logging on avian soundscapes in northern Michigan. In Chapter 4, I develop a multi-region, multi-species abundance model to quantify trends of avian species and communities using point count data across a network of National Parks in the northeastern US. In Chapters 5 and 6, I use a model-based data integration approach to yield improved inference on avian population and communities. In Chapter 5, I integrate automated acoustic recording data with point count data to estimate avian abundance, which I apply to a case study on the Eastern Wood Pewee (Contopus virens) in a National Historical Park in Vermont. In Chapter 6, I develop an integrated community occupancy model that combines multiple types of detection-nondetection data for inference on species-specific and community level occurrence dynamics, which I use to assess occurrence dynamics of a foliage-gleaning bird community in New Hampshire. These results exhibit the value of hierarchical models to partition ecological data into distinct observation and ecological components for improved inference on avian population and community dynamics. Future work should continue to leverage complex data sources within hierarchical modeling frameworks to address pressing conservation and management questions on avian populations, communities, and the ecosystem services they provide.
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Title: Intraoperative blood glucose management : a quality improvement project
Creator: Baker, Jake (Nurse)
Date: 2022
Collection: Doctor of Nursing Practice Projects
Description: Perioperative hyperglycemia is associated with a myriad of post-surgical complications including an increased incidence of surgical site infections and prolonged hospital stays. The use of an evidence-based perioperative blood glucose management protocol reduces morbidity and mortality in adult patients undergoing surgical procedures. The project team describes a cost-effective quality improvement initiative aimed at improving protocol adherence by integrating an easy-to-use protocol...
Show morePerioperative hyperglycemia is associated with a myriad of post-surgical complications including an increased incidence of surgical site infections and prolonged hospital stays. The use of an evidence-based perioperative blood glucose management protocol reduces morbidity and mortality in adult patients undergoing surgical procedures. The project team describes a cost-effective quality improvement initiative aimed at improving protocol adherence by integrating an easy-to-use protocol algorithm, order sets, and practice reminders into an existing electronic health record system.
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Title: Improving perioperative nausea and vomiting prophylaxis protocol compliance
Creator: Franz, Allison
Date: 2022
Collection: Doctor of Nursing Practice Projects
Description: Postoperative nausea and vomiting (PONV) is a significant concern in anesthesia practice. Evidence-based guidelines have sought to provide recommendations on identifying patients at risk for PONV and mitigating its effect with multimodal antiemetic strategies. An anesthesia department within a large teaching hospital uses the Anesthesiology Performance Improvement and Report Exchange guidelines to identify and manage patients at risk for PONV. These guidelines are intended to integrate best...
Show morePostoperative nausea and vomiting (PONV) is a significant concern in anesthesia practice. Evidence-based guidelines have sought to provide recommendations on identifying patients at risk for PONV and mitigating its effect with multimodal antiemetic strategies. An anesthesia department within a large teaching hospital uses the Anesthesiology Performance Improvement and Report Exchange guidelines to identify and manage patients at risk for PONV. These guidelines are intended to integrate best practices into anesthetic care and improve overall surgical outcomes. The anesthesia department currently has a PONV protocol in place that aligns with the guidelines but has not achieved their compliance benchmark. This evidence-based quality improvement project describes interventions proposed to increase compliance with the PONV protocol. To address poor PONV compliance, an anonymous survey was developed to assess anesthesia provider's current familiarity with the new PONV guidelines and identify misconceptions. A visual feedback system was implemented using a preliminary confidential list that anonymizes staff. This allowed individual providers to identify their own performance in relation to their peers in a non-punitive way. The results of this quality improvement project demonstrate that the proposed interventions increased departmental compliance.
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Title: Development and implementation of an enhanced recovery after surgery protocol for women undergoing a mastectomy
Creator: Braun, Michael
Date: 2022
Collection: Doctor of Nursing Practice Projects
Description: This evidenced-based practice initiative includes the development and implementation of an evidence-based enhanced recovery after surgery (ERAS) guideline with a specific focus on the incidence of postoperative nausea and vomiting (PONV) and opioid administration in the postoperative setting. The clinical question was in adult women, age 18 years or greater, undergoing a mastectomy procedure, does the implementation of an ERAS guideline lower the incidence of PONV and reduce morphine...
Show moreThis evidenced-based practice initiative includes the development and implementation of an evidence-based enhanced recovery after surgery (ERAS) guideline with a specific focus on the incidence of postoperative nausea and vomiting (PONV) and opioid administration in the postoperative setting. The clinical question was in adult women, age 18 years or greater, undergoing a mastectomy procedure, does the implementation of an ERAS guideline lower the incidence of PONV and reduce morphine milligram equivalent (MME) requirements in a post-anesthesia care unit (PACU)? Patients undergoing breast cancer surgery have multiple risk factors and the reported incidence of PONV reaches up to 80%. Over half of post-surgical breast cancer patients develop neuropathic pain syndromes. A mastectomy ERAS guideline was developed then applied to the perioperative course of 22 patients. It was found that following an ERAS guideline reduced the incidence of PONV by 17% and reduced the average MME by 13.5 equivalents. Project implications include potential cost savings, reduced PACU length of stay, and improved patient outcomes.
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Title: EXPLORING THE INTRICACIES OF NOVEL MIO-DEPENDENT AMINOMUTASES AND EXPANDING THEIR USE THROUGH REPURPOSING AND SCALE-UP
Creator: Walter, Tyler
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Aminomutases (AMs) catalyze the isomerization of α-amino acids to their corresponding β-amino acids. A unique class of aminomutases utilizes a 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) prosthetic group formed via post-translational modification of three consecutive residues within the active site. These MIO-dependent aminomutases likely descend from ammonia lyases, responsible for catalyzing the removal of ammonia from α-amino acids to produce the corresponding acrylates, which are...
Show moreAminomutases (AMs) catalyze the isomerization of α-amino acids to their corresponding β-amino acids. A unique class of aminomutases utilizes a 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) prosthetic group formed via post-translational modification of three consecutive residues within the active site. These MIO-dependent aminomutases likely descend from ammonia lyases, responsible for catalyzing the removal of ammonia from α-amino acids to produce the corresponding acrylates, which are important metabolites in a variety of hosts. MIO-dependent enzymes catalyze this isomerization for aromatic amino acids (i.e. Phe, Tyr, His), the products of which are vital components to several antibiotics, antifungals, and anticancer therapeutics.In 2013, a MIO-dependent tyrosine aminomutase (TAM) from Japanese rice (Oryza sativa) was discovered while searching for defense induced metabolites. The enzyme responsible for the increased β-Tyr levels they observed, OsTAM, was cloned into E. coli and studied to elucidate its isomerization mechanism and confirm the product stereochemistry. However, during the course of this investigation, we found several interesting characteristics of OsTAM that completely changed the current dogma within MIO-dependent enzyme research including (1) OsTAM releases nearly 25% p-coumarate, the corresponding acrylate of Tyr, which is over 2-fold higher than other AMs; (2) OsTAM is the first TAM derived from plants, presenting a new opportunity to compare AMs across species; and (3) OsTAM is the first TAM to catalyze the isomerization of Phe, which paves the way for further study of the residues involved in substrate selectivity. Further study of the residues near the phenyl ring of the substrate showed two key residues, Y125 and N446, that controlled both substrate selectivity and the intrinsic activity of MIO-dependent enzymes. Arguably the most studied MIO-dependent PAM, TcPAM, lies along the biosynthetic pathway towards paclitaxel, a potent chemotherapeutic. Several studies within the lab showed that TcPAM has transamination activity when supplied an amine donor and acceptor acrylate. Recently, TcPAM was shown to catalyze the ring-opening amination of exogenously supplied cinnamate epoxides to produce phenylserine, key cores of numerous biologically active compounds. Interested in the potential of scale-up of this biocatalytic scheme, we developed a batch bioreactor method to increase cell densities of TcPAM-expressing cells and therefore increase the yield of the expressed enzyme. To increase the control and convenience of this process, we adapted autoinduction media developed by Studier in a batch bioreactor system. To the best of our knowledge, this has never been optimized for overexpression of an enzyme for later biocatalysis. With this batch bioreactor system, we turned our attentions towards scale-up of phenylserine, purification from the aqueous reaction mixture, and eventual cross-coupling to create biphenyl scaffolds aimed at recent discovery of a potent inhibitor of tumor growth with this molecular architecture. Initial studies allowed us to increase phenylserine production to the low milligram scale and develop a laboratory scale method for purification using C18 resin.
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Title: Theory and Evidence on Buying Political Influence
Creator: Cox, Christian
Date: 2021
Collection: Electronic Theses & Dissertations
Description: This dissertation identifies and addresses contemporary issues in political economy related to how private interests influence elections and government decision making. The three chapters focus on spending in elections by two distinct kinds of organizations and lobbying by firms. The chapters are fundamentally empirical investigations with rigorous theoretical foundations. Chapter 1: Campaign Finance in the Age of Super PACs. The United States Supreme Court 2010 decision in Citizens United v....
Show moreThis dissertation identifies and addresses contemporary issues in political economy related to how private interests influence elections and government decision making. The three chapters focus on spending in elections by two distinct kinds of organizations and lobbying by firms. The chapters are fundamentally empirical investigations with rigorous theoretical foundations. Chapter 1: Campaign Finance in the Age of Super PACs. The United States Supreme Court 2010 decision in Citizens United v. Federal Election Commission led to a major de-regulation of election campaign finance law. A new political action committee emerged from this case, known as the Super PAC, with a relatively unfettered ability to raise and spend money in elections. How were campaign spending and electoral outcomes affected? I characterize the influence of Super PACs on U.S. Congressional general and primary elections by estimating an election contest model. I exploit variation in donor finances, background information on candidates, and the dynamic model structure to deal with candidate unobservables. Results indicate that Super PACs do not have significant influence on voting outcomes but did increase election spending between 2010-2016. They affect behavior of other committees, with differences across political party and incumbency status. Finally, Super PACs have modest effects on candidate platforms and entry. Chapter 2: Dark Money in Congressional Elections. Nonprofits in the United States play a unique role in campaign finance. Their tax-exempt status and anonymous donations combined with their recently de-regulated political status allows them to engage in political advertising spending in an unprecedented manner. I study the rise of ``dark-money'' by 501(c)(4) nonprofits in US Congressional elections by studying the pattern of spending and the effects on election outcomes. Since 501(c)(4) nonprofits are not legally required to disclose spending to the Federal Election Commission, I exploit raw advertising data to measure their behavior. I find that they do not have significant effects on vote share when accounting for the spending of candidates, parties, PACs, and Super PACs. Chapter 3: Lobbying for Government Appropriations. This chapter investigates the effect of lobbying on government contract allocation. I consider how lobbying affects both total contract spending and the distribution of contracts between firms. I solve a novel contest model which incorporates these two effects, and then structurally estimate it using a panel of federal contractors. The results suggest that lobbying increases contract spending by $8.837 billion (3.22%) per year. However, its effects on the observed contract distribution and firm revenues are relatively small. Finally, I find that increasing competition in procurement generally results in less lobbying.
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Title: LATE-GESTATION METABOLIC STRESS IN DAIRY CATTLE : ASSOCIATION WITH COLOSTRUM YIELD AND IMMUNOGLOBULIN CONTENT
Creator: May Rossi, Renato
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Despite improvements made in the dairy industry and advances on heifer management, calf morbidity and mortality are still high. Calves rely on colostrum ingestion for acquisition of passive immunity, and provision of insufficient quantity of colostrum may lead these animals to failure of transfer passive immunity, hence leading to higher risks of morbidity and mortality. Many farms do not have sufficient colostrum available at times to feed their calves. Synthesis of colostrum starts few...
Show moreDespite improvements made in the dairy industry and advances on heifer management, calf morbidity and mortality are still high. Calves rely on colostrum ingestion for acquisition of passive immunity, and provision of insufficient quantity of colostrum may lead these animals to failure of transfer passive immunity, hence leading to higher risks of morbidity and mortality. Many farms do not have sufficient colostrum available at times to feed their calves. Synthesis of colostrum starts few weeks before calving and it is at the time when cows are experiencing augmented metabolic adaptations due to increasing nutrient demands for fetal growth, colostrogenesis, and preparation for the onset of lactogenesis. The study described in Chapter 2 aimed to compare the metabolic status of dairy cows during the last 6 wk of gestation based on colostrum volume and Ig content across seasons during a year. The results in the latter study suggest that greater availability of antioxidants might support the production of higher volumes of colostrum. Therefore, the study reported in Chapter 3, aimed to evaluate whether administering a dietary antioxidant supplement during the last 3 weeks of gestation improves colostrum volume and immunoglobulin content. Our results showed that DATS increased colostrum volume. However, despite finding higher volume of colostrum in treatment group with statistical differences compared to control, the distribution of colostrum volume between groups are relatively the same, as well for IgG, IgM, and IgA.
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Title: LOCAL CONTENT DEVELOPMENT AS A SUSTAINABLE NATIONAL ECONOMIC STRATEGY : LESSONS LEARNED FROM OMAN’S OIL & GAS INDUSTRY
Creator: Alhajri, Ahmed
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Given the pressures of global changes, productive approaches to use local resources present a pathway to sustain or improve living standards. One of these productive approaches is the Local Content Development (LCD) policy, which refers to government policy to promote local sustainable development. Local content development policy can enhance government processes, promote public-private partnerships, advance the business environment, and expand value creation. This dissertation addressed how...
Show moreGiven the pressures of global changes, productive approaches to use local resources present a pathway to sustain or improve living standards. One of these productive approaches is the Local Content Development (LCD) policy, which refers to government policy to promote local sustainable development. Local content development policy can enhance government processes, promote public-private partnerships, advance the business environment, and expand value creation. This dissertation addressed how Local Content Development is an opportunity for countries and organizations to adapt development to local conditions, assets, and talent. This study aimed to evaluate the factors associated with the implementation of local content policy in Oman. The study used the oil and gas industry in Oman as an example of a typical Local Content Development policy that exemplified implementation factors, while the tourism industry is a case study of a target industry to replicate LCD policy. Research questions were answered using evidence collected from open-ended surveys with Omani stakeholders in government and business. Thematic analysis was used to compare concepts derived from literature with data derived from the survey. The findings are based on the rich experiences of major companies and offer valuable input to inform policymaking for other sectors in the contexts of sustainable development. Findings show that the state role, leadership at all levels, stakeholder collaboration, governance and accountability, coherence with national policies, corporate communication, and local capabilities influenced implementation. The absence of these factors, however, hinders effective implementation. This research showed that oil and gas LCD policy experiences provided useful insights on collaborative policymaking and policy implementation processes. Implementation factors are interconnected and applicable to a variety of settings. Replication may not be a complex task but more about leadership and human and organizational behavioral change. In the tourism context, LCD adoption and implementation provide sustainable solutions to enhance how the tourism industry benefits from economic growth. LCD enabling factors appear to exist in the tourism sector based on findings of this research and Omani regulations of Integrated Tourism Complexes the “ITC law”. The tourism industry needs leadership and champions to facilitate all other factors in a collaborative approach, as did oil and gas. More broadly, and taking into consideration implementation factors, companies can adopt and implement the Local Content Development framework to enhance their contribution to the local economy and towards the United Nations Sustainable Development Goals (SDG). Overall, this research showed the value of adoption and implementation of Local Content Development as a policy tool to enhance the private sector role to improve social and economic conditions. Local Content Development is an adaptable policy tool and it supports sustainable development principles that seek to improve people’s lives, and that could be used for countries, provinces, cities, public, and private organizations, households, and individuals.
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Title: DECIPHERING THE GENETIC BASIS OF SOLANUM CHACOENSE MEDIATED COLORADO POTATO BEETLE (LEPTINOTARSA DECEMLINEATA) RESISTANCE AND SELF- FERTILITY IN A DIPLOID SOLANUM CHACOENSE RECOMBINANT INBRED LINE POPULATION
Creator: Kaiser, Natalie
Date: 2021
Collection: Electronic Theses & Dissertations
Description: The Colorado potato beetle (Leptinotarsa decemlineata) is the most widespread and destructive insect defoliator pest of potato and its control has historically been achieved through the use of insecticide. The diploid potato species Solanum chacoense has been utilized for over four decades in an attempt to introgress glycoalkaloid-based insect resistance into cultivated tetraploid potato. Despite these efforts, insect resistant cultivars have not been achieved, due in part to the complex...
Show moreThe Colorado potato beetle (Leptinotarsa decemlineata) is the most widespread and destructive insect defoliator pest of potato and its control has historically been achieved through the use of insecticide. The diploid potato species Solanum chacoense has been utilized for over four decades in an attempt to introgress glycoalkaloid-based insect resistance into cultivated tetraploid potato. Despite these efforts, insect resistant cultivars have not been achieved, due in part to the complex genetics underlying the trait. The creation of inbred diploid lines would allow more efficient examination and deployment of this economically important trait. We introduced self-compatibility into diploid insect resistant S. chacoense germplasm and developed the first potato recombinant inbred line (RIL) population to study, understand and deploy this mechanism of host-plant insect resistance in cultivated, diploid breeding lines.We first examined the genetic features underlying leptine glycoalkaloid mediated Colorado potato beetle host plant resistance in the F2 generation derived from a cross between S. chacoense lines USDA8380-1 (80-1) and M6. Using biparental linkage mapping, a major overlapping QTL region with dominant effects was identified on chromosome 2 explaining 49.3% and 34.1% of the variance in Colorado potato beetle field resistance and leptine accumulation, respectively. Bulk segregant whole genome sequencing of the same F2 population detected QTL associated with Colorado potato beetle resistance on chromosomes 2, 4, 6, 7, and 12. Candidate genes within these QTL regions were identified by weighted gene co-expression network analysis of parental lines and resistant and susceptible F2 individuals. Second, we exploited M6-mediated self-compatibility and established vigorous, F5 inbred diploid lines to further examine loci associated with Colorado potato beetle resistance and explore the practicality of inbreeding in diploid potato. F5 inbred lines carrying Colorado potato beetle resistance equivalent to the resistant donor parent were created without field selection during the inbreeding process. We report that the ratio of acetylated to non-acetylated glycoalkaloids measured under greenhouse conditions is a powerful metabolite marker to predict field performance without incurring the costs of conducting a Colorado potato beetle field trial. Leptine production was successfully introduced into diploid breeding germplasm. Single nucleotide polymorphism (SNP) genotyping coupled with stylar analysis of pollen tube growth and self-fertility phenotyping of the F4 and F5 generations revealed that multiple factors mediate the self-compatible response in this RIL population. Third, we assessed the initial transcriptional and metabolite response to Colorado potato beetle herbivory in beetle resistant and beetle susceptible S. chacoense lines over a 48-hour time course. To facilitate genome editing modification of the leptine biosynthesis pathway, we characterized the allelic variation between S. chacoense 80-1 and M6 in a candidate leptine biosynthesis gene identified by transcriptional profiling. This work highlights the challenges of establishing inbred germplasm, reinforces the complexity of selecting for self-fertility in diploid potato, and lays the foundation for optimization of potato RIL development. The availability of highly homozygous Colorado potato beetle resistant lines will enable further genomic inquiry of the loci contributing to this trait and will facilitate rapid deployment of beetle resistant diploid potato varieties.
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Title: CHEMICAL BIOLOGY AND GENETIC STUDIES TARGETING THE MYCOBACTERIAL CELL ENVELOPE
Creator: Williams, John Tison
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Mycobacterium tuberculosis is one of the leading causes of death due to a single infectious pathogen. The evolution and spread of drug resistant strains requires new antibiotics to control the TB pandemic. Over the last decade, the lipid flippase MmpL3 has been identified as a potential drug candidate based on its essential nature for cell viability and repeated identification as the lead target of small molecule inhibitors of Mtb growth. Using a combined untargeted and targeted whole cell...
Show moreMycobacterium tuberculosis is one of the leading causes of death due to a single infectious pathogen. The evolution and spread of drug resistant strains requires new antibiotics to control the TB pandemic. Over the last decade, the lipid flippase MmpL3 has been identified as a potential drug candidate based on its essential nature for cell viability and repeated identification as the lead target of small molecule inhibitors of Mtb growth. Using a combined untargeted and targeted whole cell phenotypic screen I identified novel inhibitors of this valued target. A combination of lipid profiling and an innovative competitive binding assay supported MmpL3 as the target of these inhibitors. Cross resistance profiling of MmpL3 inhibitors against twenty-four unique mmpL3 Mtb mutants demonstrated that the level of resistance is associated with the proximity of resistant mutants to essential residues for protein function. Further, these resistance profiles suggested that MmpL3 inhibitors fall into separate clades depending on their chemical scaffolds. The results of this screen led to the development of novel potent analogs for one of the identified MmpL3 inhibitors, HC2099. These analogs were active against clinically relevant drug resistant Mtb strains that cause treatment failure in patients. Active analogs were able to kill Mtb inside of infected macrophages, an infectious niche of Mtb, without inducing cytotoxicity against these important immune cells. One of these analogs, MSU-43085, was orally bioavailable and successfully inhibited Mtb growth in infected mice, supporting further development and highlighting the therapeutic potential of this series. High throughput screens are often used to identify new inhibitors of Mtb growth. However, prioritized hits form these screens often identify similar targets such as MmpL3, lipid synthesis enzymes, redox cyclers, as well as inhibitors of the electron transport chain. Follow up studies of these inhibitors are often time consuming, costly and result in the rediscovery of previously identified targets. While this is not necessarily detrimental to Mtb drug discovery, as these reoccurring targets have therapeutic potential. The continued prioritization of inhibitors for these common metabolic pathways potentially limits the identification of inhibitors for novel targets. Therefore, additional steps that identify inhibitors of these common pathways could reshape how high throughput screen hits are prioritized. By applying the targeted mutant screen used to identify MmpL3 inhibitors to a non-prioritized library of hits from a high throughput screen, we identified more than fifty new potential MmpL3 inhibitors. Using an iterative strategy of applying additional mutants of commonly identified targets, this strategy promises to lead to parallel follow-up studies of inhibitors with known and unknown mechanisms of action. The ability of Mtb to enter into quiescent states in response to host stresses is one of the leading causes for the extended time to cure and evolution of drug resistance. These states can be induced by several environmental stresses including acidic pH, hypoxia, and others. In an effort to study this adaptation in the rapidly growing mycobacterial species M. smegmatis, we identified a lethal sodium citrate phenotype. Transcriptional profiling and genetic screening of mutants tolerant to sodium citrate indicated that this phenotype was due to the combined action of both chelation and osmotic stresses. Cell viability could be reduced from sodium citrate killing by cation and osmoprotectant supplementation. From these experiments we propose a model that can be applied to study carbon source uptake and probe the role of genes identified from the forward genetic screen with unknown function
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Title: FUSARIUM SPP. ASSOCIATED WITH PERENNIAL SPECIALTY CROPS
Creator: Getson, Sara
Date: 2021
Collection: Electronic Theses & Dissertations
Description: The genus Fusarium comprises an array of soilborne plant pathogens capable of causing crop significant loss of quality and yield. For perennial crops with significant start-up costs, infection by pathogenic Fusarium spp. can also reduce plant longevity which can be especially costly. Our objective was to determine the incidence and pathogenicity of Fusarium spp. associated with asparagus crowns and ginseng seed and roots. Fusarium causes root rot on asparagus decreasing the crop yield and...
Show moreThe genus Fusarium comprises an array of soilborne plant pathogens capable of causing crop significant loss of quality and yield. For perennial crops with significant start-up costs, infection by pathogenic Fusarium spp. can also reduce plant longevity which can be especially costly. Our objective was to determine the incidence and pathogenicity of Fusarium spp. associated with asparagus crowns and ginseng seed and roots. Fusarium causes root rot on asparagus decreasing the crop yield and plant longevity. Root lesions on ginseng root from Fusarium decreases the crop’s quality and value. Species identification was achieved via DNA extraction, PCR using EF-1 and EF-2 primers, and Sanger sequencing. Asparagus crown (491) samples were collected from commercially popular cultivars and included ‘Jersey Supreme’ (100), ‘Guelph Millennium’ (258), and ‘Guelph Eclipse’ (133). ‘Guelph Millennium’ crowns included those grown in soils fumigated pre-plant with metam sodium (131) or not fumigated (127). Seven Fusarium species were identified from asparagus crowns; F. oxysporum (92%) was most abundant. Fusarium spp. were isolated from ‘Jersey Supreme’ (39%), ‘Guelph Eclipse’ (47%), and ‘Guelph Millennium’ (30%). Fusarium spp. were isolated from 36% and 25% of the crowns grown in non-fumigated or fumigated soils, respectively. Pathogenicity of Fusarium oxysporum isolates (51) differed signficantly. Ginseng seed (1,216) and roots (222) were obtained from 11 growers. Fusarium spp. were rarely recovered from seed (5%) or roots (2%). Eight Fusarium species were isolated including F. avenaceum (62%), F. solani (11%), and F. oxysporum (10%). Pathogenicity of select isolates was tested on seedlings and fresh roots and significant differences were noted. Results will be used to develop strategies to limit Fusarium spp. affecting these perennial crops.
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Title: ANALYSIS OF SEQUENTIAL MEDIATORS IN THE RELATIONSHIP BETWEEN MISTT INTERVENTIONS AND PHYSICAL AND MENTAL HEALTH OF STROKE PATIENTS
Creator: Bridges, Michael
Date: 2021
Collection: Electronic Theses & Dissertations
Description: The Michigan Stroke Transitions Trial (MISTT) is a pragmatic, un-blinded, 3-group randomized controlled trial conducted in 3 Michigan hospitals and designed to compare patient recovery under one of two interventions, (1) social worker case management (SWCM) and (2) social worker case management in addition to an online stroke recovery resource (VSSP), relative to usual care (UC). Using a difference-in-differences approach, and comparing outcome measures at 90-days post-discharge to outcomes...
Show moreThe Michigan Stroke Transitions Trial (MISTT) is a pragmatic, un-blinded, 3-group randomized controlled trial conducted in 3 Michigan hospitals and designed to compare patient recovery under one of two interventions, (1) social worker case management (SWCM) and (2) social worker case management in addition to an online stroke recovery resource (VSSP), relative to usual care (UC). Using a difference-in-differences approach, and comparing outcome measures at 90-days post-discharge to outcomes at 7-days post-discharge, MISTT found significant positive outcomes in PROMIS physical health (p = 0.002) and Patient Activation (p = 0.06) in the VSSP treatment arm relative to UC. We hypothesized that emotional support and patient activation acted as sequential mediators in the pathway between randomly assigned treatment and physical and mental health. We estimated the direct and indirect effects of the interventions using an adapted version of the weighted approach. Multiple imputation was used to account for missing observations and bootstrapping was used to construct standard errors. We found no statistically significant (p < 0.05) mediation effects. That said, we observed a sizable positive natural direct effect of the VSSP treatment relative to usual care on patient physical health (+1.40, 95% CI: –0.56, 3.35). In addition, there appeared to be a negative partial natural indirect effect of the SWCM treatment on both mental and physical health which acted through patient activation, not emotional support. We report no mediated effects of statistical significance; however, some sizable effects bear further study. In particular, neither of our hypothesized mediators appeared to fully explain the positive effect of VSSP treatment on physical health shown in the MISTT primary results; and the lack of change in mental health found in MISTT might be explained by a decrease in patient activation found in the SWCM treatment arm.
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Title: EFFECTS OF PRESENTATIONS OF ASSESSMENT ROUNDS ON PREFERENCE STABILITY
Creator: Thomas, Alexandria
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Behavior interventions have been found to be the most effective treatments for behaviors associated with Autism Spectrum Disorder (ASD). Children diagnosed with ASD tend to experience barriers in terms of communication, thus communicating wants and needs during treatment may be difficult. As a result, clinicians have used preference assessments to identify potentially reinforcing stimuli to use during behavior interventions to increase the likelihood of desired behaviors occurring again in...
Show moreBehavior interventions have been found to be the most effective treatments for behaviors associated with Autism Spectrum Disorder (ASD). Children diagnosed with ASD tend to experience barriers in terms of communication, thus communicating wants and needs during treatment may be difficult. As a result, clinicians have used preference assessments to identify potentially reinforcing stimuli to use during behavior interventions to increase the likelihood of desired behaviors occurring again in the future. Previous research on preference assessments has looked at evaluating brief preference assessments and stability of responding across time and assessments. The purpose of this study is to evaluate the extent to which responding is stable across rounds within a single MSWO for children aged 3-5 with a diagnosis of ASD. Results showed that overall; stability in responding across rounds of a single MSWO varied across participants regardless the type of stimuli used during the assessment (all edible or all tangible stimuli).Keywords: autism, preference assessments, stability
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Title: UNDERSTANDING ACADEMIC ADVISING PRACTICE : ACADEMIC ADVISORS’ PERCEIVED IMPACT OF AN ACADEMIC ANALYTICS TOOL ON THE PRACTICE OF ACADEMIC ADVISING
Creator: Dumont, Kristy Chene
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Higher education institutions are facing growing pressure to improve retention and graduation rates. Academic analytics has emerged as a strategy to address the completion issue. Because academic advisors are integral in providing successful student success initiatives and they often maintain relationships with students throughout their entire academic careers, academic advising is the essential component to increasing completion rates. Therefore, the technologies included in the academic...
Show moreHigher education institutions are facing growing pressure to improve retention and graduation rates. Academic analytics has emerged as a strategy to address the completion issue. Because academic advisors are integral in providing successful student success initiatives and they often maintain relationships with students throughout their entire academic careers, academic advising is the essential component to increasing completion rates. Therefore, the technologies included in the academic analytics strategy most often impact academic advising work. The purpose of this study was to investigate how academic advisors perceive the practice of academic advising at Amey State University (ASU) in the context of changing technology tools, specifically the implementation of the Student Success System (SSS). The study used an exploratory qualitative methodology since there is little other research that seeks to understand the practice of academic advising from the advisors’ perspective. Using the NACADA (2017a) Academic Advising Core Competencies as the conceptual framework this study explored how the use of an academic analytics tool changed the work academic advisors do through the Conceptual (understanding), Informational (knowledge), and Relational (skills) components. The participants were all academic advisors from Amey State University, a large, four-year, public, research one institution with a high population of undergraduate students (Carnegie Classification, 2018). The findings of this study reveal that the academic advisors have a strong focus on student success yet do not identify or connect with the broader student success goals of the institution. There is a lack of trust from the advisors in upper administration in regards to decision-making and a need for clear, transparent, and frequent communication between leaders and academic advisors regarding student success mission and goals. Integration of the Student Success System (SSS) into the academic advisors’ daily practice only caused minor disruptions and little improvement to their practice of advising because of the inability to use most of the functions. This study concludes that academic advising practice is constantly changing and evolving due to internal and external forces. The increased attention to retention, completion, and persistence along with the rapid advancements in technology tools to assist these efforts will mark the next era of academic advising practice. Academic advising will need to find ways to deal with the rapid changes in technology tools and seek best practices in transitioning from one tool to another in order to keep pace with the changes.
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Title: “AM I RACIST OR ARE MY ACTIONS RACIST?” : EXPERIENCES OF FOUR MUSIC EDUCATORS WHO LEARN ABOUT CRITICAL RACE THEORY
Creator: Lewis, Amy Belinda
Date: 2021
Collection: Electronic Theses & Dissertations
Description: In this study, I critically examined the experiences of four music teachers who learned about critical race theory (CRT) in a professional learning community (PLC) in an effort to enhance teachers’ understandings of race and racism in music education. The participants engaged in readings, online reflections, discussions, and interactive lectures based on the five central CRT tenets: counternarratives, ordinariness, Whiteness as property, intersectionality, and interest convergence. The...
Show moreIn this study, I critically examined the experiences of four music teachers who learned about critical race theory (CRT) in a professional learning community (PLC) in an effort to enhance teachers’ understandings of race and racism in music education. The participants engaged in readings, online reflections, discussions, and interactive lectures based on the five central CRT tenets: counternarratives, ordinariness, Whiteness as property, intersectionality, and interest convergence. The following research questions guided the study:1. How do the music teachers’ perceptions of CRT evolve within the professional learning community experience? 2. How might an understanding of CRT influence music teachers’ practices/pedagogical choices? 3. How might participation in the PLC transform their approach toward race and racism? What, if any, transformations took place? These questions highlight teacher growth and reflection––a tool necessary for liberation (Lorde, 2007). Additionally, understanding race and racism in music education provides an opportunity to address racism through philosophical shifts and pedagogical changes. For this study, I employed an instrumental embedded case study (Yin, 2009) with multiple units of analysis in order to capture a deeper understanding of the participants’ experience. I used transformative learning theory (Mezirow, 1991) as an analytical lens to examine and explore if and/or how the participants experienced transformation throughout the PLC. I centered my analysis on the disorienting dilemmas (situations that challenge participants’ world views) the participants experienced during the PLC. The findings from this study suggest that learning about CRT in the context of a PLC can create an opportunity for participants to experience a foundational shift in understanding race and racism, both as music educators and in their individual lives. As participants expanded their understanding of racism, they critiqued common practices in music education such as the dominance of Western European classical music. Through deep, critical reflection, they questioned if they or their practices were racist. During this experience, the participants identified how their understanding of racism expanded in a way that recognizes racist structures in addition to individual racist acts. This expansion can shift perspectives and change actions inside the classroom to center and create music teaching practices that challenge structural racism.
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Title: THE IMPORTANCE OF THE FRESHWATER LANDSCAPE, CONNECTIVITY, AND REGIONAL PROCESSES FOR UNDERSTANDING SPATIAL PATTERNS AND DRIVERS OF LAKE, STREAM, AND WETLAND PROPERTIES AT MACROSCALES
Creator: King, Katelyn Beth Shank
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Freshwater ecosystems are a good model for studying questions associated with environmental change because their nutrients and biota reflect changes in their surrounding watershed. Although many studies of fresh waters focus on understanding how the terrestrial landscape affects lake, stream, and wetland properties, it is becoming more widely recognized that we must also consider the freshwater landscape, including connections (or lack thereof) among surface waters, to understand and manage...
Show moreFreshwater ecosystems are a good model for studying questions associated with environmental change because their nutrients and biota reflect changes in their surrounding watershed. Although many studies of fresh waters focus on understanding how the terrestrial landscape affects lake, stream, and wetland properties, it is becoming more widely recognized that we must also consider the freshwater landscape, including connections (or lack thereof) among surface waters, to understand and manage freshwater ecosystems. However, freshwater types continue to be studied individually (e.g., lakes or streams or wetlands) or at relatively local scales (e.g., an individual lake to tens of lakes within a watershed), whereas environmental changes such as land use intensification, climate change, and the spread of non-native species affect all freshwater types and often occur at broad spatial scales such as regions, continents, and the globe. Understanding patterns of freshwater properties at broad-extents can be complicated by the influence of drivers operating at different spatial scales (i.e. cross-scale interactions). An emergent specialty in ecology, macrosystems ecology, provides a framework for broad-extent, multi-scale, and cross-freshwater type studies, improving predictions and contributing to the understanding of freshwater ecosystem responses to change at the regional to continental extents relevant for management and policy. In addition, the recent rise of open science perspectives and advancements in computational tools makes it possible to collate data and perform analysis at the macroscale. My dissertation uses this theoretical foundation and publicly-available databases to understand macroscale patterns in nutrients and fish biodiversity across freshwater types and the processes that may underlie those patterns.In my first chapter, I compiled total phosphorus, total nitrogen, chlorophyll a, and percent macrophyte cover from over 3,500 lakes, streams, and wetlands sampled by the Environmental Protection Agency’s National Aquatic Resource Surveys across the continental U.S. This research led to the understanding that these different freshwater types may share similar patterns and drivers of nutrients across the U.S., but different patterns and drivers for biotic properties. For my second chapter, I further investigated biotic properties across lakes and streams, specifically focusing on fish biodiversity patterns and connections between lakes and streams. I used fish data from 559 lakes and 854 streams from the midwestern/northeastern U.S. and found that discrete connectivity classes helped explain variation in fish species composition and richness across lakes and streams. My third chapter is a data paper that describes methods for creating a database (LAGOS-NETWORKS) that includes a suite of surface connectivity metrics for 86,511 lakes and 898 networks in the U.S. This is the first database to provide accessible and comprehensive lake network metrics at the national scale. LAGOS-NETWORKS was used in my final chapter, where I used these continuous connectivity metrics and other multi-scale drivers to investigate how the effects of connectivity on fish species richness change with regional-scale land use. I found that connectivity had different effects on lake and stream fish species richness depending on regional-scale agricultural land use, showing a cross-scale interaction (CSI) and the effect of this CSI differed by freshwater type. Collectively, my dissertation uses multi-scale, cross-scale, and an integrated freshwater landscape approach to further understand patterns and processes in aquatic ecosystems at the macroscale.
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Title: Toward Stress-Aligned Lattice Design
Creator: Gao, Qiren
Date: 2021
Collection: Electronic Theses & Dissertations
Description: A novel approach to designing lattice structures is presented in which lattice members are aligned with the principal stress directions, and the lattice spacing and member sizing are optimized simultaneously to obtain an optimized design. By allowing both the lattice layout and the member sizes to vary during a multi-level design optimization process, this approach allows a greater flexibility in searching the design space and finding potentially higher performing designs than standard...
Show moreA novel approach to designing lattice structures is presented in which lattice members are aligned with the principal stress directions, and the lattice spacing and member sizing are optimized simultaneously to obtain an optimized design. By allowing both the lattice layout and the member sizes to vary during a multi-level design optimization process, this approach allows a greater flexibility in searching the design space and finding potentially higher performing designs than standard topology or triangularization methods. Example applications amply illustrate the capability of this approach to produce high quality designs.
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