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- Title
- Statistical and computational methods for biological data
- Creator
- Hao, Yuning
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
The development of biological data focuses on machine learning and statistical methods. In immunotherapy, gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative...
Show moreThe development of biological data focuses on machine learning and statistical methods. In immunotherapy, gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative to develop a robust deconvolution method that automatically decontaminates data by reliably detecting and removing outliers. Our development of an algorithm called adaptive Least Trimmed Square (aLTS) identifies outliers in regression models, allows us to effectively detect and omit the outliers, and provides us robust estimations of the coefficients. For the guarantees of the convergence property and parameters recovery, we also included certain theoretical results.Another interesting topic is the investigation of the association of phenotype responses with the identified intricate patterns in transcription factor binding sites for DNA sequences. To address these concerns, we pushed forward with a deep learning-based framework. On one hand, to capture regulatory motifs, we utilized convolution and pooling layers. On the other hand, to understand the long-term dependencies among motifs, we used position embedding and multi-head self-attention layers. We pursued the improvement of our model's overall efficacy through the integration of transfer learning and multi-task learning. To ascertain confirmed and novel transcription factor binding motifs (TFBMs), along with their relationships internally, we provided interpretations of our DNA quantification model.
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- Title
- Role of propionate and uncouplers of oxidative phosphorylation on hepatic metabolism and feeding behavior in dairy cows
- Creator
- Kennedy, Katherine Marie
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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The negative energy balance of dairy cows in the postpartum period is exacerbated by a suppression in appetite. Metabolic diseases resulting from negative energy balance can decrease milk production, health and fertility, increasing risk of culling. Research suggests that feeding behavior is linked to the oxidation of fuels in the liver and that an increase in oxidation of fuels causes satiety. Propionate derived from the fermentation of starch in the rumen is a major glucose precursor in...
Show moreThe negative energy balance of dairy cows in the postpartum period is exacerbated by a suppression in appetite. Metabolic diseases resulting from negative energy balance can decrease milk production, health and fertility, increasing risk of culling. Research suggests that feeding behavior is linked to the oxidation of fuels in the liver and that an increase in oxidation of fuels causes satiety. Propionate derived from the fermentation of starch in the rumen is a major glucose precursor in dairy cows but can also cause hypophagia. Because propionate is anaplerotic, it stimulates the oxidation of fuels in the liver, likely causing the hypophagic effects. In order to determine the role of anaplerotic metabolites and uncouplers of oxidative phosphorylation on hepatic metabolism and feeding behavior in dairy cows, 6 studies were conducted. First, using 8 dairy cows in a duplicated 4x4 Latin square design, the effect of feed status (before or after access to feed) on the hepatic extraction and metabolism of propionate over 20 min was determined. The results indicated that hepatic extraction and metabolism of propionate is very rapid, and that metabolite concentrations were greater after compared with before feeding. Additionally, potential bottlenecks of propionate metabolism were identified. Secondly, a study using hepatic explants incubated in [13C3]sodium propionate was conducted to test the effects of 3 different concentrations of propionate (1, 2 or 4 mM) on propionate metabolism over 60 min. An increased concentration of propionate in the range from 1 - 4 mM resulted in the conversion of propionate to acetyl CoA, likely through pyruvate, and that the acetyl CoA was incorporated into the TCA cycle for oxidation. Additionally, metabolism of [13C3]propionate occurred rapidly with significant increases of 13C enrichment detected within 0.5 min for many metabolites. Furthermore, uncoupling the electron transport chain should affect the metabolism of propionate and the feeding behavior of dairy cows as a result of inefficient oxidation of fuels. The effects of two uncouplers of oxidative phosphorylation, 2,4-dinitrophenol methyl ether (DNPME) and sodium salicylate (SAL), on feeding behavior in dairy cows were determined in 2 experiments. Treatment with DNPME and SAL decreased eating rate in dairy cows over the first 4 h following access to feed. Additionally, DNPME increased meal length over the first 4 h following access to feed. Lastly, an experiment was conducted to determine the effects of DNPME and SAL on metabolism and oxidation of propionate over 60 min using hepatic explants from 8 dairy cows. Neither DNPME nor SAL increased oxidation. The DNPME treatment did not alter metabolism of propionate except for an increase of propionate converted to succinyl CoA, however, SAL decreased glucose synthesis from propionate. From this research, we conclude that hepatic metabolism of propionate occurs rapidly and is likely having effects on feeding behavior within minutes as well. As such, the importance of short-term metabolism in regard to feeding behavior and dry matter intake should be considered in future research. Understanding the mechanisms for metabolic control of feed intake will lead to development of novel nutritional or pharmacological approaches to increase energy intake, health, and milk yield of dairy cows; thus, improving nutrient utilization and sustainability of the dairy industry.
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- Title
- Tailoring the growth and electronic structure of organic molecular heterointerfaces
- Creator
- Tan, Andrew W. J.
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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In the rapidly developing electronics industry, it has become increasingly necessary to explore materials that are cheap, flexible and versatile which have led to significant research efforts towards organic molecular thin films. Understanding and control of heterointerface between highly ordered organic molecular thin films with extended π systems and inorganic materials are therefore of critical importance for the development of modern organic electronics. Organic molecules are unique...
Show moreIn the rapidly developing electronics industry, it has become increasingly necessary to explore materials that are cheap, flexible and versatile which have led to significant research efforts towards organic molecular thin films. Understanding and control of heterointerface between highly ordered organic molecular thin films with extended π systems and inorganic materials are therefore of critical importance for the development of modern organic electronics. Organic molecules are unique compared to their inorganic atomic counterparts as their properties can be tuned drastically through chemical functionalization, offering versatility, though their extended shape and weak intermolecular interactions bring significant challenges to the control of both the growth and the electronic structures of molecular thin films. This is further complicated by interaction between organic molecules and the underlying substrate which can lead to interfacial effects such as charge transfer, chemical interaction and electrostatic screening, all of which can significantly impact device performance and/or the characteristic of the organic thin film. This dissertation will first focus on a systematic review of the growth and electronic structure of organic molecular thin films, particularly on weakly interacting substrates. The self-assembly process and how long-range ordered organic molecular thin films are established will be discussed. We will also discuss how the electronic structures of thin films are impacted by the molecule’s local electrostatic environment and its interaction with the substrate, within the context of controlling interfacial energy level alignment between organic semiconductors and electrodes in electronic devices. Employing scanning tunneling microscopy and spectroscopy, experimental studies focusing on characterizing the growth and electronic structure of organic molecules on weakly interacting substrates were carried out and discussed. Studies focusing on the electronic structure of zinc phthalocyanine (ZnPc) and its fluorinated counterpart F16ZnPc were carried out on the deactivated Si(111)-B surface and h-BN/Cu(111). We show that interfacial charge transfer occurs between the deactivated Si(111)-B substrate and the F16ZnPc monolayer, which gives rise to a pronounced spatial variation of the occupied molecular state across the molecular assembly attributed to the inhomogeneous electrostatic screening of the intra-orbital Coulomb interaction in molecular adsorbates arising from the substrate boron distribution in the deactivated Si(111)-B substrate. To circumvent this inhomogeneous effect, the donor-acceptor molecular pair was studied on weakly interacting hexagonal boron nitride (h-BN)/Cu(111) which possesses a periodic electronic corrugation. We show that the formation of the lateral heterostructure drastically increases the charge transfer between F16ZnPc molecules and the substrate, which is attributed to the greater electrostatic stability of the heterostructure compared to that of the pure phase. This study highlights the importance of the substrate, even a weakly interacting one, such as h-BN/metal, can still perturb the intermolecular charge transfer and thereby the heterostructure behaviors via interfacial processes. The focus of a secondary study was to initiate preliminary experimentation towards understanding the substrate’s influence on the exotic properties of a class of organic-based systems known as charge transfer complexes (CTC). By utilizing the unique modulation properties of various weakly-interacting substrates, control of the properties of CTCs could be attained allowing for a better understanding of their fundamental physical mechanism to be developed and a new class of thin-film CTCs which will be highly relevant towards organic electronics to be developed.
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- Title
- Testing a model of healthy marriage/healthy relationships : the prediction of parenting and child well-being
- Creator
- Shambleau, Krista M.
- Date
- 2010
- Collection
- Electronic Theses & Dissertations
- Description
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Federally funded Healthy Marriage Initiative (HMI) programs provide marriage education as well as other services to low-income diverse individuals and couples at many points along the marital continuum with improving children's well-being as the overarching purpose. These programs need appropriate measures of healthy marriage for couples with children that relate to well-being. Purposes of this research were to examine the factor structure of a healthy marriage measurement developed by...
Show moreFederally funded Healthy Marriage Initiative (HMI) programs provide marriage education as well as other services to low-income diverse individuals and couples at many points along the marital continuum with improving children's well-being as the overarching purpose. These programs need appropriate measures of healthy marriage for couples with children that relate to well-being. Purposes of this research were to examine the factor structure of a healthy marriage measurement developed by Manpower Demonstration Research Corporation (MDRC) and how it varied across (a) gender, (b) race (African American and Caucasian), and (c) marital status (married and unmarried). An additional purpose was to test a measurement model, developed by Child Trends, Inc., in which healthy marriage is hypothesized to predict parenting and child well-being. This cross-sectional quantitative survey research included 343 Head Start parents (151 males and 189 females) involved in a marriage/relationship. Overall, the unidimensional healthy marriage measurement fit for both males and females and the addition of two marital virtues, namely forgiveness and teamwork, also loaded well on this measurement. The factor loadings were significant for both males and females and results of chi-square difference tests indicated that the factor loadings for the great majority of variables were invariant across gender. However, the factor loading for relationship stability (one's assessment that their relationship is not in trouble) was larger for males whereas child commitment (one's assessment of their spouse/partner's commitment to their child) was larger for females. Path analysis demonstrated that the Child Trends, Inc. healthy marriage measurement model fit differed by gender and this was supported by further SEM analysis. The effect size for the direct path between risk and healthy marriage was significantly larger for females than for males. The effect size of this path tended to be greater for African American women and unmarried women. Results using fit indices showed that the fit of the measurement model was appropriate for the diverse sample. Mediation results revealed that for both males and females, healthy marriage partially mediates the effect that depression and stress have on parenting. For females, parenting partially mediates the effect between risk and children's social competence as well as between healthy marriage/healthy relationships and children's social competence. Findings demonstrate support for the Child Trends' measurement model that healthy marriage/healthy relationships may enhance children's social competence through positive parenting. Study results may inform federal and state healthy marriage and family initiatives as well as marriage and relationship education in terms of program delivery and evaluation.
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- Title
- The regiments : cultural histories of Zulu masculinities and gender formation in South Africa, 1816-2018
- Creator
- Timbs, Elizabeth H.
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
"This dissertation reconstructs aspects of the history of Zulu martial heritage through the prism of the amabutho (regiments, age-grades) in KwaZulu-Natal, South Africa, from the era of Shaka Zulu (ca. 1816) to the present. Based on archival research and oral history interviews, this study argues that despite being outlawed by the British colonial regime in 1879, Zulu chiefs continued to form amabutho, but for different purposes. Regiments became youth structures for commercial labor...
Show more"This dissertation reconstructs aspects of the history of Zulu martial heritage through the prism of the amabutho (regiments, age-grades) in KwaZulu-Natal, South Africa, from the era of Shaka Zulu (ca. 1816) to the present. Based on archival research and oral history interviews, this study argues that despite being outlawed by the British colonial regime in 1879, Zulu chiefs continued to form amabutho, but for different purposes. Regiments became youth structures for commercial labor recruitment and British military conscription; they enabled indigenous leaders to access martial discourse and metaphors for political mobilization; expressed cultural forms of resistance to state racism; and nurtured the sustenance of Zulu identities in a changing South Africa. Exploring the amabutho's links to the Zulu monarchy also helps to shed light on the evolving role and status of the Zulu Royal House. While both the white-run Natal and Union governments feared the influence that Shaka's successors held among Zulu-speaking Africans, the authorities also relied on Paramount Chief Solomon to recruit black volunteers from Natal and Zululand for World War I. In the apartheid era (1948-1994), the invocation of the Zulu nation's warrior legacy endured. As migrant laborers, Zulu men recreated their martial identities and manifestations of the amabutho became more abstract, emerging in society, culture, and politics in unexpected ways. As the struggle against apartheid intensified, the continued relevance of this martial heritage mobilized Zulu communities, bringing them in conflict with first the African National Congress and later the United Democratic Front. In the post-apartheid period (1994-present), the rhetoric, symbolism, and practices of Zulu regiments continues to resonate and evolve. In the case of "high politics," Zulu political leaders turn to martial metaphors to engender support, while, on the ground, local authorities throughout the province struggle to maintain the traditions that give these metaphors meaning. The historiographical significance of this dissertation is threefold. First, it extends earlier studies to consider Zulu martial masculinity over two centuries. Second, it uncovers how amabutho shaped, and have been shaped by, white anxieties about Zulu men's "violent potential" as well as a need for cheap labor. Third, this dissertation reconsiders the shifting role of chiefs and kings in South Africa since 1800."--Pages ii-iii.
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- Title
- Essays in the economics of education
- Creator
- Lee, Hwanoong
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"This dissertation comprises three essays on the Economics of Education. Its ultimate focus is to understand how different agents in the education market respond to releasing information about teacher and school performance and how public interventions influence human capital accumulation. The first essay "The Effect of Releasing Teacher Performance Information to Schools: Teachers' Response and Student Achievement" examines the effects of releasing teacher value-added (VA) information on...
Show more"This dissertation comprises three essays on the Economics of Education. Its ultimate focus is to understand how different agents in the education market respond to releasing information about teacher and school performance and how public interventions influence human capital accumulation. The first essay "The Effect of Releasing Teacher Performance Information to Schools: Teachers' Response and Student Achievement" examines the effects of releasing teacher value-added (VA) information on student performance in two settings; in the first, VA data was released to all potential employers within the district, while in the second, only the current employer received the data. I find that student achievement increased only in the district where the VA scores were provided to all potential employers. These effects were driven solely by improved performance among ex-ante less-effective teachers; the null effects in the other setting, however, were driven by moderate declines in performance among ex-ante highly-effective teachers and small improvements among less-effective teachers. These results highlight the importance of understanding how the design features of VA disclosure translate into the productivity of teachers. The second essay "The Role of Credible Threats and School Competition within School Accountability Systems: Evidence from Focus Schools in Michigan" studies the impact of receiving accountability labels on the student achievement distribution under No Child Left Behind (NCLB) waivers. Using a sharp regression discontinuity (RD) design, I examine the achievement effects of Focus (schools with the largest achievement gaps) labels and find that schools receiving the Focus label improved the performance of low-achieving students relative to their barely non-Focus counterparts, and they did so without hurting high-achieving students. The positive achievement effects for Focus schools were entirely driven by Title 1 Focus schools that faced financial sanctions associated with being labeled the following year. There is no evidence of an achievement effect associated with the Priority label. Next, I examine heterogeneous effects by looking at the number of alternative nearby schooling options. I find that when schools are exposed to a competitive choice environment, receiving the Focus label increased math test scores across the scoring distribution, while schools located in an uncompetitive choice environment improved the test scores of low achievers only. This evidence may suggest the importance of incorporating credible sanctions and school choice options into the school accountability system to maximize the effectiveness of the system on student achievement. Finally, the third essay "The Effects of School Accountability Systems Under NCLB Waiver: Evidence from Priority Schools in Michigan" investigates the impact of receiving Priority labels on the student achievement distribution under No Child Left Behind (NCLB) waivers. Using a sharp regression discontinuity (RD) design, I examine the achievement effects of the Priority (schools with the lowest performance) label and find no evidence of an achievement effect associated with the Priority label. Next, I examine whether assigning the Priority label induced the changes in the composition of students. I define several key measures of student composition and find no evidence that the Priority designation influenced the student composition of schools."--Pages ii-iii.
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- Title
- Reaction-based modeling and control of an electrically boosted diesel engine
- Creator
- Men, Yifan
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
This dissertation presents the reaction-based modeling of diesel combustion and model-based control of diesel engine air path.The dissertation first presents a control-oriented reaction-based diesel combustion model that predicts the time-based rate of combustion, in-cylinder gas temperature and pressure over one engine cycle. The model, based on the assumption of a homogeneous thermodynamic combustion process, utilizes a two-step chemical reaction mechanism that consists of six species:...
Show moreThis dissertation presents the reaction-based modeling of diesel combustion and model-based control of diesel engine air path.The dissertation first presents a control-oriented reaction-based diesel combustion model that predicts the time-based rate of combustion, in-cylinder gas temperature and pressure over one engine cycle. The model, based on the assumption of a homogeneous thermodynamic combustion process, utilizes a two-step chemical reaction mechanism that consists of six species: diesel fuel (C10.8H18.7), oxygen (O2), carbon dioxide (CO2), water (H2O), nitrogen (N2), and carbon monoxide (CO). The temperature variation rate is calculated based on the rate of change of species concentrations, and the heat loss correlation is also used to study the model performance. The accuracy of the model is evaluated using the test data from a production GM 6.6 L, 8-cylinder, turbocharged engine. The model is calibrated over large engine speed and load range as well as different injection timings and exhaust gas recirculation (EGR) rates by solving the optimization problem. The calibrated reaction-based model accurately predicts the indicated mean effective pressure, while keeping the errors of in-cylinder pressure and temperature small, and at the same time, significantly reduces the calibration effort, especially when the engine is operated under multiple fuel injection operations, comparing to Wiebe-based combustion models. The calibrated model parameters have a strong correlation to engine speed, load and injection timings, and as a result, a universal parameter calibration structure is proposed for entire operational conditions.The second part of the dissertation is to obtain a parametric understanding of diesel combustion by developing a physics-based model that is able to predict the combustion metrics, such as in-cylinder pressure, burn rate, and indicated mean effective pressure (IMEP) accurately, over a wide range of operating conditions, especially with multiple injections. In the proposed model, it is assumed that the engine cylinder is divided into three zones: a fuel zone, a reaction zone, and an unmixed zone. The formulation of reaction and unmixed zones is based on the reaction-based modeling methodology, where the interaction between them is governed by Fick's law of diffusion. The fuel zone is formulated as a virtual zone, which only accounts for mass and heat transfer associated with fuel injection and evaporation. The model is validated using test data under different speed and load conditions, with multiple fuel injections and EGR. It is shown that the three-zone model outperformed the single-zone model in in-cylinder pressure prediction and calibration effort with a mild penalty in computational time. One set of calibration parameters are used for all engine operating conditions.The third part of the dissertation is modeling and control of engine air path with an electrically assisted boosting system. A physics-based control-oriented engine air path model with electrical assistance has been developed. The model is validated with steady-state engine test data and standard driving cycle data. Through one-dimensional simulation, it is found that the electrically assisted boosting system is able to improve engine performance under both steady-state and transient conditions. A model-based controller has been developed for the electric booster (eBoost) and bypass valve to improve the transient performance of engine load response. Experiments have been performed on a Ford 6.7 L, 8-cylinder, turbocharged diesel engine equipped with a prototype eBoost and a standard EGR valve as the bypass valve. Steady-state test results have shown that eBoost is capable of improving engine efficiency by reducing pumping loss, due to reduced turbine speed when eBoost is providing additional boost energy. In the transient process, eBoost is able to significantly reduce the response time of boost pressure tracking, as validated by load step tests.
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- Title
- An exploration of mid- to high-valent transition metal complexes for application to catalysis
- Creator
- Aldrich, Kelly E.
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
"The valency or oxidation state of a transition metal in a complex plays a large role in determining the reactivity of the complex. With transition metal chemistry, historically accessible chemistry has often focused on metals in a low oxidation state. However, transformations involving transition metals in high oxidation states are of equal importance in providing complex products for use in consumer products. Expanding the applications and understanding of transition metal complexes in high...
Show more"The valency or oxidation state of a transition metal in a complex plays a large role in determining the reactivity of the complex. With transition metal chemistry, historically accessible chemistry has often focused on metals in a low oxidation state. However, transformations involving transition metals in high oxidation states are of equal importance in providing complex products for use in consumer products. Expanding the applications and understanding of transition metal complexes in high oxidation states is the focus of the research presented in this dissertation. Fundamental studies of how ligands interact with high valent metals is presented in chapters 2 and 3, where a chromium(VI) model complex has been used to study bonding interactions between this d0 transition metal and phosphine ligands. Practical application of high valent titanium(IV) catalysts to C--N bond forming reactions is presented in chapters 4--6. Finally, chapters 7 and 8 focus on the changes in the character of M--N double bonds, with M=Fe and Ru, as the metal is forced to higher oxidation states. Collectively, these studies demonstrate different approaches to the same general problems and questions of how chemists can better understand and utilize high valent transitions metals to do catalytically-target desired transformations."--Page ii.
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- Title
- Supports for student veterans in higher education : chat and understanding student veterans' sense of community in communities of practice
- Creator
- Christman, John (Graduate of Michigan State University)
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
"In this study, I examined and described the experiences of student veterans across three institutions of higher education. This dissertation has three overlapping purposes. First, this dissertation expands the existing scholarship and research on supports for student veterans in the form of student veteran resource centers, as well as how these supports illustrate others' understanding of the needs of student veterans. Second, this dissertation helps to better understand the degree to which...
Show more"In this study, I examined and described the experiences of student veterans across three institutions of higher education. This dissertation has three overlapping purposes. First, this dissertation expands the existing scholarship and research on supports for student veterans in the form of student veteran resource centers, as well as how these supports illustrate others' understanding of the needs of student veterans. Second, this dissertation helps to better understand the degree to which student veterans feel like they are part of a community and how student veterans are provided with varying levels of support. Third, I conclude by providing stakeholders in higher education with suggestions based on the findings and feedback from my two studies to take into consideration with regard to the creation and implementation of student veteran resource centers. By analyzing the experiences of student veterans, the resource centers, and the administrators who operate them, this study fills important gaps in our understanding of the purposes of these resource centers, as well as how and why student veterans choose to use them. This study pursues answers to two groups of guiding questions: 1. What are the commonalities or differences with regard to the goals of student veteran resource centers at different universities, such as how they are used and what their purposes are? Additionally, how do these commonalities and differences illustrate higher education administrators' understanding of the needs of student veterans? 2. What are the predictors that have the strongest influence on student veterans' sense of community in communities of practice, and given that each university in this study is the recipient of the same award for supporting student veterans, how does each university demonstrate this support and what are the possible differences?"--Pages ii-iii.
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- Title
- An exploration of gardener support programs, community gardeners' experiences, and associations with perceived dietary choices, food security, and food values
- Creator
- Beavers, Alyssa
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
"Gardening is associated with health behaviors, including fruit and vegetable consumption and physical activity. Maintaining these benefits is dependent on sustaining gardens and interest of gardeners, which can be challenged by lack of gardening skills and knowledge and financial cost. Gardener support programs reduce these barriers by providing gardening resources and education, especially important for new gardeners who may lack gardening skills and knowledge. The overall objectives of...
Show more"Gardening is associated with health behaviors, including fruit and vegetable consumption and physical activity. Maintaining these benefits is dependent on sustaining gardens and interest of gardeners, which can be challenged by lack of gardening skills and knowledge and financial cost. Gardener support programs reduce these barriers by providing gardening resources and education, especially important for new gardeners who may lack gardening skills and knowledge. The overall objectives of this dissertation were to understand how and why gardening influences diet, the challenges faced by new gardeners, and aspects of gardener support programs that may be most beneficial to sustaining gardens. The aims of this dissertation were to: 1. Investigate how and why gardening is perceived to influence dietary choices and food security, 2. Explore the experiences of new community gardeners, and 3. Examine the associations between garden characteristics, participation in components of a gardener support program, and continued program participation. For the first aim, in-depth semi-structured qualitative interviews were conducted with 28 experienced members of the Garden Resource Program operated by Keep Growing Detroit, a non-profit organization in Detroit, Michigan. Data were analyzed by thematic coding. Many gardeners perceived that gardening led to increased vegetable intake and decreased intake of less healthy foods, including fast food and processed foods. They perceived knowing how their food was produced, an emotional attachment to food they grew, and that home-grown produce tasted better caused these dietary changes. Gardening was perceived to influence aspects of food security by contributing to financial savings on food and providing ample access to fresh vegetables, which gardeners preserved for year-round use. In the second aim, in-depth semi-structured qualitative interviews were conducted with 15 new community gardeners participating in a randomized controlled trial of community gardening in Denver, Colorado to examine their perceptions of leadership, social interaction in the garden, and challenges. Thematic coding was used to analyze data. Key challenges described by new gardeners included limited time and lack of gardening knowledge. There was variation in new gardeners' perceptions of social interaction in the garden and support from their garden leaders. Engaged garden leaders and other experienced gardeners helped alleviate challenges by sharing their gardening knowledge and assisting new gardeners. In the third aim, data from Keep Growing Detroit's records on 2,318 gardens participating in their program from 2012-2015 was used to examine the association between components of their programming and continued garden participation using multilevel logistic regression and mediation analysis. Program components associated with continued garden participation in the Garden Resource Program included attending educational classes, volunteering, previous years of garden membership in the Garden Resource Program, and receiving seeds and plants. Comprehensive education indirectly increased the likelihood of continued garden membership through participation in other aspects of the program. Overall, these three studies advance the understanding of sustaining and expanding gardening's health impacts by demonstrating how gardening is perceived to influence dietary choices and food security and highlighting the importance of leadership and social interaction, and education and resources to sustain gardeners' participation and improve garden longevity."--Pages ii-iii.
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- Title
- The informativeness of consumer opinions on firm fundamentals : evidence from Amazon.com
- Creator
- Jin, Shunyao
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
"This study examines whether online consumer product reviews contain information that is associated with firms' earnings and stock returns around earnings announcements. Ex ante, it is unclear whether consumer reviews are useful to investors because consumer reviews have not been easily accessible or widely disseminated. Based on 18,794,143 consumer reviews posted on Amazon.com during 1996-2014, I construct quarterly measures of abnormal tone and abnormal rating of consumer reviews and link...
Show more"This study examines whether online consumer product reviews contain information that is associated with firms' earnings and stock returns around earnings announcements. Ex ante, it is unclear whether consumer reviews are useful to investors because consumer reviews have not been easily accessible or widely disseminated. Based on 18,794,143 consumer reviews posted on Amazon.com during 1996-2014, I construct quarterly measures of abnormal tone and abnormal rating of consumer reviews and link them to earnings surprises and earnings announcement returns. Focusing on concurrent earnings surprises, I find that negative abnormal tone is significantly associated with more negative earnings surprises while positive abnormal tone is not associated with positive earnings surprises. My analyses of abnormal returns around concurrent earnings announcements show that negative abnormal tone is positively associated with earnings announcement returns, but positive abnormal tone is not. Finally, I find that disagreements in review ratings (measured as the standard deviation of consumer review ratings) are positively associated with unexplained trading volume around earnings announcements, while disagreements in review tone (measured as the standard deviation of consumer review tone) are not. Taken together, these findings suggest that abnormal review tone is more useful than abnormal review rating in explaining concurrent earnings surprises and earnings announcement returns, but the disagreements reflected through the distribution of consumer ratings is more informative about the unexplained trading volume around earnings announcements. My results suggest that both the rating and the tone of consumer reviews are informative, but along different dimensions."--Page ii.
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- Title
- Impact of Predation Risk on the Behavior and Physiology of Insects in Agricultural Systems
- Creator
- Ali, Sara
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
ABSTRACTNon-consumptive effects are impacts on prey survival and performance that are related to investment in anti-predator defenses. Without considering direct consumption by predators, non-consumptive effects contribute a large portion of the net effects of predatory insects have on their prey. Because the central tenant of agricultural systems is to produce the highest profitable yield; understanding how we can harness, manipulate, and foster predator non-consumptive effects will be...
Show moreABSTRACTNon-consumptive effects are impacts on prey survival and performance that are related to investment in anti-predator defenses. Without considering direct consumption by predators, non-consumptive effects contribute a large portion of the net effects of predatory insects have on their prey. Because the central tenant of agricultural systems is to produce the highest profitable yield; understanding how we can harness, manipulate, and foster predator non-consumptive effects will be helpful in development of pest management techniques. While non-consumptive effects are now known to occur quite commonly, both the spatial and temporal scale of studies are limited (demonstrated in Chapter 1). It is therefore necessary to expand our work to better understand these interactions in natural systems over longer time periods. Here I examined the potential for non-consumptive effects in an important agricultural predator-prey system between a common herbivore prey (Pieris rapae) and ubiquitous predator (Harmonia axyridis) in both the laboratory (Chapter 2) and field (Chapter 3). Interestingly, even though these species overlap in spatial distribution and phenology, little to no effect of predation risk on prey behavior was found. Further, when examining their interactions in an open-field environment, no significant non-consumptive effects on Pieris rapae were found. However, manipulatively increasing predator cues in the open-field experiment did have significant impacts on a secondary insect pest (Aphidae spp). This work emphasizes the importance of examining community interactions at the field level. In addition, non-consumptive effects resulting from H. axyridis on aphids (Myzus persicae) were found to be strong, resulting from changes in both aphid behavior and physiology (Chapter 4). Overall, these studies demonstrate that predator non-consumptive effects are prey species dependent and that studies in natural settings, over larger spatial and temporal scales, will allow us to better understand these complex interactions.
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- Title
- Cluster structure and three-body decay in 14C
- Creator
- Carpenter, Lisa Marie
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"Recent model calculations with most advanced methods for cluster states have shown the need of experimental data to probe the structure of light exotic nuclei, including those with alpha-clustering, such as 14C. The prototype Active Target Time Projection Chamber (pAT-TPC) was used in the present study. The pAT-TPC is a gas-filled thick-target detector with high luminosity and full kinematic acceptance. This type of detector gives access to a full excitation function with a single beam...
Show more"Recent model calculations with most advanced methods for cluster states have shown the need of experimental data to probe the structure of light exotic nuclei, including those with alpha-clustering, such as 14C. The prototype Active Target Time Projection Chamber (pAT-TPC) was used in the present study. The pAT-TPC is a gas-filled thick-target detector with high luminosity and full kinematic acceptance. This type of detector gives access to a full excitation function with a single beam energy. The measurements in this work were carried out by resonant alpha-scattering of a 10Be beam at 38 and 20 MeV delivered by the TwinSol facility at the University of Notre Dame. These experiments measured resonances in 14C that can be compared to models by using R-Matrix reaction theory. Two new negative parity resonances were identified at high excitation energies. Additionally, using a Dalitz-type analysis, three-body decays were analyzed to determine probabilities of 'democratic' and 'sequential' decay. Increasing probability of democratic decay was found at high energy. Results were interpreted using Gamow Shell Model and Anti-Symmetrized Molecular Dynamics calculations which are described in detail."--Page ii.
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- Title
- Dissecting the driving forces of membrane protein folding under native conditions
- Creator
- Gaffney, Kristen Ann
- Date
- 2018
- Collection
- Electronic Theses & Dissertations
- Description
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Membrane proteins are a unique class of proteins which reside within cellular membranes. They comprise 20223C30% of all proteins in most organisms. Membrane proteins are involved in a variety of important cellular processes including ATP synthesis, photosynthesis, catalysis, molecular transport and cell signaling. Missense mutations in the genes encoding membrane proteins cause several life-threatening diseases including cystic fibrosis, Alzheimer's disease, and Charcot-Marie Tooth's disease....
Show moreMembrane proteins are a unique class of proteins which reside within cellular membranes. They comprise 20223C30% of all proteins in most organisms. Membrane proteins are involved in a variety of important cellular processes including ATP synthesis, photosynthesis, catalysis, molecular transport and cell signaling. Missense mutations in the genes encoding membrane proteins cause several life-threatening diseases including cystic fibrosis, Alzheimer's disease, and Charcot-Marie Tooth's disease. These mutations are known to cause disease majorly by impacting protein stability, rather than function, via two mechanisms: 1) protein destabilization which leads to excessive degradation and low accumulation of functional protein, 2) stabilization of non-functional misfolded forms of a protein which overwhelm cellular degradation machinery. To fundamentally understand disease mechanisms, it is necessary to understand the molecular forces and mechanisms in the folding of membrane proteins. Although the study of protein folding has been one of the major quests in molecular biology over the last 223C60 years, the understanding of membrane protein folding lags far behind that of soluble proteins. This is primarily due to the lack of available methods to control the reversible folding of membrane proteins under native conditions. Recently, steric trapping, which couples the unfolding of a doubly-biotinylated protein to monovalent streptavidin binding, has emerged as a promising technique to study membrane protein folding directly under native conditions without the use of chemical denaturants, heat, or pulling force. This work presents generalized steric trapping techniques utilizing novel tripartite chemical probes to dissect the folding energy landscape of the intramembrane protease GlpG from Escherichia coli. The new steric trap tools were employed to examine the thermodynamic stability of GlpG and the physical dimension of its unfolded state. Upon the discovery of subglobal unfolding events of GlpG in the region encompassing the active site, an intricate cooperativity network important for maintaining the stability of GlpG was identified using cooperativity profiling at side chain resolution. Finally, double-mutant cycle analysis coupled with stability measurement by steric trapping revealed the weakly coupled hydrogen bond network in the catalytic active site of GlpG.
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- Title
- Exploring influences on couple therapist violence screening practices : a qualitative study
- Creator
- Parker, Nicole
- Date
- 2018
- Collection
- Electronic Theses & Dissertations
- Description
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Intimate Partner Violence (IPV) is a tremendous social problem with devastating consequences for survivors and loved ones, with effects that often last for generations. IPV not only affects the victim but it hurts society as a whole, and costs billions of dollars to the US economy each. Yet it is a preventable problem. Many couples who experience abuse seek solutions through couple therapy, yet most therapists working with couples do not directly address nor assess for the presence of...
Show moreIntimate Partner Violence (IPV) is a tremendous social problem with devastating consequences for survivors and loved ones, with effects that often last for generations. IPV not only affects the victim but it hurts society as a whole, and costs billions of dollars to the US economy each. Yet it is a preventable problem. Many couples who experience abuse seek solutions through couple therapy, yet most therapists working with couples do not directly address nor assess for the presence of violence, one estimate finding that only 4% of therapists follow guidelines to routinely screen for partner violence. Engaging couples in treatment when violence has not been assessed is dangerous for victimized clients and ethically perilous for the therapist. There is a healthy discourse in the IPV literature about how best to respond to violence in couples seeking treatment, but what is missing from this discussion is a thorough understanding of factors which influence therapists' couple violence screening practices. Guided by two theories, Ecological Theory and Role Theory, this qualitative study explores the many factors that influence clinicians in their screening practices around the topic of violence, and highlights the individual and contextual elements that govern clinical choices by the therapist. Data was gathered from clinicians working in a variety of contexts, and was analyzed using a thematic analysis approach. Findings contribute to a growing knowledge of literature that focuses on violence detection efforts within the field of mental health, and may inform educational and training policy.
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- Title
- Controllability of hyperbolic and degenerate parabolic equations in one dimension
- Creator
- Bohn, Jonathan Matthew
- Date
- 2018
- Collection
- Electronic Theses & Dissertations
- Description
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In this thesis, we study the controllability problem for two systems of partial differential equations. We will first consider the wave equation with variable coefficients and potential in one dimension, $u_{tt} - (a(x)u_x)_x + pu = 0$, with control function $v(t)$ acting on the boundary. We consider a class of functions corresponding to a special weight function that contains the variable coefficient $a(x)$. From here, we derive a global Carleman estimate for this system, and establish the...
Show moreIn this thesis, we study the controllability problem for two systems of partial differential equations. We will first consider the wave equation with variable coefficients and potential in one dimension, $u_{tt} - (a(x)u_x)_x + pu = 0$, with control function $v(t)$ acting on the boundary. We consider a class of functions corresponding to a special weight function that contains the variable coefficient $a(x)$. From here, we derive a global Carleman estimate for this system, and establish the controllability property. We then later extend the class of admissible functions $a(x)$ for which the controllability property holds true. We then study the controllability problem for the degenerate heat equation in one dimension. For $0\leq \alpha <1$, on $(0,1) \times (0,T)$, we consider $w_t - (x^{\alpha}w_x)_x = f$. This equation is degenerate because the diffusion coefficient $x^{\alpha}$ is positive in the interior of the domain and vanishes at the boundary. We consider this problem under the Robin boundary conditions. Again, we derive a Carleman estimate for this system, taking into account the new boundary terms that arise from the Robin conditions.
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- Title
- An experimental-computational study on the plastic deformation behavior of body-centered cubic titanium alloys
- Creator
- Khademi, Vahid
- Date
- 2018
- Collection
- Electronic Theses & Dissertations
- Description
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A combined experimental-computational investigation was performed in the first part of this work to quantify the relationship between plastic strain and crystallographic misorientation. Several material characterization techniques including tensile testing, Scanning Electron Microscopy (SEM), Digital Image Correlation (DIC), and Electron Backscatter Diffraction (EBSD) were combined to study the correlation between plastic strain and crystallographic misorientation at the microscale for two...
Show moreA combined experimental-computational investigation was performed in the first part of this work to quantify the relationship between plastic strain and crystallographic misorientation. Several material characterization techniques including tensile testing, Scanning Electron Microscopy (SEM), Digital Image Correlation (DIC), and Electron Backscatter Diffraction (EBSD) were combined to study the correlation between plastic strain and crystallographic misorientation at the microscale for two body-centered cubic (bcc) titanium (Ti) alloys, namely Ti-13Cr-1Fe-3Al (wt.%) and TIMETAL-21S [Ti 15Mo-3Nb-3Al-0.2Si (wt.%)]. The results revealed that larger grains experienced more misorientation dispersion compared to smaller grains. An empirical equation was proposed to estimate the crystallographic misorientation at the grain scale as a function of plastic strain and grain size. Furthermore, the effects of crystallographic orientation and loading history on the misorientation were investigated. It was observed that {100} oriented grains (with respect to the tensile axis) exhibited more of a tendency for orientation change than {110} and {111} oriented grains. Interrupted loading resulted in higher crystallographic misorientation than monotonic (uninterrupted) loading. A qualitative comparison between the DIC-SEM strain field map and the misorientation maps revealed that there is a better correlation between the hot spots in the KAM map and the DIC-SEM strain field map compares with the correlation between the hot spots in the MD maps and the DIC-SEM stain field map. Some of the metrics, developed in the misorientation analysis, were implemented by EDAX-TSL, Inc. (Mahwah, NJ) in their latest orientation imaging microscopy (OIM) commercial software. Slip trace analysis was performed to characterize the distribution of the plastic deformation modes at RT, 200 ̊C, and 300 ̊C on three bcc Ti alloys: Ti-13Cr-1Fe-3Al (wt.%), TIMETAL-21S, and Ti-29Nb-13Ta-4.6Zr-xO (wt.%), where x is 0.1, 0.3, and 0.7 (wt.%). The results revealed that dislocation slip was the dominant plastic deformation mechanism for Ti-13Cr-1Fe-3Al (wt.%), TIMETAL-21S, Ti-29Nb-13Ta-4.6Zr-0.3O (wt.%), and Ti-29Nb-13Ta-4.6Zr-0.7O (wt.%). The {123}<111> slip systems exhibited the highest contribution, while the {110}<111> showed the least contribution of the observed traces. However, the normalized slip activity (according to the possible slip planes of each system) suggested that the activity of all the systems were relatively equal for the TCFA, while the activity of the {110}<111> was slightly greater than other two slip systems for the TIMETAL-21S. Three deformation mechanisms, i.e., stress-induced martensitic (SIM) transformation (β phase to α” phase), the {332}<113> mechanical twinning, and the slip activity activated and cooperated for the Ti-29Nb-13Ta-4.6Zr-0.1O (wt.%). In the second part of this work, the room temperature (RT) and elevated temperature strength of a low-cost Ti alloy were enhanced through thermomechanical processing (TMP). In-situ and ex-situ TMP treatments were systematically designed and conducted to increase the strength of a low-cost bcc Ti alloy. By performing heat treatments in the range of 300 ̊C to 600 ̊C, it was found that nanoscale and microscale precipitates formed in the bcc matrix, which led to enhance the strength. With an applied mechanical load, the phase transformation process was accelerated. The resulting mechanical properties depended on the type and duration of the TMP treatments. The maximum tensile strength of Ti-13Cr-1Fe-3Al (wt.%) reached approximately 1500 MPa at 410 ̊C. The TMP and alloy composition range was patented internationally.
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- Title
- Multicolor fluorescence optical tweezers methods and applications to nucleic acid folding
- Creator
- Chuang, Cho-Ying
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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Nucleic acids and proteins are fundamental molecular units of life. To understand their properties, we need powerful tools that allow investigation at the single-molecule level. Over the past three decades, the development of single-molecule force and fluorescence techniques has provided us new knowledge that was previously unattainable through ensemble measurements. However, we lack methods that allow us to precisely measure the mechanical properties of these molecules while visually...
Show moreNucleic acids and proteins are fundamental molecular units of life. To understand their properties, we need powerful tools that allow investigation at the single-molecule level. Over the past three decades, the development of single-molecule force and fluorescence techniques has provided us new knowledge that was previously unattainable through ensemble measurements. However, we lack methods that allow us to precisely measure the mechanical properties of these molecules while visually detecting multiple molecules at the same time. In this dissertation, we maximize the information obtained in single-molecule measurements by pushing the techniques to be more precise and more complex. We then utilize our instrument to directly observe the folding and unfolding of the nucleic acid G-quadruplex structure. Among the single-molecule force techniques, angstrom-resolution has been achieved by optical tweezers using the dual-trap instrument design. Dual-traps can be produced by acousto-optic (AO) devices, which have many advantages, but trap positioning inaccuracies have limited their usage at high-resolution. We have designed a method to remove the inaccuracies by randomizing the phase of the radio frequency that drives the AO device. We demonstrated that the trap inaccuracies are completely eliminated and high-resolution trapping quality is achieved. This advance allows us to perform long duration measurements with reduced drift in trap measurement over time. Next, we present instrumentation advances that combine high-resolution optical tweezers and multicolor confocal fluorescence spectroscopy along with automated single molecule assembly. Multicolor not only allows the detection of multiple observables but also increases the flexibility in the choice of fluorophores. We demonstrated the ability to simultaneously measure angstrom-scale changes in tether extension and single fluorophore signals. The biggest challenge in integrating optical tweezers and fluorescence is the potential for greatly enhanced photobleaching which can make experiments impossible. We showed that the mean number of photons emitted before bleaching is unaffected by the trap laser when interlacing the fluorescence and optical trap lasers. We investigated the photostability of quantum dots and fluorophores. Finally, we devised computer-controlled automation to conserve the fluorophore lifetime. This advance enables us to observe multiple molecules or multiple degrees of freedom within a molecular complex while mechanically manipulate and detect them. Taking advantage of these method and instrumentation advances, we investigate the folding and unfolding of a DNA secondary structure: thrombin-binding aptamer G-quadruplex (TBA-GQ). Studying the kinetics of G-quadruplex formation is essential for understanding telomere regulation (the ends of chromosomes) and therapeutic approaches for disease. TBA-GQ is the smallest G-quadruplex. Although many experiments and simulations have been done on G-quadruplex, the small size and low stability make it very difficult to observe folding and unfolding of TBA-GQ directly. Our high-resolution optical tweezers have the sensitivity and stability to directly observe TBA-GQ at very low forces. We found that with increasing force, the folding rate decreased and the unfolding rate increased. Our work demonstrates that at a given force, the TBA-GQ formation is facilitated by metal ions and is stabilized by thrombin. It also indicates that the equilibrium force increased as KCl concentration increased. From a detailed analysis of the folding and unfolding rate constants vs applied force, we were able to detect a single transition state conserved across all conditions and identify the structure of the transition state as the G-triplex structure.
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- Title
- Theoretical analysis of electronic, thermal, and mechanical properties in gallium oxide
- Creator
- Domenico Santia, Marco
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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In recent years, Ga2O3 has proven to be a promising semiconductor candidate for a widearray of power electronics and optoelectronics devices due to its wide bandgap, high breakdownvoltage, and growth potential. However, the material suffers from a very low thermalconductivity and subsequent self-heating issues. Additionally, the complexity of the crystalstructure coupled with the lack of empirical data, has restricted the predictive power of modellingmaterial properties using traditional...
Show moreIn recent years, Ga2O3 has proven to be a promising semiconductor candidate for a widearray of power electronics and optoelectronics devices due to its wide bandgap, high breakdownvoltage, and growth potential. However, the material suffers from a very low thermalconductivity and subsequent self-heating issues. Additionally, the complexity of the crystalstructure coupled with the lack of empirical data, has restricted the predictive power of modellingmaterial properties using traditional methods. The objective of this dissertation is toprovide a detailed theoretical characterization of material properties in the wide bandgapsemiconductor Ga2O3 using first-principles methods requiring no empirical inputs. Latticethermal conductivity of bulk β − Ga2O3 is predicted using a combination of first-principlesdetermined harmonic and anharmonic force constants within a Boltzmann transport formalismthat reveal a distinct anisotropy and strong contribution to thermal conduction fromoptical phonon modes. Additionally, the quasiharmonic approximation is utilized to estimatevolumetric effects such as the anisotropic thermal expansion.To evaluate the efficacy of heat removal from β − Ga2O3 material, the thermal boundaryconductance is computed within a variance-reduced Monte-Carlo framework utilizingfirst-principles determined phonon-phonon scattering rates for layered structures containingchromium or titanium as an adhesive layer between a β − Ga2O3 substrate and Au contact.The effect of the adhesive layer improves the overall thermal boundary conductancesignificantly with the maximum value found using a 5 nm layer of chromium, exceeding themore traditional titanium adhesive layers by a factor of 2. This indicates the potential ofheatsink-based thermal management as an effective solution to the self-heating issue.Additionally, this dissertation provides a detailed characterization of the effect of strainon fundamental material properties of β−Ga2O3 . Due to the highly anisotropic nature of thecrystal, the effect strain can have on electronic, mechanical, and optical properties is largelyunknown. Using the quasi-static formalism within a DFT framework and the stress-strainapproach, the effect of strain can be evaluated and combined with the anisotropic thermalexpansion to incorporate an accurate temperature dependence. It is found that the elasticstiffness constants do not vary significantly with temperature. The computed anisotropyis unique and differs significantly from similar monoclinic crystal structures, indicating theimportant role of the polyhedral linkage to the reported anisotropy in material properties.Lastly, the dependence of the dielectric function with respect to strain is evaluated using amodified stress-strain approach. This elasto-optic, or photoelastic, effect is found to be significantfor sheared crystal configurations. This opens up a potential unexplored applicationspace for Ga2O3 as an acousto-optic modulation device
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- Title
- I. Delivery of carbohydrate antigens by glycopolymers as potential anti-cancer vaccines : II. A study of the impacts of valency and density on immune response against a tumor associated carbohydrate antigen
- Creator
- Qin, Qian, 1981-
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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Tumor associated carbohydrate antigens (TACAs) are overexpressed on tumor cells, which renders them attractive targets for anti-cancer vaccines. To overcome the poor immunogenecity of TACAs, a polymer platform was designed for antigen presentation by taking advantage of the polymeric backbone to deliver TACA and helper T (Th) cell epitope on the same chain. The block copolymer was synthesized by cyanoxyl-mediated free radical polymerization followed by conjugation with a TACA Tn antigen and a...
Show moreTumor associated carbohydrate antigens (TACAs) are overexpressed on tumor cells, which renders them attractive targets for anti-cancer vaccines. To overcome the poor immunogenecity of TACAs, a polymer platform was designed for antigen presentation by taking advantage of the polymeric backbone to deliver TACA and helper T (Th) cell epitope on the same chain. The block copolymer was synthesized by cyanoxyl-mediated free radical polymerization followed by conjugation with a TACA Tn antigen and a mouse Th-cell peptide epitope derived from poliovirus (PV) to afford the vaccine construct. The glycopolymer vaccine elicited a robust immune response with significant titers of IgG antibodies and the antibodies generated recognized Tn antigens on tumor cell surface. For successful carbohydrate based anti-cancer vaccines, it is critical that B cells are activated to secret antibodies targeting TACAs. Despite the availability of many TACA based constructs, systematic understanding of the effects of structural features on anti-glycan antibody responses is lacking. In this study, a series of defined synthetic glycopolymers bearing a representative TACA, i.e., the Thomsen-nouveau (Tn) antigen, have been prepared to probe the induction of early B cell activation and antibody production via a T cell independent mechanism. Valency and density of the antigen in the polymers turned out to be critical. An average of greater than 6 Tn per chain was needed to induce antibody production. Glycopolymers with 40 antigens per chain and backbone molecular weight of 450 kDa gave the strongest stimulation to B cells in vitro, which correlated well with its in vivo activity. Deviations from the desired valency and density led to decreased antibody production or even antigen specific B cell non-responsiveness. These findings provide important insights on how to modulate anti-TACA immune responses facilitating the development of TACA based anti-cancer vaccines using glycopolymers.
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