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Pages
- Title
- The initial phase of pathogenesis in Victoria blight of oats
- Creator
- Yoder, Olen C.
- Date
- 1968
- Collection
- Electronic Theses & Dissertations
- Title
- Friction equivalents of take-offs in rectangular ducts
- Creator
- Yohn, James Harold
- Date
- 1950
- Collection
- Electronic Theses & Dissertations
- Title
- The effect of chain extender on the molecular weight and hydrolytic degradation of poly(lactic acid)
- Creator
- Limsukon, Wanwarang
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"The effect of chain extender (Cex) on the molecular weight properties and hydrolytic degradation of modified PLA films (PLA--Cex) was determined and compared with PLA without Cex (PLA--Con). Effects of the Cex content and the residence time on the molecular weight were reviewed using melt blending and compression molding. A response surface methodology was applied to design the experiments and estimate the optimal conditions for obtaining the maximum weight average and number average...
Show more"The effect of chain extender (Cex) on the molecular weight properties and hydrolytic degradation of modified PLA films (PLA--Cex) was determined and compared with PLA without Cex (PLA--Con). Effects of the Cex content and the residence time on the molecular weight were reviewed using melt blending and compression molding. A response surface methodology was applied to design the experiments and estimate the optimal conditions for obtaining the maximum weight average and number average molecular weight achieved at 1.5 wt% Cex and residence time of 17 minutes. The hydrolytic degradation experiments were run in water from 40 to 95 °C and in 50% ethanol from 40 to 85 °C. The rate of hydrolytic degradation of PLA--Cex film was estimated using mathematical models, and it was considerably lower than that of PLA--Con in all conditions. The activation energy for hydrolysis above Tg was determined using the Arrhenius equation, showing no significant difference between PLA--Cex and PLA--Con. The Vogel-Tammann-Fulcher (VTF) and the Williams-Landel-Ferry (WLF) models were used for studying the hydrolytic degradation of polymers over a broad range of temperature crossing Tg. A master curve was constructed using the time-temperature superposition principle. The experimental data at 85 °C were used to predict the degradation behavior at 40 °C. It was found that PLA--Cex would take approximately 72 percent more time than PLA--Con to degrade to soluble oligomer chains."--Page ii.
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- Title
- Therapeutically targeting autophagy in non-small cell lung cancer
- Creator
- Yco, Lisette Pangilinan
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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Autophagy is a conserved catabolic pathway which sequesters intracellular components in lysosomes to recycle macromolecules for cell maintenance. The role of autophagy in tumor cells is dynamic and depends on many factors including tumor types, tumor stages, and activity of several tumor suppressors and oncogenes. In this thesis, I wanted to improve our understanding of the unique relationship of autophagy with tumor suppressor p53 and oncogenic KRAS in cancer cells, particularly in NSCLC....
Show moreAutophagy is a conserved catabolic pathway which sequesters intracellular components in lysosomes to recycle macromolecules for cell maintenance. The role of autophagy in tumor cells is dynamic and depends on many factors including tumor types, tumor stages, and activity of several tumor suppressors and oncogenes. In this thesis, I wanted to improve our understanding of the unique relationship of autophagy with tumor suppressor p53 and oncogenic KRAS in cancer cells, particularly in NSCLC. First, I demonstrated that stabilized nuclear wild-type p53 through HDM2 inhibition with MK-8242 or nutlin-3a could induce autophagy in tumor cells through transactivation of several autophagy-related genes (DRAM, FOXO3A, SESN2, and MRCKα) and autophagy core genes (ATG4A and ULK1). In addition, I found that inhibiting of KRAS G12C signaling and suppressing mTORC1 activity by selective KRAS G12C inhibitor, ARS-853, could drive autophagy response in KRAS G12C NSCLC cell lines. Since autophagy could also promote survival under stress induced by several anticancer agents, I designed a combination study using newly reported selective ULK1 inhibitor, ULK-101, with ARS-853 in KRAS mutant NSCLC. Autophagy inhibition with ULK-101 dramatically enhanced the ability of selective KRAS G12C inhibitor to impair the viability of KRAS G12C NSCLC. Together, my study provided evidence that autophagy serves as a survival pathway in tumor cells and that future assessment of small molecule that target autophagy core proteins may be potential cancer therapeutic option in p53 wild-type and KRAS G12C NSCLC.
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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
- Guidelines to religious station management : a descriptive analysis of the objectives, and practices of station DYSR, Dumaguete City, Philippines
- Creator
- Songco, Ernesto Isip
- Date
- 1966
- Collection
- Electronic Theses & Dissertations
- Title
- Reaction-based modeling and control of an electrically boosted diesel engine
- Creator
- Men, Yifan
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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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
- Associations of four PROMIS self-efficacy for managing chronic conditions measures and the patient activation measure (PAM) among acute stroke survivors : an analysis of the Michigan Stroke Transitions Trial (MISTT) data
- Creator
- Fritz, Michele Christine
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"BACKGROUND: Successful stroke transitions rely on effective self-management abilities to address stroke deficits and to prevent recurrent stroke. Patient activation and self-efficacy (confidence) are two behavioral constructs that influence successful self-management and are associated with healthier lifestyles and better health outcomes. OBJECTIVE: This cross-sectional, secondary analysis of the Michigan Stroke Transitions Trial aimed to determine the associations between 4 PROMIS self...
Show more"BACKGROUND: Successful stroke transitions rely on effective self-management abilities to address stroke deficits and to prevent recurrent stroke. Patient activation and self-efficacy (confidence) are two behavioral constructs that influence successful self-management and are associated with healthier lifestyles and better health outcomes. OBJECTIVE: This cross-sectional, secondary analysis of the Michigan Stroke Transitions Trial aimed to determine the associations between 4 PROMIS self-efficacy (SE) measures [managing medications and treatment, activities of daily living, emotions, and social interactions] and the Patient Activation Measure (PAM). METHODS: Self-reported outcomes were collected 7-days after returning home. PAM measures skill, knowledge, and confidence to manage health and healthcare, while PROMIS SE measures confidence across 4 unique domains. Independent associations of patient characteristics with each PROMIS SE and PAM were determined using a staged multivariable regression model-building approach. Finally, multivariable regression between each PROMIS SE and PAM were explored along with confounding and interaction effects. Variables significantly associated with both SE and PAM were considered as confounders and moderators. Age and education were forced into all models. RESULTS: For 180 patients mean PAM scores were 64.5 (SD: 16) and SE T-scores were near the standard mean of 50 except for SE for managing daily activities (43.5, SD: 7.5). PAM was positively correlated with each SE measure (r=0.28 to r=0.46). Only perceived emotional support and post-stroke disability were associated with both PAM and SE. Emotional support attenuated the association between all SE domains and PAM, whereas post-stroke disability only affected SE for managing daily activities. After adjusting for potential confounders, SE for managing daily activities was no longer associated with PAM. No significant interactions were found. CONCLUSIONS: During acute stroke recovery, PROMIS SE and PAM are associated. It is important to account for perceived support and disability. Longitudinal MISTT analyses will explore mediation effects to help inform causal associations between demographic, clinical, and psychosocial factors, intervention effects, and outcomes."--Page ii.
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- Title
- The use of fungicidal sprays to reduce mold counts in black raspberries
- Creator
- Young, William Justin
- Date
- 1955
- Collection
- Electronic Theses & Dissertations
- 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
- The relative stabilities of metal-organic complexes in recent lake sediment
- Creator
- Sonaike, Susanna Yetunde
- Date
- 1975
- Collection
- Electronic Theses & Dissertations
- 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
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"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
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"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
- The reaction of organozinc compound with carbon monoxide
- Creator
- Yu, Tsenwhei Helen
- Date
- 1970
- Collection
- Electronic Theses & Dissertations
- Title
- A study of water vapor transmission rate of blister packs by USP standard and continuous gravimetric protocol
- Creator
- Mehrotra, Nikhil
- Date
- 2010
- Collection
- Electronic Theses & Dissertations
- Description
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The water vapor transmission rate (WVTR) is essential in determining the shelf life of pharmaceutical products in the package. The WVTR of blister pack was determined by using USP 671 and the continuous gravimetric protocols. The WVTR values from the two protocols were compared and the accuracy was validated.The WVTR of the blister pack determined using the USP 671 protocol was 0.0452 mg/day/blister with a standard error of 0.0010 while the WVTR using the continuous gravimetric protocol was 0...
Show moreThe water vapor transmission rate (WVTR) is essential in determining the shelf life of pharmaceutical products in the package. The WVTR of blister pack was determined by using USP 671 and the continuous gravimetric protocols. The WVTR values from the two protocols were compared and the accuracy was validated.The WVTR of the blister pack determined using the USP 671 protocol was 0.0452 mg/day/blister with a standard error of 0.0010 while the WVTR using the continuous gravimetric protocol was 0.0652 mg/day/blister with a standard error of 0.0067. The WVTR were compared using t-statistic for unequal sample size with unequal variance and no significant difference was detected. The accuracy of the two protocols was compared through the pooled variance of the data points and it was found that the USP 671 standard protocol had a pooled variance of 4.99 x 10-4 while for the continuous gravimetric protocol it was 2.13 x 10-5. Therefore the continuous gravimetric protocol showed higher accuracy than the USP standard protocol Several recommendations have been suggested for the USP standard protocol in order to make the protocol more accurate: To determine the WVTR of the blister pack, the unsteady state should be considered and excluded from the calculation, Monitoring of the relative humidity and temperature throughout the experiment is critical, Chamber size and the time of equilibrium for the specific relative humidity needs to be outlined.
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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
- A reinforced concrete stadium dormitory design
- Creator
- Snow, Arthur William
- Date
- 1947
- Collection
- Electronic Theses & Dissertations
- Title
- A comparison of the results of teacher-direction & teacher-assistance in the presentation of American & English literature to high school classes
- Creator
- Tenhaaf, Mable Cornelia
- Date
- 1940
- Collection
- Electronic Theses & Dissertations
- Title
- Controllability of hyperbolic and degenerate parabolic equations in one dimension
- Creator
- Bohn, Jonathan Matthew
- Date
- 2018
- Collection
- Electronic Theses & Dissertations
- Description
-
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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