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- Title
- Discovering plant-specific mechanisms underlying endomembrane-actin interactions and metabolic signaling
- Creator
- Cao, Pengfei
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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In eukaryotic cells, the endomembrane system compartments, including the endoplasmic reticulum, the vacuole and several other types of membrane-enclosed vesicles, are indispensable organelles and together exert essential cellular functions. In plant cells, the endomembranes interact extensively with the actin cytoskeleton, rather than the microtubules in mammalian cells, proposing significant questions of how the plant-specific endomembrane-actin interactions are established and regulated. My...
Show moreIn eukaryotic cells, the endomembrane system compartments, including the endoplasmic reticulum, the vacuole and several other types of membrane-enclosed vesicles, are indispensable organelles and together exert essential cellular functions. In plant cells, the endomembranes interact extensively with the actin cytoskeleton, rather than the microtubules in mammalian cells, proposing significant questions of how the plant-specific endomembrane-actin interactions are established and regulated. My research identified the first ER-actin anchor protein in plant cells. Moreover, the research presented in this dissertation discovered that the abundance of certain cellular nutrients stimulates the metabolic signaling and subsequently triggers re-organization of the actin cytoskeleton and actin-associated endomembranes. This revealed signaling transduction from metabolites and raw materials to manufacturing endomembrane compartments is arguably the first identified regulatory mechanism of such kind in all eukaryotes. Furthermore, additional data and considerations are expected to contribute further mechanistic understandings of the plant-specific endomembrane-actin interactions in a broad context of organelle morphogenesis, cellular functions, and plant growth.
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- Title
- New approaches to assess and improve protein efficiency in lactating dairy cows
- Creator
- Liu, Enhong
- Date
- 2020
- Collection
- Electronic Theses & Dissertations
- Description
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The long-term goal of the work is to improve protein efficiency in lactating dairy cows. To achieve this goal, four specific objectives were proposed: 1) determine the relationship of residual feed intake (RFI) to protein efficiency in lactating Holstein cows fed high or low protein diets, 2) determine whether low protein resilience (LPR) is an indicator of protein efficiency in individual dairy cows, 3) examine the association of digestibility with RFI and LPR in lactating dairy cows, and 4)...
Show moreThe long-term goal of the work is to improve protein efficiency in lactating dairy cows. To achieve this goal, four specific objectives were proposed: 1) determine the relationship of residual feed intake (RFI) to protein efficiency in lactating Holstein cows fed high or low protein diets, 2) determine whether low protein resilience (LPR) is an indicator of protein efficiency in individual dairy cows, 3) examine the association of digestibility with RFI and LPR in lactating dairy cows, and 4) quantify the importance of including body weight (BW) change in the cow response to decreased dietary protein content and develop models for predicting BW change when dietary protein is altered. Lactating Holstein cows (n= 166; 92 primiparous, 77 multiparous) with initial milk yield (MY) of 41 ± 9.8 kg/d were fed high (HP) and low (LP) protein diets in crossover experiments of two 28-35 d periods. Experiments were repeated in 69 of the 166 cows (42 primiparous, 27 multiparous) in late lactation. Low protein diets were 14% CP in peak lactation and 13% CP in late lactation and were formulated to contain adequate rumen-degraded protein to maintain rumen function. Expeller soybean meal was added to formulate the HP diet, which contained 18% CP in peak lactation and 16% CP in late lactation. Cows were milked twice daily; DMI and MY were recorded once daily. Milk composition was measured over 4 consecutive milkings weekly, and BW was measured 3 times weekly. Samples of feed ingredients, orts and feces were collected in the last 5 days of each period and analyzed to determine digestibilities of DM, NDF, and CP for each cow on each diet. Fixed effects of diet, parity, treatment sequence nested in experiment, treatment period nested in experiment, interaction of parity and diet, and random effects of experiment and cow nested within experiment were included in models to compare production of cows fed different levels of CP. Protein efficiency was calculated for each cow on each diet in both peak lactation and late lactation. Residual feed intake was estimated for each cow on each treatment based on the actual intake, milk energy output, metabolic BW, and body energy change (estimated from BW change and BCS). Low protein resilience was estimated for each cow in peak lactation and also late lactation, based on protein captured in milk and body tissue when fed the LP vs HP diet. A negative correlation was observed between RFI and protein efficiency in cows fed the HP and LP diets in peak lactation and cows fed the HP diet in late lactation. Cows with higher LPR values had similar protein efficiency on the HP diet but significantly higher protein efficiency on the LP diet. Neither RFI nor LPR was correlated with digestibility regardless of diets or lactation stages. When dietary protein content was reduced, 40-50 % of the total energy loss, 10-20 % of total protein loss, and 15-25% of total income loss were due to BW loss, indicating that considering only changes in milk production underestimates the impact of dietary protein changes. In conclusion, 1) cows with lower RFI values utilized protein more efficiently, and protein efficiency will be improved in the process of selecting dairy cattle for low RFI, 2) cows with higher LPR values are better able to maintain production and have higher protein efficiency to adapt to low-protein feeding conditions, 3) variation in digestibility cannot explain the variations of RFI or LPR among lactating dairy cows, and we suggest that post-absorptive metabolism explains most of the variation in RFI and LPR when lactating cows are fed diets with minimal NDF in peak lactation and 40% NDF in late lactation, and 4) body reserve mobilization should not be neglected when assessing the cow response to changes in dietary protein.
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- Title
- Comparison of methods for detecting violations of measurement invariance with continuous construct indicators using latent variable modeling
- Creator
- Zhang, Mingcai (Graduate of Michigan State University)
- Date
- 2020
- Collection
- Electronic Theses & Dissertations
- Description
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Measurement invariance (MI) refers to the fact that the measurement instrument measures the same concept in the same way in two or more groups. However, in educational and psychological testing practice, the assumption of MI is often violated due to the contamination by possible noninvariance in the measurement models. In the framework of Latent Variable Modeling (LVM), methodologists have developed different statistical methods to identify the noninvariant components. Among these methods,...
Show moreMeasurement invariance (MI) refers to the fact that the measurement instrument measures the same concept in the same way in two or more groups. However, in educational and psychological testing practice, the assumption of MI is often violated due to the contamination by possible noninvariance in the measurement models. In the framework of Latent Variable Modeling (LVM), methodologists have developed different statistical methods to identify the noninvariant components. Among these methods, the free baseline method (FR) is popularly employed, but this method is limited due to the necessity of choosing a truly invariant reference indicator (RI). Two other methods, namely, the Benjamini-Hochberg method (B-H) and the alignment method (AM) are exempt from the RI setting. The B-H method applies the false discovery rate (FDR) procedure. The AM method aims to optimize the model estimates under the assumption of approximate invariance. The purpose of the present study is to address the problem of RI setting by comparing the B-H method and the AM method with the traditional free baseline method through both a simulation study and an empirical data analysis. More specifically, the simulation study is designed to investigate the performances of the three methods through varying the sample sizes and the characteristics of noninvariance embedded in the measurement models. The characteristics of noninvariance are distinguished as the location of noninvariant parameters, the degree of noninvariant parameters, and the magnitude of model noninvariance. The performances of these three methods are also compared on an empirical dataset (Openness for Problem Solving Scale in PISA 2012) that is obtained from three countries (Shanghai-China, Australia, and the United States).The simulation study finds that the wrong RI choice heavily impacts the FR method, which produces high type I error rates and low statistical power rates. Both the B-H method and the AM method perform better than the FR method in this setting. Comparatively speaking, the benefit of the B-H method is that it performs the best by achieving high powers for detecting noninvariance. The power rate increases with lowering the magnitude of model noninvariance, and with increasing sample size and degree of noninvariance. The AM method performs the best with respect to type I errors. The type I error rates estimated by the AM method are low under all simulation conditions. In the empirical study, both the B-H method and the AM method perform similarly in estimating the invariance/noninvariance patterns among the three country pairs. However, the FR method, for which the RI is the first item by default, recovers a different invariance/noninvariance pattern. The results can help the methodologists gain a better understanding of the potential advantages of the B-H method and the AM method over the traditional FR method. The study results also highlight the importance of correctly specifying the model noninvariance at the indicator level. Based on the characteristics of the noninvariant components, practitioners may consider deleting/modifying the noninvariant indicators or free the noninvariant components while building partial invariant models in order to improve the quality of cross-group comparisons.
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- Title
- Optimizing revitalization planning and design guidelines for a shrinking city, Flint, MI
- Creator
- Yang, Shu (Graduate of Michigan State University)
- Date
- 2020
- Collection
- Electronic Theses & Dissertations
- Description
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Land vacancy is a persistent issue in most urban places in the United States, yet few case studies show how vacant lots are used in practice and the functions they serve in local communities. The purpose of this study is to optimize revitalization planning through an analysis of vacant land redevelopment alternatives and provide a design guideline for the Durant-Tuuri-Mott (DTM) Target Area in the shrinking city of Flint, MI. This study develops design modules in three development scenarios...
Show moreLand vacancy is a persistent issue in most urban places in the United States, yet few case studies show how vacant lots are used in practice and the functions they serve in local communities. The purpose of this study is to optimize revitalization planning through an analysis of vacant land redevelopment alternatives and provide a design guideline for the Durant-Tuuri-Mott (DTM) Target Area in the shrinking city of Flint, MI. This study develops design modules in three development scenarios based on their implementation level: 100%, 75%, and 50% development scenarios, which fit different budgets and considers the local context to adopt different design modules. To generate a comprehensive master plan with a balanced distribution of modules, the study also analyzes the surrounding cultural, natural, and built environments and conducts community participant process by collecting residents and stakeholders' opinions. By utilizing landscape performance metrics to quantify the environmental, social, and economic benefits, this study identifies an ideal optimized development scenario with a comprehensive master plan for the reuse and redevelopment of vacant lots across DTM neighborhoods and analyzes the benefits of each redevelopment scenario. Furthermore, this study provides a flexible design method for balancing objectives in vacant land redevelopment, which can be applied in other shrinking cities as well.
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- Title
- Role of hippocampal Delta-FosB in behavioral responses to chronic stress
- Creator
- Manning, Claire Elena
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"Depression is a highly prevalent mood disorder which affects up to 20% of the population. While women are twice as likely as men to be diagnosed with a mood disorder, the neurophysiological contributions to this disparity are unclear. One brain region implicated in depression-like symptoms in both humans and rodents is the hippocampus (HPC). The HPC is uniquely susceptible to stress, has distinct patterns of information flow, and functional segregation of cognitive and affective memories...
Show more"Depression is a highly prevalent mood disorder which affects up to 20% of the population. While women are twice as likely as men to be diagnosed with a mood disorder, the neurophysiological contributions to this disparity are unclear. One brain region implicated in depression-like symptoms in both humans and rodents is the hippocampus (HPC). The HPC is uniquely susceptible to stress, has distinct patterns of information flow, and functional segregation of cognitive and affective memories across the dorsoventral axis; this suggests specific hippocampal subpopulations may be involved in different aspects of learning and memory. Previously, the transcription factor Delta-FosB was shown to regulate spatial learning and cell proliferation, and was found to be induced in dHPC after stress. Herein, I elucidate Delta-FosB's contributions in hippocampal subregions among specific behavioral domains: dentate gyrus (DG) influence on spatial learning, and vHPC influence on stress-behavior in both sexes. Specifically, I show that DG SGZ FosB gene products are necessary for normal neurogenesis and learning. As the vHPC is implicated in affective learning and memory through its connectivity to limbic regions, I examined the role of vHPC Delta-FosB in stress-induced behaviors. I describe divergent patterns of behavior in males, where Delta-FosB in vHPC-NAc is necessary and sufficient for resilience to stress but Delta-FosB in vHPC-BLA is necessary for the expression of fear and anxiety. These results demonstrate that individual genes can have disparate roles within a single brain region, based not only on heterogenous cell types but on the specific projections of the neurons in which they are expressed. I also show a basal sex difference in stress susceptibility which is mediated by the vHPC-NAc circuit and adult testosterone. These data show vHPC-NAc activity is causally linked to the sex difference in susceptibility to stress-induced anhedonia. This relationship is dependent upon long-term adaptation of vHPC-NAc projections and may reflect on the biological underpinning of female vulnerability to mood disorders related to stress."--Pages ii-iii.
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- Title
- On superconvergent discontinuous Galerkin methods for Schrödinger equations and sparse grid central discontinuous Galerkin method
- Creator
- Chen, Anqi
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"In this thesis, we design and analyze a discontinuous Galerkin (DG) method for one-dimensional Schrodinger equations under a general class of numerical fluxes, and another efficient DG method for high-dimensional hyperbolic equations.In the first DG method, we develop an ultra-weak discontinuous Galerkin (UWDG) method to solve the one-dimensional nonlinear Schrödinger equation. Stability conditions and error estimates are derived for the scheme with a general class of numerical fluxes. The...
Show more"In this thesis, we design and analyze a discontinuous Galerkin (DG) method for one-dimensional Schrodinger equations under a general class of numerical fluxes, and another efficient DG method for high-dimensional hyperbolic equations.In the first DG method, we develop an ultra-weak discontinuous Galerkin (UWDG) method to solve the one-dimensional nonlinear Schrödinger equation. Stability conditions and error estimates are derived for the scheme with a general class of numerical fluxes. The error estimates are based on detailed analysis of the projection operator associated with each individual flux choice. Depending on the parameters, we find out that in some cases, the projection can be defined element-wise, facilitating analysis. In most cases, the projection is global, and its analysis depends on the resulting 2 x 2 block-circulant matrix structures. For a large class of parameter choices, optimal a priori L2 error estimates can be obtained. Numerical examples are provided verifying theoretical results.In addition to the stability and error analysis, we analyze the superconvergence properties of the UWDG method for one-dimensional linear Schrodinger equation with various choices of flux parameters. Depending on the flux choices and if the polynomial degree k is even or odd, we prove 2k or (2k - 1)-th order superconvergence rate for cell averages and numerical flux of the function, as well as (2k - 1) or (2k - 2)-th order for numerical flux of the derivative. In addition, we prove superconvergence of (k + 2) or (k + 3)-th order of the UWDG solution towards a special projection. At a class of special points, the function values and the first and second order derivatives of the UWDG solution are superconvergent with order k + 2, k + 1, k, respectively. The proof relies on the correction function techniques initiated in Cao, et. al. (2014), and applied to Cao, et. al. (2017) for direct DG (DDG) methods for diffusion problems. By negative norm estimates, we apply the post processing technique and show that the accuracy of our scheme can be enhanced to order 2k. Theoretical results are verified by numerical experiments.In the second DG method, we develop sparse grid central discontinuous Galerkin (CDG) scheme for linear hyperbolic systems with variable coefficients in high dimensions. The scheme combines the CDG framework with the sparse grid approach, with the aim of breaking the curse of dimensionality. A new hierarchical representation of piecewise polynomials on the dual mesh is introduced and analyzed, resulting in a sparse finite element space that can be used for non-periodic problems. Theoretical results, such as L2 stability and error estimates are obtained for scalar problems. CFL conditions are studied numerically comparing discontinuous Galerkin (DG), CDG, sparse grid DG and sparse grid CDG methods. Numerical results including scalar linear equations, acoustic and elastic waves are provided."--Pages ii-iii.
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- Title
- The Economic Reorganization of Ethiopia During the Interwar Period : 1918-1935
- Creator
- Edwards, Jon Russell
- Date
- 2004
- Collection
- Electronic Theses & Dissertations
- Description
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During the interwar period, 1918-1935, the expanding state apparatus of the Ethiopian government exploited infrastructural improvements to extend and preserve relations of production that limited growth and stunted economic development. Claimants to the powers and privileges inherent in Ethiopian kingship vied over the proceeds of long-distance trade with an eye towards monopolization, not maximization.Growth and development also suffered from European efforts to fashion a suitable investment...
Show moreDuring the interwar period, 1918-1935, the expanding state apparatus of the Ethiopian government exploited infrastructural improvements to extend and preserve relations of production that limited growth and stunted economic development. Claimants to the powers and privileges inherent in Ethiopian kingship vied over the proceeds of long-distance trade with an eye towards monopolization, not maximization.Growth and development also suffered from European efforts to fashion a suitable investment environment. Unable to dominate local economic affairs, England, France and Italy instead blocked the others from succeeding.The dissertation stresses ideology and superstructure because the most valued political and economic rewards within Ethiopia were philosophically prescribed, and because economic behavior and decision-making met conventional constraints upon behavior.The first four chapters examine chronologically Ethiopia’s interwar political economy. Contrary to continuing conventional belief, Ras Tafari overthrew Lij Iyasu, not because political-based rumors suggested that Iyasu exhibited Muslim tendencies, but rather to steer long-distance trade through Shoa. Tafari responded to a series of internal and external challenges to his authority. By 1930 and his coronation as Haile Selassie, an improving infrastructure permitted the Emperor to consolidate the transfer of provincial wealth to his capitol, and to maximize his control over the long-distance trade, predominately coffee and hides.Chapter five focuses upon European efforts to fashion a legal framework in order to succeed economically in Ethiopia, all in disregard of Ethiopia’s existing superstructure. Throughout, they ignored Ethiopia’s right to fiscal, legislative, and judicial affairs by establishing European controls over internal policy. The result was another brake upon Ethiopian development.The final chapter examines the main cause for the economic development that did occur. Indian and Arab merchants had long been willing to adapt to Ethiopia’s superstructural constraints. By accepting modest rates of return on their investments, these merchants successfully dominated local brokerage, marketing, and banking. Throughout the period, they worked harmoniously with the central government and kept their distance from the European powers. This chapter made use of a previously undiscovered resource, the 550 volumes of the Consular Court. These breakdowns in economic order provide an on-going record of how the economic order was meant to function.
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- Title
- Colostrum supplementation with omega-3 fatty acids may decrease oxidative stress but does not improve growth in calves
- Creator
- Opgenorth, Julie
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"Our objective was to determine if supplementing colostrum with oils rich in omega-3 fatty acids (n-3 FA) would give calves a health and performance advantage in early life. Three experiments encompassed this objective. The first utilized 16 Holstein calves (n = 16; 8 bulls and 8 heifers). Control calves (CON) received no supplement in colostrum whereas calves with treatment (FFE) received 60 mL 1:1 ratio fish and flaxseed oil with 200 mg vitamin E in the first feeding of colostrum. FFE...
Show more"Our objective was to determine if supplementing colostrum with oils rich in omega-3 fatty acids (n-3 FA) would give calves a health and performance advantage in early life. Three experiments encompassed this objective. The first utilized 16 Holstein calves (n = 16; 8 bulls and 8 heifers). Control calves (CON) received no supplement in colostrum whereas calves with treatment (FFE) received 60 mL 1:1 ratio fish and flaxseed oil with 200 mg vitamin E in the first feeding of colostrum. FFE elevated plasma N-3 FA and decreased oxidant status index (OSi) during week one. 24 Holstein calves (n = 24; 12 bulls and 12 heifers) were studied in the second experiment with the main objective of analyzing the dose response of our colostrum supplement. Treatments included CON and fish and flaxseed oil in amounts of 30, 60, and 120 mL supplemented to colostrum (FF30, FF60, and FF120, respectively). FF treatments increased n-3 FA and some n-3 FA-derived oxylipids but failed to reduce OSi. The third experiment aimed to observe health and growth of supplemented calves (n = 180; all heifers) to determine if molecular changes observed in previous experiments could have biologically relevant effects on early life performance. The three treatments were CON, FF (60 mL 1:1 fish and flaxseed oil), and FFE (60 mL 1:1 fish and flaxseed oil with 200 mg vitamin E). We found that FF and FFE did not alter health or growth. In conclusion, though n-3 FA supplemented in colostrum was a viable strategy to enhance n-3 FA content in plasma during wk 1 of life and decrease indicators of oxidative stress, a one-time dose in colostrum did not improve calf health or growth in early life."--Page ii.
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- Title
- Physical properties and transformations of low-dimensional systems
- Creator
- Liu, Dan (Graduate of Michigan State University)
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
Evolving from the macroscopic scale to the nanometer scale, inparticular by reducing the dimensionality, fundamental properties(such as electronic and mechanical properties) of certain systemsexhibit dramatic changes, which not only give rise to a wide rangeof emergent phenomena, but also boost technology developmentincluding nanoelectronics, optoelectronics and catalysis. In thisthesis, I utilized combined techniques including densityfunctional theory (DFT), molecular dynamic simulations (MD...
Show moreEvolving from the macroscopic scale to the nanometer scale, inparticular by reducing the dimensionality, fundamental properties(such as electronic and mechanical properties) of certain systemsexhibit dramatic changes, which not only give rise to a wide rangeof emergent phenomena, but also boost technology developmentincluding nanoelectronics, optoelectronics and catalysis. In thisthesis, I utilized combined techniques including densityfunctional theory (DFT), molecular dynamic simulations (MD),continuum elasticity approach, and the tight-binding model toconduct a systematic study on low-dimensional nanostructuresregarding their electronic and mechanical properties as well asunderlying microscopic transformation mechanisms between differentstructural allotropes.First, I briefly introduce the motivation and background of thisthesis. Then, in Chapter 2, I describe the computationaltechniques, mainly the DFT approach, on which most of my thesis isbased.In Chapters 3 and 4, I apply the continuum elasticity method tostudy the phonon spectrum of two-dimensional (2D) andone-dimensional (1D) systems. My results highlight advantages ofthe continuum elasticity approach especially for the flexuralacoustic phonon modes close to the $\Gamma$ point, which areotherwise extremely hard to converge in atomistic calculationsthat use very large supercell sizes.From Chapter 5 to Chapter 7, I focus on allotropes of groupIII, V and VI elements and study boththeir stability and microscopic transformation mechanisms from oneallotrope to another. First, I predicted a stable phosphorus coilstructure, which may form by reconstruction of red phosphorous,and which was synthesized by filling a carbon nanotube withsublimed red phosphorus. Second, I proposed two stable 2Dallotropes of Se and Te. I also suggested and evaluated apromising fabrication approach starting from natural 1D structuresof these elements. After considering low-dimensional chargeneutral systems, I changed my focus to study the effect of netcharge on the equilibrium structure. Considering a heterostructureof alternating electron donor layers an monolayers of boron, Ihave identified previously unknown stable 2D boron allotropes thatmay change their structure under different levels of chargetransfer.From Chapter 8 to Chapter 10, I focus mainly on carbon-basednanomaterials and their properties. In Chapter 8, I proposed a wayto enhance the density of states at the Fermi level in dopedC60 crystals in order to increase their superconductingcritical temperature to room temperature. In Chapter 9, I haveinvestigated a shear instability twisted bilayer graphene usingthe tight binding model. This system is susceptible to very smallstructural changes, since it becomes superconducting in a verynarrow range of twist angles near the 'magic angle'. In Chapter10, I introduced the cause of an unusual negative Poisson ratioand a shape-memory behavior in porous graphene with anartificially designed pattern.In Chapter 11, I finally present general conclusions of my PhDThesis.
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- Title
- The estimation of neighborhood deprivation and preterm birth using longitudinally linked natality records
- Creator
- McArdle, Cristin Elizabeth
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
This dissertation examined the association between neighborhood-level deprivation and perinatal outcomes. We studied the association between neighborhood poverty rate and pre-term birth (PTB; birth < 37 weeks) using longitudinal maternally-linked natality files of women and their infants in Michigan during the period 1990-2012. This study examined the embodiment of place and role of maternal characteristics during pregnancy in an effort to understand how selection into neighborhood may bias...
Show moreThis dissertation examined the association between neighborhood-level deprivation and perinatal outcomes. We studied the association between neighborhood poverty rate and pre-term birth (PTB; birth < 37 weeks) using longitudinal maternally-linked natality files of women and their infants in Michigan during the period 1990-2012. This study examined the embodiment of place and role of maternal characteristics during pregnancy in an effort to understand how selection into neighborhood may bias our understanding of neighborhood level associations. We looked at pregnancy outcomes across multiple pregnancies for the same woman (the mother) as she changed neighborhoods, and levels of poverty between pregnancies. In the first study examining residential mobility between pregnancies, we reported that approximately half of our sample changed residences between pregnancies. We further exploited our data structure to examine the association with prior PTB on subsequent mobility in two sub-samples restricted by parity: births 1 and 2, and births 2 and 3. We found the strongest risk factors for mobility were related to marital change (Divorce: births 1 to 2 OR: 2.5 95% CI: 2.4-2.6, births 2 to 3 OR: 3.3, 95% CI: 3.1-3.6); Married: births 1 to 2 OR: 2.8, 95% CI: 2.7-2.8, births 2 to 3 OR: 1.9, 95% CI:1.9-2.0) but not prior PTB (prior PTB: births 1 to 2 OR: 1.0, 95% CI:1.0-1.0, births 2 to 3 OR: 1.1 95%CI: 1.0-1.1). In the second study, we report that most women did not experience a change in the level of neighborhood poverty, based on quartile of neighborhood poverty. Women who remained in the poorest neighborhoods experienced the highest percentage of PTB across two births samples, Births 1 to 2 (11.4% PTB) and Births 2 to 3 (12.3% PTB). We found increased odds of PTB for births 1 to 2 with strong downward neighborhood trajectory (OR 1.2, 95% CI 1.0-1.3) but also increased odds of PTB among strong upward neighborhood poverty trajectory (OR 1.1, 95%CI: 1.1- 1.2) compared to the static trajectory group of lowest neighborhood poverty quartile. In Study 3, we then employed a novel approach, maternal fixed effects, utilizing data linked over time to compare birth outcomes for the same mother under different exposures which allows the mother to act as her own control, analogous to a case-crossover design, while comparing the contextual effects of neighborhood deprivation on PTB. We conducted logistic regression, random effects and fixed effects analysis to evaluate n=2,191,063 eligible births during our study period. Because a fixed effects model relies on variation over time within a mother to identify the estimated association of neighborhood deprivation and PTB, the primary analytic sample was restricted (n=280,277 births to 103,328 women).We found a null association between neighborhood poverty and PTB when using a maternal fixed effects analysis (OR: 1.0, 95% CI: 1.0-1.0). This was one of the first studies to profile the maternal neighborhood mobility patterns over a long period of time, between successive pregnancies and evaluated by neighborhood poverty rate.
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- Title
- Transition path theory and transition state
- Creator
- Du, Jun (Graduate of Michigan State University)
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
This thesis will mainly discuss the transition path theory and its extension to the transition state. The framework of transition path theory (TPT) is developed in the context of continuous-time Markov chains on discrete state-spaces. Under the assumption of ergodicity,Transition path theory will first choose any two subsets (mostly metastable states) in the finite state-space based on the equilibrium distribution of the transition probability, and then it analyzes the statistical properties...
Show moreThis thesis will mainly discuss the transition path theory and its extension to the transition state. The framework of transition path theory (TPT) is developed in the context of continuous-time Markov chains on discrete state-spaces. Under the assumption of ergodicity,Transition path theory will first choose any two subsets (mostly metastable states) in the finite state-space based on the equilibrium distribution of the transition probability, and then it analyzes the statistical properties of those associated reactive trajectories, for instance,those trajectories by which the random walker transits from one subset to another. Transition path theory gives properties of these trajectories, such as their probability distribution, their probability current and flux, and their rate of occurrence and finally the dominantreaction pathways. In this thesis, we will first introduce the framework of transition path theory for Markov chains, and then briefly discuss its relation to the electric resistor network theory and Laplacian eigenmaps, and also diffusion maps is discussed as well.Based on Transition Path Theory (TPT) for Markov jump processes, this thesis develops a general approach for identifying and calculating Transition States (TS) of stochastic chemical reacting networks. The thesis first extend the concept of probability current, originally defined on edges connecting different nodes in the configuration space, to each sub-network. To locate sub-networks with maximal probability current on the separatrix between reactive and non-reactive events, which will give the Transition States of the reaction, constraint optimization is conducted. The thesis further introduce an alternative scheme to compute the transition pathways by topological sorting, which is shown to be highly efficient through analysis. Finally, the theory and algorithms are illustrated in several examples.
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- Title
- Application and viability of long day lighting on a large Michigan dairy farm milking three times each day
- Creator
- VanZweden, Benjamin
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
-
"This study's goal was to add to the knowledge base regarding the energy use, controls, possible galactopoietic effects, and economic feasibility of long day lighting (LDL) on a large commercial dairy farm. The implemented system maintained a minimum illumination level of 160 lux (15 foot-candles) for 16 hours and 40 lux (4 fc) maximum for 8 hours on a large dairy farm in Michigan that milks approximately 1,100 cows. The system used dimmable 150-Watt high-bay luminaires, dimmable 60-Watt...
Show more"This study's goal was to add to the knowledge base regarding the energy use, controls, possible galactopoietic effects, and economic feasibility of long day lighting (LDL) on a large commercial dairy farm. The implemented system maintained a minimum illumination level of 160 lux (15 foot-candles) for 16 hours and 40 lux (4 fc) maximum for 8 hours on a large dairy farm in Michigan that milks approximately 1,100 cows. The system used dimmable 150-Watt high-bay luminaires, dimmable 60-Watt canopy luminaires, and a dynamic control system. The control system used daylight harvesting to save energy, dimming the LED luminaires when natural light was available in the barns. The LDL system used 67% less energy than a theoretical system with metal halide HID luminaires, and 52% less energy than an identical system with LED luminaires but no dynamic controls. Due to unforeseen challenges, there were only 3 months of original milk production data available that could be compared with post implementation data. Analysis of the 300 highest producing cows showed an estimated 10.5% increase in milk production over July-September 2019 compared to July-September 2018. Using the estimated 10.5% increase in production, the implemented system would have a payback period of less than one year. If the estimated increase is maintained for one year, the production increase would be equivalent to adding 32 more cows to the highest producing groups. The estimated 32 cows that were matched in this calculated production increase would have produced about 13,000 pounds of CH4 annually, which is equivalent to approximately 331,000 pounds of CO2e."--Page ii.
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- Title
- Inflammatory TH17 responses to infection with Mycobacterium avium subspecies paratuberculosis (MAP) in cattle and their potential role in the development of Johne's disease
- Creator
- DeKuiper, Justin Lee
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic inflammatory gastrointestinal disease of ruminants known as Johne’s disease (JD). MAP primarily colonizes the ileum of ruminants, leading to reduced nutrient absorption, chronic diarrhea, and eventually death. The percentage of dairy operations infected MAP in the US may have risen to as much as 91% from earlier reports of 68%. In correspondence, an estimated dairy industry loss has increased from $200 million to $1.5...
Show moreMycobacterium avium subspecies paratuberculosis (MAP) causes a chronic inflammatory gastrointestinal disease of ruminants known as Johne’s disease (JD). MAP primarily colonizes the ileum of ruminants, leading to reduced nutrient absorption, chronic diarrhea, and eventually death. The percentage of dairy operations infected MAP in the US may have risen to as much as 91% from earlier reports of 68%. In correspondence, an estimated dairy industry loss has increased from $200 million to $1.5 billion was due to JD. Control of JD is difficult largely due to insensitive diagnostic tools, a long subclinical stage of infection, and lack of effective vaccines. Correlates of protection are lacking in model systems of JD and the sources of inflammation due to JD are not well characterized. Inside macrophages, MAP survives and replicates. Monocyte-derived macrophages (MDMs), peripheral blood mononuclear cells (PBMCs), and various T-cells interact with MAP. Commonly studied immune responses, such as the Th1/Th2 paradigm, do not adequately explain host responses to MAP. The major remaining knowledge gaps in MAP immunopathogenesis include key inflammatory responders in the ileum, and how naïve T-cell responsive choice (Th1, Th2, Th17) is influenced. A potential role for non-classical immune responses to MAP, such as that mediated by Th17 cells, has been suggested. Indeed, MAP antigens induce mRNAs encoding the cytokines IL-23 and IL-17A in bovine PBMCs. IL-23 and IL-17A production are both associated with Th17-like immune responses. Th17 cells are also defined by surface expression of the IL-23 receptor (IL-23R). The mean relative percent (MRP) of T cell subtypes expressing IL-23R was determined by flow cytometry and indicated an increase in mean relative percent (MRP) of T cells (CD4+, CD8+, and TCR1+) in peripheral blood mononuclear cells (PBMCs) of JD+ cows with high and low expression of IL-23R (IL-23RHigh and IL-23RLow) when compared to JD- cows. Although MAP stimulates PBMCs to secrete IL-17A in-vitro, there were no differences in IL-17A levels between subclinical JD+ and JD- cows when analyzed by ELISA. Plasma with low JD+ score values had significantly more IL-17A when compared to plasma with high JD+ score values, establishing a moderate correlation between JD+ score and IL-17A. However, overall plasma from JD+ cows had significantly less IL-17A than plasma from JD- cows. Unlike IL-17A, IL-23 was greater in plasma from JD+ cows than in JD- cows. Evaluating the relationship that MAP is having on APCs and CD3+ in relation to Th17 cytokines (IL-23, IL-17A, IL-17F, IL-22, IL-27) as well as Th1 cytokine IFNγ, CD3+ were stimulated with MAP in the presence of APCs (MDMs or B cells) or alone and evaluated by RT-qPCR. MAP stimulation significantly increased production of mRNA encoding Th17 cytokines and IFNγ in CD3+ T cells regardless of APCs. However, the presence of MDMs significantly increase the quantity of mRNA. Lastly, we observed that αβ T cells (mostly CD4+) are responsible for production of Th17 cytokines as an early response to MAP in the absence of APCs. Our data suggests that Th17-like cells may indeed play a role in early immune responses to MAP infection and development or control of JD. Understanding the influences and potential novel mechanisms of an inflammatory pathway during MAP infection could be exploited for treatment, prevention, or diagnosis of JD.
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- Title
- Lateral hypothalamic neurotensin neurons orchestrate ingestive behaviors
- Creator
- Kurt, Gizem
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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"Food and water are necessary for survival but can only be obtained via ingestive behaviors (feeding, drinking and moving). Survival thus depends on the ability of the brain to coordinate the need for water and energy with appropriate behaviors to modify their intake as necessary for homeostasis. However, the balance of these behaviors also inherently determines body weight, and imbalances contribute to the development of weight disorders such as obesity and anorexia nervosa. The lateral...
Show more"Food and water are necessary for survival but can only be obtained via ingestive behaviors (feeding, drinking and moving). Survival thus depends on the ability of the brain to coordinate the need for water and energy with appropriate behaviors to modify their intake as necessary for homeostasis. However, the balance of these behaviors also inherently determines body weight, and imbalances contribute to the development of weight disorders such as obesity and anorexia nervosa. The lateral hypothalamic area (LHA) of the brain is anatomically positioned to coordinate the sensation of osmotic and energy status with goal-directed ingestive behaviors necessary to maintain homeostasis and body weight, and, hence, may hold insight into potential treatment for energy balance disorders. This work was done to evaluate how neurotensin expressing LHA neurons (LHA Nts neurons) coordinate ingestive behaviors. The central hypothesis of this thesis was that the LHA neurotensin (Nts) neurons direct drinking behavior in response to physiologic need (thirst) via neural outputs to the lateral preoptic area (LPO), but do not modify feeding via LPO. The rationale for this hypothesis was that the LHA neurons promotes drinking, but suppresses feeding. In order to understand the nature of the drinking regulation by LHA Nts neurons, we experimentally activated LHA Nts neurons and studied drinking behavior under well-hydrated and dehydrated conditions. We observed that activation of LHA Nts neurons promotes voracious drinking of water and water-based solutions and with the given choice, animals prefer water and palatable solutions, regardless of the caloric content, rather than bitter and dehydrating solutions. We also found that activation increases the motivation to drink in well hydrated and thirsty animals beyond their perceived thirst. In addition, we showed that LHA Nts neural activation is not necessary for homeostatic and need based consumption. Furthermore, we mapped the connectivity of the LHA Nts neurons within the brain and provided a list of osmo- and energy-sensory and regulatory areas which are directly connected to LHA Nts neurons. Finally, we identified LHA Nts→LPO circuit that drives the drinking effect of LHA Nts neurons, but is not the route they suppress feeding. Overall, this work suggests that control of drinking and feeding by LHA Nts circuits is divergent and modulation of specific LHA Nts circuits may be useful therapeutic targets to treat dysregulated water intake."--Pages ii-iii.
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- Title
- 3d-printed lightweight wearable microsystems with highly conductive interconnects
- Creator
- Alforidi, Ahmad Fudy
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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There is great demand for mass production of electronics in wide range of applications including, but not limited to, ubiquitous and lightweight wearable devices for the development of smart homes and health monitoring systems. The advancement of additive manufacturing in electronics industry and academia shows a potential replacement of conventional electronics fabrication methods. However, conductivity is the most difficult issue towards the implementation of highperformance 3D-printed...
Show moreThere is great demand for mass production of electronics in wide range of applications including, but not limited to, ubiquitous and lightweight wearable devices for the development of smart homes and health monitoring systems. The advancement of additive manufacturing in electronics industry and academia shows a potential replacement of conventional electronics fabrication methods. However, conductivity is the most difficult issue towards the implementation of highperformance 3D-printed microsystems. As most of 3D printing electronics utilizes ink-based conductive material for electrical connection, it requires high curing temperature for achieving low resistivity (150 °C for obtaining nearly 2.069 x 10-6 .m in copper connects), which is not suitable for most of 3D printing filaments. Thisseriously limits the availability of many lightweight 3D printable materials in microsystem applications because these materials usually have relatively low glass-transition temperatures (< 120 °C). Considering that pristine copper films thicker than 49 nm can offer a very low bulk resistivity of 1.67 x 10-8 .m, a new 3D-printing-compatible connection fabrication approach capable of depositing pristine copper structures with no need of curing processes is highly desirable. Therefore, a new technology with the ability to manufacture 3D-printed structures with high performance electronics is necessary.In this dissertation, novel 3D-printed metallization processes for multilayer microsystems made of lightweight material on planar and non-planar surfaces are presented. The incorporation of metal interconnects in the process is accomplished through evaporating, sputtering and electroplating techniques. This approach involves the following critical processes with unique features: a) patterning of metal interconnects using self-aligned 3D-printed shadow masks, b) fabrication of the temporary connections between isolated metal segments by 3D printing followed with metallization, which host the subsequent electroplating process, and c) fabrication of vertical interconnect access (VIA) features by 3D printing followed with metallization, which enable electrical connections between multilayers of the Microsystem for miniaturization.The presented technique offers approximate bulk resistivity with no curing temperature needed after deposition. Since the ultimate goal is developing lightweight wearable microsystem, this approach demonstrated for two layers and can easily extended for multilayer microsystems enabling realization and miniaturization of complex systems. In addition, the variety of filaments used in 3Dprinters provide opportunities to study implementation of these processes in many electronics fields including flexible electronics. Therefore, the integration of physical vapor deposition systems with 3D printing machines is very promising for the future industry of 3D-printed microsystems.
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- Title
- Solidarity, safety, and online sovereignty : an inquiry into the social media sharing practices of indigenous and chicana women
- Creator
- Hutchinson, Leslie A.
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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This dissertation contains a cultural, digital rhetorics inquiry into the social media sharing practices of Indigenous and Chicana women. Working alongside three women from her local community, I investigated how these women navigate concerns about online safety, intellectual property, and surveillance. To conduct my study, I integrated cultural rhetorics research methods into my research design, which informed how I collected data through hosting a talking circle and conducting follow-up...
Show moreThis dissertation contains a cultural, digital rhetorics inquiry into the social media sharing practices of Indigenous and Chicana women. Working alongside three women from her local community, I investigated how these women navigate concerns about online safety, intellectual property, and surveillance. To conduct my study, I integrated cultural rhetorics research methods into my research design, which informed how I collected data through hosting a talking circle and conducting follow-up interviews. Then, using grounded theory to analyze my data, I found that: 1) though these women experience various social oppressions within social media spaces, they find and create community to collectively act in resistance; and 2) the acts of resistance in which these women engage expand scholarly understandings of how social media platforms are designed to asymmetrically oppress users from marginalized backgrounds. Together, these findings dispel the myth that women-and particularly women of color-have had no stake in the development of online platforms. I argue, rather, that despite how these platforms are designed, women of color critically enact cultural sovereignty in online spaces through asserting their identities, fighting for political rights, and creating community in acts of not only resistance, but survivance.
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- Title
- The impact of bt crops on aflatoxin reduction
- Creator
- Yu, Jina
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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This dissertation is about how adoption of a genetically engineered plant works as a prevention method for aflatoxin, a carcinogen that commonly contaminates food crops such as corn and peanuts interacting with climate condition. First produced in the United States in 1996, Bt corn has become one of the most commonly grown transgenic crops worldwide. Aside from improving corn growers' yields, it has also resulted in an 11% decrease in insecticide use on US corn. Multiple experimental studies...
Show moreThis dissertation is about how adoption of a genetically engineered plant works as a prevention method for aflatoxin, a carcinogen that commonly contaminates food crops such as corn and peanuts interacting with climate condition. First produced in the United States in 1996, Bt corn has become one of the most commonly grown transgenic crops worldwide. Aside from improving corn growers' yields, it has also resulted in an 11% decrease in insecticide use on US corn. Multiple experimental studies found that the level of aflatoxin, a fungal toxin, can be mitigated by reducing the presence of insects because fungi colonize corn through kernel wounds from insect feeding. However, the relationship between Bt corn and aflatoxin has yet to be examined in field settings, wherein many environmental factors are at play. Given the higher environmental risks of temperature and drought, revealing the mechanism by which Bt corn reduces aflatoxin can inform farmers' decision-making on crop choices and seed choices.In the first essay, I developed a regression model that estimates causal relationships between aflatoxin-related insurance claims and Bt corn adoption rates, drought index, and climatic variables. From 2001-2016, a significant inverse correlation existed between Bt corn planting and aflatoxin-related insurance claims in the United States when controlling for temperature, drought, state, and year. Estimated benefits of Bt corn's aflatoxin reduction were about $120 million to $229 million per year in over 16 states on average. These results suggest that Bt corn is an important strategy with corresponding economic benefits for reducing aflatoxin risk in the United States. Climate change-typically increased temperature-may expand prevalence zones for aflatoxin because warm temperatures and dry conditions are associated with aflatoxin accumulation. The second essay's objectives were to predict both areas with high aflatoxin risks in 2031-2040 based on 16 climate models, as well as the extent of aflatoxin-related economic loss due climate change. To do so, growing season impacts on aflatoxin risk were modeled by allowing for the adjustment of planting season under different climate scenarios. It was found that more than 89% of corn planting areas are likely to experience increased aflatoxin risks in 2031-2040 when compared to aflatoxin risks from 2007-2016 in the United States. Ignoring health-related costs, aflatoxin-related economic loss was expected to amount to $36 million - $70 million per year.In the third essay, I examined an additional potential benefit of Bt crops (corn and cotton): a decrease in the incidence of aflatoxin in peanuts (non-Bt crops). Bt crops can help reduce aflatoxin levels by reducing insect damage, a key path of fungal infection. However, the effect of Bt crops should not be limited to the adopted crops, because insects controlled by Bt have a relationship with other crops and insects in the broader ecosystem. Furthermore, the sales of aflatoxin-contaminated peanuts are currently under regulation. As such, the negative relationship between Bt and aflatoxin in peanuts means that Bt crops can also provide a meaningful, unintended economic benefit to peanut farmers by reducing aflatoxin. In addition to the Bt crops, temperature and drought at key stages of peanut growth were included as potential confounding factors in aflatoxin-related insurance claims. The results indicate that a county with a higher Bt crops adoption rate was less likely to have aflatoxin-related insurance claims in peanuts. This means that, by reducing the incidence of aflatoxin, Bt crops adoption in the United States has saved losses of $0.45 million per year. Overall, my dissertation study increases current understandings of the unintended effects of Bt in protecting crops from aflatoxin damage in the broader ecosystem. It aims to shed light on the benefits of Bt crops in countries that suffer from aflatoxin-related damage and transgenic seed traits that are not planted. Additionally, this study contributes to improved knowledge about climate conditions that affect either aflatoxin levels or host plants (corn and peanut). As climate change is expected to increase temperature and dryness, it is likely to increase the risk of aflatoxin in the US. Bt crops and new biotechnology are thus expected to play an important role in protecting crops from aflatoxin damage.
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- Title
- Examining the acceptability, adoptability, and appropriateness of a school-based external mental health referral process : a qualitative pre-implementation study
- Creator
- Nordquist, Erica Ashley
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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Schools have been identified as a primary place where youth mental health issues are initially noticed. When schools collaborate with mental health service providers to refer youth to care, these youth experience improvement in both educational and clinical outcomes. However, such collaboration can be challenging. This dissertation explored the acceptability, adoptability, and appropriateness of implementing an external mental health referral process within several schools in an intermediate...
Show moreSchools have been identified as a primary place where youth mental health issues are initially noticed. When schools collaborate with mental health service providers to refer youth to care, these youth experience improvement in both educational and clinical outcomes. However, such collaboration can be challenging. This dissertation explored the acceptability, adoptability, and appropriateness of implementing an external mental health referral process within several schools in an intermediate school district. Qualitative key informant interviews were used to identify barriers and facilitators to implementing an external mental health referral pathway. Key informants included school and agency personnel. Twenty-three themes and three subthemes were identified. Results indicated that implementing an external mental health referral pathway was mostly acceptable, adoptable, and appropriate. Implications for practice, research, and clinical practice are discussed.
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- Title
- Optogenetic analysis of excitatory and inhibitory neurotransmission in the enteric nervous system
- Creator
- Perez-Medina, Alberto L.
- Date
- 2019
- Collection
- Electronic Theses & Dissertations
- Description
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The enteric nervous system (ENS) is embedded within the gastrointestinal (GI) tract and controls GI function. Impaired ENS function leads to altered patterns of motility and secretion, causing GI disease. For instance, functional gastrointestinal disorders (FGID) are caused by poorly understood alterations in the structure and function of nerves, smooth muscle cells (SMC), and other cell types in the GI tract. It is estimated that these disorders comprise about 41% of the total GI...
Show moreThe enteric nervous system (ENS) is embedded within the gastrointestinal (GI) tract and controls GI function. Impaired ENS function leads to altered patterns of motility and secretion, causing GI disease. For instance, functional gastrointestinal disorders (FGID) are caused by poorly understood alterations in the structure and function of nerves, smooth muscle cells (SMC), and other cell types in the GI tract. It is estimated that these disorders comprise about 41% of the total GI complications in the United States. Also, altered patterns of motility that occur in the GI muscles is a hallmark characteristic of FGIDs. Although the ENS is fairly understood, further elucidation of the enteric circuitry that governs GI motility would help to understand the pathophysiology of FGID. For that reason, identifying the contributions of classes of enteric neurons that control GI motility and secretion could aid in the identification of novel therapeutic targets for the treatment of FGIDs. A widely used method to study neural control of GI motility is sharp-electrode electrophysiological recordings from the smooth muscle or enteric neurons. Conventional, intracellular electrophysiological recordings have relied on electrical stimulation of enteric neurons which will activate all neurons in an ex vivo preparation of the ENS, and does not allow cell-specific activation of individual subpopulations of myenteric neurons. To overcome this problem, we used immunohistochemical methods to identify subpopulations of myenteric neurons and the optogenetically activated protein channelrhodopsin-2 (ChR2) that can be selectively expressed in subsets of enteric neurons. In Chapter 3, immunohistochemical studies of the mouse enteric nervous system are performed using the purinergic neuronal marker, vesicular nucleotide transporter (VNUT) along with markers for specific subsets of myenteric neurons and nerve fibers (e.g., neuronal nitric oxide synthase, choline acetyltransferase, calretinin, calbindin, and tyrosine hydroxylase),. Chapter 4 compares electrical and optogenetic electrophysiology recordings from myenteric neurons of mice that express ChR2 in nNOS neurons. The studies described in Chapter 5 use ChAT-ChR2-YFP-BAC transgenic mice which have eYFP tagged ChR2 expressed in cholinergic neurons. Optogenetics was used to isolate the cholinergic component of the ENS. The findings discussed in this dissertation provides evidence of a more sophisticated enteric circuitry of GI motility. (1) Purinergic neurons are likely a separate subpopulation of enteric neurons. VNUT is only expressed in the form of punctate varicosities at the nerve fibers and is not endogenously expressed in the soma of enteric neurons. VNUT also does not appear to colocalize with other neuronal immunoreactive markers within the myenteric plexus (mp), the tertiary plexus (tp), or circular smooth muscle layer of all tested tissue preps. (2) BLS of ChR2 expressed in nNOS neurons induced a purinergic/nitrergic biphasic IJP, suggesting that nNOS IMNs co-releases a purine as a neurotransmitter. Ectopic expression of ChR2 in non-nNOS neurons, however, could explain the biphasic IJP responses during electrophysiology recordings. Hence, the existence of separate subset populations of IMN populations (e.g., nNOS only and purinergic only IMNs) can't be ruled out. (3) BLS of ChR2 expressed in ChAT positive neurons induced EJPs and IJP responses. Inhibition of the nicotinic ACh receptor (nAChR) with mecamylamine significantly reduced the light-evoked IJP. Bath application of the purinergic P2Y1 antagonist, MRS 2179, was sufficient to abolish the IJP response, while the muscarinic ACh receptor antagonist, Scopolamine, abolished the EJP response. The data suggest that BLS of ChR2 activates cholinergic EMNs and cholinergic interneurons, and that activation of the cholinergic interneurons activates purinergic only IMNs that supply the smooth muscle, resulting in a predominant purinergic only IJP. Taken together, this work provides evidence for a diverse and more complex enteric neural circuit of GI motility. Future experiments should, however, focus on studying these enteric circuits at the level of the neuron, as these studies can provide a more in-depth analysis of the enteric circuitry.
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- Title
- Variable selection in varying multi-index coefficient models with applications to gene-environmental interactions
- Creator
- Guan, Shunjie
- Date
- 2017
- Collection
- Electronic Theses & Dissertations
- Description
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Variable selection is an important topic in modern statistics literature. And varying multi-index coefficient model(VMICM) is a promising tool to study the synergistic interaction effects between genes and multiple environmental exposures. In this dissertation, we proposed a variable selection approach for VMICM, we also generalized such approach to generalized and quantile regression settings. Their theoretical properties, simulation performance and application in genetic research were...
Show moreVariable selection is an important topic in modern statistics literature. And varying multi-index coefficient model(VMICM) is a promising tool to study the synergistic interaction effects between genes and multiple environmental exposures. In this dissertation, we proposed a variable selection approach for VMICM, we also generalized such approach to generalized and quantile regression settings. Their theoretical properties, simulation performance and application in genetic research were studied.Complicated diseases have both environmental and genetic risk factors, and large amount of research have been devoted to identify gene-environment (G×E) interaction. Defined as different effect of a genotype on disease risk in persons with different environmental exposures (Ottman (1996)), we can view environmental exposures as the modulating factors in the effect of a gene. Based on this idea, we derived a three stage variable selection approach to estimate different effects of gene variables: varying, constant and zero which respectively correspond to nonlinear G$\times$E effect, no G$\times$E effect and no genetic effect. For multiple environmental exposure variables, we also select and estimate important environmental variables that contribute to the synergistic interaction effect. We theoretically evaluated the oracle property of the three step estimation method. We conducted simulation studies to further evaluate the finite sample performance of the method, considering both continuous and discrete predictors. Application to a real data set demonstrated the utility of the method.In Chapter 3, we generalized such variable selection approach to binary response setting. Instead of minimizing penalized squared error loss, we chose to maximize penalized log-likelihood function. We also theoretically evaluated the oracle property of the proposed selection approach in binary response setting. We demonstrated the performance of the model via simulation. At last, we applied our model to a Type II diabetes data set.Compared to conditional mean regression, conditional quantile regression could provide a more comprehensive understanding of the distribution of the response variable at different quantile. Even if the center of distribution is our only interest, median regression (special case of quantile regression) could offer a more robust estimator. Hence, we extended our three stage variable selection approach to a quantile regression setting in Chapter 4. We demonstrated the finite sample performance of the model via extensive simulation. And we applied our model to a birth weight data set.
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