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Title: Polycrystalline diamond based neural interface for optogenetics and neurotransmitter detection
Creator: Fan, Bin (Electronics engineer)
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Neural interface forms a communication bridge between a human brain and external circuitries, which enables promising bioelectronics medicines for diseases treatments, such as inflammatory bowel disease, Alzheimer's disease, and restore sensorimotor function lost due to traumatic brain, spinal cord injury, and amputations. Neurons in the central nervous systems communicate with each other electrically along the axon from soma to dendrite and chemically between neuron to neuron in the synapses...
Show moreNeural interface forms a communication bridge between a human brain and external circuitries, which enables promising bioelectronics medicines for diseases treatments, such as inflammatory bowel disease, Alzheimer's disease, and restore sensorimotor function lost due to traumatic brain, spinal cord injury, and amputations. Neurons in the central nervous systems communicate with each other electrically along the axon from soma to dendrite and chemically between neuron to neuron in the synapses through release and uptake of neurotransmitters. In particular, dopamine (DA) is one of the most important neurotransmitters, which associates with many aspects of the neurophysiological processing, such as stress, memory, and addiction. External stimulation is desired to study the dynamics of DA release and uptake and its correlation to the animal behavioral changes. Previously, electrical stimulation was used as a neuromodulation technique for such purpose, which can cause a significant amount of nondopaminergic system activation and result in consequential neurological activities or dynamics not related to DA release[1]. Recent advances in optogenetics provide a unique neuromodulation technique, allowing optical control of genetically targeted specific neurons that express light-sensitive opsin proteins with sub-millisecond temporal precision. Utilizing the cell-type specificity of Optogenetics, researchers can have a more controlled manipulation of the dopaminergic system and have an unbiased study on DA related neurological diseases. The current engineering tools for Optogenetics use laser and micro light emitting diodes (μLEDs) as the light sources, where μLEDs show great promises with respect to device miniaturization, simplicity, low power and low cost of system implementation. However, using μLEDs as a light source can cause potential thermally-induced tissue damage due to μLED Joule heating. To address the localized Joule heating issue, a μLED based optrode was developed in this thesis using polycrystalline diamond as a heat spreader due to its very high thermal conductivity. Compared with an SU8 probe with the same dimensions, a diamond probe can reduce the maximum temperature variations by ~90% at 3.6V 100ms duration pulses. The functionality of the probe was tested in vivo, where light-evoked action potentials were successfully detected. Besides the very high thermal conductivity, diamond has unique features for neurotransmitter sensing, such as a larger potential window, low background current and resistance to surface fouling. In addition, diamond is a biocompatible and chemically inert material, which enables long-term device implantation. Therefore, above mentioned properties make diamond a promising candidate for Optogenetics and neurotransmitter detection. However, diamond is a rigid material and the micromotion-induced strain has been hypothesized to be the main cause of harmful immune responses and even irreversible tissue damage. Due to the process temperature intolerant, diamond cannot synthesis onto polymer substrates directly. To address this issue, a wafer-level substrate transfer process is first time proposed to transfer all diamond macro/micro patterns from a diamond growth substrate, silicon, onto a flexible Parylene substrate. The electrochemical properties of the transferred diamond-polymer electrodes were evaluated (i) using an outer sphere redox couple to study the electron transfer process and (ii) quantitative and qualitative studies of a neurotransmitter redox dopamine/dopamine-o-quinone. A linear response of the BDD sensor to dopamine concentrations of 0.5 μM to 100 μM was observed (R2 = 0.999) with a sensitivity of 0.21 μA/cm2·μM.
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Title: Characterization of axenic immune deficiency in arabidopsis thaliana
Creator: Kremer, James Michael
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Evolution of land plants began and has since occurred, in concert with complex communities of microorganisms, giving rise to a vast spectrum of plant-microbe relationships. Over the past decade, plant molecular biologists and microbial ecologists have worked together to identify drivers of microbiome composition that inspire hypotheses about microbiome functional potential, but many fall short of offering empirical evidence of microbiome-mediated influence on host phenotypes. Herein, I...
Show moreEvolution of land plants began and has since occurred, in concert with complex communities of microorganisms, giving rise to a vast spectrum of plant-microbe relationships. Over the past decade, plant molecular biologists and microbial ecologists have worked together to identify drivers of microbiome composition that inspire hypotheses about microbiome functional potential, but many fall short of offering empirical evidence of microbiome-mediated influence on host phenotypes. Herein, I introduce a new suite of tools to explore microbiome function and report that many facets of plant immunocompetence are microbiome-dependent.Chapter One summarizes the current understanding of plant innate immunity and notable progress of plant microbiome research, including: (1) detection and response to microbe-associated molecular patterns, (2) hormone signaling during biotic interactions, (3) technology for exploration of plant microbiome ecology, (4) factors that influence microbiome community structure, and (5) a review of relevant model systems and gnotobiotic growth platforms. Chapter Two describes the development of a novel “FlowPot” growth system: a peat-based platform conducive to axenic (microbe-free), gnotobiotic (defined microbiota), and holoxenic (undefined, complex microbiota) Arabidopsis thaliana growth. This system provides the ability to maintain control of abiotic parameters and exogenous microbiota, thus providing a valuable platform for discovery for plant microbiome research. The FlowPot system and offers a substantial improvement over alternative growth systems regarding plant health, tractability to greenhouse conditions, and maintenance of bacterial alpha diversity upon inoculation with soil-derived microbiota. An implementation of the growth system is detailed in Chapter Three, featuring a comparative analysis of the axenic vs. holoxenic Arabidopsis transcriptome, metabolome, and immunocompetence. Axenic Arabidopsis has a reduced level of defense- and immunity-associated gene expression and the defense hormone salicylic acid (SA). We report that axenic Arabidopsis is compromised in defense against the foliar pathogen Pseudomonas syringae pv. tomato DC3000 (Pst). Immune elicitation experiments revealed that axenic Arabidopsis is also compromised in the ability to recognize and/or mount normal defense responses to the microbe-associated molecular pattern flg22. Axenic susceptibility to Pst is partially explained by defective innate immunity. Finally, we report the identity of differentially abundant metabolites and transcripts in axenic and holoxenic Arabidopsis that may be involved in microbiome-influenced host phenotypes. Collectively, research described in this dissertation provides new tools and a discovery platform to empirically characterize the function of plant microbiota, as well as detailed characterization of axenic phenotypes and axenic immune deficiency.
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Title: Freezing and thawing of frost-susceptible soils : (development of a reliable predictive model)
Creator: Rajaei, Pegah
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Frost depth is an important factor that affects the design of various transportation infrastructures including pavements, retaining structures, bridge foundations, utility lines, and so forth. Soil freezing can lead to frost heave and heave pressure, which may cause serious stability issues. On the other hand, at the beginning of spring season, the ice starts to thaw from the top down and to a lesser extend from the bottom up. The melted water below the pavement surface is trapped (setting on...
Show moreFrost depth is an important factor that affects the design of various transportation infrastructures including pavements, retaining structures, bridge foundations, utility lines, and so forth. Soil freezing can lead to frost heave and heave pressure, which may cause serious stability issues. On the other hand, at the beginning of spring season, the ice starts to thaw from the top down and to a lesser extend from the bottom up. The melted water below the pavement surface is trapped (setting on impermeable frozen materials). It saturates the top part of the upper pavement layer. Consequently, the stiffness of the saturated layer decreases causing substantial decrease in its load bearing capacity and high deformations, which lead to premature and localized failure. To decrease the spring thaw damage, Spring Load Restrictions (SLR) signs are usually placed along the roads. The objectives of this study are to develop accurate and reliable frost and thaw depth and frost heave prediction models, estimate heave pressure and develop a reliable SLR policy. After extensive literature review, various existing frost depth models were identified and tested. These include the finite difference UNSAT-H, the Stefan, the Modified Berggren, and the Chisholm and Phang models. Unfortunately, some of these models require substantial input data that are not available and all models yielded inaccurate results. Therefore, statistical frost depth models were developed using frost depth and air temperature data collected by Michigan Department of Transportation (MDOT); one for clayey soils and one for sandy soil. The two models were then combined using the measured thermal conductivity of clayey and sandy soils. The combined statistical model was then verified using frost depth and air temperature data collected by Minnesota Department of Transportation (MnDOT). Additionally, The Gilpin's mechanistic-empirical model was employed to predict frost heave. The model produced inaccurate and counterintuitive results in some cases. Therefore, the model was modified and the empirical frost depth model developed in this study was incorporated into the model. The resulting model was then simplified to replace some of the required of input data that are not available. The modified model accuracy was assessed using the frost heave data measured at 5 sites in Oakland County, Michigan. Further, the relationship between frost heave and heave pressures were established for four soil types.Moreover, a new statistical model was developed for calculating the cumulative thaw degree-day (CTDD) using pavement surface temperature and air temperate data collected by MDOT. Then, the thaw depth data measured in the state of Michigan were used to assess Nixon and McRoberts thaw depth predictions model. Since the model did not produce accurate and acceptable results, statistical thaw depth models were developed using the calculated CTDD values and thaw depth data collected by MDOT and MnDOT; one for clayey soils and one for sandy soils. The models were then verified using the calculated CTDD values and thaw depth data collected by MnDOT. Finally, based on the results of thaw depth model a new SLR policy was proposed.
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Title: Mechanistic connections between the proton motive force and ATP homeostasis in higher plant photosynthesis under dynamic environmental conditions
Creator: Carrillo, Leticia Ruby
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Through photosynthesis, plants can capture light energy from the sun for the conversion to a more stable high-energy form, ATP and NADPH. These products are then used to fuel an array of metabolic processes including the biosynthesis of sugars and complex carbohydrates. Yet, the abundant source of solar energy used in the process is highly varied and fluctuates throughout the day, directly impacting the photosynthetic apparatus and carbon assimilation. This dissertation focuses on several...
Show moreThrough photosynthesis, plants can capture light energy from the sun for the conversion to a more stable high-energy form, ATP and NADPH. These products are then used to fuel an array of metabolic processes including the biosynthesis of sugars and complex carbohydrates. Yet, the abundant source of solar energy used in the process is highly varied and fluctuates throughout the day, directly impacting the photosynthetic apparatus and carbon assimilation. This dissertation focuses on several mechanisms by which plants are able to respond to the dynamic environmental pressures through modulation of the proton motive force (pmf) and ATP homeostasis.ATP is the primary energy currency in cells and is synthesized in plastids by the chloroplast ATP synthase. However, unlike other stromal thiol-regulated enzymes that incrementally become redox-activated in response to light, chloroplast ATP synthase acts more like an on-off switch, only requiring minimal irradiance to become fully active. Previous work suggested that the rapid sensitivity to light could be explained by the relative redox potentials of the regulatory thiols on the γ-subunit of ATP synthase. This work uncovered a new, unexpected component, NADPH thioredoxin reductase C (NTRC) that controls thiol regulation specifically under low light intensities. Mutants lacking NTRC show strong photosynthetic phenotypes, e.g., increased nonphotochemical quenching and inhibition of linear electron flow, at low irradiances, consistent with an inability to activate ATP synthase resulting in a buildup of the thylakoid pmf. We predict both NTRC and the canonical ferredoxin-thioredoxin reductase system co-regulate the thiol state of ATP synthase at specific light intensities using different reducing potentials (NADPH versus ferredoxin) that allow for added flexibility.Photosynthesis copes with, and adapts to, fluctuating environments using a wide range of mechanisms. While most of the research has been devoted to the processes occurring inside the plastid, work described here on the nucleotide triphosphate transporter (NTT) illuminates an additional mechanism of augmenting and balancing ATP. Previous work suggested that the chloroplast transporter, NTT, acted primarily as an importer of ATP during the night cycle, presumably under non-photosynthesizing conditions. However, isolated intact chloroplasts from both spinach and Arabidopsis thaliana export ATP at rapid rates that can constitute a large fraction of that generated by the light reactions. Furthermore, these findings suggest that earlier results of minimal rates of ATP transport were based on suboptimal assay conditions and incorrect characterization of T-DNA knockout lines, rendering NTT essential for seed germination. Work on double NTT knock-down lines (NTTdKD) have decreased gene expression levels of ntt1 and ntt2 and show strong photosynthetic responses, particularly in the pH and energy-dependent quenching response (qE) with related accumulation of the pmf under fluctuating light and/or decreased CO2 levels. These results indicate a greater role for NTT in balancing ATP levels between the stromal and cytosolic pools than previously thought.
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Title: The experiences and decision making processes of couples with a child with a childhood genetic disorder
Creator: McKee, Kate Szubeczak
Date: 2017
Collection: Electronic Theses & Dissertations
Description: There is a disparity in the research between the individual's and the family as a whole's interactional processes in the collection and dissemination of genetic information. There is a gap in our understanding of how couples deal with genetic information, especially when a child is diagnosed with an inherited genetic condition. Also, there is a lack of understanding of the decision-making processes regarding genetic testing. Furthermore, medical professionals and family therapists are...
Show moreThere is a disparity in the research between the individual's and the family as a whole's interactional processes in the collection and dissemination of genetic information. There is a gap in our understanding of how couples deal with genetic information, especially when a child is diagnosed with an inherited genetic condition. Also, there is a lack of understanding of the decision-making processes regarding genetic testing. Furthermore, medical professionals and family therapists are becoming more aware of the effect these tests will have on family systems and on the health beliefs of the family. Once a diagnosis has been received, families now have the task of making sense of the diagnosis and deciding on how the family system needs to change or adapt in order to accommodate the genetic disorder. The purpose of this qualitative study was to understand the lived experiences of couples who have a child suffering from a genetic disorder (affected child) and to understand the couple's experiences of receiving the diagnosis of an inherited genetic disorder in a child, and how they as a couple, and by extension, their family, adapted to that diagnosis. Nine couples from the Midwestern United States were interviewed using a semi-structured, joint interview process. Using thematic analysis and the couples' own words, two studies emerged from the data. The focus of study 1 was on the decision-making processes about genetic testing and the decision to have future children of couples who have a child with an inherited genetic disorder. The focus of study 2 was on how the family adapted after receiving the diagnosis for their child. Implications and further considerations for family therapists are addressed.
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Title: Real Fantasies in Mathematics Education : numeracy, Quantitative Reasoners, and Transdisciplinary Wicked Problems
Creator: Craig, Jeffrey Carl
Date: 2017
Collection: Electronic Theses & Dissertations
Description: This dissertation has seven chapters. In chapter one, I discuss through why I am doing this dissertation, my positionality, and how I learned from and with all of my committee members.Chapter two is where I situate my dissertation study through developing a social theory of quantitative literacy by translating a social theory of literacy (Barton & Hamilton, 2000). I also describe my epistemological stance towards research as a creative act, my theoretical commitments to critical postmodernism...
Show moreThis dissertation has seven chapters. In chapter one, I discuss through why I am doing this dissertation, my positionality, and how I learned from and with all of my committee members.Chapter two is where I situate my dissertation study through developing a social theory of quantitative literacy by translating a social theory of literacy (Barton & Hamilton, 2000). I also describe my epistemological stance towards research as a creative act, my theoretical commitments to critical postmodernism, and summarize my methodologies and methods for each of the three articles. Chapter three is my first article. In this article, I historicize the numeracy discourse by writing a genealogy that traces how statements about numeracy emerge in scholarship, with a focus on the United States. Scholars’ statements about numeracy form a discourse that pressures mathematics education to reform. These pressures are sustained when scholars connect numeracy to historically powerful justifications for reform. I name these as three promises embedded in the discourse: (1) numeracy promises to reflect modern reality, (2) numeracy promises to empower, and (3) innumeracy promises to have social costs. I conclude with a discussion of the literacy myth and its implications for mathematics education. Chapter four is my second article. In this article, I take the quantitative reasoner to be a persona embodying the goals mathematics educators describe for who our students should become. The quantitative reasoner has both cognitive and affective dimensions; they know and feel particular things about mathematics and statistics. As a member of a curriculum design team, I invoked the value of students becoming quantitative reasoners to defend new courses existing. My students helped me see that the quantitative reasoner is an incomplete person who is a fantasy of mathematics educators, including myself. Together, we re-humanized the quantitative reasoner and each other. Chapter five is my third article. This article describes findings from a study on students’ projects during a mathematics course in quantitative literacy. The issues students chose to research turned out to be connected to a particular class of problems. Across places and disciplines, people are working on these wicked problems which are messy, global, connected, responsive, and unavoidable. Wicked problems are in contrast to curricula that may center tame problems. This apparent mismatch provided the impetus to consider education for wicked problems. After coding students’ projects using the Rittel & Weber’s (1973/1984) ten characteristics of wicked problems, I found three themes: complexity, transdisciplinarity, and openness. Chapter six is my conclusion. In the chapter I synthesize what I have done in my dissertation and revisit some of my theoretical work – most notably my social theory of quantitative literacy. I also use my dissertation to revisit mathematics education as a whole, including research, and try to make some new connections and trouble my conclusions. Chapter seven is my parting thoughts. In it, I return to my positionality by discussing an aesthetic choice I have engaged during this dissertation. That aesthetic is the metamodern aesthetic and it involves the juxtaposition of incredible seriousness with playful detachment. I think about the metamodern aesthetic and my millennial identity in order to reframe doing education research.
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Title: Deep sequencing driven protein engineering : new methods and applications in studying the constraints of functional enzyme evolution
Creator: Wrenbeck, Emily Elizabeth
Date: 2017
Collection: Electronic Theses & Dissertations
Description: "Chemical engineers have long sought enzymes as alternatives to traditional chemocatalytic routes as they are highly selective and have evolved to function under mild conditions (physiological temperature, neutral pH, and atmospheric pressure). Enzymes, the workhorses of biological chemistry, represent a vast catalogue of chemical transformations. This feature lends their use in a variety of industrial applications including food processing, biofuels, engineered biosynthetic pathways, and as...
Show more"Chemical engineers have long sought enzymes as alternatives to traditional chemocatalytic routes as they are highly selective and have evolved to function under mild conditions (physiological temperature, neutral pH, and atmospheric pressure). Enzymes, the workhorses of biological chemistry, represent a vast catalogue of chemical transformations. This feature lends their use in a variety of industrial applications including food processing, biofuels, engineered biosynthetic pathways, and as biocatalysts for preparing specialty chemicals (e.g. pharmaceutical building blocks). The totality of an enzymatic bioprocess is a function of its catalytic efficiency (specificity and turnover), product profile (i.e. regio- and enantio-selectivity), and thermodynamic and kinetic stability. For native enzymes, these parameters are seldom optimal. Importantly, they can be modified using protein engineering techniques, which generally involves introducing mutation(s) to a protein sequence and screening for beneficial effects. However, robust enzyme engineering and design based on first principles is extremely challenging, as mutations that improve one parameter often yield undesired tradeoffs with one or more other parameters. In this thesis, deep mutational scanning - the testing of all possible single-amino acid substitutions of a protein sequence using high-throughput screens/selections and DNA counting via deep sequencing - was used to address two fundamental constraints on functional enzyme evolution. First, how do enzymes encode substrate specificity? To address this question, deep mutational scanning of an amidase on multiple substrates was performed using growth-based selections. Comparison of the resulting datasets revealed that mutations benefiting function on a given substrate were globally distributed in both protein sequence and structure. Additionally, our massive datasets permitted the most rigorous testing to date of theoretical models of adaptive molecular evolution. These results have implications for both design of biocatalysts and in understanding how natural enzymes function and evolve. Another fundamental constraint of enzyme engineering is that mutations improving stability (folding probability) of an enzyme are often inactivating for catalytic function, and vice versa. Towards overcoming this activity-stability constraint, I sought to improve the heterologous expression and maintain the catalytic function of a Type III polyketide synthase from Atropa belladonna. This was accomplished using deep mutational scanning and high-throughput GFP-fusion stability screening, followed by novel filtering methods to only accept beneficial mutations with high probability for maintaining function. Lastly, deep mutational scanning relies on the construction of user-defined DNA libraries, however current available techniques are limited by accessibility or poor coverage. To address these limitations, I will present the development of Nicking Mutagenesis, a new method for the construction of comprehensive single-site saturation mutagenesis libraries that requires only double-stranded plasmid DNA as input substrate. This method has been validated on several gene targets and plasmids and is currently being used in academic, government, and industry laboratories worldwide."--Pages ii-iii.
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Title: Information seeking of scholars in the field of higher education
Creator: Fitzgerald, Sarah Rose
Date: 2017
Collection: Electronic Theses & Dissertations
Description: This study examines the information seeking of scholars in the field of Higher Education. I interviewed Higher Education scholars about their use of the web, library resources, and interpersonal networking for their research. I also spoke with them about how the faculty reward system shapes their information seeking habits. I drew on information behavior concepts to describe their behaviors. Because Higher Education is an interdisciplinary field, there is a broad swath of literature Higher...
Show moreThis study examines the information seeking of scholars in the field of Higher Education. I interviewed Higher Education scholars about their use of the web, library resources, and interpersonal networking for their research. I also spoke with them about how the faculty reward system shapes their information seeking habits. I drew on information behavior concepts to describe their behaviors. Because Higher Education is an interdisciplinary field, there is a broad swath of literature Higher Education scholars might draw from. This study examined how these scholars seek information in an information rich environment with limited time. The findings of this study describe how the career expectations for Higher Education scholars shapes their information seeking choices, how scholars change their information seeking over time, how emotional and interpersonal factors influence their choices, and how the tools available for information seeking influence their research. Many of the findings appear to apply to faculty engaged in research across disciplines, particularly other applied social sciences. Scholars publish work that advances their careers, but this doesn't include all the work that could enhance the body of knowledge about Higher Education. Events in society and changes in educational policy which have a great impact on Higher Education do not necessarily get addressed by scholarship in the field. Keeping up with the scholarly literature in Higher Education will not keep one abreast of all the developments in Higher Education. Scholars' professional confidence, passion, and relationships effect their ambition in searching for information, branching out to new topics, and sharing their expertise. Information seeking and sharing is influenced by the supportiveness of the community of scholars they work in. This includes senior scholars in the field, scholars outside the field, and librarians. An individual's disposition may determine how willing they are to seek information and help, which can determine how successful they will be as a scholar.The technologies for information seeking are constantly and rapidly changing. It's important to keep faculty up to date with new developments and changes to library resources so they do not develop a static view of tools that are constantly in flux. Scholars should be aware that tools change and they should be on alert for new developments.
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Title: Climate change and algal blooms
Creator: Lin, Shengpan
Date: 2017
Collection: Electronic Theses & Dissertations
Description: "Algal blooms are new emerging hazards that have had important social impacts in recent years. However, it was not very clear whether future climate change causing warming waters and stronger storm events would exacerbate the algal bloom problem. The goal of this dissertation was to evaluate the sensitivity of algal biomass to climate change in the continental United States. Long-term large-scale observations of algal biomass in inland lakes are challenging, but are necessary to relate...
Show more"Algal blooms are new emerging hazards that have had important social impacts in recent years. However, it was not very clear whether future climate change causing warming waters and stronger storm events would exacerbate the algal bloom problem. The goal of this dissertation was to evaluate the sensitivity of algal biomass to climate change in the continental United States. Long-term large-scale observations of algal biomass in inland lakes are challenging, but are necessary to relate climate change to algal blooms. To get observations at this scale, this dissertation applied machine-learning algorithms including boosted regression trees (BRT) in remote sensing of chlorophyll-a with Landsat TM/ETM+. The results show that the BRT algorithm improved model accuracy by 15%, compared to traditional linear regression. The remote sensing model explained 46% of the total variance of the ground-measured chlorophyll-a in the first National Lake Assessment conducted by the US Environmental Protection Agency. That accuracy was ecologically meaningful to study climate change impacts on algal blooms. Moreover, the BRT algorithm for chlorophyll-a would not have systematic bias that is introduced by sediments and colored dissolved organic matter, both of which might change concurrently with climate change and algal blooms. This dissertation shows that the existing atmospheric corrections for Landsat TM/ETM+ imagery might not be good enough to improve the remote sensing of chlorophyll-a in inland lakes. After deriving long-term algal biomass estimates from Landsat TM/ETM+, time series analysis was used to study the relations of climate change and algal biomass in four Missouri reservoirs. The results show that neither temperature nor precipitation was the only factor that controlled temporal variation of algal biomass. Different reservoirs, even different zones within the same reservoir, responded differently to temperature and precipitation changes. These findings were further tested in 1157 lakes across the continental United States. The results show that mean annual algal biomass generally increased with annual temperature. Greater increase was found in lakes with more nutrients. Mean annual algal biomass generally decreased with annual total precipitation. In both the "low" and the "high" greenhouse-gas emission scenarios, mean annual algal biomass in lakes generally increased with climate change, and greater increases are predicted from the high emission scenario."--Pages ii-iii.
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Title: Mentor teachers as teacher educators : a qualitative study of educative mentoring
Creator: Yates, Claire (Claire Fredrick)
Date: 2017
Collection: Electronic Theses & Dissertations
Description: There is increasing pressure on Education Preparation Providers to provide clinically rich opportunities for interns that are connected with and embedded in local schools. Providing these clinically rich opportunities has become the primary responsibility of the mentor teachers that oversee the development of the interns placed in their schools. If mentor teachers are to become teacher educators, they need greater support to develop educative mentoring practices. The purpose of this study was...
Show moreThere is increasing pressure on Education Preparation Providers to provide clinically rich opportunities for interns that are connected with and embedded in local schools. Providing these clinically rich opportunities has become the primary responsibility of the mentor teachers that oversee the development of the interns placed in their schools. If mentor teachers are to become teacher educators, they need greater support to develop educative mentoring practices. The purpose of this study was to learn more about the experiences of mentor teachers as they applied educative mentoring strategies and to discover how their professional learning could be supported by Education Preparation Providers. This qualitative study, based on the experiences of six secondary level mentor teachers that mentored interns in year-long placements, interviewed them about their personal histories and values, captured specific mentoring moments with their interns, and conducted reflective interviews about their current mentoring practices. The central research question was: How do mentors use their knowledge and/or vision of teaching to provide learning opportunities for their interns? Four additional supportive questions were asked to provide a more robust picture of the mentor teachers' practices: ¥ How do mentors determine the professional development needs of their interns?¥ How do mentor teachers explicitly or implicitly use their knowledge and values about teaching in their mentoring of interns? ¥ What strategies do mentor teachers use to promote reflection on the part of interns?¥ How can experienced mentors continue to learn about mentoring? The results of this study showed that mentor teachers utilized a variety of mentoring strategies to develop the interns' vision of teaching. These methods allowed them to move beyond the transmission model of mentoring to a more transformative stance grounded in the values of educative mentoring.
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Title: Analysis of wind turbine blade vibration and drivetrain loads
Creator: Ramakrishnan, Venkatanarayanan
Date: 2017
Collection: Electronic Theses & Dissertations
Description: The reliability of wind turbines is a major issue for the industry. Drivetrain and blade failures are common, costly and not fully understood. Designers must thus examine and understand the key parameters that influence reliability. As wind turbines increase in size, the blades are designed to be more lightweight and flexible, increasing the potential for large-displacement oscillations during operation. This necessitates the incorporation of nonlinearity in the formulation of the blade model...
Show moreThe reliability of wind turbines is a major issue for the industry. Drivetrain and blade failures are common, costly and not fully understood. Designers must thus examine and understand the key parameters that influence reliability. As wind turbines increase in size, the blades are designed to be more lightweight and flexible, increasing the potential for large-displacement oscillations during operation. This necessitates the incorporation of nonlinearity in the formulation of the blade model to better understand the dynamics and stability characteristics. Also, oscillations in the blade impart dynamic loading onto the gearbox. Understanding these dynamic loads is essential for the design of reliable gears and bearings, and hence economically viable wind turbines. Traditional studies of wind turbines have focused on the aerodynamic performance of the blades, the reliability of gearbox and its components, grid connectivity and improvements in power distribution. The aspect of blade vibration from a dynamics point of view has garnered interest but not been fully developed and understood. In this work, the partial and ordinary differential equations that govern the in-plane and out-of-plane motion of a wind turbine blade subject to gravitational and aerodynamic loading are developed using Hamilton's principle and Lagrange formulations respectively. These differential equations include nonlinear terms due to nonlinear curvature and nonlinear foreshortening, as well as parametric and direct excitation at the frequency of rotation. The equations are reduced using an assumed uniform cantilevered beam mode to produce single second-order ordinary differential equations (ODE) to approximate the blade model for the case of constant rotation rate. Embedded in the ODE's are terms of a forced Mathieu equation with cubic nonlinearity. Different variations of the forced Mathieu equation are analyzed for resonances by using the method of multiple scales. The forced Mathieu equation has instabilities and resonances at multiple superharmonic and subharmonic frequencies. Second-order expansions are used to unfold the expressions that govern the amplitude of response at these critical resonances. The equations of motion (EOM's) also have regions of instability and we employ perturbation analysis to identify the stability transition curves of the system. These calculations compare well with numerical simulations for simple systems under study. The formulation is then extended to wind turbine blades. The effect of various parameters on the amount of blade oscillation is demonstrated using the amplitude-frequency curve. Aerodynamic forces on the wind turbine blades are calculated using the Blade Element Momentum (BEM) theory and its extensions. Commercial software, such as FAST, have also been used to simulate responses for specific blades to understand influence of various blade parameters. For current production wind turbine blades, the parameters are such that the superharmonic resonances are not excited significantly. From parametric studies of the blade EOM we can understand the parameter values at which these resonances become dominant. It is shown that as wind turbine blades become larger they are prone to superharmonic resonances, whose existence may not be within the scope of current design strategies. The amplitude of response at all resonances tend to become amplified for much larger blades. Both in-plane and out-of-plane responses will increase the loading at the rotor hub and consequently, increase the loads and moments on the wind turbine drivetrain. To capture the effect of increased loading on the wind turbine drivetrain, we follow two approaches. First, using RomaxWind, we model the 750 kW gearbox used as a part of the Gearbox Reliability Collaborative (GRC) headed by National Renewable Energy Labs (NREL). For this, we partnered with Romax Technology Ltd. to analyze the sensitivities of the load on the elements of the gearbox to variations in the input loads. Using the Romax gearbox model, we suggest methods to optimize the gear geometry to improve reliability of the drivetrain by minimizing influence of manufacturing and assembly tolerances and misalignments. We also designed novel approaches to predict gearbox vibration using the models and suggested changes that are required to improve the overall design of the gearbox (these have been implemented while manufacturing newer generations of the NREL GRC gearbox). Second, for the case of in-plane blade vibration, we use a simple torsional model of the wind turbine gearbox to study the influence of a time varying load on the torsional response of the drivetrain. The effect of increased loading on larger wind turbine systems is shown by scaling values of blade and gearbox properties. The fundamental work formulated in this thesis can be extended to more complex models to understand other system level dynamics of interest (multi-mode interaction, multi-blade resonance, etc.). More detailed formulation of aerodynamic loads (for example by using ONERA semi-empirical approach) would also improve model fidelity for predicting the influence of aerodynamic loads on blade vibration.
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Title: Urban and cluster agglomeration economies's effects on rural households in Asia
Creator: Hu, Chaoran
Date: 2017
Collection: Electronic Theses & Dissertations
Description: "Agglomeration effects play important roles for rural households in participating in farm and nonfarm activities. With the rapid growth of cities of different sizes and the development of food value chain, how these agglomerations of urban effects, networks, and food value chain clusters will affect rural households' participation in nonfarm employment and farm behavior (technology adoption) are not yet well known. The dissertation consists of three chapters that aim to assess the impacts of...
Show more"Agglomeration effects play important roles for rural households in participating in farm and nonfarm activities. With the rapid growth of cities of different sizes and the development of food value chain, how these agglomerations of urban effects, networks, and food value chain clusters will affect rural households' participation in nonfarm employment and farm behavior (technology adoption) are not yet well known. The dissertation consists of three chapters that aim to assess the impacts of these urban and cluster agglomeration economies' on rural households in Asia."--Excerpted from abstract.
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Title: Field modeling, symplectic tracking, and spin decoherence for EDM and muon g-2 lattices
Creator: Valetov, Eremey Vladimirovich
Date: 2017
Collection: Electronic Theses & Dissertations
Description: "While the first particle accelerators were electrostatic machines, and several electrostatic storage rings were subsequently commissioned and operated, electrostatic storage rings pose a number of challenges. Unlike motion in the magnetic field, where particle energy remains constant, particle energy generally changes in electrostatic elements. Conservation of energy in an electrostatic element is, in practice, only approximate, and it requires careful and accurate design, manufacturing,...
Show more"While the first particle accelerators were electrostatic machines, and several electrostatic storage rings were subsequently commissioned and operated, electrostatic storage rings pose a number of challenges. Unlike motion in the magnetic field, where particle energy remains constant, particle energy generally changes in electrostatic elements. Conservation of energy in an electrostatic element is, in practice, only approximate, and it requires careful and accurate design, manufacturing, installation, and operational use. Electrostatic deflectors require relatively high electrostatic fields, tend to introduce nonlinear aberrations of all orders, and are more challenging to manufacture than homogeneous magnetic dipoles. Accordingly, magnetic storage rings are overwhelmingly prevalent. The search for electric dipole moments (EDMs) of fundamental particles is of key importance in the study of C and CP violations and their sources. C and CP violations are part of the Sakharov conditions that explain the matter-antimatter asymmetry in the universe. Determining the source of CP violations would provide valuable empirical insight for beyond-Standard-Model physics. EDMs of fundamental particles have not to this date been experimentally observed. The search for fundamental particle EDMs has narrowed the target search region; however, an EDM signal is yet to be discovered. In 2008, Brookhaven National Laboratory (BNL) had proposed the frozen spin (FS) concept for the search of a deuteron EDM. The FS concept envisions launching deuterons through a storage ring with combined electrostatic and magnetic fields. The electrostatic and magnetic fields are in a proportion that would, without an EDM, freeze the deuteron's spin along its momentum as the deuteron moves around the lattice. The radial electrostatic field would result in a torque on the spin vector, proportional to a deuteron EDM, rotating the spin vector out of the midplane. The principle of an anomalous magnetic dipole moment (MDM) measurement using a storage ring, shared by BNL's completed E821 Experiment and the ongoing E989 Experiment operated by Fermi National Accelerator Laboratory (FNAL), requires injecting muons into a magnetic ring at the so-called magic momentum. The magic momentum, as defined in this context, would freeze the muon's spin vector along its momentum if the anomalous MDM was zero. The spin precession in the horizontal plane relative to the momentum is proportional to the anomalous MDM. Storage rings for measurement of EDM and anomalous MDM present a new frontier in tracking code accuracy requirements. For accurate tracking of storage rings with electrostatic particle optical elements, it is necessary to model the fringe fields of such elements accurately, in particular, because not doing so provides a mechanism for energy conservation violation. However, the previous research on fringe fields tended to focus on magnetic rather than electrostatic particle optical elements. We will study and model the fringe fields of several electrostatic deflectors. Field falloffs of electrostatic deflectors are slower than exponential, and Enge functions are not suitable for accurate modeling of these falloffs. We will propose an alternative function to model field falloffs of electrostatic deflectors. We will use conformal mapping methods to obtain the main field of the Muon g-2 storage ring high voltage quadrupole, and we will calculate its fringe field and effective field boundary (EFB) using Fourier analysis. Furthermore, we will study tracking of storage rings with electrostatic elements using map methods. We will find that, for simultaneous symplecticity and energy conservation, it is only necessary to enforce symplecticity in COSY INFINITY. We will model and track several benchmark lattices - an electrostatic spherical deflector, a homogeneous magnetic dipole, and a proton EDM lattice - in COSY INFINITY and MSURK89, our in-house eighth order Runge-Kutta-Verner tracking code. Finally, we will investigate spin decoherence and systematic errors in FS and quasifrozen spin (QFS) lattices. Spin decoherence effects are similar in FS and QFS lattices, and spin decoherence in said lattices often remains in the same range over time, indicating the feasibility of EDM measurement using FS and QFS lattices."--Pages ii-iii.
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Title: Examining off-campus students' sense of belonging and behaviors in a town-gown context
Creator: Carter, Erin Hundley
Date: 2017
Collection: Electronic Theses & Dissertations
Description: The current study emerged from the need to address student behavior issues in town-gown communities and the practical need to know more about off-campus students as central actors in these behaviors. Off-campus students have long been labeled as commuter students because of limited recognition of the known diversity within the commuter population (Dugan, Garland, Jacoby, & Gasiorski, 2008) and an absence of town-gown scholarship focused on college student residents of the local community ...
Show moreThe current study emerged from the need to address student behavior issues in town-gown communities and the practical need to know more about off-campus students as central actors in these behaviors. Off-campus students have long been labeled as commuter students because of limited recognition of the known diversity within the commuter population (Dugan, Garland, Jacoby, & Gasiorski, 2008) and an absence of town-gown scholarship focused on college student residents of the local community (Kemp, 2013). The current study sought to remedy the little attention given to off-campus students through the exploration of their sense of belonging to the local community, and in turn, how sense of belonging influenced behavior in the town-gown context. An American college town was the town-gown context chosen for the current study because of its capacity to showcase the unique influence the university has on the character of the town (Gumprecht, 2008). Using a stratified random sampling, the sample (n = 645) was drawn from the population of undergraduate students living off campus in the City of East Lansing, Michigan. Strata were determined based on residential density levels due to an interest in assessing how residential environments of varying densities influenced sense of belonging in off-campus students. The current study utilized sense of belonging and town-gown literature to guide the selection of exogenous and intervening predictor variables relevant in the town-gown context. These predictor variables included demographic characteristics (e.g., age, sex, race, year in school) and density categorization along with intervening variables such as environmental perceptions, social interactions, and behavior participation. Criterion variables included sense of belonging and positive and negative behavior participation. Hierarchical regression analyses were used to determine the extent these demographic and community factors influenced sense of belonging, as well as how sense of belonging influenced participation in positive and negative behaviors in the town-gown context. The study concluded off-campus students were a unique cohort in the student population, warranting future attention from scholars and practitioners. Sense of belonging was not predicted by demographic and density characteristics, but was positively influenced by perceptions of community (e.g., reliability, friendliness) and positive behavior participation (e.g., attending community events, utilizing city services). Number of roommates, semesters lived off-campus, and residential density associated with houses were positive predictors of behavior participation, both positive and negative. Environmental and social relations constructs were positive predictors of both positive and negative behavior participation. Sense of belonging was a positive predictor of positive behavior participation, but was not a predictor of negative behaviors. The discussion offers insights and direction for town-gown administrators tasked with creating policy and practical interventions aimed at supporting off-campus students, while also addressing the unique challenges stemming from student behaviors in the local community.
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Title: Examining the results of an intervention to influence factors of group dynamics in video conferencing learning environments
Creator: Cain, William Christopher
Date: 2017
Collection: Electronic Theses & Dissertations
Description: "The following study was framed around a simple question: when a group of people is engaged in video conferencing, what sort of things can they do to improve their group dynamics? This is an important question for current and future educational practice because web-based video conferencing has increasingly become an important tool for use in online and distance education programs. Using computer-based audio and visual equipment, web-based video conferencing allows groups of students and...
Show more"The following study was framed around a simple question: when a group of people is engaged in video conferencing, what sort of things can they do to improve their group dynamics? This is an important question for current and future educational practice because web-based video conferencing has increasingly become an important tool for use in online and distance education programs. Using computer-based audio and visual equipment, web-based video conferencing allows groups of students and teachers to see and hear each other in real-time, providing a channel of communication that is often rich in information. Informal video chat, using applications like Skype, FaceTime, and Google Hangouts, has become a popular means of communication in much the same way as phone calls. Formal group video conferencing, however, is a different communication and interaction format from informal video chat, and many teachers and students often unfamiliar with rules and norms associated with it. For example, best practices literature on video conferencing stress that things like framing, lighting, proximity to the camera, and the composition of background can all affect the way a person is perceived by others. These factors can also affect the overall quality of the video conferencing session, making it easier or harder for people to hold sustained interactions with each other. In short, formal group video conferencing requires people to be mindful of certain things that they may not pay attention to when they are engaged in either face-to-face conversations or informal video chats. When people are not mindful, they can cause serious disruptions to overall group dynamics. Group dynamics play a role in any setting where people come together for a period of time. Forsyth defines a group as "two or more individuals who connected by and with social relationships" (Forsyth, 2009, p. 4). Dynamics are the interactions between and among factors in a context or system of elements. Group dynamics therefore refers to the qualities of interaction with one another in a group. Factors that influence group dynamics include morale, belongingness, tone, atmosphere, influence, participation, trust, leadership, conflict, competition, cooperation, etc. (Hanson, 2005). The goal of this study was to design an intervention based on a series of activities that instructors or facilitators could use with students in simulated high-stakes video conferencing learning environments. The results were illuminating but not in a way the author intended. The intervention at the heart of this study was not implemented as it was originally designed, which affected not only the results but the entire direction of analysis. This is not necessarily a bad thing. This study shows the importance of intervention design and the role that facilitators play in bringing the benefits of an intervention to those who need it. The different chapters in this dissertation discuss why the author felt this study was important and necessary, how he went about designing the central intervention, what the results suggest about intervention design and implementation, and his recommendations for future research in the area of group dynamics in video conferencing learning environments. It is the author's wish that readers gain a new appreciation for the complexity of research in this area, as well as a newfound or renewed interest in seeing this research continue."--Pages ii-iii.
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Title: Inhibitors of mycobacterium tuberculosis DosRST signaling and persistence
Creator: Zheng, Huiqing
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Tuberculosis (TB) is one of the most deadly infectious diseases in human history and is caused by the bacterium Mycobacterium tuberculosis (Mtb). Current TB therapy requires 6-9 months of treatment with four different antibiotics, including isoniazid, rifampin, ethambutol and pyrazinamide. However, due to the long course of TB therapy and the evolution of drug-resistant Mtb strains, first-line anti-mycobacterial drugs are not sufficient to control the TB epidemic. Therefore, it is urgent to...
Show moreTuberculosis (TB) is one of the most deadly infectious diseases in human history and is caused by the bacterium Mycobacterium tuberculosis (Mtb). Current TB therapy requires 6-9 months of treatment with four different antibiotics, including isoniazid, rifampin, ethambutol and pyrazinamide. However, due to the long course of TB therapy and the evolution of drug-resistant Mtb strains, first-line anti-mycobacterial drugs are not sufficient to control the TB epidemic. Therefore, it is urgent to develop new drugs with novel targets to shorten the course of therapy, control the spread of drug-resistant TB and eradicate this deadly disease. In response to host immune cues, Mtb modulates its metabolism to establish a state of low metabolic activity called non-replicating persistence (NRP). During NRP, Mtb can remain viable in the host without causing disease symptoms, a state known as latent TB. DosRST is a two-component regulatory system that plays an essential role to establish and maintain NRP in Mtb. It is induced by host immune stimuli, such as hypoxia, carbon monoxide and nitric oxide, through the histidine kinase sensors DosS and DosT. The response regulator DosR regulates about 50 genes in the dormancy regulon. NRP bacilli are problematic for two reasons: 1) they are insensitive to several anti-mycobacterial agents and drive the long course of TB therapy; and, 2) they can resuscitate for growth once the immune system weakens, thereby serving as a source for reactivation of disease and infectious transmission of the Mtb. Therefore, inhibiting the DosRST pathway may help reduce the population of NRP bacteria during infection and thus function to reduce drug tolerance and shorten TB treatment. This dissertation presents a whole-cell phenotypic high-throughput screen of a ~540,000 compound small-molecule library. The screen employed a DosR-dependent, hypoxia-inducible fluorescent reporter strain, CDC1551(hspX::GFP), and successfully identified six distinct, novel chemical inhibitors of DosRST signaling, named HC101A-106A. Physiological and mechanistic studies were performed to characterize HC101-104 and HC106A. All five inhibitors are shown to inhibit genes of the DosRST regulon and persistence-associated physiologies, such as triacylglycerol accumulation. HC101A, HC102A, HC103A and HC106A also reduce Mtb survival when cultured under strongly hypoxic conditions. UV-visible spectroscopy studies show that HC101A (artemisinin) and HC106A target the heme group of sensor kinases DosS/T via distinct mechanisms. For example, artemisinin modulates the redox status of DosS/T and alkylates the heme to form artemisinin-heme adducts, whereas HC106A interacts with DosS heme in a similar manner to direct CO-heme or NO-heme interactions. In contrast, HC102A and HC103A do not target the heme group, but instead inhibit sensor kinase autophosphorylation activity. Electrophoretic mobility assays suggest that HC104A functions by directly inhibiting DosR DNA binding activity. Overall, this dissertation provides proof-of-concept that multiple components of the DosRST pathway can be targeted by small molecules to inhibit Mtb persistence and antibiotic tolerance. Additionally, this dissertation presents the discovery of a new chemical inhibitor, HC2091, that kills Mtb by targeting the mycolic acid transporter MmpL3. MmpL3 is an essential protein that functions to transport trehalose monomycolate across mycomembranes for trehalose dimycolate biosynthesis. HC2091 is bactericidal against Mtb in a dose- and time- dependent manner in vitro. It also has activity against Mtb inside of macrophages. Whole genome sequencing spontaneous mutants resistant to HC2091 identified five single nucleotide variants primarily located in the C-terminus of MmpL3, and HC2091-treated Mtb exhibits decreased mycolic acid synthesis, thus supporting that MmpL3 is the target of HC2091.
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Title: Guilt, empathy, and compliance in a naturalistic moral scenario : predicting prosocial and externalizing behavior in 3-7-year-old children
Creator: Listro, Caitlin J.
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Current science offers only limited answers concerning the development of empathy disturbances. Indeed, few studies have attempted to empirically identify the developmental trajectory of empathy to define either normal or aberrant developmental patterns. The present study aimed to use an observational approach to assess empathy, guilt, and obedience in children, and to validate this approach by exploring how these observational measures of child moral behavior associated with characteristics...
Show moreCurrent science offers only limited answers concerning the development of empathy disturbances. Indeed, few studies have attempted to empirically identify the developmental trajectory of empathy to define either normal or aberrant developmental patterns. The present study aimed to use an observational approach to assess empathy, guilt, and obedience in children, and to validate this approach by exploring how these observational measures of child moral behavior associated with characteristics theoretically linked to moral development and antisocial behavior. We utilized a videotaped Picture Tearing task in which the child is presented with a moral dilemma. Trained coders rated the tasks for several child behaviors (e.g. guilt, gaze avoidance, defiance) using a coding scheme adapted from the Lab-TAB (Goldsmith et al., 1993). Variations in moral behavior were investigated using person-centered (cluster analysis) and variable-centered (factor analysis) methods, then associations between resulting behaviors and other relevant child characteristics (temperament, externalizing behaviors) were examined concurrently and over time. In general, results indicated that empathic verbalizations and defiance were consistently associated with externalizing pathology. This association was observed concurrently; empathy did not predict externalizing over time. Overall, these results suggest that compliant without complaint is the most adaptive response at this age. Furthermore, the Picture Tearing task does provide useful data about empathic behavior and its associations in young children. Recommendations are made for adaptations to the task and coding scheme to improve the measurement of moral behavior in future research.
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Title: Defining the characteristics and roles of functional genomic sequences using computational approaches
Creator: Lloyd, John P.
Date: 2017
Collection: Electronic Theses & Dissertations
Description: "Advances in biotechnology have provided a wealth of sequencing data that is transforming our view of a genome. Eukaryotic genomes, initially thought to contain discrete genes in a sea of non-functional DNA, have been found to exhibit pervasive biochemical activity, particularly transcription. However, whether this biochemical activity is functional (i.e. under evolutionary selection) or the result of noisy activity of cellular machinery represents a fundamental debate of the post-genome era....
Show more"Advances in biotechnology have provided a wealth of sequencing data that is transforming our view of a genome. Eukaryotic genomes, initially thought to contain discrete genes in a sea of non-functional DNA, have been found to exhibit pervasive biochemical activity, particularly transcription. However, whether this biochemical activity is functional (i.e. under evolutionary selection) or the result of noisy activity of cellular machinery represents a fundamental debate of the post-genome era. The research described in this dissertation focuses on two open questions confronting genome biology: 1) Where are the functional elements within a genome? 2) What roles are functional elements performing? For the first question, I focused on transcribed regions in unannotated, intergenic regions of genomes, which represent functionally ambiguous sequences. To determine which and how many intergenic transcribed regions (ITRs) represent functional sequences, machine learning-based function prediction models were established using Arabidopsis thaliana as a model. The prediction models were able to successfully distinguish between benchmark functional (phenotype genes) and non-functional sequences (pseudogenes) using evolutionary, biochemical, and sequence-based structural features. When applied to ITRs, 400303% of ITRs were predicted as functional, suggesting ITRs primarily represent transcriptional noise. I further investigated the evolutionary histories of ITRs in four grass (Poaceae) species. ITRs were found to be primarily species-specific and exhibit recent duplicates, with rare examples of ancient duplicate retention. In addition, ITR duplicates and orthologs were usually not expressed. Function prediction models were also generated in Oryza sativa (rice) that predicted 600303% of rice ITRs as nonfunctional. The results of function prediction models and evaluating evolutionary histories both suggest ITRs are primarily non-functional sequences. However, I also provide a list of potentially-functional ITRs that should be considered high priority targets for future experimental studies. For the second question, I established a machine learning framework to predict mutant phenotypes, which provide potent evidence for the role of a gene. Phenotype predictions were focused on essential genes (those with lethal mutant phenotypes) in A. thaliana, as these genes represent a historically well-studied group. Combining 57 expression, duplication, evolutionary, and gene network characteristics through machine learning methods accurately distinguished between genes with lethal and non-lethal mutant phenotypes. Additionally, essential gene prediction models could be applied across species; essential gene prediction models generated in A. thaliana could identify essential genes in rice and Saccharomyces cerevisiae. Thus, machine-learning represents a promising avenue of prioritization of candidate genes for large-scale phenotyping efforts. Overall, the research described in this dissertation highlight computational approaches as highly effective in defining functional sequences and classifying the likely roles of genes."--Pages ii-iii.
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Title: ResBos2 : precision resummation for the LHC ERA
Creator: Isaacson, Joshua Paul
Date: 2017
Collection: Electronic Theses & Dissertations
Description: With the precision of data at the LHC, it is important to advance theoretical calculations to match it. Previously, the ResBos code was insufficient to adequately describe the data at the LHC. This requires an advancement in the ResBos code, and led to the development of the ResBos2 package. This thesis discusses some of the major improvements that were implemented into the code to advance it and prepare it for the precision of the LHC.The resummation for color singlet particles is improved...
Show moreWith the precision of data at the LHC, it is important to advance theoretical calculations to match it. Previously, the ResBos code was insufficient to adequately describe the data at the LHC. This requires an advancement in the ResBos code, and led to the development of the ResBos2 package. This thesis discusses some of the major improvements that were implemented into the code to advance it and prepare it for the precision of the LHC.The resummation for color singlet particles is improved from approximate NNLL+NLO accuracy to an accuracy of N$^3$LL+NNLO accuracy. The ResBos2 code is validated against the calculation of the total cross-section for Drell-Yan processes against fixed order calculations, to ensure that the calculations are performed correctly. This allows for a prediction of the transverse momentum and $\phi^*_{\eta}$ distributions for the $Z$ boson to be consistent with the data from ATLAS at a collider energy of $\sqrt{s}=8$ TeV. Also, the effects of choice of resummation scheme are investigated for the Collins-Soper-Sterman and Catani-deFlorian-Grazzini formalisms. It is shown that as long as the calculation of each of these is performed such that the order of the $B$ coefficient is exactly 1 order higher than that of the $C$ and $H$ coefficients, then the two formalisms are consistent. Additionally, using the improved theoretical prediction will help to reduce the theoretical uncertainty on the mass of the $W$ boson, by reducing the uncertainty in extrapolating the $\frac{d\sigma}{dp_T^W}$ distribution from the data for the $\frac{d\sigma}{dp_T^Z}$ distribution by taking the ratio of the theory predictions for the $Z$ and $W$ transverse momentum. In addition to improving the accuracy of the color singlet final state resummation calculations, the ResBos2 code introduces the resummation of non-color singlet states in the final state. Here the details for the Higgs plus jet calculation are illustrated as an example of one such process. It is shown that it is possible to perform this resummation, but the resummation formalism needs to be modified in order to do so. The major modification that is made is the inclusion of the jet cone-size dependence in the Sudakov form factor. This result resolves, analytically, the Sudakov shoulder singularity. The results of the ResBos2 prediction are compared to both the fixed order and parton shower calculations. The calculations are shown to be consistent for all of the distributions considered up to the theoretical uncertainty. As the LHC continues to increase their data, and their precision on these observables, the ability to have analytic resummation calculations for non-color singlet final states will provide a strong check of perturbative QCD.Finally, the calculation of the terms needed to match to N$^3$LO are done in this work. Once the results become sufficiently publicly available for the perturbative calculation, the ResBos2 code can easily be extended to include these corrections, and be used as a means to predict the total cross-section at N$^3$LO as well.
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Title: Part A : iridium catalyzed C-H borylation of arenes ; engineering selectivity by ligand design. Part B: Z-selective palladium catalyzed cross coupling of E-vinyl germanes
Creator: Miller, Susanne L.
Date: 2017
Collection: Electronic Theses & Dissertations
Description: ABSTRACTPART A: IRIDIUM CATALYZED C-H BORYLATION OF ARENES; ENGINEERING SELECTIVITY BY LIGAND DESIGN.By Susanne L. MillerIridium catalyzed C-H borylation has gained popularity as a means to functionalize simple aromatic and heterocyclic substrates under mild conditions which tolerate a variety of functional groups. Initial efforts to develop this chemistry made use of sterically driven selectivity to achieve contra-electronic substitution patterns of aromatic and heterocyclic building blocks...
Show moreABSTRACTPART A: IRIDIUM CATALYZED C-H BORYLATION OF ARENES; ENGINEERING SELECTIVITY BY LIGAND DESIGN.By Susanne L. MillerIridium catalyzed C-H borylation has gained popularity as a means to functionalize simple aromatic and heterocyclic substrates under mild conditions which tolerate a variety of functional groups. Initial efforts to develop this chemistry made use of sterically driven selectivity to achieve contra-electronic substitution patterns of aromatic and heterocyclic building blocks that were not easily obtainable by conventional organic chemistry prevalent before the discovery of this chemistry in 1999. As methodology and substrate scope rapidly expanded, steric selectivity became a limitation, as more diverse substitution patterns and higher selectivities were sought. These limitations were partially overcome by the extensive development of directing groups which enabled more traditional ortho substitution patterns to be accessed by the same mild conditions that made Ir-C-H borylation popular. While steric limitations that result in mixtures by the standard borylation protocols can now be overcome by directing groups, a serious challenge remains for the meta-functionalization of substrates which lack common directing groups or have small substituents. This work seeks to address this limitation by ligand-directed selectivity which can be instituted by the rational design of catalysts and ligands to achieve different selectivity outcomes depending on the desired product. The design and development of ligands which make use of either steric or electronic properties to achieve a given outcome was realized, and borylation meta to fluorine in simple arenes which lack directing groups was achieved. By varying the substituents on this ligand framework, the selectivity of the borylation can be shifted from steric to electronic selectivity.PART B: Z-SELECTIVE PALLADIUM CATALYZED CROSS COUPLING OF E-VINYL GERMANES.Germanium cross coupling reactions were born out of efforts to replace toxic organo-tin reagents used in the Stille cross coupling reaction for the construction of C-C bonds. Initial interest in germanium as a transmetalation partner peaked in the mid to late 1990s, but eventually waned due to poor reactivity of organo-germanium reagents and the harsh conditions needed to activate Ge-C bonds towards cross coupling. One such effort from the Maleczka group in the early 2000s, although suffering from poor conversion and unreliable results, gained modest attention by displaying a reactivity distinct from typical Stille coupling selectivity. Instead of retention of geometry, the major product of the E-vinyl germanium coupling reaction exhibited inverted Z- olefin geometry. In the reverse case, Z-vinylgermanes likewise gave inverted E-olefins as the major coupling products. Early studies of the reaction led to the hypothesis of a Heck-like insertion with subsequent germyl elimination to form the inverted product. The proposed mechanism featured a palladium-germyl elimination in preference to a possible b-H elimination. Based on the substrate scope and the organo-germane's required possession of a tertiary allylic alcohol, the Pd- Ge elimination theory was discarded in favor of the formation of a reactive epoxide intermediate, which eliminated germanium upon carbopalladation. The observation of the unactivated cross coupling of allylic germanium epoxides with iodo-arenes supported this hypothesis. Expansion of this chemistry was hampered by inconsistent results and a very narrow substrate scope. Further investigation suggested involvement of Pd nanoparticles.
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