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Title: Gaining a better understanding of teacher absenteeism
Creator: Gardner, Jacqueline A.
Date: 2020
Collection: Electronic Theses & Dissertations
Description: This study explores the reasons for chronic teacher absenteeism, which is a growing concern in Michigan schools and districts because teacher absenteeism is expensive and has implications for student learning. In total, 21 elementary teachers from seven different Michigan school districts were interviewed about their experiences with and perceptions of teacher absenteeism. Using an interpretive lens from the management literature on employee absenteeism, this study finds chronically absent...
Show moreThis study explores the reasons for chronic teacher absenteeism, which is a growing concern in Michigan schools and districts because teacher absenteeism is expensive and has implications for student learning. In total, 21 elementary teachers from seven different Michigan school districts were interviewed about their experiences with and perceptions of teacher absenteeism. Using an interpretive lens from the management literature on employee absenteeism, this study finds chronically absent teachers used paid time off for job-related mental health more often than for personal reasons compared to non-chronically absent teachers. The contributors to job-related mental health include three elusive, intangible characteristics: job stress, low perceived organizational support, and job dissatisfaction. The sources of job stress, low perceived organizational support, and job dissatisfaction are negative student behaviors, large class sizes, accountability pressures, lack of building support, lack of administration support, increased workload, performing additional duties above and beyond teaching, and not having enough district financial support for classroom materials and resources. The findings suggest organizational factors, or challenges with school and district culture and climate, contribute to chronic teacher absenteeism and must be improved upon. Implications for research, policy, and practice are discussed, along with opportunities for future research on both chronic teacher absenteeism and the culture and climate of schools and districts.
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Title: Recycling nursery runoff : understanding plant sensitivity to nutrients and residual pesticides
Creator: Poudyal, Shital
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Runoff generated from landscape nursery operations contains agrochemicals such as pesticides and fertilizers, which, if released off-site, may pollute the environment. Nursery producers are increasingly interested in alternatives to using freshwater for irrigation due to increased environmental awareness and reduced water availability. As a result, some progressive nursery growers are already adopting the Runoff generated from landscape nursery operations contains agrochemicals such...
Show moreRunoff generated from landscape nursery operations contains agrochemicals such as pesticides and fertilizers, which, if released off-site, may pollute the environment. Nursery producers are increasingly interested in alternatives to using freshwater for irrigation due to increased environmental awareness and reduced water availability. As a result, some progressive nursery growers are already adopting the Runoff generated from landscape nursery operations contains agrochemicals such as pesticides and fertilizers, which, if released off-site, may pollute the environment. Nursery producers are increasingly interested in alternatives to using freshwater for irrigation due to increased environmental awareness and reduced water availability. As a result, some progressive nursery growers are already adopting the practice of retaining and recycling nursery runoff water for irrigation. While retaining and recycling runoff may be a practical solution, growers' concerns about the potential negative impact of residual pesticides on crop growth and quality still impede its adoption. Therefore the objectives of my studies were to reduce the concentration of nutrients in runoff water and to evaluate the impact of irrigating with recycled runoff water on growth and physiology of nursery crops.The first study was to identify minimum phosphorus concentration required for the optimum morphological and physiological performance in three common woody ornamental taxa; Hydrangea quercifolia (Queen of hearts), Cornus obliqua (Redtwig dogwood) and Physocarpus opulifolius (Seward). The optimum phosphorus concentrations for growth and photosynthetic biochemistry ranged between 4 and 7 mg·L-1, depending on taxa. For the second study, I investigated the response of common landscape nursery plants to residual pesticide commonly found in nursery runoff. Hydrangea paniculata (Limelight), Cornus obliqua (Powell Gardens), Hosta (Gold Standard) were exposed to low residual concentrations of isoxaben, chlorpyrifos and oxyfluorfen, simulating irrigation with nursery runoff. Exposure to oxyfluorfen produced phytotoxicity symptoms (visual leaf damage), while chlorpyrifos and isoxaben did not produce phytotoxicity. Among the three taxa, H. paniculata was the most sensitive species, and C. obliqua was the most resistant. Therefore the effects of pesticides were pesticide-specific and taxa-specific. For the third study, I investigated whether phytotoxicity in response to residual herbicide exposure was dependent on the growth stage of plants. In this study, H. paniculata plants were exposed to a low residual concentration of oryzalin and oxyfluorfen at the various growth stages, starting shorty after bud-break. Residual herbicide exposure had more impact on growth and photosynthetic physiology at early growth stages; however, the recovery rate of those plants was also rapid. For my final study, I conducted three-year field research replicating an actual nursery grower practice of recycling nursery water. Six ornamental species were irrigated with recycled water obtained from a nursery bed receiving ten different pesticides. In addition, the efficacy of woodchip bioreactors to reduced pesticides in water was also tested. Results from this study established the possibility of using recycled water to irrigate ornamentals plants such as Hydrangea macrophylla (Let's dance blue jangles), Hydrangea paniculata (Limelight), Thuja occidentalis (American Pillar), Juniperus horizontalis (Blue rug), Hydrangea arborescens (Invincibelle Spirit II®) and Rosa sp. (Oso Easy Double Red®) without impacting the growth and physiology of those plants. Woodchips bioreactor was also found to be effective in remediating pesticides from water. The results of three greenhouse studies and a field study together provide new information on reducing the concentration of nutrients and pesticides in nursery runoff water and demonstrate the possibility of recycling nursery runoff. The findings of this dissertation are vital in solving the emerging problem of agrochemical pollution and water scarcity that is currently faced by nursery growers.
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Title: Reaction-based knock predictive modeling and model-based stochastic knock limit control of spark-ignition engines
Creator: Li, Ruixue
Date: 2020
Collection: Electronic Theses & Dissertations
Description: This dissertation studies the spark-ignition (SI) engine knock phenomenon, abnormal combustion due to the auto-ignition of end-gas ahead of the propagated flame front, resulting in the rapid chemical energy release with aggressive combustion, limiting the further improvement of thermal efficiency and even damaging the engine mechanically. A control-oriented combustion and pressure wave model with satisfactory accuracy and low computational effort is a necessity for the knock control strategy...
Show moreThis dissertation studies the spark-ignition (SI) engine knock phenomenon, abnormal combustion due to the auto-ignition of end-gas ahead of the propagated flame front, resulting in the rapid chemical energy release with aggressive combustion, limiting the further improvement of thermal efficiency and even damaging the engine mechanically. A control-oriented combustion and pressure wave model with satisfactory accuracy and low computational effort is a necessity for the knock control strategy design. This dissertation develops a control-oriented knock predictive model that includes a two-zone reaction-based combustion model and a pressure wave model. This knock predictive model is capable of accurately describing the combustion process of a spark-ignited engine and predict the in-cylinder pressure oscillations under knocking combustion in real-time. Based on this model, a feedforward and feedback stochastic knock limit control strategy is developed to reduce the knock cyclic variability and control the knock mean-intensity below a desired up bound while keeping spark timing as close to engine maximum brake torque (MBT) timing as possible. A control-oriented two-zone reaction-based model to accurately describe the combustion process of a SI engine is first developed. Instead of using the conventional pre-determined Wiebe-based combustion model, a two-step chemical reaction model is utilized to predict the combustion process along with important thermodynamic parameters such as the mass-fraction-burned, in-cylinder pressure, temperatures and individual species mass changes in both zones. Sensitivities of model parameters are analyzed during the model calibration process. As a result, one set of calibration parameters are used to predict combustion characteristics over all engine operating conditions studied in this paper, which is the major advantage of the proposed method. Also, the proposed modeling approach is capable of modeling the combustion process for real-time simulations. As the by-product of the model, engine knock can also be predicted based on the Arrhenius integral in the unburned zone, which is valuable for model-based knock control. The proposed combustion model is intensively validated using the experimental data with a peak relative prediction error of 6.2% for the in-cylinder pressure. Based on this validated combustion model, a control-oriented pressure wave model for SI engines is further developed. This model is capable of predicting the in-cylinder pressure oscillations under knocking combustion in real-time and can be used for the model-based knock prediction and control. A pressure wave equation including the knock deadening behavior is proposed, simplified, and used to calculate the pressure perturbations generated by the knocking combustion. The boundary and initial conditions at knock onset are analyzed and the analytic solution of the pressure wave equation is obtained. The model is calibrated and validated over two different engine operating conditions at knock limit. The chemical kinetic-based Arrhenius integral (ARI) and the KI20 are used as the evaluation methods for knock onset and intensity prediction, and the knock frequency is studied with a fast Fourier transform of the filtered in-cylinder pressure oscillations. Especially, the knock characteristics associated with gas mixture properties at intake valve closing is analyzed based on the experimental data and their effect to knock cycle-to-cycle variation is also studied for the proposed model. In addition, this dissertation studies the correlation between in-cylinder mixture temperature at intake valve closing and the engine knock, along with knock cyclic variability based on the knock predictive model. A strong correlation between the intake temperature and knock intensity has been obtained and validated based on the simulation investigation and experiment data obtained at knock limit. Therefore, a model-based feedforward and feedback stochastic knock limit control strategy is developed to reduce the knock cycle-to-cycle variability and maintain the knock mean-intensity within a desired up bound by controlling the spark timing as close to MBT timing as possible. The control performance is validated with the simulation results to show the capability of the model-based feedforward and feedback stochastic knock limit control in significantly reducing the knock cyclic variability and improving the knock intensity distribution for the best fuel economy.
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Title: Women's rights in repetition : nation building, solidarity, and Islam in Zanzibar
Creator: Ott, Jessica Marie
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Women's rights are commonly understood as having emerged out of major women's conferences from the 1970s onward and as aligned with major UN conventions. But contemporary women's rights in Zanzibar reflect a longer history of women's movements on the islesand a greater diversity of influences, including socialist state feminism in the 1960s and the increasing engagement of activists with transnational Islamic feminist network. This dissertation explores historical continuities and...
Show moreWomen's rights are commonly understood as having emerged out of major women's conferences from the 1970s onward and as aligned with major UN conventions. But contemporary women's rights in Zanzibar reflect a longer history of women's movements on the islesand a greater diversity of influences, including socialist state feminism in the 1960s and the increasing engagement of activists with transnational Islamic feminist network. This dissertation explores historical continuities and discontinuities between three women's movements in Zanzibar, beginning with a socialist state feminist movement in the 1960s that presented women as embodying umoja [unity] and as at the front lines of building and developing the nation. Second, in the late 1990s and early 2000s, in the wake of a global human rights and democratization movement, a media-based women's movement emerged on the isles. Women journalists translated transnational women's rights ideas into a Zanzibari cultural context, in the process imbuing them with language and imagery from the socialist past. Third, in the 2010s, Zanzibari women's rights activists engaged with a transnational Islamic feminist network as they sought to reform the archipelago's Islamic kadhi's courts. Representing a departure from UN understandings of women's rights, Zanzibari civil society activists relied most heavily on Islamic feminist arguments in their 2017 kadhi's court reform efforts.In my dissertation, I put forth several arguments related to rights and memory, including an overarching methodological argument that women's rights are best understood from an ethnohistorical approach. In Chapter 1, I argue that Zanzibari women's understanding of rights-which are often imbued with language from the socialist 1960s-are informed by their own political alignments and by memory. Using a case study approach, I argue in Chapter 2 that one woman's appropriation of historical language during a millennial media-based women's movement did not represent her endorsement of the past but rather her efforts to mediate collective memory. I argue throughout my dissertation that anthropological frameworks for understanding human rights should incorporate historical memory as a central analytic concept.In Chapter 3, I transition from relying on archival evidence and a few oral histories to relying on participant observation, interviews, and media sources. I chronicle the efforts of a coalition of Zanzibari women's rights activists to reform the archipelago's Islamic legal system, during which they relied on a transnational Islamic feminist network and to a lesser degree on transnational women's rights conventions. Activists passed some reforms but were unable to convince lawmakers to allow women to serve as kadhis [Islamic judges], which highlights the limits of transnationalism in a local context. Activists plan to harness an increasingly faith-based umoja in their continuing efforts to ensure the right of women to serve as kadhis. Chapter 4 is similarly ethnographic and explores the grassroots social involvements of a non-elite woman from the Tanzanian mainland in a women's madrasa [Islamic studies group] and in a women's vicoba [savings cooperative]. Her negotiations of agency across different social groups are multiple, nonlinear, and often contradictory, which reflects relational understandings of rights and obligations as well as the multiplicity and diversity of Zanzibari communities. It also highlights the continuing resonance of gendered language, ideas, and imagery from the socialist past, even in the midst of a deeply rooted Islamic revival. The future for women in Zanzibar will depend in part on how they negotiate multiple solidarities-that often come with different expectations and obligations in their daily lives.
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Title: Peacekeeping during times of terror : terrorism and UN peacekeeping operations in African civil wars
Creator: Bentley, Thomas William
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Since the end of the Cold War, the frequency of intrastate conflict increased dramatically. Unsurprisingly, the rise of intrastate conflict has been met with an increase in third-party interventions such as those carried out by the United Nations. United Nations (UN) peacekeeping operations have become a common tool the international community employs to manage the devastating consequences of civil war and as a means to facilitate conflict resolution in the midst of armed violence. Despite...
Show moreSince the end of the Cold War, the frequency of intrastate conflict increased dramatically. Unsurprisingly, the rise of intrastate conflict has been met with an increase in third-party interventions such as those carried out by the United Nations. United Nations (UN) peacekeeping operations have become a common tool the international community employs to manage the devastating consequences of civil war and as a means to facilitate conflict resolution in the midst of armed violence. Despite the substantial increase in UN deployments and the propensity to use peacekeeping as a tool for conflict resolution, evidence remains mixed as to whether or not the UN's is effective in reducing hostilities and ending active armed conflict.Extant studies have found that peacekeeping reduces battlefield violence and civilian victimization during active civil war. These studies suggest that as the number of UN troops increases in size at the monthly level, there is an associated decrease in violence. However, peacekeepers are increasingly put on the frontlines against rebel groups that frequently use terrorism as a tactic. This dissertation provides the first empirical examination of UN peacekeeping and terrorism during civil war. I analyze how the number of UN peacekeeping personnel deployed to civil war influences the use of terrorism in all civil wars in Africa from 1992 to 2011. The results find an associated increase in terrorism when UN military peacekeepers deploy. This relationship is robust even when examining across different units of analysis and under various modeling specifications and techniques. Given this finding, this dissertation also examines in greater depth the target preferences of rebel groups and the tactical diversity in which rebel groups pursue given the presence of 'blue helmets.' I broadly find that attacks against hard and soft targets increase as the number of UN troops increase in African civil wars. However, I find that rebel groups are less likely to focus on these targets as the number of UN police increases during civil war - perhaps a silver lining to UN missions. Moreover, rebel groups respond to peacekeeping operations by diversifying their tactics in response to increase pressures incurred by UN military troop deployments. The more comprehensive array of tactics enables armed actors to undercut peacekeeping operations since UN peacekeeping operations are primarily defensive in nature, and thus limited in ways in which the mission can successfully defend areas and respond to increasing and diverse threats. While the majority of this dissertation examines peacekeeping at the macro-level of analysis, the final chapter examines at the sub-national level the relationship between UN peacekeeping operations and terrorism. The results substantiate the main finding in the previous chapters that increases in UN peacekeeping forces leads to an increase in terror attacks. However, sheds greater light to the notion that rebel groups exhibit variation in their target preferences as the number of UN peacekeepers increase in size. Optimistically, when considering the consolidated effect of local peacekeeping, that is the number of neighboring troops in proximity to a given location, there is a reduction in the frequency of attacks against 'soft targets.' However, when examining the number of UN troops in a given space-time, non-state actors increase attacks against 'hard targets.' Collectively, these findings provide greater understanding to ways in which the UN can improve current and future missions and equally underscores an important policy implication that has been met with friction - is counterterrorism a bridge to far for UN peacekeeping operations.
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Title: Empowered or entitled to lead? : an evolutionary psychological perspective of how managers navigate structural empowerment
Creator: Lee, Hun Whee
Date: 2020
Collection: Electronic Theses & Dissertations
Description: With the recognition that traditional bureaucratic structures are less likely to respond effectively to volatile and complex business environments, the movement toward structural empowerment has been touted as one of the most significant changes in modern organizations. However, research to date has advanced opposing viewpoints on whether or not structural empowerment will psychologically empower managers and enhance group functioning. The aim of my dissertation is to provide a more nuanced...
Show moreWith the recognition that traditional bureaucratic structures are less likely to respond effectively to volatile and complex business environments, the movement toward structural empowerment has been touted as one of the most significant changes in modern organizations. However, research to date has advanced opposing viewpoints on whether or not structural empowerment will psychologically empower managers and enhance group functioning. The aim of my dissertation is to provide a more nuanced view of the downstream consequences of how managers navigate structural empowerment through the lens of evolutionary psychology. I developed a comprehensive model of how evolved motives for social influence--prestige and dominance--and situational constraints--resource scarcity and outcome interdependence--guide managers' cognition and behavior in the context of structural empowerment. To test my arguments, I utilized experimental (Study 1) and field survey (Study 2) methodologies. My dissertation contributes to the literature in three important ways: 1) I complement the predominant focus on the link between structural empowerment and psychological empowerment by providing accounts for an unintended consequence of structural empowerment, namely entitled managers; 2) my focus on managers' external resource acquisition and sharing as outcomes of structural empowerment expands conceptual boundaries of the role of leadership in the literature; and 3) my dissertation provides an example of how insights from evolutionary psychology can be leveraged to gain a better understanding of why managers do what they do within contemporary organizational structures.
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Title: Immunomodulation by small molecules for prevention or treatment of cancer
Creator: Zhang, Di (Graduate of Michigan State University)
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Cancer is the second leading cause of deaths worldwide. Lung cancer and breast cancer, specifically, are two of the most common cancers in the U.S. except skin cancer. With the increasing medical and economic burden of these diseases, developing effective cancer prevention and treatment strategies is important and urgent. Cancer is characterized by uncontrolled cell proliferation. Targeting the tumor cells directly to inhibit their growth and increase cell death has been the major focus of...
Show moreCancer is the second leading cause of deaths worldwide. Lung cancer and breast cancer, specifically, are two of the most common cancers in the U.S. except skin cancer. With the increasing medical and economic burden of these diseases, developing effective cancer prevention and treatment strategies is important and urgent. Cancer is characterized by uncontrolled cell proliferation. Targeting the tumor cells directly to inhibit their growth and increase cell death has been the major focus of cancer treatment since the last century. Cancer is also described as a wound that does not heal. Inflammation plays critical roles in cancer development and progression. The immune system is a powerful host defense mechanism against infections and diseases including cancer. However, tumor cells are able to edit and suppress the immune system to evade the immune attack. Targeting immune cells to unleash the power of immune surveillance has become a research priority. The recent breakthroughs in cancer immunotherapy have revolutionized the landscape of cancer treatment. As immunotherapy becomes the first line of therapy in cancer treatment, it is essential to understand how other drugs modulate the immune system, so that we can deliver more effective and less toxic combinations. In this thesis project, I focused on four therapeutic targets (bromodomain proteins, retinoid X receptors, Nrf2 transcription factors, poly (ADP-ribose) polymerase) and explored their effects on the immune cells. Small molecules targeting these proteins were tested in various preclinical mouse models in the context of either cancer prevention or treatment. My studies not only demonstrated enhanced efficacy and reduced toxicity with all four classes of compounds but also provided some novel insights into the immunomodulatory effects of these clinically relevant signaling pathways. This work is highly translational and could have direct impact on human patients.
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Title: Searching for kinetic control of excited-state evolution in Fe(II) polypyridyl chromophores
Creator: Adelman, Sara Linnae
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Iron(II) polypyridyl chromophores represent an earth-abundant alternative to ruthenium-based complexes in photo-induced electron transfer applications, yet the sub-150 fs metal-to-ligand charge transfer (MLCT) excited-state lifetime endemic to low-spin Fe(II) polypyridyls has hampered their widespread use. One promising avenue towards achieving a longer-lived MLCT excited-state lifetime is through the exertion of kinetic control, made possible through the identification and subsequent...
Show moreIron(II) polypyridyl chromophores represent an earth-abundant alternative to ruthenium-based complexes in photo-induced electron transfer applications, yet the sub-150 fs metal-to-ligand charge transfer (MLCT) excited-state lifetime endemic to low-spin Fe(II) polypyridyls has hampered their widespread use. One promising avenue towards achieving a longer-lived MLCT excited-state lifetime is through the exertion of kinetic control, made possible through the identification and subsequent disruption of the nuclear coordinate of excited-state deactivation. With this aim, a series of structurally similar iron(II) polypyridyl complexes spanning from low-spin to high-spin, including a spin crossover complex, were synthesized, which allowed for the determination of reorganization energy from the lowest-energy excited state (5T2) to the ground state (1A1) through a combination of variable temperature transient absorption and magnetic susceptibility measurements. In addition to experimentally determining the reorganization energy and electronic coupling constant associated with this conversion, we will deduce the kinetically competent degree of freedom associated with this transition through a convergence of analyses from semi-classical to fully quantum mechanical non-radiative decay theories. A ruthenium(II)-based analog of the spin crossover complex provided insight into the geometric distortions coupled to the deactivation of the MLCT excited states. Coupled together, these results offered new guidelines for ligand design, inspiring the synthesis of new iron(II) complexes with unique photophysical dynamics and establishing new roadmaps towards controlling excited-state dynamics in this class of compounds.
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Title: Measurement of the charged current muon neutrino differential cross section on scintillator with zero pions in the final state with the T2K on/off-axis near detectors
Creator: Cudd, Andrew Bruce
Date: 2020
Collection: Electronic Theses & Dissertations
Description: The Tokai to Kamioka (T2K) is a long-baseline neutrino oscillation experiment in Japan producing precise measurements of neutrino oscillations and neutrino interactions with nuclear targets. T2K utilizes a muon (anti-)neutrino beam produced at the J-PARC proton accelerator facility which is measured at a suite of near detectors, ND280 and INGRID, and the far detector, Super-Kamiokande. One of the dominant systematic uncertainties for the oscillation analysis is from the uncertainty in...
Show moreThe Tokai to Kamioka (T2K) is a long-baseline neutrino oscillation experiment in Japan producing precise measurements of neutrino oscillations and neutrino interactions with nuclear targets. T2K utilizes a muon (anti-)neutrino beam produced at the J-PARC proton accelerator facility which is measured at a suite of near detectors, ND280 and INGRID, and the far detector, Super-Kamiokande. One of the dominant systematic uncertainties for the oscillation analysis is from the uncertainty in neutrino interaction modeling with complex nuclei, which will eventually become the limiting uncertainty for the next generation of neutrino oscillation experiments. Therefore measurements of neutrino cross sections on nuclear targets is essential for understanding how to model these complicated nuclear interactions. This thesis presents a novel neutrino cross section measurement utilizing both of the T2K near detectors, ND280 and INGRID, in a joint statistical fit. Because the T2K near detectors are exposed to neutrinos from the same beamline, the uncertainties in the neutrino flux prediction will be correlated. This fact combined with the different neutrino energy spectra seen at each detector will allow for some separation of flux and cross section effects, and presents an opportunity to study the neutrino cross section as a function of energy using the same neutrino beam. This analysis is the first cross section measurement on T2K to use samples from multiple detectors in the same beamline. This thesis presents a description of the statistical analysis framework, the event selection, the treatment of systematic uncertainties, and the extracted muon neutrino CC0pi double differential cross section in bins of muon kinematics for ND280 and INGRID, including the correlations between the detectors.
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Title: Online innovization : towards knowledge discovery and achieving faster convergence in multi-objective optimization
Creator: Gaur, Abhinav
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Ì0300nnovization'' is a task of learning common principles thatexist among some or all of the Pareto-optimal solutions in amulti-objective optimization problem. Except a few earlierstudies, most innovization related studies were performed onthe final non-dominated solutions found by an evolutionary multi-objective algorithm eithermanually or by using a machine learning method.Recent studies have shown that these principles can be learnedduring intermediate iterations of an optimization run...
Show moreÌ0300nnovization'' is a task of learning common principles thatexist among some or all of the Pareto-optimal solutions in amulti-objective optimization problem. Except a few earlierstudies, most innovization related studies were performed onthe final non-dominated solutions found by an evolutionary multi-objective algorithm eithermanually or by using a machine learning method.Recent studies have shown that these principles can be learnedduring intermediate iterations of an optimization run and simultaneously utilized in thesame optimization run to repair variables to achieve a fasterconvergence to the Pareto-optimal set. This is what we are calling as ò0300nline innovization'' as it is performed online during the run of an evolutionary multi-objective optimization algorithm. Special attention is paid to learning rules that are easier to interpret, such as short algebraic expressions, instead of complex decision trees or kernel based black box rules.We begin by showing how to learn fixed form rules that are encountered frequently in multi-objective optimization problems. We also show how can we learn free form rules, that are linear combination of non-linear terms, using a custom genetic programming algorithm. We show how can we use the concept of k0300nee' in PO set of solutions along with a custom dimensional penalty calculator to discard rules that may be overly complex, or inaccurate or just dimensionally incorrect. The results of rules learned using this custom genetic programming algorithm show that it is beneficial to let evolution learn the structure of rules while the constituent weights should be learned using some classical learning algorithm such as linear regression or linear support vector machines. When the rules are implicit functions of the problem variables, we use a computationally inexpensive way of repairing the variables by turning the problem of repairing the variable into a single variable golden section search.We show the proof of concept on test problems by learning fixed form rules among variables of the problem, which we then use during the same optimization run to repair variables. Different principleslearned during an optimization run can involve differentnumber of variables and/or variables that arecommon among a number of principles. Moreover, a preferenceorder for repairing variables may play an important role forproper convergence. Thus, when multiple principles exist, itis important to use a strategy that is most beneficial forrepairing evolving population of solutions.The above methods are applied to a mix of test problems and engineering design problems. The results are encouraging and strongly supportsthe use of innovization task in enhancing the convergence of an evolutionary multi-objective optimization algorithms. Moreover, the custom genetic program developed in this work can be a useful machine learning tool for practitioners to learn human interpretable rules in the form of algebraic expressions.
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Title: "My life is changed but the trust ain't there to trust somebody else" : experiences of recovery from intimate partner abuse of women of Mexican heritage in a mid-size city in Michigan
Creator: Palma-Ramirez, Evangelina
Date: 2020
Collection: Electronic Theses & Dissertations
Description: This exploratory qualitative study aimed to gain an understanding of the experiences of recovery from intimate partner abuse (IPA) of 17 women of Mexican heritage in a mid-size urban city in Michigan. IPA was defined as any type of physical, sexual, stalking, psychological harm or coercive control by a former intimate partner or spouse. Two aspects were explored: experiences of abuse and experiences of recovery from abuse. The study used a feminist theory and intersectionality perspective as...
Show moreThis exploratory qualitative study aimed to gain an understanding of the experiences of recovery from intimate partner abuse (IPA) of 17 women of Mexican heritage in a mid-size urban city in Michigan. IPA was defined as any type of physical, sexual, stalking, psychological harm or coercive control by a former intimate partner or spouse. Two aspects were explored: experiences of abuse and experiences of recovery from abuse. The study used a feminist theory and intersectionality perspective as a guiding framework to understand the experiences of women considering their contextual situation. Data were collected using a semi-structured questionnaire and analyzed using a constructivist grounded theory by Charmaz. The findings revealed that women understand their experiences of abuse as being connected to their early socialization about gender roles, history of child abuse, lack of sexual education, and the influence of the environment. Also, the participants revealed they experienced overlapping types of abuse: psychological, coercion, economic, physical, sexual, and stalking. Despite the negative impact of the abuse on participants' physical and mental health, findings showed that women were able to recover from the abuse and to move on with their lives. Data suggested that the recovery was a gradual ongoing process of physical and psychological healing. Participants identified empowering experiences that helped them in their recovery from IPA. Such empowering experiences included life-changing religious realizations, receiving services in Spanish, acquiring more education, receiving counseling services, and getting a job. Receiving social support from family and friends and having access to resources were identified as factors that aided in the recovery from IPA. However, some participants experienced limited access to such resources due to economic constraints, cultural beliefs about gender roles, and the impact of immigration policies.Lastly, findings revealed that experiences of recovery from IPA vary based on whether women decided to leave their partners or to remain with them. Implications for culturally sensitive interventions for Latinas of Mexican heritage are discussed as well as implications for future research on issues of recovery for this specific Latino subgroup.
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Title: Transmission timing modulation for information coding in energy-constrained wireless networks
Creator: Feng, Dezhi
Date: 2020
Collection: Electronic Theses & Dissertations
Description: The objective of this thesis is to develop a framework of transmission timing-based modulation framework for improving energy efficiency, security, and information transfer capacity in embedded wireless networks with very thin energy budgets. The key idea is to modulate both intra-PDU (Protocol Data Unit) and inter-PDU timing for addressing energy, security, and information transfer capacity in wireless embedded networks. As for energy efficiency, we developed a novel pulse position-coded PDU...
Show moreThe objective of this thesis is to develop a framework of transmission timing-based modulation framework for improving energy efficiency, security, and information transfer capacity in embedded wireless networks with very thin energy budgets. The key idea is to modulate both intra-PDU (Protocol Data Unit) and inter-PDU timing for addressing energy, security, and information transfer capacity in wireless embedded networks. As for energy efficiency, we developed a novel pulse position-coded PDU (PPCP) paradigm. The core idea is to encode a protocol data unit (PDU) in terms of the silence duration between two sets of delimiter pulses, whose positions are modulated based on the value of the PDU. This PPCP architecture achieves significant energy savings by using a lesser amount of bit/pulse transmissions, and by eliminating long multi-bit preambles and headers, which are normally used in traditional packets. The proposed multi-access pulse-based PDU scheme enables medium sharing among many sensor nodes without requiring per-PDU frame synchronization. As for security, we developed the concept of a novel chaotic pulse position coded protocol data unit (CPPCP) for secure embedded networking. The core idea of CPPCP is to encode a protocol data unit (PDU) with a wideband pulse train with chaotically-varied inter-pulse intervals. The architecture ensures communication security by introducing randomness between data symbols, noise-like frequency spectrum, and significant energy savings by using a smaller number of pulse transmissions compared to existing secure coding schemes such as Bluetooth Low Energy (BLE). Compared with the traditional key-based cryptographic techniques, CPPCP suppresses decipherable information by eliminating symbol periodicity. The mechanism can also be piggy-backed on traditional cryptography solutions to achieve higher levels of security. Finally, for enhancing the information transfer capacity, we developed a data packet position modulation (DPPM) paradigm. Packet transmissions in low duty cycle networks are often scheduled as TDMA slots, whose periodicity is determined based on application sampling requirements and the energy in-flow, often in the form of energy harvesting. The key idea of DPPM is to modulate the inter-packet spacing for coding additional information without incurring additional transmission energy expenditures. We first developed a have a DPPM based networking solution for single-hop transmit-only networks in which a number of low-energy nodes transmit data to an aggregator. The architecture is developed for a two-node point-to-point link, followed by a multipoint-to-point multi-access network. Detailed analytical and simulation models are developed to demonstrate the performance of a symmetric and an asymmetric version of DPPM.
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Title: Multi-band reconfigurable RFICs in Si-based technologies for a compact and adaptive RF front-end
Creator: Nawaz, Asad Ali
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Recent advances in the wireless communication market have led to the coexistence of several networks such as cellular network, personal area network (PAN), wireless local area network (WLAN), etc. along with several different air interfaces (802.11a, 802.11g, Bluetooth, wireless code division multiple access (WCDMA), etc.). Thus, all the wireless devices need to be compatible with the different communication standards while still keeping similar performance, smaller die area and lower power...
Show moreRecent advances in the wireless communication market have led to the coexistence of several networks such as cellular network, personal area network (PAN), wireless local area network (WLAN), etc. along with several different air interfaces (802.11a, 802.11g, Bluetooth, wireless code division multiple access (WCDMA), etc.). Thus, all the wireless devices need to be compatible with the different communication standards while still keeping similar performance, smaller die area and lower power consumption. The need to enable the "global roaming'' capability between a wide variety of networks operating at different frequencies calls for the development of reconfigurable radio-frequency integrated circuits (RFICs) which can achieve maximum hardware sharing between different standards and across various functions. The objective of this dissertation is to present novel topologies for RF components and blocks that can yield a Si-based frequency-agile RF front-end. The targeted applications for this work are 5G multi-band wireless communication and reconfigurable short/long range phased arrays for automobile radars. However, the concept of the proposed reconfigurable RF elements is generic in nature and can be applied to all emerging applications which require on-chip reconfigurability at microwave and mm-wave frequencies.To demonstrate the concept of a reconfigurable RF front end, a Ka/V band-switchable TRX amplifier is developed in 0.13um BiCMOS SiGe process and a 18-50 GHz receiver is developed in 45nm SOI CMOS process. Unlike the traditional approach for a multi-band radio - where the dedicated single band transceivers composed of fixed RF components are designed and multiplexed with the help of switches - the proposed idea utilizes the switches inside each RF block; thus, adding the reconfigurability inside each block and eliminating the need for separate front-ends. However, the catch in the latter approach is to maintain the RF performance while still being able to save the real estate and power consumption. The proposed Ka/V band-switchable TRX amplifier consists of a band-switchable LNA, a band-switchable PA, and integrated T/R switches which saves a lot of area. The band-switch functionality is realized using thin-film microstrip based shunt stubs with reverse saturated SiGe switches. Design techniques for switch loss reduction and size miniaturizations are presented. This work illustrates that with the optimization of switch loss, appropriate selection of each block between wideband or bandswitching topology and co-design of RF blocks, a highly integrated multi-band transceiver can be designed with the minimal degradation to the RF performance compared to state-of-the-art dedicated single band transceivers. To further explore reconfigurable transceivers, a direct quadrature down-conversion mixer first receiver with active channel select filters has been designed. The receiver supports 200MHz instantaneous RF bandwidth and can be reconfigured to receive any 200 MHz channel within 18-50 GHz frequency range. With the ever-evolving wireless standards like 4G/5G/6G, equipment manufacturers are required to add more functionality into the chips while still maintaining the backward compatibility with previous standards or fallback option to lower frequency bands. A low power, highly integrated, multi-band and multi-standard chipset has thus become a requisite in commercial products. The proposed concept of in-block reconfigurability and the presented design techniques to realize mm-wave frequency reconfigurable transceivers have a huge potential in this regard.
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Title: Use of administative claims data to design and emulate a clinical trial in acute stroke patients comparing rehabilitation at inpatient rehabilitation facilities to skilled nursing facilities
Creator: Simmonds, Kent P.
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Stroke affects nearly 800,000 people every year in the United States and is a leading cause of adult disability. After hospitalization half of stroke patients continue to require medical and rehabilitation services provided at inpatient rehabilitation facilities (IRFs) or skilled nursing facilities (SNFs). In general, IRFs provide time-intensive therapy for two to three weeks, while SNFs provide moderately intensive therapy for four- to five-weeks. There is substantial variation in the...
Show moreStroke affects nearly 800,000 people every year in the United States and is a leading cause of adult disability. After hospitalization half of stroke patients continue to require medical and rehabilitation services provided at inpatient rehabilitation facilities (IRFs) or skilled nursing facilities (SNFs). In general, IRFs provide time-intensive therapy for two to three weeks, while SNFs provide moderately intensive therapy for four- to five-weeks. There is substantial variation in the utilization of these alternative rehabilitation settings, but their relative comparative effectiveness remains uncertain. A randomized controlled trial (RCT) would provide an unbiased comparative effectiveness estimate, but the design of such a trial is complicated by several practical and ethical issues. The overarching purpose of this dissertation was to use Medicare claims data to inform the design and to emulate such a trial. In the first aim, we sought to identify patient and hospital level factors that were associated with IRF or SNF discharge and characterize the heterogeneity of hospital effects that influenced discharge to an IRF (vs. SNF). From a retrospective cohort of 145,894 stroke patients, we used multi-level multivariable models to identify several patient- and hospital- level factors that were independently associated with discharge setting. We also showed that hospitals contributed around a third of the variation in IRF (vs. SNF) discharge, but there was substantial variation in the effect that specific hospitals had on influencing IRF discharge. The second aim, was to identify a target trial population that optimized the explanatory-pragmatic balance of a subsequent RCT. To identify this population, we profiled hospitals based on their propensity to discharge stroke patients to IRFs (vs. SNFs) and inferred IRF and SNF referral networks for each hospital. The final target trial population included 44,950 patients (30.8% of the starting sample) who were treated at 441 hospitals (14.5%) and subsequently discharged to 745 IRFs (64.8%) and 5,974 SNFs (48.2%).The third aim was to emulate three alternate RCTs that compared patient outcomes at IRFs vs. SNFs. Trial #1 used the target trial population identified in Aim 2, while trials #2 and 3 excluded increasingly infrequently used IRFs and SNFs. Comparative effectiveness was estimated using a matched propensity score analysis. Overall, on a relative basis, patients treated at IRFs were between 18-35% more likely to be successfully discharged home (i.e., alive and at home for >30 days) and were between 11-15% less likely to die within one year of acute care discharge. The variation in the effect size estimates across the trials was driven by poorer outcomes among patients treated at infrequently used SNFs. Finally, we identified that a moderate sized unmeasured confounder would nullify the observed differences.In conclusion, we identified that referring hospitals are a major driver of IRF or SNF use, and that patients treated at IRFs had better outcomes (relative to SNF patients). However, our results were limited by the inability to adjust for potentially important unmeasured confounders. A pragmatic RCT would eliminate such biases and provide a more valid comparative effectiveness estimate of these two alternative rehabilitation settings.
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Title: Understanding free-carrier accumulation in semiconductor nanomaterials : plasmonic behavior, charge storage energetics, and quantum confinement resilience of colloidal indium nitride nanocrystals
Creator: Liu, Zhihui
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Heavily doped semiconductor nanocrystals (NCs) are promising materials that can reversibly and substantially store electrical charges. Indium nitride (InN) is a particularly interesting semiconductor material for studying charge storage processes. Colloidal InN NCs are spontaneously degenerately doped with carrier densities large enough to lead to strong localized surface plasmon resonances (LSPR) in the infrared (IR) part of the spectrum. Unfortunately, many fundamental quantities that...
Show moreHeavily doped semiconductor nanocrystals (NCs) are promising materials that can reversibly and substantially store electrical charges. Indium nitride (InN) is a particularly interesting semiconductor material for studying charge storage processes. Colloidal InN NCs are spontaneously degenerately doped with carrier densities large enough to lead to strong localized surface plasmon resonances (LSPR) in the infrared (IR) part of the spectrum. Unfortunately, many fundamental quantities that ultimately control the behavior of colloidal InN NCs are currently unknown. In this thesis, we focused on advancing our current understanding of the properties of colloidal InN NCs, with special emphasis on the quantification of free electron density, the LSPR behavior, the charge storage ability, the screening effect on phonon behaviors and few other important fundamental quantities such as the electron effective mass, Fermi level, conduction band (CB) edge potential and IR transition oscillator strength.To understand the LSPR behavior of InN NCs, we first evaluated the free carrier density with a direct, model-independent quantification. We found that the number of free electrons per as-prepared InN NC is directly proportional to the NC volume, such that the free electron density is a size-independent quantity. Furthermore, we demonstrated that free electrons in InN NCs can be reversibly extracted with redox species, which leads to a direct way to manipulate the LSPR. Importantly, the LSPR energy in InN NCs barely shifts with free electron density, a behavior strikingly at odds with what is typically observed in other semiconductor plasmonic systems. These unusual plasmonic signatures are shown to arise from the nonparabolicity of the CB dispersion, which leads to a change in the electron effective mass with the number of free electrons per NC, thus mitigating the shift of LSPR in InN NCs.Consequently, we estimated the charge storage capability of InN NCs by pinning the chemical potential of InN NCs to redox-active molecular species. These studies directly yielded precise information on the Fermi level and on the chemical capacitance of InN NCs, which allowed the CB edge potential of InN NCs to be quantitatively determined for the first time. Surprisingly, the CB edge in InN NCs hardly showed any sign of quantum confinement effects, even for NCs sizes that were clearly smaller than the excitonic Bohr radius of InN. This "resilience to quantum confinement" effect was shown to also arise from the same nonparabolic dispersion effects described above.In addition, the light harvesting ability of free electrons in InN NCs was evaluated by calculating the molar absorptivity per free electron. This value directly yielded the optical oscillator strength of LSPR. We found that optical oscillator strength (per free electron) is independent of NC.Finally, the effects of free electrons on lattice vibrations were also explored. We demonstrated that free electrons weakened the A1(LO) phonon mode by screening the Coulombic restoring force induced by the lattice distortion. The A1(LO) mode frequency red-shifted linearly with the increasing free electron density. This relationship provided a fast way to estimate free electron density of InN NCs by measuring Raman spectroscopy.
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Title: Developmental plasticity : early life environment, DNA methylation, and later life phenotype in spotted hyenas
Creator: Laubach, Zachary M.
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Animals, including humans, vary in their phenotypes. While this phenomenon is partially explained by genotype, an organism's environment (and its experiences within a given environment) also contributes to trait variability. Of particular relevance to my dissertation is the notion of developmental plasticity, or variability in an organism's phenotype due to specific environmental exposures experienced across ontogeny. In my dissertation, I discuss theory (Chapter 2) and test empirical...
Show moreAnimals, including humans, vary in their phenotypes. While this phenomenon is partially explained by genotype, an organism's environment (and its experiences within a given environment) also contributes to trait variability. Of particular relevance to my dissertation is the notion of developmental plasticity, or variability in an organism's phenotype due to specific environmental exposures experienced across ontogeny. In my dissertation, I discuss theory (Chapter 2) and test empirical hypotheses (Chapters 3-5) regarding the role of developmental plasticity via DNA methylation in the relationship between early life environment and adult phenotype. Leveraging a wild population of spotted hyenas in the Masai Mara, Kenya (The Mara Hyena Project), my analytical Chapters 3-5 specifically focus on social and ecological measures of the early life environment in relation to global (via the luminometric assay [LUMA] of %CCGG methylation) and genome-wide DNA methylation (via Enhanced Reduced Representation Bisulfite Sequencing [ERRBS]). I then explore associations of each with adult stress phenotype, as indicated by fecal corticosterone concentrations. In Chapter 3, I detected differences in %CCGG methylation across the hyena genome with respect to both social and ecological factors early in life, suggesting that these characteristics may impact future phenotype through epigenetic modifications like global DNA methylation. In Chapter 4, I found that higher maternal care and greater social connectedness during early life are associated with higher %CCGG methylation and lower fecal corticosterone concentrations during adulthood, both of which are indicators of positive health. Finally, in Chapter 5, I identified differential methylation in CpG sites involved in inflammatory processes that were associated with both early life maternal care and adult fecal corticosterone levels, thereby implicating these sites as possible mediators to the relationship between early life maternal care quality/quantity and future stress phenotype.These findings are an important extension to current understanding of developmental plasticity that stems from rodent models and studies of captive primates. Biomedical models of developmental plasticity often utilize laboratory rodents, which lack the natural social structure and intact life history involved in development of complex and variable phenotypes. Studies of captive primates typically focus on extreme measures of early life social deprivation that do not capture the naturally occurring spectrum of social experiences in wild mammals. In wild spotted hyenas, I was able to test hypotheses surrounding the concept of developmental plasticity in a gregarious mammal with a complex social structure that is also subject to natural selection. Furthermore, use of data and samples from The Mara Hyena Project enabled me to characterize multiple aspects of the early life environment, DNA methylation, and stress phenotypes in the same individuals - a feat rarely accomplished even in well-established human cohort studies.
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Title: Variable selection in high-dimensional setup : a detailed illustration through marketing and MRI data
Creator: Majumder, Atreyee
Date: 2017
Collection: Electronic Theses & Dissertations
Description: In the times of big data and ever growing information, variable selection is an integral part of statistical analysis. With the advancement of technology, we are able to store and access large volumes of data, only part of which is required for inference. Variable selection is a statistical technique that helps us retain valuable information while discarding everything that is non-significant. To understand variable selection, we perform a comparative study of various popular frequentist...
Show moreIn the times of big data and ever growing information, variable selection is an integral part of statistical analysis. With the advancement of technology, we are able to store and access large volumes of data, only part of which is required for inference. Variable selection is a statistical technique that helps us retain valuable information while discarding everything that is non-significant. To understand variable selection, we perform a comparative study of various popular frequentist variable selection techniques. This study analyses the difference of performance of models based on Ridge, LASSO and Elastic Net methods of penalized regression. The comparison of these methods is done for both continuous and binary outcome. We further emphasize the importance of tuning parameter selection in penalized regression models. This is done by comparing 6 different methods of tuning parameter selection for each penalized approach. The best performing method is then chosen to build statistical models for market research data of 4 varied countries. This exercise is an application of variable selection. Here, we showcase the applicability of such models in handling large information efficiently, for managerial decisions. We show how managers can leverage this technique for better resource allocation in their business decisions.Next, we build a model for variable selection in a Bayesian setup. This is motivated by the fact that the frequentist approaches have unstable inference. Here, we analyze Alzheimer's Disease Neuroimaging Initiative (ADNI) with a Bayesian model. This is done by building a Bayesian hierarchical model with multivariate Laplace priors in spike and slab prior style. This model is able to select a group of related variables. The frequentist counterpart of this estimator, group lasso, is also discussed. We build a classification model that is able to select the significant brain regions in Alzheimer's disease with 80\% accuracy. Instead of using standard MAP thresholding, we use posterior median thresholding for variable selection. Furthermore, the consistency of this estimator is also proved.Lastly, we build a Bayesian structured model for variable selection based on magnetic resonance imaging (MRI) data. This model is an extension of the second method but takes into account bi-level selection and spatio-temporal correlation. Voxels in brain regions have spatial correlation and repeated measurements for each voxel which brings in temporal correlation. This model is applied on a simulated functional MRI (fMRI) type data and real data. The real data detects blood oxygenation level dependent (BOLD) activation. The data is large on the account of numerous voxels present in the brain. Our method, successfully, detects the activated brain regions in the presence of a stimuli. Thus, this thesis delves into various scenarios of variable selection with three different real data application studies. The focus is mainly on Bayesian variable selection and the use of hierarchical modeling with iterative sampling from posterior distribution in the group lasso setup. Our application of using group lasso structure to identify brain regions and voxels is an innovative approach in the context of present literature review. All of these methods have practical implication that can be used to solve relevant real world problems.
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Title: Development of structurally defined platforms for long-range biological electron transfer
Creator: Huang, Jingcheng (Graduate of Michigan State University)
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Electron transfer reactions are vital for life: they are the essential steps in all the major biological energy conservation pathways and the rate of electron transfer sometimes determines the fate of energy flow. While the rates of electron transfer over 1-2 nanometers in proteins can largely be described by well-known theories, it is not well understood how these processes scale to microscopic distances, for example, micrometer length microbial nanowires. Electron transfer reactions are...
Show moreElectron transfer reactions are vital for life: they are the essential steps in all the major biological energy conservation pathways and the rate of electron transfer sometimes determines the fate of energy flow. While the rates of electron transfer over 1-2 nanometers in proteins can largely be described by well-known theories, it is not well understood how these processes scale to microscopic distances, for example, micrometer length microbial nanowires. Electron transfer reactions are known to be highly sensitive to the chemical properties of the electron carriers and distances between carriers, yet, this information is not available for naturally occurring microbial nanowires. On the other hand, microbial nanowires have inspired the development of novel biological conductive materials and bioelectronics, although these biomimicking materials would significantly benefit from a higher degree of structural definition, which would greatly improve rational redesign.This dissertation work presents two distinct approaches for arranging electron carriers (heme) into structurally defined arrays that can facilitate electron transfer:1) A crystalline lattice of small tetraheme cytochromes that form a well-defined, three-dimensional network of closely spaced redox centers was used to demonstrate the multi-step electron hopping over a micrometer scale.2) A heme attachment strategy was developed that allows one to introduce redox active cofactor hemes into non-heme-binding proteins, while maintaining the proteins' original function. Adding hemes to a nanotube-forming self-assembling protein was used to demonstrate the potential of this strategy to form a structurally defined heme array.The first crystal approach provides detailed information about structure and electronic states which can be used as a platform for testing theories, while the second heme-attaching approach is an engineering platform that allows researchers to introduce redox properties into other well-studied proteins with minimal effort. These two approaches, from two perspectives, lay the foundation of building structurally defined architectures for the understanding of microbial nanowires and the application of biological long-range electron transfer materials.
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Title: ER stress sensor IRE1-alpha and its implications in progression of hepatocellular carcinoma
Creator: Oak, Amrita
Date: 2019
Collection: Electronic Theses & Dissertations
Description: "The endoplasmic reticulum (ER) is the site for protein folding and maturation. ER stressors, both physiological and pharmacological, can result in activation of the unfolded protein response (UPR). Palmitate, a saturated fatty acid, is one such ER stressor and leads to induction of the UPR. This is primarily through the activation of Inositol Requiring Enzyme-1 (IRE1) leading to splicing of XBP1 mRNA. However, the mechanism of this activation is unclear. With the aid of a bimolecular...
Show more"The endoplasmic reticulum (ER) is the site for protein folding and maturation. ER stressors, both physiological and pharmacological, can result in activation of the unfolded protein response (UPR). Palmitate, a saturated fatty acid, is one such ER stressor and leads to induction of the UPR. This is primarily through the activation of Inositol Requiring Enzyme-1 (IRE1) leading to splicing of XBP1 mRNA. However, the mechanism of this activation is unclear. With the aid of a bimolecular fluorescence complementation (BiFC) assay, we identified two crucial residues on the transmembrane domain (TM) of IRE1, S450 and W457, that are drivers of palmitate mediated activation. Previous research from our group suggested that IRE1 also has binding sites for palmitate on its cytosolic domain (CD). However, IRE1-CD protein expressed in E. coli was over-phosphorylated which possibly affected its binding to PA. To investigate this, we developed a protocol for expression and purification of wild type and mutant IRE1-CD protein in insect Sf21 cells. A fluorescence polarization based binding assay was performed to determine whether palmitate binds to residues on the IRE1-CD protein. Previously our laboratory demonstrated that palmitate induced the migration of cancer cells as well as transcription factors (TF) involved in epithelial-to-mesenchymal transition (EMT). Here, we investigated the role of IRE1 activation on these processes. Using CRISPR gene editing to generate IRE1 knockouts in liver and breast cancer cell lines, we observed that IRE1 mediates the upregulation in EMT-TFs, a decrease in the expression of the desmoplakin (DSP) protein, and an increase in the migration of liver and breast cancer cells. DSP is a critical component of desmosomes, which function to maintain the structural integrity at adjacent cell-cell contacts.In addition to migration, the effect of XBP1 splicing on metabolism has not been studied. We found the activation of IRE1-XBP1 is accompanied by changes in the metabolic genes involved in glycolysis, fatty acid oxidation, gluconeogenesis, and ceramide metabolism, suggesting that some of the metabolic effects of palmitate are mediated through IRE1. These results could have implications on the development of chemotherapeutic strategies. This study paves the way for further investigations into the far-reaching effects of activation of the UPR on cell survival, metabolism, and chemo-tolerance."--Pages ii-iii.
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Title: Interpretable machine learning in plant genomes : studies in modeling and understanding complex biological systems
Creator: Azodi, Christina Brady
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Complex systems are ubiquitous in genetics and genomics. From the regulation of gene expression to the genetic basis of complex traits, we see that complex networks of diverse cellular molecules underpin the natural world. Driven by technological advances, today's researchers have access to large amounts of omics data from diverse species. At the same time, improvements in computer processing and algorithms have produced more powerful computational tools. Taken together, these advances mean...
Show moreComplex systems are ubiquitous in genetics and genomics. From the regulation of gene expression to the genetic basis of complex traits, we see that complex networks of diverse cellular molecules underpin the natural world. Driven by technological advances, today's researchers have access to large amounts of omics data from diverse species. At the same time, improvements in computer processing and algorithms have produced more powerful computational tools. Taken together, these advances mean that those working at the interface of data science and biology are poised to better model and understand complex biological systems. The research in this dissertation demonstrates how a data-driven approach can be used to better understand three complex systems: (1) transcriptional response to single and combined heat and drought stress in Arabidopsis thaliana, (2) the genetic basis of flowering time, a complex trait, in Zea mays, and (3) the social basis for opinions and beliefs about biotechnology products.To study the first system, we generated models of the cis-regulatory code from information about DNA sequence and additional omics levels using both classic machine learning and deep learning algorithms. We identified 1,061 putative cis-regulatory elements associated with different patterns of response to single and combined heat and drought stress and found that information about additional levels of regulation, especially chromatin accessibility and known transcription factor binding, improved our models of the cis-regulatory code. To study the second system, we generated phenotype prediction models for flowering time, height, and yield based on either genetic markers or transcript levels at the seedling stage. We found that, while genetic marker-based models performed better than transcript level-based models, models that integrated both types of data performed best. Furthermore, transcript-based models were more useful for finding genes known to be associated with flowering time, highlighting how using additional levels of omics data can improve our ability to understand the genetic basis of complex traits. Finally, to study the third system, we integrated 29 characteristics about a person (e.g. age, political ideology, education, values, environmental beliefs) into a machine learning model that would predict an individual's beliefs and opinions about five different types of biotechnology products (e.g. biofortification, biopharmaceuticals). While this approach was particularly usefully for identifying individuals that were broadly supportive of biotechnology, finding characteristics of individuals with negative or conditional (i.e. support product A, but not B) opinions was more challenging, highlighting the complexity of public opinions about biotechnology.
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