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Many factors are at play within the genome of an organism, contributing to much of the diversity and variation across the tree of life. While the genome is generally encoded by four nucleotides, A, C, T, and G, this code can be expanded. One particular mechanism that we examine in this thesis is modification of bases—more specifically, methylation of Adenine (m6A) within the GATC motif of Escherichia coli. These methylated adenines are especially important in a process called methyl-directed mismatch repair (MMR), a pathway responsible for repairing errors in the DNA sequence produced by replication. In this pathway, methylated adenines identify the parent strand and direct the repair proteins to correct the erroneous base in the daughter strand. While the primary role of methylated adenines at GATC sites is to direct the MMR pathway, this methylation has also been found to affect other processes, such as gene expression, the activity of transposable elements, and the timing of DNA replication. However, in the absence of MMR, the ability of these other processes to maintain adenine methylation and its targets is unknown.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
ContributorsBoyer, Gwyneth (Author) / Lynch, Michael (Thesis director) / Behringer, Megan (Committee member) / Geiler-Samerotte, Kerry (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Social insect colonies adeptly make consensus decisions that emerge from distributed interactions among colony members. How consensus is accomplished when a split decision requires resolution is poorly understood. I studied colony reunification during emigrations of the crevice-dwelling ant Temnothorax rugatulus. Colonies can choose the most preferred of several alternative nest cavities, but the colony sometimes initially splits between sites and achieves consensus later via secondary emigrations. I explored the decision rules and the individual-level dynamics that govern reunification using artificially split colonies. When monogynous colonies were evenly divided between identical sites, the location of the queen played a decisive role, with 14 of the 16 colonies reuniting at the site that held the queen. This suggests a group-level strategy for minimizing risk to the queen by avoiding unnecessary moves. When the queen was placed in the less preferred of two sites, all 14 colonies that reunited did so at preferred nest, despite having to move the queen. These results show that colonies balance multiple factors when reaching consensus, and that preferences for physical features of environment can outweigh the queen's influence. I also found that tandem recruitment during reunification is overwhelmingly directed from the preferred nest to the other nest. Furthermore, the followers of these tandem runs had a very low probability (5.7%) of also subsequently conducting transports.
ContributorsDoering, Grant Navid (Author) / Pratt, Stephen (Thesis director) / Pavlic, Theodore P. (Committee member) / Sasaki, Takao (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Musical interpretation is challenging when one's goal is to evoke an emotional response from an audience. In order to develop a well-informed interpretation of Mozart's Fantasia in D minor K. 397, a study was conducted on the historical background of the piece and various performances by well-regarded performers. Fantasias are written works, but improvisatory by nature. Mozart's fantasias were influenced by C. P. E. Bach's, which included sudden changes in emotion. An Emil Gilels performance provided a classically trained approach, while Mitsuko Uchida's performance provided an emotional approach. Colin Tilney and John Irving performances elucidated the sound of the instruments that Mozart would have been composing with. Altogether, the research culminated in an interpretation of the D minor Fantasia that endeavored to capture the essence of fantasy, improvisation and emotion.
ContributorsMo, Gina Nan (Author) / Emmery, Laura (Thesis director) / Creviston, Hannah (Committee member) / Department of Psychology (Contributor) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Workplace productivity is a result of many factors, and among them is the setup of the office and its resultant noise level. The conversations and interruptions that come along with converting an office to an open plan can foster innovation and creativity, or they can be distracting and harm the performance of employees. Through simulation, the impact of different types of office noise was studied along with other changing conditions such as number of people in the office. When productivity per person, defined in terms of mood and focus, was measured, it was found that the effect of noise was positive in some scenarios and negative in others. In simulations where employees were performing very similar tasks, noise (and its correlates, such as number of employees), was beneficial. On the other hand, when employees were engaged in a variety of different types of tasks, noise had a negative overall effect. This indicates that workplaces that group their employees by common job functions may be more productive than workplaces where the problems and products that employees are working on are varied throughout the workspace.
ContributorsHall, Mikaela Starrantino (Author) / Pavlic, Theodore P. (Thesis director) / Cooke, Nancy (Committee member) / Industrial, Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Physical inactivity is a major contributor to chronic illnesses and mortality globally. However, most interventions to address it rely on static, aggregate models that overlook idiographic (i.e., individual-level) dynamics, limiting intervention effectiveness. Leveraging mobile technology and control systems engineering principles, this dissertation provides a novel, comprehensive framework for personalized behavioral interventions that have been tested experimentally under the Control Optimization Trial (COT) paradigm. Through careful design of experiments, elaborate signal processing and model estimation, and judicious formulation of behavior intervention optimization as a control system problem, this dissertation develops tools to overcome challenges faced in the large-scale dissemination of mobile health (mHealth) interventions. A novel Three-Degrees-of-Freedom Kalman Filter-based Hybrid Model Predictive Control (3DoF-KF HMPC) controller is formulated for physical activity interventions and evaluated in a clinical trial, demonstrating its effectiveness. Furthermore, this dissertation expands on understanding the underlying dynamics influencing behavior change. Engineering principles are applied to develop a conceptual approach to generate dynamic hypotheses and translate these into first-principle dynamic models. The generated models are used in concert with system identification principles to enhance the design of experiments that yield dynamically informative data sets for behavioral medicine applications. Additionally, sophisticated search, filtering, and model estimation algorithms are applied to optimize and personalize model structures and estimate dynamic models that account for nonlinearities and “Just-in-Time” (JIT; moments of need, receptivity, and opportunity) context in behavior change systems. In addition, the pervasive issue of data missingness in interventions is addressed by integrating system identification principles with a Bayesian inference model-based technique for data imputation. The findings in this dissertation extend beyond physical activity, offering insights for promoting healthy behaviors in other applications, such as smoking cessation and weight management. The integration of control systems engineering in behavioral medicine research, as demonstrated in this dissertation, offers broad impacts by advancing the field's understanding of behavior change dynamics, enhancing accessibility to personalized behavioral health interventions, and improving patient outcomes. This research has the potential to radically improve behavioral interventions, increase affordability and accessibility, inspire interdisciplinary collaboration, and provide behavioral scientists with tools capable of addressing societal challenges in mHealth and preventive medicine.
ContributorsEl Mistiri, Mohamed (Author) / Rivera, Daniel E. (Thesis advisor) / Deng, Shuguang (Committee member) / Muhich, Christopher (Committee member) / Pavlic, Theodore P. (Committee member) / Zhang, Wenlong (Committee member) / Arizona State University (Publisher)
Created2024
Description
Excessive weight gain during pregnancy is a significant public health concern and has been the recent focus of novel, control systems-based interventions. Healthy Mom Zone (HMZ) is an intervention study that aims to develop and validate an individually tailored and intensively adaptive intervention to manage weight gain for overweight or obese pregnant women using control engineering approaches. Motivated by the needs of the HMZ, this dissertation presents how to use system identification and state estimation techniques to assist in dynamical systems modeling and further enhance the performance of the closed-loop control system for interventions.
Underreporting of energy intake (EI) has been found to be an important consideration that interferes with accurate weight control assessment and the effective use of energy balance (EB) models in an intervention setting. To better understand underreporting, a variety of estimation approaches are developed; these include back-calculating energy intake from a closed-form of the EB model, a Kalman-filter based algorithm for recursive estimation from randomly intermittent measurements in real time, and two semi-physical identification approaches that can parameterize the extent of systematic underreporting with global/local modeling techniques. Each approach is analyzed with intervention participant data and demonstrates potential of promoting the success of weight control.
In addition, substantial efforts have been devoted to develop participant-validated models and incorporate into the Hybrid Model Predictive Control (HMPC) framework for closed-loop interventions. System identification analyses from Phase I led to modifications of the measurement protocols for Phase II, from which longer and more informative data sets were collected. Participant-validated models obtained from Phase II data significantly increase predictive ability for individual behaviors and provide reliable open-loop dynamic information for HMPC implementation. The HMPC algorithm that assigns optimized dosages in response to participant real time intervention outcomes relies on a Mixed Logical Dynamical framework which can address the categorical nature of dosage components, and translates sequential decision rules and other clinical considerations into mixed-integer linear constraints. The performance of the HMPC decision algorithm was tested with participant-validated models, with the results indicating that HMPC is superior to "IF-THEN" decision rules.
Underreporting of energy intake (EI) has been found to be an important consideration that interferes with accurate weight control assessment and the effective use of energy balance (EB) models in an intervention setting. To better understand underreporting, a variety of estimation approaches are developed; these include back-calculating energy intake from a closed-form of the EB model, a Kalman-filter based algorithm for recursive estimation from randomly intermittent measurements in real time, and two semi-physical identification approaches that can parameterize the extent of systematic underreporting with global/local modeling techniques. Each approach is analyzed with intervention participant data and demonstrates potential of promoting the success of weight control.
In addition, substantial efforts have been devoted to develop participant-validated models and incorporate into the Hybrid Model Predictive Control (HMPC) framework for closed-loop interventions. System identification analyses from Phase I led to modifications of the measurement protocols for Phase II, from which longer and more informative data sets were collected. Participant-validated models obtained from Phase II data significantly increase predictive ability for individual behaviors and provide reliable open-loop dynamic information for HMPC implementation. The HMPC algorithm that assigns optimized dosages in response to participant real time intervention outcomes relies on a Mixed Logical Dynamical framework which can address the categorical nature of dosage components, and translates sequential decision rules and other clinical considerations into mixed-integer linear constraints. The performance of the HMPC decision algorithm was tested with participant-validated models, with the results indicating that HMPC is superior to "IF-THEN" decision rules.
ContributorsGuo, Penghong (Author) / Rivera, Daniel E. (Thesis advisor) / Peet, Matthew M. (Committee member) / Forzani, Erica (Committee member) / Deng, Shuguang (Committee member) / Pavlic, Theodore P. (Committee member) / Arizona State University (Publisher)
Created2018