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Description
This dissertation treats a number of related problems in control and data analysis of complex networks.

First, in existing linear controllability frameworks, the ability to steer a network from any initiate state toward any desired state is measured by the minimum number of driver nodes. However, the associated optimal control energy

This dissertation treats a number of related problems in control and data analysis of complex networks.

First, in existing linear controllability frameworks, the ability to steer a network from any initiate state toward any desired state is measured by the minimum number of driver nodes. However, the associated optimal control energy can become unbearably large, preventing actual control from being realized. Here I develop a physical controllability framework and propose strategies to turn physically uncontrollable networks into physically controllable ones. I also discover that although full control can be guaranteed by the prevailing structural controllability theory, it is necessary to balance the number of driver nodes and control energy to achieve actual control, and my work provides a framework to address this issue.

Second, in spite of recent progresses in linear controllability, controlling nonlinear dynamical networks remains an outstanding problem. Here I develop an experimentally feasible control framework for nonlinear dynamical networks that exhibit multistability. The control objective is to apply parameter perturbation to drive the system from one attractor to another. I introduce the concept of attractor network and formulate a quantifiable framework: a network is more controllable if the attractor network is more strongly connected. I test the control framework using examples from various models and demonstrate the beneficial role of noise in facilitating control.

Third, I analyze large data sets from a diverse online social networking (OSN) systems and find that the growth dynamics of meme popularity exhibit characteristically different behaviors: linear, “S”-shape and exponential growths. Inspired by cell population growth model in microbial ecology, I construct a base growth model for meme popularity in OSNs. Then I incorporate human interest dynamics into the base model and propose a hybrid model which contains a small number of free parameters. The model successfully predicts the various distinct meme growth dynamics.

At last, I propose a nonlinear dynamics model to characterize the controlling of WNT signaling pathway in the differentiation of neural progenitor cells. The model is able to predict experiment results and shed light on the understanding of WNT regulation mechanisms.
ContributorsWang, Lezhi (Author) / Lai, Ying-Cheng (Thesis advisor) / Wang, Xiao (Thesis advisor) / Papandreoou-Suppappola, Antonia (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2017
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Description
The portability of genetic tools from one organism to another is a cornerstone of synthetic biology. The shared biological language of DNA-to-RNA-to-protein allows for expression of polypeptide chains in phylogenetically distant organisms with little modification. The tools and contexts are diverse, ranging from catalytic RNAs in cell-free systems to bacterial

The portability of genetic tools from one organism to another is a cornerstone of synthetic biology. The shared biological language of DNA-to-RNA-to-protein allows for expression of polypeptide chains in phylogenetically distant organisms with little modification. The tools and contexts are diverse, ranging from catalytic RNAs in cell-free systems to bacterial proteins expressed in human cell lines, yet they exhibit an organizing principle: that genes and proteins may be treated as modular units that can be moved from their native organism to a novel one. However, protein behavior is always unpredictable; drop-in functionality is not guaranteed.

My work characterizes how two different classes of tools behave in new contexts and explores methods to improve their functionality: 1. CRISPR/Cas9 in human cells and 2. quorum sensing networks in Escherichia coli.

1. The genome-editing tool CRISPR/Cas9 has facilitated easily targeted, effective, high throughput genome editing. However, Cas9 is a bacterially derived protein and its behavior in the complex microenvironment of the eukaryotic nucleus is not well understood. Using transgenic human cell lines, I found that gene-silencing heterochromatin impacts Cas9’s ability to bind and cut DNA in a site-specific manner and I investigated ways to improve CRISPR/Cas9 function in heterochromatin.

2. Bacteria use quorum sensing to monitor population density and regulate group behaviors such as virulence, motility, and biofilm formation. Homoserine lactone (HSL) quorum sensing networks are of particular interest to synthetic biologists because they can function as “wires” to connect multiple genetic circuits. However, only four of these networks have been widely implemented in engineered systems. I selected ten quorum sensing networks based on their HSL production profiles and confirmed their functionality in E. coli, significantly expanding the quorum sensing toolset available to synthetic biologists.
ContributorsDaer, René (Author) / Haynes, Karmella (Thesis advisor) / Brafman, David (Committee member) / Nielsen, David (Committee member) / Kiani, Samira (Committee member) / Arizona State University (Publisher)
Created2017
Description
Myocardial infarction (MI) remains the leading cause of mortality and morbidity in the U.S., accounting for nearly 140,000 deaths per year. Heart transplantation and implantation of mechanical assist devices are the options of last resort for intractable heart failure, but these are limited by lack of organ donors and potential

Myocardial infarction (MI) remains the leading cause of mortality and morbidity in the U.S., accounting for nearly 140,000 deaths per year. Heart transplantation and implantation of mechanical assist devices are the options of last resort for intractable heart failure, but these are limited by lack of organ donors and potential surgical complications. In this regard, there is an urgent need for developing new effective therapeutic strategies to induce regeneration and restore the loss contractility of infarcted myocardium. Over the past decades, regenerative medicine has emerged as a promising strategy to develop scaffold-free cell therapies and scaffold-based cardiac patches as potential approaches for MI treatment. Despite the progress, there are still critical shortcomings associated with these approaches regarding low cell retention, lack of global cardiomyocytes (CMs) synchronicity, as well as poor maturation and engraftment of the transplanted cells within the native myocardium. The overarching objective of this dissertation was to develop two classes of nanoengineered cardiac patches and scaffold-free microtissues with superior electrical, structural, and biological characteristics to address the limitations of previously developed tissue models. An integrated strategy, based on micro- and nanoscale technologies, was utilized to fabricate the proposed tissue models using functionalized gold nanomaterials (GNMs). Furthermore, comprehensive mechanistic studies were carried out to assess the influence of conductive GNMs on the electrophysiology and maturity of the engineered cardiac tissues. Specifically, the role of mechanical stiffness and nano-scale topographies of the scaffold, due to the incorporation of GNMs, on cardiac cells phenotype, contractility, and excitability were dissected from the scaffold’s electrical conductivity. In addition, the influence of GNMs on conduction velocity of CMs was investigated in both coupled and uncoupled gap junctions using microelectrode array technology. Overall, the key contributions of this work were to generate new classes of electrically conductive cardiac patches and scaffold-free microtissues and to mechanistically investigate the influence of conductive GNMs on maturation and electrophysiology of the engineered tissues.
ContributorsNavaei, Ali (Author) / Nikkhah, Mehdi (Thesis advisor) / Brafman, David (Committee member) / Migrino, Raymond Q. (Committee member) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Synthetic manipulation of chromatin dynamics has applications for medicine, agriculture, and biotechnology. However, progress in this area requires the identification of design rules for engineering chromatin systems. In this thesis, I discuss research that has elucidated the intrinsic properties of histone binding proteins (HBP), and apply this knowledge to engineer

Synthetic manipulation of chromatin dynamics has applications for medicine, agriculture, and biotechnology. However, progress in this area requires the identification of design rules for engineering chromatin systems. In this thesis, I discuss research that has elucidated the intrinsic properties of histone binding proteins (HBP), and apply this knowledge to engineer novel chromatin binding effectors. Results from the experiments described herein demonstrate that the histone binding domain from chromobox protein homolog 8 (CBX8) is portable and can be customized to alter its endogenous function. First, I developed an assay to identify engineered fusion proteins that bind histone post translational modifications (PTMs) in vitro and regulate genes near the same histone PTMs in living cells. This assay will be useful for assaying the function of synthetic histone PTM-binding actuators and probes. Next, I investigated the activity of a novel, dual histone PTM binding domain regulator called Pc2TF. I characterized Pc2TF in vitro and in cells and show it has enhanced binding and transcriptional activation compared to a single binding domain fusion called Polycomb Transcription Factor (PcTF). These results indicate that valency can be used to tune the activity of synthetic histone-binding transcriptional regulators. Then, I report the delivery of PcTF fused to a cell penetrating peptide (CPP) TAT, called CP-PcTF. I treated 2D U-2 OS bone cancer cells with CP-PcTF, followed by RNA sequencing to identify genes regulated by CP-PcTF. I also showed that 3D spheroids treated with CP-PcTF show delayed growth. This preliminary work demonstrated that an epigenetic effector fused to a CPP can enable entry and regulation of genes in U-2 OS cells through DNA independent interactions. Finally, I described and validated a new screening method that combines the versatility of in vitro transcription and translation (IVTT) expressed protein coupled with the histone tail microarrays. Using Pc2TF as an example, I demonstrated that this assay is capable of determining binding and specificity of a synthetic HBP. I conclude by outlining future work toward engineering HBPs using techniques such as directed evolution and rational design. In conclusion, this work outlines a foundation to engineer and deliver synthetic chromatin effectors.
ContributorsTekel, Stefan (Author) / Haynes, Karmella (Thesis advisor) / Mills, Jeremy (Committee member) / Caplan, Michael (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2019
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Description
This study asks the question: does gender-based discrimination exists within Arizona State University's Army Reserve Officer Training Corps (ROTC), and if so, what are the effects of such discrimination? Within this study, discrimination is defined as: the treatment or consideration of, or making a distinction in favor of or against,

This study asks the question: does gender-based discrimination exists within Arizona State University's Army Reserve Officer Training Corps (ROTC), and if so, what are the effects of such discrimination? Within this study, discrimination is defined as: the treatment or consideration of, or making a distinction in favor of or against, a person or thing based on the group, class, or category to which that person or thing belongs, rather than on individual merit. The researcher predicted that this study would show that gender-based discrimination operates within the masculine military culture of Army ROTC at ASU, resulting from women's hyper-visibility and evidenced by their lack of positive recognition and disbelief in having a voice in the program. These expectations were based on background research claiming that the token status of women in military roles causes them to be more heavily scrutinized, and they consequentially try to attain success by adapting to the masculine military culture by which they are constantly measured. For the purposes of this study, success is defined as: the attainment of wealth, favor, or eminence . This study relies on exploratory interviews and an online survey conducted with male and female Army ROTC cadets of all grade levels at Arizona State University. The interviews and survey collected demographic information and perspectives on individual experiences to establish an understanding of privilege and marginalization within the program. These results do support the prediction that women in Army ROTC at ASU face discrimination based on their unique visibility and lack of positive recognition and voice in the program. Likewise, the survey results indicate that race also has a significant impact on one's experience in Army ROTC, which is discussed later in this study in regard to needs for future research. ASU Army ROTC includes approximately 100 cadets, and approximately 30-40 of those cadets participated in this study. Additionally, the University of Arizona and the Northern Arizona University Army ROTC programs were invited to participate in this study and declined to do so, which would have offered a greater sample population. Nonetheless, the results of this research will be useful for analysis and further discussion of gender-equality in Army ROTC at Arizona State University.
ContributorsAllemang, Lindsey Ann (Author) / Wood, Reed (Thesis director) / Switzer, Heather (Committee member) / School of Politics and Global Studies (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Breast microcalcifications are a potential indicator of cancerous tumors. Current visualization methods are either uncomfortable or impractical. Impedance measurement studies have been performed, but not in a clinical setting due to a low sensitivity and specificity. We are hoping to overcome this challenge with the development of a highly accurate

Breast microcalcifications are a potential indicator of cancerous tumors. Current visualization methods are either uncomfortable or impractical. Impedance measurement studies have been performed, but not in a clinical setting due to a low sensitivity and specificity. We are hoping to overcome this challenge with the development of a highly accurate impedance probe on a biopsy needle. With this technique, microcalcifications and the surrounding tissue could be differentiated in an efficient and comfortable manner than current techniques for biopsy procedures. We have developed and tested a functioning prototype for a biopsy needle using bioimpedance sensors to detect microcalcifications in the human body. In the final prototype a waveform generator sends a sin wave at a relatively low frequency(<1KHz) into the pre-amplifier, which both stabilizes and amplifies the signal. A modified howland bridge is then used to achieve a steady AC current through the electrodes. The voltage difference across the electrodes is then used to calculate the impedance being experienced between the electrodes. In our testing, the microcalcifications we are looking for have a noticeably higher impedance than the surrounding breast tissue, this spike in impedance is used to signal the presence of the calcifications, which are then sampled for examination by radiology.
ContributorsWen, Robert Bobby (Co-author) / Grula, Adam (Co-author) / Vergara, Marvin (Co-author) / Ramkumar, Shreya (Co-author) / Kozicki, Michael (Thesis director) / Ranjani, Kumaran (Committee member) / School of Molecular Sciences (Contributor) / Electrical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Breastfeeding has been shown by a number of studies to have numerous benefits on both the mother and the infant. Major health organizations such as the World Health Organization (WHO), now agree that breastfeeding should be encouraged and supported in all countries. But like many things, the wheels of the

Breastfeeding has been shown by a number of studies to have numerous benefits on both the mother and the infant. Major health organizations such as the World Health Organization (WHO), now agree that breastfeeding should be encouraged and supported in all countries. But like many things, the wheels of the law are slow to catch up with scientific evident. Although breastfeeding is supported, working women do not have the option of breastfeeding without consequences. For example, in 2003, Kirstie Marshall, a then member of parliament in Australia was ejected from the lower house chamber on February 23, for breastfeeding her baby [3]. According to standing order 30 at the time, "Unless by order of the House, no Member of this House shall presume to bring any stranger into any part of the House appropriated to the Members of this House while the House, or a Committee of the whole House, is sitting" [3]. The rules did not specify the age of strangers, so the then 11-day-old baby, Charlotte Louise and her mother were shown the exit door of parliament. She had to choose between being present at times of major discussions or leaving the house to breastfeed her child, she chose to leave. More recent statistics show that developed nations like the US and Australia which also have high rates of women employment had low rates of breastfeeding. This might mean that workplace policies do not favor breastfeeding or expressing milk at work. Fortunately, laws have since been introduced in both the United States and Australia that support breastfeeding at the workplace. The next step would be to access how these laws affect breastfeeding statistics and how variation between these two countries like the paid parental leave in Australia (which is not present in all US states) would affect these numbers.
ContributorsSakala, Lydia (Author) / Alison, Alison (Thesis director) / Reddy, Swapna (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The number of undergraduate students participating in short-term experiences in global health (STEGHs) abroad has increased dramatically in recent years (Eyler 2002, Drain et al. 2007). These experiences, in tandem with classroom learning, are designed to help students master skills related to global health competencies, including cultural humility and sensitivity,

The number of undergraduate students participating in short-term experiences in global health (STEGHs) abroad has increased dramatically in recent years (Eyler 2002, Drain et al. 2007). These experiences, in tandem with classroom learning, are designed to help students master skills related to global health competencies, including cultural humility and sensitivity, collaborating with community partners, and sociocultural and political awareness. Although STEGHs offer potential benefits to both students and to sending institutions, these experiences can sometimes be problematic and raise ethical challenges. As the number of students engaged in STEGHs continues to increase, it is important to better understand the impact of these programs on student learning. Current ethical and best practice guidelines for STEGHs state that programs should establish evaluation methods to solicit feedback from students both during and on completion of the program (Crump et al. 2010). However, there is currently no established method for gathering this feedback because of the many different global health competency frameworks, types and duration of programs, and different models of student engagement in such programs. Assessing the quality of a STEGH is a profoundly important and difficult question that cannot be answered as succinctly and quantitatively as classroom performance, which has more standard and established assessment metrics. The goal of this project is to identify the most appropriate and useful assessment metric(s) for determining educational quality and impact for STEGHs at ASU by comparing a typical quantitative evaluation tool (pre-post survey with brief open-ended questions) to a more in-depth qualitative method (key informant interviews). In performing my analysis I seek to examine if the latter can produce a richer narrative of student experiences to inform ongoing program evaluations. My research questions are: 1. What are the current qualitative and quantitative evaluation methods available to assess student learning during short-term experiences in global health? 2. How can current methodology for assessing student experiences with short-term experiences in global health be adapted to collect the most information from students? 3. How do student knowledge and attitudes change before and after their short-term experience in global health? Why is understanding those changes important for adapting programs? My end goal would be to use these new, optimal assessment methods for gathering student perspectives and experiences to adapt pre-departure trainings and post-experience debriefings for study abroad programs, both of which I believe will lead to more sustainable partnerships and a healthier understanding of global health work for students.
ContributorsHale, Brittany Ann (Author) / Jehn, Megan (Thesis director) / Wutich, Amber (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Genocide studies have traditionally focused on the perpetrator’s intent to eradicate a particular identity-based group, using the Holocaust as their model and point of comparison. Although some aspects of the Holocaust were undoubtedly unique, recent scholars have sought to challenge the notion that it was a singular phenomenon. Instead, they

Genocide studies have traditionally focused on the perpetrator’s intent to eradicate a particular identity-based group, using the Holocaust as their model and point of comparison. Although some aspects of the Holocaust were undoubtedly unique, recent scholars have sought to challenge the notion that it was a singular phenomenon. Instead, they draw attention to a recurring pattern of genocidal events throughout history by shifting the focus from intent to structure. One particular branch of scholars seeks to connect the ideology and tactics of imperialism with certain genocidal events. These anti-imperialist genocide scholars concede that their model cannot account for all genocides, but still claim that it creates meaningful connections between genocides committed by Western colonialist powers and those that have occurred in a neoimperialist world order shaped according to Western interests. The latter includes genocides in postcolonial states, which these scholars believe were shaped by the scars of their colonial past, as well as genocides in which imperial hegemons assisted local perpetrators. Imperialist and former colonial powers have contributed meaningfully to all of these kinds of genocides, yet their contributions have largely been ignored due to their own influence on the creation of the current international order. Incorporating the anti-imperialist perspective into the core doctrine of genocide studies may lead to breakthroughs in areas of related policy and practice, such as prevention and accountability.
ContributorsParker, Ashleigh Mae (Author) / Thies, Cameron (Thesis director) / Sivak, Henry (Committee member) / School of Politics and Global Studies (Contributor) / School of Social Transformation (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Ketone bodies are produced in the liver from the acetyl CoA derived from fatty acids that cannot enter the Krebs cycle. This is a sub-analysis of a larger study which had numerous outcome markers. This analysis focuses on the relationship between ketone blood levels and cognition. The study looked at

Ketone bodies are produced in the liver from the acetyl CoA derived from fatty acids that cannot enter the Krebs cycle. This is a sub-analysis of a larger study which had numerous outcome markers. This analysis focuses on the relationship between ketone blood levels and cognition. The study looked at the relationship between Time Restricted Feeding (TRF), a method of intermittent fasting. TRF is something that can be easily adapted into an individual’s lifestyle and has been shown to have multiple advantages. This 8-week study began with 23 enrolled participants, but due to COVID-19 only 11 participants could be tested for cognition and blood ketone levels after week 4. All participants had similar ranges of weight, height, age, BMI, hip, and waist measurements at baseline. Moreover, these demographic variables were not related to ketone levels or cognition. The data indicate that ketone bodies increased in participants practicing TRF and that the increase in ketone bodies in the blood, specifically β-hydroxybutyrate was strongly correlated to increased cognitive function. This is consistent with theories that elevated ketone levels allowed for early hunter-gather communities and other mammals to survive prolonged periods of nutrient deprivation while keeping high cognitive function.
ContributorsTaha, Basel Mahmoud (Author) / Johnston, Carol (Thesis director) / Karen, Sweazea (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05