• The Leucine-Repeat Rich Receptor-Like Kinases XIP1/CEPR1 and CEPR2 Control Lateral Root Initiation and Elongation in Arabidopsis

      Dimitrov, Ivan D. (The University of Arizona., 2018)
      Roots serve both to anchor plants in the soil, and to help plants acquire water and nutrients. Plants have to optimize the growth of their root system, as roots cost energy to expand and maintain. This is accomplished through short and long distance signaling pathways that connect environmental conditions of the roots and available energy in shoots. XIP1/CEPR1 and CEPR2 are two Leucine-Rich Repeat Receptor-Like Kinase that are important for root growth responses to differing nitrogen levels in the environment. While previous results implicated these two receptors in signaling from roots to shoots, here I have shown that they are part of a short-range pathway within roots that controls lateral root initiation. Furthermore, through the use of genetic tests I have connected a group of physically-interacting proteins to XIP1/CEPR1 and CEPR2-related phenotypes. I have shown that these receptors and interacting proteins play roles in controlling early growth, flowering time, silique maturation, and lateral root initiation, emergence and elongation.
    • The Effect of Cortical Spreading Depression Induced Episodic Headache on Blood-Brain Barrier Structure and Function

      Cottier, Karissa Ellen (The University of Arizona., 2018)
      Previous research has demonstrated that BBB structure and function are altered as a result of various neurological disorders including ischemic stroke, traumatic brain injury, epilepsy, and infections of the brain. Additionally, the BBB has also been shown to alter its function in response to nociception. Despite the strong evidence for BBB alterations in both neurological disorders and pain, there is still debate on whether BBB permeability is altered in episodic headache disorders such as migraine. Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to both headache production and BBB changes. In previous studies examining BBB changes in response to CSD, animals were anesthetized during the study, preventing any behavioral assessments. Additionally, in studies examining CSD induced nociceptive behaviors, BBB permeability was not assessed. Therefore, this work represents the first joint assessment of nociceptive responses and BBB integrity in response to CSD. In these studies, we observed a transient increase in BBB paracellular permeability in the cortex, but not brainstem, in response to KCl induced CSD. Additionally, at corresponding time points, we found that KCl induced CSD reduced periorbital withdrawal thresholds and rearing behavior, indicative of a state of facial mechanical allodynia. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the BBB may partially account for this disparity. In this work, we demonstrated that KCl induced CSD increased the CNS uptake of radiolabeled sumatriptan in both the cortex and the brainstem. We also found that KCl induced CSD increased the expression of the putative sumatriptan transporter Oatp1a4 in the brainstem, which likely underlies the observed increased brainstem permeability to sumatriptan following CSD induction. Repeated CSD events may be harmful long-term. Therefore, we also investigated whether pre-treatment with the migraine prophylactic topiramate could prevent the CSD induced increase in BBB permeability. In these studies a single dose of topiramate was not able to block CSD induced BBB changes; importantly, topiramate and other migraine prophylactic drugs are typically given chronically to reduce the occurrence and severity of attacks. Therefore further studies should be conducted to determine if chronic topiramate treatment has any protective effects on the BBB in this model. Often, changes in BBB permeability are accompanied by decreases in tight junction protein expression, including occludin, claudin-5, and ZO-1. Here, however, we did not observe any changes in expression of either occludin or claudin-5 in response to cortical KCl induced CSD. BBB permeability can also be decreased through changes in TJ protein localization. We observed a change in claudin-5, but not occludin or ZO-1, localization in rats where CSD was induced with cortical KCl injections. This was recapitulated in an in vitro model using bEnd.3 mouse brain endothelial cells. Additionally, treatment of these cells with a CSD cocktail comprised of KCl, ATP, and glutamate with a pH of 6.8 was also able to cause claudin-5 relocalization. Interestingly, potassium influx mechanisms including the Na+/K+ ATPase and Kir6 channels have been implicated in BBB regulation. We found that blockade of these mechanisms with digoxin or AMP-PNP, respectively was able to prevent KCl or CSD cocktail-induced claudin-5 relocalization. Since claudin-5 is the component of the BBB which regulates permeability to ions and small molecules, these changes may represent the BBB’s effort to re-establish membrane ionic equilibrium. Finally, this work addresses sex differences in migraine, particularly as they relate to the BBB. In previous studies, female sex hormones have been shown to facilitate both nociception and CSD production. Here, we found that female rats had a more intense response to cortical KCl induced CSD. Additionally, we demonstrated that the female sex hormone 17-β-estradiol can, on its own, induce nociceptive behaviors in rats. Finally we observed several changes in BBB structure and function related to sex hormones. Consistent with previous studies, we found that ovariectomy increased BBB permeability. When investigating estradiol induced molecular changes at the BBB, we turned our attention to the sodium/hydrogen exchanger NHE1 due to its role in regulating cell excitability, its reported functional regulation by estradiol, and in vitro data implying expression may play a role in triptan uptake. Here, we found that estradiol reduces NHE1 expression in a concentration dependent manner in GPNT rat brain endothelial cells, but not other CNS cell types such as microglia or astrocytes. Additionally, we found that testosterone did not affect its expression. These data suggest that estradiol may control CNS ion balance and excitability due to its regulation of BBB ion exchangers such as NHE1. Together, the results presented herein demonstrate that CSD induces episodic headache-like behaviors that coincide with alterations in BBB structure and function. These changes can be taken advantage of clinically, by dosing drugs at specific times to increase their access to the CNS. On the other hand, episodic headache induced BBB changes may also produce long-term deleterious effects. Therefore, further studies should be conducted to fully elucidate the mechanisms behind headache induced BBB changes so that they may be prevented through appropriate therapeutic interventions.
    • The Streetcar Effect: Capital, Revitalization and the Battle over Gentrification in a Sunbelt City

      Launius, Sarah Anne (The University of Arizona., 2018)
      This dissertation investigates how, after three decades of failed attempts to revitalize Tucson’s downtown, reinvestment increased rapidly amid the Great Recession and the elements that seemed to have coalesced to build momentum. The findings presented herein center on the early stages of contemporary gentrification and redevelopment to expand our analysis of those state actions that create the possibilities for each. As such, this dissertation expands on our understanding of the economic cycles that lead to gentrification by looking specifically at actions fostered by the state that create the possibility for profit in Tucson’s downtown. The political priorities and possibilities envisioned by governments and quasi-governmental agencies shape the scale and content of redevelopment in Tucson’s downtown. Through these three central papers, findings demonstrate that active state intervention in the property market plays a critical role in both producing the conditions for redevelopment and spurring downtown investment. Specifically, public incentives function as gap financing (Appendix A), allowing local developers to gain construction loans in a credit-constrained city. In the case of investment attributed to the streetcar (Appendix B), much of the purported $1 billion in investment is from public coffers to the disadvantage of actual transit riders. Finally, these more contemporary actions are rooted within a long history of property dispossession in the United States, a process supported by the state against racialized peoples – a process that is maintained, in part, through patterns of uneven development that foster redevelopment and displacement (Appendix C). Taken together, these three papers extend the theorization of the so-called entrepreneurial state and the new techniques to channel public investments in a way that drives tax revenues into a pauper-state’s coffers. Yet, these moves are not simply about the state’s role in driving innovative redevelopment schemes. Rather, these papers discuss what’s at stake in urban revanchism as well as, and through, the on-going pathologization of nonwhite land and property.
    • Design of Photonic Network-on-Chip Architectures Using Multilevel Signaling and Link Allocation Pareto-Optimization

      Kao, Tzyy-Juin (The University of Arizona., 2018)
      Parallel computer systems built with multiprocessors have become ubiquitous in all high-performance computing domains. Performance gains due to the parallel processing will come from the proliferation of processing cores, leading to hundreds of cores integrated on a single chip. The Network-on-Chip (NoC) design paradigm overcomes the problems of wire delays and limited communication bandwidth by replacing conventional shared buses with an interconnection network that allows simultaneous communication and thereby increasing system performance. Silicon photonic devices are compatible with standard CMOS technology and use photons instead of electrons to bring light onto a chip. Photonic links feature high data transmission rates and low propagation losses, especially suitable for replacing long-distance wires. In the wavelength-division multiplexing technique, several dozen wavelengths share a waveguide without interference and can be modulated and received individually. Recent advancements in NoC designs have leveraged the benefits of silicon photonics. However, many photonic NoC architectures require 3D-stacking technology and more dies to place the additional photonic devices, resulting in higher manufacturing costs. In this dissertation, we study how to design high-performance NoC architectures using silicon photonics. We propose a compact structure of optical multilevel signaling link (OMLS), high bandwidth OMLS-NoC architectures, and an automated link allocation Pareto-optimization framework. The OMLS link doubles the transmission bandwidth of each waveguide by transmitting data into a 4-ASK signal. It exhibits great potential for improving bandwidth, area, and cost of optical interconnects, and for NOCs in particular. To highlight the potential advantages of OMLS for NoCs, an OMLS implementation approach is proposed to satisfy communication demands of future multicore architectures. Finally, the Pareto- optimization framework utilizes both deterministic and stochastic optimization algorithms to achieve optimal link allocations based on performance objectives, such as latency and power, to generate computer-designed NoC architectures and automate architecture design in the future.
    • Care Coordination for Pediatric Patients at Federally Qualified Health Centers in Arizona

      Chartrand, Hong (The University of Arizona., 2018)
      Childhood chronic diseases have increased dramatically in the past few decades in the United States. Care coordination in patient- or family-centered medical home (PCMH/FCMH) models is one evidence-based strategy to help better manage childhood chronic diseases. Federally qualified health centers (FQHCs) primarily serve uninsured, Medicaid, low-income and/or minority populations, and many incorporate PCMH/FCMH care coordination models. To date, few studies have investigated care coordination understanding by FQHC personnel. Limited studies have examined the levels of care coordination activities in urban versus rural FQHC locations. The effect of FQHC location on care coordination for childhood health conditions has not been well documented in the literature. In an effort to address gaps in information, this study employed a mixed-methods approach to investigate how FQHC personnel understood and practiced care coordination for pediatric patients and identified the relationship between FQHC location and levels of care coordination activities, using an ecological model. The findings suggest that neither the personnel’s occupational title nor the FQHC location is a contributory factor in terms of understanding of care coordination, but FQHC location matters in terms of levels of care coordination activities. Overall, both urban and rural FQHCs tended to provide greater levels of care coordination activities; however, the urban FQHC was more likely to provide greater levels of care coordination activities than the rural FQHC. Limited resources, including medical and non-medical resources, are barriers to the rural FQHC’s providing greater levels of care coordination activities in general, compared to its urban counterpart. In order to improve outcomes associated with care coordination, having a solid working definition of care coordination, taking care of patients’ medical and non-medical needs, building all levels of partnerships, reimbursing care coordination activities and certifying care coordinators should be explored.
    • Oxidative Dearomatization / Diels-Alder Approaches to Maoecrystal V and the Gibberellin Family of Natural Products

      Smith, Brandon Robert (The University of Arizona., 2018)
      Synthetic approaches to the complex natural product maoecrystal V and the gibberellin family of natural products are presented. The two approaches are united by an oxidative dearomatization / intramolecular Diels Alder strategy for the construction of [2.2.2]- bicyclooctenes. Chapter 1 highlights previous synthetic approaches for the synthesis of maoecrystal V and Chapter 2 chronicles my efforts toward a double-Diels-Alder approach toward maoecrystal V. In the course of investigating a hetero-Diels-Alder strategy for construction of maoecrystal V’s tetrahydrofuran ring several fragmentation and rearrangements of the [2.2.2]-bicyclooctene core were encountered. One of these, a novel skeletal rearrangement from [2.2.2] to [3.2.1]-bicyclooctene, was then utilized for entry into the gibberellin family of natural products. Chapter 3 discusses previous syntheses of gibberellins while Chapter 4 details my entry into this family of natural products and further exploration of the novel skeletal rearrangement. Chapter 5 discusses my contributions to the field of bicyclic and tricyclic guanidine synthesis. Finally, Chapter 6 highlights my work related to pharmaceutical drug analysis, focusing on less commonly utilized elemental substitutions.
    • Genomic Insights: Comparative Genomics in the Big Data Age

      Haug-Baltzell, Asher (The University of Arizona., 2018)
      Perhaps the most influential and pivotal discovery in biology was that genomes, the organism- specific DNA transmitted generation-to-generation, are the foundational “code of life” which contain the instructions necessary to form each and every living organism. Today, the rapid advancement of genome sequencing technology is providing scientists in many disciplines with an unprecedented toolkit for deep insights into how this code generates and maintains life on earth. It is upon this technical toolkit – the ability to decode genomic information – which this dissertation is built. This dissertation is not intended to answer a single question, but rather to highlight three original research articles in the field of comparative genomics and provide additional discussion into how they were enabled by a scientific training focused on building computational thinking and skills in addition to learning topical background knowledge. My goal here is multifaceted; primarily, I aim to help advance our scientific understanding of how evolution has shaped modern genomes, but in this process, I hope to also inspire my fellow scientists to more deeply integrate computational thinking into their biological research. The included articles cover a broad range of topics, yet all stem from the unifying question “how can we effectively and efficiently compare genomes against each other, and what can we learn by performing these comparisons?”. Following a narrative introduction discussing the impact of genome sequencing technology on the field of biology and science as a whole (Chapter 1), a series of chapters guide the reader through three original research manuscripts. These manuscripts cover the development of a comparative genomics tool (Chapter 2), the discovery of an interesting aspect of dopamine receptor evolution (Chapter 3), and the dissection of a set of proposed genomic predictors in human disease treatment (Chapter 4). Next, a white paper styled discussion chapter investigates two specific aspects of computational thinking which are especially relevant to scientific researchers, especially in an era defined by “big data” (Chapter 5). The final conclusion (Chapter 6) ties the distinct parts together into a cohesive message, poses some thoughts on the future of genomic research, and discusses some of the ethical implications which stem from our growing knowledge of the genome.
    • Analysis of In-Situ Shear and Normal Forces During Metal Cmp, Electrical Interface States of Sulfur-Passivated Sige Moscaps, and Reaction Kinetics of Pyrite Nanocrystal Purity

      Peckler, Lauren Tiffany (The University of Arizona., 2018)
      The first study presented in this dissertation concerns the synthesis of pyrite (FeS2) nanocrystals (NC). Since 1980s, pyrite has been studied as a potential replacement of silicon as the absorber layer in photovoltaics. The main objective in our study has been to synthesize pyrite NCs in one stage by reacting ferrous chloride with elemental sulfur in oleylamine (OLA) without needing an additional ligand for NC growth. Results show that the synthesized pyrite NCs are cubic and 88 ± 14 nm on each side. NCs are synthesized at 200 °C, with a sulfur to iron precursor ratio of 6, and 1 hour of reaction time in OLA. We establish that the phase purity of the pyrite NCs depends on the sulfur to iron ratio. For near stoichiometric ratios, at least 24 hours of reaction time is required to achieve phase purity. This is remarkable, because, up until this study, literature indicated that there was a threshold to achieving phase purity, specifically at a ratio of 6. The rate-determining step of the synthesis reaction is shown to involve sulfur, as addition of sulfur precursor increases the rate of pyrite formation. We propose a mechanism for pyrite NC formation. FeS, H2S and polysulfides of the form Sn2- form in OLA. The slow step is the reaction between FeS and these molecules. Then, Fe2+S2- is attacked nucleophilically by H2S and Sn2, with S2- converting to S- and the remaining sulfur transferred to form pyrite Fe2+S2-. The second study presented is an investigation into the next generation transistor material, silicon germanium (SiGe). SiGe has better p-type carrier mobility than silicon, and should, theoretically, produce a better performing transistor. One challenge in implementing this material is the unstable native germanium oxides that form on its surface during processing. These oxides are electrical defects. Our goal in this study is to remove all native silicon and germanium oxides, and then passivate the germanium atoms with sulfur to prevent re-oxidation. Capacitors (MOSCAPs) from the passivated starting surface are fabricated to mimic the gate the stack in the transistor. X-ray photoelectron spectroscopy (XPS) is used extensively to monitor surface oxides on the passivated SiGe surface. Capacitance-voltage profiling is employed to monitor electrical defects from the oxides or otherwise on the SiGe surface, and bulk electrical defects within the dielectric layer grown on this surface in the process of making the full capacitor. An alloy of 25% germanium is used for all experiments in the study. Wet passivation of the germanium oxides is accomplished through aqueous solutions (non-acidic and more acidic) of ammonium sulfide. This study finds that, in non-acidic ammonium sulfide solutions, sulfur does not bond with germanium and oxides of both silicon and germanium regrow during the passivation treatments, after successfully being removed through a hydrofluoric acid/hydrochloric acid solution treatment. Acidic aqueous ammonium sulfide solutions result in sulfur bonding with germanium, but oxide regrowth is even more severe. However, any passivation treatment results in a decrease in density of electrical defects, compared to the non-passivated MOSCAPs. Bulk fixed charge oxide defects in the dielectric later are present in all MOSCAPs. The third, fourth and fifth studies presented analyze spectral signatures and variances of in-situ forces during chemical mechanical planarization (CMP) of metal thin films for the purposes of improving endpoint detection, in particular, and helping us gain a better fundamental understanding of CMP processes, in general. A new parameter, directivity () is defined and used throughout all three studies. In the third study, CMP directivity is introduced as a ratio of shear and normal forces generated during polishing. This parameter is inspired by a parameter of the same name used to assess violins. Sound quality of individual violins is often evaluated through directivity by violin makers and physicists, which is the ratio of the variance of pressure exerted on the top plate of the violin to the variance of pressures exerted on its bottom plate. Older violins are known to have higher values of directivity than modern violins. A directivity greater than unity is indicative of sound traveling from the violin being more unidirectional. The physical components of the CMP polisher have quite a few parallels to the violin. For example, the strings of the violin are like the pad in the polisher. Typical coefficients of friction (COF) at the bow-rosin-string and wafer-slurry-pad interfaces are even similar, being in the range of 0.3 to 0.8 for both violins and CMP processes. This study observes the natural resonances of the polisher through spectral shear force signatures, and finds that the signature changes with added vibrations from the environment. The classic hammer strike test, which is common in testing the spectral signature response in violins, is applied to a polisher to show this effect. In the fourth and fifth studies, CMP of copper and tungsten is carried out with different pad surface micro-textures, generated from two different, commercially available conditioning discs. In-situ shear and normal force measurements are captured for all polishing experiments. The experiments are conducted with a variety of polishing pressures and sliding velocities. In a separate study, the removal rate (RR) from these studies is determined, as well as the coefficient of friction (COF). The surface of the pad after in-situ conditioning and polishing is imaged with confocal microscopy (CM) and various parameters are derived from the optical image data such as contact area between pad and wafer (CA), contact density between pad and wafer () and the microhydrodynamic lubrication layer (MHDLL) thickness. From the raw in-situ force data, variances of forces and spectral signatures are analyzed. For spectral analysis, the time domain is converted into the frequency domain with a fast Fourier transform, to distinguish a fingerprint of the experiment, or common force peaks between experiments. We then focus on the shear force because it represents the force that is most closely associated with friction at the pad-slurry-wafer interface. Variance of shear force is interpreted as stick-slip events at the interface. Results show that higher directivity values correlate in nearly all experiments (regardless of wafer material) with higher RR, larger CA and thinner MHDLL thickness. This clear correlation highlights the potential for directivity being used for endpoint detection in CMP. Several of the FFT shear force peaks from 0 to 150 Hz in every polishing experiment are shown to be harmonic peaks of force vibrations corresponding to the sliding velocity of the platen.
    • Detecting Preventable Disease Risk on Social Media

      Bell, Dane Edward (The University of Arizona., 2018)
      The incidence of type 2 diabetes mellitus is rising in the United States and worldwide. Diabetes is a common, debilitating, and deadly disease that begins with a long asymptomatic period, during which its severity can be limited through intervention. Intervention improves with earlier detection, but most prediabetic individuals are unaware of their risk. This study uses machine learning for the linguistic analysis of social media text to detect diabetes risk. To this end, it seeks to answer the questions "What linguistic features most indicate diabetes risk," "What algorithms best detect diabetes risk from these features," and "How can the data to train such algorithms best be collected?" To address these questions, I describe findings from an experiment in eliciting participation in data collection through an initial risk classifier based on public sources. I continue by comparing various linguistic feature sets and machine learning algorithms in detecting body mass index (kg/m^2, a risk factor for diabetes) as well as a more complete diabetes risk measure. Results show that participant engagement with the results of research is robust, but few of these individuals are willing to participate in the research when any personally identifiable data is collected. From these results, it is also evident that limiting feature sets to lexicons of domain-relevant words such as food and exercise terms can be effective, and that modeling a writer's gender and a text's recency can improve detection, along with distinguishing quoted text from original text. This work is a first step toward detecting diabetes risk, with the ultimate goal of designing effective, automated, and individualized interventions through social media. It has shown that language is a valuable predictor of important health variables, and proposes a novel method for accounting for a writer's gender when analyzing their text. Future work will benefit from pursuing larger datasets, potentially through methods described in this work, and from multimodal algorithms capitalizing from the interplay between text and images.
    • Synthesis and Characterization of Bio-inspired Glycolipid Surfactants

      Pacheco, Ricardo Palos (The University of Arizona., 2018)
      Surfactants are a commodity in the human civilization. Their unique ability of powerfully affecting the interfacial tension and their tendency of forming supramolecular aggregates in solution have been utterly exploited in several technological products now indispensable in the modern society. Evidence of their technological application date back to 5000 years ago. Currently, surfactants are used in practically all the industrial sectors. Due to their importance and demand, the science and technology to manufacture and characterize surfactant systems is highly developed. Nevertheless, there is a large room for improvement given the environmental challenges we are facing. For example, the surfactants that currently dominate the market are not readily biodegradable and their building blocks come from non-renewable sources like oil. For this reason, there is a growing interest in learning how to design and manufacture greener surfactant molecules. Bio-surfactants figured for several decades as potential greener replacements of the synthetic commercial counterparts. These materials have outstanding surfactant performances, and since most bio-surfactants are glycolipids, their biodegradability is favorable and the building blocks can be obtained from renewable and abundant feedstocks. However, their manufacture is problematic: biotechnological methods produce unpredictable mixtures with irreproducible yields, while their chemical synthesis is often impractical to be performed at scales relevant to the demand. As part of this quest for determining the best way to make bio-surfactants a feasible option, our laboratories developed a cost-effective methodology to chemically synthesize rhamnolipids, a class of bio-surfactant, allowing to explore its structure-performance relationship. However, despite its undisputable and unbeatable advantages, due to the structural complexity of rhamnolipids, this synthetic method has similar limitations to the mentioned above that precludes the manufacturing of naturally occurring rhamnolipids at industrial scales and at competitive costs with the oil-based counterparts. The present dissertation examines and demonstrates the possibility of employing what is known from the structure-performance relationship of rhamnolipid bio-surfactants to design molecules that are easier to manufacture while keeping similar or better performance. In sequence, a thorough exploration of the structure-performance relationship of these novel bio-inspired materials is presented to define the limits of their tailorability. This exploration includes the contributions to understand the relationship of surfactant performance of bio-inspired rhamnolipids with: i) the absolute configuration of the carbinols at the lipid tails and ii) the symmetry of the lipid tails of diastereomeric mixtures. These studies involved chemical synthesis and the characterization of the physicochemical properties of colloidal aqueous solutions. Evidence of the synthesis and isolation of the final products and building blocks is provided in form of nuclear magnetic resonance. The thermodynamics of their surface activity are described by surface tensiometry at the air-water interface at pH 8. Characteristics of their aggregation behavior in aqueous solutions including hydrodynamic radius, aggregation number, and aggregate morphology are determined using dynamic light scattering and time-resolved fluorescence quenching. The overall impact of this work is to push the frontier to make glycolipid surfactants a feasible alternative for their eventual introduction to wider markets.
    • Geographies of Home, Memory, and Heart: Mohawk Elder Praxis, Land, Language, and Knowledge Woven in Place

      Holmes, Amanda L. (The University of Arizona., 2018)
      Kanien'keha:ka and Rotinonhshonni languages, knowledges, teachings, philosophies, epistemologies, and ethical systems exist in relation to the living presence of lands and the natural world, ancestral homelands, the presence of Ancestors and ancestral knowledge, collective narrative memory (McLeod, 2007), from within places of ancient relationship and meaning. Kanien'keha:ka-Rotinonhshonni knowledge is carried within the language and teachings by Elders and Knowledge Holders; as beloved Oneida Knowledge Bearer Bob Antone (2013b) says, “Elders [are] the wisdom-keepers of repository knowledge” (p. vii). Attention to this intricate interweaving, this network of relationships – and the ways they are lived and embodied by Kanien'keha:ka-Rotinonhshonni Elders – holds the potential for the renewal and resurgence of Kanien'keha:ka-Rotinonhshonni languages, worldviews, knowledge systems, ways of knowing-being, and oral intergenerational practices that interrupt and transform the processes of knowledge and language loss that are a direct result of Settler-Colonial invasion. This research theorizes Elder Praxis, Indigenous Elders’ critical thinking and ethical action, their voice and vision, the ways they provide guidance, perception, wisdom, humor, knowledge, ways of knowing and being, paying careful attention to the re-envisioning and renewal of ancient memory, listening for the relationalities between language, knowledge, and memory that cycle through the everyday of today, the transformative capacity of intergenerational relationship guided by the praxis of Onkwehon:we Elders. Theorizing Onkwehon:we Elder Praxis suggests a re-orientation, a re-centering, of critical and transformative relationships, practices, ethics, and protocols, an intergenerational, oral-relational framework for the restoration, renewal, and resurgence of Onkwehon:we languages, community-centered knowledges and practice, mediated by and rooted within the lived, everyday ways of knowing-being of Elders. Restoring and re-storying oral, intergenerational relationships locates Haudenosaunee Elders at the center of a process of renewal and resurgence, a critical nexus of cultural meaning, knowledge, and practice within the generations, “maintain[ing] those cycles of continuous creation,” as Kanien’keha:ka midwife Katsi Cook puts it (Cook, 2008, p. 165). Theorizing Elder Praxis remembers and situates Indigenous Elders at the heart of Indigenous cultural, linguistic, and intellectual resurgence. Correspondingly, this dissertation also elaborates a “new” theoretical framework of Critical Indigenous Language Restoration and Renewal, re-conceptualizing and re-contextualizing Indigenous language revitalization from within a Kanien'keha:ka-Rotinonhsionni network or matrix of intergenerational relationships to each other, to Ancestors, to future generations, to our Mother the Earth, and to the natural world of Creation, quickened and mediated by the knowledge ways and praxis of Onkwehon:we Elders. Conceptualizing and contextualizing in new ways, from different centers, a critical framework for renewing relationships to language and cultural knowledge deepens the healing, regeneration, and possibilities for the resurgence of Rotinonhsionni community, held within the epistemologies, philosophies, teachings, and cultural practices of a Kanien'keha:ka-Rotinonhsionni universe.  Kanatsiohareke Mohawk Community, as a reflection of Tom Porter’s Mohawk Elder Praxis, embodies a re-envisioning and re-imagining of the contemporary meaning and relevance of well-worn pathways, intergenerational continuities, collective narrative memory (McLeod, 2007), persistence, and presence within Kanien:keh, Mohawk lands and ancestral homelands. Kanatsiohareke forms a Kanien'keha:ka and Rotinonhshonni resistance to the hegemony of Settler-Colonial invasion and overculture by re-centering within Kanien’keha:ka meaning, lifeways, and worldviews, a self-determining restoration, renewal, and resurgence. In the process of Mohawk re-visioning, re-narrating and re-imagining, the reciprocity of intergenerational presence-ing to each other mediated by the praxis of a Mohawk Elder, Mohawk and Iroquois people re-connect to intergenerational relationships of language and knowledge, to a Kanien'keha:ka-Rotinonhsionni universe, in the context of traditional community. As they return to this context of ancestral homeland and traditional Kanien’keha:ka community, to older patterns and orientations in this place, they re-weave relations and reciprocities between language, cultural knowledge, memory, identity, generations, land, and the natural-spiritual world. In these ways, they are awakening ancient coherence, consciousness, and action, engaging the aspiration of what John Mohawk calls cultural re-development, reminding us that “the redevelopment of culture on a human scale is the only practical way that people and peoples can regain control of their lives and their destinies” (Mohawk in Barreiro, 2010, p. 199).
    • Comparing Different Approaches to the Implementation of a New Chemistry Curriculum

      Hou, Ying (The University of Arizona., 2018)
      In recent years, educational researchers have investigated teacher-student interactions in science classrooms, paying particular attention to interaction patterns and the purpose of such interactions. Although different patterns and purposes have been uncovered through these investigations, there is little research on how college instructors use in-class interactions to help students construct ideas. Instructors' decisions and actions are important when interacting with students and they can be expected to depend on their teaching experience, instructional strategies, and educational purposes when implementing in-class activities. Thus, we have carried out a qualitative study using in-class observations and semi-structured interviews as the main data collection tools to explore the differences in how diverse instructors interact with students during in-class activities in the new “Chemical Thinking” curriculum for General Chemistry at the University of Arizona. The participants of this study included six instructors with different backgrounds and teaching experiences. We identified major types of discourse moves instructors used when interacting with students. Main findings indicate that although participants shared similarities in the interaction patterns and discourse moves they followed in the classroom, they approached the implementation on in-class activities in different ways and their decisions and actions had an impact on the quality of the opportunities to learn that they created. The results of our study are relevant to chemistry educators interested in helping college instructors improve their practice when implementing collaborative group activities in the classroom.
    • The Shared Meaning of Compassion Fatigue among Registered Nurses Working in Skilled Nursing Facilities

      Steinheiser, Marlene (The University of Arizona., 2018)
      Purpose: The purpose of this research study was to describe the shared meaning of compassion fatigue (CF) among registered nurses (RNs) caring for older adults in skilled nursing facilities (SNFs). Background: Nurses who care for older adults in SNFs expend compassion energy when caring for suffering patients, thus increasing the risk their compassion fatigue. In the most commonly used conceptual model of CF, compassion satisfaction is defined as the positive feelings of providing care and the negative feelings from the environment (burnout) and from one’s emotional response (secondary traumatic stress). Symptoms of CF can include physical illness, detachment from patients, work-life imbalance and emotional distress. CF can negatively impact patient outcomes, is associated with decreased quality of care, and can be a reason why nurses leave the profession entirely. Method: The hermeneutic interpretive phenomenology method was used to describe shared meaning of CF among RNs caring for older adults in SNFs. Eight participants were recruited for participation, with the assistance of key nursing leaders and snowball sampling. Each participant was interviewed three times, and concurrent data analysis helped to formulate mutual understanding of the phenomenon while also informing subsequent interviews. Self-reflection, journaling, record keeping, and use of direct quotes enhanced trustworthiness. Findings: The participants (N= 8) described their experiences caring for older adults in a SNF. Four shared meanings were abstracted:1) I feel conflicted and that causes my CF; 2) physical and emotional manifestations of CF; 3) CF is infused in every aspect of my life; 4) We are trying to cope with CF. The participants shared the central desire to make a difference in the lives of their patients, which was of paramount importance. When participants felt they were unable to make the desired difference, they began to develop symptoms of CF. Symptoms were compounded when they experienced the death of patients they felt close to. Implications: A comprehensive resiliency program incorporating individual and organizational involvement could positively impact the participants’ professional quality of life. Future qualitative and quantitative research is needed to better understand CF and effective interventions among this population of nurses.
    • The Role of 14-3-3 Gamma in Promoting Genomic Instability

      Gomes, Cecil (The University of Arizona., 2018)
      The 14-3-3 family members are a group of highly conserved scaffolding proteins that are present in all eukaryotes. Despite having limited endogenous activity, the 14-3-3s bind to numerous client proteins and directly modulate their activities by a variety of mechanisms. In mammals, there are seven isoforms (beta, gamma, epsilon, eta, sigma, theta, and zeta), and between them over 200 known binding partners, which allow them to function in nearly every aspect of cellular biology. The 14-3-3 family has long been studied in regards to cancer, as aberrant changes in their expression patterns have been associated with numerous human cancers. It is, therefore, a shared goal, among many, to elucidate the role of 14-3-3 proteins in tumorigenesis. For the last decade, our laboratory has been keenly focused on the tumor-promoting roles of 14-3-3 proteins in the context of lung cancer, as their expression patterns are highly dysregulated in this cancer setting. Herein, we expand on this area of research and demonstrate that four of the seven 14-3-3 isoforms are significantly elevated in both adenocarcinomas and squamous cell carcinomas of the lung. We then investigated the consequences of these isoforms being increased in malignant lung tissues and showed that when upregulated, 14-3-3 sigma, gamma, and zeta correlate with poorer prognosis in patients with lung adenocarcinoma (LUAD). Interestingly, these associations with survival were not observed in patients with lung squamous cell carcinoma (LUSC), suggesting that the upregulation of these 14-3-3 isoforms may influence patient survival and serve as suitable prognostic biomarkers. To explore the cellular consequences of 14-3-3 upregulation, our laboratory previously overexpressed 14-3-3 gamma, the isoform that demonstrated the strongest prognostic capacity in the LUAD-TCGA dataset, in human lung adenocarcinoma cells. Overexpression of this isoform caused a fraction of cells to become polyploid, meaning they contained more than two sets of chromosomes. Amassing data have demonstrated that polyploid cells are uniquely resistant to chemo- and radiotherapy, making polyploid cells integral components in driving the ongoing evolution of the patient disease and recurrence. We, therefore, became interested in illuminating the molecular mechanism(s) driving 14-3-3 gamma-induced polyploidy, the net effect these cells had on genomic integrity, and whether this phenomenon occurred in vivo. By utilizing the fluorescence ubiquitin cell cycle indicator (FUCCI) system, we were able to show that overexpression of 14-3-3 gamma resulted in inhibition of mitotic entry, forcing some cells to bypass mitosis entirely, thereby facilitating the polyploid phenotype. In pursuit of investigating whether these polyploid cells could re-enter the cell cycle and undergo cell division, we developed a widely-applicable, nontoxic procedure for measuring DNA content in live cells by fluorescence microscopy. This capacity allowed a cell’s temporal location within the cell cycle and its DNA ploidy to be coupled with a variety of imaging directed analyses. By tracking these polyploid cells over time in combination with the nuclear-reporter H2B-GFP, we were able to show that these polyploid cells are capable of entering mitosis, and when they do, they experience a prolonged and error-prone cell division. Collectively, these data demonstrated that the overexpression of 14-3-3 gamma resulted in a genetically unstable polyploid intermediate with the capacity to undergo mitosis and plausibly facilitate the transition into an aneuploid cell state. Equipped with this knowledge, we examined whether this phenomenon occurred in vivo. To do this, we turned back to the TCGA and confirmed that polyploid tumors had significantly elevated expression of 14-3-3 gamma compared to diploid tumors. This data may explain one avenue as to why elevated expression of 14-3-3 gamma correlates with more reduced survival in patients with lung adenocarcinomas. Taken together, our studies suggest that 14-3-3 gamma may play a role in tumorigenesis by inducing polyploidy, which may set the stage for further changes that lead to neoplastic progression.
    • Pattern Generation and Control in Semiconductor Quantum Well Microcavities

      Luk, Ming Ho (The University of Arizona., 2018)
      Many physical phenomena have been observed in semiconductor quantum well microcavities, such as polariton Bose-Einstein condensation, pattern formation, optical spin Hall effect (OSHE), solitons and more. An optically pumped cavity system has the advantage of strong nonlinear couplings between polaritons, and easy detection with photons emitted from the cavity. This thesis presents the theoretical studies of far-field pattern formations, transfer matrix calculations, optical control of the OSHE, and generation of orbital angular momentum (OAM) in optically pumped single- and double-cavities, and comparison with experimental outcomes. This work is a collaboration between theoretical groups at the University of Arizona (USA), Chinese University of Hong Kong (Hong Kong), University of Parderborn (Germany), and an experimental group at CNRS (France). Far-field transverse patterns originates from the nonlinear coupling of polaritons. Patterns, such as 2-spot and hexagon, are observed in optically pumped semiconductor quantum well microcavities when the pumping intensity is above the modulation instability threshold. The first part of this work studies the generation of far-field patterns in an optically pumped semiconductor double quantum well microcavities using a microscopic model of exciton and cavity photon fields, and introduce a simple control mechanism utilizing the light-house effect to control the orientation of 2-spot patterns. Transfer matrix calculations are performed to provide the connection between the microscopic model and the experimental cavity. This work aims to provide simple and robust control mechanisms for future optical communication devices. The second part of this work shows the formation and control of the OSHE in an optically pumped double-cavity. The OSHE is a linear optical effect of exciton polaritons in semiconductor microcavities. It originates from the polaritonic spin-orbit coupling, and can lead to observable spin/polarization textures in the near and far field under appropriate excitation conditions. An alternative description is based on a pseudo-spin model. The formation of the OSHE texture can be described by an effective magnetic field generated by the splitting of the transverse-magnetic and transverse-electric (TE-TM) polariton modes. Here we show theoretically that the orientation of the pseudo-spin texture can be controlled all-optically, which matches the experimental observation. We establish the relation between the incident light intensity and the degree of rotation of the far-field pattern using both the simplified pseudo-spin model and the double-cavity spinor-polariton equations. This scheme provides a simple and robust control mechanism for future spinoptronic devices utilizing OSHE. Potential applications of the orbital angular momentum (OAM) of light range from the next generation of optical communication systems to optical imaging and optical manipulation of particles. In the third part of this work we propose a micron-sized semiconductor source, based on a polaritonic quantum fluid in a single-cavity, that emits light with predefined OAM pairs. We show how modulational instabilities can be controlled and harnessed for the spontaneous formation of OAM pairs not present in the pump source. Once created, the OAM states exhibit exotic flow patterns in the quantum fluid, characterized by generation-annihilation pairs.
    • Explicitly Correlated Gaussian Functions and Rovibrational Spectra of Diatomic Molecules

      Jones, Keith (The University of Arizona., 2018)
      Explicitly correlated Gaussian functions are implemented in order to calculate the rovibrational spectra of various diatomic molecules with and without the Born- Oppenheimer approximation. Matrix elements and gradients for the overlap, potential, and kinetic energy are derived for two different bases corresponding to the second rotationally excited state, one with the approximation that the rotational excitation of the system is due primarily to the excitation of the nuclei and the other allowing all particles to contribute to the rotational excitation. Matrix elements of the nuclear nuclear correlation function and interparticle distance are also derived in the former basis. Comparisons with experimental data and other computational work are provided. Implemented improvements in the Born-Oppenheimer code are also introduced, with results shown for the HeH$^+$ molecule. A new project involving confined molecules will be briefly introduced.
    • Investigating the Role of Obesity and Obstructive Sleep Apnea in Hepatocellular Carcinoma Progression

      Sweeney, Nathan (The University of Arizona., 2018)
      Primary liver cancer is the seventh most common cancer worldwide and the second highest cause of cancer mortality. The incidence of hepatocellular carcinoma (HCC) has increased 80% in the past two decades and now comprises 85% of all primary liver cancer. Obesity increases the risk of developing HCC two-fold in women and five-fold in men. Co-morbidities common to obesity including non-alcoholic steatohepatitis (NASH), hepatic inflammation, and lipid accumulation increase the risk of developing HCC. Obstructive sleep apnea (OSA), a state of chronic intermittent hypoxia which is common in obese individuals, also increases the incidence of NASH. With a U.S. population that is approximately 33% obese, having OSA at 30-50%, we estimate the co-incidence of obesity and OSA is 10-16.5% of the entire U.S. population. Diet-induced obesity or intermittent hypoxia induces hepatic lipid accumulation and diet-induced obesity was recently shown to promote HCC tumor development. Whether obesity, chronic intermittent hypoxia, and their combination hasten hepatic lipid accumulation and HCC tumor progression remains unclear. In our studies, we monitored tumor development utilizing micro-computed tomography imaging and discovered that tumors developed fastest in mice that consumed a high fat diet. Upon further investigation, these mice also tended to have higher serum levels of AST and ALT and gained more weight than their counterparts. However, the addition of hypoxia lead to a decrease in weight gained, as well as a reduction in hepatic lipid accumulation and tumor formation. Extraction of mRNA from mouse livers revealed an up-regulation HIF-1α in mice fed a high fat diet without treatment with hypoxia that correlated strongly with tumorigenesis. Remarkably, hypoxia was found in mice treated with hypoxia as well as the mice that were fed a high fat diet only. These findings suggest that hepatic lipid accumulation produces endogenous hepatic hypoxia which associates with increased hepatic HIF-1α expression that correlates with tumorigenesis. Collectively, these data reveal a mechanism that potentially explains progression from early liver disease to HCC.
    • Investigating the Economic Consequences of Atmospheric Nuclear Testing

      Meyers, Keith Andrew (The University of Arizona., 2018)
      During the Cold War the United States detonated hundreds of atomic weapons at the Nevada Test Site (NTS). Many of these nuclear tests were conducted above ground and released tremendous amounts of radioactive pollution into the environment. The primary aim of this dissertation research is to answer empirical questions regarding the social costs of atmospheric nuclear testing. My research focuses on two broad areas: 1) how do economic agents respond to the adverse effects of environmental shocks, and 2) how does policy shape responses to said shocks. My studies combine data from a myriad of agricultural, environmental, and public health sources and rely upon clearly identified reduced-form models to estimate the social costs of NTS activities. The United States’ nuclear weapons testing program had much larger effects than previously known. I find that radioactive iodine generated from nuclear testing contributed to hundreds of thousands of excess deaths from 1951 to 1978. Increases in mortality rates due to fallout occurred throughout the entire country and that substantial damage occurred in places far from the region typically considered to be ``Downwind"" of the NTS. This radioactive material also harmed agricultural production and led to billions of dollars of lost output (2016$). Expanding upon these results, I use fallout measures to instrument for agricultural productivity and study how policy shapes agricultural producers’ responses to adverse productivity shocks. Fallout shocks allow me to measure how farmers respond to adverse productivity shocks when the cause of the shock is unobserved and unanticipated from the perspective of the agent.
    • Validation of Hearing Aid Fittings by the Arizona Sonora Borders (ARSOBO) Projects for Inclusion

      Beukelman, Page Naomi (The University of Arizona., 2018)
      The Arizona Sonora Border (ARSOBO) Projects for Inclusion Hearing Healthcare clinic provides comprehensive audiologic evaluations and low-cost hearing aids to individuals in Nogales, Sonora, Mexico. After identifying the need for a fitting guide to properly adjust the hearing aids, we collected 110 patient audiograms and grouped the six most common configurations of hearing loss. Using simulated real-ear measures, we fit the hearing aids to each of the six common configurations of hearing loss, and recorded the appropriate settings to serve as a starting point for future hearing aid fittings. In an effort to determine the success of these hearing aid fittings (and others performed by the ARSOBO Hearing Healthcare program), we administered 29 questionnaires assessing hearing aid effectiveness. The International Outcome Inventory for Hearing Aids (IOI-HA) was the chosen outcome measure due to its international applicability and quick and simple format. In general, the hearing health care provided by ARSOBO yielded positive outcomes and favorable outcomes in each category of the IOI-HA. Potential confounding variables, limitations and future directions of the program are outlined. Additionally, the specific results of these outcome measures and the implications of our project/fitting guide on humanitarian audiology is discussed.
    • Between Menace and Model Citizen: Lima's Japanese-Peruvians, 1936-1963

      DuMontier, Benjamin John (The University of Arizona., 2018)
      The Japanese-Peruvian community in Lima, Peru used different understandings of race to assert its role in the country. This dissertation examines the changing racial and ethnic characterizations of Japanese residents in Peru between 1936 and 1963. Using archival research and oral histories this dissertation traces the category of “enemy alien” in Peruvian policy, a racial and legal category which overlapped with global conversations about anti-Asian “yellow peril” fears. This analysis pays close attention to one national context – Peru—and takes a long view on nation-state policies that influenced the lives of immigrants. In this context, I argue that understandings of race among Japanese-Peruvians had to do with the placement of Japan in global politics—and were not uniformly negative, depending on the historical moment. Peruvian officials formed their political agenda – and the subsequent treatment of Japanese-Peruvians –not solely in response to U.S. policies and interests in national security. Instead, domestic policies in the 1930s and actions by Japan abroad shaped the changing ways of addressing Japanese-Peruvians before, during, and after World War II. After the war, however, the Japanese-Peruvian community developed their own survival strategies amid changing national and global designations for their racial and political identities. They exploited the racial ambiguity that newspapers, government policies, and Peruvian laborers had towards Japan to claim new citizenship rights. This dissertation uses oral histories to trace how changing international political relations – and war – affected the efforts of immigrants to create a new homeland.