• Numerical Investigations of Receptivity, Stability and Transition for High-Speed Boundary Layers

      Fasel, Hermann F.; Haas, Anthony Paul; Craig, Alex; Hanquist, Kyle; Wernz, Stefan H.; Brio, Moysey (The University of Arizona., 2022)
      Numerical tools for receptivity and stability investigations in high-speed boundary layers were developed: A local Linear Stability Theory (LST) solver applicable for axisymmetric geometries as well as linear and nonlinear disturbance flow formulation solvers suitable for complex geometries. Explicit, implicit and time-spectral time-integration schemes were considered. Although explicit methods are comparatively simpler to implement for disturbance flow formulation solvers, the allowable time-step for stability reasons can be much smaller than that required by accuracy considerations. This is especially the case for receptivity problems involving sharp nose geometries, such as cones or wedges, because the resolution requirements in the nose region can lead to severe restrictions of the time-step for explicit schemes. The new solvers were verified and validated for a variety of flow conditions, geometries, and instabilities. Three investigations are presented. First, the effects of (small) leading edge bluntness on the linear stability of flat-plate boundary layers was investigated. For the conditions investigated, it was found that very small nose radii had already a significant effect on the stability characteristics. Second, the receptivity of a Mach 10 boundary layer on a 7 degree half-angle cone to freestream acoustic disturbances was considered. A detailed analysis as well as comparisons with LST are provided. For the case considered, slow acoustic waves converted rather naturally into the unstable mode S, while fast acoustic waves followed the trend of mode F until a specific downstream location where a switch occurred. Finally, linear and nonlinear cross-flow instability computations are presented for an infinite span swept wing with biconvex airfoil at Mach 2. The stability characteristics as well as flow structures associated with the linear, secondary instability and nonlinear regimes are presented and discussed.
    • The Richtmyer-Meshkov Instability in Reshock in a Dual Driver Vertical Shock Tube

      Jacobs, Jeffrey W.; Ferguson, Kevin; Little, Jesse; Craig, Stuart A.; Brio, Moysey (The University of Arizona., 2022)
      We present experiments on the Richtmyer-Meshkov Instability (RMI) in reshock, conducted in a Dual-Driver Vertical Shock Tube (DDVST). The DDVST is a new shock tube that was designed, optimized, constructed, and utilized as part of this work. The DDVST, in effect, consists of two traditional single driver shock tubes, each consisting of a single driver and driven section, oriented vertically opposed on opposite sides of a test section. This new configuration permits a controllable time between the arrival of the first shock that initiates the RMI and the second shock that initiates the reshock regime. Additionally, the dual driver configuration also permits the strength of the first and second shocks to be individually controlled so as to allow for a prescribed post-reshock bulk interface velocity. This capability allows for the post-reshock bulk interface motion to be halted which in turn allows for the cameras used for imaging to be brought closer to the test section, increasing imaging resolution while maintaining a long temporal window in which the RMI may be observed. The DDVST was designed with the goal of achieving the longest post-reshock growth period possible within the physical and practical constraints of the laboratory setting in which the tube resides. The design process was assisted by coupling a numerical solver for 1D compressible flow within a shock tube to a genetic optimization routine with the aim of finding the combination of shock tube section lengths that produce the longest window in which the RMI in reshock may be observed. Different optimal designs corresponding to different light shock Mach numbers were calculated to examine whether a longer effective period of RMI evolution could be obtained for a given light shock Mach number. A single design was selected from these candidate designs based on its performance over a range of expected experimental parameters, which was then constructed and used for this work. The DDVST uses the method of Jones and Jacobs (Phys. Fluids \textbf{9} (10), October 1997) to generate the initial interface between the two test fluids without the use of a membrane which may influence the flow. This method forms the initial interface between two gases of differing density by flowing the more dense gas into to the tube from below a set of holes drilled at the desired interface location while simultaneously flowing a less dense gas from above the same holes. These two gas streams meet at the set of holes and flow out of the tube, forming a stable, stratified, and slightly diffuse interface. Multimode, three-dimensional, random initial perturbations are then imposed on the interface using a pair of voice coil actuators. The test gases for all experiments are Air and Sulfur Hexafluoride (SF$_6$) which yields an Atwood number of 0.67. The experiments presented as part of this work have a nominal light gas shock wave Mach number $M_L = 1.17~(\sigma = 0.007)$ and heavy gas shock wave Mach number $M_H = 1.18~(\sigma = 0.004)$ for all experiments, where $\sigma$ is the standard deviation. This results in the bulk interface motion being halted following the passage of the second shock. The experiments presented examine the influence of changing the length of time between shock and reshock on the behavior of the RMI in reshock for a range of shock to reshock times. Also examined is the influence on the order of arrival of the two shock waves, with both the traditional (light shock first) and reversed (Heavy shock first) configurations considered. The shock to reshock times examined are between -4.0 (Heavy shock first) and +3.8 (Light shock first) ms. The growth exponent, $\theta$, extracted from a fit of $h(t) = a t^\theta$ to the width of the mixing layer versus time for each experiment, appears to be insensitive to changes in the shock-to-reshock time or order of arrival of the two shocks, with an average value of $\theta_{H,W} = 0.365 \pm 0.018$ (95\%) and $\theta_{L,W} = 0.381 \pm 0.02$ (95\%) for heavy shock first and light shock first experiments, respectively, where (95\%) denotes the 95\% confidence interval of the result. The rate of decay of TKE appears to be affected by the order of arrival of the two shock waves, using a fit of $TKE(t) = a t^p$ to the total amount of TKE in the mixing layer for each experiment, yielding an average value of $p_H = -0.823 \pm 0.06$ (95\%) and $p_L = -1.061 \pm 0.032$ (95\%) for the heavy and light shock first experiments, respectively. The method of Thornber, Drikakis, Youngs, et al. (J. Fluid Mech. \textbf{654}, 2010) is used to extract a value of the growth exponent from these rate of decay of TKE measurements, yielding values of $\theta_{H,TKE} = 0.392 \pm 0.02$ (95\%) and $\theta_{L,TKE} = 0.312 \pm 0.011$ (95\%) for the heavy and light shock first experiments, respectively. Analysis of the anisotropy of the mixing layer over time is performed by examining the Reynolds anisotropy tensor in addition to the anisotropy ratio. An early time trend towards isotropy following reshock is found, with experiments with longer shock-to-reshock times demonstrating a more rapid trend towards isotropy than those with a shorter shock-to-reshock time. The anisotropy ratio of the mixing layer approaches an average minimum value of $A \approx 1.2$ for the longest shock-to-reshock times, and $A \approx 1.3$ for shorter shock to reshock times. The mixing layer becomes increasingly anisotropic over the remainder of the experiment, with no notable difference in the degree of anisotropy versus shock-to-reshock time or order of arrival of the two shock waves. The analysis of the spectrum of anisotropy shows that the largest scales of the flow have a trend towards anisotropy, but those at smaller scales tend to be isotropic. The Reynolds number, defined as $Re = h \dot{h} / \nu_{avg}$, is analyzed versus shock-to-reshock time. For shock-to-reshock times $\gtrapprox$ 1 ms, the Reynolds number is found to approach $Re \approx 1 \times 10^5$ for both heavy shock first and light shock first experiments. This is excess of the $Re > 1 \times 10^4$ proposed by Dimotakis (J. Fluid Mech. \textbf{409}, 2000) for a transition to turbulent mixing, though it does not meet the suggested critical value of $Re > 1.6 \times 10^5$ suggested by Zhou (Phys. Plasmas, \textbf{14} (8), 2007). Analysis of these experiments using the time-dependent turbulent length scales and associated turbulent transition criteria of Zhou, Robey, and Buckingham (Phys. Reveiw E, \textbf{67} (5), 2003) suggests that these experiments are beginning to transition to a fully turbulent state.
    • The Interplay of Light and Melatonin in Biological Timekeeping: Conservation, Divergence, and Translation of the Drosophila Timekeeping Network

      Zinsmaier, Konrad; Dollish, Hannah Katherine; Zarnescu, Daniela; Fernandez, Fabian; Bhattacharya, Martha (The University of Arizona., 2022)
      The central pacemaker for biological rhythms in mammals is located in a 10,000-cell structure known as the suprachiasmatic nucleus (SCN) in the anterior hypothalamus (Hastings_2018, Meijer_1996). Clock cells in the suprachiasmatic nucleus work together to generate a coordinated and synchronous output that results in an intrinsic endogenous “ticking” of the biological clock at a set periodicity (Liu_1997). Circadian rhythms are generated by the daily fluctuation of a transcription-translation feedback loop between clock proteins and genes located in clock cells. Master pacemaker cells in the SCN project to peripheral pacemaker cells in various organs and tissues in the body. All biological rhythms oscillate at a set period known either as the intrinsic or endogenous period and is determined by the oscillatory speed of the transcription-translation feedback loop determined by the individual organism’s genetics (Jin_1999, Liu_1997). The endogenous period is not typically aligned optimally with the external 24-hour period of the earth’s daily rotation about its axis. The amount of time it takes for an animal to return to the same phase of its endogenous rhythm without an external natural or artificial cycle to align to is known as the free running period. Mammals do not have endogenous periods that cycle at exactly 24-hours but generally have free running periods ranging between 22 and 26 hours, with diurnal mammals typically exhibiting free running periods above 24-hours (Aschoff_1981). The difference in cycling between the endogenous period and the external 24-hour photoperiod (the period of light and dark denoting one complete rotation of the earth about its axis), eventually results in a drift and subsequent misalignment of important behaviors, which lead to negative and in some cases fatal health outcomes for living organisms (Aschoff_1981, Lewy_2009). In order to prevent misalignment and optimally time behaviors to the external photoperiod, the biological clock evolved a process known as entrainment. Entrainment of biological rhythms to an external zeitgeber is achieved through advancing or delaying internal rhythms based on the animal’s previous photic history, so that they optimally align with the 24-hour external period (Julius_2019). The first chapter in this section will cover the anatomy and circuitry of the SCN, mechanisms of the mammalian molecular and biological clock, and explore the mechanisms of entrainment for optimally phase aligning biological rhythms to a 24-hour photoperiod. In the second chapter, I will describe the Drosophila biological time keeping network, discuss what mechanisms and functions are conserved or diverge between mammals and Drosophila, and where possible translational overlap between mammals and Drosophila can occur to further our understanding of entrainment of circadian and seasonal rhythms. The final chapter in this section will present published data on a comprehensive seasonal phase response curve (PRC) atlas of phase shifts in the activity rhythms of Drosophila ananassae under different seasonal photoperiods. Timing behavior and physiology to the 24-hour solar cycle has enabled life to persist and thrive on Earth. The most powerful time cue, light, is used for aligning endogenous rhythms to the day and night cycle; however, the clock also heavily relies on another internal rhythm, melatonin secretion, to help adjust circadian but primarily seasonal rhythms cooperatively with light input (Aschoff_1978, Ardent_2009). Melatonin and light work synergistically to entrain endogenous rhythms to the external photoperiod set by the solar cycle (Wood_2013, Wehr_1997). Together, both light and melatonin optimize interconnecting suites of behavior and physiology so that they are expressed during the most conducive parts of the day-and-year to enhance biological fitness. Regarding circadian/seasonal function, it is impossible to talk about melatonin without also understanding (1) the control that ambient light exerts over its secretion and (2) how melatonin feeding back onto the clock can work to adjust oscillatory behavior the clock makes in response to light exposure, especially during the subjective night.Melatonin functions as an important biological imprint of night-length by supplementing daytime light information collected by the brain’s circadian pacemaker. The suprachiasmatic nucleus (SCN) acts as the mammalian biological clock; and the Lateral and Dorsal Nuclei (LN and DN respectively) comprise the Drosophila clock network (Taghert_2006, Ardent_2009). Melatonin has its primordial role as an antioxidant that directly and indirectly – through metabolite cascades – sequesters free-radicals to help prevent oxidative stress (Zhao_2014, Manchester_2015). Melatonin freely circulates throughout the body and passes through lipid membranes and the blood brain barrier (Pardridge_1980, Costa_1995). These two features contribute heavily to its potency as an antioxidant in both the plant and animal kingdoms. Timing of melatonin secretion is important to optimize its antioxidant properties and to phase-lock various biological behaviors to occur at the optimal phase of the day-night cycle. Its enhanced secretion at night tracks closely to periods of high oxidative stress that occur during the day when solar UV radiation and system energy demand are at their highest (Haldar_2010). This is thought to keep oxidative processes to a minimum during the day and time the bulk of them to occur during the evening when there is less demand on the system from UV-radiation and environmental conditions. The history of melatonin’s functionality, from just an antioxidant in simpler species to evolving more of a modulatory role for circadian and seasonal behaviors in higher invertebrates, avian species, and mammals, is an interesting one. It stemmed from melatonin’s ability to orchestrate and participate directly in restorative processes that work best in the absence of light (such as DNA methylation and sequestration of free radicals) (Zhao_2019). More of its evolutionary history will be discussed later, but it is interesting to note that melatonin concentration is highest in mitochondria, where many reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated during the citric acid cycle. Finally, data will be presented on a comprehensive seasonal study on melatonin secretion in Drosophila ananassae across different seasonal photoperiods. This data was collected in an attempt to draw a phylogenetic line between where melatonin took on its circadian and seasonal role and where it acts solely as an antioxidant. This data also sought to understand what, if any, circadian and seasonal properties of melatonin are conserved between the Drosophila and mammalian systems. Using the gold standard of melatonin measurement, mass spectrometry (Markey_1981), and over 18,000 animals, we measured melatonin secretion in 4 photoperiods from high summer (16:8), equatorial (12:12), and high winter (8:16) photoperiods. Animals were also exposed to an extreme arctic summer photoperiod (20:4) to evaluate the potential suppressive effects of light on melatonin secretion in this species in addition to a physiologically extreme photoperiod.
    • Carcinoembryonic Antigen Cell Adhesion Molecule 6 Enhances Invasiveness and Immune Suppression in Pancreatic Adenocarcinoma

      Mahadevan, Daruka; Al Khinji, Aisha; Ellis,, Nathan; Matsunaga, Terry; Wang, Pei (The University of Arizona., 2022)
      Pancreatic adenocarcinoma (PDA) is the most common pancreatic cancer and most lethal solid tumor. It is the seventh most common cause of cancer-related mortality worldwide. Desmoplasia and fibrotic microenvironment remain challenging in PDA and contribute to its poor prognosis. Thus, identifying a predictive biomarker and target protein that can alleviate desmoplasia and minimize disease metastasis is urgently needed. Carcinoembryonic antigen cell-adhesion molecule 6 (CEACAM6) is a member of the immunoglobulin superfamily and is located at the cell surface protein. It is anchored via glycophosphotide inositol (GPI) and possesses no transmembrane domain. Additionally, it is an adhesive molecule that plays a vital role in tumor growth, immune response, and signal transduction in PDA. CEACAM6 regulates several cellular functions despite its unique structure. Thus, protein-protein interaction must exhibit its oncogenic role. The precise mechanism by which it operates remains poorly explained. Additionally, PDA is known as a ‘cold’ tumor. There is a strong association between desmoplasia and immune evasion. Besides the physical barrier induced by dense fibrotic stroma, that traps cytotoxic T lymphocytes (CTLs), there is a profound infiltration of immunosuppressive cells and molecules such as myeloid-derived suppressive cells and immune checkpoint inhibitors. Adhesion molecules contribute to increased deposition of collagen and other extracellular protein in TME that further obstruct CTLs infiltration and abrogate CTLs activity. While CEACAM6 promotes tumor aggressiveness as an adhesive molecule, it also has a role in immune regulation. Thus, I proposed that CEACAM6 promotes tumor invasiveness and enhances proliferation mediated through binding to a neighbor protein within the TME. I speculate that since CEACAM6 lacks a transmembrane domain, it will be useful to determine the mechanistic role of focusing on protein-protein interaction. I identified a potential mediator such as integrin B4 based on different experimental models that proved the association between the two proteins. The connection between CEACAM6 and integrin B4 explains the contribution of CEACAM6 in altering the mechanical properties upon measuring elasticity, adhesion, and deformation using atomic force microscopy. I speculated that CEACAM6 suppresses the host immune response and directly and indirectly drives immune evasion in PDA. Thus, I determined the mechanism by generating an in-vitro co-culture model that recapitulates the immune microenvironment. Also, I anticipated that since CEACAM6 is an adhesive molecule, the CTLs recruitment and infiltration would be impaired. In addition, to the direct immune inhibitory role, there was an indirect way to suppress CTLs trafficking and chemotaxis by regulating the chemokine and cytokines secretion. I found that CEACAM6 manipulates the immune environment and there was a significant improvement in cytotoxicity once knocked out. In conclusion, I showed by using differential experimental methodology that CEACAM6 promotes tumor progression and mediates its function through binding to integrin B4. Additionally, blocking CEACAM6 upregulates cytokines with tumoricidal activity such as TNF- and upregulates TNFR1, which stimulates apoptosis-. In this dissertation, first, I will provide background related to PDA and CEACAM6 in cancer and immunity, I will discuss the current understanding of the PDA in metastasis and immune response, and in a comprehensive summary of what was known about CEACAM6 in PDA, including the prior findings of this work. Second, I will explain the main hypothesis and describe all the aims and talk about each aim in a separate chapter. Finally, I will summarize the whole dissertation and discuss the future direction.
    • Education, Wellbeing, and Society

      Deil-Amen, Regina J.; Cochran, Stacey; Ricker, Mari A.; Ramirez, Cristina D. (The University of Arizona., 2022)
      Using organizational change theory to conduct an institutional ethnography that examines cultural beliefs regarding wellbeing in educational contexts and their implications for an enduring democracy, the author makes use of autoethnography to present mixed methods and participant action research designed to prioritize wellbeing at a large public university in the United States. In so doing, the author presents a sustainable change model and theory for wellbeing to improve the culture, policies, and practices of educational systems within democratic societies.
    • Scalable and Sparse Class Probability Estimation with Weighted Support Vector Machines

      Zhang, Hao; Zeng, Liyun; Watkins, Joseph C.; Hao, Ning (The University of Arizona., 2022)
      Classification problems have broad applications in many scientific areas such as biology, engineering, finance, and medicine. Support vector machines (SVMs) are popular classification tools due to their flexibility, accuracy, and fast computation for high dimensional datasets. However, standard SVMs can not estimate the probability of a data point belonging to a given class and hence fails to provide a confidence measure of uncertainty for label prediction. This drawback can be tackled by weighted SVMs (wSVMs) (Wang et al., 2008; Wu et al., 2010; Wang et al., 2019), which estimate class probabilities by aggregating multiple classification rules trained by weighted samples. Despite their promising performance, existing wSVMs have limitations in their theory, computation, and applications. Specifically, they do not perform variable selection, so both their classification accuracy and interpretability may suffer when too many noise features are present in the data. Also, the multiclass wSVM algorithm proposed by Wang et al. (2019) has a polynomial complexity in K (the number of classes), which is suboptimal. To address these issues, my Ph.D. research work is devoted to developing new ideas to improve existing wSVMs from three different perspectives. This thesis consists of three projects under the unified theme of weighted SVMs. The first project develops more efficient and scalable algorithms to reduce the complexity of K-class wSVMs from polynomial time to linear time. The second project develops a new robust classification method, called the SIBOW-SVM, for brain MRI image analysis and shows that it can outperform the state-of-art convolutional neural networks (CNNs). The third project proposes a set of new frameworks to achieve sparse learning in binary wSVMs and perform simultaneous variable selection, classification, and probability estimation in high-dimensional data. For each project, I present new statistical methods and algorithms, as well as extensive numerical studies and real examples to demonstrate finite sample performance.
    • Air Traffic, Internal Migration, and Economics in the United States

      Fishback, Price; Wang, Chao; Reynolds, Stanley; Woutersen, Tiemen; Varela, Mauricio (The University of Arizona., 2022)
      This thesis studies the causal effects on the local labor market from two types of major changes: air travel service and internal migration. Both direct estimations suffer from endogeneity concerns because of the interdependence between the changes and local economic outcomes. Therefore, I construct instrumental variables to control for the endogeneity problem in the estimation process. In the case of changes in air traffic growth, I constructed instruments in two different ways and have a chapter devoted to each. In the first chapter, I apply a Bartik (1991) shift-share instrument to construct predicted air traffic to address the endogeneity concern and study the causal effects on local economic outcomes in the US metropolitan areas from 1993 to 2016. Instruments for small airports and large hubs are constructed differently because of their different operating systems. For small airports, I multiply the air traffic growth in each hub by their shares in the small airport in the initial year of 1993 and then sum the products across hubs as an instrument for air traffic. I apply the K-Means clustering unsupervised machine learning technique to choose hubs under the hub-and-spoke system. The instrument for air traffic at large hubs is constructed similarly based on the airlines located at the hubs in 1993 and the growth rates of activity for those airlines at the national level. The results for cities with small airports reveal that a 10% increase in air traffic growth leads to a 0.64% increase in local employment growth, implying 3,200 new jobs created in a typical city. No statistically significant effects exist in cities with large hubs. The mechanism of these effects is mainly through labor demand. Financial service sectors are the primary beneficiary of air traffic growth. In the second chapter, I exploit changes in the number of airline routes due to hub activities and airline mergers to construct the instruments for local air traffic growth and estimate the effects on the local population, income, and employment growth at the county level from 1990 to 2014. The results confirm a positive correlation between air service and omitted variables in the OLS estimation. From the IV results, a 1% percent change in air service will significantly increase the population growth rate in the associated county by 0.159% and the local employment growth rate by 0.225%. There is a small and statistically insignificant effect of air service on the local per capita income growth rate, which is consistent with findings from the earlier literature about the rigidity in the per capita income adjustment. In the third chapter, I investigate the causal effect of internal migration on three local labor market outcomes: earnings, employment, and the probability of migrating out. For the endogeneity concern that migrants may be attracted to cities with good economies, I construct predicted in-migration and out-migration rates as instruments for the net-migration rate into the cities in two steps. First, I use the variation in the shift-share measures and weather events to predict the migrant flows to and from U.S. cities. Then I estimate migrants’ settlement patterns by the distance between the sending and receiving areas. The predicted in-migration (out-migration) rate is the sum over all sending (receiving) areas of the products between predicted out-migration (in-migration) flows and the corresponding probabilities of migrating to (from) that destination. The results show that net migration had little effect on the earning outcomes but did influence the hours worked in a usual week. Also, existing residents seem not to be crowded out by the in-migrants. However, net-migration flows into a metropolitan area significantly increase the employment status of existing residents. Relative to being part-time and unemployed, a one percent increase in the net-migration rate led to a 0.335% higher probability of being full-time employed. The probability of being in part-time employment was decreased by 0.171%, and the unemployment probability was reduced by 0.164%, with a one percent increase in the net-migration rate. These results imply that workers are working longer under the same wage payment system in response to internal migration instead of direct wage reduction.
    • Dynamic Kindlin-2 Complexes Containing α6β1 Integrin Are Responsive to Hypoxia

      Cress, Anne; Hernandez-Cortes, Daniel; Cress, Anne; Mouneimne, Ghassan; Warfel, Noel; Smith, Catharine; Wondrak, Georg (The University of Arizona., 2022)
      Aggressive prostate cancer (PCa) uses mechanosensitive membrane receptors called laminin-binding integrins (LBIs) to migrate and invade into and through barriers, such as the hypoxic muscle capsule of the prostate gland. Both membrane protrusions and focal adhesions (FAs) are required for cell migration, and both contain β1 integrin heterodimers. A key regulator of β1 integrin activation and signaling is kindlin-2, a cytoplasmic protein that binds membrane phosphoinositides and contains domains for directly binding β1 integrin for activation and scaffolding proteins such as paxillin (PXN) and the integrin-linked kinase (ILK) for FA assembly. The purpose of this study was to determine the dynamic cellular and biochemical distribution of a specific LBI, α6β1 integrin and kindlin-2 within membrane protrusions (defined by lamellipodin, RAPH1, or Ras-associated and pleckstrin homology domains-containing protein 1) or FAs (defined by PXN) during hypoxia within individual PCa cells. We determined whether limiting kindlin-2 protein expression would preferentially compromise either lamellipodial protrusions or FAs. Within individual tumor cells, hypoxia triggered a significant 3-fold increase in membrane protrusions within 4h, and a significant increase in FA number and area per cell up to a 2-fold and 1.5-fold maximum increases, respectively, at 16h of exposure. A non-biased selection of up to 23 cellular descriptors confirmed that non-random stabilization of FAs during 8h of hypoxia exposure. Up to a 1.5-fold increase in the formation of kindlin-2-α6β1 integrin complexes was observed using immunoprecipitation and immunofluorescence microscopy within early (4 and 8h) exposure to hypoxia that returned to normal levels at 12 and 16h of exposure without changing the constitutive expression of the proteins. Notably, kindlin-2-α6β1 integrin complexes were found exclusively within lamellipodial protrusions and were not observed within PXN-containing FAs. A CRISPR-Cas9 heterozygous deletion of the fermt-2 gene decreased constitutive kindlin-2 levels to approximately 20% and resulted in the loss of the time-dependent increase of the number and area of FAs/cell. Taken together, the results indicate that kindlin-2-α6β1 complexes are uniquely associated with FA-independent lamellipodial protrusions induced by hypoxia and a hypoxia induced increase in both FA number and area, and the membrane protrusions are particularly vulnerable to kindlin-2 constitutive levels. Since hypoxia is a physiologically relevant tumor microenvironment (TME) associated with aggressive PCa, targeting novel kindlin-2-α6β1 complexes or kindlin-2-containing FAs may represent an actionable pharmacological target to block escape of organ confined disease to impact therapeutic options and prevent recurrent disease. This study shows that the microenvironment environment of hypoxia through the formation of kindlin-2 cell adhesion complexes is a plausible mechanism of aggressive disease in PCa.
    • Hispanic Serving Institution Counterstory: Critical Agency of Managerial Professionals & Support Staff

      Deil-Amen, Regina; Cruze-Silva, Karla E.; Rhoades, Gary; Franco, Marla (The University of Arizona., 2022)
      The number of Hispanic Serving Institutions grow each year. Within HSI’s are the managerial professionals and support staff who work with students each and every day. However, little is known about the experiences of managerial professionals and support staff at HSIs. This study examined the experiences of managerial professionals and support staff working at a Hispanic Serving Institution in the Southwest area of the United States of America. I conducted a qualitative study and interviewed a total of 24 participants. Participants were also asked to complete two activities during their interviews. One activity highlighted their support networks and the other asked them to reimagine their institutions mission statement as an HSI. My findings indicate that the work being done to designate an institution as an HSI is largely done by managerial professionals and support staff. My findings also indicate that the servingness component of HSIs largely comes by the work being done by managerial professionals and support staff. These staff members are often overworked and underpaid, the majority are also women and Black, Indigenous, People of Color.
    • Fully Implantable Wireless and Battery-Free Organ Interfaces

      Gutruf, Philipp; Burton, Alex; Witte, Russell S.; Bilgin, Ali; Kang, Dongkyun (The University of Arizona., 2022)
      Seamless organ interfaces combined with high fidelity readouts and modulation capabilities offer unparalleled insights into the central and peripheral nervous system and musculo-skeletal system. A new class of wireless, battery-free platforms enable long-term experiments with continuous uninterrupted recording and stimulation, with capabilities that match or exceed those of current wired or battery-powered platforms. Combined with soft and flexible mechanics, these devices are fully implantable in small animal models enabling studies without impacting the subject’s behavior or mobility, with fast recovery times post-surgery, with reduced infection risks, and operate with lifetimes that exceed those of the test subjects. Development of this new class of device is critical to bridge the gap between preclinical and clinical research to enable new diagnostic tools to dissect understudied organ systems and to further the development of therapeutic tools for motor disorders and spinal cord injuries.Specifically, I have expanded these platforms with antenna designs optimized for use in highly miniaturized form factor to facilitate subdermal implantation in freely moving young mice. This allows long-term experiments to study complex behavioral circuits by recording cell-specific neural dynamics1. I have also implemented communication protocols that allow existing systems to receive programmed stimulation parameters without requiring additional circuity or power. This allows miniature systems to be subdermally implanted in rats to electrically modulating cell specific neural pathways, in the deep brain using surface engineered microelectrodes to study stimulation dosing and their use in therapeutic treatment of motor disorders2. I also extended the technological platform for osseosurface electronics to allow for two-way communication for devices with multimodal capabilities of stimulation and recording. This enabled devices to capture long-term metrics of bone health in real time, paving the way for personalized treatment of the musculoskeletal system3. Combined, I have advanced wireless battery-free platforms to effectively study targeted organs in freely moving subjects through the optimization of antenna and system designs, device mechanics and flexible electronics fabrication schemes and implementation of communication protocols. These systems have also led to the expansion of current experimental paradigms to study freely behaving subjects which can provide significant insight into functional mechanisms of the nervous system and musculoskeletal system which are currently substantially limited by conventional tethered, and battery powered approaches.
    • Heating of Small Solar System Body Materials

      Harris, Walter M.; Springmann, Alessondra; Carter, Lynn M.; Mueller, Beatrice; Woodney, Laura M.; Lauretta, Dante S. (The University of Arizona., 2022)
      Small bodies, including asteroid and comet populations, are leftover material from planet formation 4.6 Gya. Near-Earth objects, asteroids and comets with closest approaches to the sun of <1.3 au, are a convenient source of extraterrestrial materials, including leftovers from Solar System formation. By studying the heating of near-Earth asteroid analogue material in carbonaceous chondrite meteorites, and gas and dust interactions between the nucleus and inner coma of a Jupiter-family comet, we can learn about composition and history of these bodies. The thermal response of elements in meteorites is important for quantifying the degree of thermal isolation necessary for asteroid sample return missions, in particular the OSIRIS-REx mission to asteroid (101955) Bennu; understanding the effects thermal processing has on an asteroid surface and "rock comets" such as (3200) Phaethon; and future in situ resource utilization of asteroids and other planetary bodies for water mining. Studying materials released from short-period Jupiter-family comets (JFCs) as seen in their inner comæ, the envelope of gas and dust forming as the comet approaches the Sun, provides an improved understanding of the evolution and origin of these objects. In 2017, a 1.2-km JFC, 45P/Honda-Mrkos-Pajdušáková, passed 0.08 au from Earth, presenting an excellent opportunity to observe this object at close range to study its inner coma, resolving gas and dust structures and characterizing the properties of large (>2 cm) grains leaving the nucleus. Detailed measurements from ground-based visible-wavelength and radar observations were made of 45P’s inner coma, a region typically too far away to obtain adequate spatial resolution, and/or typically obscured by photodissociation products of the volatile species targeted by this work. Connecting dust grain observations from continuous wave radar with visible imaging of volatile species and smaller dust particles, as well as radar-derived shape models of nuclei, allows for a more holistic understanding of processes occurring in the inner comæ of JFCs.
    • Origins of the Mexica People: Perpectives from the Mexica Culture

      Short, Kathy G.; Nicholas, Sheilah E.; Tirado-Paredes, J. Carmen; Garcia, Jeremy (The University of Arizona., 2022)
      The purpose of this research study is to understand the origins and philosophies of the Mexica people, commonly known as the Aztecs from Central Mexico, from the perspectives of those who identify as Mexica. Today in modern day academia these understandings of who the Mexica are and how they originated are constructed by those outside Mexica cultural perspectives and continue to dominate the rhetoric of scholarly research on the Mexica People. This means that there is an enormous void in the literature, because Mexica voices and Mexica cultural perspectives are left out of the literature. This research study has the main goal to address the following research question from within Mexica cultural perspectives: Who are the Mexica people and what are their origins? This research study utilizes a basic design for qualitative research methods with person-to-person semi-structured interviews as the means of collecting data. To be selected for these interviews, the participants had to be considered Mexica Elders or Mexica leaders within their Mexica communities. The research analysis is rooted in the Oral Tradition story of Xolotl and Nahui Mitl (Four Arrows) as told by Tlakaelel (1998) a highly respected Mexica-Tolteca Elder. In this story, Tlakaelel (1998) talks about the origins of the Mexica people and the founding of their capital city named Mexico-Tenochtitlan in the valley of Mexico. This Oral Tradition story has been passed down from generation to generation and was given to Tlakaelel by the Acolhua Council of Elders. For this reason, I have chosen to use this Oral Tradition story as the touchstone story for the origins of the Mexica people. I break down the key events that describe the different aspects of the origins of the Mexica people from the story of Xolotl and Nahui Mitl Four Arrows. I present the data collected from the interviews with the Mexica Elders/leaders and connect their information to the key events. Then I compare the accounts from the perspectives from those outside Mexica culture to the accounts from Tlakaelel’s Oral Tradition story and to the accounts from the interviews with the Mexica Elders/leaders. A discussion on the significances and nuances of the comparisons and differences between the accounts by scholars outside the Mexica culture to the accounts told by elders and leaders from within Mexica culture is presented in the final chapter. Also presented in the last chapter are the implications from this research on the Mexica people from Mexica cultural perspectives. These implications look at the implications for future research, the significance of Oral Tradition, the 2000-year-old vision of the Mexica people, and the implications for the development of a Mexica educational paradigm grounded in the Mexica culture in relation to being Citizens from the Center of the Universe.
    • VR and Vocabulary Acquisition: Exploring Participant Vocabulary Outcomes, Tendencies, and Perceptions of Game Narrative and Task

      Nicol, Janet; Monzingo, Jacob A.; Reinhardt, Jonathon; Ecke, Peter (The University of Arizona., 2022)
      Recent developments in Virtual Reality (VR) technologies are creating a shift in Second Language Acquisition (SLA) studies. Multiple studies have been performed that examine language learning in two dimensional (2D) and three dimensional (3D) software based virtual worlds (Lim, 2009; Lloyd et al. 2017; Sadler, 2017; Schwienhorst, 2002; Lin and Lan, 2015). Theories of embodied cognition, where essentially the human body and its capacity for any type of environmental interaction influence how a learner can process information, suggest that these new VR technologies may create enhanced learning through embodiment (Atkinson, 2010; Shapiro, 2011). However, significant research utilizing VR Head Mounted Displays (HMDs) has been limited to concrete experience words (Moseley et al, 2016; Repetto et al, 2015) while much remains to be studied within Second Language Acquisition. Considering that the most frequently touted benefit of VR-HMDs is an affordance for full integration in highly immersive environments (Lloyd et al. 2017; Sadler, 2017), and the preponderance of data available regarding VR before the advent of HMDs centered on digital games as environments that provide foci for participant immersion, it becomes increasingly critical to determine what constitutes those immersive environments, learner immersion, and what, if any, are the different learner tendencies that influence those affordances (Boot et al, 2011; Cornillie et al, 2012; Culbertson et al, 2016; DeHaan et al, 2010; Gonzalez-Lloret, 2017; Koops et al, 2016; Lim, 2009; O’Brien et al, 2009; Peterson, 2010; Ryan, M.L, 2001; Reinders, 2017; Reinhardt & Sykes, 2013; Wang et al, 2017).In this study, multiple instruments will be used to measure and determine what benefits VR-HMDs afford second language learners during vocabulary recall. Three evenly distributed groups of participants will perform the same tasks under three different conditions in the target language using comparative analysis between a Picture Recognition Task (control group), a Standard PC game task (experimental group 1), and a VR-HMD task (experimental group 2) using the commercially available game Fallout4 and Fallout4VR (published by Bethesda, 2017). Additionally, participants in the two experimental groups will be given an emotionally affective narrative to determine in what ways VR may enhance/diminish emotion and recall. All participants will provide survey data regarding their immersive tendencies, game-play preferences (if any), their immersion experience, and they will perform pre/post vocabulary tests. These conditions will provide insight into the intersections of qualities of immersion, gamer tendencies and perspectives, and VR-HMDs.
    • Enhanced Recommender Systems by Biclustering

      Zhang, Hao; Chung, Kyung Mi; Hao, Ning; Fan, Neng; Tang, Xueying (The University of Arizona., 2022)
      Recommender systems play a very important role to explore and suggest personalized recommendations to users from a huge number of choices. In this thesis, we propose a new class of enhanced recommender systems, called BiRDS (meaning Biclustering Recommendation Systems) and develop three different modeling approaches under the new framework: iBiRDS (imputation BiRDS), rBiRDS (regularization BiRDS), lBiRDS (logistic BiRDS). All the three methods utilize biclustering to incorporate correlational traits between users and items. In this research work, we propose to identify the biclusters of associated users and items through a weighted bipartite network of users' feedback and a fast community detection algorithm. Concurrent information of users and items is either imputed or integrated into the singular value decomposition (SVD) framework without requiring any domain knowledge. Computationally, the BiRDS estimation avoids large matrices operation and memory storage, making it advantageous to attain scalability for massive datasets. Moreover, the BiRDS can effectively combat the ``cold-start" issue by utilizing bicluster effects of associated users and items while most collaborative filtering methods depend on subject-specific parameters only. For the proposed BiRDS methods, we develop their estimation framework and computational algorithms, study their computational complexity and convergence properties, and establish their theoretical guarantee in terms of the asymptotic properties. In addition, we perform extensive numerical experiments to evaluate the performance of the new methods and compare them with existing techniques in the literature. Our simulation studies and several real data analysis demonstrate that the proposed methods can enhance prediction accuracy of recommender systems with significantly less computing time compared to existing competitive approaches.
    • Effective Field Theory of Quantum Scattering States

      van Kolck, Ubirajara; Fleming, Sean; Balalhabashi, Jaber; Gralla, Samuel; Meinel, Stefan; Su, Shufang (The University of Arizona., 2022)
      Low-energy scattering in the quantum regime can reveal a lot about the long-range interactions of particles. An efficient tool for studying these reactions is effective field theory (EFT) in which the physics of short-range interactions are encapsulated inthe effective parameters of long-range interactions. In this thesis, EFTs are applied to various shallow quantum scattering states. Since resonances are of particular importance to the scattering of particles in quantum mechanics, low-energy EFTs are built for two-body scattering which includes a low-energy S-wave resonance. Manifestly renormalized scattering amplitudes up to next-to-leading order are constructed in a systematic expansion. The starting point is the most general Lagrangian with only short-range contact interactions that are organized into various orders to generate a systematic expansion for an S matrix with two low-energy poles. The pole positions are restricted to the lower half of the complex momentum plane by renormalization at leading order, where the common feature is a non-positive effective range. The use of contact interactions is limited to the broad resonances due to complications of resummation, therefore the study of S-wave scattering systems is extended to other types of resonances by using an auxiliary field with the quantum numbers of the resonance. For a narrow resonance, the amplitude is perturbative except in the immediate vicinity of the resonance poles, and it naturally has a zero in the low-energy region, analogous to the Ramsauer-Townsend effect. For a broad resonance, the leading-order amplitude is nonperturbative almost everywhere in the regime of validity of the EFT. An additional fine-tuning leading to a low-energy amplitude zero even for a broad resonance is also considered. In all cases when the auxiliary field is not a ghost, the requirement of renormalizability ensures the resonance poles are in the lower half of the complex momentum plane, as expected from other arguments. The systematic convergence of EFT results for resonances with or without auxiliary field is examined and compared with an underlying toy model — a spherical well with a delta shell at its border. Finally, auxiliary fields (dibaryons) along with perturbative pions are used for the uncoupled P-wave channels of two-nucleon scattering. Reasonable fit to phase shifts is obtained up to a center-of-mass momentum of about 400 MeV.
    • Teaching the Grammars of Suffering: The Anti-Black Technologies of White Womanhood in Teacher Discourse

      Koyama, Jill; Wedig, Rachel Miranda; Demps, Dawn; Bertrand, Melanie (The University of Arizona., 2022)
      Students today are more likely to have a white woman teacher than a teacher of any other race and gender combination. White women teachers have become so prevalent that to have a teacher of color and/or a male or otherwise non-woman teacher is exceptional. In this way, the white womaness of teaching is all but assumed and surely has broad implications for the perceptions and practices of teaching as well as the educational system as a whole. Attention has been paid to the whiteness of teaching as well as the “feminization” of the teaching profession, however these are often treated as separate studies – those which attend to race and those which attend to gender. What this paper hopes to propose is an alternative way for thinking about white women teachers, one which acknowledges that such identities as race and gender cannot be so easily parsed from one another and are actually co-constitutive. This project attempts to explore this entanglement and how deeply it has rooted itself in our current conceptions of the educational system as well as any efforts at reform within it.
    • Phenomenology in Nuclear and Hadronic Physics Using Effective Field Theories

      Fleming, Sean; Lieffers, Justin; van Kolck, Ubirajara; Stafford, Charles; Meinel, Stefan; Varnes, Erich (The University of Arizona., 2022)
      Effective Field Theories (EFTs) are used to provide precision results of phenomenological problems in nuclear and hadronic physics. First, Soft Collinear Effective Theory (SCET) is reviewed in brief. It is then applied to the problem of Semi-Inclusive Deep Inelastic Scattering (SIDIS) in order to extract information about the nonperturbative nature of Transverse Momentum Dependent Parton Distributions (TMDPDFs). We apply a Hybrid Momentum space impact parameter resummation scheme to reduce the amount of nonperturbative physics that is modeled by a resummation scheme. The results are compared to data from the HERMES experiment and are used to inform further improvements for extractions from the future EIC measurements. Second, Chiral Perturbation Theory and Chiral Effective Theory (Chiral EFT) are introduced and reviewed. In the Chiral EFT framework, one can extract information about beyond Standard Model operators at the nuclear scale. This has been applied to neutrinoless double beta decay problems. In order to have a properly renormalized description of this phenomenon we need constrains on a lepton number violating (LNV) operator. This operator is similar to a charge Independence breaking (CIB) operator. All it requires is a rescaling and isospin rotation. We calculate CIB potentials for up to four body interactions in order to constrain this operator and thus get constraints on the LNV operator needed for extractions of neutrinoless double beta decay. Finally we take a brief look at the photo-production of quarkonium and how resolving current disagreements can make this a powerful tool for the extraction of the gluon TMDPDF.
    • Positive Youth Development (PYD) Among Latinx Adolescents

      Carvajal, Scott; Delgado, Melissa Y.; Coulter, Kiera; Nair, Rajni; Nuño, Velia (The University of Arizona., 2022)
      Background: Deficits-based approaches have predominated research on Latinx adolescents. Positive youth development (PYD) frameworks are needed within studies on Latinx youth to illuminate how their assets and strengths relate to their adjustment. Research should examine the applicability and roles of PYD constructs in Latinx adolescents’ development. Objective: This dissertation examines the measurement and developmental salience of PYD constructs among Latinx youth specifically. This overarching objective is divided into a scoping review and two empirical studies, drawing from an ethnically-homogenous Latinx adolescent sample. The studies focus on various components of the Five C’s model of PYD, a widely utilized and empirically supported PYD framework. Methods: The first study is a scoping review that examined the conceptualization and operationalization of future orientation constructs in studies of Latinx adolescents, as well as summarized the associations between future orientation constructs and indices of adjustment. The second study tested and compared factor structures of the PYD-Short Form (PYD-SF) using confirmatory factor analyses within a sample of Latinx adolescents, and examined the criterion validity of the Five C’s with key developmental outcomes. The third study utilized latent growth curve modeling to assess trajectories of thriving and the Five C’s over the transition to high school among Latinx adolescents, and tested factors hypothesized to have a promotive effect on thriving per the Five C’s model of PYD. Results: Within the scoping review, 31 studies were included in the full-text analysis. The articles examined various dimensions of future orientation as opposed to global future orientation. Future orientation constructs were promotive factors, buffers of risk, and key mechanisms in associations between Latinx youth’s cultural milieu and adjustment. The second study provided empirical support for the five-correlated factors model within a Latinx adolescent sample, and showed that the Five C’s were associated with important indicators of adolescent well-being (i.e., externalizing behaviors, internalizing behaviors, and academic achievement). The third study showed that thriving and the Five C’s displayed slight declines over the transition to high school. Select individual assets (i.e., educational expectations, emotional school engagement) and ecological assets (i.e., maternal warmth, paternal warmth) were promotive of baseline levels of thriving and the Five C’s, but were not positively related to the linear slope terms in the models. Conclusions: Together, these studies suggested the developmental salience of PYD constructs (i.e., future orientation and the Five C’s of PYD) in Latinx adolescents’ development. However, more investigation is needed to improve the measurement of future orientation and global PYD (i.e., overall thriving). The Five C’s model of PYD may need to be expanded to capture sociocultural factors that relate to thriving among Latinx youth specifically.
    • Portraying Chilean Educators: Motivations and Practices to Address Educational Inequities for Immigrant Students in an Elementary School in the Bio-Bio Region

      Bertrand, Melanie; Mendoza Mardones, Ana Isabel; Nguyen, Chi; Schutz, Paul; Combs, Mary Carol (The University of Arizona., 2022)
      In the last decade, Chile has abruptly multiplied the number of international migrant families living in the country. This new reality has affected Chilean society, principally public schools where Chilean teachers have not been prepared to work in an intercultural context. It has developed two types of literature in the area: one, remarking the challenges for elementary teachers working with immigrant students and the situations of racism and classism in the classrooms. While other literature stating the practices of excellence developed for teachers to create trusting relationship with their international migrant students. This research aims to gain a better understanding of teachers’ reasons and practices readdressing inequities for immigrant students. A derived goal is starting the discussion about classism and racism in Chile. A hybrid qualitative method of case study and grounded theory let the description of Chilean elementary teachers’ motivations, practices, and representations working with international migrant students. The finding for Chilean teacher reasons, shows the empathy about context life of their immigrant students, and the vocación for teaching. In addition, teachers claim for the development of welcoming protocol and a major government-school support in their new multicultural classrooms. They focus their practices on the academic area and some of them are beyond the school, visiting students and families. The good, intended practices have a superficial approach far of a critical praxis. Teachers’ representations present the complexity of racism in Chile, with teachers aware about the reality and the other extreme denying its existence. Finally, are presented the unique characteristics of this group of elementary teachers. Chilean elementary teachers’ actualization of critical theories and a deep reflection about significant practices looking for social justice are necessary.
    • Intergenerational Counternarratives of Creative Agency: Reimagining Inclusive Practices Through Youth Participatory Action Research

      Kraehe, Amelia M.; Crabbe, Kendall Marie; Wilson, Gloria J.; DiCindio, Carissa; Cammarota, Julio (The University of Arizona., 2022)
      Since the 1990s, art museums across North America and Europe began actively recruiting teen or adolescent audiences, often through co-created programs aimed at increasing youth participation in the arts. Scores of these programs target young people–and youth of color, specifically–to grow and diversify art museum attendance. Although there is growing interest and investment in youth audiences to diversify museum attendance, there is limited research that examines the hidden tensions of such programs and their efficacy for youth development (Tzibazi, 2013). Inspired by post-critical ethnographic approaches (Noblet et al., 2004) to Youth Participatory Action Research (Cammarota, 2008), this study centers the intergenerational desires and perceptions of youth and adult co-researchers in a teen-centric program (Szekely, 2012). By investigating the counternarratives (Solórzano & Yosso, 2002) of teen and adult co-researchers, we sought to learn more about participation and creative agency from those at the center of these programs. In service of these aims, the following research questions were asked: As a YPAR collective, how did we navigate and negotiate our participation in a teen-centric program? And, how did we work together to develop creative agency? This dissertation draws from a three-year longitudinal qualitative case study of a YPAR collective that worked inside and outside a Southwestern Art Museum. Data were generated collectively through participant observations; in-depth individual and focus group interviews; and program materials such as artworks, designs, and other artifacts. The complete dataset was analyzed inductively and in collaboration with youth co-researchers (Marshall & Rossman, 2016; Ladson-Billings, 2009). The analysis of data was informed by critical theory; in particular, the concepts of interest convergence (Bell, 1980); critical conceptual frameworks for arts participation (Bae-Dimitriadis, 2017; Kraehe, 2017; Simon, 2016; Yosso, 2005); and mestiza consciousness (Anzaldúa, 1987; Torre & Ayala, 2009). This conceptual and theoretical framework helped illuminate how the neoliberal art museum unwittingly contributes to maintaining white supremacy even as it seeks and speaks of cultural equity. The findings of this study offer critical insights on youth creative agency, participation, and inclusivity discourses within neoliberal art museums. The conclusions suggest that the paradoxical realities young people face in art museums can offer a radical space of possibility to foster creative agency and resistance.