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Now showing items 41-60 of 108218

    • Environmental Heat Stress Response and Adaptation in Ruminants

      Diaz, Duarte; Rios Lugardo, Andrea; Limesand, Sean W.; Garcia, Samuel; Wulf, Duane (The University of Arizona., 2024)
      Environmental heat stress represents a worldwide problem for ruminant production, negatively impacting areas such as lactation, fetal development, and muscle growth. The aims of this dissertation were to determine the impact of environmental heat stress during gestation on the lactation performance of ewes, and the consequences of maternal heat stress on the post-natal performance of their offspring. Further, we tested the effect of supplementation with ß-adrenergic agonists on the growth performance of beef cattle exposed to environmental HS. To determine the influence of maternal heat stress (HS) on milk production, nineteen Columbia-Rambouillet pregnant ewes carrying singleton were exposed to hot ambient environment (n=7) or thermoneutral (TN) conditions during mid-gestation. Dry matter intake (DMI) and water intake (WI) were measured daily. At lambing, placental weight and colostrum production were measured, and for 21 days, daily milk yield was evaluated. Heat stressed ewes had lighter placental and fetal weight than TN ewes; however, colostrum production was not different. TN ewes had a similar total milk production than HS ewes. Daily milk production was higher on TN ewes on days 2, 5, and 6. HS during gestation negatively affects placental mass and milk production, impacting the nutrient sources for the fetus and causing growth restriction. In order to determine the impact of maternal heat stress on the offspring's growth performance and insulin response, twenty-one Columbia Rambouillet crossbred lambs (TN=12 and FGR=9) were used. Milk, feed, and body weights were recorded daily for eight weeks. Body measurements were taken weekly for eight weeks. Glucose tolerance tests were performed at four and eight months of age to evaluate the insulin response. HS fetuses were growth-restricted because HS lambs were 27% lighter than TN lambs at birth, indicating maternal HS caused FGR. Body weight of FGR lambs was lighter than that of TN lambs for the next eight weeks or until weaning. However, the average daily gain (ADG) and gain to feed (G:F) were not different between groups. FGR lambs presented smaller body measurements than TN lambs, except for head length (HL), which was similar between group treatments. After the intravenous glucose challenge, insulin concentrations were lower in FGR lambs than in TN lambs at four and eight months of age. FGR lambs presented asymmetric growth restriction in utero and had abnormal insulin secretion response. The use of ß-adrenergic agonists was evaluated with twenty-four Brahman steers exposed to two environmental conditions, TN and HS, and supplemented with or without Zilpaterol hydrochloride for 21 days. DMI, water intake, respiratory rate (RR), and rectal temperature (RT) were measured daily. After 21 days of supplementation, Brahman steers were relocated to the feedlot and harvested at an average weight of 544 kg post supplementation/environmental treatment, and carcass merit was evaluated. RR was higher on Brahman exposed to HS. Non-supplemented Brahman steers exposed to HS presented higher RT than TNZL steers on day eight. Heat-stressed steers supplemented with ZL had higher RT on day eleven than TNCN steers. ADG and G:F did not present significance nor carcass merit. No negative impact on growth and carcass characteristics was seen on Brahman steers exposed to HS. Zilpaterol supplementation did not affect the carcass merit, demonstrating an option to mitigate HS's adverse effect on Bos indicus. Environmental heat stress is a global problem that affects all stages of ruminant production and impacts the economy. Maternal heat stress during gestation results in a smaller placenta, decreasing the nutrients available to the fetus and fetal birth weights, causing asymmetric growth and a decrease in insulin secretion concentration. Maternal heat stress also affects milk production in lactated ewes, directly impacting the availability of milk nutrients. Similarly, HS postnatally decreases muscle growth in ruminants.
    • Enhancing Educational Choices: A Study of Mathematics Directed Self-Placement at a Community College

      Lopez, Jameson D.; Garcia, Angela J.; Deil-Amen, Regina; Salazar, Karina (The University of Arizona., 2024)
      Mathematics placement and courses can be a key factor in determining the pace and success of student educational pursuits. This study delves into the potential effectiveness of Directed Self-Placement (DSP), also referred to as Guided Self-Placement or Self-Directed Placement, as opposed to traditional placement methods, in fostering successful completion of college-level math courses within two semesters at one particular institution. Using a quantitative research design, this investigation employed logistic regression analysis to compare the outcomes of students placed via DSP with those placed through more traditional procedures. The study further explored the interplay between students' demographics and their chosen level of math course.The findings reveal a nuanced landscape where, predominantly, students who engaged in DSP exhibited a higher likelihood of completing their requisite college-level math courses within the designated two semesters. However, intriguing exceptions emerged, particularly among students majoring in science, technology, engineering, or mathematics (STEM), where traditional placement methods seemed to offer an edge. Moreover, the analysis uncovered intriguing relationships between the choice of math course in the DSP process and the subsequent success rates. This research contributes to the ongoing discourse on academic placement strategies in community colleges, highlighting the potential of DSP to enhance educational outcomes while also recognizing its limitations and the need for a nuanced application. The implications of these findings are significant for educators, administrators, and policymakers striving to optimize placement processes and, ultimately, to support students in achieving their academic and professional goals efficiently.
    • Efficient and Robust Inference of Neutron Star Parameters From Pulse Profile Modeling

      Chan, Chi-kwan; Zhao, Tong; Wolgemuth, Charles; Krause, Elisabeth; Su, Shufang; Psaltis, Dimitrios; Ozel, Feryal (The University of Arizona., 2024)
      Modeling of X-ray pulse profiles from millisecond pulsars offers a promising method of inferring the mass-to-radius ratios of neutron stars. Recent observations with NICER resulted in measurements of radii for two neutron stars using this technique. In this dissertation, I explore correlations between model parameters and the degree to which individual parameters can be inferred from pulse profiles, using an analytic model that allows for an efficient and interpretable exploration. I introduce a new set of model parameters that reduce the most prominent correlations and allow for an efficient sampling of posteriors. I use this framework to show that the uncertainties in the model parameters for neutron stars for which the polar cap temperature falls outside of the NICER energy range are significantly degraded. I also demonstrate that the degree of beaming of radiation emerging from the neutron star surface has a large impact on the uncertainties in the inferred model parameters. In particular, when a model with an incorrect beaming function is used to fit data, the inferred neutron star mass-to-radius ratio can be significantly larger than the true value. This has important implications for interpreting and assessing the radii of neutron stars inferred through pulse profile modeling.
    • Ecology and Evolution of Melanin Pigmentation Plasticity in a Complex World

      Davidowitz, Goggy; Britton, Sarah Elizabeth; Bronstein, Judith; Dornhaus, Anna; Matzkin, Luciano (The University of Arizona., 2024)
      Phenotypic plasticity is the ability of a single genotype to produce multiple phenotypes in response to different environmental stimuli. Plasticity is a widespread phenomenon that takes many forms and is often thought to be adaptive, helping organisms optimally match phenotypes to a heterogenous environment. Organisms experience and respond to many dimensions of environmental variation at once. Many plastic traits are induced by multiple environmental cues and are under more than one selective pressure. Together, these environments determine the functional roles of a trait and the constraints on a trait. To determine if plasticity is adaptive, it is necessary to understand the balance of these functions versus constraints. In the following studies I investigate melanin pigmentation plasticity in the white-lined sphinx moth, Hyles lineata (Sphingidae). During the late larval instars this species displays melanin plasticity (plasticity in the degree of melanin pigmentation), which is induced by multiple environmental cues. I investigated two potential functional roles of melanin: thermoregulation and desiccation prevention. While I did not find support for a role of melanin in desiccation prevention, I did find evidence that melanin is adaptive in cold environments. More melanic larvae outperform less melanic larvae in cold environments, while suffering no costs of melanization in a warm environment. I then considered two potential constraints on melanin: resource limitation and resource allocation trade-offs. I found that tyrosine, the amino acid precursor of melanogenesis can constrain the production of melanin, although it is still prioritized in certain contexts. Furthermore, larval melanin pigmentation trades off with other important traits, including immunity and adult pigmentation, which may be costly in certain environments. Finally, I tested whether patterns of melanin plasticity have diverged adaptively between populations from different thermal environments. I found that reaction norms differed between populations, although the patterns were only partially consistent with a role of climate in driving differences in plasticity. Overall, I show that to determine whether melanin plasticity is adaptive in this species, it is important to consider not just the thermal environment but also the nutritional environment and the costs of producing melanin. Understanding both the functional roles of and the constraints on a plastic trait are necessary to determine the adaptive value of its plasticity.
    • Dominick Argento’s I Hate and I Love: A Comprehensive Analysis for Conductors

      Vanderlee, Jeff; Seo, Hyoungil; Schauer, Elizabeth; Davis, M. Nicole (The University of Arizona., 2024)
      Dominick Argento was an American contemporary composer who achieved great fame as a composer of vocal music, especially lyric opera. The theatrical devices in his works make his compositions distinctive, and Argento's use of symbolic motivic cells is one of the main characteristics that drives the narrative structure in his works. Dominick Argento's I Hate and I Love is an intricate choral work in which Argento masterfully blends twelve-tone techniques with traditional harmonic language to convey the complex emotional interplay between love and hate as expressed in the poetry of Gaius Valerius Catullus. In this document, I explore Argento's compositional methods, focusing on his use of symbolic motivic cells, harmonic structures, and dramatic elements that align with the text. By analyzing these techniques, I reveal how Argento's music serves not only as a reflection of Catullus's emotional turmoil but also as an omniscient commentary that adds layers of meaning beyond the explicit text. This research contributes to the broader academic discourse on Argento's choral works, providing deeper insights into his innovative approach to choral composition and his unique integration of serialism with sonorism.
    • Development of Novel Deep Learning Techniques for Accelerated Diffusion MRI

      Bilgin, Ali; Martin, Phillip; Cao, Siyang; Marcellin, Michael (The University of Arizona., 2024)
      Diffusion Magnetic Resonance Imaging (dMRI) is an imaging modality of MRI that features a non-invasive technique for qualitatively and quantitatively characterizing microstructural characteristics in tissue. This is achieved by dMRI being sensitive to the Brownian motion of water molecules in tissue measured over an applied magnetic field gradient. The directional orientations of motion of water molecules are estimated over an isotropic gaussian propagator. This capability enables dMRI to achieve resolution of microstructural features of up to 2-3 orders of magnitude below the resolution limit of conventional MRI. However, delineation of resolving features and characteristics with high degrees of architectural specificities requires making underlying assumptions of the underlying diffusion signals and invoking appropriate mathematical and computational solutions to achieve this. One computational technique of interest for dMRI is Diffusion Tensor Imaging (DTI). DTI enables anisotropic measurements to be acquired by fitting multiple diffusion-weighted images (DWIs) to a tensor, enabling 3D reconstructions of microstructural features of the brain, including the ability to reconstruct trajectories of white-matter tracts. Some of the challenges of performing DTI in routine clinical and research studies include long data acquisition times required to obtain sufficiently large number of DWIs for outputting robust tensor estimates. This involves long scan times and typically introduces undesired image distortions and artifacts that deteriorate image quality. In addition, DTI has limitations in accurately delineating more complex microstructural features in white-matter tracts. Models in Diffusion Kurtosis Imaging (DKI) and Constrained Spherical Deconvolution (CSD) offer improvements over DTI. However, these models require considerably more data than DTI and are generally more complex to implement. Although some prior deep learning (DL) techniques have addressed limitations of conventional diffusion models, these techniques typically involve supervised-learning frameworks that require large amounts of clean training data to successfully produce robust estimates of metrics and are typically constrained to diffusion-specific models. For this research, we propose DL techniques that address some of these challenges. The contributions made by this dissertation involve a Self-Supervised with Fine-Tuning DL pipeline that can produce robust DTI metrics for an accelerated acquisition of DWIs and reduces the need of a large volume of clean training data. We also demonstrate a Generative Diffusion Deep Learning model that can effectively leverage uncertainty to generalize well to the underlying distribution of tensor model metrics in DTI and DKI and bypasses the need for diffusion-model fits. We also present a DL pipeline, AcceleraTed deep-LeArning for model-free and multi-Shell (ATLAS) DWI, that can predict a full acquisition of DWIs across multiple shells, given an accelerated acquisition in one shell or multiple shells. This enables for the potential for robust DTI tensor estimates, overcoming the requirement for large amounts of clean training labels, and eliminates the constraint of diffusion-specific models, which introduces the exciting potential to obtain diffusion metrics that more accurately delineate white-matter tracts.
    • Des Sons Harmoniques: Mazas’s Legacy on Violin Pedagogy, Discussion of the Violin Duo Genre, and Analysis of Mazas’s Violin Duos

      Kantor, Timothy; Zhou, Yang; Buchholz, Theodore; Alejo, Philip (The University of Arizona., 2024)
      This project provides a comprehensive analysis of Jacques-Féréol Mazas’s contributions to violin pedagogy through his extensive oeuvre, particularly focusing on the educational and artistic value of his violin duos. It explores Mazas’s life, his pedagogical methodologies, and his influence on the violin duo genre, framing these within the context of broader music education trends. By dissecting works such as the foundational Violin Method, Op. 34, his intermediate collection of Six duos faciles et progressies, Op. 46, Twelve Little Duets, Op. 38, and his most demanding duo compositions, Six duos concertans, Op. 71 and Six grands duos, Op. 41, the study illustrates how Mazas’s duos effectively prepare students for advanced solo violin and diverse chamber music performances. The project outlines a developmental trajectory for violin students, from basic techniques to complex performance skills, highlighting Mazas’s unique approach to integrating technical proficiency with expressive musicality through duo works. The research underscores Mazas’s lasting impact on violin pedagogy, providing insights into the use of his duos as a structured pathway from foundational training to professional artistry.
    • Cyber-physical Identity Binding for Autonomous Vehicles using Monocular Cameras

      Lazos, Loukas; Koplon, Lewis William; Li, Ming; Cao, Siyang (The University of Arizona., 2024)
      We address the problem of cyber-physical access control for connected autonomous vehicles. The goal is to bind a vehicle's digital identity to its physical identity represented by its trajectory. We highlight that simply complementing digital authentication with sensing information remains insecure. A remote adversary with valid or compromised cryptographic credentials can hijack the physical identities of nearby vehicles detected by sensors. We propose a cyber-physical challenge-response protocol named Cyclops that relies on low-cost monocular cameras to perform cyber and physical identity binding. In Cyclops, the ego vehicle acts as a verifier who challenges a prover vehicle to prove its claimed trajectory. The prover constructs a response by capturing a series of scenes in the common Field of View (cFoV) between the prover and the verifier. Verification is achieved by matching the dynamic targets in the cFoV (other vehicles crossing the cFoV). The security of Cyclops relies on the spatiotemporal traffic randomness. We validate the security of Cyclops via simulations on the CARLA simulator and on-road real-world experiments in an urban setting.
    • Creating from Our Mothers' Gardens: Intergenerational Hair Narratives and Black Adolescent Identity Development

      Yoon, Jina; Beard, Kayla; Perfect, Michelle; Mayes, Renae (The University of Arizona., 2024)
      In the context of identity development, hair is a large factor in how women and girls feelabout themselves and serves as a base for their personal merit, value, and worth (Mbilishaka, 2018). Messaging around hair in media, communities, and schools can impact the quality of the lens girls use to evaluate themselves. Black parent’s child rearing sets the tone for the formation of their child’s self-conceptualization and racial identity development (Davis Tribble et al., 2019; Mbilishaka & Apugo, 2020). This study aimed to bring light to issues that are relevant and prevalent to the lived experiences of Black adolescent girls regarding their hair. Using womanism and critical narrative inquiry, the stories of five Black girls were collected and analyzed for notable themes. Through their stories, the girls indicated that their mothers served in primarily supportive roles for their hair experiences, and they used shared and varied hair stories of female family members to make sense of their own hair stories. The findings also indicated hair as a powerful medium for self-expression for Black girls and they revealed how the girls transform negative hair experiences into dreams for a better future. The findings of this study suggest deeper exploration of hair’s role in Black girl identity development, especially as it relates to family experiences and school dynamics, to ensure the fullest and widest breath of support for Black girl sense of self. This study adds to existing literature, highlighting hair as an underutilized intervention point for building up adolescent Black girls’ positive racialized and gendered identity development.
    • Concert Music for Horn by Cinematic Composers

      Lundy, Johanna; Lu, Yuxin; Mugmon, Matthew; Reid, Edward (The University of Arizona., 2024)
      This document delves into four representative pieces for solo horn by cinematic composers: Concerto for Horn and Orchestra by John Williams, Wingspan by Gary Kuo, Cape Horn by Otto M. Schwarz, and Remembrances for horn and piano, op 130, by Michael Conway Baker. I explore the ways these four compositions are similar to cinematic music and what they share with traditional classical music. I focus on the background, compositional elements, and musical characteristics of each piece, and I include performance notes for each piece. This document will allow readers to better understand the relationship between concert music and cinematic music.
    • Care and Freedom from Below: Experiments in Trans Autonomy through DIY

      Geary, Adam; Hayward, Eva; Barksdale, Alex; Stryker, Susan (The University of Arizona., 2024)
      Care and Freedom from Below examines trans do-it-yourself (DIY) health practices, with a focus on gender-affirming hormone therapy, as a communal form of care responding to oppressive, alienating, and inaccessible trans medicine. I use anarchism as my conceptual framework to theorize the political meanings, potentials, and limits of these practices. By analyzing the public texts of this community, including guides, websites, and zines, this dissertation presents trans DIY as a field of knowledge, a set of ethical principles, and a political imagination for trans autonomy. Though not an explicitly anarchist practice, I argue trans DIY shares an affinity with anarchism through its values and forms of organization, including autonomy, nonhierarchy, direct action, mutual aid, and harm reduction. Trans DIY represents a fundamental challenge to the medicalization, alienation, and gatekeeping at the heart of institutional trans medicine. Through autonomous knowledge production and communal resources, trans DIYers work to make self-medication as safe and effective as possible. Moreover, DIY enables new pathways for and meanings around transition that escape the medicalized model. Ultimately, though, DIY is not a solution to the barriers and contradictions within trans medicine, nor is it a ready blueprint for postcapitalist healthcare. Rather, trans DIY practices are imperfect experiments in autonomy, convoking a trans radical imagination of how care might look otherwise.
    • An Investigation into Components of 'Flexibility' and its Relationship to Psychopathology

      Allen, John JB; Benjamin, Jasmine Somer; Grilli, Matthew D.; O'Connor, Mary-Frances; Sbarra, David A. (The University of Arizona., 2024)
      Flexibility, often regarded as crucial for mental health, remains a construct that lacks a clear definition despite its potential clinical utility. This study conceptualizes flexibility as the ability to manage interference or distress by taking appropriate actions that align with situational demands and support the pursuit of personal goals or values. We assessed cognitive control components—updating, inhibition, and shifting—using affective (happy and sad faces) and neutral (male and female faces) versions of n-back, Go/No-Go, and stimulus-response mapping shifting tasks. Additionally, participants completed self-report measures of cognitive and psychological flexibility, mood disturbance (including symptoms of depression and anxiety), emotion regulation (difficulties, use of contrast avoidance, perseverative thinking), psychological wellbeing, subjective social status, and physical health. Data were collected remotely from 751 undergraduate students during the COVID-19 pandemic, using two recruitment sources pooled for analysis: a university psychology research pool and a commercial research site. Latent profile analysis and multiple linear regression results indicate that participants who exhibit greater modulation of cognitive control in response to emotional stimuli report lower levels of distress and higher levels of wellbeing across self-report measures.
    • A Conductor’s Analysis of Mongol Shatar by Se Enkhbayar

      Schauer, Elizabeth; Jiang, Mengda; Decker, Pamela; Vanderlee, Jeffrey K (The University of Arizona., 2024)
      As one of the first Chinese composers to publish choral works in the United States, Se Enkhbayar (b. 1956) stands as a towering figure in Chinese choral music. His works are heavily influenced by folk songs and have a strong ethnic color. Mongol Shatar (Mongolian Chess) is a three-movement choral tone poem for SATB choir with divisi, tenor and bass soloists, and Guzheng (a plucked instrument) that Se Enkhbayar composed in 2002. In this composition, Se Enkhbayar uses the game of Mongolian chess as an analogy for life. In studying and performing this work, scholars and conductors can benefit from historical, musical and cultural context, including regarding the features and particular techniques of traditional Mongolian music, especially folk music; biographical information about and compositional characteristics of the composer; and information about the game of Mongolian chess. In addition, I have provided a musical analysis of the work, an English translation of the Mongolian text, and performance practice information about the traditional Khöömei and Kargyraa music featured in the work.
    • PIM Kinase Alters the Prostate Tumor Immune Microenvironment

      Warfel, Noel A.; Clements, Amber Nicole; Warfel, Noel A.; Miranti, Cynthia; Campos, Samuel K.; Wilson, Justin (The University of Arizona., 2024)
      Immunotherapy has changed the treatment paradigm for many types of cancer, but immune checkpoint inhibitors (ICIs) have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source of inflammatory cytokine production is the inflammasome. Here, we identify PIM kinases as important regulators of inflammasome activation in tumor associated macrophages (TAMs). Analysis of clinical data from a cohort of treatment naïve, hormone responsive PCa patients revealed that tumors from patients with high PIM1/2/3 display an immunosuppressive TME characterized by high inflammation (IL-1β and TNF) and a high density of repressive immune cells, most notably TAMs. Strikingly, macrophage-specific knockout of PIM reduced tumor growth in syngeneic models of prostate cancer. Transcriptional analyses indicate that eliminating PIM from macrophages enhanced the adaptive immune response and increased cytotoxic immune cells. Combined treatment with PIM inhibitors and ICIs synergistically reduced tumor growth. Immune profiling revealed that PIM inhibitors sensitized PCa tumors to ICIs by increasing tumor suppressive TAMs and increasing the activation of cytotoxic T cells. Collectively, our data implicate macrophage PIM as a driver of inflammation that limits the potency of ICIs and provides preclinical evidence that PIM inhibitors are an effective strategy to improve the efficacy of immunotherapy in prostate cancer.
    • Pivotal role of transition density in circularly polarized luminescence

      Chen, Zhanxiang; Huang, Manli; Zhong, Cheng; Gong, Shaolong; Coropceanu, Veaceslav; Brédas, Jean-Luc; Yang, Chuluo; Department of Chemistry and Biochemistry, The University of Arizona (Royal Society of Chemistry, 2023-05-12)
      Realizing high luminescence dissymmetry factor (g) in circularly polarized luminescence (CPL) materials remains a big challenge, which necessitates understanding systematically how their molecular structure controls the CPL. Here we investigate representative organic chiral emitters with different transition density distributions and reveal the pivotal role of transition density in CPL. We rationalize that to obtain large g-factors, two conditions should be simultaneously satisfied: (i) the transition density for the S1 (or T1)-to-S0 emission must be delocalized over the entire chromophore; and (ii) the chromophore inter-segment twisting must be restricted and tuned to an optimal value (∼50°). Our findings offer molecular-level insights into the CPL of organic emitters, with potential applications in the design of chiroptical materials and systems with strong CPL effects.
    • The Discovery of Small Molecule Kinase Inhibitors (SMKIs) for the Treatment of Solid Tumors

      Hulme, Christpher; Fistrovich, Alessandra; Jewett, John; McGrath, Dominic; Tomasiak, Thomas (The University of Arizona., 2024)
      Glioblastoma Multiforme (GBM) is an aggressive stage IV cancer that is difficult to detect, commonly inoperable, and associated with a poor prognosis. Challenges in targeting this disease are due to the various pro-survival signaling pathways, four different cellular states that encompass malignant GBM, and the individual heterogeneity of each tumor. Marketed FDA-approved drugs for GBM have shown improvement for this disease, but it is noted that these drugs have demonstrated poor IC50 values, toxicity issues, and cancerous cells can display resistance to treatment. Further investigation into pathway breakdowns involved in GBM led to the discovery of the Dual- specificity tyrosine phosphorylation-regulated kinases (Dyrks) and CDC2-like kinases (CLKs) upregulation in these pro-survival pathways. Evidence suggests that the inhibition of the DYRKs and CLKs is involved in various signaling pathways that affect the proliferation, spread, invasiveness, and malignancy commonly associated with GBM. Based on our initial hit DYR600 results, the series was discovered to have a unique MOA and display affinity for the PI3Ks and PDGFRs. Through a pKa-driven approach, DYR726 was discovered, a highly soluble with a high predicted permeability that has demonstrated significant kinase inhibition against GBM, while inducing reduction in growth, proliferation, invasion, and malignancy across various patient-derived GBM cell lines. Optimization to improve the known metabolic liabilities of DYR726, lead to the discovery of DYR895 an orally bioavailable, safe, and +CNS penetrant molecule. The POC DYR726 and lead DYR895 are currently being evaluated in-vivo for glioma, but their unique polypharmacology allows them also to be evaluated for other solid tumors like CRC and TNBC.
    • Paint Production and the Performance of Power in the Chaco World (A.D. 850–1200)

      Mills, Barbara J.; Hanson, Kelsey; Odegaard, Nancy; Montgomery, Lindsay M.; Jolie, Edward A.; Inomata, Takeshi (The University of Arizona., 2024)
      The advent of the Chaco World transformed the Greater Southwest, but despite centuries of study, most models of Chaco sociopolitical organization rely upon categorical types rooted in neoevolutionary schema such as chiefdoms and city-states. Many Indigenous scholars question the universal applicability of such models, arguing that knowledge and relationships serve as a more salient foundation of power in Indigenous societies. In the Pueblo World of the U.S. Southwest, this is expressed mostly clearly in performances in which cultural knowledge is shared through song, dance, and chromatic metaphor. Paint produced for performance embeds many layers of symbolism and knowledge and is produced following strict adherence to sodality-maintained protocol, making it an ideal material to explore diachronic relationships between knowledge and power. Paint is one of the oldest human technologies, yet it remains poorly understood and largely unproblematized in archaeological discourse. In this dissertation, I embrace archaeological collections of paint, paint production tools, and painted media as a material archive of relationships. Although a wide range of colors is used and rendered in paint, I focus on the technology of blue-green paint. Blue-green is one of the most significant colors, with important symbolic ties to all-important rain and vegetation, and is also one of the most challenging to render in paint. I suggest that similarities in archaeological paint compositions reflect shared production environments and can be extended to reconstruct the social groups responsible for their production. I reconstruct archaeological paint recipes using a combination of polarized light microscopy, X-ray fluorescence, and Raman spectroscopy. I accomplish this through a novel approach to analysis of archaeological paint that relies upon the non-destructive analysis of micro-samples of material that is often routinely discarded during routine museum handling. The analysis of blue-green paint from Pueblo Bonito, Chetro Ketl, Pueblo del Arroyo, Aztec West, and Kin Kletso has resulted in several key findings. First, despite archaeologists’ long-held assumption that blue-green paint was made with copper carbonate minerals, such as azurite and malachite, I demonstrate that copper sulfate minerals served as the primary colorants and is made with the closely related minerals of antlerite and brochantite. I suggest that this constitutes a single recipe for blue-green, which was circulated among great houses in Downtown Chaco, Aztec West in the Middle San Juan, and at the McElmo phase great house of Kin Kletso. Rooms with evidence for the preparation and storage of blue-green paint and painted media are strongly associated with rooms associated with Pueblo Bonito’s founding families in the northern room block, or in rooms that articulate with plaza space in symbolic spaces that show that the display of blue-green painted media was a key component of plaza-based performances. The widespread circulation of a single recipe for blue-green suggests that communities of practice involved in the production of performances cross-cut great house affiliations. Ultimately, I argue that participation in performances offered a way for members of founding families to continually legitimize their power by managing the dissemination of knowledge, but also offered a way to integrate newcomers into Chaco society through cross-cutting institutions such as sodalities. Performance in the Chaco World created a dynamic arena for the circulation of knowledge, and for the continual creation and recreation of relationships. By focusing on the role of paint as a means of reconstructing relationships of knowledge, this research calls attention to the importance of knowledge sharing and the integration of diverse people as fundamental drivers of Chaco society.
    • Costs and Benefits of Mutualism to Datura and its Mutualistic Partners

      Bronstein, Judith L.; Karnish, Alex; Dlugosch, Katrina M.; Ferriere, Regis; Pringle, Elizabeth G.; Venable, D. Lawrence (The University of Arizona., 2024)
      Mutualisms are species interactions in which both species receive a net benefit. They are crucial drivers of both population and community dynamics in habitats worldwide. The net benefit of an interaction is determined by subtracting the cost of participating in the interaction from the benefit received; hence, an interaction is called mutualistic if the benefits exceed the costs. Often, the net benefits of a mutualism are readily evident and relatively easily quantified. In contrast, the costs of mutualism have been largely ignored, in part because they are difficult to measure and compare to benefits. My dissertation focuses on how both costs and benefits impact plant resource allocation to structures that mediate mutualisms. It also explores how both the costs and benefits impact the behavior and quality of pollinators and seed dispersers. To examine the effects of costs and benefits I have used a variety of methods, both greenhouse (Appendix A) and field experiments (Appendix C and D), supplemented with a literature review (Appendix B). First, I looked at how two species of Datura (Solanaceae) allocate resources to growth and structures associated with two potentially costly mutualisms, pollination and seed dispersal (Appendix A). Overall, when resources were reduced, growth was also reduced in the two species, but the size of individual flowers and dispersal structures was maintained. One species, D. discolor, also reduced the total number of flowers produced per plant when resources were reduced, which in turn reduced the total number of seeds produced. This study demonstrates that investment into mutualisms can be costly and that plants may experience an additional trade-off between mutualistic structure quality and quantity. Second, I reviewed our current understanding of myrmecochory, seed dispersal by ants (Appendix B). I provide an overview of elaiosome traits, summarize how ants choose and interact with elaiosome-bearing seeds, describe our current understanding of how elaiosomes evolved, and touch on how ant seed dispersal may respond to anthropogenic change. I also review the known costs and benefits of myrmecochory to both plants and seed-dispersing ants. Third, I examined how both costs and benefits of diaspores (seed with attached dispersal structure, in this case an elaiosome) influence the removal of Datura seeds by the seed-dispersing ant, Novomessor cockerelli (Hymenoptera: Formicidae) (Appendix C). To do this, I first demonstrated that larger diaspores are more costly for ants to move, in terms of time. I then manipulated both the benefit (elaiosome mass) and cost (seed mass) of Datura diaspores and measured the removal rate by ants. I found that ants chose diaspores offering higher benefits and lower costs, ultimately increasing the net benefit of removing a seed. They did this through three distinct avenues: choosing diaspores that confer higher benefits, choosing diaspores that inflict lower costs, or both at once. This study emphasized the importance of studying the costs of mutualism rather than benefits or net benefits alone. Finally, in a brief note, I explored how flower size and number on D. wrightii plants can influence pollen deposition on stigmas by the hawkmoth, Manduca sexta (Sphingidae)(Appendix D). One explanation for the continued production of large flowers is the preference of M. sexta. In this short experiment, I measured pollen deposition on the stigmas of flowers of varying sizes and plants with varying numbers of open flowers. I found that the number of flowers open on a plant did not affect pollen deposition and that stigmas on larger flowers, contrary to our initial hypothesis, received fewer pollen grains than those of smaller flowers. Together these results demonstrate the importance of both costs and benefits to the dynamics of mutualisms as well as highlight the need to further quantify and study the costs of mutualism.
    • Advancing Refractive Error Care Through Novel Methods of Measuring Prescription Lens and Ocular Distortion

      Willomitzer, Florian; Sawyer, Travis W.; Guan, Yuanxin; Barton, Jennifer K. (The University of Arizona., 2024)
      Refractive error is one of the most common eye disorders worldwide, affecting over one billion people globally. Uncorrected refractive error can lead to severe vision problems. Therefore, optimizing vision using correction schemes is essential for elevating all aspects of life. Spectacle lenses are one of the most reliable and effective ways to correct refractive errors. Various procedures need to be undertaken for eyecare professionals to prescribe spectacles accurately. Verifying the prescriptions of an existing pair of spectacles is a standard first step for obtaining an objective estimation of the prescriptions before the subjective refraction exam. Existing clinical prescription measurement approaches are limited to specialized lensmeters, which are inaccessible to a large proportion of the population. To address this gap, a novel approach to measure prescriptions of spectacle lenses is developed to be a convenient, low-cost alternative to the current standard of care. This system is presented in Chapter Two with details. The measurements are analyzed and presented as proof of concept. Correction schemes are valuable, yet they could be only a temporary solution to refractive error. To prevent refractive error on-set and progression, many attempts to find the causes of this process have been investigated over the years to find the root of the problem. This includes an extensive amount of animal model research as well as human research. One implication is the potential role of the retina in the myopia progression process, as shown by the findings of deprivation-induced, lens-induced myopia, and so on. These results give rise to the hypothesis that a purely physical stimulus on the retina level may trigger this development. Other physical stimuli, including chromatic aberration, have been investigated, but one such stimulus that has yet to be investigated is the presence of ocular distortion. In the third chapter, we will demonstrate a system that allows us to measure ocular distortion from retinal images of an artificial human eye model. Our system presents a first step towards answering the bigger question of whether distortions on the retinal level could lead to myopia progression. Besides the concept and setup, the results will be shown and evaluated in depth in Chapter 3. Ultimately, this dissertation lays the foundation for several optical imaging methods that could benefit refractive error care, enhancing patient outcomes, and improving life quality.
    • The Association Between Endometriosis and Cardiovascular Disease Risk Factors

      Farland, Leslie; Acharya, Aishwarya; Chen, Zhao; Klimentidis, Yann (The University of Arizona., 2024)
      Background: Prior research suggests that women with endometriosis are at a greater risk of cardiovascular disease outcomes. Therefore, our objective was to investigate the association of endometriosis related infertility and cardiovascular disease risk factors such as hypertension, type 2 diabetes, and hypercholesterolemia among postmenopausal women. Methods: We used data from Women’s Health Initiative (WHI), a prospective cohort followed for 17 years since 2005, (N= 161,705). Participants were considered to have endometriosis if they self- reported infertility and the reason for their infertility was endometriosis (n=1,970). We used Cox proportional hazards to estimate hazard ratios of incident hypertension, type 2 diabetes and hypercholesterolemia among women with endometriosis-related infertility. We additionally investigated differences in the relationship between endometriosis-related infertility and CVD risk outcomes by BMI (<30 Kg/m2 vs BMI < 30 kg/m2). We also used log-binomial regression to estimate risk ratios of ever having a CVD risk factor. Results: In women with a history of endometriosis-related infertility we observed no increased risk of hypertension (HR: 1.00 ,95% CI: 0.93 - 1.08). We observed a 18% increased risk of incident diabetes (HR: 1.18, 95% CI: 1.01 - 1.37) and a 10% increased risk of incident hypercholesterolemia (HR: 1.10, 95% CI: 1.01 - 1.19). After adjustment for a priori confounding factors, the associations with incident diabetes (HR: 1.07, 95% CI: 0.92 - 1.25) and hypercholesterolemia (HR: 1.01, 95% CI: 0.93 - 1.10) attenuated and were no longer statistically significant. The association of endometriosis related infertility and hypercholesterolemia was stronger among women with BMI < 30 kg/m2 (p-value, test for interaction:0.02) in the main analyses investigating incident diagnoses, as well as in the sensitivity analyses investigating ever having a CVD risk factor. Conclusion: Women with endometriosis related infertility were not at an increased risk of cardiovascular disease risk factors such as hypertension, type 2 diabetes, and hypercholesterolemia. However, among subgroups of leaner women (BMI<30kg/m2), endometriosis related infertility was associated with an elevated risk of hypercholesterolemia.