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SPATIAL METHODS WITH GEOPHYSICAL AND GENOMIC APPLICATIONS
No full textWith the rapid advancement of modern technology, data containing spatial informa- tion are being generated at unprecedented scale and complexity, posing significant statistical challenges across scientific domains. This thesis develops and applies statistical methodologies for analyzing spatially structured data, with applications in both genomics and machine learning. On the genomics side, motivated by the growing popularity of spatial transcriptomics, we propose a novel statistical frame- work to investigate cell–microenvironment interactions across multiple samples. By leveraging spatial context, the method reveals biologically meaningful insights into the cellular dynamics, particularly in cancer immunology. On the machine learning front, we introduce geospatial neural networks, which integrate classical geostatistical modeling with neural network architectures. We demonstrate both theoretically and empirically that incorporating spatial priors enhances prediction performance while maintaining computational efficiency. Furthermore, we show that geospatial neural networks represent a special case of graph neural networks, suggesting avenues for future extensions to more general deep learning frameworks. As a practical outcome, we develop the open-source package geospaNN, a flexible tool for spatial estimation and prediction, aimed at enabling scientists to perform efficient and accessible spatial analysis across disciplines
The Dynamics and Transport of the Stratospheric Polar Vortices on Titan
Get PDFPolar vortices are a prominent feature in the stratosphere of Titan, the largest moon of Saturn, and are thought to play a major role in the transport of hydrocarbons throughout the middle atmosphere. Detailed observations of the temperature and composition of the northern polar vortex were made by the Cassini spacecraft from 2005 - 2017; however due to the length of a Titan year, these observations only covered from the northern mid-winter to the southern winter solstice, missing a large portion of the seasonal cycle of the polar vortex and leaving many open questions regarding the movement of material into and out of the polar regions. Therefore, this thesis was developed to bridge the gap left behind by observations and utilize atmospheric modeling to answer these questions. By analyzing a TitanWRF general circulation model (GCM) simulation covering a full Titan-year, it was revealed that the polar vortices of both hemispheres undergo a non-monotonic seasonal evolution, with a minimum in polar vortex strength occurring between the winter solstice and spring equinox, forming an annular potential vorticity structure. This structure was hypothesized to be less stable and potentially allow material to escape the polar regions, so an analysis of both 2D shallow-water and 3D GCM simulations was done to show that annular and monopolar polar vortices both maintain a horizontal mixing barrier throughout the entire lifetime of the polar vortex, which isolates the polar regions from the mid-latitudes. Finally, using the TitanWRF and TAM GCMs, it was shown that the seasonal evolution of Titan’s polar vortex facilitates the movement of hydrocarbon depleted air from the lower latitudes poleward in the upper stratosphere, allowing the transport of air over top of the polar vortex and associated mixing barrier in the mid-winter but not in the fall or late-winter. This complete study revealed that Titan’s polar vortex is a very dynamic and important feature of Titan’s stratosphere, and is key to understanding the observed distributions of hydrocarbons within its middle atmosphere
STEM PATHWAYS AND BARRIERS: COURSE-TAKING, STRUCTURAL OPPORTUNITY, AND STRESS ACROSS COLLEGE AND WORKFORCE TRANSITIONS
No full textThis dissertation examines how structural opportunity, institutional alignment, and embodied stress shape STEM trajectories from high school to early adulthood. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health), it first identifies high school STEM opportunity communities based on math and science course-taking patterns and evaluates their influence on college STEM major selection. Second, it constructs a bipartite network of major-to-occupation (CIP–SOC) transitions to model institutional alignment and assess how structural pathway types predict early career outcomes. Third, it examines how psychological distress and physiological stress (allostatic load) affect STEM occupational entry and interact with structural opportunity environments.
Findings show that high school STEM opportunity is a strong predictor of college majoring in STEM, and that structural alignment between college major and occupation significantly predicts early career prestige and STEM entry. Stress processes independently constrain persistence, with depressive symptoms and high allostatic load linked to lower odds of entering STEM careers, even after controlling for academic background. Gender and racial disparities persist across all stages, reflecting compounded structural and embodied disadvantage. These results advance theories of educational stratification by integrating structural and physiological factors in the study of STEM participation. They highlight the need for policies that address both institutional alignment and chronic stress to improve equity and retention in STEM fields
INVESTIGATING MECHANISMS OF TUMOR PROGRESSION AND RESISTANCE TO CHEMORADIOTHERAPY IN LUNG CANCER
No full textLung cancer represents a significant health burden, accounting for the highest number of cancer deaths worldwide. The most common types of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Major contributors to the high mortality of lung cancer are aggressive tumor progression, early metastasis, and rapid acquisition of resistance to conventional therapies such as chemo- and radiotherapy (CRT). It is therefore crucial to elucidate molecular mechanisms underlying these aspects of lung cancer biology. In this work, we investigated targets and pathways governing cancer progression and CRT resistance in lung squamous cell carcinoma (LSCC), a subtype of NSCLC, and SCLC.
Currently, for patients with locally advanced LSCC, the only available treatment options include CRT and adjuvant immunotherapy. However, the efficacy of CRT is limited due to dose-limiting toxicity and the development of resistance. Thus, there is a critical need for the development of effective chemo-radiosensitizers for LSCC. By utilizing in vitro and in vivo models of LSCC, we identified TRAF2 and NCK-interacting protein kinase (TNIK), which is amplified in 40% of LSCC patients, as an actionable radiosensitizing target. Genetic and pharmacological targeting of TNIK enhanced the anti-tumor effects of ionizing radiation (IR) in TNIK-high LSCC. Mechanistically, TNIK inhibition disrupted the DNA damage response and cell cycle arrest in irradiated cancer cells, thereby amplifying the efficacy of IR. Our data suggests that TNIK inhibition could be a viable radiosensitizing strategy for LSCC patients with TNIK amplification.
SCLC is a deadly malignancy characterized by early metastasis, aggressive progression, and rapid development of therapy resistance. Data from multiple SCLC model systems suggest a correlation between upregulation of the epithelial-mesenchymal transition (EMT) program and the EMT transcription factor TWIST1 and SCLC progression and treatment resistance. Here, to directly interrogate the roles of EMT in SCLC, we developed a novel transgenic mouse model termed “RPGT” in which EMT can be inducibly activated in SCLC tumors. By characterizing RPGT mice and additional in vitro SCLC models, we observed that EMT and TWIST1 promoted SCLC heterogeneity and metastasis. TWIST1 and EMT also induced resistance to CRT in SCLC by promoting DNA repair
From Learning to Leading: A Narrative Inquiry into Interprofessional Collaboration Among Dental Healthcare Providers
Get PDFPatient-centered care is designed to enhance patient safety and effectiveness, which necessitates collaboration among various individuals to inform decision-making that impacts those receiving care (Lown et al., 2011). Joint decision-making among healthcare professionals may help align care plans to reflect the unique needs of every patient. Interprofessional collaboration and interprofessional education are central elements in the healthcare industry that can improve the quality of patient care, as no single healthcare professional can meet all the needs of a patient (Avrech Bar et al., 2018; Hachoumi et al., 2023; Karam et al., 2018; Varley et al., 2020).
This paper examines the factors associated with interprofessional collaboration and professional development programs in relation to quality patient care. A narrative inquiry analysis has been conducted to provide a thorough and comprehensive understanding of the experiences of dental healthcare professionals. As quantitative factors alone cannot fully capture the enactment of IPC, utilizing narrative inquiry to explore lived experiences provides valuable insights into the mechanisms underlying its adoption. Team-based care models may contribute to a greater alignment of goals, team coordination, and continuous patient care (Nystrom et al., 2017). Lifelong learning may lead to the continuous development of professional and adaptive skills that enable effective responses to evolving health circumstances
Meeting the Needs of Diverse Populations in Summer Programs for Advanced Learners
Get PDFMeeting the needs of diverse learners can be challenging for educators. The changing dynamics within the United States and the world, such as the effects of the COVID-19 pandemic, the rise in virtual learning, and rising rates of loneliness and depression among teens and adults, highlight the importance of focusing not only on the academic needs of students but their social and emotional needs as well. A needs assessment study explored international and domestic student satisfaction within an educational summer program for advanced learners. The findings showed no statistically significant difference in how international and domestic students perceive their satisfaction in academic and residential spaces. Summer program staff members commonly said they value more training about integrating international students and diverse student populations into the residential hall and classroom environments. An intervention was implemented to determine if the inclusion of the Student Life Curriculum modules affected staff members’ readiness with and perceptions and understandings of working with diverse populations and what effect the modules had on the community experience for students and staff. The Student Life Curriculum modules were based on the Collaborative for Academic, Social, and Emotional Learning framework for social and emotional learning. Staff members participating in the program presented these modules to students on-site outside of the academic day. A pre-program and post-program climate survey based on the Faculty Classroom Diversity Questionnaire was given to all staff members, and post-program semi-structured interviews were completed with nine administrative staff members. Quantitative data from the pre- and post-program survey showed no statistically significant differences in an increase in staff readiness or experience and no significant increases in staff members’ feelings related to the importance of specific diversity characteristics in contributing to the quality of learning or social and emotional
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growth. Qualitative data were mixed, with some respondents expressing that their work in the program positively affected their readiness and experience in working with diverse populations. In contrast, other respondents felt their work outside the program contributed more to their work with diverse populations. Insufficient data were present to determine whether the Student Life Curriculum modules affected the community experience. More data would be needed on applying the Student Life Curriculum modules and their on-site use to assess their impact on students and staff
"WHAT IS" VS "WHAT IS PROMISED": IMPROVING THE STATE OF INSTRUCTION IN SMALL, PRIVATE, RURAL INSTITUTIONS
Get PDFSmall, private, rural institutions (SPRIs) primarily ask faculty to focus on teaching, and for many faculty at these institutions, this teaching priority is one of their primary attractions. Indeed, these institutions readily advertise a focus on excellent teaching. However, several factors may compromise SPRIs ability to deliver on this promise. SPRIs, with their small endowments, small enrollments, and small donor base, have limited resources from which to draw and put into maintaining and improving teaching effectiveness; faculty at SPRIs contend with widely varying responsibilities that are often not related to teaching efforts; and geographic realities restrict the hiring and retaining of qualified faculty and may necessitate the continued employment of credentialed but ineffective faculty. This work examines the state of teaching and learning at SPRIs to first understand the state of teaching and learning at SPRIs, as research in this context is scant. Then, with a better understanding of the beliefs held and practices employed by faculty at SPRIs, efforts to improve teaching and learning are offered. As such, the first part of this work explores those factors that support and impinge teaching effectiveness in this context. The second part describes a mixed methods needs assessment conducted with instructors from selected SPRIs. This study revealed that while faculty utilized many evidence-supported teaching practices and held some student-centered beliefs pertaining to teaching and learning, other impactful practices were not being implemented or were underutilized, and some faculty-held beliefs were more instructor-oriented than student-oriented. Thus, the final part of this work describes a proposed faculty development program that attempts to move faculty beliefs from instructor-centered to student-centered and to help instructors implement more evidence-based teaching practices. The proposed program can be tailored to meet the needs of individual SPRIs and their faculty, thus allowing SPRIs to more closely tie teaching to their institution’s specific values and helping SPRIs deliver on their promise of high-quality learning environment
MINDING THE GAP: ECHOLOCATING BATS MODIFY BEHAVIOR TO CONTEND WITH MISSING SENSORY INFORMATION
Get PDFFor many animal species, integrating sensory cues over time plays a pivotal role in coordinating crucial behaviors, but this can be challenged through a loss of access to sensory information, either through external environmental interference or through internal processing deficits. Investigating the strategies animals employ to compensate for gaps in incoming sensory information not only sheds light on how sensory cues are processed but also unveils fundamental mechanisms that underpin complex behaviors. During my doctoral research, I used the insectivorous bat Eptesicus fuscus to explore the behavioral response to missing sensory information. These bats use an active sensory system, emitting ultrasonic vocalizations and using the spectrotemporal features of returning echoes to perform complex navigation and target tracking tasks. I explored this dynamic system in a set of experiments that made use of naturalistic behaviors and novel methodologies. First, I examined the tracking strategy of the echolocating bat when tracking a moving target. I interrupted sensory access to targets to demonstrate that E. fuscus can integrate echoes over time to predict the future position of a target. Then, I used chemogenetic techniques to inactivate the inferior colliculus (IC) to internally limit sensory processing of auditory cues. When bats are faced with internal sensory processing deficits, they are able to make adaptive shifts in their behavior rapidly to maintain functional navigation in a simple navigational task, including changes to flight and vocal behavior.
Elucidating R-loop Formation Kinetics and The Impact of 5’UTR G-quadruplexes on Transcription and Translation
No full textR-loops and G-quadruplexes (G4s) are secondary structures that arise during transcription. R-loops can form when nascent RNA anneals with the template strand of DNA, displacing the non-template DNA strand. G4s are noncanonical secondary structures that form in G-rich regions of single-strand DNA and RNA. Sequencing studies have revealed considerable overlap between R-loops and potential G4-forming sequences (PQSs). G4s have been shown to stabilize R-loop formation. R-loops and G4s are enriched in regulatory genes and oncogenes as built-in genetic switches that can contribute to gene regulation. The misregulation of both R-loops and G4s are disease hotspots and promote genome instability. Previous studies have identified where R-loop formation occurs in the genome, but the kinetics underlying R-loop formation have not been studied. We sought to investigate what transcriptional conditions promote R-loop formation. Understanding the conditions that induce R-loop formation and the mechanisms by which R-loop assembles can help shed light on ways to prevent excessive and genotoxic R-loop formation. Additionally, it is known that G4s are involved in gene regulation, but how their composition affects transcription and translation remains to be determined. This work studies varying PQS sequences and positions within the 5’UTR to determine the impact of G4s on transcription and translation in mammalian cells. Determining what characteristics of G4s have the most effect on gene regulation can help to understand better and predict how genomic G4s will impact genetic regulation
DIMERIZATION-DEPENDENT GEL-LIKE CONDENSATION WITH DSDNA UNDERPINS THE ACTIVATION OF HUMAN CGAS: GOING BEYOND SIMPLE LIQUID-LIQUID PHASE SEPARATION
Get PDFEukaryotic cells sequester dsDNA in the nucleus and mitochondria, thus cytosolic dsDNA acts a major danger signal of catastrophic cellular events (genome instability, pathogenic invasion, etc.). Cyclic G/AMP synthase (cGAS) is the predominant cytosolic dsDNA sensor. cGAS binds to and dimerizes on dsDNA which activates the enzyme to cyclize ATP and GTP into the unique second messenger 2’-5’,3’-5’ cGAMP. cGAMP then binds to Stimulator of Interferon Genes (STING) triggering a type 1 interferon innate immune response. cGAS – dsDNA dimers can form higher order assemblies, resulting in Liquid-Liquid phase separated (LLPS) condensates. The role of LLPS condensates in regulating cGAS function remains controversial, with some linking it to catalytic activity, while others suggest that it protects dsDNA from degradation. Further complicating things, cGAS has been found to undergo LLPS with nucleic acids other than dsDNA (such as ssRNA or ssDNA).
Given this controversy, I sought to understand two related questions. The first is what exactly is the role of condensates in cGAS function? The second is what makes dsDNA-cGAS condensates unique among cGAS-nucleic acid condensates? I utilized time-lapse fluorescence imaging, biochemical, and biophysical assays to characterize the properties of human cGAS:nucleic acid condensates. I examined how dimerization affects cGAS:dsDNA phase separation by utilizing recombinant full-length wild-type human cGAS or two well characterized dimerization mutants (K394E and CC396/397AA), in addition to how this system behaves in HEK293T cells. I utilize the same methods to character the properties of cGAS: non-cognate nucleic acids condensates alone, and with dsDNA. Finally, I investigated how ATP mobility is affected by cGAS condensate formation.
I report here that cGAS-dsDNA condensates undergo gel-like condensation, creating an expansive network with irregular morphology and limited mobility. This gel-like condensation is intrinsically tied to dimerization; impairing dimerization through a mutation at the cGAS dimer interface (K394E) or with non-cognate nucleic acids (ssDNA, ssRNA etc.) results in highly dynamic liquid droplets. The gel-like condensation limits NTP mobility and may facilitate intermediate recapturing over the liquid droplets. My observations suggest that cGAS dimerization instills order in a disordered microenvironment to maximize its signaling efficiency