Digital Commons Network^™

Delineating Contributions Of Genotype And Lineage To Lung Cancer Therapy Response, Kassandra Jo Naughton

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) heterogeneity is a major challenge for determining effective treatment strategies. Adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) are histologically and epigenetically distinct subtypes of NSCLC. Patients with ADC tumors harboring mutations in both KRAS and LKB1 (aka STK11) have lower survival rates than those with KRAS-only tumors. KRAS/LKB1 tumors are not only aggressive, but also respond poorly to immunotherapy. However, these data are limited to ADCs, and it is unclear if SCCs with this genotype are also resistant to immunotherapy. We developed a mouse model of Kras^mut/Lkb1^mut capable of producing …

Rps6kb1 Is A Critical Target For Overcoming Tumor Lineage Plasticity And Therapy Resistance, Saptadwipa Ganguly

Theses and Dissertations--Toxicology and Cancer Biology

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms which can be classified as intrinsic or extrinsic resistance. The intrinsic resistance is usually present prior to any treatment whereas the extrinsic resistance develops as a result of exposure to some kind of therapy. In order to target these “therapy resistant” tumor cells an unbiased screen of an FDA-approved drug library against cancer cells was performed. This was followed by synthesis of chemical analogs of the most effective drug.

The studies led to the identification of a derivative of the antihistamine drug ebastine, designated Super-ebastine …

Generating Climate Resilience Or Intensifying Vulnerabilities? A Feminist Poltitical Ecology Analysis Of Climate Resilient Agriculutre Projects In Sri Lanka’S Dry Zone, Nethmi Sachithma Perera Bathige

Theses and Dissertations--Geography

Conserving water for irrigation of crops has become a concern in the dry zone of Sri Lanka due to changes in climate patterns. In response, the United Nations Development Program (UNDP) has developed climate-resilient water management projects designed to build climate-resilience and water management practices among farmers. One such program called ‘Wew Gam Pubuduwa’ disseminates climate smart home gardening techniques, where women farmers receive sprinkler and drip irrigation systems, seeds and fertilizers, as well as training on water management methods. This study draws on a feminist political ecology framework to analyze the experiences of women home gardeners who …

Redefining Ed Utilization: A Rabies Post-Exposure Prophylaxis Perspective, David Bennington

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Rabies, though rare in the United States, remains a lethal viral disease with significant public health implications. Post-exposure prophylaxis (PEP) through timely administration of rabies vaccines and rabies immune globulin (RIG) is critical for preventing the progression of the virus following potential exposure. However, the current system of healthcare delivery in the United States has witnessed an alarming trend: the unnecessary utilization of emergency department (ED) visits for rabies PEP, including follow-up vaccinations. This paper aims to examine and address this issue through a review of the factors contributing to the inappropriate use of ED services for rabies treatment.

Through …

Zebrafish Drug Screening Identifies Erlotinib As An Inhibitor Of Wnt/ Β-Catenin Signaling And Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd A. Al-Hamaly, Anna H. Cox, Meghan G. Haney, Wen Zhang, Emma C. Arvin, Shilpa Sampathi, Mary Wimsett, Chunming Liu, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The effi- cacy of the top hit, Erlotinib, extended to human cells, where it …

Equestrian Activities And Health Outcomes: A Multidimensional Analysis Of Physical Activity, Injury Patterns, And Occupational Concerns, Michaela Keener

Theses and Dissertations--Rehabilitation Sciences

Over 6 million participate in equestrian activities each year. However, research focusing on the benefits and risks around equestrian activities is limited to epidemiological research and small sample sizes. Equestrian participation ranges from recreational to occupational, and little research has evaluated how the risks of participation change based on the level of participation. Special consideration needs to be given to the occupational equestrians as equestrian participation is their livelihood. The first two aims of this study were to evaluate the physical activity engagement, perceptions of equestrian as a sport, acute injury history, and chronic pain frequency of equestrians across all …

The Effect Of Adding Perceptual-Cognitive Load To Assessments And Intervention Strategies In Healthy Adults, Ke'la H. Porter

Theses and Dissertations--Rehabilitation Sciences

In collegiate athletes, approximately one in four injuries require more than seven days before the athlete can return to full participation. Additionally, there are significant long-term consequences associated with these injuries, such as pain and osteoarthritis. Despite the role that the sensorimotor system and cognitive function play in athletic competition, the interaction between these systems in relation to sport-related injury is commonly overlooked. The sensorimotor system integrates and processes sensory, motor, and central mechanisms to produce a motor response. Further, cognition constructs, such as visual attention or processing speed, allow athletes to navigate the chaotic sporting environment. When there are …

A Social History Of Opioids’ Crimedical Cycle, Jerel M. Ezell, Alex Rains, Babatunde Patrick Ajayi, Kyle Miller, Erin Augustine, Dawn Goddard-Eckrich, Elizabeth N. Kinnard, Michelle R. Lofwall

Behavioral Science Faculty Publications

Historically, public and political discourse around people who nonmedically use opioids has largely been rendered via a deficits-oriented lens, presenting this population as weak, disinterested, and deviant,and thus undesirable and ill-positioned for wellness and communal integration. These narratives, and subsequent policies used to engage people who use opioids, are intermittently formed and disrupted by geopolitical changes, as public and institutional attitudes, often driven by racial and class-related considerations, shift. As part of what we term the crimedical cycle, a population’s behaviors fluctuate between periods of medicalization and criminalization. Strengths-based theory, an offshoot of ‘positive psychology’ that helps contextualize the crimedical …

Adgrl1 Is A Glucose Receptor Involved In Mediating Energy And Glucose Homeostasis, Kavaljit H Chhabra, Siresha Bathina, Tumininu S Faniyan, Dennis J Samuel, Muhammad Ummear Raza, Leticia Maria De Souza Cordeiro, Gonzalo Viana Di Prisco, Brady K Atwood, Jorge Robles, Lauren Bainbridge, Autumn Davis

Pharmacology and Nutritional Sciences Faculty Publications

AIMS/HYPOTHESIS: The brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.

METHODS: Here we used a high molecular mass glucose-biotin polymer to enrich glucose-bound mouse hypothalamic neurons through cell-based affinity chromatography. We then subjected the enriched neurons to …

Abnormalities In Pharyngeal Arch-Derived Structures In Satb2-Associated Syndrome, Yuri A. Zarate, Katherine Bosanko, Nada Derar, Jennifer L. Fish

Pediatrics Faculty Publications

SATB2-associated syndrome (SAS, glass syndrome, OMIM#612313) is a neurodevelopmental autosomal dominant disorder with frequent craniofacial abnormalities including palatal and dental anomalies. To assess the role of Satb2 in craniofacial development, we analyzed mutant mice at different stages of development. Here, we show that Satb2 is broadly expressed in early embryonic mouse development including the mesenchyme of the second and third arches. Satb2-/- mutant mice exhibit microglossia, a shortened lower jaw, smaller trigeminal ganglia, and larger thyroids. We correlate these findings with the detailed clinical phenotype of four individuals with SAS and remarkable craniofacial phenotypes with one requiring mandibular distraction in …

Astrocytic Mitochondrial Transfer To Brain Endothelial Cells And Pericytes In Vivo Increases With Aging, Gopal V. Velmurugan, Hemendra J. Vekaria, Samir P. Patel, Patrick G. Sullivan, W. Brad Hubbard

Neurology Faculty Publications

Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries in vivo is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. …

Using Digital Pathology To Analyze The Murine Cerebrovasculature, Dana M. Niedowicz, Jenna L. Gollihue, Erica M. Weekman, Panhavuth Phe, Donna M. Wilcock, Christopher M. Norris, Peter T. Nelson

Neurology Faculty Publications

Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and crossreactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed …

The Relationship Between Self-Reported Depressive Symptoms At 3 Timepoints And Infant Sleep Practices At 6-Month Follow-Up In A Population Of Mothers In Santo Domingo, Ecuador, Kassidy Lane

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Abstract

Background

Previous studies have linked maternal depression with poor infant sleep (e.g., waking up at night and infants having trouble settling to sleep). This study examined the relationship between maternal depressive symptoms at three time points and safe infant sleep at 6-month follow-up.

Methods

Data was collected from a randomized clinical trial including 100 women recruited from a health center in Santo Domingo, Ecuador during their third trimester of pregnancy. Log-binomial regression was used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) of safe infant sleeping at 6 months among mothers who reported depressive symptoms at 3 …

Using Naturalistic Language Interventions To Increase Expressive Communication Of Aac Users With Autism, Kacey Eaton

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

This study's purpose was to use naturalistic language interventions to increase the communication rate via alternative and augmentative communication during play with young children with autism. A nonconcurrent multiple baseline design was used to evaluate the effectiveness of a combination of naturalistic language interventions when implemented during 10-minute play sessions within the participants resource classroom. Naturalistic language interventions utilized include aided language modeling, environmental arrangements, naturalistic time delay, and language expansions. Results indicated that naturalistic language interventions are effective in increasing expressive communication via AAC with children with autism.

Training Paraprofessionals In The Implementation Of Aided Language Modeling With Individuals With Intellectual Disabilities And Ccn, Julianne Hill

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

The purpose of this research is to train special education paraprofessionals in the implementation of Aided Language Modeling (ALM) through a coaching program. A single-case multiple probe design across three paraprofessional/student dyads was used to analyze data. Coaching procedures included a single 20-minute training workshop with the researcher between baseline and intervention and post-session conversations after each intervention trial. The research took place in a public school in the southeastern United States. The school was located outside of a metropolitan area in a suburban school district. The study took place to answer the following questions: (1) With the implementation of …

Pixels Or People: A Comparison Of The Differenital Effects Of Animated And Human Video Models On Exercise Behaviors For Hgh School Students With Intellectual Disability, Jade Alexis Fulkerson

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Individuals with intellectual disabilities, with or without autism spectrum disorder, often require structured programming to facilitate acquisition of skills. Video modeling, an evidence-based strategy, offers a promising avenue for skill instruction. While research has demonstrated the effectiveness of human-modeled video interventions, limited research has been conducted into the efficacy of animated models. Addressing this gap, the present study employed an alternating treatments design to compare the effectiveness of human and animated models in teaching exercise behaviors to high school students with intellectual disabilities, with or without autism spectrum disorder. Results revealed variability among participants: one individual exhibited superior performance with …

Comparison Of Video Modeling And In-Vivo Language Instruction In Preschool, Jessah Marlee Hughes

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Early communication and language development in young children is critically important and those identified as having a language delay, would benefit from intervention. There is a rise in screen time exposure in young children, with some watching variations of popular evidence-based practices (time delay, video modeling, etc.) Most notably, Ms. Rachel is an early childhood learning YouTube sensation. This study seeks to compare the effectiveness and efficiency of video modeling and time delay in the differential use of early sentences during play-based activities.

The Effects Of Hierarchical Training On The Emergence Of Emotion-Related Metaphors In Autistic Children, Katherine Lynch

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Recently, research on derived relational responding has increased in volume, along with the publication of assessments, curricula, and textbooks on this topic. The allure of engineering derived relations due to purported accelerated learning makes this topic interesting to researchers and practitioners. Recent reviews have examined types of verbal operants, and specific relational frames studied in this body of literature, but there is scarcity in terms of the instructional procedures and variations thereof, and there is little available to focus on single case design (SCD) evaluations of these procedures. Hierarchical training (HT) to produce derived relations between arbitrary stimuli has shown …

The Impacts Of Gut-Supporting Feed Additives On The Growth Performance, Gut Health, Blood Chemistry, And Immune Status Of Broiler Chickens Exposed To Different Stressors, Richard A. Adefioye

Theses and Dissertations--Animal and Food Sciences

Three experiments were conducted to examine the effects of different feed additives in mitigating stress in broiler chickens. Experiment 1 used 504-day-old male by-product Cobb breeder chicks with 8 treatments replicated 9 times with 7 birds per replicate cage, structured as a 2x4 factorial arrangement of treatments. All birds were on the experimental diets for 20 days. There were 2 levels of lipopolysaccharide (LPS) challenge [no challenge vs. LPS challenge at 1 mg/kg BW) and 4 types of feed additives [no additive, 0.05% PostB, 0.1% PostB, and 0.1% Tynagen^TM]. In experiment 2, 672-day-old male by-product Cobb breeder chicks …

A Critical Assessment Of The First Step Act's Recidivism-Reduction Measures, Raquel Wilson

Law Faculty Scholarly Articles

The First Step Act of 2018 (“FSA”) is the most impactful federal sentencing reform of the past 40 years. While the Act represents a partial resurgence of the rehabilitative model of imprisonment, which had fallen out of favor decades before, it also represents a missed opportunity to fully integrate evidence-based rehabilitation programs for those offenders who pose the greatest risks to public safety.

The public has a strong interest in reducing recidivism, particularly among violent offenders, most of whom will be released from federal prison eventually. The FSA incentivizes participation in evidence-based, recidivism-reducing programs offered by the Bureau of Prisons …

Developing An Immunomodulatory Strategy Using Biophysical Cues To Modulate Macrophage Phenotype For Fracture Healing And Bone Regeneration, Harshini Suresh Kumar

Theses and Dissertations--Biomedical Engineering

Chronic inflammation is a major cause of the pathogenesis of musculoskeletal diseases such as fragility, fracture, and nonunion. Studies have shown that modulating the immune phenotype of macrophages from proinflammatory to pro-healing can heal recalcitrant bone defects. Current therapeutic strategies predominantly apply biochemical cues, which often lack target specificity, and controlling their release kinetics in vivo is challenging spatially and temporally. We have developed a magnetic iron-oxide nanocomplexes (MNC)-based therapy for resolving chronic inflammation in the context of promoting fracture healing. Here, we show that MNC internalized macrophages, when coupled with an external magnetic field, can exert an intracellular magnetic …

Relating Temperature, Sleep, And Pathology In Mouse Models Of Alzheimer's Disease, Jun Wang

Theses and Dissertations--Biomedical Engineering

It is well established that sleep plays an important role in Alzheimer’s disease (AD) pathology. There is growing evidence that sleep issues may accelerate AD pathology by interrupting the physiological clearance of amyloid‐β (Aβ) from the brain, which mainly occurs in normal sleep. As the over-accumulation of amyloid‐β (Aβ) is believed to lead the cascade effect that eventually causes neurodegeneration in AD patients, development of therapeutic strategies for improving sleep quality may help slow disease progression. It is well documented that the composition and dynamics of sleep are sensitive to changes in ambient temperature. We therefore developed a sleep enhancement …

Development Of Iron Oxide Nanozyme For Cancer Therapy, Zhongchao Yi

Theses and Dissertations--Biomedical Engineering

Cancer therapies that leverage reactive oxygen species (ROS) have shown potential for cancer inhibition due to their ability to induce oxidative stress in tumor cells. Iron oxide nanoparticles (IONPs) have garnered significant attention as a promising platform for ROS-dependent disease treatment, owing to their remarkable biocompatibility and Fenton catalytic activity. However, the low catalytic activity of IONPs has been a major hurdle in their clinical translation. To overcome this challenge, IONPs of different compositions are examined for their Fenton reaction under pharmacologically relevant conditions in this work. The results show that wüstite (Fe_1-xO) nanoparticles exhibit higher catalytic activity …

The Effect Of Visual Signaling On Psychomotor Learning: An Explanatory Mixed Methods Study In Physical Therapy Education, Julie Pfeiffer

Theses and Dissertations--Education Sciences

The signaling principle states that people learn better when cues are used to highlight important information in a multimedia presentation. Prior research has shown that visual signaling improves learning by directing the learner’s attention to the relevant information of the instruction, improving the learner’s ability to select essential words and pictures. While the visual signaling principle has been applied to learning in the cognitive domain, the effect of visual signaling on learning within the psychomotor domain is limited. The purpose of this study is to investigate the effect of the signaling principle on learning psychomotor skills from multimedia instruction, specifically …

The Aesthetics Of Environmental Risk In Paolo Bacigalupi’S The Windup Girl And The Water Knife, David Schwartz

Theses and Dissertations--English

Any work of environmentally oriented fiction that seeks to represent the wide-reaching effects of climate change is faced with the problem of scale. These texts must render visible change which is at once ubiquitous and microscopic, along with the cascade of side-effects generated in the wake of rising temperature, rising sea levels, and winnowing biodiversity. In short order, these texts must fully imagine what it means to live within the modern global risk society. Borrowing this sociological model from the late Ulrich Beck, I analyze the literary work of Paolo Bacigalupi, one of the foremost authors in the growing genre …

The Dark Sides Of Giving: Representations Of Philanthropy And Gifts In Eighteenth-Century Literature, C.1750-1820, Jillian Winter

Theses and Dissertations--English

This dissertation explores representations of the gift in popular women’s novels of the long eighteenth century. Gift transactions in women’s fiction from this period reveal larger cultural reflections about the limitations placed on women who try to give and to help others. The primary works discussed in this project include Frances Burney’s Cecilia; or, Memoirs of an Heiress (1782), Eliza Haywood’s The History of Miss Betsy Thoughtless (1751), Mary Hays’s Memoirs of Emma Courtney (1796), Sarah Fielding’s The History of Ophelia (1760), and Maria Edgeworth’s Belinda (1801). Frequently, the novels considered in this dissertation showcase the complicated conditions, oftentimes troubling …

Trust And Knowing In Nineteenth-Century American Literature: Fictional Genres And Metacognitive Disruptions, Jessica Marie Van Gilder

Theses and Dissertations--English

This dissertation investigates how constructions of trust can be undermined or reinforced by examining trust’s entanglement with our compulsive and subjective desire to know in nineteenth-century American literature. Specifically, I analyze how different fictional genres – satire, historical romance, fantastic, and gothic – respond to our desire to know through the types of trust fictional texts feature and construct with the reader. In doing so, I demonstrate how genres of fiction in nineteenth-century America function as dynamic social contracts that amplify and undermine the reader’s trust in larger sociopolitical systems (e.g., national identity) and the epistemologies that underpin those systems …

Functional Analyses Of The Polycomb-Group Genes In Sea Lamprey Embryos Undergoing Programmed Dna Loss, Cody Saraceno

Theses and Dissertations--Biology

During early embryonic development, the sea lamprey (Petromyzon marinus) undergoes programmatic elimination of DNA from somatic progenitor cells in a process termed programmed genome rearrangement (PGR). Eliminated DNA eventually becomes condensed into micronuclei, which are then physically degraded and permanently lost from the cell. Previous studies indicated that many of the genes eliminated during PGR have mammalian homologs that are bound by polycomb repressive complex (PRC) in embryonic stem cells. To test whether PRC components play a role in the faithful elimination of germline-specific sequences, we used a combination of CRISPR/Cas9 and lightsheet microscopy to investigate the impact …

Effects Of Neonatal Estradiol Treatment On Regulating Sexual Differentiation Of Daily Rhythms Underlying Diet-Induced Obesity In Female Mice, Samuel Nwadialo

Theses and Dissertations--Biology

Sex differences of the brain and behavior often require the combination of organizational and activational effects of sex hormones. The activational effects of estrogens in adult female mice protect daily eating and activity rhythms from disruption by high-fat diet feeding and inhibit diet-induced obesity. However, male mice have disrupted eating rhythms when fed high-fat diet and this causes obesity. Treatment of adult male mice with estradiol does not protect rhythms from disruption by high-fat diet, as it does in females. In this study, we sought to determine whether the organizational effects of estradiol masculinize the daily eating and activity rhythms …

Investigations Across Biology And Education: Exploring The Gut Microbiome Of Freshwater Mussels And Understanding Undergraduate Biology Student Motivation, Mary Foley

Theses and Dissertations--Biology

A PhD aims to make a unique contribution to the current body of knowledge while developing as an independent researcher and critical thinker. This dissertation covers a wide range of topics, from microbiome analysis to biology education. Although there is no broad overarching research theme, all the chapters are connected by the process of scientific inquiry and by their contribution to the completion of a PhD.

Chapter One serves as a comprehensive literature review, delving into the standard methods of measuring the health of at-risk species. It describes direct measures of health (e.g., birth and death rates) crucial for predicting …