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Potent Mor Agonists From 2′-Hydroxy-5,9-Dimethyl-N-Phenethyl Substituted-6,7-Benzomorphans And From C8-Hydroxy, Methylene And Methyl Derivatives Of N-Phenethylnormetazocine, Madhurima Das, George W. Ward, Agnieszka Sulima, Dan Luo, Thomas E. Prisinzano, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, Kenner C. Rice

Pharmaceutical Sciences Faculty Publications

(−)-5,9-Dimethyl-6,7-benzomorphan (normetazocine) derivatives with a para-OH or ortho-F substituent in the aromatic ring of the N-phenethyl moiety were synthesized and found to have subnanomolar potency at MOR, and both were fully efficacious in vitro. These new compounds, (1R,5R,9R)-6,11-dimethyl-3-(2-fluorophenethyl)-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-ol and (1R,5R,9R)-6,11-dimethyl-3-(4-hydroxyphenethyl)-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d] azocin-8-ol, were more potent than the unsubstituted compound N-phenethylnormetazocine and about 30 or 40 times more potent than morphine, respectively. A variety of substituents in the ortho, meta, or para position in the aromatic ring of the N-phenethyl moiety were synthesized, 25 of these compounds, and found to have varying effects on potency and efficacy as determined by the forskolin-induced …

The Gas And Stellar Content Of A Metal-Poor Galaxy At Z = 8.496 As Revealed By Jwst And Alma, K. E. Heintz, C. Giménez-Arteaga, S. Fujimoto, Gabriel B. Brammer, D. Espada, S. Gillman, J. González-López, T. R. Greve, Yuichi Harikane, B. Hatsukade, K. K. Knudsen, Anton M. Koekemoer, K. Kohno, V. Kokorev, M. M. Lee, Georgios E. Magdis, E. J. Nelson, F. Rizzo, Ryan L. Sanders, D. Schaerer, Alice E. Shapley, V. B. Strait, S. Toft, F. Valentino, A. Van Der Wel, A. P. Vijayan, D. Watson, F. E. Bauer, Amber Christiansen, C. R. Christiansen, S. N. Wilson

Physics and Astronomy Faculty Publications

We present a joint analysis of the galaxy S04590 at z = 8.496 based on NIRSpec, NIRCam, and NIRISS observations obtained as part of the Early Release Observations program of the James Webb Space Telescope (JWST) and the far-infrared [C ii] 158 μm emission line detected by dedicated Atacama Large Millimeter/submillimeter Array (ALMA) observations. We determine the physical properties of S04590 from modeling of the spectral energy distribution (SED) and through the redshifted optical nebular emission lines detected with JWST/NIRSpec. The best-fit SED model reveals a low-mass (M _⋆ = 10^7.2-10⁸ M _⊙) galaxy with a …

The Prevalence Of Opioid Use Disorder In Kentucky’S Counties: A Two-Year Multi-Sample Capture-Recapture Analysis, Katherine L. Thompson, Joshua A. Barocas, Chris Delcher, Jungjun Bae, Lindsey R. Hammerslag, Jianing Wang, Redonna Chandler, Jennifer Villani, Sharon L. Walsh, Jeffery Talbert

Pharmacy Practice and Science Faculty Publications

Background: Kentucky has one of the highest opioid overdose mortality rates in the United States. Accurate estimates of people with opioid use disorder (OUD) are critical to plan for the scope of interventions required to reduce overdose and opioid misuse. Commonly used household surveys are known to underestimate OUD at the state-level and do not provide county-level estimates.

Methods: We performed a multi-sample capture-recapture analysis to estimate OUD prevalence in Kentucky in 2018 and 2019. We utilized four statewide datasets that were linked at the individual level: 1) Registry of Vital Statistics, 2) Emergency Medical Services (EMS), 3) Kentucky’s Prescription …

Two Essays On Industrial Hemp Firms In The United States, Abraham Olakunle Ajibade

Theses and Dissertations--Agricultural Economics

After a long absence from American fields, industrial hemp was reintroduced to growing fields starting with state pilot programs in 2014 and received the green light for commercial cultivation in the US through the 2018 Farm Bill. Being an industry in its resurgence, investment is crucial for growth and the stock market and over-the-counter markets help US hemp firms get these much-needed funds for growth and expansion. This thesis consists of two essays on US hemp firms.

The first essay uses descriptive statistics, correlation analysis, and the Kruskal-Wallis Test to investigate how US hemp stocks compare to mid-cap and large-cap …

Pedestrian And Bicycle Improvement Scoring Method For Shift–2024, Nikiforos Stamatiadis, Daria Korostina, Teng Wang, Reginald Souleyrette

Kentucky Transportation Center Research Report

State transportation agencies have limited funding to deliver multimodal transportation programs that address the needs of all users. To allocate project funding in an impartial and objective manner, many agencies have adopted data-driven scoring systems that are used to evaluate the merits of proposed capital improvement projects. The Kentucky Transportation Cabinet introduced the Strategic Highway Investment Formula for Tomorrow (SHIFT) for this purpose. Until now SHIFT, has evaluated projects based five core variables — congestion, safety, benefit-cost ratio, asset management, economic growth. To address local needs, SHIFT has also allocated points that Area Development Districts, metropolitan planning organizations, and Cabinet …

Increasing Efficiency Of Finishing Beef Production: Strategies To Optimize Starch Digestion, Improve Flake Quality, And Reduce Methane Emissions, Ronald J. Trotta

Theses and Dissertations--Animal and Food Sciences

To continue to meet the demands of increasing food production and environmental sustainability, new strategies are needed to enhance the efficiency of finishing cattle production. A review of the literature identified several nutritional and physiological constraints that limit the ability for cattle to digest starch and absorb glucose from the small intestine. Comparative sequencing analyses revealed a missing region of the sucrase-isomaltase protein which could affect the capacity for starch digestion in cattle. Post-flaking sampling and handling recommendations were generated based on a series of experiments to improve estimates of starch availability and flaking consistency for commercial feedlots and laboratories. …

Plant Cell Wall Composition And In Vitro Fermentation Characteristics Of Cool-Season Forage Grasses From Two Growing Seasons In Central Kentucky, Sophia Danielle Newhuis

Theses and Dissertations--Animal and Food Sciences

Grass cell walls are rich in cellulose, hemicellulosic arabinoxylan (AX) polysaccharides, and lignin. AX structural differences such as degree and pattern of branching and the ester-linked phenolic acid content could affect plants’ digestibility when used as forage for livestock. However, there is little information about how these structural elements change over the growing season in the vegetative tissue of cool-season perennial grasses. Enhanced information about the cell wall composition and carbohydrate structure of forage material will provide a foundation for expanding our knowledge of how forage cell wall carbohydrate structures are utilized by ruminants. The objectives of this study were …

Evaluation Of Boron Supplementation In Swine And Poultry, Tyler B. Chevalier

Theses and Dissertations--Animal and Food Sciences

The objectives of this dissertation were to evaluate dietary boron (B) supplementation as sodium borate in various swine models and broiler chicks through a series of experiments. The initial experiment evaluated supplemental B (0, 25, 50, and 100 ppm B) on serum insulin, glucose, and clinical chemistry panel of growing pigs. Serum insulin/glucose ratio tended to decrease linearly with increasing supplemental B in a fasting state (P = 0.08). These findings were more noticeable (linear effect, P = 0.02) in a postprandial state (~ 50 minutes following a meal). A series of follow-up studies further evaluating B supplementation (0, 5, …

Evaluation Of Increasing Levels Of Mycotoxin-Containing Corn Fines On Diet Choice And Growth Performance Of Nursery Pigs, Duncan B. Paczosa

Theses and Dissertations--Animal and Food Sciences

Pigs fed mycotoxin contaminated diets at high concentrations will result in a detriment to health and performance. An initial study and a follow-up study were conducted to evaluate the effects of feeding increasing levels of mycotoxin-containing corn fines on growth performance, diet preference of pigs, and two possible mitigants.

The initial study was a 3 x 2 factorial containing three levels of fines (0, 10, and 20%, Diets 1-3, respectively) and either 0 ppm (Diets 1-3) or 40 ppm boron (Diets 4-6; Diets 4-6 were Diets 1-3, respectively, plus boron) as sodium tetraborate decahydrate as a possible mitigant. In this …

Profiling The Cell Wall Polysaccharides Of Hemp (Cannabis Sativa L.) Inflorescence And Hempseed And Exploring Their Application As Ruminant Feed Ingredients, Miranda Agbana

Theses and Dissertations--Animal and Food Sciences

Hemp (Cannabis sativa L.) is used in the United States as a source of CBD oil, fiber, and grain. While hempseeds are consumed whole or as dehulled hemp hearts, hempseed oil is also a desirable seed oil in human nutrition. The process of collecting hempseed oil leaves behind hempseed cakes that are abundant in protein and fiber. Feeding of hempseed cakes to animals, including ruminants, has only initially been explored. Extraction of CBD from hemp inflorescences generates organic waste that may find a second purpose as a fiber feed for cattle. Little is known about the exact fiber composition …

Ultrasound-Based Structural And Functional Modifications Of Oat Protein: Complementary Effects Of High Pressure, Cysteine, And Flavonoids, Runnan Li

Theses and Dissertations--Animal and Food Sciences

Oat (Avena sativa L.), a specialty cereal grain belonging to the Poaceae family, is relatively abundant in nutritious protein (12–20%) and dietary fiber (β-glucan). The balanced hydrophilic/hydrophobic amino acid profile in oat protein relative to other plant sources provides numerous possibilities for formulating oat protein isolate (OPI) into a wide range of food products. Yet, there has been limited research on OPI and the application of this valuable protein source is hampered by its low solubility at neutral and mildly acidic conditions. This dissertation research aimed to elucidate the efficacy of high-intensity ultrasound (HIU) for structural modification of OPI …

Precision Livestock Farming And Personality As Tools To Understand Dairy Calf Individual Variation In Performance, Behavior, And Response To Stress, Megan Marie Woodrum Setser

Theses and Dissertations--Animal and Food Sciences

Individual differences impact animal responses to their environments and can be observed with animal personality (stable behavioral differences with populations) and food neophobia (avoidance of unfamiliar feeds). These individual differences can influence cattle performance and welfare. Precision technologies, such as automatic feeding systems (AFS) and accelerometers continuously measure feeding behaviors and activity and may allow us to relate individual differences to behaviors in the home environment. Therefore, the first objective was to determine if food neophobia was associated with feeding behaviors measured by AFS. Food neophobia was associated with rewarded visits to the AFS, but to no other feeding behaviors. …

Campylobacter Vaccination Reduces Diarrheal Disease And Infant Growth Stunting Among Rhesus Macaques, Sara M. Hendrickson, Archana Thomas, Hans-Peter Raué, Kamm Prongay, Andrew J. Haertel, Nicholas S. Rhoades, Jacob F. Slifka, Lina Gao, Benjamin K. Quintel, Ian J. Amanna, Ilhem Messaoudi, Mark K. Slifka

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Campylobacter-associated enteric disease is estimated to be responsible for more than 160 million cases of gastroenteritis each year and is linked to growth stunting of infants living under conditions of poor sanitation and hygiene. Here, we examine naturally occurring Campylobacter-associated diarrhea among rhesus macaques as a model to determine if vaccination could reduce severe diarrheal disease and infant growth stunting. Compared to unvaccinated controls, there are no Campylobacter diarrhea-associated deaths observed among vaccinated infant macaques and all-cause diarrhea-associated infant mortality is decreased by 76% (P = 0.03). By 9 months of age, there is a 1.3 cm increase in dorsal …

Chronic Alcohol Consumption Dysregulates Innate Immune Response To Sars-Cov-2 In The Lung, Sloan A. Lewis, Isaac R. Cinco, Brianna M. Doratt, Madison B. Blanton, Cherise Hoagland, Natali Newman, Michael Davies, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background Alcohol consumption is widespread with over half of the individuals over 18 years of age in the U.S. reporting alcohol use in the last 30 days. Moreover, 9 million Americans engaged in binge or chronic heavy drinking (CHD) in 2019. CHD negatively impacts pathogen clearance and tissue repair, including in the respiratory tract, thereby increasing susceptibility to infection. Although, it has been hypothesized that chronic alcohol consumption negatively impacts COVID-19 outcomes; the interplay between chronic alcohol use and SARS-CoV-2 infection outcomes has yet to be elucidated.

Methods In this study we employed luminex, scRNA sequencing, and flow cytometry to …

Monoclonal Antibody Therapy Of Breastfeeding Patient Infected With Sars-Cov-2: A Case Report, Nicole E. Marshall, Madison B. Blanton, Brianna M. Doratt, Delphine C. Malherbe, Monica Rincon, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Introduction: Although safety data demonstrated the efficacy and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination for all individuals over 6 months of age, including pregnant and breastfeeding individuals, optimal treatment courses for symptomatic pregnant and lactating individuals infected with SARS-CoV-2 remain to be defined. Case Description: A coronavirus disease 2019 (COVID-19)-vaccinated breastfeeding woman received anti-SARS-CoV-2 monoclonal antibody treatment casirivimab–imdevimab 5 days after diagnosis of a symptomatic breakthrough SARS-CoV-2 infection. Results and Conclusions: The patient did not present with obvious defects in innate or adaptive cellular subsets, but compared with controls had minimal maternal antibody response to recommended …

Mild/Asymptomatic Covid-19 In Unvaccinated Pregnant Mothers Impairs Neonatal Immune Responses, Brianna M. Doratt, Suhas Sureshchandra, Heather E. True, Monica Rincon, Nicole E. Marshall, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Maternal SARS-CoV-2 infection triggers placental inflammation and alters cord blood immune cell composition. However, most studies focus on outcomes of severe maternal infection. Therefore, we analyzed cord blood and chorionic villi from newborns of unvaccinated mothers who experienced mild/asymptomatic SARS-CoV-2 infection during pregnancy. We investigated immune cell rewiring using flow cytometry, single-cell RNA sequencing, and functional readouts using ex vivo stimulation with TLR agonists and pathogens. Maternal infection was associated with increased frequency of memory T and B cells and nonclassical monocytes in cord blood. Ex vivo T and B cell responses to stimulation were attenuated, suggesting a tolerogenic state. …

Integrated Single Cell Analysis Shows Chronic Alcohol Drinking Disrupts Monocyte Differentiation In The Bone Marrow, Sloan A. Lewis, Brianna M. Doratt, Qi Qiao, Madison B. Blanton, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic heavy alcohol drinking (CHD) rewires monocytes and macrophages toward heightened inflammatory states with compromised antimicrobial defenses that persist after 1-month abstinence. To determine whether these changes are mediated through alterations in the bone marrow niche, we profiled monocytes and hematopoietic stem cell progenitors (HSCPs) from CHD rhesus macaques using a combination of functional assays and single cell genomics. CHD resulted in transcriptional profiles consistent with increased activation and inflammation within bone marrow resident monocytes and macrophages. Furthermore, CHD resulted in transcriptional signatures associated with increased oxidative and cellular stress in HSCP. Differentiation of HSCP in vitro revealed skewing toward …

Multimodal Profiling Of Term Human Decidua Demonstrates Immune Adaptations With Pregravid Obesity, Suhas Sureshchandra, Brianna M. Doratt, Heather E. True, Norma Mendoza, Monica Rincon, Nicole E. Marshall, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to …

Three Essays On Rural Education: Descriptive Studies Focused On Federal Rural Definitions And Policy Changes, Kyung Ha Oh

Theses and Dissertations--Public Policy and Administration

Rural education issues in K-12 public schools are understudied despite a large rural student population in the U.S. This dissertation studies how different federal definitions of rural change how rural school districts and their diverse communities are portrayed, in comparison to their non-rural counterparts. This study also explores the recent federal rural policy changes on rural district revenue and student academic outcomes.

This dissertation consists of three descriptive essays. The first chapter shows how we choose to define ‘rural’ changes what differences are accentuated between rural and non-rural districts. Definitions of ‘rural’ is closely related to who gains access to …

Giving Retakes Their Best Chance To Improve Learning., Thomas Data Guskey

Educational, School, and Counseling Psychology Faculty Publications

Assessment retakes can improve student learning if educators clear up a few misconceptions and avoid common missteps.

Politics And The Criminal Enforcement Of Superfund, Joshua Ozymy, Melissa Jarrell Ozymy

Kentucky Journal of Equine, Agriculture, & Natural Resources Law

No abstract provided.

Retention Strategies Among Those On Community Supervision In The South: Lessons Learned During The Covid-19 Pandemic., Breana J. Uhrig Castonguay, Katherine Lemasters, Chris Corsi, Evan J. Batty, Taylor J. Krajewski, Madelene Travis, Craig Waleed, Carrie B. Oser, Kathryn M. Nowotny, Lauren Brinkley-Rubinstein

Sociology Faculty Publications

OBJECTIVES: Cohort studies must implement effective retention strategies to produce internally valid and generalizable results. Ensuring all study participants are retained, particularly those involved in the criminal legal system, ensures study findings and future interventions will be relevant to this group, who are often lost to follow-up: critical to achieving health equity. Our objective was to characterize retention strategies and describe overall retention among an 18-month longitudinal cohort study of persons on community supervision prior to and during the COVID-19 pandemic.

METHODS: We implemented various retention strategy best-practices (e.g., multiple forms of locator information, training study staff on rapport building, …

Statistical Analyses To Identify Genetic Variants Associated With Neuropathological And Mri-Based Endophenotypes Of Alzheimer’S Disease, Lincoln M. P. Shade

Theses and Dissertations--Epidemiology and Biostatistics

Aged individuals often accumulate multiple brain pathologies that contribute individually and synergistically to cognitive decline and dementia. Alzheimer’s disease (AD) is the most commonly diagnosed form of dementia, constituting over 50% of dementia diagnoses, and poses an enormous burden on human health and well-being. In the United States alone, over six million individuals are living with AD, and the disease imposes financial costs of treatment and care of over $300 billion annually. The most common form of AD, late-onset AD (LOAD), presents in individuals aged 65 years and older and is highly heritable, with twin and family studies estimating its …

Understanding The Role Of Peroxiredoxin Iv In Colorectal Cancer Development, Pratik Thapa

Theses and Dissertations--Toxicology and Cancer Biology

Reactive oxygen species (ROS) are oxygen-containing free radicals and/or molecules that are more reactive than O₂. ROS such as hydroxyl radical (•OH) and hydrogen peroxide (H₂O₂) are produced naturally in the body as a result of reactions such as aerobic respiration and oxidative protein folding. ROS undergo reduction-oxidation (redox) reactions and mediate cell signaling. Accumulation of excessive ROS can damage DNA, RNA, protein and lipids. Antioxidants are enzymes and small molecules that react with ROS to modulate redox signaling and to prevent and repair oxidative damage. Examples of antioxidants include glutathione, thioredoxin, superoxide dismutase, …

Understanding And Targeting The Tph1-Serotonin-Htr3a Axis In Small Cell Lung Cancer, Yanning Hao

Theses and Dissertations--Toxicology and Cancer Biology

Small cell lung cancer (SCLC), which accounts for 10-15% of all lung cancer, is the most malignant type that tends to grow fast and spread in its early stages. The 5-year survival rate remains low at 6% overall. Thus, new therapeutic methods and pharmacological targets for SCLC patients are urgently needed. We present novel data indicating that the synthesis of serotonin is upregulated in SCLC compared to normal bronchial epithelial cells and non-small cell lung cancer. Serotonin signaling plays a critical role in various physiological and pathological processes. However, its contribution to SCLC development has not been well understood. The …

Targeting Ezh2 To Improve Outcomes Of Lung Squamous Cell Carcinoma, Tanner Ducote

Theses and Dissertations--Toxicology and Cancer Biology

Only 20% of patients diagnosed with lung squamous cell carcinoma (LSCC) respond to immunotherapy. Anti-PD1 immunotherapy is most commonly prescribed to these patients; however, most will become refractory. It is important to understand the mechanisms underlying this problem to increase durability and survival. Building upon the work of other groups, our lab has demonstrated that the inhibition of the histone methyltransferase, EZH2, is crucial to maintaining an immunologically responsive microenvironment. Based on our data, we hypothesize that combining EZH2 inhibitors with anti-PD1 therapy will increase response and durability. To study non-small cell lung cancers (NSLC) our lab uses a variety …

Hoarding Lifesaving Knowledge While Millions Die: The Political Economy Of Global Covid-19 Vaccine Apartheid, Kenneth Stancil

Theses and Dissertations--Geography

Coronavirus vaccines saved millions of lives, but experts estimate that the suboptimal production and inequitable distribution of shots resulted in nearly 3 million preventable Covid-19 deaths in 2021 and 2022 as well as millions of indirect deaths during the pandemic. These avoidable fatalities are inseparable from the grotesquely unequal vaccination rates between rich and poor nations. Dose hoarding by high-income countries contributed to vaccine inequality, but the “vaccine apartheid” inflicted on low-income countries reflects an even more fundamental injustice: knowledge hoarding by profit-maximizing pharmaceutical corporations—aided and abetted by wealthy governments—which deprived generic manufacturers of the right to produce additional lifesaving …

Discussions And Creations: Experiences Of Black Music Therapy Graduate Students Building Community And Belonging, Rebekah Irene Spann

Theses and Dissertations--Music

There is currently a lack of racial diversity within the music therapy field and a lack of research on the experiences of Black music therapy graduate students wanting to build community and belonging. The purpose of this study was to understand the experiences of three Black graduate music therapy students at the University of Kentucky seeking to build community and belonging with their Black peers. To further understand the experiences of these Black graduate music therapy students, this study followed participatory action research (PAR) methodology. Throughout the research process, I worked with participants to shape the project in a way …

An Exploration And Performance Of Underrepresented Composers For Cello, Anna M. Watrous

Libraries Award for Undergraduate Scholarship

As I was preparing for my senior degree cello recital (the performance component of this thesis) last summer, I realized that all the composers I planned on programming were famous composers that were white men. As a woman cellist, teacher, and arts advocate, I knew this was not the story that I wanted to tell through my recital. I realized that there was no reason to wait until after graduation when I was “finished learning” to be an advocate for those underrepresented in the arts, I could start with this recital. Through the process of programming, preparing, and performing this …

A Peculiar Institution: White Supremacy And The Black Guides Of Mammoth Cave, Seth Garcia

Libraries Award for Undergraduate Scholarship

Intensive tourist operations at Mammoth Cave began in 1838 when Frank Gorin purchased the cave property. He brought with him Stephen Bishop, an enslaved person who would become famous across the Western world for his explorations of the cave and his knowledge of its geology. Gorin would also lease Nicholas and Matterson Bransford, and these three men would begin a 100-year history of black guides at Mammoth Cave. This essay utilizes source material written by white visitors in diaries, guidebooks, and travelers’ accounts to better understand white supremacy during the mid to late 19th century. The guides were in a …