Digital Commons Network^™

Examining Caf Heterogeneity In Pancreatic Cancer, Nidhi V. Dwivedi

Theses & Dissertations

This thesis delves into the complexities of pancreatic ductal adenocarcinoma (PDAC) and its microenvironment. This study centers on unraveling the heterogeneity of pancreatic cancer-associated fibroblasts (CAFs) using a panel of patient-derived pancreatic fibroblasts. Additionally, it delves into the realm of G-protein-coupled receptors (GPCRs), with a specific emphasis on the Endothelin receptors (ETAR and ETBR), all within the context of PDAC.

A key achievement is the development of immortalized patient-derived pancreatic fibroblasts (iPDPFs), replicating CAF heterogeneity in PDAC. The iPDPFs were able to recapitulate the PDAC CAF heterogeneity, plasticity, and the overlapping nature of the tumor stroma. Functional characterization of iPDPFs …

Towards A Mode Of Action For The Anti-Schistosomal Aryl Hydantoins, Thomas Schulze

Theses & Dissertations

Schistosomiasis is a significant human disease caused by the helminth parasite Schistosoma mansoni. Praziquantel remains the only clinically used treatment, yet it is rapidly metabolized and only effective against the adult stage worm infection. Ro 13-3978 (AR02) is a potent antischistosomal compound with activity against multiple S. mansoni life stages; however, it manifests anti-androgenic activity. Additionally, the mechanism of action for worm clearance remains unknown. The structure of Ro 13-3979 was used to generate optimized derivatives, including AR102, that show increased potency towards worms, reduced off-target anti-androgen effects, and extended half-life thereby increasing the feasibility for a single-dose curative treatment. …

Impacts Of Perinatal Oxycodone Exposed Offspring In Early Adolescence, Adrian Flores

Theses & Dissertations

The Opioid Epidemic has been a point of public health interest for the last twenty years. In this time, use of prescription opioids has grown exponentially, including use by pregnant women. The initial crisis has been focused on mitigating immediate problems such as lowering the significant loss of life in overdoses and providing support to cessation. Despite these advancements a separate phenomenon is on the rise: The rise in neonatal opioid withdrawal syndrome in neonatal care and associated challenges for these children as they age.

Currently preclinical research and epidemiological data suggests that exposed children are at risk for experiencing …

Interactive Effects Of Sublethal Concentrations Of Fracking Biocides And Abandoned Mine Drainage On Amphipod Behavior, Kelly Lenhart

Electronic Theses and Dissertations

This thesis examined the sublethal effects of three pollutants, namely glutaraldehyde, 4,4-dimethyloxazolidine (DMO), and abandoned mine drainage (AMD), on amphipods. The primary objective was to investigate their combined effects on amphipods. The three pollutants, despite having the potential to combine in the environment, have not been studied to determine their potential for detrimental interactive effects which could result in unexpected environmental damage.

The research employed a series of experimental setups involving controlled exposure of amphipods to varying, putatively sublethal, concentrations of the chemicals of interest. Subsequently, effects were assessed via both behavioral and feeding assessments. To facilitate this analysis, novel …

An Evangelical Theology Of Engagement With Religious Others, Michael Urton

Witness

No abstract provided.

A Virtual Reality Conditioned Place Preference In Undergraduates With Nicotine Use, Lukas Klin

Honors Scholar Theses

This study was conducted to determine if a Conditioned Place Preference (CPP) could be established for a Virtual Reality (VR) environment that was previously paired with virtual nicotine stimuli. 254 undergraduate students with varying levels of nicotine use from the University of Connecticut were recruited to participate in the study. Participants completed six, three-minute conditioning sessions where they were confined to one of two VR rooms with one room containing virtual nicotine stimuli while the other was neutral. Participants then completed a three-minute test session, in which they were allowed access to both rooms and there were no virtual nicotine …

Interrogation Of The Molecular Mechanisms That Finetune Fcεri Signaling And Mast Cell Outcomes, Derek A. Rinaldi

Biomedical Sciences ETDs

FcεRI is the ITAM receptor primarily responsible for the allergic response and immune hypersensitivity diseases such as asthma. Regulation of the strength of both FcεRI signaling, and the resulting outcomes, is accomplished via a complex array of molecular mechanisms whose interactions remain unclear. Here, I explored how the biophysical properties of antigens, crosstalk between FcεRI and integrin signaling and Arf6-mediated control of trafficking and exocytosis tune mast cell outcomes. I first found significant differences in FcεRI aggregation, phosphorylation and granule secretion after crosslinking with the multivalent antigen DNP-BSA or the small, trivalent antigen DF3. I also revealed a bi-directional, Syk-mediated …

Pkcε Activator Protects Hippocampal Microvascular Disruption And Memory Defect In 3×Tg-Alzheimer's Disease Mice With Cerebral Microinfarcts, Huaixing Wang, Zongxiu Zhang, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 …

Gpr84-Mediated Signal Transduction Affects Metabolic Function By Promoting Brown Adipocyte Activity, Xue-Nan Sun, Yu A An, Vivian A Paschoal, Camila O De Souza, May-Yun Wang, Lavanya Vishvanath, Lorena Ma Bueno, Ayanna S Cobb, Joseph A Nieto Carrion, Madison E Ibe, Chao Li, Harrison A Kidd, Shiuhwei Chen, Wenhong Li, Rana K Gupta, Da Young Oh

Faculty, Staff and Student Publications

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes …

Acidosis-Mediated Increase In Ifn-Γ-Induced Pd-L1 Expression On Cancer Cells As An Immune Escape Mechanism In Solid Tumors, Philipp Knopf, Dimitri Stowbur, Sabrina H L Hoffmann, Natalie Hermann, Andreas Maurer, Valentina Bucher, Marilena Poxleitner, Bredi Tako, Dominik Sonanini, Balaji Krishnamachary, Sanhita Sinharay, Birgit Fehrenbacher, Irene Gonzalez-Menendez, Felix Reckmann, David Bomze, Lukas Flatz, Daniela Kramer, Martin Schaller, Stephan Forchhammer, Zaver M Bhujwalla, Leticia Quintanilla-Martinez, Klaus Schulze-Osthoff, Mark D Pagel, Marieke F Fransen, Martin Röcken, André F Martins, Bernd J Pichler, Kamran Ghoreschi, Manfred Kneilling

Faculty, Staff and Student Publications

Immune checkpoint inhibitors have revolutionized cancer therapy, yet the efficacy of these treatments is often limited by the heterogeneous and hypoxic tumor microenvironment (TME) of solid tumors. In the TME, programmed death-ligand 1 (PD-L1) expression on cancer cells is mainly regulated by Interferon-gamma (IFN-γ), which induces T cell exhaustion and enables tumor immune evasion. In this study, we demonstrate that acidosis, a common characteristic of solid tumors, significantly increases IFN-γ-induced PD-L1 expression on aggressive cancer cells, thus promoting immune escape. Using preclinical models, we found that acidosis enhances the genomic expression and phosphorylation of signal transducer and activator of transcription …

Living Among Wildlife: Elevating Human-Wildlife Interactions And Coexistence, Bridget Rebecca Murphy

Graduate Student Portfolios, Professional Papers, and Capstone Projects

After a semester of learning, both in class and in nature, my writing honed in further on this human-nature divide. To me, I see humans as part of nature – as we are mammals, animals, part of the food chain, biological beings no higher than others on our planet. We have simply constructed this false narrative around us within our societies, minds and media that embeds this division between us and nature, between us and wildlife. Humans have been managing, stewarding, living off and within landscapes for thousands of years. As time and technology evolved, a lot of people began …

Habitat And Demography Of The Ozark Chinquapin (Castanea Ozarkensis) At Roaring River State Park In Barry County, Missouri, Danielle Evilsizor

Electronic Theses & Dissertations

The Ozark chinquapin, Castanea ozarkensis Ashe, is a chestnut tree with a range concentrated in the Interior Highlands of North America. Like other North American members of Castanea, it was reduced from an overstory tree to an understory shrub by the invasive chestnut blight fungus (Cryphonectria parasitica [Murrill] M.E. Barr) during the early 20^th century. However, relatively little is known about the habitat of this species or its health and reproductive capability post chestnut blight. Chapter one of this study analyzed the habitat of this species through a random forest species distribution model (SDM) to predict where …

Castor Oil Polyol-Based Adhesives With Additional Crosslinker For Improvement In Mechanical And Thermal Properties., Yash Desai

Electronic Theses & Dissertations

Polyurethanes (PU) have been promising polymeric materials with many applications, including adhesives. Projecting an estimated revenue from 42.8 billion $ in 2021 to 61.5 billion $ by 2026. However, a large number of PU adhesives are sourced from petroleum products. Therefore, to lower the dependence on non-renewable resources and provide sustainable and affordable alternatives. In this work will synthesize bio-based adhesives of polyurethane from modified castor oil-based polyol. Generally, polyurethane reaction depends on the properties of polyol and isocyanates. The most important aspect of these reactions is the OH number of the polyol, which is responsible for the crosslinking and …

Oregon State Rank Assessment For Margined Sculpin (Cottus Marginatus), Misty Nelson

Institute for Natural Resources Publications

Oregon state conservation status assessment for margined sculpin (Cottus marginatus) using NatureServe methodology, 2023.

Understanding The Lived Experiences Of Ethnic-Racial Minority Former Foster Youth Who Identify As Queer, Cristian A. Lemus

Doctoral Dissertations

This qualitative study used Interpretative Phenomenological Analysis to explore the lived experiences and meaning making of former foster youth of color who identify as both ethnic-racial minorities and as either gender or sexual minorities. A total of three participants took part in this study. All participants identified as a former foster youth with at least one foster care placement in the United States, as an ethnic-racial minority, and as a gender or sexual minority. In the lived experiences of the participants three themes, and several subthemes, emerged: identity, cultural prejudice, and power dynamics. The findings supported the hypothesis former foster …

Dark Moon Shallow Sea (The Gods Of Night And Day Series, Vol. 1) By David R. Slayton, Phillip Fitzsimmons

Faculty Articles & Research

Book review of Dark Moon Shallow Sea (The Gods of Night and Day Series, vol 1) by author David R. Slayton. Book review by Phillip Fitzsimmons.

From Doormats To Three-Dimensions: The Evolution Of Female Characters In Anime’S Action Genre, Sajina Shrestha

Capstones

Strong female characters have always been an outlier and not the trend in the action genre of anime. However, new writers are bringing fleshed-out female characters to the forefront, making for better viewing.

https://docs.google.com/document/d/1p3FROe7uFQNNTR0rwrnwlTlmXzqpvqCvQotshTUZMxs/edit?usp=sharing

Erasing Race, Emily Swanson

Capstones

Since the murder of George Floyd, the Minneapolis Police Department has increasingly lagged in its reporting of race data.

Dark Moon Shallow Sea, By David R. Slayton. Reviewed By Phillip Fitzsimmons., Phillip Fitzsimmons

Mythprint Book Reviews

Mythprint is the quarterly bulletin of the Mythopoeic Society, a nonprofit educational organization devoted to the study, discussion, and enjoyment of myth and fantasy literature, especially the works of J.R.R. Tolkien, C.S. Lewis, and Charles Williams. To promote these interests, the Society publishes three magazines, maintains a World Wide Web site, and sponsors the annual Mythopoeic Conference and awards for fiction and scholarship, as well as local discussion groups.

Independent Writing At The Kindergarten Level, Carley K. Andrus

Masters Projects

Abstract

Writing has become an important component of literacy instruction in early childhood classrooms. Young learners are being faced with challenges in writing workshops, leaving them unable to develop age appropriate work on their own. Research was done to further the understanding for teachers and administration on the important strategies that will support student writing. Studies have found that peer instruction, oral language and self regulation strategies are all important factors when developing student independence. In order to have students meet the high demanding literacy standards, teachers need to feel comfortable and confident in their practices. This project can assist …

Bayesian Longitudinal Tensor Response Regression For Modeling Neuroplasticity, Suprateek Kundu, Alec Reinhardt, Serena Song, Joo Han, M Lawson Meadows, Bruce Crosson, Venkatagiri Krishnamurthy

Faculty, Staff and Student Publications

A major interest in longitudinal neuroimaging studies involves investigating voxel-level neuroplasticity due to treatment and other factors across visits. However, traditional voxel-wise methods are beset with several pitfalls, which can compromise the accuracy of these approaches. We propose a novel Bayesian tensor response regression approach for longitudinal imaging data, which pools information across spatially distributed voxels to infer significant changes while adjusting for covariates. The proposed method, which is implemented using Markov chain Monte Carlo (MCMC) sampling, utilizes low-rank decomposition to reduce dimensionality and preserve spatial configurations of voxels when estimating coefficients. It also enables feature selection via joint credible …

Mitochondrial Metabolism In Blood More Reliably Predicts Whole-Animal Energy Needs Compared To Other Tissues, Stefania Casagrande, Maciej Dzialo, Lisa Trost, Kasja Malkoc, Edyta T. Sadowska, Michaela Hau, Barbara J. Pierce, Scott R. Mcwilliams, Ulf Bauchinger

Biology Faculty Publications

Understanding energy metabolism in free-ranging animals is crucial for ecological studies. In birds, red blood cells (RBCs) offer a minimally invasive method to estimate metabolic rate (MR). In this study with European starlings Sturnus vulgaris, we examined how RBC oxygen consumption relates to oxygen use in key tissues (brain, liver, heart, and pectoral muscle) and versus the whole-organism measured at basal levels. The pectoral muscle accounted for 34-42% of organismal MR, while the heart and liver, despite their high mass-specific metabolic rate, each contributed 2.5-3.0% to organismal MR. Despite its low contribution to organismal MR (0.03-0.04%), RBC MR best predicted …

Combining The Tyrosine Kinase Inhibitor Cabozantinib And The Mtorc1/2 Inhibitor Sapanisertib Blocks Erk Pathway Activity And Suppresses Tumor Growth In Renal Cell Carcinoma, Yige Wu, Siqi Chen, Xiaolu Yang, Kazuhito Sato, Preet Lal, Yuefan Wang, Andrew T Shinkle, Michael C Wendl, Tina M Primeau, Yanyan Zhao, Alanna Gould, Hua Sun, Jacqueline L Mudd, Jeremy Hoog, R Jay Mashl, Matthew A Wyczalkowski, Chia-Kuei Mo, Ruiyang Liu, John M Herndon, Sherri R Davies, Di Liu, Xi Ding, Yvonne A Evrard, Bryan E Welm, David Lum, Mei Yee Koh, Alana L Welm, Jeffrey H Chuang, Jeffrey A Moscow, Funda Meric-Bernstam, Ramaswamy Govindan, Shunqiang Li, James Hsieh, Ryan C Fields, Kian-Huat Lim, Cynthia X Ma, Hui Zhang, Li Ding, Feng Chen

Faculty, Staff and Student Publications

Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor …

Plants As Vectors For Environmental Prion Transmission, Christina M Carlson, Samuel Thomas, Matthew W Keating, Paulina Soto, Nicole M Gibbs, Haeyoon Chang, Jamie K Wiepz, Annabel G Austin, Jay R Schneider, Rodrigo Morales, Christopher J Johnson, Joel A Pedersen

Faculty, Staff and Student Publications

Prions cause fatal neurodegenerative diseases and exhibit remarkable durability, which engenders a wide array of potential exposure scenarios. In chronic wasting disease of deer, elk, moose, and reindeer and in scrapie of sheep and goats, prions are transmitted via environmental routes and the ability of plants to accumulate and subsequently transmit prions has been hypothesized, but not previously demonstrated. Here, we establish the ability of several crop and other plant species to take up prions via their roots and translocate them to above-ground tissues from various growth media including soils. We demonstrate that plants can accumulate prions in above-ground tissues …

Leaf Thermal Regulation Strategies Of Canopy Species Across Four Vegetation Types Along A Temperature And Precipitation Gradient, Yingying Zhou, Nawatbhrist Kitudom, Sophie Fauset, Martijn Slot, Zexin Fan, Jianping Wang, Weiwei Liu, Hua Lin

School of Geography, Earth and Environmental Sciences

The ecophysiological processes of leaves are more related to leaf temperature (Tl) than air temperature (Ta). Transpiration and leaf physical traits enable plants to maintain Tl within a thermal range. However, it is challenging to quantitatively study leaf thermal regulation strategies, due to the complex interaction between thermal effects of transpiration and leaf physical traits. We utilized a 3-T method that compares Tl, Ta, and Tn (the temperature of non-transpiring leaves) investigate thermal regulation strategies of dominant canopy species in four vegetation types, including a savanna woodland, a tropical rain forest, a subtropical evergreen broad-leaved forest, and a temperate mixed …

Organic Dining Behaviour In British Restaurants, Lokman Dinc, Rong Huang

Plymouth Business School

The organic food market has experienced significant growth in recent decades all over the world. Within the context of the UK, a remarkable rise can be seen considering the recent popularisation of organic food products. With these trends in mind, the aim of this research is to develop better understanding of organic dining behaviour in British restaurants. To achieve this aim, this research used questionnaire technique and analyse the data using SEM.The key findings of the research confirmed that a range of factors, including advertisements through social media, knowledge, price, taste, quality, availability, and labelling, all significantly influence consumer intention …

"How Could Anyone But A Madman Have Thought This Sleeping Girl Dead?": L.T. Meade's Approach To The "Buried Alive" Literary Tradition In Support Of Death Certification Reform, Shelby Johnson

Theses and Dissertations

A March 1866 issue of The Lancet observes, "If a newspaper were in want of a startling story with which to enliven a dull copy in the 'off season,' it could not do better than select one with the heading "'Buried Alive'"("Premature Interment" 295). Stories of being buried alive gave readers of all backgrounds a thrill. However, the stories frustrated the medical and scientific communities who were quick to dismiss the threat of live burial as a possibility in a modern world. Drawing on the literary history of "buried alive" stories and medical knowledge surrounding death signs and catalepsy, this …

Myod-Skp2 Axis Boosts Tumorigenesis In Fusion Negative Rhabdomyosarcoma By Preventing Differentiation Through P57kip2 Targeting, Silvia Pomella, Matteo Cassandri, Lucrezia D’Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S. Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R. Vakoc, Enrico Velardi, Beat W. Schafer, Ernesto Guccione, Susanne A. Gatz, Lucio Miele

School of Medicine Faculty Publications

Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic …

Best Practices To Manage Nitrate Contamination Of Groundwater In Agricultural Zones: A Comparative Analysis Of Farming Impacts On Areas Of Central Valley And High Plains Aquifers, Rekha Duthulur

Master's Projects and Capstones

Nitrate is one of the most common contaminants in groundwater and causes multiple health impacts when consumed. Contamination is most significant in agricultural areas and has increased steadily since the 1950s with the introduction of nitrogen fertilizers. The depth of an aquifer, sediment type, hydrogeology, redox conditions, microbe activity, fertilizer application, natural nitrogen deposits, and well construction influence the degree of nitrate contamination of an aquifer. The sources of nitrate pollution are fertilizer, manure, concentrated feeding lots, natural nitrogen deposits, atmospheric deposition, septic systems, wastewater treatment plants, and industrial activities. Nitrogen compounds applied on the surface are stored in the …

Assessing Wastewater Treatment In Yopal Colombia Using Gis, Leydi P. Puerto Bohorquez

Master's Projects and Capstones

The amount of wastewater has surged alongside population growth, urbanization, and economic development, which can influence the wastewater treatment process, especially in the treatment capacity, particularly in developing countries. In Colombia, the low coverage of Wastewater Treatment Plants (WWTP) leads to a complex environmental issue. This has threatened water quality and aquatic ecosystems of waterbodies that receive this type of water by increasing disease prevalence and creating hypoxic conditions. To determine how a WWTP could impact water quality, it was necessary to understand the treatment process and the physicochemical parameters being monitored. The focus is to answer the central research …