Digital Commons Network^™

Design And Synthesis Of Small Molecular Probes For Cns And Kidney Disorders, Swagat H. Sharma

Theses & Dissertations

The G protein regulated inwardly rectifying potassium channels (GIRK) are a family of inwardly rectifying potassium channels and are key effectors in signaling pathways. GIRK 1/2 channel subunit, predominantly found in the brain, is involved pathophysiology of various neurological disorders including, but not limited to, epilepsy, anxiety, Parkinson's, pain, reward, and addiction. Previously, our laboratory had identified a series of urea containing molecules as GIRK1/2 preferring activators. Unfortunately, the urea series suffers from significant PK liabilities (solubility, brain penetration and high clearance). The chapter 1 of the dissertation describes our efforts in developing three new series of activators with improved …

Usp11 And Usp7 Deubiquitinases Regulate Sprtn Auto-Proteolysis And Sprtn-Mediated Dna-Protein Crosslink Repair, Megan C. Perry

Theses & Dissertations

DNA repair pathways that recognize and remove damaged DNA are vital for maintenance of genomic stability and prevention of tumorigenesis. Conversely, these pathways may be robust in tumor cells, thus diminishing the anti-cancer potential of available therapies. DNA-protein crosslinks (DPCs) are particularly deleterious DNA adducts that occur when proteins become irreversibly covalently bound to the DNA. DPCs represent a diverse group of lesions, as any protein can be crosslinked to the DNA duplex by non-specific crosslinking agents like reactive aldehydes and radiation. Additionally, functional DNA-binding proteins such as topoisomerases may become permanently crosslinked to DNA ends by abortive enzymatic processes …

Delivery Of Sirna With Drugs Targeting Polyamine Metabolism As Combinational Cancer Treatment, Ao Yu

Theses & Dissertations

Cancer has been a major public health issue worldwide for years and is the second leading cause of death in the United States. Important barrier must be broken to extend the life expectancy in every country. The standard care for cancer causes severe side effects which affects patients’ physical health and quality of life. Polyamines are highly related with the cell proliferation and apoptosis. Dysregulated polyamine metabolism in cancer leads to increased polyamine concentration in neoplastic cells. Thus, polyamine metabolism for cancer therapy can be an intriguing target. However, the heterogeneity affecting key cancer pathways poses significant challenges for effective …

Glad To Be Out. I Was Running Out Of Womb: A Study Of Omega-6 And Omega-3 Fatty Acid Metabolites At Delivery And Their Relationship To Infant Growth, Prematurity, And Admission To The Neonatal Intensive Care Unit, Maranda Thompson

Theses & Dissertations

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled it can lead to poor infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and omega-6 fatty acids have been shown to be metabolized into bioactive metabolites that effect inflammation. The presence and importance of these metabolites at the time of delivery are not well understood. Therefore, the purpose of this dissertation was to first quantify omega-3 and omega-6 metabolites in maternal plasma, cord plasma, and placental tissue. Then the relationships between metabolites and infant outcomes, including birth weight percentile, length percentile, head circumferences …

Molecular Investigation Into The Biologic And Prognostic Elements Of Peripheral T-Cell Lymphoma With Regulators Of Tumor Microenvironment Signaling Explored In Model Systems, Tyler Herek

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is heterogenous group of mature T-cell neoplasms characterized by distinctive transcriptional and genetic lesions. Herein, we investigated DNMT3A mutations in angioimmunoblastic T-cell lymphoma (AITL, n = 176) and novel molecular subtypes (i.e., PTCL-GATA3, n = 61 and PTCL-TBX21, n = 80) within PTCL- NOS and observed significant biological and prognostic differences associated with DNMT3A mutations. DNMT3A-mutated PTCL-TBX21 cases showed inferior overall survival (OS; p < 0.005), with DNMT3A mutations (DNMT3A-MT) skewed toward the methyltransferase domain and in the dimerization domain (S881-R887). Transcriptional profiling demonstrated significant enrichment of activated CD8⁺ T-cell cytotoxic gene signatures in the tumor microenvironment of DNMT3A-MT PTCL-TBX21 cases. Genome-wide methylation analysis of DNMT3A-R882/Q886 versus wild-type in PTCL-TBX21 cases demonstrated hypomethylation in target genes regulating T-cytotoxic genes, TCR …

Northern Dene Astronomical And Sky-Related Knowledge: A Comparative Anthropological Study, Chris M. Cannon

Anthropology

The sky and its contents are routinely overlooked in Northern Dene ethnology as a meaningful part of linguistic and cultural knowledge. However, more than 11 years of primary fieldwork learning with and from elders, speakers, and culture bearers from 12 Northern Dene groups across 32 communities in Alaska and Canada has shown that astronomical knowledge is deeply rooted in both practical and sacred ways of knowing. With a focus on detail and breadth, this comparative ethnological study utilized an experience-based approach to investigate the ways in which Northern Dene Peoples perceive, conceptualize, and integrate the sky and its contents into …

Bridging The Cultural Divide: Creating Culturally Diverse Therapeutic Foster Homes In Rural Alaska, Erica A. Dillard

Justice

The disproportionate number of American Indian and Alaska Native children being removed from their homes and communities by Child Protective Services is statistically alarming. Despite the current resources available, many families are unable to take advantage of these resources due to issues caused by their rural environments. This paper reviews the causes leading up to the removal of American Indian and Alaska Native children from their homes and communities, examines the importance of cultural identity, and discusses the resources that are needed to prevent these removals from occurring.

Air Quality And Mental Health: Evidence, Challenges And Future Directions, K Bhui, J Newbury, R Latham, M Ucci, Z Nasar, B Turner, C O'Leary, Hl Fisher, E Marczylo, P Douglas, S Stansfeld, S Jackson, S Tyrrel, A Rzhetsky, R Kinnersley, P Kumar, C Duchaine, F Coulon

School of Biomedical Sciences

No abstract provided.

A Literature Review Of Wetland Treatment Systems Used To Treat Runoff Mixtures Containing Antibiotics And Pesticides From Urban And Agricultural Landscapes, Emily R. Nottingham, Tiffany L. Messer

Biosystems and Agricultural Engineering Faculty Publications

Wetland treatment systems are used extensively across the world to mitigate surface runoff. While wetland treatment for nitrogen mitigation has been comprehensively reviewed, the implications of common-use pesticides and antibiotics on nitrogen reduction remain relatively unreviewed. Therefore, this review seeks to comprehensively assess the removal of commonly used pesticides and antibiotics and their implications for nitrogen removal in wetland treatment systems receiving non-point source runoff from urban and agricultural landscapes. A total of 181 primary studies were identified spanning 37 countries. Most of the reviewed publications studied pesticides (n = 153) entering wetlands systems, while antibiotics (n = 29) had …

Dm Ii Bugging You? Probiotics May Help Reach Your Glycemic Goals, Robert Kime, Kayla Siford

Physician Assistant Capstones, 2020-current

Objective: To determine the effects of probiotics on glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) in patients with Type II Diabetes (T2DM) controlled with oral medications. Design: Systematic Literature Review. Methods: Searches were conducted on PubMed using the terms: prebiotic, probiotic, type 2 diabetes, non-insulin dependent, and microbiota. Searches refined with parameters for Randomized Control Trials, written in English, and available texts. Results: Firouzi et al. did not show a significant change in the FBG between groups and a decrease in the HbA1c in the intervention group. Ejtahed et al. showed a significant decrease in …

The Effect Of Platelet Rich Plasma On The Treatment Of Androgenetic Alopecia Compared To Placebo, Mackenzie D. Comstock, Hannah E. Stephenson

Physician Assistant Capstones, 2020-current

Objective: To assess the efficacy of plasma rich proteins (PRP) compared to placebo in the treatment of androgenetic alopecia (AGA).

Design: Systematic literature review

Methods: Searches were done in PubMed utilizing the terms PRP, plasma rich protein, autologous activated PRP, autologous activated plasma rich protein, androgenetic alopecia, placebo, hair count, hair density, hair follicles, hair loss, therapeutic effect, growth factors, dermatology, and regenerative medicine. Articles were excluded if they were published before 2013, involved animal studies, compared minoxidil only in their research, included only female participants, non-English articles, studies with no quantifiable data, review research articles, and injections besides the …

Training The Next Generation Of Climate Science Integrators: Lessons From The Landscape Conservation Cooperatives, Fiona Rowles

Natural Resources

Science that can be readily applied to policy or decision-making is a critical component of adapting to the climate emergency. Boundary spanning facilitates the creation of credible, relevant, and legitimate science for use in policy and decision making. Individuals who are adept at navigating the interface between science and decision making (referred to as "boundary spanners") are crucial in developing science that fits the needs of managers. Though the attributes and skills needed to be an effective boundary spanner are well-defined, individuals are not often trained for these roles. This study incorporates two sets of interviews conducted with employees and …

Development Of Polymeric Cxcr4 Targeting Carriers For Sirna Delivery To Treat Acute Kidney Injury, Weimin Tang

Theses & Dissertations

Acute kidney injury (AKI) is a major kidney disease that is characterized by a sudden loss of renal function which manifests by a decrease in urine output and an increase in serum creatinine. AKI is a global healthcare burden associated with high morbidity, mortality, and increasing cost. Currently there are no effective pharmacological treatments available. Apoptosis induced by p53 has been demonstrated as an important pathological mechanism for the development of AKI. Meanwhile, CXCR4/SDF-1 axis has been associated with the inflammation during AKI, and CXCR4 is overexpressed on injured tubules. This dissertation hypothesized that polycations with CXCR4 targeting ability could …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

The Rotator Cuff Tendon-To-Bone Interface: Maturation, Aging, And 3d Bioprinting For Regeneration, Xiping Jiang

Theses & Dissertations

Rotator cuff tendon injuries often occur at the tendon-to-bone interface (i.e., enthesis) area with a high prevalence for the elderly population. In addition, regeneration of the gradient structure of the enthesis is still a significant clinical challenge. Our studies aim to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging, and develop a novel therapeutic method using three-dimensional (3D) bioprinting technique to regenerate a functional enthesis. Striking variations of the entheses were observed both histologically and biomechanically during the maturation process. The histological features did not show many differences at the insertion site …

Understanding The Impact Of Chlamydia Trachomatis Infection On Host Vesicular Trafficking, Lisa M. Jorgenson

Theses & Dissertations

Chlamydia trachomatis is a highly evolved obligate intracellular bacterial pathogen. During infection, organisms reside within a host epithelial cell in a membrane-bound vacuole called the inclusion. The inclusion membrane contains both pathogen and host components, including unique chlamydial type III effector proteins called Incs and host lipids like cholesterol and sphingomyelin. The inclusion membrane serves as the main barrier between the bacteria and the host cytosol, and thus, functions as the platform supporting host-chlamydial interactions. Via the inclusion membrane, C. trachomatis intercepts components of host vesicular traffic including many host SNARE proteins, which are a conserved family of eukaryotic proteins …

Humanized Mice For Brain Infection Of Emerging Viruses, Edward Makarov

Theses & Dissertations

Studies on the pathogenesis of emerging viruses that present a global threat are critical for pathogen classification and therapeutic development. Humanized mice enable investigation of viral pathogens, including Human immunodeficiency virus (HIV-1), Zika virus (ZIKV), Coronavirus 2 (SARS-CoV-2), and Dengue virus (DENV), offering an advanced understanding into the mechanisms of viral perseverance in its natural human host cells and for therapeutic discovery. Realizing the diverse dynamics of various viral infections with the capacity to establish an innovative acuity for therapeutics and mechanics when utilizing humanized mice contributes a formerly inaccessible insight into human-specific viral pathogenesis and treatment. We recently developed …

Utility Of S100a12 As An Early Biomarker In Patients With St-Segment Elevation Myocardial Infarction, Xiaolin Zhang, Minghui Cheng, Naijing Gao, Yi Li, Chenghui Yan, Xiaoxiang Tian, Dan Liu, Miaohan Qiu, Xiaozeng Wang, Bo Luan, Jie Deng, Shouli Wang, Hongyan Tian, Geng Wang, Xin-Liang Ma, Gregg W Stone, Yaling Han

Department of Emergency Medicine Faculty Papers

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis.

Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI).

Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort.

Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral …

A Protocol For The Induction Of Experimental Necrotizing Enterocolitis In Neonatal Mice, Lila S Nolan, Qingqing Gong, Heather N Hofmeister, Misty Good

Open Access Publications

Recapitulating human NEC using animal models has been insightful in dissecting the signaling pathways, immune-mediated mechanisms, genetic signatures, and the intestinal architecture of NEC. This protocol describes an

The Analysis Of Microdroplet Arrays, Alex Austin

Mechanical Engineering and Materials Science Independent Study

The primary objective of my research this semester was the investigation into the optimization of the micropillar array both through simulations and physical testing. Where ancillary objectives include the familiarization of SEM imaging, Surface Evolver, and COMSOL. Significant progress has been made in all these objectives. Specifically in the construction of different asymmetrical droplets that were combined to form an array.

The Mrna-Lnp Platform's Lipid Nanoparticle Component Used In Preclinical Vaccine Studies Is Highly Inflammatory, Sonia Ndeupen, Zhen Qin, Sonya Jacobsen, Aurélie Bouteau, Henri Estanbouli, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of …

Environmental Influence On Size Frequency Distributions Of The Pacific Blue Mussel (Mytilus Trossulus) In Two Glacially Inlfuenced Estuaries, Amy Dowling

Marine Biology

The Pacific blue mussel (Mytilus trossulus) is a foundation species in high-latitude intertidal and estuarine systems that can create complex habitats, provide sediment stability, serve as food for top predators, and act as connectors between the water column and the benthos. M. trossulus also makes an ideal model species to assess biological responses to environmental variability, as its size frequency distributions can be influenced by the environment in which it lives. Size frequency distributions can provide valuable information about ecological systems that are experiencing environmental change (e.g., increased global temperatures). M. trossulus populations in high latitude estuaries receive freshwater runoff …

Fasting Status Of Steller Sea Lion Pups, Stephanie G. Crawford

Biological Sciences

Following population declines in species of concern, wildlife managers often seek to identify underlying causes to understand and predict population dynamics for better future management. Often, physiological and/or behavioral metrics are measurable markers of decline, and these are often detectable well before declines are measurable through population surveys. During the 1970's, 80's, and 90's Steller sea lion (SSL; Eumetopias jubatus) populations in the western portion of their breeding range declined by ~85%. Though declines in most regions have since stabilized or exhibited modest recovery, some subpopulations breeding in the Aleutian Islands continue to decline. In contrast, SSL subpopulations in eastern …

Rooted In Environmental Justice: Phytogeography And Ethnoecology Of Serianthes, Else Demeulenaere

Biological Sciences

Serianthes Benth. (Fabaceae) is one of the most endangered plant genera in the world, with 12 of the 18 species listed on the IUCN Red List of Threatened Species. Serianthes trees are culturally important to island communities of the Indo-Pacific region for canoes, boats, traditional houses, and medicine. Habitat loss and ecosystem degradation increased pressure on these trees, also threatening its Indigenous cosmology and traditional practices. This interdisciplinary study integrated genomic, biogeographic and ethnoecological approaches to develop appropriate policies that protect the Indigenous biocultural diversity of Serianthes. Phylogenomics of 401 nuclear exons and non-coding flanking regions using both a multi-species …

Immunological Factors Associated With Siv/ Shiv Persistence In Diverse Tissue Niches, Omalla A. Olwenyi

Theses & Dissertations

The significant challenge towards a successful HIV cure lies in eradicating persistent viral reservoirs across diverse tissue niches. As a result, HIV-infected individuals have to resort to lifelong antiretroviral therapy. Recent news of supposed HIV eradication in a second patient has further re-invigorated the fields of HIV cure. However, a few barriers remain, such as the lack of currently available assays to accurately quantify viral reservoirs, limited information on cellular factors associated with persistence, and varied dynamics of the viral reservoir in various body compartments. Lastly, HIV-infected individuals live different lifestyles stemming from comorbid substance abuse including consumption of morphine, …

Otolith Derived Hatch Dates, Growth Rates, And Microchemistry Of Arctic Cod (Boreogadus Saida) Support The Existence Of Several Spawning Populations In Alaskan Waters, Zane M. Chapman

Fisheries

The changing climate in the Arctic is resulting in increased air and water temperatures as well as a reduction in sea ice, affecting native species that evolved to live in the unique habitats of the Arctic Ocean. One species of significant importance to Arctic marine ecosystems is the Arctic Cod (Boreogadus saida), a keystone species that serves as vital prey for many marine mammals, seabirds, and fishes. Arctic Cod have a strong association with sea ice for spawning and for much of their early life history. In the Pacific Arctic, little is known about their early life history, especially with …

The Effects Of Ocean Acidification And Warming On The Metabolic Physiology Of Juvenile Northern Spot Shrimp (Pandalus Platyceros), Jamie Lee Musbach

Fisheries

Northern spot shrimp (Pandalus platyceros) support important commercial, subsistence, sport, and personal use fisheries in Alaska. This species is currently experiencing population declines in Southeast Alaska, mandating fishery closures in previously productive regions. Northern spot shrimp are harvested as adults and declining populations may be a result of limited recruitment into the fishery. Very little is known about the physiology of P. platyceros early life history stages and no known data exists on how early life history stages may be affected by environmental stressors such as ocean acidification (OA) and ocean warming (OW). OA is a result of increased anthropogenic …

Ultrasound Modulation Of Macaque Prefrontal Cortex Selectively Alters Credit Assignment–Related Activity And Behavior, Davide Folloni, Elsa Fouragnan, Marco K. Wittmann, Lea Roumazeilles, Lev Tankelevitch, Lennart Verhagen, David Attali, Jean François Aubry, Jerome Sallet, Matthew F.S. Rushworth

School of Psychology

Credit assignment is the association of specific instances of reward to the specific events, such as a particular choice, that caused them. Without credit assignment, choice values reflect an approximate estimate of how good the environment was when the choice was made—the global reward state—rather than exactly which outcome the choice caused. Combined transcranial ultrasound stimulation (TUS) and functional magnetic resonance imaging in macaques demonstrate credit assignment–related activity in prefrontal area 47/12o, and when this signal was disrupted with TUS, choice value representations across the brain were impaired. As a consequence, behavior was no longer guided by choice value, and …

Connecting Human Dignity, Non-Violence, And Environment For Healthcare Ethics In Nigeria, John Mark Ogu

Electronic Theses and Dissertations

Abstract

Connecting Human Dignity, Non-violence, and Environment in Health Care for Nigeria

By

John Mark Chinaemerem Ogu

December 2021

Dissertation supervised by Peter Ikechukwu Osuji, Ph.D.

This dissertation presents a global public health ethical approach based on social justice that connects human dignity, non-violence, and the environment in Nigeria. Recently, different places globally are witnessing uprisings and violence; some of these are linked to environmental scarcity. These are threats to global health, peace, development, and security because violence of any type or form is a global public health and security menace and an affront to human dignity. Environmental scarcity, especially …

Sacubitril/Valsartan Versus Angiotensin Inhibitors And Arrhythmia Endpoints In Heart Failure With Reduced Ejection Fraction, Sandra Chaparro

All Publications

No abstract provided.