Digital Commons Network^™

Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm

Theses and Dissertations

Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects …

Mef2-Bound Genes May Influence Ethanol Sedation In Drosophila Melanogaster, Katlyn M. Myers

Theses and Dissertations

Alcohol Use Disorder (AUD) is a global health issue that affects millions of people every year. This disorder has serious negative mental and physical consequences. Currently, treatment options for this disorder are largely limited to psychological therapy, with very few medications available to treat it. Being able to identify the environmental and genetic components that influence AUD can help improve diagnosis and treatment options. Previous studies in humans have shown a link between initial sensitivity and risk for alcohol abuse. Our laboratory uses Drosophila melanogaster as a model to study the genetic and environmental components of alcohol-related behaviors. Previous lab …

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …

Modeling Gardnerella Host-Pathogen Interaction: Characterization Of Vaginolysin And The Opacity Phenotype, Erin M. Garcia

Theses and Dissertations

Bacterial vaginosis (BV) describes a dysbiotic state of the vaginal mucosa, during which the dominance by beneficial lactobacilli species is lost, the vaginal pH increases, and the flora comprising the vaginal microbiome becomes more diverse. Bacterial taxa associated with this dysbiotic state interact to form a dense polymicrobial biofilm on the surface of the vaginal epithelium. This shift in the vaginal microflora is clinically important, even when symptoms are not noted, as women with BV are at increased risk for acquisition of other sexually transmitted infections, including HIV, and are more than two times as likely to experience preterm birth. …

Evidence Of Local Adaptation To Climate In An Invasive Ectotherm: A Study On The Eurasian Gypsy Moth (Lymantria Dispar) In North America, Phillip M. Gibbs

Theses and Dissertations

Invasive species exist in nearly every ecosystem both terrestrial and aquatic. Improving our understanding of the mechanisms that shape the ability of these organisms to physiologically cope with their surroundings will be crucial to preparing for future impacts of climate change. The Gypsy Moth (Lymantria dispar) has been expanding its range across North America over the last 100+ years since its arrival in Medford, Massachusetts. This study quantifies upper thermal limits (UTL) across 8 different populations of L. dispar in North America and seeks to determine if signals of local adaptation to climate across a latitudinal gradient may …

Towards A Greener Route To Blockbuster Statin Drugs: Harnessing The Power Of Biocatalysis And Integrating Cross-Coupling Catalysis In The Synthesis Of Rosuvastatin, Chanaka M. Amarasekarage

Theses and Dissertations

As global and political awareness about green and sustainable practices sharpens in the face of dramatic climate change and environmentally detrimental practices, one attractive approach is to harness the catalytic potential of enzymes. Thus influenced, our efforts focused on the development of an innovative chemoenzymatic route to widely prescribed Blockbuster statin drugs, specifically rosuvastatin. In this work, we engineered novel deoxyribose phosphate aldolase (DERA) variants via rationally designed site-directed mutagenesis to accept non-natural, less polar substrate, acrolein, along with acetaldehyde. Several of new mutants displayed elevated tolerance towards aldehydes and showed effective incorporation of acrolein into the unprecedented enzymatically-derived chiral …

Ceramide Synthase 2 Interacts With Ceramide Synthases 5 And 6 At The Mrna And Protein Levels, Dorothy Yen

Theses and Dissertations

Ceramides and sphingolipids make up major portions of the plasma membrane and therefore are crucial for cell proliferation, survival, and death. With dysregulation comes numerous pathophysiological conditions, such as Alzheimer's, Huntington's Disease, Creutzfeldt-Jakob, cardiovascular disease, and many cancers. However, the regulation of the enzymes responsible for catalyzing the formation of ceramides is still not well understood. In this experiment, three isoforms were of focus: CerS2, CerS5, and CerS6. Through mRNA, protein, and immunofluorescence analysis, it can be concluded that these isoforms do indeed interact within the human cell in order to upregulate their activity. It was also found that cells …

Beneficiation Of Coal Using Supercritical Water And Carbon Dioxide Extraction, Matthew Decuir Virginia Commonwealth University Cl

Theses and Dissertations

This work explores the use of carbon dioxide, water, and their mixtures as solvent for the pre-combustion beneficiation of raw coal without using any toxic mineral acids in the temperature range of 200-400℃. The fluid polarity, ionic constant, and supercritical point can be adjusted by H₂O/CO₂ ratio and temperature. Adding carbon dioxide to hydrothermal fluid also increases the ionization by forming carbonic acid. Extractions with supercritical fluids have several benefits including enhanced mass transport, ease of separation and recycle, wide range of extractive capability and tunability, better inherent safety, and in the case of carbon dioxide and …

Bee Diversity Of Three Appalachian Shale Barren Sites, Olivia C. Latham

Theses and Dissertations

Insect pollination is vital to ecosystem function. However, climate change, habitat loss, pesticides, and a variety of other anthropogenic sources are contributing to a decline in pollinator diversity. Fragile small ecosystems with a high composition of specialized plant species that rely on specific pollinators such as Appalachian shale barrens, are especially at risk of losing biodiversity. This study combines the use of active sweep net sampling of endemic shale barren forbs and passive trap methods over the course of a bloom season (April-August) in three barren sites to identify bee community populations and visitation relationships between pollinator species and endemic …

Sphingolipids In Cancer Health Disparities And As Prospective Targets For Cancer Therapy, April E. Boyd

Theses and Dissertations

Lung cancer is the deadliest cancer both in the United States and worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. However, lung cancer disparities are not shared equally across racial groups, with large differences between African American and Caucasian populations. Advances in research have revealed roles of lipid mediators in cancer biology and disease progression, but sphingolipid alterations in tissues should be explored further. To address this, using mass spectrometry (MS), extensive sphingolipidomic characterization of NSCLC tumors and adjacent uninvolved tissues from African American and Caucasian patients were performed. This study revealed that NSCLC …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

Integration Of Multi-Omic Platforms To Understand The Regulation Of Genes In Human Disease, Eva Lancaster

Theses and Dissertations

Epigenetic mechanisms have been hypothesized to modify gene expression (GE) in response to both genetic variation and environmental exposures, ultimately contributing to the development of complex traits. Epigenome-wide association studies (EWAS) aim to test the theory that marks of DNA methylation (DNAm) have downstream consequences that result in the development of complex diseases. Although these methods have been successful in identifying DNAm patterns in complex traits, specific molecular mechanisms involved in the etiology of complex diseases remain unidentified. This knowledge gap does not originate from a lack of DNAm-trait associations, but rather stems from study design issues that affect the …

Multi-Label Classification Models For Heterogeneous Data: An Ensemble-Based Approach., Jose Maria Moyano Murillo

Theses and Dissertations

In recent years, the multi-label classification gained attention of the scientific community given its ability to solve real-world problems where each instance of the dataset may be associated with several class labels simultaneously, such as multimedia categorization or medical problems.

The first objective of this dissertation is to perform a thorough review of the state-of-the-art ensembles of multi-label classifiers (EMLCs). Its aim is twofold: 1) study state-of-the-art ensembles of multi-label classifiers and categorize them proposing a novel taxonomy; and 2) perform an experimental study to give some tips and guidelines to select the method that perform the best according to …

Lpa Receptors Modulate Gene Expression During Oligodendrocyte Differentiation, Samantha A. Spencer

Theses and Dissertations

LPA, produced by the lysoPLD activity of ATX, binds its cognate receptors and regulates the development of multiple brain cells, including oligodendrocytes (OLGs). OLGs progress through a lineage from precursor (OPC) to early OLG to immature OLG, until finally the cells mature and enwrap axons to enable saltatory conduction and provide trophic support. The studies in this dissertation characterized the receptors LPA4 and LPA6 as inhibitors of OPC differentiation. Western blot analysis of MS patient lesion tissue found a negative correlation between ATX levels and levels of LPA4 and LPA6. A previously created homology model for LPA4 was used to …

The Analysis Of Neural Heterogeneity Through Mathematical And Statistical Methods, Kyle Wendling

Theses and Dissertations

Diversity of intrinsic neural attributes and network connections is known to exist in many areas of the brain and is thought to significantly affect neural coding. Recent theoretical and experimental work has argued that in uncoupled networks, coding is most accurate at intermediate levels of heterogeneity. I explore this phenomenon through two distinct approaches: a theoretical mathematical modeling approach and a data-driven statistical modeling approach.

Through the mathematical approach, I examine firing rate heterogeneity in a feedforward network of stochastic neural oscillators utilizing a high-dimensional model. The firing rate heterogeneity stems from two sources: intrinsic (different individual cells) and network …

The Impact Of The Fda Warning On Post-Tonsillectomy Opioid Prescribing In Publicly And Privately Insured Children, Dianna J. Soelberg

Theses and Dissertations

Due to reports of significant adverse events, the U.S. FDA placed a Boxed Warning on the opioid codeine in February 2013 – contraindicating its use in pediatric patients undergoing tonsillectomy and/or adenoidectomy. Studies conducted in privately insured children showed a reduction in codeine prescribing and a slight increase in alterative opioid prescribing following the FDA warning, yet the extent to which the FDA warning impacted prescribing in publicly insured children is unknown. Using a quasi-experimental interrupted time series design, this study evaluated codeine and alternative opioid prescribing before and after the FDA warning in both publicly and privately insured children …

Black Women And Body Image: Implications Of The Racialized Beauty Aesthetic, Rachel L. Boutte

Theses and Dissertations

Black women have the highest prevalence of overweight and obesity relative to any other demographic group in the United States, however current weight management interventions appear least effective for them. Although several hypotheses have been proposed to explain these outcomes, few studies have collected data to evaluate how well they fit the lived experiences of Black women. In particular, the potential roles of body image and body dissatisfaction in the development and maintenance of overweight and obesity in Black women are not well understood. Extant literature largely reports that Black women are inoculated from body dissatisfaction due to cultural factors, …

Exosomes As Systemic Mediators Of Nanotube Induced Neurotoxicity, Christopher G. Canal

Theses and Dissertations

Extra-pulmonary effects of nanoparticle inhalation have been well documented; however, mechanisms for conveying peripheral bioactivity remain elusive. Recent studies point to indirect molecular mediators shed into the circulation. Protein and lipid alternatives to cytokines or chemokines have been proposed, yet the diversity among responses suggests a broader assemblage of factors. Recently we have proposed proteolytic fragment peptides as an additional source of bioactivity, which interestingly were significantly associated with exosomal proteins after enrichment analysis. Here we tested whether modeled exposure to multi-walled carbon nanotubes (MWCNT) could alter the composition and bioactivity of circulating exosomes. Male C57BL/6 mice were exposed by …

Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil

Theses and Dissertations

Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …

Development And Validation Of Predictive Risk And Multiple Criteria Decision Analysis Models To Evaluate Cardiovascular Outcomes Among Cancer Patients, Purva N. Parab

Theses and Dissertations

Objective: The objectives of our study were to characterize the study population with cancer and cardiovascular diseases (CVD) both as compared to those without and to build a predictive model using machine learning (ML) algorithms that can predict the risk of CVD in cancer patients. In addition, our objective was also to evaluate characteristics associated with cardiotoxic adverse events of breast cancer therapies and develop a multiple criteria decision analysis (MCDA) model to conduct benefit-risk assessment of breast cancer therapy regimens. Methods: We used Medical Expenditure Panel Survey (MEPS) and FDA Adverse Events Reporting System (FAERS) 2005-2015 files along with …

Differential Identification Of Hyperacusis And Misophonia: Implications Of Discrete Decreased Sound Tolerance (Dst) Condition Subtypes, Rachel E. Wallace

Theses and Dissertations

Hyperacusis and misophonia are two conditions of decreased sound tolerance (DST) studied in the psychological literature due to their association with psychological symptoms and mechanisms. DSTs are differentiated from normal sound sensitivity due to the reported impairment and distress individuals experience. Researchers suggest that DSTs are differentiated by types of sounds and emotional reactions elicited, such that hyperacusis is a fear and pain response to ordinary environmental sounds perceived as uncomfortably loud, and misophonia is an anger and disgust response to human-made sounds, but these distinctions, and associated characteristics, have not been empirically demonstrated. Undergraduate students (N = 1572) …

Ca2+/Calmodulin-Dependent Protein Kinase Type Ii (Camkii) Regulates Histone Methylation To Promote Zebrafish Hematopoietic Stem Cell Specification, Sanyam Patel

Theses and Dissertations

Ca²⁺/calmodulin dependent protein kinase II (CaMKII) is an important signaling molecule involved in many developmental processes. This project aims to understand the role of CaMKII in specification of hematopoietic stem cells (HSCs) in zebrafish. HSCs undergo hematopoiesis to specify all cells that constitute blood. The process of hematopoiesis along with the specification of hematopoietic stem cells is conserved in vertebrates. CaMKII is expressed in tissues important for HSC specification, including the somites, notochord, and dorsal aorta. The dorsal aorta is the site of HSC specification in zebrafish. Injection of camk2g1 translational blocking antisense oligonucleotides (MO) or Cas9 guide …

Development Of A Screening Assay For Type Iii Secretion System Inhibitors And High Throughput Screening Campaign Of Inhibitors Of Prp Of Staphylococcus Aureus, Heather A. Pendergrass

Theses and Dissertations

Antibiotics inhibit the growth or survival of bacteria by targeting their essential functions.¹ Due to weaknesses in traditional antibiotics and the increasing prevalence of antibiotic resistance genes, virulence factors are being targeted for therapeutic treatment of bacterial infection.² We have developed an assay to quantify and observe type III secretion system (T3SS) activity. The type III secretion system (T3SS) is a virulence factor present in some Gram-negative pathogens including enteropathogenic and enterohemorrhagic E. coli (EPEC and EHEC, respectively),³ and others.^4–9 The T3SS between EPEC and EHEC are highly conserved and share over 90% sequence identity with …

Hypothetical Human Immune Genome Complex Gradient May Help To Explain The Congenital Zika Symdrome Catastrophe In Brazil: A New Theory, F. R. S. Oliveira, C. C. Bresani-Salvi, C. N. L. Morais, A. W. Bigham, U. Braga-Neto, Gladys E. Maestre, John L. Vandeberg, E. T. A. Marques, B. Acioli-Santos

School of Medicine Publications

There are few data considering human genetics as an important risk factor for birth abnormalities related to ZIKV infection during pregnancy, even though sub-Saharan African populations are apparently more resistant to CZS as compared to populations in the Americas. We hypothesized that single nucleotide variants (SNVs), especially in innate immune genes, could make some populations more susceptible to Zika congenital complications than others. Differences in the SNV frequencies among continental populations provide great potential for Machine Learning techniques. We explored a key immune genomic gradient between individuals from Africa, Asia and Latin America, working with complex signatures, using 297 SNVs. …

The Independence Effects Of Gravitational And Inertial Forces On Gait Transitions In Humans, Nathan Frakes

Cal Poly Humboldt theses and projects

The Dynamic Similarity hypothesis suggests gravitational and inertial forces plays a role in determining preferred transition speed (PTS) for walk to run transitions (WRT) and run to walk transitions (RWT), and that humans prefer to transition gait when the ratio of inertial force (IF) to gravitational force (GF) (i.e. Froude #) is ~0.5. Purpose: To investigate the effect of gravitational and inertial forces on PTS, Froude # (Fr) and kinematics for both WRT and RWT. Methods: Twelve healthy adults (9 M, 3 F) performed WRT and RWT trials on a treadmill across seven combinations of altered body weight (BW) and …

Habitat Use And Prey Selection By Mountain Lions In An Altered Sagebrush Steppe Environment, Jonathan Ewanyk

Cal Poly Humboldt theses and projects

Throughout the American West there is an increasing trend of encroachment of woody vegetation on previously open sagebrush steppe habitat. The Modoc Plateau in northeastern California has not been excluded from this encroachment trend and has seen an increase in western juniper (Juniperus occidentalis) densities, likely as a result of long-term fire suppression. Mountain lions (Puma concolor) have not previously been studied on the Modoc Plateau, and there is potential for an increase in cover due to juniper encroachment to benefit the hunting behavior of lions. To better understand if the presence of cover is being …

Efficacy Of Forest Restoration Treatments Across A 40-Year Chronosequence At Redwood National Park, Kevin Soland

Cal Poly Humboldt theses and projects

Following 20^th century logging, much of the natural coast redwood (Sequoia sempervirens) range consists of dense second-growth stands with slow tree growth and low biodiversity. There is a landscape-scale effort in much of coastal northern California to increase tree growth rates and ecosystem biodiversity via thinning treatments, thereby hopefully accelerating the development of old-growth forest characteristics. Redwood National Park (RNP) has been experimenting with thinning in these forest types since the 1970s. Given the interesting history of logging and restoration in RNP and the future plans for widespread thinning in this region, my thesis examined the effects …

Changing Seasons Of Resistance: Impacts Of Settler Colonialism And Climate Change In Indigenous Worlds, Elizabeth Jackson

Cal Poly Humboldt theses and projects

This paper looks at the relationship between neoliberal capitalism, genocide, the biopolitics of settler colonialism and the impacts of climate change on the cultures and traditional lifeways of Indigenous communities. It also explores Indigenous modes and methods of adaptation and resilience. Climate Change is almost certainly the most urgent social problem in the history of human life on planet Earth. Many Indigenous people are more vulnerable to the effects of climate change due to marginalization and their commitment to land-based practices. Using in depth interviews with Indigenous Peoples, primarily from the Pacific Northwest, and the analysis of existing literature, this …

A Tale Of Two Cervids: Habitat Selection And Spatial Ecology Of Roosevelt And Tule Elk In California, Adam S. Mohr

Cal Poly Humboldt theses and projects

California’s Roosevelt (Cervus canadensis rooseveltii) and tule elk (C. c. nannodes) populations have experienced a remarkable recovery after over-hunting and habitat loss nearly extirpated them from the state. Greater clarity of Roosevelt and tule elk habitat selection patterns would help managers continue to effectively support the recovery of these two iconic subspecies. As the manner in which elk populations balance their competing resource needs is unique to each population (Skovlin et al. 2002), I have examined Roosevelt and tule elk habitat selection patterns in separate analyses and present these results in independent chapters. In both cases, …

Changes In Prey Mortality: The Efects Of Multiple Predators And Temperature On California Mussels, Wesley Hull

Cal Poly Humboldt theses and projects

Organisms serve as prey to a variety of predators within natural systems, detecting threats through physical and chemical means. While predator feeding behavior is also affected by the presence of other predators, it is unclear whether differing modes of detection have similar effects on predator feeding behavior. In rocky intertidal zones in northern California, the California mussel (Mytilus californianus) is a competitively dominant foundation species consumed by a variety of predators. I quantified the individual and combined effects of ochre star (Pisaster ochraceus) and rock crab (Romaleon antennarium) predation on mussels by implementing mussel …