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River Bank Inducement Influence On A Shallow Groundwater Microbial Community And Its Effects On Aquifer Reactivity, Natalie June Gayner Dec 2018

River Bank Inducement Influence On A Shallow Groundwater Microbial Community And Its Effects On Aquifer Reactivity, Natalie June Gayner

Theses and Dissertations

Placing groundwater wells next to riverbanks to draw in surface water, known as riverbank inducement (RBI), is common and proposed as a promising and sustainable practice for municipal and public water production across the globe. However, these systems require further investigation to determine risks associated with river infiltration especially with rivers containing wastewater treatment plant (WWTP) effluent. Since microbes drive biogeochemical transformations in groundwater and largely affect water quality, it is important to understand how the microbial communities in drinking water wells are affected by river infiltration. This study investigated if, and to what extent, the microbial community in a …


Inducible Dna Cross-Linking Agents: Design, Synthesis, Mechanism, And Anticancer Activity, Heli Fan Dec 2018

Inducible Dna Cross-Linking Agents: Design, Synthesis, Mechanism, And Anticancer Activity, Heli Fan

Theses and Dissertations

This thesis focuses on investigating the reactivity of DNA towards a wide variety of aromatic compounds as novel DNA cross-linking agents and exploring their biomedical applications.

In the first part, we synthesized three series of bifunctional aromatic compounds with various core structures, aromatic substituents, and benzylic leaving groups and investigated their reactivity towards DNA. Most of these compounds efficiently form DNA interstrand cross-links (ICLs) via carbocations generated upon irradiation at 350 nm. The efficiency of DNA ICL formation and the pathway of carbocation formation strongly depend on core structures, aromatic substituents and leaving groups. Mono benzene analogues bearing an electron …


Renalase As An Intracellular Metabolite Repair Enzyme, Matthew Robert Hoag Dec 2018

Renalase As An Intracellular Metabolite Repair Enzyme, Matthew Robert Hoag

Theses and Dissertations

The human enzyme renalase was discovered in 2005 by nephrologist Gary Desir, who claimed the enzyme is secreted by the kidney into the blood where it was said to catabolize catecholamines in order to modulate blood pressure and heart rate. It has since been shown that the enzyme is expressed in all tissues and does not react with catecholamines. The research detailed in this dissertation led to the discovery that renalase oxidizes two highly toxic isomers of NAD(P)H to form innocuous NAD(P)+. We surmised that such an important cellular function would be pervasive in nature, and our lab was the …


Auditory And Contextual Contributions To Memory Lability And Synaptic Destabilization In The Amygdala, Nicole Christine Ferrara Aug 2018

Auditory And Contextual Contributions To Memory Lability And Synaptic Destabilization In The Amygdala, Nicole Christine Ferrara

Theses and Dissertations

Pavlovian fear conditioning provides a way to investigate memory formation and retrieval. During fear conditioning, a conditional stimulus (CS) is paired with an aversive outcome and the CS acquires aversive value over several pairings. The CS may then be presented during a retrieval session where fear responding is measured as an indicator of memory strength. Retrieval sessions may allow for the incorporation of new information into the original memory trace by destabilizing amygdala synapses. However, the specific circuits and neural inputs that contribute to memory lability and synaptic destabilization during a retrieval session are poorly understood. Previous work has shown …


Conservation Genomics Of Cascades Frogs (Rana Cascadae) At The Southern Edge Of Their Range, Bennett Hardy Aug 2018

Conservation Genomics Of Cascades Frogs (Rana Cascadae) At The Southern Edge Of Their Range, Bennett Hardy

Theses and Dissertations

Cascades frogs (Rana cascadae) in the southern Cascades Range of California have been declining over the last 30 years, primarily due to the fungal pathogen, Batrachochytrium dendrobatidis (Bd). In the Lassen Region of the southern Cascades, at least six of the eleven remaining localities face extirpation within 50 years. These small and isolated populations are prone to negative genetic effects including reduced diversity and increased inbreeding which could potentially exacerbate declines. I used a large dataset of SNP loci generated from high-throughput sequencing to characterize patterns of genetic structure and diversity in twelve R. cascadae populations in California to prioritize …


Cultivating Ecosystems: Microbial Communities In Recirculating Aquaculture Systems, Ryan Bartelme Aug 2018

Cultivating Ecosystems: Microbial Communities In Recirculating Aquaculture Systems, Ryan Bartelme

Theses and Dissertations

Intensive cultivation of fish is necessary to meet future global market demands. Recirculating aquaculture systems (RAS) enable dense growth of fish, while occupying less space than traditional aquaculture farms. However, RAS often experience complications and high fish mortalities due to disease and improper waste management. In properly functioning systems, the microorganisms associated with fish (gut, scales) as well as those found in the system environment (water, component surfaces) remove waste and maintain fish health by discouraging growth of opportunistic pathogens. Previous RAS microbiome studies are small in scope, utilize coarse methods, and contain limited long-term spatial or temporal data. With …


Investigating The Hip And Trunk Kinematic And Strength Differences Between Those With A History Of Exertional Medial Tibial Pain And Healthy Controls, Allison Hocking Aug 2018

Investigating The Hip And Trunk Kinematic And Strength Differences Between Those With A History Of Exertional Medial Tibial Pain And Healthy Controls, Allison Hocking

Theses and Dissertations

Introduction: Exertional medial tibial pain (EMTP) has been shown to be one of the leading injuries in females who have weakened hip strength. Increased trunk and hip kinematic excursion and decreased hip external rotation and hip abductor strength are related to injury in the athletic population but there is a lack of research in the role of hip strength in the development of exertional medial tibial pain in competitive female runners. Purpose: Therefore, the purpose of this study is to investigate differences in hip strength, hip kinematics, and trunk kinematics between those with a previous history of exertional medial tibial …


Hpa Axis Genetic Variation And Life Stress Influences On Functional Connectivity In Resting State Networks, Tara Ann Miskovich Aug 2018

Hpa Axis Genetic Variation And Life Stress Influences On Functional Connectivity In Resting State Networks, Tara Ann Miskovich

Theses and Dissertations

Stressful or traumatic experiences are a key risk factor for developing psychopathology, primarily through the impact that chronic stress has on hypothalamic-pituitary-adrenal (HPA) axis functioning. The HPA axis regulates the stress response but can become dysregulated with chronic activation and impact brain functioning. In addition to environmental stressors, genetic variation in genes in the HPA axis appear to influence HPA axis functioning and is also related to disruption in brain functioning, particularly in the context of high life stress. The current study focused on examining potential mechanisms through which trauma and stress interacts with HPA axis genes to impact key …


Exploring Positive Body Image And Motives For Exercise As Predictors Of Intuitive Exercise And Exercise Behavior Among Women, Natalie Michelle Ramsey Aug 2018

Exploring Positive Body Image And Motives For Exercise As Predictors Of Intuitive Exercise And Exercise Behavior Among Women, Natalie Michelle Ramsey

Theses and Dissertations

Purpose: To explore three facets of positive body image and motives for exercise as predictors of women’s intuitive exercise and exercise behavior.

Scientific significance: Positive body image has been associated with health-promoting behaviors such as utilizing sun protection techniques and intuitive eating. Despite these findings and the known benefits of exercise, there are no known published studies exploring if positive body image and exercise motivation predict intuitive exercise and exercise behavior in women. Understanding these relationships could facilitate the design of interventions targeting improvements in both psychological well-being and exercise behavior.

Methodology: This cross-sectional study included 391 women (18-91 years; …


Baked And Buzzed: Investigating The Influence Of Co-Use Of Cannabis And Alcohol On White Matter Integrity In Emerging Adults, Natasha E. Wright Aug 2018

Baked And Buzzed: Investigating The Influence Of Co-Use Of Cannabis And Alcohol On White Matter Integrity In Emerging Adults, Natasha E. Wright

Theses and Dissertations

Objective: Growing evidence suggests alcohol and cannabis use independently alter neural structure and functioning, particularly during sensitive developmental time periods such as adolescence and emerging adulthood. However, there has been minimal investigation into the effects co-occurring use of these two substances, despite preliminary evidence of unique acute and psychopharmacological changes due to using alcohol and cannabis together.

Method: Data drawn from the IDEAA Consortium was utilized to assess white matter integrity as measured by FreeSurfer’s TRACULA in emerging adults (n=192; 16-27 years old). Timeline Follow-Back was used to calculate past month cannabis use, alcohol use, co-use days, binge alcohol episode, …


Replacing Sedentary Behavior With A Light Intensity Physical Activity In The Homes Of Older Adults, Nicholas Louis Lerma Aug 2018

Replacing Sedentary Behavior With A Light Intensity Physical Activity In The Homes Of Older Adults, Nicholas Louis Lerma

Theses and Dissertations

Aging is positively correlated with time spent in sedentary behavior (SB), which has been found to be linked to premature mortality, cardiovascular disease risk, and functional limitations. Moderate-to-vigorous-intensity physical activity (MVPA) is a potent stimulus for preventing and improving functional limitations in older adults, but less than 17% of the older adult population meets the recommended PA guidelines. While increased time spent in SB is detrimental to health in all, the impact among those that are physically inactive appear to be most pronounced. Recent evidence suggests increasing light-intensity physical activity (LPA) in these populations may provide health benefits and could …


Abnormal Reward Processing And Visual Selective Attention: An Event-Related Potential Investigation With Remitted Depressed Adults, Kevin Haworth Aug 2018

Abnormal Reward Processing And Visual Selective Attention: An Event-Related Potential Investigation With Remitted Depressed Adults, Kevin Haworth

Theses and Dissertations

Feedback, rewarding and non-rewarding, received from the environment can facilitate learning, influence motivation and shape behavior (Skinner, 1963; Thorndike, 1898). Recent research has indicated that reward can also enhance cognitive processes such as visual selective attention (Anderson, Laurent, & Yantis, 2011a; Anderson, Laurent, & Yantis, 2011b; Della Libera, Perlato, & Chelazzi, 2011; Krebs, Boehler, Egner, & Woldorff, 2011). Depression is one of the most common, debilitating, and costly forms of mental illness (Katon, 1996; Kessler et al., 2005; Mathers, Fat, & Boerma, 2008) and has been characterized by reduced responsiveness to reward (Henriques, Glowacki, & Davidson, 1994; Henriques & Davidson, …


The Effects Of G-Protein-Coupled Estrogen Receptor (Gper) On Cell Signaling, Dendritic Spines, And Memory Consolidation In The Female Mouse Hippocampus, Jae Kyoon Kim Aug 2018

The Effects Of G-Protein-Coupled Estrogen Receptor (Gper) On Cell Signaling, Dendritic Spines, And Memory Consolidation In The Female Mouse Hippocampus, Jae Kyoon Kim

Theses and Dissertations

One of the most seminal findings in the literature on hormones and cognition is that the potent estrogen 17β-estradiol (E2) significantly increases the density of dendritic spines on pyramidal neurons in the CA1 region of the dorsal hippocampus (DH). However, the extent to which this E2-induced increase in hippocampal spinogenesis is necessary for memory formation remains unclear. The memory-enhancing effects of E2 in the DH can be mediated by intracellular estrogen receptors (ERs) or by the membrane-bound ER called G-protein coupled estrogen receptor (GPER). We previously reported that infusion of a GPER agonist, G-1, into the DH of ovariectomized female …


Neural Correlates Of Memory Decisions Made In The Face Of Conflict, Elaine Mahoney Aug 2018

Neural Correlates Of Memory Decisions Made In The Face Of Conflict, Elaine Mahoney

Theses and Dissertations

We’ve all experienced moments where, for some reason or another, we don’t want to reveal to others what we truly know. The current experiment investigated questions about the behavioral and neural correlates of these types of memory decisions made in the face of a conflicting goal. Participants in this experiment studied several scene-face pairs and were tested with three-face displays preceded by studied scene cues. They were instructed to indicate whether the three-face display contained the matching associate or not. Critically, half of the participants were instructed to simulate feigned memory impairment (i.e. simulators), while the remainder were instructed to …


Differential Migration Of Cd4+ And Cd8+ T Cells During An Immune Response, Jacob Parrott Aug 2018

Differential Migration Of Cd4+ And Cd8+ T Cells During An Immune Response, Jacob Parrott

Theses and Dissertations

ABSTRACT

DIFFERENTIAL MIGRATION OF CD4+ AND CD8+ T CELLS DURING AN IMMUNE RESPONSE

by

Jacob Parrott

The University of Wisconsin-Milwaukee, 2018

Under the Supervision of Professor Douglas Steeber

Lymphocyte migration is critical for recognizing pathogenic challenges in a timely manner and generating effective, rapid immune responses. Lymphocyte numbers in secondary lymphoid tissues such as lymph nodes are rapidly and dramatically increased during an immune response. Lymphocytes use specific adhesion molecules and intracellular signaling cascades to migrate and enter secondary lymphoid tissues under resting conditions. It is not clear if the same migration and/or entry pathways are utilized when secondary lymphoid …


Novel Algorithms For Merging Computational Fluid Dynamics And 4d Flow Mri, Ali Bakhshinejad Aug 2018

Novel Algorithms For Merging Computational Fluid Dynamics And 4d Flow Mri, Ali Bakhshinejad

Theses and Dissertations

Time-resolved three-dimensional spatial encoding combined with three-directional velocity-encoded phase contrast magnetic resonance imaging (termed as 4D flow MRI), can provide valuable information for diagnosis, treatment, and monitoring of vascular diseases. The accuracy of this technique, however, is limited by errors in flow estimation due to acquisition noise as well as systematic errors. Furthermore, available spatial resolution is limited to 1.5mm - 3mm and temporal resolution is limited to 30-40ms. This is often grossly inadequate to resolve flow details in small arteries, such as those in cerebral circulation. Recently, there have been efforts to address the limitations of the spatial and …


Does Restricting Anterior Movement Of The Knees During A Barbell Back Squat Alter Lower Extremity Biomechanics?, Lucy Hayward Koshewa Aug 2018

Does Restricting Anterior Movement Of The Knees During A Barbell Back Squat Alter Lower Extremity Biomechanics?, Lucy Hayward Koshewa

Theses and Dissertations

INTRODUCTION: The strength implications of the barbell back squat make it ideal for use in training programs, rehabilitation, and competition. Even though the back squat is an integral part of these programs, there are also concerns about injury risk due to improper biomechanics. Restricted squats (knees kept behind the toes) are noted to reduce joint loading at the knees but may not take into account added potential risks for the entire lower extremity. Unrestricted squats are more representative of natural movement patterns but may increase joint loading especially at the knees. Research has explored the biomechanics of back squats in …


Studies In Molecular Recognition: Non-Proteogenic Amino Acids For Antibiotic Studies And Chemosensors For Recognition And Reporting Of Metal-Ions, Sarah Anne Oehm Aug 2018

Studies In Molecular Recognition: Non-Proteogenic Amino Acids For Antibiotic Studies And Chemosensors For Recognition And Reporting Of Metal-Ions, Sarah Anne Oehm

Theses and Dissertations

The field of molecular recognition focuses on the selective and reversible binding of small guest molecules to larger host molecules. This dissertation describes synthesis of small molecules as binding guests for enzymatic substrates as well as molecules as host chemosensors to detect and identify metal ions. Two approaches to new antibiotic drugs have been explored, and an array of sensors for the quantitation of aqueous metals is being commercialized.

As strains of deadly bacteria emerge with evolved resistance to known antibiotics, new drugs are needed with novel mechanisms of action. Natural product antibiotics containing enduracididine, a non-canonical amino acid derived …


A Discrete-Event Simulation Approach For Modeling Human Body Glucose Metabolism, Buket Aydas Aug 2018

A Discrete-Event Simulation Approach For Modeling Human Body Glucose Metabolism, Buket Aydas

Theses and Dissertations

This dissertation describes CarbMetSim (Carbohydrate Metabolism Simulator), a discrete-event simulator that tracks the blood glucose level of a person in response to a timed sequence of diet and exercise activities. CarbMetSim implements broader aspects of carbohydrate metabolism in human beings with the objective of capturing the average impact of various diet/exercise activities on the blood glucose level. Key organs (stomach, intestine, portal vein, liver, kidney, muscles, adipose tissue, brain and heart) are implemented to the extent necessary to capture their impact on the production and consumption of glucose. Key metabolic pathways (glucose oxidation, glycolysis and gluconeogenesis) are accounted for by …


Effects Of Life History And Brain Size On Cognition And Behavior: Studies On Prey-Searching In The Spider Pholcus Phalangioides, Joseph Kilmer Aug 2018

Effects Of Life History And Brain Size On Cognition And Behavior: Studies On Prey-Searching In The Spider Pholcus Phalangioides, Joseph Kilmer

Theses and Dissertations

There is tremendous diversity in body size across animals, including many examples of derived miniaturization. A reduction in body size is accompanied by a reduction in brain size, which is predicted to lead to limitations in cognition, but we have yet to find empirical evidence indicating what these limitations might be. I used a behavioral assay common in web spiders to explore this topic. I observed spiders as they searched for prey that they recently captured and lost. This assay has the advantage of being easily quantifiable while reflecting a spider’s evaluation and memory of lost prey. I conducted a …


Structural And Functional Brain Connectivity In Middle-Aged Carriers Of Risk Alleles For Alzheimer's Disease, Laura Korthauer Aug 2018

Structural And Functional Brain Connectivity In Middle-Aged Carriers Of Risk Alleles For Alzheimer's Disease, Laura Korthauer

Theses and Dissertations

Single nucleotide polymorphisms (SNPs) in APOE, COMT, BDNF, and KIBRA have been associated with age-related memory performance and executive functioning as well as risk for Alzheimer’s disease (AD). The purpose of the present investigation was to characterize differences in brain functional and structural integrity associated with these SNPs as potential endophenotypes of age-related cognitive decline. I focused my investigation on healthy, cognitively normal middle-aged adults, as disentangling the early effects of healthy versus pathological aging in this group may aid early detection and prevention of AD. The aims of the study were 1) to characterize SNP-related differences in functional connectivity …


Sources Of Variation In Social Plasticity In Female Mate Preferences And Male Traits, Daniel Neelon May 2018

Sources Of Variation In Social Plasticity In Female Mate Preferences And Male Traits, Daniel Neelon

Theses and Dissertations

Female preferences are an important cause of selection on male traits, and exploring the sources of variation in these preferences has been the focus of intense behavioral research. This is due to the fact that understanding this variation is integral to understating the maintenance of variation and complexity in male traits, as well as the evolution and divergence of populations. This project aims to explore the sources of variation in these mating preferences, as well as examine whether similar sources affect components of male traits. This was accomplished using the well-studied mating system of the Green Treefrog, Hyla cinerea that …


Invertebrate Paleoecology Of High Paleo-Latitude Carboniferous Strata Of The Tepuel-Genoa Basin, Argentina, Kate M. Gigstad May 2018

Invertebrate Paleoecology Of High Paleo-Latitude Carboniferous Strata Of The Tepuel-Genoa Basin, Argentina, Kate M. Gigstad

Theses and Dissertations

The Late Paleozoic Ice Age (LPIA), which began in the latest Devonian and ended in the Late Permian, was a time of active environmental changes. During this time, glaciers waxed and waned over the ancient continent of Gondwana that was situated over the southern pole. This time of transition from icehouse to greenhouse in the Permian is our closest analogue to our current environmental conditions and increased knowledge of our planetary past will greatly influence our future. Much of the previous research on marine invertebrate paleoecology during the LPIA occurs in far-field or low paleolatitude localities, but less is known …


Fat And Caloric Content Of Breast Milk Of Mothers Of Premature Infants: Comparison Of High Vs. Low Volume Producers And The Impact Of Volume In Single Pumping Sessions And The Interval Between Pumping Sessions, Barbara Haase May 2018

Fat And Caloric Content Of Breast Milk Of Mothers Of Premature Infants: Comparison Of High Vs. Low Volume Producers And The Impact Of Volume In Single Pumping Sessions And The Interval Between Pumping Sessions, Barbara Haase

Theses and Dissertations

Premature birth affects 8-18% of all infants worldwide and is the leading cause of death in children less than the age of 5 years. The premature birth rate has been on the rise between 2014-2016 in the United States and 1 in 10 infants are born prematurely. Infants who are born prematurely are at considerable risk of serious infections, visual impairments and neurodevelopmental problems. Human milk, specifically mother’s own milk (MoM), is associated with decreased rates of necrotizing enterocolitis, pneumonia, chronic lung disease and late onset sepsis. MoM is also associated with improved neurodevelopmental outcomes in premature infants.

Although MoM …


Assessment And Mapping Of The Milwaukee Estuary Habitat, Brennan Dow May 2018

Assessment And Mapping Of The Milwaukee Estuary Habitat, Brennan Dow

Theses and Dissertations

Rivermouth regions such as the Milwaukee Harbor, are the habitat interface between watersheds and the Great Lakes proper, and can host a large diversity of fishes. To facilitate an ecosystem approach management strategy, I developed a layered map that includes bathymetry, side scan sonar images, shoreline substrate classifications, and initial data of aquatic vegetation and centrarchid spawning locations. The 60 km perimeter of the study area consisted of 59% hardened shoreline. Ground truthing of substrate classifications via Ponar grabs or video had about 95% accuracy for fine and rocky boulder substrates. Rocky fine was the most inaccurate classification (35%), but …


How Does Anxiety Affect Cognitive Control? Proactive And Reactive Control Under State Anxiety, Youcai Yang May 2018

How Does Anxiety Affect Cognitive Control? Proactive And Reactive Control Under State Anxiety, Youcai Yang

Theses and Dissertations

Cognitive control is a construct that prioritizes how we process stimuli and information and execute behaviors to flexibly and efficiently adapt to internal goals and external environmental changes. A recent theory, the Dual Mechanism of Control (DMC), distinguishes this phenomenon by two distinct cognitive control operations: proactive control and reactive control (Braver, 2012). Anxiety increases the allocation of attentional and working memory resources to threat-related stimuli, which impairs cognitive performance (Sarason, 1988), but additional work is needed to assess how anxiety impacts these two distinct forms of cognitive control. In this study, I examined how state anxiety affected proactive control, …


Georac: An Rna-Seq Atlas Constructor For The Gene Expression Omnibus, Aurash A. Mohaimani May 2018

Georac: An Rna-Seq Atlas Constructor For The Gene Expression Omnibus, Aurash A. Mohaimani

Theses and Dissertations

The meteoric rise of next-generation sequencing technologies over the past 15 years has resulted in a voluminous amount of data generated by modern biological and clinical studies. RNA sequencing, colloquially referred to as RNA-Seq, is a next-generation approach capable of surveying and quantifying whole organism transcriptomes. RNA-Seq methods are valued over microarray assays for their ability to avoid cross-hybridization signal noise, to quantify gene or transcript expression without assay-specific upper limits, to natively provide single-nucleotide genomic resolution, and to allow for de novo transcriptome assemblies. Many thousands of RNA-Seq studies have been published over the past seven years, and a …


Time-Resolved Structural Enzymology At X-Ray Free Electron Lasers, Tyler Norwood May 2018

Time-Resolved Structural Enzymology At X-Ray Free Electron Lasers, Tyler Norwood

Theses and Dissertations

Within the last decade, X-ray Free Electron Lasers (XFELs) have emerged across the world. These XFELs produce X-ray pulses with a duration on the order of femtoseconds, each of which contains 1012 photons. Before the XFEL, the brightest X-ray sources were 3rd generation synchrotrons. While these facilities are still very important for many experiments, XFELs allow for time-resolved experiments with femtosecond time resolution and mixing experiments that are not possible at the synchrotron. Enzymatic processes have promising prospects for medicine which use proteins as drug targets and enhance our understanding of these important biomolecules.

A number of procedures are involved …


Plumage Ornaments Signal Male Physiological Quality In Common Yellowthroats, Amberleigh E'Vaughn Henschen May 2018

Plumage Ornaments Signal Male Physiological Quality In Common Yellowthroats, Amberleigh E'Vaughn Henschen

Theses and Dissertations

Elaborate ornaments are thought to honestly signal quality to potential mates. These ornaments may signal a variety of physiological processes that affect health and fitness. I examined the relationship between ornaments and physiological quality in a bird, the common yellowthroat (Geothlypis trichas). Male common yellowthroats have two plumage ornaments, a black (eumelanin-based) mask and a yellow (carotenoid-based) bib. Males with larger masks are preferred by females for both extra-pair and social mates. I found that both the mask and the bib of male common yellowthroats honestly signal their ability to resist oxidative stress. Males with larger masks and more colorful …


New Direct Acting Anti-Virals Inhibiting Hepatitis C Virus Helicase And Insights Into How Atp Fuels Helicase Action, Mark Yerukhimovich May 2018

New Direct Acting Anti-Virals Inhibiting Hepatitis C Virus Helicase And Insights Into How Atp Fuels Helicase Action, Mark Yerukhimovich

Theses and Dissertations

According to the World Health Organization, Hepatitis C Virus (HCV) has infected 130-150 million people worldwide. Approximately 700,000 of those die each year from chronic HCV related causes such as cirrhosis or cancer. Currently, there are numerous HCV drugs on the market; they target the protease, polymerase and NS5A proteins encoded by of HCV. These drugs are expensive and HCV can become resistant, thus there is constant need for new DAAs. The first part of this thesis examines the search for additional drugs that function by inhibiting the NS3 helicase, which have been challenging to develop.

Part of the reason …