Digital Commons Network^™

In Silico Investigation Of Cardiac Arrhythmia Susceptibility In Long Qt Phenotype, Anthony Owusu-Mensah, Victoria Lam, Bright Tsevi, Michel Audette, Makarand Deo

Electrical & Computer Engineering Faculty Publications

Long QT Syndrome (LQTS) is associated with cardiac arrhythmia and sudden cardiac death. The Long QT Type 2 (LQT2) phenotype, which accounts for 35–40 % of all LQTS patients, is caused by mutations in HERG gene. The mechanisms of arrhythmia in presence of LQT2 conditions are not fully understood. We utilized anatomically and electrophysiologically realistic numerical simulations to elucidate the mechanisms of arrhythmia initiation in presence of blockade in rapid component of delayed rectifier potassium current, I_Kr. We utilized a 3D finite element model of rabbit ventricles integrated with His-purkinje network to simulate whole heart response to LQT2 …

Evaluation Of Spinal Anatomy Segmentation Methods Using Synthetic Computed Tomography Volumes, Austin Tapp, Michel Audette

Electrical & Computer Engineering Faculty Publications

Severe adolescent idiopathic scoliosis (AIS) is corrected by surgical procedures that necessitate ligament releases. To determine appropriate release allotments, soft tissues must be localized on a patient-specific basis, However, routine computer tomography (CT) imaging precludes traditional, voxel-based soft tissue localization. Fortunately, recent studies have proposed top-down segmentation methods, which elucidate soft tissues using pre-operative CT volumes. While the accuracy of vertebral segmentations obtained from these methods has not been determined, the accuracy of soft tissue segmentations has not. To ensure the soft tissue segmentation methods are clinically applicable, soft tissue validation must occur. This study presents an evaluation measure for …

Modeling And Simulation Of Electromagnetic Fields To Maintain Bone Density During Prolonged Low Gravity Exposure, Austin Tapp, Michael Francis, Michel A. Audette

Electrical & Computer Engineering Faculty Publications

Astronauts in a long term, low-gravity environments experience bone density loss at 10 times the rate of those diagnosed with osteoporosis. One treatment effective at maintaining bone density in osteoporotic individuals is electromagnetic field (EMF) therapy. Tools that induce EMFs are becoming increasingly prevalent, but to amplify osteogenesis and encourage superior bone density retention for astronauts, ideal EMF therapy parameters must be determined on patient-specific bases. Therefore, this study explores simulation environments that elucidate highly favorable EMF factors. Pulsed electromagnetic field and combined magnetic field generating devices are variably introduced near partient-specific, finite element (FE) models of the femur, spine, …

An Examination Of Post-Traumatic Stress Symptoms And Aggression Among Children With A History Of Adverse Childhood Experiences, Elizabeth M. Mcrae, Laura Stoppelbein, Sarah E. O'Kelley, Paula Fite, Shana B. Smith

Research, Publications & Creative Work

Childhood aggression is associated with many deleterious outcomes and is a common reason for psychiatric referral (Card and Little 2006; Gurnani, Ivanov, and Newcorn 2016). One factor associated with childhood aggression is Adverse Childhood Experiences (ACEs; Felitti et al. 1998). However, existing research remains equivocal on which characteristics of ACEs (e.g., cumulative impact, typology, etc.) are significantly elated to aggression, especially when considering differential effects of ACEs on proactive aggression (PA) and reactive aggression (RA; Dodge and Coie, 1987). Post-traumatic stress symptoms (PTSS) are a common negative sequalae of ACEs and are characterized by disruptions in several cognitive, emotional, and …

“It Didn’T Matter What The Bill Said...”: Influences On Abortion Policy Legislative Decision-Making In Georgia, Erica Barton, Subasri Narasimhan, Dabney P. Evans

Journal of the Georgia Public Health Association

Background: In March 2019 the Georgia legislature passed HB 481 described as a “heartbeat bill”, prohibiting abortion at around six weeks gestation. Given the prevalence of anti-abortion legislation and the public health implications of abortion restrictions, we sought to understand how Georgia legislators made decisions on this early abortion ban legislation.

Methods: We conducted in-depth interviews with nine legislators from the Georgia House of Representatives who participated in the 2019 legislative session. In-depth interviews were conducted in-person and over the phone. Interview recordings were transcribed verbatim and inductive codes identified. Codes focused primarily on views of: abortion in general; specific …

Health Reform Reconstruction, Lindsay F. Wiley, Elizabeth Y. Mccuskey, Matthew B. Lawrence, Erin C. Fuse Brown

Faculty Articles

This Article connects the failed, inequitable U.S. coronavirus pandemic response to conceptual and structural constraints that have held back U.S health reform for decades and calls for reconstruction. For more than a half-century, a cramped “iron triangle” ethos has constrained health reform conceptually. Reforms aimed to balance individual interests in cost, quality, and access to health care, while marginalizing equity, solidarity, and public health. In the iron triangle era, reforms unquestioningly accommodated four legally and logistically entrenched fixtures — individualism, fiscal fragmentation, privatization, and federalism — that distort and diffuse any reach toward social justice. The profound racial disparities and …

Plasmodium Tlap-2 Is A Microtubule-Associated Protein With Microtubule Stabilization Properties, Grifin Berge

Master's Theses

Microtubules facilitate major cellular and morphological changes in eukaryotic cells, including the protozoan parasite Plasmodium. Microtubule-associated proteins (MAPs), only very few of which have been characterized in the malaria parasite, regulate the highly dynamic microtubules. Thioredoxin-like associated protein 2 (TLAP2) is a MAP unique to the phylum apicomplexa, which in addition to Plasmodium includes the important human pathogen Toxoplasma. Here we report on the cloning and microtubule-binding activity of TLAP2 of the rodent malaria parasite Plasmodium berghei (PbTLAP2). PbTLAP2 is coded by a single exon gene and consists of 598 amino acids. The protein contains a putative C-terminal microtubule-binding domain. …

Why Is Race A Risk Factor For Infants Born With Birth Defects?: Deconstructing The Biological Basis Of Race In Maternal-Fetal Medicine Through The Lens Of Reproductive Justice, Amrita Bhagia

Master's Theses

Several studies have shown that marginalized populations, especially those of non-white race/ethnicity, have an increased risk of having infants born with severe birth defects. Existing hypotheses from the scientific literature on the topic of birth defects have primarily suggested that these trends may be the result of differential genetic susceptibilities within certain racial groups, a theory that reifies the (currently disproven) biological basis of race. Through this thesis, I argue that the myth of the biological basis of race continues to exist within maternal-fetal medicine today, where it is used to further the narrative that the bodies of women of …

Chga-Depleted Urothelial Amp And Immune Response During Urinary Tract Infection, Theadora Jane Ceccarelli

Master's Theses

Women are 8 times more likely than men to experience a urinary tract infection (UTI) with up to 60% of women reporting a UTI in their lifetime. This significant healthcare burden is caused by the infection of uropathogenic Escherichia coli in the urinary tract. At this time, treatment is limited to antibiotic therapy, which is challenged by antibiotic-resistance. These factors make UTIs an NIH priority and are motivation for our research.CgA is a protein of the granin family co-released with catecholamines from neuroendocrine cells throughout the body. Pro-hormone convertases post-translationally cleave CgA into peptides, like catestatin, which can have antimicrobial …

Population-Matched Transcriptome Prediction Increases Discovery And Replication Rate In Twas, Elyse Geoffroy

Master's Theses

Most genome-wide and transcriptome-wide association studies (GWAS, TWAS) focus on European populations; however, these results cannot always be accurately applied to non-European populations due to differences in genetic architecture. Using summary statistics from GWAS in the Population Architecture using Genomics and Epidemiology (PAGE) study, which comprises ~50,000 Hispanic/Latinos, African Americans, Asians, Native Hawaiians, and Native Americans, we perform transcriptome-wide association studies to determine gene-trait associations. Initially, we compared results using two transcriptome prediction models derived from the Multi-Ethnic Study of Atherosclerosis (MESA) populations: the African American (AFA) model and the Hispanic/Latino (HIS) model. We identified 141 unique genome-wide significant trait-associated …

The Identification Of Lxr-Dependent Pathways In The Dorsal Root Ganglia In Models Of Obesity, Nadia Elshareif

Master's Theses

Peripheral Neuropathy is characterized as injury to the peripheral nervous system. In terms of sensory neuropathy, metabolic syndrome is involved in chronic inflammation and ER stress pathways induced by lipid overload, leading to the structural and physiological damage of afferent sensory nerves. To protect the cell from lipid-induced ER stress, Liver X Receptors (LXRs) are sterol-activated nuclear transcription factors that are of particular interest due to its role in the regulation of lipid homeostasis, membrane phospholipids, and inflammation in metabolic tissues. Their role in the peripheral nervous system remains to be elucidated. LPCAT3, regulated by LXRs, has been shown to …

Function Of Mllt3 In Liver Metabolism, Grace Ann Hammack

Master's Theses

The chromatin regulator MLLT3 recognizes target genes through the YEATS domain that identifies post-translationally modified histones, with preference for crotonyl and acetyl marks, and recruits different multiprotein effector complexes through its C-terminal domain to target genes. To study the role of MLLT3 in gene regulation, the Zeleznik-Le and Hemenway labs developed Mllt3 whole-body knockout (Mllt3;Rosa26-CreERT2) mice. These mice have a hematopoietic stem cell phenotype and an unexpected obesity and hepatic steatosis phenotype. It was unknown whether these phenotypes were from liver intrinsic effects or influenced by other parts of the body. To study this fatty liver phenotype further, Mllt3;Alb-Cre were …

The Utilization And Optimization Of Omics Trait Prediction Models Within And Across Diverse Populations, Ashley Mulford

Master's Theses

Most cancer chemotherapeutic agents are ineffective in a subset of patients; thus, it is important to consider the role of genetic variation in drug response. Lymphoblastoid cell lines (LCLs) derived from 1000 Genomes Project populations of diverse ancestries are a useful model for determining how genetic factors impact variation in cytotoxicity. In our study, LCLs from three 1000 Genomes Project populations of diverse ancestries were previously treated with increasing concentrations of eight chemotherapeutic drugs and cell growth inhibition was measured at each dose with half-maximal inhibitory concentration (IC50) or area under the dose-response curve (AUC) as our phenotype for each …

Assessing The Role Of The Interaction Between Polyamines And Heparan Sulfate In Coxsackievirus B3 Viral Infection, Oreoluwa Omoba

Master's Theses

Non-polioenteroviruses are highly infectious viruses that typically cause mild asymptomatic cases but can cause severe disease such as aseptic meningitis and dilated cardiomyopathy. Coxsackievirus B3 (CVB3) is a member of this group and is prevalent in the United States and Eastern Asia. Viruses like CVB3 rely on the host cell for many molecules in order to replicate. One such set of molecules is the polyamines. Polyamines are small, positively charged molecules that play a role in a multitude of cellular processes including RNA/DNA stabilization, gene expression, translation, and regulating membrane fluidity. Previous studies have shown CVB3 relies on polyamines for …

Characterization Of Alcohol-Mediated Promotion Of Breast Cancer Stem Cells, Mckenna Below

Master's Theses

Breast cancer is the leading cause of cancer-related death in women globally, and one in eight women will be diagnosed with breast cancer at some point in her life. Alcohol consumption has been linked to increase breast cancer risk and increased risk of tumor recurrence. Understanding the molecular mechanisms of modifiable lifestyle factors such as alcohol consumption will help to lower these risks and design more effective therapeutic approaches. Estrogen Receptor positive (ER+) breast cancer comprises approximately 70% of all breast cancers, and these tumors are effectively targeted by endocrine therapy in the form of estrogen deprivation with aromatase inhibitors, …

Beta-Adrenergic Receptor Mediated Transcriptional Dysregulation In Hematopoeitc Stem And Progenitor Cells Leads To Bone Marrow Erythroid Suppresion In Multiple Myeloma Patients - Ex Vivo Investigations, Vimal Ravi Subramaniam

Master's Theses

The sympathetic nervous system (SNS) regulates our body’s involuntary response to stress or harm. Once activated, it releases hormones and neurotransmitters known as catecholamines throughout the body to mediate its recovery. The catecholamines bind to adrenergic receptors located on various cells in a process designated as adrenergic signaling to elicit this response. This process is not always to our benefit. Adverse symptoms such as anemia can result due to adrenergic signaling. Our laboratory previously showed that burn injury triggers adrenergic receptor stimulation resulting in anemia induced by diminished erythropoiesis. The development of anemia in these studies was found to be …

Advancing Our Understanding Of Mechanosensitive Microtubule Acetylation In Neurons, Margaret Earl Utgaard

Master's Theses

Stiffness is a signaling cue in the brain, and neuronal response to stiffness impacts development, injury and disease. Mechanotransduction is the process of cells interpreting and converting mechanical cues to biochemical signals. Tubulin acetylation increases microtubule stability and could be mechanosensitive. The impact of stiffness on tubulin acetylation and role of septins is the focus of this project.It was hypothesized that stiffer surfaces would increase tubulin acetylation. SH-SY5Y cells were plated on varying stiffness and the ratio of acetylated to alpha tubulin was measured using immunocytochemistry. This study found SH-SY5Y cells had the highest acetylation on hard surfaces. SH-SY5Y cells …

Characterization And Targeting Of Voltage-Gated Ion Channels In Meningioma Cell Lines, Erik White

Master's Theses

Meningiomas (MN) are primary brain tumors originating in the meningeal covering of the central nervous system. These tissues can evolve through familial inheritance (NF2, Cowden Syndrome, or Werner Syndrome) or sporadic mutations. The WHO categorizes MNs into three grades (I-III); Grade I contain benign tumors and Grade III the most aggressive. Increasing grade coincides with an increase in genetic diversity, making universal treatments difficult. MNs are typically treated with hydroxyurea (HU), but this chemotherapy agent has many adverse side effects, leading to research in less toxic options. This study uses ion channel antagonists for T- and L-type calcium channels using …

Anthropogenic Particle (Including Microplastic And Microfiber) Transport And Retention In Streams Under Varied Environmental Conditions, Elizabeth Marjorie Berg

Master's Theses

Microplastics (plastic particles <5 mm) and other anthropogenic particles (i.e., synthetic, semi-synthetic and anthropogenically modified cellulose particles < 5mm) are pollutants of concern in aquatic ecosystems worldwide. Anthropogenic particles enter food chains, adsorb harmful chemical pollutants, and are ubiquitous in aquatic ecosystems. Streams are key sites of anthropogenic particle input, retention, and transport, and empirical measurements of particle movement in lotic ecosystems are needed to inform global budgets of anthropogenic particles and microplastics. However, factors that influence anthropogenic particle retention in lotic ecosystems are poorly understood. We demonstrate how environmental characteristics affect plastic transport and retention in streams in experimental and observational studies. In our experimental study, we used particle spiraling metrics to directly measure microplastic retention in outdoor, experimental streams at Notre Dame's Linked Experimental Ecosystem Facility (ND-LEEF). We tested the impact of stream discharge (i.e., high, low), benthic biofilms (i.e., well-established biofilms, reduced biofilms post-scouring), and benthic substrate type (i.e., cobble, pea gravel, sand, mixed substrate) on retention of microplastic fibers using pulsed releases and synchronized water sample collection at 3 sites downstream. We also collected benthic surface samples for biomass and microplastic density. Samples were filtered directly (water samples) or after peroxide digestion (benthic samples), and experimental microplastic fibers were enumerated visually using a dissecting microscope. Microplastic deposition rates were significantly higher with (1) higher discharge, (2) well established benthic biofilm (as opposed to bare substrate), and (3) larger and more homogeneous substrates. The observational study examined anthropogenic particles (including microplastics and microfibers) in the Milwaukee River during storm events. Lotic ecosystems are highly variable (e.g., seasonal changes, storm events), and most research assessing anthropogenic particle pollution extrapolates stream particle loads based on measurements during only one point in time. This limits the accuracy of anthropogenic particle and microplastic dynamics models in rivers, where frequent changes in discharge drives retention and transport of fine particles. In this study, we used automated samplers to collect water from the Milwaukee River during four distinct storm events in the spring and summer of 2018. We quantified anthropogenic particle abundance using standard methods and used nearby USGS gauges to determine discharge. Anthropogenic particle concentrations varied significantly among the four sampling periods, highlighting the temporal variability of anthropogenic particle transport across dates. When data from the sampling periods were pooled, there was a decrease in anthropogenic particle concentration in the water column after storm events, indicating that floods may "flush" microplastics from the river. Unexpectedly, anthropogenic particle concentrations were not correlated with other water quality metrics, including concentrations of total suspended solids, fecal coliform, chloride, nitrate, and sulfate, indicating that these metrics cannot be used to estimate microplastic concentrations and likely have distinct driving factors. These results provide novel insights into the environmental factors controlling anthropogenic particle and microplastic fate and are critical to understanding the role of lotic retention and transport in global plastic budgets.

Pseudomonas Aeruginosa Prophages And Engineered Temperate Phages, Genevieve Johnson

Master's Theses

The rising rate of antibiotic-resistant bacteria is a global health concern, and the Pseudomonas aeruginosa is estimated to be a leader in serious threats. Bacteriophages, or viruses that infect bacteria, have gained renewed interest in Western Medicine as an alternative to antibiotics. Phage therapy of P. aeruginosa infections has primarily focused on obligately lytic phages. However, prophages, or phages in the lysogenic life cycle, are estimated to far outnumber obligately lytic phages. In theory, these prophages can be genetically modified to be obligately lytic and thus ideal candidates for phage therapy. To date there has not been a comprehensive analysis …

Rethinking Intimacy: Liberation Through Decolonial & Queer World-Making, Michelle Mae Mcguire

Master's Theses

Relationships play an important role in both the private and public spheres of our lives. If we understand our bodies to be the vessels through which we interact with all other objects, we come to understand the process of world-making as a summation of our relationships. Intimacy is the prevailing structure that helps assign meaning to these relationships. Intimacy binds together unfixed spatial and social relations that stretch across time and space. This essay examines the three intersecting sets of relations involved in intimacy as a means to deconstruct heteropatriarchal order and highlight the multiplicity of attachments and relationships that …

Lactobacillus Metabolite-Mediated Induction Of Bacteriophage, Taylor Miller-Ensminger

Master's Theses

Once considered sterile in the absence of an infection, the female urinary tract is home to a diverse community (microbiota) of bacterial species and bacteriophage (phage), viruses that infect bacteria A dominant member of the female urinary microbiota is the bacterial genus Lactobacillus. Several Lactobacillus species are even associated with urinary health. Phage infectious of bacteria in the urinary tract tend to replicate through one of two life cycles: the lytic (active) life cycle or the lysogenic (dormant) life cycle. Temperate phage can switch from the lysogenic life cycle to the lytic life cycle in the presence of an environmental …

Menstrual Pain Trajectories And Their Psychological And Behavioral Predictors, Hannah Marie Alves Hagy

Master's Theses

Despite the high prevalence of menstrual pain (i.e., dysmenorrhea) and the negative impact on quality of life, there is a dearth of research on how menstrual pain changes over time. There is also a critical need to understand psychological and behavioral predictors of these menstrual pain trajectories because dysmenorrhea is a known risk factor for the development of chronic pelvic pain (CPP) and chronic non-pelvic pain (CNPP). Given that current treatments for CPP and CNPP have had limited success, developing preventative strategies for dysmenorrhea is of high importance. Relying on longitudinal survey data collected as part of a larger investigation, …

Kinship Involvement And Strength Development In The Child Welfare System, Nicole Amper Hodgkinson

Master's Theses

For youth involved in the Child Welfare System (CWS), maltreatment and ecological losses pose enormous challenges to healthy development. Kin and fictive kin involvement, a current CWS priority, may have the potential to aid in strength development; however, little is known about its role in this process. The current study explored the following aims: (1) identify the role of kin and fictive kin in strength development (2) investigate the impact of maltreatment on initial strength levels and their development over time and (3) examine the extent to which kinship involvement interacts with prior maltreatment to buffer the impact of maltreatment …

The Evolutionary And Morphological Diversification Of The Subtribe Papionina, Sophie B. Labelle

Master's Theses

Analysis of variation is critical in understanding evolutionary processes. The subtribe Papionina, defined commonly as baboons and their closest relatives, is a highly morphologically diverse group of primates that is useful for the examination of the relationship between variation and evolution. The subtribe is also a valuable behavioral, ecological, and morphological analogy for hominins. This study uses landmark-based cranial geometric morphometric data and multivariate analysis to test whether the pattern of morphological diversification present in Papionina is consistent with genetic drift and/or selection. The study sample consists of six extant genera of Papionin, represented by ~500 individuals collected by Michelle …

A Role For Notch Signaling In Drosophila Spermatogenesis, Adrianna Soriano

Master's Theses

The Notch signaling pathway has diverse functions in male and female gonad development. In Drosophila male embryos, Notch specifies hub cell fate in somatic gonadal precursor cells (SGPs), which are important for maintaining germline stem cells and somatic cyst stem cells throughout the lifetime of adult flies. However, a role for Notch signaling in adult males has only started to emerge recently. Nonetheless, we still don’t understand how the Notch pathway functions to regulate spermatogenesis. Notch has been established to be important for the fertility of multiple systems, including mammals, and must be properly regulated for proper spermatogenesis, but the …

Anthropogenic Litter In Illinois Streams: Monitoring, Distribution, And Relationship To Biological Indicators Of Stream Health, Lauren Wisbrock

Master's Theses

Anthropogenic litter (i.e., trash; AL) is increasing in aquatic ecosystems worldwide. AL shows a patchy, uneven distribution in lotic ecosystems due to heterogeneity in its sources, how it moves, and mechanisms of retention. In addition, the diversity of material types, size, and mobility makes developing techniques to measure AL assemblage in rivers a challenge. In rivers, watershed land-use and riparian features likely impact AL abundance and composition, but this impact is not fully understood. Measuring AL can be time consuming and labor intensive, so rapid assessments are needed for ecosystem managers to quantify the level of AL impairment in a …

Deep Neural Network Analysis Of Pathology Images With Integrated Molecular Data For Enhanced Glioma Classification And Grading, Linmin Pei, Karra A. Jones, Zeina A. Shboul, James Y. Chen, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel …

Plasma-Treated Solutions (Pts) In Cancer Therapy, Hiromasa Tanaka, Sander Bekeschus, Dayun Yan, Masaru Hori, Michael Keidar, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to …

Joint Modeling Of Rnaseq And Radiomics Data For Glioma Molecular Characterization And Prediction, Zeina A. Shboul, Norou Diawara, Arastoo Vossough, James Y. Chen, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

RNA sequencing (RNAseq) is a recent technology that profiles gene expression by measuring the relative frequency of the RNAseq reads. RNAseq read counts data is increasingly used in oncologic care and while radiology features (radiomics) have also been gaining utility in radiology practice such as disease diagnosis, monitoring, and treatment planning. However, contemporary literature lacks appropriate RNA-radiomics (henceforth, radiogenomics) joint modeling where RNAseq distribution is adaptive and also preserves the nature of RNAseq read counts data for glioma grading and prediction. The Negative Binomial (NB) distribution may be useful to model RNAseq read counts data that addresses potential shortcomings. …