Disease Modeling Commons^™

Modeling An Infection Outbreak With Quarantine: The Sibkr Model, Mikenna Dew, Amanda Langosch, Theadora Baker-Wallerstein

Rose-Hulman Undergraduate Mathematics Journal

Influenza is a respiratory infection that places a substantial burden in the world population each year. In this project, we study and interpret a data set from a flu outbreak in a British boarding school in 1978 with mathematical modeling. First, we propose a generalization of the SIR model based on the quarantine measure in place and establish the long-time behavior of the model. By analyzing the model mathematically, we determine the analytic formulas of the basic reproduction number, the long-time limit of solutions, and the maximum number of infection population. Moreover, we estimate the parameters of the model based …

A Tale Of Two Viruses: Why Smallpox Was Eradicated And Polio Persists, Katherine G. Mcgough, Erin N. Bodine

Spora: A Journal of Biomathematics

The smallpox and poliomyelitis (polio) viruses were, at a time, one of the largest threats to global public health killing millions until global eradication campaigns were put into effect. Vaccination led to the eradication of smallpox and the elimination of polio for most of the world. However, polio continues to persist at endemic levels in Pakistan and Afghanistan. We developed ODE models of smallpox and polio to explore differences in transmission dynamics and determine if the underlying biology has made poliomyelitis more difficult to eradicate. Our model analysis shows there are multiple factors which should allow polio to have a …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Regulation Of Mirnas In Obesity And Diabetes, Eva Maher, Ava O'Meara, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Introduction: The prevalence of obesity and obesity-related secondary disorders has increased dramatically in recent years. Dysregulated microRNA (miRNA) expression has been linked to the development of obesity and its associated disorders. Adipose derived stem cells (ADSCs) are promising cell models of obesity, obesity-related inflammation and diabetes. Furthermore, miRNA expression profiles have emerged as promising targets for the novel treatment of diseases such as obesity. In order to enhance miRNA-based therapies, the miRNA expression profile of obesity and its related disorders must be monitored to further understand the underlying mechanisms of obesity and to identify novel targets.

Aim: The aim of …

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …

Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson

Electronic Theses and Dissertations

Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …

An Ode Model For Investigating The Sleep-Pain Relationship In Sickle Cell Disease, Quindel Jones, Angela Reynolds, Rebecca Segal, Reginald Mcgee

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Predicting Dengue Incidence In Central Argentina Using Google Trends Data, Sahil Chindal

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Physics-Informed Neural Networks For Agent-Based Epidemiological Model Calibration, Alvan C. Arulandu, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Msis-Robertson: A Stochastic Multi-Host Model For West Nile Virus, Suzanne Robertson, Emily Horton

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Potential Effects Of Masking, Quarantine, Treatment, And Vaccines On Swine Flu, Helen Pennington, Erin Bodine

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

An Investigation Of Mitigation Measures On The Spread Of Covid-19 In A College Classroom Using Agent-Based Modeling, Saharsh Talwar, Anne E. Yust

Spora: A Journal of Biomathematics

In this manuscript, we describe the process of using agent-based modeling in NetLogo to create a simulation of COVID-19 spread in a traditional college classroom. The model allows for an evaluation of different preventative measures implemented by the University of Pittsburgh, including the cohort classroom attendance model, mask and vaccine mandates, contact tracing, and classroom sanitation. Through the use of the model's interactive interface, the impact of adjusting specific measures by the institution could be visualized, providing a valuable tool for combating diseases that spread through droplet transmission.

Muscle Defects Lead To Skeletal Deformities In A Zebrafish Model Of Distal Arthrogryposis, Emily A. Tomak

Electronic Theses and Dissertations

Distal Arthrogryposis Type 1 (DA1) involves mild muscle weakness and limb skeletal abnormalities thought to be caused by paralysis in utero. Why the limbs are particularly affected in DA1 and the degree of paralysis that leads to these skeletal deformities in utero remains unclear. Several muscle genes are known to cause DA1, including MYLPF (myosin light chain phosphorylatable), which encodes a myosin light chain protein that binds close to the force-generating head of myosin heavy chains. The zebrafish mylpfa^-/- mutant displays a phenotype consistent with DA1, including impaired myosin activity, reduced muscle force overall, and complete fin paralysis. I …

In Vitro And In Vivo Diabetic Models For Assessment Of Tissue Engineered Vascular Grafts, Juan Carlos Carrillo Garcia

All Dissertations

Diabetes has become one of the leading causes of lower-limb loss worldwide. Every 30 seconds, a person loses a limb due to diabetic-related vascular complications. About one-third of patients needing lower-limb bypass surgery have debilitated autologous vessels unsuitable for use, and no other good long-term options are available. These detrimental effects on the vasculature are caused mainly by the hyperglycemic and hyperlipidemic conditions derived from diabetes. Under these conditions, an increase in advanced glycation end products (AGEs) and reactive oxygen species leads to irreversible crosslinks of extracellular matrix proteins, accelerating vascular pathology through vascular stiffening, endothelial dysfunction, inflammation, atherosclerosis, fibrosis, …

A Larval Zebrafish (Danio Rerio) Model Of Adherent-Invasive Escherichia Coli Infections, Erika Flores, Erika Flores

Dissertations & Theses (Open Access)

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a broad term for chronic intestinal disorders that severely impact patient morbidity and quality of life. The global prevalence of IBD is rising, with over one million patients affected in the US alone. Adherent-invasive E. coli (AIEC) is a pathobiont frequently found in IBD biopsies. AIEC adhere to and invade epithelial cells, and can survive inside macrophages in vitro. However, how AIEC contributes to IBD in vivo remains unclear. Here a larval zebrafish (Danio rerio) model of AIEC was established, which facilitates the study of the …

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

Relative Efficacy Of Resource Constrained Forward And Backward Contact Tracing In An Open Population, Nicholas Roberts

Biology and Medicine Through Mathematics Conference

No abstract provided.

Functional Evaluation Of A Novel Rpl30 Mutation And Its Role In Diamond Blackfan Anemia (Dba), Alexandra Prosser, Alexandria Cockrell, Danny Miller, Chris Seidel, Tamara Potapova, John M. Perry, Midhat Farooqi, Erin M. Guest, Jennifer Gerton

Research Days

Background: Bone marrow failure is life-threatening and requires prompt, intensive treatment, which is dependent upon identification of genetic drivers. Although there has been investigation into associated genetic mutations, especially in Diamond Blackfan anemia (DBA), the relationship between genotype and phenotype remains unclear.DBA has been identified as a ribosomopathy, also known as a disease associated with defects in ribosome biogenesis. We identified a novel heterozygous variant (c.167+769C >T) in the noncoding region of RPL30 in a patient with clinical diagnosis of DBA. Clinical RNA sequencing (RNA-seq) suggests the variant generates a novel splice acceptor site resulting in truncated RPL30 transcripts. Elucidation …

The Role Of Food Accessibility In Weight Loss In A Rat Model Of Parkinson’S Disease, Anjali Kikkisetti, Nicole Charles, Francois Gould

Rowan-Virtua Research Day

Parkinson’s disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms. The goal of this project was to understand whether the weight loss seen with Parkinson’s disease was due to the lack of being able to access the food because of the food placement or because of inability to chew the food due to degeneration of muscles required for chewing food. Both treatment groups, Adjusted Diet and Unadjusted Diet, lost weight after injections started, whereas control weights were stable throughout the experiment. There is no statistically significant difference in weight loss between adjusted and unadjusted …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Rowan-Virtua Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

Maackia Amurensis Seed Lectin (Masl) Increases Movement Velocity Of Mice With Tnfα Induced Rheumatoid Arthritis, Amanda A. Greenspan, Kelly L. Hamilton, Alan J. Shienbaum, Bradford Fischer, Andrea Bottaro, Gary S. Goldberg

Rowan-Virtua Research Day

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Cardiovascular Disease Prediction Modelling: A Machine Learning Approach, Usmaan Al-Shehab, Maduka Gunasinghe, Yousuf Elkhoga, Nimay Patel, Juliana Yang

Rowan-Virtua Research Day

The objective of this project is to utilize the UCI Heart Disease dataset to identify physiological biomarkers that are highly correlated with heart disease incidence. A predictive model can then be developed using these biomarkers to estimate the likelihood of someone having or developing a heart-related condition. This study compares the efficacy of predicting cardiovascular disease as an outcome using three machine learning algorithms: Support Vector Machine, Gaussian Naive Bayes, and logistic regression. Support Vector Machine works by creating hyperplanes between data points to conduct classification. Gaussian Naive Bayes works by using the conditional probabilities of events to classify the …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

Protective Effect Of Betulinic Acid Administration On Kidney Damage In Acetaminophen-Induced Nephrotoxicity Model, Eda Dokumacioglu, Hatice İskender, Armagan Hayirli, Guler Yenice, Kubra Asena Terim Kapakin, Ismail Bolat, Esra Manavoglu Kirman

Makara Journal of Health Research

Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate the potential protective effects of BA treatment through an experimental kidney damage rat model administered with APAP.

Methods: Sprague–Dawley male rats were randomly divided into four groups: control, BA (25 mg/kg for 15 days), APAP (1 g/kg), and APAP + BA groups. BA was administered via oral gavage at a dose of 25 mg/kg for 15 days. APAP was dissolved in hot …