Disease Modeling Commons^™

When Brain Meets Artificial Intelligence, Lu Zhang

Computer Science and Engineering Dissertations - Archive

When we review the history of development of artificial intelligence (AI), we will find that brain science plays a pivotal role in fostering breakthroughs in AI, such as artificial neural networks (ANNs). Today, AI has made remarkable strides, particularly with the emergence of large language models (LLMs), surpassing expectations and achieving human-level performance in certain tasks. Nonetheless, an insurmountable gap remains between AI and human intelligence. It is urgent to establish a bridge between brain science and AI, promoting their mutual enhancement and collaborations. This involve establishing connections from brain science to AI (brain-inspired AI), and reversely, from AI to …

Impacts Of Climate Change On Vector-Borne Disease Burden In The United States: Exploring The Epidemiological Evidence, Leah V. Loetman

Honors Theses

Climate change models predict shifts in vector-borne diseases (VBDs) around the world, including in the United States. However, to my knowledge there has yet to be a comprehensive descriptive epidemiological study examining prevalence, geographic distribution, and trends for all tick- and mosquito-borne diseases in the United States. I compiled data from the U.S. Centers for Disease Control (CDC), which publishes yearly case numbers for 17 vector-borne diseases. However, these publications depend on a scattered framework of state regulations regarding disease reporting. I compiled data from the CDC to determine the current geographic distribution, prevalence, and trends of tick- and mosquito-borne …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Human Cell Modeling Of Cdkl5-Deficiency Disorder With Patient-Derived Organoids And Hd-Mea, Alyssa Paynton

Cal Poly Humboldt theses and projects

CDKL5 deficiency disorder (CDD) is an X-linked disorder that leads to severe cognitive impairments as well as infantile epilepsy. The only FDA approved therapy helps to reduce seizure frequency, however there are currently no cures approved. While murine models have proven useful in characterizing CDD, there are limitations due to differences in brain structure and development across species that may lead to the reported lack of spontaneous seizures in the mouse, a hallmark in humans affected by this disorder. By the utilization of patient-specific iPSCs generated into cerebral organoids, a more comprehensive and in-depth analysis into rare neurological disorders, such …

Employing A Machine Learning Approach In Precision Oncology To Predict Pik3ca Functional Status And Identify Phenocopying Variants Of Deleterious Pik3ca Mutations, Javier Castillo

CMC Senior Theses

The following proposal describes a modular machine learning approach that detects malfunctioning genes and pathways in cancer using the transcriptome of cancer patients. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. Applied to the PI3K/AKT/mTOR pathway, this method can be used to predict PIK3CA functional status and identify phenocopying variants of deleterious PIK3CA mutations. The classifier will do this by integrating RNA-seq, copy number, and mutation data from tumors to determine the functional status of PIK3CA using a set of learned gene-specific weights. The classifier will then be …

Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks

Electronic Theses & Dissertations (2024 - present)

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expression of expanded CUG (CUG^exp) repeat RNA from the myotonic dystrophy protein kinase (DMPK) gene. This CUG^exp repeat RNA’s gain-of-function mechanism leads to the sequestration of muscleblind-like (MBNL) proteins, resulting in widespread alternative splicing dysregulation across tissues. Despite significant research, there are currently no approved therapeutics targeting the underlying causes of DM1. This dissertation explores the development and optimization of a novel class of small molecules, Modified Polycyclic Compounds (MPCs), designed to address splicing dysregulation in DM1. MPCs were designed from previously published …

Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser

Dissertations, Master's Theses and Master's Reports

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. …

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 …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

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 …

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 …

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.

Demarcating Psychopathologies: Nosology, Validity, And The Taxonomic Problem In Psychiatric Medicine, Julia Zentz Kolak

Dissertations, Theses, and Capstone Projects

In this dissertation, I argue that the discussion surrounding the role of values in the conceptualization of mental disorders is reproduced in critical debates surrounding the issue of reliability and validity in a psychiatric nosology. In so doing, I oppose the conventional separation of the demarcation problem and the crisis of validity in psychiatric classification, arguing instead that they are inextricably linked. After drawing out the intersection between these literatures in the conceptual history of the DSM and its much-maligned transition to an etiologically neutral taxonomy of mental disorders, I consider Carl Hempel’s proposed conciliation between descriptive and theoretical systematization …

Understanding And Quantifying Bioaerosol Fate Within The Aerobiological Pathway: Physical Transport, Environmental Decay, And Mitigation, Sean Kinahan

Theses & Dissertations

The recent COVID-19 pandemic has highlighted the need for better tools to understand and characterize phases of the aerobiological pathway, a model for understanding how infectious bioaerosols are sourced, generated, transported, deposit, and affect human health. This dissertation presents validation of methodologies for studying transport of airborne biological agents and variations on their consequences, especially focusing on their physical and chemical fate. Chapter 1 focuses on a parallel comparison of two methods of aging bioaerosols in real-world outdoor environments with complex sunlight, atmospheric chemistry, and pollutants. Both capture on microfibers and the use of Goldberg rotating drums to keep a …