Biomedical Engineering and Bioengineering Commons^™

The Role Of Trpm7 In Mouse Development And Immune Cell Function, Jananie Rockwood

Browse all Theses and Dissertations

Transient receptor melastatin 7 (TRPM7) functions both as an ion channel and a protein kinase. TRPM7 has been implicated in Mg2+ homeostasis, embryogenesis, cardiac automaticity, and immunity. The purpose of this research was to deepen our understanding of TRPM7 channel and kinase functions. To this end, we used two transgenic mouse models: the TRPM7 gain-of-function (GOF) and TRPM7 kinase-dead (KD) mice to address the consequences of increased channel activity and kinase inactivation, respectively. Global deletion of TRPM7 or the kinase domain alone are embryonic lethal, therefore, we used the TRPM7 GOF mouse to investigate germline transmission. We examined embryo development …

Induced Reduction Of N-Glycosylation Leads To Heart Failure, Anthony M. Young

Browse all Theses and Dissertations

Cardiovascular disease is the leading cause of death and contributes to the increasing global prevalence of heart failure (HF). N-glycosylation is a common co-/post-translational modification where branching oligosaccharides are bound to the extracellular domain of membrane proteins. This creates a diverse range of glycan structures and requires the coordination of hundreds of regulated genes. Inherited mutations in glycan synthesis frequently present with cardiomyopathies leading to HF with reduced ejection fraction (HFrEF). Additionally, gene expression studies of HFrEF patients have shown altered expression of glycosylation-related genes, including alpha-1,3-mannosyl-glycoproten 2-beta-N acetlyglucosaminyltransferase (Mgat1). This gene encodes N-acetylglucosaminyl transferase 1 (GlcNAcT1) which is required …

The Impact Of Ahr And Hs1.2 Enhancer Genetic Variations On Igh Expression And Antibody Production In Human B Cells, Mili Santosh Bhakta-Yadav

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Antibody production is an essential component of the immune response against pathogens. The immunoglobulin heavy chain (IgH) gene codes for the heavy chain of antibodies. The IgH constant regions Cμ, Cδ, Cγ1-4, Cα1-2, and Cε encode the five major classes of antibodies, i.e., IgM, IgD, IgG1-4, IgA1-2, and IgE, respectively. The transcription of the IgH gene and class switch from IgM to other isotypes is regulated by two 3’ IgH regulatory regions (3’IgHRRs), each of which is a cluster of three enhancer regions (hs3, hs1.2 and hs4). The genetic variations in the hs1.2 enhancer have been identified; a ~53 bp …

Electro-Vascular Dynamics During Auditory Processing: Variation Along The Schizotypy Continuum, John P. Mclinden

Open Access Dissertations

Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) are complementary noninvasive neuroimaging modalities that have contributed greatly to our understanding of the mechanisms of auditory processing. As an emerging technology, fNIRS has produced promising insights into the mechanisms of auditory processing, although considerable work remains to characterize hemodynamic responses in auditory tasks. In addition, the complementary nature of EEG and fNIRS and the relationships between the signals they record have been underexplored. In particular, nonlinear interactions between these signals remain under-characterized, despite the potential benefit to future multimodal neuroimaging studies. A challenge in understanding these interactions is the influence of systemic …

Robust Quantification Of Cortical Hemodynamic Response To Tactile Stimulation: A Comprehensive Fnirs Methodology To Mitigate Physiological Confounds, Mohsen Hozan

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

This dissertation establishes a quantitative framework for studying somatosensory processing using functional Near-Infrared Spectroscopy (fNIRS), with a focus on applications in neurorehabilitation. The central aim is to investigate how the brain's hemodynamic response is modulated by the velocity of patterned tactile stimulation. While fNIRS is a promising neuroimaging tool, its data quality is often compromised by physiological noise and motion artifacts, challenging the reliability of its findings and hindering the development of effective, quantifiable neurotherapeutics.

Two preliminary investigations informed the final experimental design. The first pilot study confirmed that pneumotactile stimulation of the hand, during both passive (somatosensory) and active …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

Functional Assessment Of Migration And Adhesion To Quantify Cancer Cell Aggression, Lauren E. Mehanna, James D. Boyd, Chloe G. Walker, Adrianna R. Osborne, Martha E. Grady, Brad J. Berron

Markey Cancer Center Faculty Publications

During epithelial-to-mesenchymal transition (EMT), cancer cells lose their cell–cell adhesion junctions as they become more metastatic, altering cell motility and focal adhesion disassembly associated with increased detachment from the primary tumor and a migratory response into nearby tissue and vasculature. Current in vitro strategies characterizing a cell’s metastatic potential heavily favor quantifying the presence of cell adhesion biomarkers through biochemical analysis; however, mechanical cues such as adhesion and motility directly relate to cell metastatic potential without needing to first identify a cell specific biomarker for a particular type of cancer. This paper presents a comprehensive comparison of two functional metrics …

Investigation Using Single Point Incremental Forming (Spif) To Fabricate Patient-Specific, Titanium Orbital Floor Implants, Elizabeth M. Mamros, Lauren E. Blaha Md, Christian A. Kauffman Md

Faculty Conference Papers and Presentations

The floor of the human orbit is composed of thin bone that is prone to traumatic fracture. This leads to a loss of support for the eye, which can cause vision changes. Therefore, fractures may need surgical reconstruction using a thin, sheet-like implant. Titanium implants are available off-the-shelf in standard sizes, but fitting to each patient’s unique anatomy requires surgeons to cut, file, and bend these plates. This can be time-consuming and imprecise. To both save time and ensure a perfect fit for the patient, a custom plate can be created prior to surgery. This investigation focuses on single-point incremental …

Globus Pallidus Internus Dynamics During Freezing Of Gait, Nicholas Druck, Dean J. Krusienski, Josephine Wallner

Graduate Research Posters

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting ~1 in 1000 individuals over age 45. Freezing of Gait (FOG), a debilitating symptom in late-stage PD, affects up to 63% of patients and contributes to falls and reduced quality of life. While deep brain stimulation (DBS) of the subthalamic nucleus (STN) helps some symptoms, FOG remains difficult to treat. Given the complexity of basal ganglia circuitry, the role of related basal ganglia nuclei, such as the Globus Pallidus internus (GPi), in FOG deserves further investigation.

Methods: Five PD patients with FOG, implanted with Medtronic Percept DBS systems …

3d Bioprinting Technology Innovation In Female Reproductive System, Siyao Chen, Tongxin Wang, Jiaqi Chen, Mingxing Sui, Luyao Wang, Xueyu Zhao, Jianqiao Sun, Yingli Lu

Department of Obstetrics & Gynecology Faculty Publications

Several diseases affect the female reproductive system, and both disease factors and treatments impact its integrity and function. Consequently, understanding the mechanisms of disease occurrence and exploring treatment methods are key research focuses in obstetrics and gynecology. However, constructing accurate disease models requires a microenvironment closely resembling the human body, and current animal models and 2D in vitro cell models fall short in this regard. Thus, innovative in vitro female reproductive system models are urgently needed. Additionally, female reproductive system diseases often cause tissue loss, yet effective tissue repair and regeneration have long been a bottleneck in the medical field. …

Lung Uptake Of Two Spect Markers Identifies Sensitivity To Hyperoxia-Induced Acute Respiratory Distress Syndrome In Rats, Anne V. Clough, Taheri Pardis, Guru P. Sharma, Ming Zhao, Elizabeth R. Jacobs, Said H. Audi

Biomedical Engineering Faculty Research and Publications

Introduction: Exposure of adult rats to hyperoxia is a well-established model of human Acute Respiratory Distress Syndrome (ARDS). Although rats exposed to 100% O₂ display clinical evidence of lung injury after ∼40 h and death by 72 h, rats exposed to 60% O₂ for up to 7 days show little sign of injury. However, when subsequently exposed to hyperoxia, these pre-exposed rats become more susceptible to ARDS. The objective of this study is to evaluate the ability of imaging biomarkers to track this hyperoxia susceptibility and to elucidate underlying mechanisms.

Methods: Sprague-Dawley rats were exposed to either room …

Online Parameter Adaptation Of Lqr Controllers Via Rls For Prosthetic Joint Control: Experimental Validation On A Quanser Qube-Servo 2 Platform, Cynthia Lopez-Jordan

Theses and Dissertations

This thesis develops and experimentally validates an online adaptive Linear Quadratic Regulator (LQR) control method for prosthetic joint systems using Recursive Least Squares (RLS)-based real-time parameter estimation on the Quanser QUBE-Servo 2 platform. Traditional LQR controllers assume a fxed system model, which limits adaptability and results in reduced tracking accuracy, poor robustness, and loss of optimal performance when applied to dynamically changing prosthetic joints, infuenced by load variations, user gait changes, and mechanical wear. Limited experimental validation exists for combining RLS with online LQR adaptation in prosthetic-like systems.

To address these limitations, an RLS-driven Adaptive LQR framework was implemented to …

Engineering Nanomaterials From Phase-Change Biological Materials Reacting With Carbon Dioxide, Qingyang Li

Graduate Theses, Dissertations, and Problem Reports (ETD)

The current global situation concerning CO2 emissions is increasingly alarming, with rising concentrations of CO2 significantly worsening climate change and global warming. Atmospheric CO2 levels are now at their highest in millions of years, driving a host of catastrophic effects, including but not limited to extreme weather events, rising sea levels, ocean acidification, disrupted ecosystems, deteriorating air quality, respiratory health issues, heat-related illnesses, threats to food and water security, and escalating social and geopolitical tensions. To keep global warming to no more than 1.5°C higher than that of pre-industry – as called for in the Paris Agreement – emissions need …

Finite Element Modeling And Experimental Characterization Of Overmolded Gold-Palladium Composite Leads And Their Mechanical Behavior Under Cyclic Fatigue For Long-Term Implant Applications, Tanner Davis

Graduate Theses, Dissertations, and Problem Reports (ETD)

Auditory Nerve Interface (ANI) devices, currently in developmental stages, represent an emerging neuroprosthetic approach to restore hearing in severe sensorineural loss patients by directly stimulating the auditory nerve via the Utah Slanted Electrode Array (USEA). Conventional implant leads are comprised of multiple wires made from materials such as platinum-iridium and MP35N stainless steel that are overmolded in an insulative material. These materials are not possible to bond with to electrode array used in the ANI device, necessitating the evaluation of a new material like Au-Pd to ensure its functionality and durability under cyclic stresses. This gap necessitates characterization of alternative …

Leveraging Deep Learning For The Automated Detection Of Hemophilic Arthropathy In Knee Radiographs, En-Wei Lin, Edzer Wu, Ming-Ching Shen, Shao-Li Han

Rehabilitation Practice and Science

Background/Purpose:

Hemophilic arthropathy (HA) is a progressive joint disease caused by recurrent hemarthroses in patients with hemophilia. Early radiographic identification of HA is critical for timely intervention and long-term joint preservation. This study aimed to develop and evaluate deep learning models for automated detection of HA in knee radiographs.

Methods:

A retrospective dataset of 849 knee radiographs (AP and lateral views) was used to train three convolutional neural networks: ResNet-34, DenseNet-121, and EfficientNet-B0. Model performance was assessed using standard classification metrics, including accuracy, precision, recall, F1-score, and AUC. Interpretability was evaluated using Grad-CAM heatmaps.

Results:

DenseNet-121 achieved balanced performance on …

Application-Driven Materials Development Of Solid-State Conductive Composites Of Ultra-High Molecular Weight Polyethylene, Peder Solberg

Dartmouth College Ph.D Dissertations

Ultra-high molecular weight polyethylene (UHMWPE) is a linear long chain homopolymer valued for its toughness, wear resistance, and chemical inertness. In the medical field, these properties make it the material of choice for bearing surfaces despite recognized tradeoffs between wear resistance, toughness, and oxidation resistance. Electrically conductive composites of UHMWPE show promise to enable new types of smart and active load-bearing implants in a future of personalized medicine, if beneficial properties can be maintained with the addition of solid-state additives.

Clinical need-finding conducted through Dartmouth’s Training Program in Surgical Innovation revealed several potential applications for conductive, load-bearing polymers. These include: …

Molecular Characterization Of Leptin Gene In Sheep (Ovis Aries), Shahenda M. Hegazy, Mohamed Fouda, Ahmed Ateya, Huda A. El Emam

Mansoura Veterinary Medical Journal

INTRODUCTION: Advances in molecular genetic techniques have simplified the process of identifying individual differences at the DNA level. Genetic polymorphisms at candidate genes controlling economic features have recently drawn a lot of scholarly attention due to their potential as a tool for genetic selection and the identification of evolutionary linkages in livestock. OBJECTIVE: This work aimed to detect nucleotide sequence variants in Lep gene as genetic markers for growth and heat tolerance traits in Barki and Abudeleik sheep using PCR-DNA sequencing approach in search of single nucleotide polymorphisms (SNPs). METHODS: 30 female ewes, 15 of each breed (Barki and Aboudeleik) …

The Study Of Knee And Ankle Sagittal Plane Angles For On-Court Versus Off-Court Cutting, Alexi Rebecca Hempe

Dissertations and Theses

Lower extremity injuries are common among basketball athletes. Majority of these injuries are non-contact and therefore preventable. While previous research has explored high-risk movements associated with lower extremity injuries, limited research has explored the influence of settings for these movement patterns, particularly on a basketball court. This study aims to examine the knee and ankle joint angles in the sagittal plane of a 90-degree cut for on-court versus off court. Thirteen (13) subjects, four males (19.5 ± 1.0 years of age; 198.8 ± 4.8 cm of height; 198.8 ± 13.8 lbs. of weight) and nine females (19.8 ± 1.5 years …

Interfacing Neural Models: Biocompatibility And Fabrication Of A Flexible, Self-Folding Microelectrode Array, Fernando A. Pesantez Torres

Electronic Theses & Dissertations (2024 - present)

Neurodegenerative diseases pose a formidable challenge in modern medicine, necessitating the development of advanced research tools that can elucidate their complex pathophysiology. Recent advancements in neurodegenerative disease research have led to the development of three-dimensional (3D) neurodegenerative organoids using human induced pluripotent stem cells (hiPSCs). These organoids closely mimic human brain architecture and functionality, providing a valuable tool for understanding complex diseases. Additionally, the ability to generate and study brain organoids consistently and in large quantities holds potential for a controlled in vitro setting and high-throughput drug screening. However, these models are complex systems requiring specialized maintenance, analysis, and manipulation …

The Implementation And Miniaturization Of A New Current Source Into The Consolidated Layout Of An Electrical Impedance Tomography Probe With A Novel Approach To Electrode Layout, Katherine M. Bullion

Dartmouth College Master’s Theses

Prostate cancer is the most highly diagnosed form of cancer in male subjects in the United States. As a result, over 100,000 radical prostatectomies are performed annually in the US [1]. However, it is currently very difficult for surgeons to confirm that all impacted tissues have been effectively removed from the patient. Positive surgical margins are an independent risk factor for the recurrence of cancer, yet currently there is no method to efficiently, intraoperatively assess the status of surgical margins during a radical prostatectomy. There is a need for a new tool that is small enough to fit into a …