Biomedical Engineering and Bioengineering Commons^™

A Novel Approach To Detect Modified Cytosines In A Nanopore Sequencer, Benjamin Davidorf

McKelvey School of Engineering Graduate Student Theses & Dissertations

Epigenetic changes, such as DNA methylation, have been seen in various types of cancers, diseases, and neurological disorders. A common form of methylation occurs when a methyl group is added to the C-5 position of a cytosine, which is called 5-methyl-cyosine (5- mC). Hydroxymethylated is a type of methylation where 5mC is oxidized to 5-hydroxy-methyl- cytosine (5hmC), which has been linked to normal brain development. Current methods to sequence DNA methylation patterns (5-mC and 5-hmC) at a genome-wide level have several limitations, so there remains a need for a method to efficiently map DNA methylation. The state- of-the-art method for …

Understanding The Mechanisms By Which Cable Sway Produces Motion Artifact In Mobile Electroencephalography, David Rojas

Electronic Theses and Dissertations, 2020-2023

Mobile brain/body imaging utilizes electroencephalography (EEG) to record brain activity during human walking in dynamic environments. Motion artifact from cable sway affects the quality of EEG signals collected from the scalp, masking contributions of synchronously firing neurons. Previous studies have explored cable sway-induced motion artifact, but only during vigorous exercise or controlled sinusoidal motion. Therefore, a need remains to further understand the underlying mechanisms of this artifact, as it may help with developing real-time mitigation methods, reducing reliance on offline signal processing. In this thesis, I aimed to show that controlled cable sway could produce specific motion artifact waveforms in …

Improving Peripheral Nerve Regeneration Through Rehabilitation And Biomaterial-Based Drug Delivery Strategies, Yunfan Kong

Theses & Dissertations

Peripheral nerve injury (PNI) is a common problem worldwide, with trauma being a common cause. PNI can lead to loss of sensory and motor functions, chronic neuropathic pain, and mental health issues, significantly impacting patients' family life, work, and social situation. Recent studies revealed that beyond the topical injury site at peripheral nerves, PNIs can also induce dysfunctions in the central nervous system (CNS) by causing maladaptive plasticity, which will result in exaggeration and exacerbation of the pathological condition caused by primary injuries. The common therapy strategies for PNI treatment are using sutures, nerve autografts or conduits in cases requiring …

The Effects Of Mechanical Strain On Vascular Calcification And The Canonical Wnt Pathway, Hannah E. Douglas

Theses and Dissertations

Cardiovascular disease is a significant health crisis, representing 32% of deaths worldwide in 2019. Vascular calcification (VC), a major contributor to cardiovascular disease, is a regulated biomineralization process whose exact mechanisms are unknown. Additionally, vascular smooth muscle cells (VSMCs) significantly contribute to VC by undergoing a phenotypic switch and differentiating into osteoblast-like cells. When factors like hypertension cause disturbed laminar flow in the body’s vasculature, the mechanical stress promotes the phenotypic switch and calcification of VSMCs via mechanotransduction. VC is also induced by the Wnt pathway, which is activated via mineral imbalance and mechanical stimulation. However, the exact mechanisms behind …

Multi-Objective Design Optimization Of Two Configurations Of Ventricular Shunts For Hydrocephalus, Will Kirkpatrick

Theses and Dissertations

Hydrocephalus is developed when the flow of cerebrospinal fluid is obstructed in the ventricles and a pressure build-up is generated within the brain. Ventricular shunts are used to remove excess fluid from the brain, but these shunts have a common problem of failure due to the shunt being obstructed by the build-up of astrocytes. To address this, two sets of 27 designs of ventricular shunts were identified and analyzed with parameters that could potentially reduce obstruction risks. The performance of these designs was examined using fluid simulations on these two sets of 27 designs. One set explored close-tipped shunt designs, …

Nanoscale Modeling Of Membrane Systems Under Mechanical Deformation In Traumatic Brain Injury Using Molecular Dynamics, Anh Thi Ngoc Vo

Theses and Dissertations

Neuronal membrane disruption and mechanoporation are nanoscale damage mechanisms that critically affect brain cell viability during traumatic brain injury (TBI). These nanoscale cellular impairments are elusive in experiments and necessitate in silico approaches such as molecular dynamics (MD) simulations. Implementing MD, this research aims to investigate the effects of different key factors related to membrane deformation and damage, including force field resolutions, lipid compositions, and loading conditions.

To examine the impact of force field resolution, MD deformation simulations were conducted on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer membranes, using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) force fields. The mechanical responses …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Polyethylene Glycol-Mediated Directional Conjugation Of Biological Molecules For Enhanced Immunoassays At The Point-Of-Care, Dheerendranath Battalapalli, Purbali Chakraborty, Disha Jain, Umut A. Gurkan, Robert A. Bonomo, Mohamed S. Draz

Faculty Scholarship

Rapid and reliable point-of-care (POC) diagnostic tests can have a significant impact on global health. One of the most common approaches for developing POC systems is the use of target-specific biomolecules. However, the conjugation of biomolecules can result in decreased activity, which may compromise the analytical performance and accuracy of the developed systems. To overcome this challenge, we present a polymer-based cross-linking protocol for controlled and directed conjugation of biological molecules. Our protocol utilizes a bifunctional thiol-polyethylene glycol (PEG)-hydrazide polymer to enable site-directed conjugation of IgG antibodies to the surface of screen-printed metal electrodes. The metal surface of the electrodes …

Scanning Electron Microscopy Analysis Of Murine Renal, Aortic, And Cardiac Tissue, Sarah E. Grev, Luke E. Schepers, Jennifer Anderson, Craig J. Goergen

Discovery Undergraduate Interdisciplinary Research Internship

Scanning electron microscopy (SEM) is a tool that provides detailed insight into objects invisible to the human eye. As the name suggests, an electron beam is used to create an image down to the nanometer scale. The beam focuses on the surface of a sample using lenses in the electron column. In this project, we use SEM to study three types of murine tissue. First, we examine the glomerulus, found in the kidney, that is primarily responsible for filtering blood. Following a left renal vein (LRV) stenosis, SEM is used to observe changes to the glomeruli. Differences in the left …

Development Of Air-Jetting System For Bioprinting Of Alginate Micro-Droplets, Nathan Lingenfelter

Electronic Theses and Dissertations

Transplantation of organoids has been demonstrated to be a promising cure to many diseases including Type-1 diabetes. However, achieving consistent and robust derivations of mature organoids from human pluripotent stem cells (hPSCs) is challenging. Cellular mechano-transduction, where mechanical stimuli is sensed and converted to biochemical signaling, has been proposed to overcome this challenge. This pathway relies on encapsulating hPSCs in a small volume of a biomaterial such as alginate, which has been widely used as cell encapsulation materials due to its biocompatibility and selective permeability. In this project, we focused on developing an air-jetting based technique to generate small and …

Efficient Scopeformer: Toward Scalable And Rich Feature Extraction For Intracranial Hemorrhage Detection, Yassine Barhoumi, Nidhal Carla Bouaynaya, Ghulam Rasool

Henry M. Rowan College of Engineering Departmental Research

The quality and richness of feature maps extracted by convolution neural networks (CNNs) and vision Transformers (ViTs) directly relate to the robust model performance. In medical computer vision, these information-rich features are crucial for detecting rare cases within large datasets. This work presents the “Scopeformer,” a novel multi-CNN-ViT model for intracranial hemorrhage classification in computed tomography (CT) images. The Scopeformer architecture is scalable and modular, which allows utilizing various CNN architectures as the backbone with diversified output features and pre-training strategies. We propose effective feature projection methods to reduce redundancies among CNN-generated features and to control the input size of …

Hemodynamic Assessment Of Y-Incision Aortic Root Enlargement Using Computational Simulations, Astitwa Ghimire

Electronic Theses and Dissertations

The Yang procedure is a new aortic root enlargement technique used to enlarge the aortic annulus by multiple valve sizes. The procedure prevents patient prosthesis mismatch and establishes a viable platform for future valve-in-valve implantation. This study used the Yang procedure to investigate the hemodynamics in the aortic root and bioprosthetic valve regions after aortic root enlargement. Results indicate the velocity magnitude at the sinus regions of a patient who underwent the Yang procedure was slower, indicating risks of flow stasis and thrombosis. Simulation results denote computational models can be created for optimization of surgical procedures.

Site-Specific Glyco-Engineering Of Recombinant Thrombomodulin, Joseph M. Keil

ETD Archive

Thrombomodulin (TM), a membrane glycoprotein predominately expressed on endothelium, plays essential roles in regulating local hemostatic balance. Particularly, TM modulates the activity of thrombin from a procoagulant to an anticoagulant protease. When bound to TM, thrombin activates plasma protein C, which selectively inactivates coagulation factors Va and VIIIa. At the same time, TM-bound thrombin is unable to cleave fibrinogen or to activate platelets diminishing its procoagulant activity. recombinant TM456 is a promising anticoagulant candidate, but it has a very short half-life. TM is a proteoglycan and its O-linked glycosaminoglycan (GAG), chondroitin sulfate (CS), on the D3 domain contributes to TM’s …

Quantification And Identification Of Neuro-Electrophysiological Markers And Brain Network For Biomedical Applications, Shu Kang

Bioengineering Dissertations - Archive

Electroencephalogram (EEG) can detect and monitor neuro-electrophysiological signals in the human brain, including assessing brain function in newborns at risk of neurological injury and healthy adults undergoing intervention with prefrontal transcranial photobiomodulation (tPBM). Moreover, EEG-based brain functional connectivity can be assessed in either resting-state or task-based measurements using graph-theoretical network modeling. However, the management of newborns with mild hypoxic ischemic encephalopathy (HIE) is controversial, and no study has investigated the EEG-based brain network and information flow resulting from HIE. Also, the underlying electrophysiological mechanism of tPBM is still unclear, and further research is needed to determine optimal parameters for tPBM …

Tandem Peptides Targeting Her2 For Delivery Of Cd44 Sirna Into Her2+ Breast Cancer Cells In Vitro, James Kalogeros

All Theses

More than 300,000 women will be diagnosed with breast cancer, and approximately 48,000 women will die this year due to the disease in the United States. HER2+ breast cancer accounts for 20-25% of invasive breast cancer, and it has a worse prognosis and higher early-stage mortality rate than other breast cancer subtypes. Common treatments for HER2+ breast cancer involve surgical removal of the breast or systemic therapy with chemotherapeutic drugs, both of which cause damage to healthy tissue. Due to the lack of a natural ligand for the HER2 receptor, there is a need for improved targeting strategies for the …

Computational Comparison Of Medializing Tibial Tubercle Osteotomy And Trochleoplasty In Patients With Trochlear Dysplasia, Clare K. Fitzpatrick, Robert N. Steensen, Oliver Alvarez, Amy E. Holcomb, Paul J. Rullkoetter

Mechanical and Biomedical Engineering Faculty Publications and Presentations

Medial patellofemoral ligament reconstruction (MPFLR) has emerged as the procedure of choice for recurrent patellar dislocation. This addresses soft tissue injury but does not address underlying anatomic factors, including trochlear dysplasia, that are commonly present and increase risk of dislocation. Quantification of the stability offered by other surgical interventions, namely, medializing tibial tubercle osteotomy (mTTO) and trochleoplasty, with and without MPFLR, may provide insight for surgical choices in patients with trochlear dysplasia. We developed subject-specific finite element models based on magnetic resonance scans from a cohort of 20 patients with trochlear dysplasia and recurrent patellar dislocation. The objectives of this …

Prevention And Reversal Of Elastin-Associated And Phosphate-Dependent Arterial Calcification Using Targeted Nanotherapeutics In Pre-Clinical Models, Fatema Tuj Zohora

All Dissertations

Vascular calcification can be life-threatening, involving calcium phosphate crystal deposits in the blood vessels. The calcification in the intimal layer of the arterial wall is usually associated with atherosclerotic plaque build-up that, in the advanced stage, harbors ‘dispersed’ and ‘spotty’ deposits of calcium phosphate crystals in the necrotic core of the plaque. In contrast, medial arterial calcification (MAC) can form independently of atherosclerosis and appears as ‘Railroad-like’ calcific deposits along degraded elastin lamellae in the medial layer of arteries. The mechanisms of such elastin-associated medial arterial calcification and potential therapies are the key concerns of this dissertation. MAC is common …

Visual Complexity Of The Time-Frequency Image Pinpoints The Epileptogenic Zone: An Unsupervised Deep-Learning Tool To Analyze Interictal Intracranial Eeg, Sarvagya Gupta

Graduate Masters Theses

Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, continues to pose significant challenges in diagnosis and treatment, particularly among children. Despite substantial advancements in medical technology and treatment modalities, localization of the part of brain that causes seizures (Epileptogenic Zone) remains a difficult task. Intracranial EEG (iEEG) is often used to estimate the epileptogenic zone (EZ) in children with drugresistant epilepsy (DRE) and target it during surgery. Conventionally, iEEG signals are inspected in the time domain by human experts aiming to locate epileptiform activity.

Visual scrutiny of the iEEG time-frequency (TF) images can be an alternative way to review …

Development & Validation Of Needle-Based Metrics For Hemodialysis Cannulation Skill Assessment, Ziyang Zhang

All Dissertations

Dialysis is a vital medical treatment for patients with end-stage renal disease. An arteriovenous fistula, a surgically created connection between an artery and a vein, is the preferred vascular access for dialysis due to superior clinical outcomes. However, cannulation complications caused by needle-related errors are common and dangerous, necessitating the need for effective cannulation training. Despite cannulation being a challenging and complex clinical procedure, little is known about the quantitative aspects of needle insertion dynamics necessary for skilled cannulation. The aim of this study was to develop meaningful and instructive needle-based metrics for cannulation skill assessment and training.

Two iterations …

Investigating The Potential Of A Cell-Based Gene Editing Therapy For Inherited Metabolic Liver Disease, Ilayda Ates

All Dissertations

Inherited metabolic diseases (IMDs) affecting the liver are relatively rare but collectively have a prevalence of 1 in 800 live births. These diseases result from autosomal recessive single-gene mutations, leading to organ dysfunction and potentially fatal consequences if left untreated. One potential therapeutic strategy for IMDs of the liver involves using CRISPR-Cas9-induced loss of function mutations. However, translating this approach into the clinic is limited by the need for safe and effective CRISPR delivery methods. Adeno-associated viral vectors (AAVs), commonly used for CRISPR delivery, are associated with significant safety and efficacy concerns, including risks for immunogenicity, off-target mutagenesis, and genotoxicity …