Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang

All Dissertations

Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …

Ti-6al-4v Β Phase Selective Dissolution: In Vitro Mechanism And Prediction, Michael A Kurtz

All Dissertations

Retrieval studies document Ti-6Al-4V β phase dissolution within total hip replacement systems. A gap persists in our mechanistic understanding and existing standards fail to reproduce this damage. This thesis aims to (1) elucidate the Ti-6Al-4V selective dissolution mechanism as functions of solution chemistry, electrode potential and temperature; (2) investigate the effects of adverse electrochemical conditions on additively manufactured (AM) titanium alloys and (3) apply machine learning to predict the Ti-6Al-4V dissolution state. We hypothesized that (1) cathodic activation and inflammatory species (H₂O₂) would degrade the Ti-6Al-4V oxide, promoting dissolution; (2) AM Ti-6Al-4V selective dissolution would occur …

Engineering Next-Generation Cardiovascular Therapies, Ryan Walker Barrs

All Dissertations

Cardiovascular diseases are the leading cause of death worldwide. Heart disease, in particular, accounted for 1 in every 5 deaths in the United States in 2021, representing a substantial public health burden that will require more effective treatment options to alleviate. Heart transplant surgery is currently the only option to completely restore cardiac function, but many patients die while waiting for a transplant due to a longstanding organ donor shortage. Thus, there is a dire need for accessible treatment options that can repair damaged hearts. Recent advances in tissue engineering and regenerative medicine have accelerated the development of therapies for …

Experimental And Computational Platforms For Studying Systems Mechanobiology, Brendyn Miller

All Dissertations

Mechanical stimulation through physical activity has been shown to play an important role in treating and preventing several non-communicable diseases such as hypertension, lower back pain (LBP), type-2 diabetes mellitus, and several cancers. This is accomplished through the regulation of cellular behavior and tissue remodeling within the body at both the micro- and macro-scale levels. The goal of mechanobiology research is to gain in-depth knowledge and understanding of how cells sense physical forces in conjunction with other biochemical cues and translate those factors into important biological functions that either maintain tissue homeostasis or lead to pathological states. Understanding these processes …

Assessing Chondrocyte Viability Of Articular Cartilage Using Label-Free Imaging Methods, Hongming Fan

All Dissertations

ABSTRACT

Articular cartilage covers the ends of bones, providing a protective layer that can endure forces during movement. Chondrocytes, the only cell type found in articular cartilage, produce collagen fibers and proteoglycans that maintain the extracellular matrix (ECM). Cartilage damage impairs chondrocytes and their ability to maintain tissue stability. There are various factors that can cause cell death, which can be broadly classified into two categories: programmed cell death (apoptosis) and non-programmed cell death (necrosis). The consequences of cell death can have significant impacts on the extracellular matrix (ECM). The ECM is a complex network of proteins and carbohydrates that …

An In Vitro Platform To Characterize Myocardial Wound Remodeling, Jonathan Heywood

All Dissertations

Heart Failure, sometimes called Congestive Heart Failure, is a collection of pathological disruptions in which the heart is unable to pump blood properly. It affects over 6 million people in the United States, with the cost-per-patient at approximately $30,000 and the total cost estimated to be $160 billion by 2030. There is no single cause of heart failure, as it can manifest as a varying array of diseases, disorders, and syndromes. However, many of these underlying diseases result specifically from dysregulation of mechanically active cells called cardiac fibroblasts, which play a critical role in the remodeling of the extracellular matrix …

An Improved Saliency Map With Trustworthiness For Localizing Abnormalities In Medical Imaging, Nolan C. Skelly

Theses and Dissertations

Saliency maps are a widely used methodology to make deep learning models more interpretable. They provide post-hoc explanations through identification of the most pertinent areas of an input medical image. These techniques have been assessed based on 1) localization utility, 2) sensitivity to model weight randomization, 3) repeatability, and 4) reproducibility. Ten saliency map techniques will be tested, Grad, Smooth Grad, Integrated Gradients, Smooth Integrated Gradients, XRAI, Grad-CAM, Guided Backpropagation, Guided GradCAM, GradCAM++, and ScoreCAM. The neural networks used to predict and read medical information require a reliable solution to provide medical practitioners intelligible results. Using the information of two, …

Design Of Human Serum Albumin And Adenovirus Conjugation Via Catcher/Tag Molecular Glue, Peijie Zhao

McKelvey School of Engineering Graduate Student Theses & Dissertations

Adenovirus (Ad) has been the ideal cargo delivery mechanism, and its moderate immunological response makes it ideal for in vivo gene therapies since its discovery in 1953. However, the robust immunogenicity of the Ad capsid and low vaccine absorption via mucous membranes and epithelium put a limit on the process of developing intranasal vaccines. Efforts are being made to enhance the effectiveness of Ad vectors and numerous studies have demonstrated the remarkable capacity of human serum albumin (HSA) to extend plasma half-life and facilitate targeted intranasal delivery. In this study, we devised an innovative method for employing the Catcher/Tag molecular …

Improving And Integrating Quantitative Single Cell Spatial Biology For Theranostic Medicine, Peng Lu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Disease states are the result of a complex interplay of many different cell types interacting in close proximity in the context of often heterogeneous tissues. Alpha particles are drawing intense research and clinical interest because of their potent cytotoxic effects and their short path lengths. Analyzing the dose distribution and tissue micro-environment for alpha therapy plays a key role in predicting the efficacy of this targeted radiotherapy. However, to date there have been no direct on-tissue analytical methods for alpha dose distributions and the corresponding tissue microenvironments.

Therefore, we have developed a pipeline to overcome this limitation by utilizing quantitative …

Evaluating Differences In Optical Properties Of Indolent And Aggressive Murine Breast Tumors Using Quantitative Diffuse Reflectance Spectroscopy, Joel Rodriguez Troncoso, Umme Marium Mim, Jesse D. Ivers, Santosh K. Paidi, Mason G. Harper, Khue G. Nguyen, Sruthi Ravindranathan, Lisa Rebello, David E. Lee, David A. Zaharoff, Ishan Barman, Narasimhan Rajaram

Biomedical Engineering Faculty Publications and Presentations

We used diffuse reflectance spectroscopy to quantify tissue absorption and scattering-based parameters in similarly sized tumors derived from a panel of four isogenic murine breast cancer cell lines (4T1, 4T07, 168FARN, 67NR) that are each capable of accomplishing different steps of the invasion-metastasis cascade. We found lower tissue scattering, increased hemoglobin concentration, and lower vascular oxygenation in indolent 67NR tumors incapable of metastasis compared with aggressive 4T1 tumors capable of metastasis. Supervised learning statistical approaches were able to accurately differentiate between tumor groups and classify tumors according to their ability to accomplish each step of the invasion-metastasis cascade. We investigated …

Surface Antibody Changes Protein Corona Both In Human And Mouse Serum But Not Final Opsonization And Elimination Of Targeted Polymeric Nanoparticles, Sara Capolla, Federico Colombo, Luca De Maso, Prisca Mauro, Paolo Bertoncin, Thilo Kähne, Alexander Engler, Luis Núñez, Gustavo Larsen, Et Al.

Department of Chemical and Biomolecular Engineering: Faculty Publications

Background: Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Another important improvement in the use of nanoparticles as delivery systems is the conjugation of a targeting agent that enables the nanoparticles to accumulate in a specific tissue. Despite these advantages, the clinical translation of therapeutic approaches based on nanoparticles is prevented by their interactions with blood proteins. In fact, the so-formed protein corona (PC) drastically alters the biological identity of the particles. Adsorbed …

Investigating The Effects Of Collagen Alignment And Tricalcium Phosphate Incorporation On Osteoblast Cell Response, Kathryn Elizabeth Bock

Theses and Dissertations

Every year, over 20 million people globally are affected by bone tissue loss due to disease or trauma. Bone tissue engineering (BTE) is touted as a promising approach to promote bone tissue repair and regeneration. In this realm, development of collagen-based scaffolds incorporated with a bioceramic is often attempted to generate tissue scaffolds that resemble the organic and inorganic composition of native bone. In addition, a variety of different collagen processing techniques have been employed to produce anisotropically aligned scaffolds that can provide the essential biochemical and structural cues to guide cell response. While there have been numerous studies on …

Development Of A Physics-Informed Neural Network For Prediction Of Blood Flow, Marcello Vittorio Mattei Di Eugenio

Theses and Dissertations

Abstract—Objective: We propose a new neural network architecture that accepts point clouds and outputs 3D velocity profiles for aneurysm geometries. Methods: We generated a synthetic aneurysm 3D flow dataset using CFD and used it to train our model architecture and compare it with other popular architectures like U-net and PointNet. We incorporate tools for improving model performance such as incorporating a distance function, a physics-informed loss to enforce the law of mass conservation, and the Huber loss to learn patterns across heterogeneous velocity components of multiple dimensions. Results: The tools implemented together with our architecture achieved the best performance on …

A Framework Of Flow Models For The Development And Testing Of Cardiovascular Devices, Megan Laughlin

Graduate Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death worldwide and its treatment continues to improve due to the advancement of innovative cardiovascular medical devices. In vitro and in silico models serve to replicate the in vivo environment for the development and testing of these devices prior to using animals for testing, and eventually humans in clinical trials. However, limitations related to these models exist in multiple areas including general, cardiac, and venous applications. Specifically, current gaps have been identified with customizable, tissue-mimicking phantoms (general), 2D Blood Speckle Imaging (BSI) (cardiac) and a bioprosthetic venous valve (venous). This dissertation focuses …

Tissue-Engineered Models For Investigating Nerve Infiltration In Fibrotic Microenvironments, Nikolas Ala-Kokko

Graduate Theses and Dissertations

Neuron infiltration is involved in a multitude of diseased states and is critical in the regeneration of physiologic conditions. Modeling of innervation in three-dimensional, heterogenous, environments would allow early investigation in the crosstalk of neurons and native cells in normal and pathophysiologic microenvironments to gain an understanding of mechanistic functions. This would allow for greater insight into the role of metabolism, cell adhesion, microenvironmental alternations, cellular crosstalk, and signaling pathways that play a role in the promotion and prevention of neurite growth. In this thesis, with the construction of collagen-based hydrogels as the foundation for cell culture, we investigate cell …

Deep Learning And Generative Ai Approaches For Automated Diagnosis And Personalized Treatment: Bridging Machine Learning, Medicine, And Biomechanics In Predicting Tissue Mechanics And Biomaterial Properties., Yasin Shokrollahi

Theses and Dissertations

Machine learning, particularly deep neural networks, has demonstrated significant potential in predicting high-dimensional tasks across various domains. This work encompasses a detailed review of Generative AI in healthcare and three studies integrating machine learning with finite element analysis for predicting biomechanical behaviors and properties. Initially, we provide a comprehensive overview of Generative AI applications in healthcare, focusing on Transformers and Denoising Diffusion models and suggesting potential research avenues to address existing challenges.

Subsequently, we addressed soccer-related ocular injuries by combining finite element analysis and machine learning to predict retinal mechanics following a soccer ball hit rapidly. The prediction errors are …

Characterizing Intervertebral Disc Strain Under Dynamic Loading Conditions Using Ultrasound Texture Analysis, Radhika Kulkarni

Discovery Undergraduate Interdisciplinary Research Internship

Herniated discs in the spine are a significant patient burden, with potential links to lower back and leg discomfort and a considerable impact on daily life. These discs, located between spinal vertebrae, are comprised of the annulus fibrosus (AF) and the nucleus pulposus (NP). Herniations happen when the NP protrudes through a full-thickness annular tear, possibly compressing spinal nerves. The mechanical factors underlying herniated discs are poorly understood, necessitating research into these mechanisms and accessible diagnostic techniques. Our study employs high-resolution ultrasound and texture correlation to quantify strain patterns in intervertebral discs during dynamic loading.

A motion segment from the …

Controlled Radiation Capsule For Precision And Rapid Cancer Treatment, Hoseon Lee, Zsolt Kollar, Bailey R. White, Junia Nguyen, David Roque, Sowjanya Palagani

Symposium of Student Scholars

This research aims to transform cancer treatment through the optimization of brachytherapy, with a focus on reducing treatment duration, setup complexities, and financial burdens, all while emphasizing patient safety. Patients living at a distance from radiation clinics, particularly those undergoing extended Low Dose Radiation brachytherapy, often struggle with the formidable financial challenges associated with securing nearby accommodations. In response to these issues, the research introduces a radiation capsule designed to condense the conventional six-month treatment period to approximately just one week, thereby significantly reducing the duration of required accommodations. This capsule is especially relevant considering the construction cost of $40 …

Deep Multi-Stage System For Liver And Lesions Segmentation Using Ct Images, Nermeen Elmenabawy, Mervat El-Seddek, Hossam El-Din Moustafa, Ahmed Elnakib

Mansoura Engineering Journal

Accurate tumor segmentation plays a pivotal role in cancer diagnosis and treatment planning. This study introduces an automated system for segmenting liver and tumors in CT images through a multi-stage process. Initial preprocessing improves image quality, followed by feature extraction using pretrained VGG16-Segnet and FCNAlexnet models. Outputs from both models are combined using a parallel fusion operation. Finally, pixel-wise classification designates pixels as liver, tumor, or background. Evaluation on the MICCAI'2017 LiTS database yielded a Dice coefficient of 95.3% for liver and 78.1% for tumors using 5-fold cross-validation. Comparative studies highlight the superior accuracy of our approach in liver and …

Occlusive Membranes For Guided Regeneration Of Inflamed Tissue Defects., Woojin Choi, Utkarsh Mangal, Jin-Young Park, Ji-Yeong Kim, Taesuk Jun, Ju Won Jung, Moonhyun Choi, Sungwon Jung, Milae Lee, Ji-Yeong Na, Du Yeol Ryu, Jin Man Kim, Jae-Sung Kwon, Won-Gun Koh, Sangmin Lee, Patrick T J Hwang, Kee-Joon Lee, Ui-Won Jung, Jae-Kook Cha, Sung-Hwan Choi, Jinkee Hong

Henry M. Rowan College of Engineering Departmental Research

Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration …

The Effects Of Engineering Summer Camps On Middle And High School Students’ Engineering Interest And Identity Formation: A Multi-Methods Study, Timothy Robinson, Adam Kirn, Jenny Amos, Indira Chatterjee

Journal of Pre-College Engineering Education Research (J-PEER)

This multi-methods study explores changes in engineering interest and identity of middle and high school students (n = 79) attending introductory-level engineering summer camps at a large western land grant university. Middle school is a critical time when student interest, identity, and subsequently career choice begin to emerge and hence it is important that at this age students are given accurate information about engineering majors in college and future career opportunities in engineering. Data were collected over a period of two years in six summer camps. Three separate populations of middle and high school students participated in the summer …

Real-Time Arrhythmia Detection Using Convolutional Neural Networks, Thong Vu, Tyler Petty, Kemal Yakut, Muhammad Usman, Wei Xue, Francis M. Haas, Robert A. Hirsh, Xinghui Zhao

Henry M. Rowan College of Engineering Departmental Research

Cardiovascular diseases, such as heart attack and congestive heart failure, are the leading cause of death both in the United States and worldwide. The current medical practice for diagnosing cardiovascular diseases is not suitable for long-term, out-of-hospital use. A key to long-term monitoring is the ability to detect abnormal cardiac rhythms, i.e., arrhythmia, in real-time. Most existing studies only focus on the accuracy of arrhythmia classification, instead of runtime performance of the workflow. In this paper, we present our work on supporting real-time arrhythmic detection using convolutional neural networks, which take images of electrocardiogram (ECG) segments as input, and classify …

Evolutionary Conservation And Times Of Action Of Heterochronic Genes, Maria Ivanova

Theses and Dissertations

The heterochronic pathway of C. elegans is the most well-characterized system to date for controlling the sequence and timing of developmental events. However, we still have critical unanswered questions to address. First, little is known about the evolution of the heterochronic pathway, and of developmental timing in general. To determine if the roles of major heterochronic genes are conserved, I made mutants in orthologs of these genes in C. briggsae, using CRISPR/Cas9. My studies revealed a significant drift in the roles of some of the genes, although all of them are still involved in the developmental timing regulation, and several …

Development Of Novel Biosensors For Direct Measurement Of Proteasome Activity In Intact Single Cells, Alireza Rahnama

LSU Doctoral Dissertations

Enzymes regulate nearly all cellular and biochemical processes governing cellular proliferation, metabolism, and migration. One example is the ubiquitin-proteasome system (UPS), a highly complex, tightly regulated pathway responsible for the recognition and degradation of misfolded or damaged proteins inside the cell. Protein degradation requires posttranslational addition of a polyubiquitin chain to target the protein to the proteasome for degradation which can be reversed by deubiquitinating enzymes (DUBs) which remove the chain. Dysregulation of the UPS is associated with many diseases including cancer which has resulted in the development of inhibitors, like Bortezomib and Carfilzomib, driving higher median patient survival rates …

Differential Impact Of Blood Pressure Control Targets On Epicardial Coronary Flow After Transcatheter Aortic Valve Replacement, Brennan Vogl, Alejandra Chavez-Ponce, Adam Wentworth, Eric Erie, Pradeep Yadav, Vinod H. Thourani, Lakshmi Prasad Dasi, Brian Lindman, Mohamad Alkhouli, Hoda Hatoum

Michigan Tech Publications

Background: The cause for the association between increased cardiovascular mortality rates and lower blood pressure (BP) after aortic valve replacement (AVR) is unclear. This study aims to assess how the epicardial coronary flow (ECF) after AVR varies as BP levels are changed in the presence of a right coronary lesion. Methods: The hemodynamics of a 3D printed aortic root model with a SAPIEN 3 26 deployed were evaluated in an in vitro left heart simulator under a range of varying systolic blood pressure (SBP) and diastolic blood pressure (DBP). ECF and the flow ratio index were calculated. Flow index value …

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 …

Integrative Transcriptomics And Proteomics Profiling Of Arabidopsis Thaliana Elucidates Novel Mechanisms Underlying Spaceflight Adaptation, Gbolaga O. Olanrewaju, Natasha J. Haveman, Michael J. Naldrett, Anna-Lisa Paul, Robert J. Ferl, Sarah E. Wyatt

Nebraska Center for Biotechnology: Faculty and Staff Publications

Spaceflight presents a unique environment with complex stressors, including microgravity and radiation, that can influence plant physiology at molecular levels. Combining transcriptomics and proteomics approaches, this research gives insights into the coordination of transcriptome and proteome in Arabidopsis’ molecular and physiological responses to Spaceflight environmental stress. Arabidopsis seedlings were germinated and grown in microgravity (μg) aboard the International Space Station (ISS) in NASA Biological Research in Canisters – Light Emitting Diode (BRIC LED) hardware, with the ground control established on Earth. At 10 days old, seedlings were frozen in RNA-later and returned to Earth. RNA-seq transcriptomics and TMTlabeled LC-MS/MS proteomic …

Computational Modeling Using A Novel Continuum Approach Coupled With Pathway-Informed Neural Networks To Optimize Dynein-Mediated Centrosome Positioning In Polarized Cells, Arkaprovo Ghosal, Padmanabhan Seshaiyar Dr., Adriana Dawes Dr., General Genomics Inc.

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Multicellular And Multiscale Models Of Microbes And Host Systems, Elebeoba May

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

A Multi-Organ Maize Metabolic Model Connects Temperature Stress With Energy Production And Reducing Power Generation, Niaz Bahar Chowdhury, Margaret Simons- Senftle, Berengere Decouard, Isabelle Quillere, Martine Rigault, Karuna Anna Sajeevan, Bibek Acharya, Ratul Chowdhury, Bertrand Hirel, Alia Dellagi, Costas Maranas, Rajib Saha

Department of Chemical and Biomolecular Engineering: Faculty Publications

Climate change has adversely affected maize productivity. Thereby, a holistic understanding of metabolic crosstalk among its organs is important to address this issue. Thus, we reconstructed the first multi-organ maize metabolicmodel, iZMA6517, and contextualized itwith heat and cold stress transcriptomics data using expression distributed reaction flux measurement (EXTREAM) algorithm. Furthermore, implementing metabolic bottleneck analysis on contextualized models revealed differences between these stresses. While both stresses had reducing power bottlenecks, heat stress had additional energy generation bottlenecks.We also performed thermodynamic driving force analysis, revealing thermodynamics-reducing power-energy generation axis dictating the nature of temperature stress responses. Thus, a temperaturetolerant maize ideotype can …