Biomedical Engineering and Bioengineering Commons^™

Engineering A High-Throughput Screening Platform For Assessing Developmental Neurotoxicity Throughout Head- Regeneration In Schmidtea Mediterranea, Johnathan James Morris

Theses and Dissertations

The increase in commercially used chemicals that are inadequately evaluated for safety and risk to development has created a reticent threat to human health. Addressing these deficiencies is compounded by limited methodologies to determine the etiology of exposure-related developmental neurotoxicity (DNT). Current means of assessing DNT are largely retrospective and limited by the expensive, time-consuming, and labor-intensive use of laboratory animal models, thereby motivating a global research effort to produce alternative chemical screening assays. In this work, we have developed a novel high- throughput platform that serves as a new tool to evaluate the effects of exogenous chemical exposure on …

In Situ Imaging Of Bacterial Outer Membrane Projections And Associated Protein Complexes Using Electron Cryo-Tomography, Mohammed Kaplan, Georges Chreifi, Lauren Ann Metskas, Janine Liedtke, Cecily R. Wood, Catherine M. Oikonomou, William J. Nicolas, Poorna Subramanian, Lori A. Zacharoff, Yuhang Wang, Yi-Wei Chang, Morgan Beeby, Megan J. Dobro, Yongtao Zhu, Mark J. Mcbride, Ariane Briegel, Carrie L. Shaffer, Grant J. Jensen

Veterinary Science Faculty Publications

The ability to produce outer membrane projections in the form of tubular membrane extensions (MEs) and membrane vesicles (MVs) is a widespread phenomenon among diderm bacteria. Despite this, our knowledge of the ultrastructure of these extensions and their associated protein complexes remains limited. Here, we surveyed the ultrastructure and formation of MEs and MVs, and their associated protein complexes, in tens of thousands of electron cryo-tomograms of ~90 bacterial species that we have collected for various projects over the past 15 years (Jensen lab database), in addition to data generated in the Briegel lab. We identified outer MEs and MVs …

Comparative Evaluation Of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using A Sheep Model, Leyla Hasandoost, Daniella Marx, Paul Zalzal, Oleg Safir, Mark Hurtig, Cina Mehrvar, Stephen D. Waldman, Marcello Papini, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO₂-CaO-SrO-P₂O₅-Ta₂O₅, were investigated. Working and setting times, pH, ion release, …

High Shear Stress Enhances Endothelial Permeability In The Presence Of The Risk Haplotype At 9p21.3, Evan L. Tang, Evan M. Masutami, Benjamin Yeoman, Jessica Fung, Rachel Lian, Brenda Ngo, Aditya Kumar, Jesse K. Placone, Valentina Lo Sardo, Adam J. Engler

Physics & Engineering Faculty Publications

Single nucleotide polymorphisms (SNPs) are exceedingly common in non-coding loci, and while they are significantly associated with a myriad of diseases, their specific impact on cellular dysfunction remains unclear. Here, we show that when exposed to external stressors, the presence of risk SNPs in the 9p21.3 coronary artery disease (CAD) risk locus increases endothelial monolayer and microvessel dysfunction. Endothelial cells (ECs) derived from induced pluripotent stem cells of patients carrying the risk haplotype (R/R WT) differentiated similarly to their non-risk and isogenic knockout (R/R KO) counterparts. Monolayers exhibited greater permeability and reactive oxygen species signaling when the risk haplotype was …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Tools And Strategies For The Patterning Of Bioactive Molecules And Macromolecules, Daniel J. Valles

Dissertations, Theses, and Capstone Projects

Hypersurface Photolithography (HP) is a printing method for fabricating structures and patterns composed of soft materials bound to solid surfaces and with ~1 micrometer resolution in the x, y, and z dimensions. This platform leverages benign, low intensity light to perform photochemical surface reactions with spatial and temporal control of irradiation, and, as a result, is particularly useful for patterning delicate organic and biological material. In particular, surface- initiated controlled radical polymerizations can be leveraged to create arbitrary polymer and block- copolymer brush patterns. Chapter 1 will review the advances in instrumentation architectures from our group that have made these …

Biological Resurfacing In A Canine Model Of Hip Osteoarthritis, Bradley T. Estes, Masataka Enomoto, Franklin T. Moutos, Megan A. Carson, Jeffrey M. Toth, Peter Eggert, Jonathan Stallrich, Vincent P. Willard, Deborah J. Veis, Dianne Little, Farshid Guilak, B. Duncan X. Lascelles

Biomedical Engineering Faculty Research and Publications

Articular cartilage has unique load-bearing properties but has minimal capacity for intrinsic repair. Here, we used three-dimensional weaving, additive manufacturing, and autologous mesenchymal stem cells to create a tissue-engineered, bicomponent implant to restore hip function in a canine hip osteoarthritis model. This resorbable implant was specifically designed to function mechanically from the time of repair and to biologically integrate with native tissues for long-term restoration. A massive osteochondral lesion was created in the hip of skeletally mature hounds and repaired with the implant or left empty (control). Longitudinal outcome measures over 6 months demonstrated that the implant dogs returned to …

Comparison Of Whole-Head Functional Near-Infrared Spectroscopy With Functional Magnetic Resonance Imaging And Potential Application In Pediatric Neurology, Julie C. Wagner, Anthony Zinos, Wei-Liang Chen, Lisa Conant, Marsha Malloy, Joseph Heffernan, Brendan Quirk, Jeffrey Sugar, Robert W. Prost, Julian B. Whelan, Scott A. Beardsley, Harry T. Whelan

Biomedical Engineering Faculty Research and Publications

Background

Changes in cerebral blood flow in response to neuronal activation can be measured by time-dependent fluctuations in hemoglobin species within the brain; this is the basis of functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS). There is a clinical need for portable neural imaging systems, such as fNIRS, to accommodate patients who are unable to tolerate an MR environment.

Objective

Our objective was to compare task-related full-head fNIRS and fMRI signals across cortical regions.

Methods

Eighteen healthy adults completed a same-day fNIRS-fMRI study, in which they performed right- and left-hand finger tapping tasks and a semantic-decision tones-decision …

Cell-Permeable Succinate Increases Mitochondrial Membrane Potential And Glycolysis In Leigh Syndrome Patient Fibroblasts, Ajibola B. Bakare, Raj R. Rao, Shilpa Iyer

Biomedical Engineering Faculty Publications and Presentations

Mitochondrial disorders represent a large group of severe genetic disorders mainly impacting organ systems with high energy requirements. Leigh syndrome (LS) is a classic example of a mitochondrial disorder resulting from pathogenic mutations that disrupt oxidative phosphorylation capacities. Currently, evidence-based therapy directed towards treating LS is sparse. Recently, the cell-permeant substrates responsible for regulating the electron transport chain have gained attention as therapeutic agents for mitochondrial diseases. We explored the therapeutic effects of introducing tricarboxylic acid cycle (TCA) intermediate substrate, succinate, as a cell-permeable prodrug NV118, to alleviate some of the mitochondrial dysfunction in LS. The results suggest that a …

Gradient Free Sign Activation Zero One Loss Neural Networks For Adversarially Robust Classification, Yunzhe Xue

Dissertations

The zero-one loss function is less sensitive to outliers than convex surrogate losses such as hinge and cross-entropy. However, as a non-convex function, it has a large number of local minima, andits undifferentiable attribute makes it impossible to use backpropagation, a method widely used in training current state-of-the-art neural networks. When zero-one loss is applied to deep neural networks, the entire training process becomes challenging. On the other hand, a massive non-unique solution probably also brings different decision boundaries when optimizing zero-one loss, making it possible to fight against transferable adversarial examples, which is a common weakness in deep learning …

Towards Adversarial Robustness With 01 Lossmodels, And Novel Convolutional Neural Netsystems For Ultrasound Images, Meiyan Xie

Dissertations

This dissertation investigates adversarial robustness with 01 loss models and a novel convolutional neural net systems for vascular ultrasound images.

In the first part, the dissertation presents stochastic coordinate descent for 01 loss and its sensitivity to adversarial attacks. The study here suggests that 01 loss may be more resilient to adversarial attacks than the hinge loss and further work is required.

In the second part, this dissertation proposes sign activation network with a novel gradient-free stochastic coordinate descent algorithm and its ensembling model. The study here finds that the ensembling model gives a high minimum distortion (as measured by …

Towards Understanding The Role Of Central Processing In Release From Masking, Nima Alamatsaz

Dissertations

People with normal hearing have the ability to listen to a desired target sound while filtering out unwanted sounds in the background. However, most patients with hearing impairment struggle in noisy environments, a perceptual deficit which current hearing aids and cochlear implants cannot resolve. Even though peripheral dysfunction of the ears undoubtedly contribute to this deficit, surmounting evidence has implicated central processing in the inability to detect sounds in background noise. Therefore, it is essential to better understand the underlying neural mechanisms by which target sounds are dissociated from competing maskers. This research focuses on two phenomena that help suppress …

Temporal Evolution Of Structure And Function In The Periphery And Central Auditory Systems With Mild Blast Induced Tinnitus In Rat Animal Models, Ningning Shao

Dissertations

Exposure to blast causes debilitating trauma including tinnitus among soldiers and civilians (Cave et al., 2007; Remenschneider et al., 2014; Singh et al., 2016). Tinnitus is a constant ringing noise perception without external acoustic event; it affects sleep, concentration, behavior, leading to suicidal tendencies (Swan et al., 2017). Though blast induced tinnitus has been studied, structural and functional dysfunctions along auditory systems have not been systematically studied. It was hypothesized in this work that blast causes tinnitus even while the ears are mechanically protected, and the damage occurred in both central and peripheral auditory systems, which contributed to increased anxiety …

Drug Releasing Hydrogels For Opioid Use Disorder, Kaytlyn M. Crowe

Theses

Ease of access to prescription opioids and the strength of synthetic opioids have contributed to the rise in over use disorders, overdose, and death rates during the opioid epidemic. The current overdose standard of care, rescue NLX (NLX), is a competitive antagonist to the μ-opioid receptor but has a relatively short period of action compared to opioid agonists, especially synthetic agonists. Rises in the abuse of these synthetic and semi-synthetic agents in recent years have shown the weaknesses of rescue NLX, as it can leave overdose patients vulnerable to renarcotization and precipitated withdrawal. To prevent both from occurring, we developed …

Alcohol As A Catalyst For Hiv-Associated Neuroinflammation And Tbi-Induced Iron Toxicity, Agnieszka Agas

Dissertations

Alcohol has long been considered an exacerbator of diseases, disorders, and injuries as well as many of the accompanying symptoms. As an alternative approach, this dissertation explores alcohol as a catalyst for two different human disease conditions, human immunodeficiency virus (HIV)-associated neuroinflammation and traumatic brain injury (TBI)-induced iron toxicity. In HIV-1 infection, this dissertation presents a novel anti-viral drug, called Drug-S, for a possible inhibition and treatment of HIV-1 disease progression.

The first aim explores the influence of alcohol with HIV-associated neuroinflammation on macrophage migration across an in vitro model of the blood brain barrier. There is a gap in …

Silk-Cellulose Acetate Biocomposite Materials Regenerated From Ionic Liquid, Ashley Rivera-Galetti, Chrtstopher R. Gough, Farhan Kaleem, Michael Burch, Chris Ratcliffe, Ping Lu, David Salas-De La Cruz, Xiao Hu

College of Science & Mathematics Departmental Research

The novel use of ionic liquid as a solvent for biodegradable and natural organic biomaterials has increasingly sparked interest in the biomedical field. As compared to more volatile traditional solvents that rapidly degrade the protein molecular weight, the capability of polysaccharides and proteins to dissolve seamlessly in ionic liquid and form fine and tunable biomaterials after regeneration is the key interest of this study. Here, a blended system consisting of Bombyx Mori silk fibroin protein and a cellulose derivative, cellulose acetate (CA), in the ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIMAc) was regenerated and underwent characterization to understand the structure and physical …

A Computational Model For Calcium Signaling In Osteocyte Cell Cultures Under Mechanical Stimulation, Courtney Rose Ogando

Theses - ALL

Bone is a highly complex and organized tissue that is composed of an abundance of cells including the osteocyte. While it is known that osteocytes are responsible for the control of the bone remodeling process and the maintenance of calcium (Ca2+) homeostasis using their network of gap junction connections, their complete role is not yet fully understood. It is also known that various bone related diseases as well as cancer demonstrate an alteration of Ca2+ homeostasis during the progression of the disease. Previous researchers have combined computational modeling with experimental studies to gain a better understanding of cell-to-cell Ca2+ signaling …

Blood–Brain Barrier Breakdown And Astrocyte Reactivity Evident In The Absence Of Behavioral Changes After Repeated Traumatic Brain Injury, Celeste Dunn, Nasya Sturdivant, Sara Venier, Syed Ali, Jeffery Wolchok, Kartik Balachandran

Biomedical Engineering Faculty Publications and Presentations

Repeated traumatic brain injuries (TBIs) cause debilitating effects. Without understanding the acute effects of repeated TBIs, treatment options to halt further degeneration and damage cannot be developed. This study sought to examine the acute effects of blood–brain barrier (BBB) dysfunction, edema, inflammation and behavioral changes after either a single or double TBI using a C57BL/6 mouse model. We examined the effects of one or two TBIs, of either a mild or moderate severity. Double injuries were spaced 7 days apart, and all analysis was performed 24 h post-injury. To examine edema and inflammation, protein levels of glial fibrillary acidic protein …

Cfd Analysis Of Subcutaneous Deposition And Dispersion Of Insulin In Adipose Tissue, Ryan C. Lubbers

Masters Theses

Drug delivery is the most important factor of many therapies, but a lack of technology and research have led to a very generalized understanding of drug kinetics. Insulin pump therapy for the treatment of Type 1 Diabetes depends on precise delivery of the hormone into the adipose region between the dermis and underlying muscle. The kinetics of insulin within the adipose tissue environment is not well understood and varies greatly case to case. The use of computation fluid dynamics (CFD) models to study insulin kinetics in relation to influential factors will lead to a better understanding of the characteristics of …

The Effect Of Severe Intraventricular Hemorrhage On The Biorhythms Of Feeding In Premature Infants, Ira H. Gewolb, Babatunde T. Sobowale, Frank L. Vice, Abhijit R. Patwardhan, Nino Solomonia, Eric W. Reynolds

Biomedical Engineering Faculty Publications

Background: Suck-swallow rhythmicity and the integration of breathing into infant feeding are developmentally regulated. Neurological injury and breathing abnormalities can both impact feeding in preterm infants.

Objective: To determine the effects of neurologic injury independent of effects of disordered breathing on feeding biorhythms in premature infants.

Methods: Low-risk preterm infants (LRP), infants with Grade 3–4 Intraventricular Hemorrhage (IVH), those with bronchopulmonary dysplasia (BPD), and those with both BPD and IVH (BPD+IVH) were identified. Forty-seven infants, 32–42 weeks Postmenstrual Age (PMA) were evaluated on one or more occasions (131 studies). Of these, 39 infants (81 studies) were performed at >35 weeks …