Biomedical Engineering and Bioengineering Commons^™

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Enabling Daily Tracking Of Individual’S Cognitive State With Eyewear, Soha Rostaminia

Doctoral Dissertations

Research studies show that sleep deprivation causes severe fatigue, impairs attention and decision making, and affects our emotional interpretation of events, which makes it a big threat to public safety, and mental and physical well-being. Hence, it would be most desired if we could continuously measure one’s drowsiness and fatigue level, their emotion while making decisions, and assess their sleep quality in order to provide personalized feedback or actionable behavioral suggestions to modulate sleep pattern and alertness levels with the aim of enhancing performance, well-being, and quality of life. While there have been decades of studies on wearable devices, we …

Unobtrusive Assessment Of Upper-Limb Motor Impairment Using Wearable Inertial Sensors, Brandon R. Oubre

Doctoral Dissertations

Many neurological diseases cause motor impairments that limit autonomy and reduce health-related quality of life. Upper-limb motor impairments, in particular, significantly hamper the performance of essential activities of daily living, such as eating, bathing, and changing clothing. Assessment of impairment is necessary for tracking disease progression, measuring the efficacy of interventions, and informing clinical decision making. Impairment is currently assessed by trained clinicians using semi-quantitative rating scales that are limited by their reliance on subjective, visual assessments. Furthermore, existing scales are often burdensome to administer and do not capture patients' motor performance in home and community settings, resulting in a …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Enhancing The Intracellular Availability Of Protein Cargoes In Polymer-Mediated Delivery, Christopher R. Hango

Doctoral Dissertations

Protein drugs, including antibodies, are rapidly emerging as the top-selling pharmaceuticals worldwide owing to their unparalleled specificity and biocompatibility. However, none of the currently-approved protein therapeutics act intracellularly, despite the vast majority of potential drug targets residing within the cell. This is due mainly to the paramount challenge of transporting hydrophilic macromolecular cargoes across the plasma membrane. As such, effective protein carriers are essential for the advancement of modern medicine. Despite significant advances, many challenges still plague protein delivery. Following membrane transduction, delivery vectors must preserve the structure and activity of their cargoes while transporting them to the correct subcellular …

Motor Control-Based Assessment Of Therapy Effects In Individuals Post-Stroke: Implications For Prediction Of Response And Subject-Specific Modifications, Ashley Rice

Doctoral Dissertations

Producing a coordinated motion such as walking is, at its root, the result of healthy communication pathways between the central nervous system and the musculoskeletal system. The central nervous system produces an electrical signal responsible for the excitation of a muscle, and the musculoskeletal system contains the necessary equipment for producing a movement-driving force to achieve a desired motion. Motor control refers to the ability an individual has to produce a desired motion, and the complexity of motor control is a mathematical concept stemming from how the electrical signals from the central nervous system translate to muscle activations. Exercising a …

Susceptibility Of Riverine Fishes To Anthropogenically-Linked Trauma: Strikes From Hydropower Turbine Blades, Ryan K. Saylor

Doctoral Dissertations

Hydropower accounts for nearly 40% of renewable electricity generation in the US; however, dams significantly impact the surrounding aquatic ecosystems. One of the most visible impacts of hydropower―beyond the dam itself―is the direct negative impacts (injury or death) to fish populations that must pass through hydropower turbines to access desired downstream habitat. During passage, fishes face many potential stressors that can cause severe injuries and often leads to high rates of mortality. In this dissertation, I have focused on quantifying how fishes respond to impacts from turbine blades that may occur during turbine passage. Laboratory research into blade strike impact …

Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta

Doctoral Dissertations

Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also …

Controlled Membrane Remodeling By Nanospheres And Nanorods: Experiments Targeting The Design Principles For Membrane-Based Materials, Sarah Zuraw-Weston

Doctoral Dissertations

In this thesis we explore two experimental systems probing the interactions of nanoparticles with lipid bilayer membranes. Inspired by the ability of cell membranes to alter their shape in response to bound particles, we report two experimental studies: one of nanospheres the other of long, slender nano-rods binding to lipid bilayer vesicles and altering the membrane shape. Our work illuminates the role of particle geometry, particle concentration, adhesion strength and membrane tension in how membrane morphology is determined. We combine giant unilamellar vesicles with oppositely charged nanoparticles, carefully tuning adhesion strength, membrane tension and particle concentration. In the case of …

Approaches To Studying Bacterial Biofilms In The Bioeconomy With Nanofabrication Techniques And Engineered Platforms., Michelle Caroline Halsted

Doctoral Dissertations

Studies that estimate more than 90% of bacteria subsist in a biofilm state to survive environmental stressors. These biofilms persist on man-made and natural surfaces, and examples of the rich biofilm diversity extends from the roots of bioenergy crops to electroactive biofilms in bioelectrochemical reactors. Efforts to optimize microbial systems in the bioeconomy will benefit from an improved fundamental understanding of bacterial biofilms. An understanding of these microbial systems shows promise to increase crop yields with precision agriculture (e.g. biosynthetic fertilizer, microbial pesticides, and soil remediation) and increase commodity production yields in bioreactors. Yet conventional laboratory methods investigate these micron-scale …

Deep Learning For Digitized Histology Image Analysis, Sudhir Sornapudi

Doctoral Dissertations

“Cervical cancer is the fourth most frequent cancer that affects women worldwide. Assessment of cervical intraepithelial neoplasia (CIN) through histopathology remains as the standard for absolute determination of cancer. The examination of tissue samples under a microscope requires considerable time and effort from expert pathologists. There is a need to design an automated tool to assist pathologists for digitized histology slide analysis. Pre-cervical cancer is generally determined by examining the CIN which is the growth of atypical cells from the basement membrane (bottom) to the top of the epithelium. It has four grades, including: Normal, CIN1, CIN2, and CIN3. In …

Applications Of Machine Learning In Nuclear Imaging And Radiation Detection, Shaikat Mahmood Galib

Doctoral Dissertations

"The main focus of this work is to use machine learning and data mining techniques to address some challenging problems that arise from nuclear data. Specifically, two problem areas are discussed: nuclear imaging and radiation detection. The techniques to approach these problems are primarily based on a variant of Artificial Neural Network (ANN) called Convolutional Neural Network (CNN), which is one of the most popular forms of 'deep learning' technique.

The first problem is about interpreting and analyzing 3D medical radiation images automatically. A method is developed to identify and quantify deformable image registration (DIR) errors from lung CT scans …

Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund

Doctoral Dissertations

The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of …

Design And Synthesis Of Analogs Of Myo-Inositol, Serine, And Cysteine To Enable Chemical Biology Studies, Tanei J. Ricks

Doctoral Dissertations

Phosphorylated myo-inositol compounds including inositol phosphates (InsPs) as well as the phosphatidylinositol polyphosphate lipids (PIP_ns) are critical biomolecules that regulate many of the most important biological processes and pathways. They are aberrant in many disease states due to their regulatory function. The same is true of the phospholipid phosphatidylserine (PS) which can serve as a marker to begin apoptosis. However, the full scope of activities of these structures is not clear, particularly since techniques that enable global detection and analysis of the production of these compounds spatially and temporally are lacking. With all of these obstacles in …

Analyses Of Densely Crosslinked Phenolic Systems Using Low Field Nmr, Jigneshkumar Patel

Doctoral Dissertations

A uniform dispersion of reactants is necessary to achieve a complete reaction involving multi-components, especially for the crosslinking of rigid high-performance materials. In these reactions, miscibility is crucial for curing efficiency. This miscibility is typically enhanced by adding a third component, a plasticizer. For the reaction of the highly crystalline crosslinking agent hexamethylenetetramine (HMTA) with a strongly hydrogen-bonded phenol formaldehyde resin, furfural has been traditionally used as the plasticizer. However, the reason for its effectiveness is not clear. In this doctoral thesis work, miscibility and crosslinking efficiency of plasticizers in phenolic curing reactions are studied by thermal analysis and spectroscopic …

Protein-Nanoparticle Co-Engineering: Self-Assembly, Intracellular Protein Delivery, And Crispr/Cas9-Based Gene Editing, Rubul Mout

Doctoral Dissertations

Direct cytoplasmic delivery of gene editing nucleases such CRISPR/Cas9 systems and therapeutic proteins provides enormous opportunities in curing human genetic diseases, and assist research in basic cell biology. One approach to attain such a goal is through engineering nanotechnological tools to mimic naturally existing intra- and extracellular protein delivery/transport systems. Nature builds transport systems for proteins and other biomolecules through evolution-derived sophisticated molecular engineering. Inspired by such natural assemblies, I employed molecular engineering approaches to fabricate self-assembled nanostructures to use as intracellular protein delivery tools. Briefly, proteins and gold nanoparticles were co-engineered to carry complementary electrostatic recognition elements. When these …

Understanding The Surface Fouling Mechanism Of Ultrananocrystalline Diamond Microelectrodes Using Microfluidics For Neurochemical Detection, An-Yi Chang

Doctoral Dissertations

Electrochemical methods are widely used for chronic neurochemical sensing, but thus far, the organic solution redox reactions fouled the electrodes' surface. It caused the reduction of sensitivity and the electrodes' lifetime.

Here, we present the boron-doped nanocrystalline diamond microelectrodes (BDUNCD) as the next generation electrode material for neurochemical sensor development. To aid in long-term chronic monitoring of neurochemicals, they have a wide window of electrochemical potential, extremely low background current, and excellent chemical inertness. The main research goal is to reduce the rate of electrode fouling due to the reaction by-products, and significantly extend their useful lifetime.

We systematically characterize …

Anxiolytic Effects Of Propranolol And Diphenoxylate On Mice And Automated Stretch-Attend Posture Analysis, Kevin Scott Holly

Doctoral Dissertations

The prevention of social anxiety, performance anxiety, and social phobia via the combination of two generic drugs, diphenoxylate HC1 (opioid) plus atropine sulfate (anticholinergic) and propranolol HCl (beta blocker) was evaluated in mice through behavioral studies. A patent published on a September 8, 2011 by Benjamin D. Holly, US 2011/0218215 Al, prompted the research. The drug combination of diphenoxylate and atropine plus propranolol could be an immediate treatment for patients suffering from acute phobic and social anxiety disorders. Demonstrating the anxiolytic effects of the treatment on mice would validate a mouse model for neuroscientist to be used to detect the …

Generalized Partial Directed Coherence And Centrality Measures In Brain Networks For Epileptogenic Focus Localization, Joshua Aaron Adkinson

Doctoral Dissertations

Accurate epileptogenic focus localization is required prior to surgical resection of brain tissue for treatment of patients with intractable temporal lobe epilepsy, a clinical need that is partially fulfilled to date through a subjective, and at times inconclusive, evaluation of the recorded electroencephalogram (EEG). Using brain connectivity analysis, patterns of causal interactions between brain regions were derived from multichannel EEG of 127 seizures in nine patients with focal, temporal lobe epilepsy (TLE). The statistically significant directed interactions in the reconstructed brain networks were estimated from three second intracranial multi-electrode EEG segments using the Generalized Partial Directed Coherence (GPDC) and validated …

Mutlifunctional Platforms For Gene And Drug Delivery For Cancer Therapy, Jeffery J. Ambrose Jr.

Doctoral Dissertations

The National Cancer Institute and the American Cancer Society estimate that 1.6 million new cancer incidences and over half a million cancer related deaths occur annually [1][2]. Cancer the second most common cause of death in the United States [1], [2]. Although the causes of cancer can vary depending on cell type, all or almost all instances of cancer arise from a mutation or from an abnormal activation of the cellular genes that control cell growth and mitosis [3].

Treatment of a given cancer type depends on the subtype, stage and progression of the cancer. Varieties of cancer therapy include …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …

Detecting, Segmenting And Tracking Bio-Medical Objects, Mingzhong Li

Doctoral Dissertations

"Studying the behavior patterns of biomedical objects helps scientists understand the underlying mechanisms. With computer vision techniques, automated monitoring can be implemented for efficient and effective analysis in biomedical studies. Promising applications have been carried out in various research topics, including insect group monitoring, malignant cell detection and segmentation, human organ segmentation and nano-particle tracking.

In general, applications of computer vision techniques in monitoring biomedical objects include the following stages: detection, segmentation and tracking. Challenges in each stage will potentially lead to unsatisfactory results of automated monitoring. These challenges include different foreground-background contrast, fast motion blur, clutter, object overlap and …

The Discovery And Study Of Fluvirucin B1 Polyketide Synthase, Tsung-Yi Lin

Doctoral Dissertations

Rapidly decreasing numbers of viable therapeutic leads in the pharmaceutical pipeline demand new, sustainable methods for improved drug discovery and development. Despite vast improvements in de novo drug design and target recognition, Nature remains the richest source of small molecule therapeutics. Among many natural products, polyketides are not only the most promising ones for developing new antibiotic leads, but also exhibit unusually high therapeutic value ranging from clinical use as anticancer, antiviral, and immunosuppressant drugs. Modular polyketide synthases (PKSs) are dedicated nano-machinery that can be manipulated to produce a structurally diverse library for drug discovery programs. The ability to manipulate …

Modeling And Control Of Nanoparticle Bloodstream Concentration For Cancer Therapies, Scarlett S. Bracey

Doctoral Dissertations

Currently, the most commonly used treatments for cancerous tumors (chemotherapy, radiation, etc.) have almost no method of monitoring the administration of the treatment for adverse effects in real time. Without any real time feedback or control, treatment becomes a "guess and check" method with no way of predicting the effects of the drugs based on the actual bioavailability to the patient's body. One particular drug may be effective for one patient, yet provide no benefit to another. Doctors and scientists do not routinely attempt to quantifiably explain this discrepancy. In this work, mathematical modeling and analysis techniques are joined together …

Femtosecond Laser Patterned Templates And Imprinted Polymer Structures, Deepak Rajput

Doctoral Dissertations

Femtosecond laser machining is a direct-write lithography technique by which user-defined patterns are efficiently and rapidly generated at the surface or within the bulk of transparent materials. When femtosecond laser machining is performed with tightly focused amplified pulses in single-pulse mode, transparent substrates like fused silica can be surface patterned with high aspect ratio (>10:1) and deep (>10 μm) nanoholes. The main objective behind this dissertation is to develop single-pulse amplified femtosecond laser machining into a novel technique for the production of fused silica templates with user-defined patterns made of high aspect ratio nanoholes. The size of the …

New Microarray Image Segmentation Using Segmentation Based Contours Method, Yuan Cheng

Doctoral Dissertations

The goal of the research developed in this dissertation is to develop a more accurate segmentation method for Affymetrix microarray images. The Affymetrix microarray biotechnologies have become increasingly important in the biomedical research field. Affymetrix microarray images are widely used in disease diagnostics and disease control. They are capable of monitoring the expression levels of thousands of genes simultaneously. Hence, scientists can get a deep understanding on genomic regulation, interaction and expression by using such tools.

We also introduce a novel Affymetrix microarray image simulation model and how the Affymetrix microarray image is simulated by using this model. This simulation …

Nonlinear Granger Causality And Its Application In Decoding Of Human Reaching Intentions, Mengting Liu

Doctoral Dissertations

Multi-electrode recording is a key technology that allows the brain mechanisms of decision making, cognition, and their breakdown in diseases to be studied from a network perspective. As the hypotheses concerning the role of neural interactions in cognitive paradigms become increasingly more elaborate, the ability to evaluate the direction of neural interactions in neural networks holds the key to distinguishing their functional significance.

Granger Causality (GC) is used to detect the directional influence of signals between multiple locations. To extract the nonlinear directional flow, GC was completed through a nonlinear predictive approach using radial basis functions (RBF). Furthermore, to obtain …

A Novel Microfluidic Enrichment Technique For Carbonylated Proteins, Bryant C. Hollins

Doctoral Dissertations

Proteins are the building blocks of cells in living organisms, and are composed of amino acids. The expression of proteins is regulated by the processes of transcription and translation. Proteins undergo post-translational modifications in order to dictate their role physiologically within a cell.

Not all post-translational modifications are beneficial for the protein or the cell. One type of post-translational modification, called carbonylation, irreversibly places a carbonyl group onto an amino acid residue, most commonly proline, lysine, arginine, and threonine. This modification can have severe consequences physiologically, including loss of solubility, loss of function, and protein aggregation.

Carbonylated proteins have commonly …

Development And Experimental Analysis Of Wireless High Accuracy Ultra-Wideband Localization Systems For Indoor Medical Applications, Michael Joseph Kuhn

Doctoral Dissertations

This dissertation addresses several interesting and relevant problems in the field of wireless technologies applied to medical applications and specifically problems related to ultra-wideband high accuracy localization for use in the operating room. This research is cross disciplinary in nature and fundamentally builds upon microwave engineering, software engineering, systems engineering, and biomedical engineering. A good portion of this work has been published in peer reviewed microwave engineering and biomedical engineering conferences and journals. Wireless technologies in medicine are discussed with focus on ultra-wideband positioning in orthopedic surgical navigation. Characterization of the operating room as a medium for ultra-wideband signal transmission …

Poly(Ethylenedioxythiophene) Based Electronic Devices For Sensor Applications, Jie Liu

Doctoral Dissertations

Organic electronic devices, based on Poly (3,4-ethylenedioxythiophene)-Poly (styrene sulfonic acid) (PEDOT-PSS) as the active layer for sensor applications, have been studied. Two sets of sensors have been developed. In one case, sensors consisting of PEDOT-PSS resistors have been realized and demonstrated for soil moisture monitoring. The resistor model for the soil moisture sensor enables the sensor device to be fabricated at low cost and easily tested with a simple structure. Unlike the large dimension device used in Time Domain Reflectometry (TDR), the sensors are small and are capable of capturing microscale behavior of moisture in soil which is useful for …