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Doctoral Dissertations

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Articles 1 - 19 of 19

Full-Text Articles in Biological Engineering

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian Oct 2022

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 …


Surface Enhanced Raman Spectroscopy (Sers) As An Approach For The Emerging Liquid Biopsy Diagnostics, Nariman Banaei Jun 2021

Surface Enhanced Raman Spectroscopy (Sers) As An Approach For The Emerging Liquid Biopsy Diagnostics, Nariman Banaei

Doctoral Dissertations

Large Molecule bioanalysis and biosensor development are essential techniques that are required in many applications, including biotherapeutic development, in vitro diagnostic, biomarker detection, and early detection. These techniques should be highly specific and sensitive enough to identify and quantify an analyte of interest with minimum sample pretreatment requirements. This work explores the development and application of chip-scale bioassays based on surface-enhanced Raman scattering (SERS). It introduces sensing techniques to quantify various disease biomarkers, specifically pancreatic cancer. Blood is the best source of information about our body's function. There are many biomarkers in the blood, and each biomarker's high expression level …


Non-Contact Techniques For Human Vital Sign Detection And Gait Analysis, Farnaz Foroughian May 2021

Non-Contact Techniques For Human Vital Sign Detection And Gait Analysis, Farnaz Foroughian

Doctoral Dissertations

Human vital signs including respiratory rate, heart rate, oxygen saturation, blood pressure, and body temperature are important physiological parameters that are used to track and monitor human health condition. Another important biological parameter of human health is human gait. Human vital sign detection and gait investigations have been attracted many scientists and practitioners in various fields such as sport medicine, geriatric medicine, bio-mechanic and bio-medical engineering and has many biological and medical applications such as diagnosis of health issues and abnormalities, elderly care and health monitoring, athlete performance analysis, and treatment of joint problems. Thoroughly tracking and understanding the normal …


Susceptibility Of Riverine Fishes To Anthropogenically-Linked Trauma: Strikes From Hydropower Turbine Blades, Ryan K. Saylor May 2021

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 …


Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma Dec 2020

Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma

Doctoral Dissertations

The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …


Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois Dec 2020

Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois

Doctoral Dissertations

Cancer is a significant global health concern; and traditional therapies, including chemotherapeutics, are often simultaneously toxic yet ineffective. There is a critical need to develop targeted cancer therapeutics which specifically inhibit molecules or molecular pathways essential for tumor growth and maintenance. Furthermore, a targeted therapy is only effective when a patient's tumor expresses the molecular target; therefore, companion diagnostics, including molecular imaging agents, are a necessary counterpart of targeted therapies. Mesothelin (MSLN) is a cell surface protein overexpressed in numerous cancers, including triple-negative breast, pancreatic, ovarian, liver, and lung, with limited expression in normal tissues. Aberrant MSLN expression promotes tumor …


Engineering Platforms For Advancing Plant Synthetic Biology, Tayler Marie Schimel Mcneillie Dec 2020

Engineering Platforms For Advancing Plant Synthetic Biology, Tayler Marie Schimel Mcneillie

Doctoral Dissertations

This work describes research aimed at adapting advanced engineering systems for plant biotechnology. The droplet interface bilayer (DIB) is a robust and versatile platform for replicating model cell membranes, providing a bottom-up approach for synthetic cell- and tissue-like structures. In this work, a microfluidic device featuring five inlets, one for the continuous oil phase and four discrete aqueous channels for droplet generation was designed. Droplet production rates were controlled by adjusting the applied pressure of each inlet; and thus, altering the droplet sequence for capturing linear DIB networks in a downstream hydrodynamic trapping array. This microfluidic system provides a high-throughput …


Building The Outer Membrane Protein G (Ompg) Nanopore Library: From The Discrimination Of Biotin-Binding Proteins In Serum To Resolving Human Carbonic Anhydrase From Human Red Blood Cells, Bib Yang Mar 2019

Building The Outer Membrane Protein G (Ompg) Nanopore Library: From The Discrimination Of Biotin-Binding Proteins In Serum To Resolving Human Carbonic Anhydrase From Human Red Blood Cells, Bib Yang

Doctoral Dissertations

The use of pore-forming proteins (PFPs) in nanopore sensing has been fruitful largely due to their nanoscale size and the ease with which protein nanopores can be manipulated and consistently reproduced at a large scale. Nanopore sensing relies heavily on a steady ionic current afforded by rigid nanopores, as the change in current is indicative of analyte detection, revealing characteristics of the analyte such as its relative size, concentration, and charge, as well as the nanopore:analyte interaction. Rigid PFPs have been used in applications such as DNA sequencing, kinetic studies, analyte discrimination, and protein conformation dynamics at the single-molecule level. …


Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz Nov 2018

Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz

Doctoral Dissertations

Breast cancer is plagued by two key clinical challenges; drug resistance and metastasis. Most work to date probes these events on an extremely rigid plastic surface, which recapitulates few aspects of these processes in humans. A malignant cell first resides in breast tissue, then likely travels to the bone, brain, liver, or lung, each of which has a distinct mechanical and biochemical profile. Cells transmit mechanical forces into intracellular tension and biochemical signaling events, and here we hypothesize that this mechanotransduction influences drug response, growth, and migration. To probe the impact of extracellular matrix on drug resistance, we defined a …


Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund Jul 2018

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 …


Managing Exoelectrogenic Microbial Community Development Through Bioprocess Control For Conversion Of Biomass-Derived Streams, Alex James Lewis Aug 2017

Managing Exoelectrogenic Microbial Community Development Through Bioprocess Control For Conversion Of Biomass-Derived Streams, Alex James Lewis

Doctoral Dissertations

Bioelectrochemical systems are an emerging technology capable of utilizing aqueous waste streams generated during biomass conversion of lignocellulosic feedstocks to produce valuable co-products and thus, have potential to be integrated into biorefineries. In a microbial electrolysis cell, organic compounds are converted to electrons, protons, and CO2 by fermentative and exoelectrogenic bacteria in the anode compartment. By having the ability to extract electrons from waste streams, these systems can treat water while also producing hydrogen, and thus can improve the efficiency of biomass to fuel production by minimizing external hydrogen requirement and enabling water recycle. The overall goal of this …


Characterization And Manipulation Of Lipid Self-Assembly To Construct Stable, Portable Synthetic Lipid Bilayers, Guru Anand Venkatesan May 2017

Characterization And Manipulation Of Lipid Self-Assembly To Construct Stable, Portable Synthetic Lipid Bilayers, Guru Anand Venkatesan

Doctoral Dissertations

The overarching goal of this research work is to further our understanding of lipid self-assembly and its organization at an oil-water interface to support the development of synthetic lipid bilayer systems that can be used in biologically relevant fields such as membrane biophysics, protein electrophysiology, development of synthetic biomolecules, drugs, nanoparticles and other applications. Self-assembly kinetics and interfacial properties of lipid monolayers formed at a liquid-air and liquid-liquid interface are characterized using Langmuir-Blodgett trough and pendant drop tensiometer. Insights gained from these studies not only allow us to answer questions related to droplet interface bilayer (DIB; a promising technique to …


Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney Nov 2016

Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney

Doctoral Dissertations

To metastasize, a cell must travel through circulation to a secondary tissue, and this process causes 90% of all cancer deaths. Although inefficient, metastasis is not random, and only capable seeds in hospitable soils are capable of outgrowing into detectable metastases. The overall hypothesis in this work is that the secondary tissue microenvironment, particularly the extracellular matrix (ECM), mediates metastasis. We posit that the ability of metastatic cells to survive dormancy, exit quiescence, and colonize a tissue depends upon the ability of the soil to sustain survival, and subsequently trigger outgrowth. We created a simple biomaterial platform with systematic control …


Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen Jul 2016

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …


In Silico Driven Metabolic Engineering Towards Enhancing Biofuel And Biochemical Production, Richard Adam Thompson May 2016

In Silico Driven Metabolic Engineering Towards Enhancing Biofuel And Biochemical Production, Richard Adam Thompson

Doctoral Dissertations

The development of a secure and sustainable energy economy is likely to require the production of fuels and commodity chemicals in a renewable manner. There has been renewed interest in biological commodity chemical production recently, in particular focusing on non-edible feedstocks. The fields of metabolic engineering and synthetic biology have arisen in the past 20 years to address the challenge of chemical production from biological feedstocks. Metabolic modeling is a powerful tool for studying the metabolism of an organism and predicting the effects of metabolic engineering strategies. Various techniques have been developed for modeling cellular metabolism, with the underlying principle …


Improving Droplet Interface Bilayers As Models For Cell Membranes, Graham Jeffery Taylor May 2016

Improving Droplet Interface Bilayers As Models For Cell Membranes, Graham Jeffery Taylor

Doctoral Dissertations

This work describes research aimed at improving the droplet interface bilayer (DIB) platform for creating and characterizing biologically relevant model cell membranes. Improvements are made possible in part through the development of a portable, compact platform for controlling temperature with DIBs. Feedback-controlled heating allows studies to be conducted across a range of temperatures, from ambient up to at least 80°C, and also provides new understanding of methods to form DIBs using mixtures of total lipids extracted from bacterial and eukaryotic cells. The membranes formed from total lipid extracts (TLE) are introduced along with evidence that model membranes formed using lipid …


The Discovery And Study Of Fluvirucin B1 Polyketide Synthase, Tsung-Yi Lin Nov 2014

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 …


Femtosecond Laser Patterned Templates And Imprinted Polymer Structures, Deepak Rajput May 2013

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 …


Modification And Evaluation Of Continuous Roll Prediction Model For Front Drive Mowers, Xinyan Wang Dec 2005

Modification And Evaluation Of Continuous Roll Prediction Model For Front Drive Mowers, Xinyan Wang

Doctoral Dissertations

The recently approved ASAE Standard S547 “Tip-Over Protective Structure (TOPS) for Front Wheel Drive Turf and Landscape Equipment” addressed a continuous roll prediction model for Roll-Over Protective Structure (ROPS) design. The existing model described in this Standard did not take into account the influence of the mower deck on the rollover behavior. In order to evaluate the accuracy of the original model, according to the ASAE S547 requirement, a 4.05 meters long and 3.42 meters wide slope of 35 degrees was constructed at the University of Tennessee. Lateral upset tests for Deere F925 front drive mower with regular and inverted …