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Comparison Of The Bi-Directional Performance Of Micro-Channel Sieve And Thin-Film Time Peripheral Nerve Interfaces, Robert Coker

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sophisticated motorized prosthetic limbs contain multiple degrees of freedom of motion as well as embedded pressure and angle transducers to provide sensory feedback in amputees. Although several central neural recording and stimulation modalities exist for both controlling these motions and providing sensory feedback from a prosthetic limb, directly interfacing the peripheral nerves which originally innervated the limb has many advantages. A difficulty with this bi-directional approach is that electrically stimulating axons to provide haptic feedback creates stimulation artifacts at neighboring recording sites within the nerve that are several orders of magnitude larger than the electroneurogram used for control. In this …

Locality-Aware Concurrency Platforms, Jordyn Chrystopher Raymond Maglalang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Modern computing systems from all domains are becoming increasingly more parallel. Manufacturers are taking advantage of the increasing number of available transistors by packaging more and more computing resources together on a single chip or within a single system. These platforms generally contain many levels of private and shared caches in addition to physically distributed main memory. Therefore, some memory is more expensive to access than other and high-performance software must consider memory locality as one of the first level considerations.

Memory locality is often difficult for application developers to consider directly, however, since many of these NUMA affects are …

Accurate Determination And Application Of Local Strain For Studying Tissues With Gradients In Mechanical Properties, John Boyle

McKelvey School of Engineering Graduate Student Theses & Dissertations

Determination of the mechanical behavior of materials requires an understanding of deformation during loading. While this is traditionally accomplished in engineering by examining a force displacement curve for a whole sample, these techniques implicitly ignore local geometric complexities and local material inhomogeneities commonly found in biologic tissues. Techniques such as normalized cross correlation have been classically applied to address this issue and resolve deformation at the local level; however, these techniques have proven unreliable when deformations become large, if the sample undergoes a rotation, and/or if strain fields become incompatible (e.g. at or near failure).

Presented here is a toolbox …

Coupling Of Oxidation-Reduction Reactions Of Chromium, Iron And Manganese: Implications For The Fate And Mobility Of Chromium In Aquatic Environments, Chao Pan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Both within the United States and internationally, hexavalent chromium (Cr(VI)) is a contaminant of concern in drinking water supplies. The U.S. Environmental Protection Agency is considering a Cr(VI)-specific standard. Thus improved technologies for Cr(VI) removal in drinking water are needed. Iron electrocoagulation for Cr(VI) removal was examined at conditions directly relevant to drinking water treatment, and humic acid (HA) affects the performance of electrocoagulation in multiple ways. The success of the chromium treatment or remediation also relies on the stability of the Cr(III)-containing solids with respect to reoxidation under groundwater conditions. Manganese is ubiquitous in aquatic and terrestrial environments, and …

Multiscale Imaging Of The Mouse Cortex Using Two-Photon Microscopy And Wide-Field Illumination, Jonathan Richard Bumstead

McKelvey School of Engineering Graduate Student Theses & Dissertations

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing …

Two-Component Hydrogel As Biomimetic Vitreous Substitutes, Sruthi Santhanam

McKelvey School of Engineering Graduate Student Theses & Dissertations

The vitreous humor of the eye is a biological hydrogel principally composed of fibrillary collagen interspersed with semi-flexible polyelectrolyte, hyaluronic acid (HA). Certain pathological conditions necessitate its removal and replacement. Current vitreous substitutes, such as silicone oils and perfluorocarbons, are hydrophobic, do not resemble the properties of the vitreous, and have known complications. An ideal vitreous substitute should have properties of the natural vitreous, perform its functions, and be biocompatible in the eye. Inspired by the structure and composition of the natural vitreous, we used bio-mimicry to develop an injectable two-component hydrogel. The hydrogel is composed of a fibrillary gellan, …

Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.

First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for …

A Generalized Biophysical Model Of Transcription Factor Binding Specificity And Its Application On High-Throughput Selex Data, Shuxiang Ruan

Arts & Sciences Graduate Student Theses and Dissertations

The interaction between transcription factors (TFs) and DNA plays an important role in gene expression regulation. In the past, experiments on protein–DNA interactions could only identify a handful of sequences that a TF binds with high affinities. In recent years, several high-throughput experimental techniques, such as high-throughput SELEX (HT-SELEX), protein-binding microarrays (PBMs) and ChIP-seq, have been developed to estimate the relative binding affinities of large numbers of DNA sequences both in vitro and in vivo. The large volume of data generated by these techniques proved to be a challenge and prompted the development of novel motif discovery algorithms. These algorithms …

Influenza A Virus Genomic Reassortment And Packaging, Graham Devin Williams

Arts & Sciences Graduate Student Theses and Dissertations

Influenza A viruses (IAV) are a major human and environmental pathogen. IAV successfully infects a diverse host range and adaptation of new viral strains to humans may cause pandemic events with high morbidity and mortality. As a member of the Orthomyxoviridae family, IAV inherently possesses a segmented genome, which enables a process of segment transmission between viruses following cellular co-infection, a process termed reassortment. The high rate of IAV mutation and continued co-circulation of diverse viral strains in divergent host species leads to the persistent prospect for emergence of new IAV with pandemic potential. Therefore, it is of great importance …

Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell

Arts & Sciences Graduate Student Theses and Dissertations

Regulation of gene expression is essential to life. Post-transcriptional regulation of gene expression is a complex process with many inputs that lead to changes in localization, translation and stability of mRNAs. The translation and stability of many mRNAs is regulated by cis-elements, such as mRNA-structure or codon optimality; and by trans-acting factors such as RBPs and miRNAs. Here I report on the complex interactions between RBPs, miRNAs and characteristics of their target mRNAs in respect to effects on translation and RNA stability.Using a reporter based approach we studied modulation of microRNA-mediated repression by various mRNA characteristics. We observed the influence …

Longitudinal Cerebrospinal Fluid Biomarkers Of Alzheimer Disease: Movement Toward The Diagnosis, Prognosis And Staging Of Disease, Courtney Sutphen

Arts & Sciences Graduate Student Theses and Dissertations

Alzheimer’s disease (AD) is a devastating neurodegenerative disease that slowly claims the memories and experiences that comprise the life experiences of individuals that suffer from the disease. Despite a continually accelerating pace of research and discovery, a viable therapeutic intervention for AD has yet to be realized. There are a multitude of factors that may contribute to this difficulty including the challenge of separating the overall disease of Alzheimer’s from the clinically recognizable memory loss that occurs in what is now known to be the end-stage of the disease. Efforts to treat AD have increasingly turned toward very early disease …

Fast Monte Carlo Simulations For Quality Assurance In Radiation Therapy, Yuhe Wang

Arts & Sciences Graduate Student Theses and Dissertations

Monte Carlo (MC) simulation is generally considered to be the most accurate method for dose calculation in radiation therapy. However, it suffers from the low simulation efficiency (hours to days) and complex configuration, which impede its applications in clinical studies. The recent rise of MRI-guided radiation platform (e.g. ViewRay’s MRIdian system) brings urgent need of fast MC algorithms because the introduced strong magnetic field may cause big errors to other algorithms. My dissertation focuses on resolving the conflict between accuracy and efficiency of MC simulations through 4 different approaches: (1) GPU parallel computation, (2) Transport mechanism simplification, (3) Variance reduction, …

The Chemistry And Biology Of Iron-Scavenging Natural Products From Pathogenic Acinetobacter Baumannii, Justin Shapiro

Arts & Sciences Graduate Student Theses and Dissertations

Multidrug resistant (MDR) Gram-negative bacteria represent a global health crisis. Traditional antibiotics create selective pressure and breed resistance, making our current drugs less and less effective. Targeting of bacterial virulence factors has gained interest as an alternative strategy to potentially circumvent this problem. Virulent Acinetobacter baumannii synthesize and secrete pre-acinetobactin, a small molecule metal chelator that scavenges life-sustaining iron and is critical for establishing infection. The work described herein sheds light on the unusual properties of a non-enzymatic isomerization from pre-acinetobactin to acinetobactin and proposes a siderophore-swapping mechanism by which A. baumannii expands its pH window for virulence. Knowledge from …

Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur

Arts & Sciences Graduate Student Theses and Dissertations

Regulation of gene expression is essential for cellular development and survival. The great variety and complexity of regulatory mechanisms underscores this fact. Messenger RNA stability and translational efficiency are often key determinants of gene expression. mRNA surveillance pathways, discovered for their role in degradation of aberrant mRNA, are now known to be instrumental in the regulation of physiologically correct mRNA stability. Thus, the study of cis elements in a transcript that can induce mRNA surveillance pathways has become an area of particular interest.Here I report on the mechanism of gene regulation by coding polyA tracks, defined as a sequence of …

Structured Illumination Diffuse Optical Tomography For Mouse Brain Imaging, Matthew Reisman

Arts & Sciences Graduate Student Theses and Dissertations

As advances in functional magnetic resonance imaging (fMRI) have transformed the study of human brain function, they have also widened the divide between standard research techniques used in humans and those used in mice, where high quality images are difficult to obtain using fMRI given the small volume of the mouse brain. Optical imaging techniques have been developed to study mouse brain networks, which are highly valuable given the ability to study brain disease treatments or development in a controlled environment. A planar imaging technique known as optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional …

Investigation Of Neonatal Pulmonary Structure And Function Via Proton And Hyperpolarized Gas Magnetic Resonance Imaging, Nara Savoye Higano

Arts & Sciences Graduate Student Theses and Dissertations

Magnetic resonance imaging (MRI) is a modality that utilizes the phenomenon of nuclear magnetic resonance (NMR) to yield tomographic images of the body. Proton (1H) MRI has historically been successful in soft tissues but has suffered in the lung due to a variety of technical challenges, such as the low proton-density, rapid T2* relaxation time of the lung parenchymal tissue, and inherent physiological motion in the chest. Recent developments in radial ultrashort echo time (UTE) MRI have in part overcome these issues. In addition, there has been much progress in techniques for hyperpolarization of noble gases (3He and 129Xe) out …

The Nets Of Style: Shaping Modernist Literary Narrative, Kelly Lynn Oman

Arts & Sciences Graduate Student Theses and Dissertations

Literary modernism is often defined by a stylistic distinctiveness generated by experiments in subject and form. Given that these experiments necessarily break with convention, how are we to make sense of this style without those conventions to guide us? In “The Nets of Style: Shaping Modernist Literary Narrative,” I reveal how critical definitions of modernist style often rely on the individualist poses struck and critical pronouncements made by modernists themselves. My research is situated in a body of work in modernist studies that argue, as Paul Sheehan does in Modernism and the Aesthetics of Violence, that “modernism seeks to transform …

Roles Of Peroxisomes And Peroxisome-Derived Products In Controlling Plant Growth And Stress Responses, Elizabeth May Frick

Arts & Sciences Graduate Student Theses and Dissertations

The peroxisome is a vital organelle conserved through the entire eukaryotic lineage. In all examined species, peroxisomes are responsible for such essential processes as fatty acid beta-oxidation and metabolism of reactive oxygen species (ROS). In plants, peroxisomes have taken on additional specialized roles, such as production of some plant hormones and vitamins. In this work, I have uncovered novel factors regulating peroxisome number in model species Arabidopsis thaliana, and novel mechanisms governing how peroxisomes respond to salt stress. I discovered a role for Arabidopsis MAP KINASE17 (MPK17) as a negative regulator of peroxisome division that acts in the salt-stress response …

Understanding The Paradox Of Genetic Diversity In Uropathogenic E. Coli: The Uncommon Evolution Of A Common Pathogen, Henry Louis Schreiber

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are the second most common bacterial infection of people in the U.S.A and are frequently recurrent, as an initial UTI is quickly followed by a second episode in 30-35% of cases despite appropriate antibiotic treatment and clearance of the bacteria from the urine. The vast majority, >80%, of UTIs are caused by uropathogenic Escherichia coli (UPEC). UPEC that colonize the bladder are thought to originate in the gut, where they live as commensal organisms. UPEC can be shed in feces to colonize the vagina and/or periurethral area, and then can ascend into the bladder to start …

Analysis Of Argonaute-Small Rna-Transcription Factor Circuits Controlling Leaf Development, John Steen Hoyer

Arts & Sciences Graduate Student Theses and Dissertations

Experimental studies of plant development have yielded many insights into gene regulation, revealing interactions between core transcriptional and post-transcriptional regulatory pathways present in all land plants. This work describes a direct connection between the three main small RNA-transcription factor circuits controlling leaf shape dynamics in the reference plant Arabidopsis thaliana. We used a high-throughput yeast 1-hybrid platform to identify factors directly binding the promoter of the highly specialized ARGONAUTE7 silencing factor. Two groups of developmentally significant microRNA-targeted transcription factors were the clearest hits from these screens, but transgenic complementation analysis indicated that their binding sites make only a small contribution …

Functional Bio-Nano Hybrids Through A Precise Control Of Interfacial Interactions At The Nanoscale, Sirimuvva Tadepalli

McKelvey School of Engineering Graduate Student Theses & Dissertations

During the course of evolution, proteins have evolved to perform exquisite functions including structural support, signal transduction, actuation, sensing, catalysis, trafficking, gating, light-harvesting, charge transfer, molecular recognition, self-assembly, self-organization, or combinations of two or more of these functions. A precise control and manipulation of the structure and function of proteins is conceivable with the advent of nanotechnology, which has facilitated the integration of nanomaterials with functional biomolecules to realize bio-nano hybrids with synergistically enhanced functionalities.

At the genesis of bionanotechnology, a paucity in the fundamental understanding of the bio-nano interfaces is a grave impediment to the progress of the field. …

Bio-Inspired Multi-Spectral And Polarization Imaging Sensors For Image-Guided Surgery, Nimrod Missael Garcia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Image-guided surgery (IGS) can enhance cancer treatment by decreasing, and ideally eliminating, positive tumor margins and iatrogenic damage to healthy tissue. Current state-of-the-art near-infrared fluorescence imaging systems are bulky, costly, lack sensitivity under surgical illumination, and lack co-registration accuracy between multimodal images. As a result, an overwhelming majority of physicians still rely on their unaided eyes and palpation as the primary sensing modalities to distinguish cancerous from healthy tissue. In my thesis, I have addressed these challenges in IGC by mimicking the visual systems of several animals to construct low power, compact and highly sensitive multi-spectral and color-polarization sensors. I …

Image Reconstruction Of The Speed Of Sound And Initial Pressure Distributions In Ultrasound Computed Tomography And Photoacoustic Computed Tomography, Thomas Paul Matthews

McKelvey School of Engineering Graduate Student Theses & Dissertations

Ultrasound computed tomography (USCT) and photoacoustic computed tomography (PACT) are two emerging imaging modalities that have a wide range of potential applications from pre-clinical small animal imaging to cancer screening in human subjects. USCT is typically employed to measure acoustic contrasts, including the speed of sound (SOS) distribution, while PACT typically measures optical contrasts or some related quantity such as the initial pressure distribution. Their complementary contrasts and similar implementations make USCT and PACT a natural fit for a hybrid imaging system. Still, much work remains to realize this promise. First, USCT image reconstruction methods based on the acoustic wave …

Reconstruction Algorithms For Novel Joint Imaging Techniques In Pet, Homayoon Ranjbar

McKelvey School of Engineering Graduate Student Theses & Dissertations

Positron emission tomography (PET) is an important functional in vivo imaging modality with many clinical applications. Its enormously wide range of applications has made both research and industry combine it with other imaging modalities such as X-ray computed tomography (CT) or magnetic resonance imaging (MRI). The general purpose of this work is to study two cases in PET where the goal is to perform image reconstruction jointly on two data types.

The first case is the Beta-Gamma image reconstruction. Positron emitting isotopes, such as ¹¹C, ¹³N, and ¹⁸F, can be used to label molecules, and tracers, such …

System Optimization And Iterative Image Reconstruction In Photoacoustic Computed Tomography For Breast Imaging, Yang Lou

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic computed tomography(PACT), also known as optoacoustic tomography (OAT), is an emerging imaging technique that has developed rapidly in recent years. The combination of the high optical contrast and the high acoustic resolution of this hybrid imaging technique makes it a promising candidate for human breast imaging, where conventional imaging techniques including X-ray mammography, B-mode ultrasound, and MRI suffer from low contrast, low specificity for certain breast types, and additional risks related to ionizing radiation. Though significant works have been done to push the frontier of PACT breast imaging, it is still challenging to successfully build a PACT breast imaging …

Abiotic- And Biotic-Formation Of Manganese Oxides And Their Fate In Environmental Systems, Haesung Jung

McKelvey School of Engineering Graduate Student Theses & Dissertations

Manganese (hydr)oxide (Mn (hydr)oxide) minerals are ubiquitous in aquatic and terrestrial environments. These minerals have high surface areas and are highly sorptive and redox active. From decades of accumulated knowledge about natural redox cycling, we have found that Mn (hydr)oxides play critical roles as electron donors and acceptors in elemental geochemical cycling and biological metabolisms in nature. Thus, Mn (hydr)oxides have garnered increasing interest to understand natural systems. Considering the variety of redox reactions with Mn (hydr)oxides in nature, it is also expected that there should be diverse pathways to form Mn (hydr)oxides through abiotic and biotic processes. Previous studies …

Regulation Of Early Zebrafish Embryogenesis By Calcium Signaling And Dachsous1b Cadherin, Jiakun Chen

Arts & Sciences Graduate Student Theses and Dissertations

Early animal embryogenesis entails a dynamic combination of embryonic cleavages, axial patterning, and gastrulation movements to shape a basic body plan. The underlying molecular signaling responsible for regulating this process remains poorly understood. In this thesis work, I first review recent progress in understanding of gastrulation movements in various model organisms brought by advances in imaging techniques. The externally developing and optically translucent zebrafish embryo is an ideal model organism to study vertebrate embryonic development by in vivo imaging. The objective of my thesis research is to leverage experimental advantages in the zebrafish model to uncover novel regulators and elucidate …

The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger

Arts & Sciences Graduate Student Theses and Dissertations

Brain extracellular concentration of the peptide amyloid-β (Aβ) is a major contributor to Alzheimer’s disease (AD) pathogenesis. High Aβ levels in the extracellular space precipitate aggregation of the peptide into soluble and insoluble toxic species. This process begins decades before cognitive impairment and triggers the cascade of pathology that eventually leads to AD. Synaptic activity is key to the regulation of extracellular Aβ levels. Presynaptic activity drives the production of Aβ, while postsynaptic receptor activation exhibits more nuanced regulation. For example, high levels of NMDA receptor (NMDA-R) activation have been shown to decrease Aβ production through the extracellular signal-regulated kinase …

Knowledge Driven Approaches And Machine Learning Improve The Identification Of Clinically Relevant Somatic Mutations In Cancer Genomics, Benjamin John Ainscough

Arts & Sciences Graduate Student Theses and Dissertations

For cancer genomics to fully expand its utility from research discovery to clinical adoption, somatic variant detection pipelines must be optimized and standardized to ensure identification of clinically relevant mutations and to reduce laborious and error-prone post-processing steps. To address the need for improved catalogues of clinically and biologically important somatic mutations, we developed DoCM, a Database of Curated Mutations in Cancer (http://docm.info), as described in Chapter 2. DoCM is an open source, openly licensed resource to enable the cancer research community to aggregate, store and track biologically and clinically important cancer variants. DoCM is currently comprised of 1,364 variants …

New Ventures In Amidine-Based Catalyst Design, Nicholas Alan Ahlemeyer

Arts & Sciences Graduate Student Theses and Dissertations

Two new cascade transformations of α,β-unsaturated thioesters catalyzed by amidine-based catalysts have been developed. First, a reagent-free transformation of o-formylaryl cinnamoyl thioesters catalyzed by HBTM-2 to produce 2-substituted thiochromenes achieved high enantioselectivities and yields while forming carbon dioxide as the only byproduct. Second, a highly diastereo- and enantioselective tandem rearrangement of less reactive enone thioesters into tricyclic thiochromanes in the presence of electron-rich amidine-based catalysts was developed. These catalysts were designed with the help of DFT calculations. H-PIP, the first chiral amidine-based catalyst synthesized in our group, performed the best overall in the thiochromane synthesis.The second chapter of this thesis …