Digital Commons Network^™

Modeling Of Cantú Syndrome In Zebrafish, Soma Sekhara Singareddy

McKelvey School of Engineering Theses & Dissertations

Although rare, Cantú syndrome (CS) is a debilitating syndrome without any specific therapy, caused by gain-of-function (GOF) mutations in KCNJ8 and ABCC9 genes that encode ATP-sensitive potassium (KATP) channels. To better understand the link between molecular dysfunction and the complex pathophysiology, animal models that can rigorously mirror human CS are essential. Using ABCC9-mutated zebrafish, which can provide significant advantages over mice as an appropriate vertebrate model, GOF has been demonstrated at a cellular level in the ventricular cardiomyocytes. This also marks the first-known characterization of KATP currents in teleost hearts. In addition, sulfonylurea sensitivities of the channels have been …

Electroless Nickel Plating And Spark Plasma Sintering Of Nano Zro2 For Mechanical Property Enhancement, Kunlong Jia

McKelvey School of Engineering Theses & Dissertations

A new approach of combined electroless nickel plating (ENP) and spark plasma sintering (SPS) was used to determine the feasibility of fracture toughness improvement of ZrO2. Nano-grained yttria stabilized zirconia (YSZ) particles of 100nm average diameter were coated with about 1-5 nm of nickel coating by ENP. To reduce nano particle agglomeration throughout the ENP process; vigorous agitation with an ultrasonic horn was used. The coated powder was characterized using Scanning Electron Microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDX) and Transmission electron microscopy (TEM) to study the microstructure and coating characteristics. The coating was identified to be predominantly nickel and of …

Numerical Simulations Of Flow Past A Triangular Airfoil And In A Sweeping Jet Actuator Using Different Turbulence Models, Han Yang

McKelvey School of Engineering Theses & Dissertations

The goal of this research is to perform 2D turbulent flow simulations to predict the flow past a triangular airfoil used for a Mars air vehicle and in a sweeping jet actuator used for active flow control. Simulations are performed using the commercial CFD software ANSYS Fluent.

The thesis consists of two parts. The first part of the thesis deals with the CFD simulations of a triangular airfoil in low-Reynolds-number compressible flow. This airfoil is one of the candidates for propeller blades on a possible future Martian air vehicle design. The aerodynamics and flow physics of the triangular airfoil is …

Multifunctional Nanocomposites Based On Bacterial Cellulose, Qisheng Jiang

McKelvey School of Engineering Theses & Dissertations

Cellulose is biodegradable, renewable, and abundant in nature thus cellulose (or paper)-based products can be inexpensively produced and recycled. Among cellulosic materials, bacterial nanocellulose (BNC) draws a special research attention due to the inherent three-dimensional nanofibrous structure, excellent mechanical flexibility, high purity and well-defined surface chemistry, and cost-efficient, scalable and environment-friendly synthesis. BNC can be biosynthesized by Gluconacetobacter xylinus, which is the most characterized BNC producer among various microorganisms. BNC is composed of highly pure cellulose nanofibrils, produced from well-defined dextrose through biochemical steps and subsequent self-assembling of the secreted cellulose fibrils which has the dimension ranges from 25 to …

Radiolabeled Nanohydroxyapatite As A Platform For The Development Of New Pet Imaging Agents, Stacy Lee Queern

Arts & Sciences Electronic Theses and Dissertations

Positron emission tomography (PET) imaging utilizes drugs labeled with positron emitters to target and evaluate different biological processes occurring in the body. Tailoring medicine to the individual allows for higher quality of care with better diagnosis and treatment and is a key purpose for advancing research into developing new platforms for PET imaging agents. A PET nuclide of high interest for the development of these agents is 89Zr. This can be attributed to the long half-life of 3.27 days and low positron energy of 89Zr.

In this work, we developed a production method for 89Zr using Y sputtered coins that …

Graphene Oxides In Water: Characterization, Reactivity, And Application, Siyuan An

McKelvey School of Engineering Theses & Dissertations

Recently discovered, graphene and graphene oxide materials have drawn considerable research attention due to outstanding and novel properties, which underpin wide material potential for a number of advanced applications including supercapacitors, solar cells, sensors, catalysts, semiconductors, sorbents, and membranes, among others. Graphene oxides (GO), which are considered as a family of oxidized graphene materials (derivatives), is a key precursor to the synthesis of free-standing graphene via oxidation-exfoliation-reduction pathways. GO properties depend on the synthesis routes/conditions (i.e. derivatization), including partially maintaining graphene (i.e. sp2) properties. Further, oxygen-containing functionalities (epoxy, hydroxyl, carbonyl, and carboxyl groups) render GO hydrophilic – and correspondingly stability …

Molecular Basis Of Class Ib Drug Interactions With The Nav Channel Macromolecular Complex: A Route To Personalized Medicine For Cardiac Arrhythmia, Wandi Zhu

McKelvey School of Engineering Theses & Dissertations

The heart rhythm is precisely controlled by the electrical impulse that propagate in the cardiac tissue. In single cardiomyocytes, the electrical activity generated by action potentials (AP). Cardiac NaV channels (NaV1.5) carry a large influx of Na+ that mediates the initiation and propagation of the AP in both atria and ventricles. Disruption of NaV1.5 function by genetic variants or external factors can result in deadly arrhythmias, such as long QT syndrome and Brugada syndrome. Thus, NaV channels are import therapeutic targets. The class I antiarrhythmics are the modulators of the NaV channels. Although they have been used clinically for over …

Decoding Complexity In Metabolic Networks Using Integrated Mechanistic And Machine Learning Approaches, Tolutola Timothy Oyetunde

McKelvey School of Engineering Theses & Dissertations

How can we get living cells to do what we want? What do they actually ‘want’? What ‘rules’ do they observe? How can we better understand and manipulate them? Answers to fundamental research questions like these are critical to overcoming bottlenecks in metabolic engineering and optimizing heterologous pathways for synthetic biology applications. Unfortunately, biological systems are too complex to be completely described by physicochemical modeling alone.

In this research, I developed and applied integrated mechanistic and data-driven frameworks to help uncover the mysteries of cellular regulation and control. These tools provide a computational framework for seeking answers to pertinent biological …

Effects Of Secondary Stall And Unsteady Free-Stream On Blade Drag And Pitching Moments, Michael Malick

McKelvey School of Engineering Theses & Dissertations

Dynamic stall is a complex aerodynamic phenomenon occurring in helicopter rotors, limiting the flight envelope and causing control linkage damage and instabilities. The Peters-Modarres semi-empirical dynamic stall model is extended to simulate pitching moment and drag in unsteady freestream and yawed flow, including the effects of secondary stall. The aerodynamics are implemented as a state-space model, suitable for time-marching or aeroelastic analyses. With small modifications to the original stall model, secondary stall effects and unsteady freestream can be simulated without adding additional states. An optimization routine determines sets of parameters that minimize the error between the modeled solution and experimental …

Investigating Cyanobacteria Metabolism And Channeling-Based Regulations Via Isotopic Nonstationary Labeling And Metabolomic Analyses, Mary Helen Abernathy

McKelvey School of Engineering Theses & Dissertations

Cyanobacteria have the potential to be low-cost and sustainable cell factories for bio-products; however, many challenges face cyanobacteria as biorefineries. This dissertation seeks to advance non-model photosynthetic organisms for biotechnology applications by characterizing central carbon metabolism and its regulations. Cyanobacteria phenotypes for bio-production are examined and their intracellular metabolism is quantified. Using isotopic labeling experiments, phenotypic relationships between biomass composition, central carbon fluxes, and metabolite pool sizes are investigated. Metabolic analyses of cyanobacteria led to new investigations of flux regulation mechanisms via protein spatial organizations or metabolite channeling. Metabolite channeling is further explored as a hypothesis to explain enigmatic labeling …

Basis Vector Model Method For Proton Stopping Power Estimation Using Dual-Energy Computed Tomography, Shuangyue Zhang

McKelvey School of Engineering Theses & Dissertations

Accurate estimation of the proton stopping power ratio (SPR) is important for treatment planning and dose prediction for proton beam therapy. The state-of-the-art clinical practice for estimating patient-specific SPR distributions is the stoichiometric calibration method using single-energy computed tomography (SECT) images, which in principle may introduce large intrinsic uncertainties into estimation results. One major factor that limits the performance of SECT-based methods is the Hounsfield unit (HU) degeneracy in the presence of tissue composition variations. Dual-energy computed tomography (DECT) has shown the potential of reducing uncertainties in proton SPR prediction via scanning the patient with two different source energy spectra. …

Mechanisms Of Calcium Phosphate Mineralization On Biological Interfaces And Their Engineering Applications, Doyoon Kim

McKelvey School of Engineering Theses & Dissertations

All living organisms utilize phosphorus (P) as an essential component of their cell membranes, DNA and RNA, and adenosine triphosphate. Bones, in addition to bearing loads, play an important role in balancing P levels in our bodies. In bones, a network of collagen templates and calcium phosphate (CaP) nanocrystals builds hierarchical levels, from nano- to macroscale. Within this architecture, the thermodynamic properties of CaP minerals are influential. Despite the importance of nucleation, growth, and crystallization in collagen structures for tissue development, little kinetic study of these processes has been conducted due to the limited in situ techniques for monitoring these …

Information-Based Analysis And Control Of Recurrent Linear Networks And Recurrent Networks With Sigmoidal Nonlinearities, Deslin Menolascino

McKelvey School of Engineering Theses & Dissertations

Linear dynamical models have served as an analytically tractable approximation for a variety of natural and engineered systems. Recently, such models have been used to describe high-level diffusive interactions in the activation of complex networks, including those in the brain. In this regard, classical tools from control theory, including controllability analysis, have been used to assay the extent to which such networks might respond to their afferent inputs. However, for natural systems such as brain networks, it is not clear whether advantageous control properties necessarily correspond to useful functionality. That is, are systems that are highly controllable (according to certain …

Multifunctional Nanocomposites Based On Bacterial Cellulose, Qisheng Jiang

McKelvey School of Engineering Theses & Dissertations

Cellulose is biodegradable, renewable, and abundant in nature thus cellulose (or paper)-based products can be inexpensively produced and recycled. Among cellulosic materials, bacterial nanocellulose (BNC) draws a special research attention due to the inherent three-dimensional nanofibrous structure, excellent mechanical flexibility, high purity and well-defined surface chemistry, and cost-efficient, scalable and environment-friendly synthesis. BNC can be biosynthesized by Gluconacetobacter xylinus, which is the most characterized BNC producer among various microorganisms. BNC is composed of highly pure cellulose nanofibrils, produced from well-defined dextrose through biochemical steps and subsequent self-assembling of the secreted cellulose fibrils which has the dimension ranges from 25 to …

Towards Engineering Advanced Nanomaterials: Elucidating Fundamental Particle Behavior In Water And Critical Sorption Dynamics, Changwoo Kim

McKelvey School of Engineering Theses & Dissertations

As advanced nanomaterials, inorganic-organic nano composites have received great interest as potential platform (nano) structures for sensor, catalyst, sorbent, and environmental applications. Here, my Ph.D. research has focused on the design, synthesis, and characterization of advanced water-stable engineered metal-oxide nanoparticles functionalized by organic frames for environmental applications. For the environmental applications, I have evaluated particleoptimized sorption processes for the remediation and separation of arsenic, chromium, and uranium under environmentally relevant conditions. More specifically, I have explored the critical role of organic coating on sorption mechanisms and performances using engineered iron oxide -based, manganese oxide -based, and manganese ferrite -based (core) …

Tunable Electronic And Optical Properties Of Low-Dimensional Materials, Shiyuan Gao

Arts & Sciences Electronic Theses and Dissertations

Two-dimensional (2D) materials with single or a few atomic layers, such as graphene, hexagonal boron nitride (h-BN) and transition metal dichalcogenides (TMDCs), and the heterostructures or one-dimensional (1D) nanostructures they form, have attracted much attention recently as unique platforms for studying many condensed-matter phenomena and holds great potentials for nanoelectronics and optoelectronic applications. Apart from their unique intrinsic properties which has been intensively studied for over a decade by now, they also allow external control of many degrees of freedom, such as electrical gating, doping and layer stacking. In this thesis, I present a theoretical study of the electronic and …

Effects Of Secondary Stall And Unsteady Free-Stream On Blade Drag And Pitching Moments, Michael Malick

McKelvey School of Engineering Theses & Dissertations

Dynamic stall is a complex aerodynamic phenomenon occurring in helicopter rotors, limiting the flight envelope and causing control linkage damage and instabilities. The Peters-Modarres semi-empirical dynamic stall model is extended to simulate pitching moment and drag in unsteady freestream and yawed flow, including the effects of secondary stall. The aerodynamics are implemented as a state-space model, suitable for time-marching or aeroelastic analyses. With small modifications to the original stall model, secondary stall effects and unsteady freestream can be simulated without adding additional states. An optimization routine determines sets of parameters that minimize the error between the modeled solution and experimental …

Kcnq1/Kcne1 Interaction In The Cardiac Iks Channel And Its Physiological Consequences, Jiajing Xu

McKelvey School of Engineering Theses & Dissertations

Dynamic conformational changes of ion channel proteins during activation gating determine their function as carriers of current. The relationship between these molecular movements and channel function over the physiological timescale of the action potential (AP) has not been fully established due to limitations of existing techniques. We constructed a library of possible cardiac IKs protein conformations and applied a combination of protein segmentation and energy linearization to study this relationship computationally. Simulations reproduced the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and function, observed in experiments. Mechanistically, KCNE1 increased the probability of “visiting” conducting pore conformations on …

Nanopower Analog Frontends For Cyber-Physical Systems, Kenji Aono

McKelvey School of Engineering Theses & Dissertations

In a world that is increasingly dominated by advances made in digital systems, this work will explore the exploiting of naturally occurring physical phenomena to pave the way towards a self-powered sensor for Cyber-Physical Systems (CPS). In general, a sensor frontend can be broken up into a handful of basic stages: transduction, filtering, energy conversion, measurement, and interfacing. One analog artifact that was investigated for filtering was the physical phenomenon of hysteresis induced in current-mode biquads driven near or at their saturation limit. Known as jump resonance, this analog construct facilitates a higher quality factor to be brought about without …

Biosensing By “Growing” Antennas And Error-Correcting Codes, Mingquan Yuan

McKelvey School of Engineering Theses & Dissertations

Food-borne disease outbreaks not only cause numerous fatalities every year but also contribute to significant economic losses. While end-to-end supply chain monitoring can be one of the keys to preventing these outbreaks, screening every food product in the supply chain is not feasible considering the sheer volume and prohibitive test costs. Fortunately, two converging economic trends promise to make this end-to-end supply chain monitoring possible. The first trend is that passive radio-frequency identification (RFID) tags and quick response (QR) codes are now widely accepted for food packaging. The second trend is that smartphones are now equipped with the capability to …

Linking Structure And Dynamics In Metallic Liquids: A Combined Experimental And Molecular Dynamics Approach, Robert Ashcraft

Arts & Sciences Electronic Theses and Dissertations

A major outstanding problem in condensed matter physics is the nature of the glass transition, in which a rapidly cooled liquid can bypass the transition into a crystalline state and the liquid structure is "frozen-in" due to kinetic arrest. To characterize the fundamental features behind this transition the liquid, both in the high temperature (equilibrium) and supercooled state, needs to be better understood. By examining the relationship between structure and dynamics a better characterization of the liquid state and a determination of the mechanisms that are ultimately important for the formation of the glass can be gained. In this dissertation, …

Numerical Simulation And Optimization Of Blalock-Taussig Shunt, Thomas Hess, Ramesh K. Agarwal

McKelvey School of Engineering Theses & Dissertations

The goal of this study is to create an optimized Blalock-Taussig shunt used to temporarily repair pulmonary vascular blockages allowing a child time to grow so a more permanent surgical repair of the heart and vasculature can be performed. Blalock-Taussig or BT shunts are a surgical procedure performed on infants suffering from cyanosis or “Blue Baby Syndrome.” A BT shunt is an artificial vessel placed between the right ventricle and the pulmonary artery to increase blood flow in the lung and blood oxygen saturation levels. In a study of 96 patients with currently in use modified BT shunts, 32 patients …

Acetylation Profiles Of Histone And Non-Histone Proteins In Breast Cancer, Alla Karpova

McKelvey School of Engineering Theses & Dissertations

This study evaluates the impact of protein acetylation on breast cancer gene expression and the regulation of metabolism. Acetylation is the second abundant post-translational modification after phosphorylation, regulating protein activity and function. The alterations in acetylation of both histone and non-histone proteins is known to be related to many human diseases, including cancer. Acetylation and deacetylation of histones is closely associated with the regulation of gene expression, while acetylation of non-histone proteins may have a broad effect on major cellular processes, such as proliferation, metabolism, cell cycle and apoptosis, imbalanced regulation of which is essential for cancer development. Therefore, it’s …

Self-Powered Time-Keeping And Time-Of-Occurrence Sensing, Liang Zhou

McKelvey School of Engineering Theses & Dissertations

Self-powered and passive Internet-of-Things (IoT) devices (e.g. RFID tags, financial assets, wireless sensors and surface-mount devices) have been widely deployed in our everyday and industrial applications. While diverse functionalities have been implemented in passive systems, the lack of a reference clock limits the design space of such devices used for applications such as time-stamping sensing, recording and dynamic authentication. Self-powered time-keeping in passive systems has been challenging because they do not have access to continuous power sources. While energy transducers can harvest power from ambient environment, the intermittent power cannot support continuous operation for reference clocks. The thesis of this …

Development And Evaluation Of Biocompatible Engineered Nanoparticles For Use In Ophthalmology, Bedia Begum Karakocak

McKelvey School of Engineering Theses & Dissertations

The synthesis and design of biocompatible nanoparticles for targeted drug delivery and bioimaging requires knowledge of both their potential toxicity and their transport. For both practical and ethical reasons, evaluating exposure via cell studies is a logical precursor to in vivo tests. As a step towards clinical trials, this work extensively investigated the toxicity of gold nanoparticles (Au NPs) and carbon dot (CD) nanoparticles as a prelude to their in vivo application, focusing specifically on ocular cells. As a further step, it also evaluated their whole-body transport in mice. The research pursued two approaches in assessing the toxicity of engineered …

Noninvasive Multi-Modality Studies Of Cardiac Electrophysiology, Mechanics, And Anatomical Substrate In Healthy Adults, Arrhythmogenic Cardiomyopathy, And Heart Failure, Christopher Andrews

McKelvey School of Engineering Theses & Dissertations

Heart disease is a leading cause of death and disability and is a major contributor to healthcare costs. Many forms of heart disease are caused by abnormalities in the electrical function of heart muscle cells or the cardiac conduction system. Electrocardiographic Imaging (ECGI) is a noninvasive modality for imaging cardiac electrophysiology. By combining recordings of the voltage distribution on the torso surface with anatomical images of the heart-torso geometry, ECGI reconstructs voltages on the epicardium. This thesis applies ECGI to novel studies of human heart function and disease and explores new combinations of ECGI with additional imaging modalities.

ECGI was …

Lignin Conversion To Value-Added Products Via Heterogeneous Catalysts, Yu Gao

McKelvey School of Engineering Theses & Dissertations

Increasing world population has led to great demands for fuels, chemicals, and materials, and has raised concerns over the depletion of non-renewable resources and the environmental impacts of their processing and utilization. However, the biorefinery concept suggests lignocellulosic biomass can be used as an alternative resource for producing a range of fuels, chemicals and materials to fulfill these demands in a sustainable way. Hence, fermentation technologies are widely developed to efficiently utilize lignocellulosic carbohydrates. However, the non-carbohydrate fraction of biomass, lignin, is still considered as waste and is under-utilized as low-grade fuel, mainly for local heat and electricity production. Since …

Exploring Fatty Acid Metabolism For The Biosynthesis Of Non-Natural Chemicals, Wen Jiang

McKelvey School of Engineering Theses & Dissertations

The global energy crisis and increasing environmental concerns have spurred the sustainable production of biofuels and other fossil-fuel-derived chemicals. One approach is to engineer microbial metabolic pathways to convert renewable feedstocks (e.g. lignocellulosic biomass) to compounds that have structures similar to those of petroleum-derived fuels and chemicals. The microbial fatty acid (FA) biosynthetic pathway is attractive because FAs are common precursors that can be converted to several types of chemicals, including alkanes, alkenes, alcohols, and esters. These chemicals have numerous applications as fuels, fragrances, emollients, plasticizers, thickeners, and detergents. Most work has used Escherichia coli as the microbial host due …

Aromatic Tolerance And Utilization Mechanisms Of Rhodococcus Opacus Pd630 To Produce Value-Added Products From Lignin, Wiliam Henson

McKelvey School of Engineering Theses & Dissertations

Lignocellulosic biomass is a potential renewable feedstock for the microbial production of fuels and chemicals. For microbial utilization, lignocellulosic biomass must undergo pretreatment (e.g., thermochemical and enzymatic processing) to release fermentable sugars.

Lignin comprises ~15-30% of lignocellulosic biomass, and lignin-derived aromatic compounds released during pretreatment can inhibit the microbial conversion of lignocellulosic sugars to bioproducts. Additionally, cost-effective separation of lignin and lignin by-products from lignocellulosic sugars remains a challenge, and current processes generate large waste streams that are typically burned or discarded. Thus, efforts are underway to improve microbial tolerance to lignin by-products and to develop approaches for valorizing waste …

Radiological Pathological Correlations In Chronic Traumatic Encephalopathy, Mihika Gangolli

McKelvey School of Engineering Theses & Dissertations

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that has been increasingly linked to traumatic brain injury. The neuropathology that distinguishes CTE from other tauopathies includes hyperphosphorylated tau (pTau) tangles and tau positive astrocytes irregularly distributed in cortical sulcal depths and clustered around perivascular foci. These features are clearly identified using immunohistochemistry, but are undetectable to current clinical imaging methods. Diffusion imaging has been proposed as a noninvasive method to detect the pathognomonic lesion of CTE in vivo because of its high sensitivity to microstructural alterations in tissue structure. While several diffusion imaging approaches, ranging from diffusion tensor imaging …