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Probabilistic Uncertainty Quantification And Experiment Design For Nonlinear Models: Applications In Systems Biology, Vu Cao Duy Thien Dinh
Probabilistic Uncertainty Quantification And Experiment Design For Nonlinear Models: Applications In Systems Biology, Vu Cao Duy Thien Dinh
Open Access Dissertations
Despite the ever-increasing interest in understanding biology at the system level, there are several factors that hinder studies and analyses of biological systems. First, unlike systems from other applied fields whose parameters can be effectively identified, biological systems are usually unidentifiable, even in the ideal case when all possible system outputs are known with high accuracy. Second, the presence of multivariate bifurcations often leads the system to behaviors that are completely different in nature. In such cases, system outputs (as function of parameters/inputs) are usually discontinuous or have sharp transitions across domains with different behaviors. Finally, models from systems biology …
Hierarchical Cell Fluid Extracellular Matrix Interaction In Cell Microenvironment, Soham Ghosh
Hierarchical Cell Fluid Extracellular Matrix Interaction In Cell Microenvironment, Soham Ghosh
Open Access Dissertations
Hierarchical structural interactions between components of cell microenvironment, the extracellular matrix (ECM), cytoplasm, nucleus and fluid, are important phenomena that decide cell level physiological process and tissue engineering applications. One of those tissue engineering modalities is freezing of biomaterials, important in a wide variety of biomedical applications including cryopreservation and cryosurgeries. In order to design these applications, freezing-induced changes of the cells and tissues and corresponding biophysical mechanisms need to be well understood. Although the effects of freezing on cells in suspension have been extensively studied, the intracellular mechanics of cells embedded in the extracellular matrix (ECM) during freezing are …
Quantitative Modeling Of Spatiotemporal Systems: Simulation Of Biological Systems And Analysis Of Error Metric Effects On Model Fitting, James Hengenius
Quantitative Modeling Of Spatiotemporal Systems: Simulation Of Biological Systems And Analysis Of Error Metric Effects On Model Fitting, James Hengenius
Open Access Dissertations
Understanding the biophysical processes underlying biological and biotechnological processes is a prerequisite for therapeutic treatments and technological innovation. With the exponential growth of computational processing speed, experimental findings in these fields have been complemented by dynamic simulations of developmental signaling and genetic interactions. Models provide means to evaluate "emergent" properties of systems sometimes inaccessible by reductionist approaches, making them test beds for biological inference and technological refinement.^ The complexity and interconnectedness of biological processes pose special challenges to modelers; biological models typically possess a large number of unknown parameters relative to their counterparts in other physical sciences. Estimating these parameter …
Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson
Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson
Open Access Dissertations
The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of …
Towards A Paradigm Shift In The Modeling Of Soil Organic Carbon Decomposition For Earth System Models, Yujie He
Open Access Dissertations
Soils are the largest terrestrial carbon pools and contain approximately 2200 Pg of carbon. Thus, the dynamics of soil carbon plays an important role in the global carbon cycle and climate system. Earth System Models are used to project future interactions between terrestrial ecosystem carbon dynamics and climate. However, these models often predict a wide range of soil carbon responses and their formulations have lagged behind recent soil science advances, omitting key biogeochemical mechanisms. In contrast, recent mechanistically-based biogeochemical models that explicitly account for microbial biomass pools and enzyme kinetics that catalyze soil carbon decomposition produce notably different results and …
Identification And Characterization Of Signal Components In Early Aba Signaling In Arabidopsis, Yueh-Ju Hou
Identification And Characterization Of Signal Components In Early Aba Signaling In Arabidopsis, Yueh-Ju Hou
Open Access Dissertations
The phytohormone abscisic acid (ABA) regulates growth, development, and response to abiotic stress in plants. The core ABA signaling has three key components: ABA receptors PYRABACTIN RESISTANCE 1 and PYR1-Like protein (PYR1/PYLs), type 2C protein phosphatases (PP2Cs) and SNF1- related protein Kinase 2s (SnRK2s). In the presence of ABA, PYR1/PYLs bind to and inhibit PP2Cs, leading to the release of SnRK2s from suppression, to activate downstream events such as ABA-responsive gene expression. To identify new components in the ABA signaling pathway, we performed a yeast two-hybrid screen for PYLs and SnRK2s interactors. We identified two proteins that interact with PYLs …
Development Of Planar Patch Clamp With Potentiometric Calcium Ion-Selective Electrode, Kul Inn
Development Of Planar Patch Clamp With Potentiometric Calcium Ion-Selective Electrode, Kul Inn
Open Access Dissertations
Ion channels are proteins in cell lipid bilayer membranes and act as pores which can adopt closed and open states, thus gating the flow of ions in and out of the cell. Patch clamp technology has been the proven standard for fundamental studies of ion channel activities. However, the technique has some basic limitations: low throughput, time consuming nature of its process, need of highly skilled personnel and inability to identify ionic composition of electrophysiological events. Many different materials and fabrication methods have been introduced to replace traditional patch clamp setup to overcome limitations.^ In this dissertation, a planar patch …
Quantum Mechanics In Complex Systems, Ross Douglas Hoehn
Quantum Mechanics In Complex Systems, Ross Douglas Hoehn
Open Access Dissertations
This document should be considered in its separation; there are three distinct topics contained within and three distinct chapters within the body of works. In a similar fashion, this abstract should be considered in three parts. Firstly, we explored the existence of multiply-charged atomic ions by having developed a new set of dimensional scaling equations as well as a series of relativistic augmentations to the standard dimensional scaling procedure and to the self-consistent field calculations. Secondly, we propose a novel method of predicting drug efficacy in hopes to facilitate the discovery of new small molecule therapeutics by modeling the agonist-protein …
Cellular And Molecular Regulation Of Skeletal Muscle Regeneration, Chunhui Jiang
Cellular And Molecular Regulation Of Skeletal Muscle Regeneration, Chunhui Jiang
Open Access Dissertations
Skeletal muscle regeneration provides a powerful model to study the cellular and molecular mechanism governing stem cell function since the whole process is mediated by a population of muscle-resident stem cells called satellite cells. The overall aim of this dissertation is to explore the roles of Notch signaling and a novel gene (Bex1) in satellite cell function and skeletal muscle regeneration. ^ The first part of this thesis is to examine how the Notch signaling pathway regulates the satellite cell self-renewal in a disease model. The MDX mouse is a well-established model for Duchenne muscular dystrophy (DMD) and characterized by …
How Do Metalloenzymes Propagate And Control Chemical Reactions?, Whitney F Kellett
How Do Metalloenzymes Propagate And Control Chemical Reactions?, Whitney F Kellett
Open Access Dissertations
Enzymes control and propagate a dizzying array of chemical reactions, including radical reactions and reactions cleaving carbon-carbon bonds. Metalloenzymes, which contain a metal cofactor, are particularly adept at propagating these reactions. This thesis focuses on several metalloenzymes; each an example of a different unique reaction control strategy. Both experimental and computational methodologies have been employed in order to identify specific residues or features which contribute to each enzyme's ability to control the reaction. Emphasis is made on special properties of the metal Manganese. Controlling residues include not only first shell or active site residues, but also residues more distant from …
Development Of Novel Strategies To Combat Multidrug Resistance Mediated By Efflux Transporters And Intracellular Bacteria, Jerrin Kuriakose
Development Of Novel Strategies To Combat Multidrug Resistance Mediated By Efflux Transporters And Intracellular Bacteria, Jerrin Kuriakose
Open Access Dissertations
Multidrug resistance (MDR) is the condition where cancer cells or microorganisms cease to respond to multiple drugs. MDR conferred by efflux transporters, that deprive the bioavailability of drugs at their site of action, are a threat to cancer and malarial chemotherapy. Specifically, the mammalian ABC transporter Pglycoprotein (P-gp) has undermined many drugs in treatment of cancer and other disease states. Mutations in the parasitic transporter Plasmodium falciparum chloroquine resistance transporter (PfCRT) have given rise to strains unsusceptible to the aminoquionoline family of antimalarials. Using the very drug substrates, we have developed bivalent inhibitors of P-gp. Here, click chemistry has been …
Identification And Characterization Of Factors Involved In Dna Demethylation And Anti-Silencing In Arabidopsis, Zhaobo Lang
Identification And Characterization Of Factors Involved In Dna Demethylation And Anti-Silencing In Arabidopsis, Zhaobo Lang
Open Access Dissertations
DNA methylation is a key epigenetic mark for transcriptional gene silencing in many eukaryotes. DNA methylation status can be dynamically controlled by methylation and active demethylation processes. Compared to the well-known mechanisms of DNA methylation, the mechanisms of DNA demethylation and its regulation are poorly understood. In order to better understand the DNA demethylation pathway, we developed two genetic screening systems in Arabidopsis to identify new components involved in the DNA demethylation. In the first system, which is based on 35S promoter driven SUC2 (sucrose transporter 2) transgene, a mutant (91-1) was isolated and map-based cloning identified the …
The Modification Of Brucine Derivatives As Chiral Ligands And Its Application In The Asymmetric Synthesis, Jian-Yuan Li
The Modification Of Brucine Derivatives As Chiral Ligands And Its Application In The Asymmetric Synthesis, Jian-Yuan Li
Open Access Dissertations
The modification of brucine derivatives as chiral ligands and the use of a multifaceted chiral ligand, brucine diol, under different reaction conditions to produce various optical isomers is described. In Chapter 1, the generation of a number of brucine derivatives is described. Taking the advantage of brucine-diol's excellent molecular recognition capability for multiple organic functional groups, we focused on the synthetic modifications of brucine-diol and the synthesis of brucine N-oxide. We also produced various brucine derivatives with different functional moieties in good yields and selectivities. ^ In Chapter 2, we described the investigation of brucine N-oxide catalyzed Morita-Baylis-Hillman …
Karyopherin Alpha Subtypes And Porcine Early Stage Embryo Development, Yanfang Li
Karyopherin Alpha Subtypes And Porcine Early Stage Embryo Development, Yanfang Li
Open Access Dissertations
Intracellular communication between the nucleus and cytoplasm is critically important for coordinating cellular events during embryogenesis. The karyopherin α/β heterodimer is an intracellular nuclear trafficking system that mediates nuclear import of proteins that bear classical nuclear localization signals (NLSs). Seven karyopherin α subtypes have been identified in the domestic pig, and while each of these karyopherin α subtypes is able to bind to a nuclear localization signal, individual karyopherin α subtypes have been shown to transport specific NLS-bearing proteins. The objective of this study was to determine the developmental requirements of karyopherin α subtypes (KPNAs) during cleavage development in porcine …
Embodied Interaction With Visualization And Spatial Navigation In Time-Sensitive Scenarios, Yu-Ting Li
Embodied Interaction With Visualization And Spatial Navigation In Time-Sensitive Scenarios, Yu-Ting Li
Open Access Dissertations
Paraphrasing the theory of embodied cognition, all aspects of our cognition are determined primarily by the contextual information and the means of physical interaction with data and information. In hybrid human-machine systems involving complex decision making, continuously maintaining a high level of attention while employing a deep understanding concerning the task performed as well as its context are essential. Utilizing embodied interaction to interact with machines has the potential to promote thinking and learning according to the theory of embodied cognition proposed by Lakoff. Additionally, the hybrid human-machine system utilizing natural and intuitive communication channels (e.g., gestures, speech, and body …
Theory For Diffusional Encounters In Heterogeneous Environments And Multivalent Electrolyte Screening Of Charged Interface, Ran Li
Open Access Dissertations
We develop a theory for encounter rates in a three-dimensional system of connected compartments. The model of connected compartments exhibits the length-scale dependent diffusion that is observed in many heterogeneous environments, such as porous catalysts and biological environments. We discovered a dimensionless number that is the dominant scaling variable and obtained, for the first time, an analytical expression for the encounter rate. The new theory generalizes the classic Smoluchowski diffusion limit to the case of heterogeneous environments. The new theory is tested using Brownian dynamics simulations.^ We also experimentally investigated the behavior of multivalent electrolyte near a charged solid-liquid interface. …
The Impact Of National Science Foundation Investments In Undergraduate Engineering Education Research: A Comparative, Mixed Methods Study, Jeremi Shavonda London
The Impact Of National Science Foundation Investments In Undergraduate Engineering Education Research: A Comparative, Mixed Methods Study, Jeremi Shavonda London
Open Access Dissertations
The U.S. invests billions of taxpayers' dollars in research tied to the national priorities that contribute to its competitiveness in a global economy. As the federal funding agency with an explicit focus on engineering education, the National Science Foundation (NSF) contains a portfolio of projects focused on improving the quantity of engineering graduates and the quality of engineering programs. Within the agency, the Division of Undergraduate Education invests approximately $190 million (FY 2012) annually on science, technology, engineering and mathematics (STEM) education projects. Although the DUE portfolio includes a suite a projects with different foci supporting national initiatives and Principal …
Multidimensional Approach To Comparative Avian Visual Systems, Bret Alan Moore
Multidimensional Approach To Comparative Avian Visual Systems, Bret Alan Moore
Open Access Dissertations
Since the birth of visual ecology, comparative studies on how birds see their world have been limited to a small number of species and tended to focus on a single visual trait. This approach has constrained our ability to understand the diversity and evolution of the avian visual system. The goal of this dissertation was to characterize multiple visual dimensions on bird groups that are highly speciouse (e.g., Passeriformes), and test some hypotheses and predictions, using modern comparative tools, on the relationship between different visual traits and their association with visual information sampling behaviors. First, I developed a novel method …
Culturally Responsive Engineering Education: A Case Study Of A Pre-College Introductory Engineering Course At Tibetan Children's Village School Of Selakui, Marisol Mercado Santiago
Culturally Responsive Engineering Education: A Case Study Of A Pre-College Introductory Engineering Course At Tibetan Children's Village School Of Selakui, Marisol Mercado Santiago
Open Access Dissertations
Culturally responsive teaching has been argued to be effective in the education of Indigenous youth. This approach emphasizes the legitimacy of a group's cultural heritage, helps to associate abstract academic knowledge with the group's sociocultural context, seeks to incorporate a variety of strategies to engage students who have different learning styles, and strives to integrate multicultural information in the educational contents, among other considerations. ^ In this work, I explore the outcomes of a culturally responsive introductory engineering short course that I developed and taught to Tibetan students at Tibetan Children's Village of Selakui (in Uttarakhand, India). Based on my …
Excited States Of Chromophores And Vibronic Interactions, Benjamin T. Nebgen
Excited States Of Chromophores And Vibronic Interactions, Benjamin T. Nebgen
Open Access Dissertations
The main focus of my Ph.D. work has been on building a vibronic coupling model for multichromophores and extending that model to more general systems. This Dissertation serves as both a summary of this work as well as a manual for the two vibronic coupling programs I have written. It is my hope that the instructions written here are complete enough for any who would like to replicate my work on vibronic coupling on other systems. ^ Additionally, I have also worked on a few purely computational projects not directly related to the vibronic coupling work. The status of these …
Acrolein As A Novel Therapeutic Target For Spinal Cord Injury Induced Neuropathic Pain, Jonghyuck Park
Acrolein As A Novel Therapeutic Target For Spinal Cord Injury Induced Neuropathic Pain, Jonghyuck Park
Open Access Dissertations
Despite years of research, post-spinal cord injury (SCI) chronic neuropathic pain remains refractory to treatment and drastically impairs quality of life for SCI victims beyond paralysis. Although inflammation and free radicals contribute to neuropathic pain in SCI, the mechanism is not completely clear. We have recently demonstrated that acrolein, a product and catalyst of lipid peroxidation, induces a vicious cycle of oxidative stress, amplifying its effects and perpetuating oxidative stress and inflammation. In the current study, we have confirmed that acrolein is elevated significantly at least two weeks post-SCI which coincides with the emergence of hyperalgesia (mechanical, cold and thermal). …
Structure-Functionality Relationship Of Collagen Scaffolds For Tissue Engineering, Seungman Park
Structure-Functionality Relationship Of Collagen Scaffolds For Tissue Engineering, Seungman Park
Open Access Dissertations
Tissue engineering is a promising technology that enables scientists to create artificial organs or replace damaged tissues using animal cells and other components. For successful tissue regeneration, many factors should be taken into account, however, three components are most crucial: cell, scaffold, and soluble factor(s). In order to check the functionality after regeneration of desired tissues, various approaches have been attempted, depending on the physical, biological, and chemical properties of the tissues. Recently, the importance of the extracellular matrix (ECM) microstructure is being considered to be important in this regard. The ECM is closely associated with various functional properties of …
Energy Production, Distribution, And Pollution Controls: Combining Engineering And Economic Analysis To Enhance Efficiency And Policy Design, David F. Perkis
Energy Production, Distribution, And Pollution Controls: Combining Engineering And Economic Analysis To Enhance Efficiency And Policy Design, David F. Perkis
Open Access Dissertations
Three published articles are presented which focus on enhancing various aspects of the energy supply chain. While each paper adopts a different methodology, all three combine engineering data and/or techniques with economic analysis to improve efficiency or policy design within energy markets. ^ The first paper combines a chemical engineering plant design model with an economic assessment of product enhancements within an ethanol production facility. While a new chemical process is shown to achieve greater ethanol yields, the animal feed by-products are denatured and decrease in value due to the degradation of a key nutritional amino acid. Overall, yield increases …
Modulation Of Host Phosphatidylinositol Phosphates By Salmonella Effector Protein Sopb, Heather L. Piscatelli
Modulation Of Host Phosphatidylinositol Phosphates By Salmonella Effector Protein Sopb, Heather L. Piscatelli
Open Access Dissertations
Salmonella spp. are gram negative bacteria capable of infecting a number of eukaryotic hosts. In humans, Salmonella infection can range anywhere from acute gastroenteritis to typhoid fever which can oftentimes be fatal.Salmonella are facultative intracellular pathogens that have acquired the ability to enter non-phagocytic cells such as those lining the intestinal epithelium. Uptake into epithelial cells is mediated by the Salmonellapathogenicity island 1 (SPI1) encoded type III secretion system (T3SS), a needle-like complex composed of over 20 proteins that translocates effector proteins directly into the host cell cytosol. Salmonella possess a second type III secretion system encoded on …
Development Of A Static Bioactive Stent Prototype And Dynamic Aneurysm-On-A-Chip(Tm) Model For The Treatment Of Aneurysms, Lisa M. Reece
Development Of A Static Bioactive Stent Prototype And Dynamic Aneurysm-On-A-Chip(Tm) Model For The Treatment Of Aneurysms, Lisa M. Reece
Open Access Dissertations
Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. While these procedures can be effective, it would be advantageous to design a biologically active stent, modified with magnetic stent coatings, allowing cells to be manipulated to heal the arterial lining. Further, velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, but the shear force mechanisms effecting wound closure is elusive. Due to these factors, there is a definite need to cultivate …
Migratory Ecology Of Sea Turtles, Nathan Jack Robinson
Migratory Ecology Of Sea Turtles, Nathan Jack Robinson
Open Access Dissertations
Establishing the movement patterns of free-ranging animals is imperative to understanding their behavior and ecology, and is often necessary for designing effective conservation-strategies. This is especially true for migratory species, such as sea turtles, whose long-distance movements form a major component of their life history. In this thesis, I investigated which factors are driving the migratory behavior of the leatherback turtleDermochelys coriacea. Firstly, I examined whether the timing of the nesting season (nesting phenology) is influenced by oceanographic conditions along the pre-nesting migratory route or by variation in population structure. The discovery that nesting phenology appears more influenced by …
Soil Quality And Nitrogen Cycling Dynamics Altered By Fertility Amendments In Intensively Managed Vegetable Production Systems, Matt A. Rudisill
Soil Quality And Nitrogen Cycling Dynamics Altered By Fertility Amendments In Intensively Managed Vegetable Production Systems, Matt A. Rudisill
Open Access Dissertations
Fresh market vegetable production in the Midwest U.S. is growing rapidly as a result of increased demand for locally-sourced food. High tunnels are becoming increasingly popular among Midwest vegetable growers as these structures offer many production benefits including season extension. However, vegetables require substantial fertility inputs, particularly nitrogen (N), in order to meet desired levels of productivity, and some fertility management strategies can negatively impact soil and environmental quality. This can be particularly problematic in high tunnels, where longer production periods and modification of the growing environment put these systems at greater risk for soil degradation. Identification of fertility practices …
Silica Nanoparticles As Vehicles For Therapy Delivery In Neurological Injury, Desiree Schenk
Silica Nanoparticles As Vehicles For Therapy Delivery In Neurological Injury, Desiree Schenk
Open Access Dissertations
Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. This aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation (LPO), effectively regenerating its self. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of …
A Multilevel Analysis Of Project Lead The Way Implementation In Indiana, Brandon H. Sorge
A Multilevel Analysis Of Project Lead The Way Implementation In Indiana, Brandon H. Sorge
Open Access Dissertations
Using data from the 2010 Indiana public high school graduating class (N=55612), this project employed a multi-level analysis to determine, what if any differences occurred in majoring in STEM and freshman to sophomore year persistence, between students attending a school that offers Project Lead the Way and students that don't, while controlling for being a PLTW student. Additionally, this project explored the mitigating institutional factors that influenced a student majoring in STEM or persisting from their freshman to sophomore year in post-secondary education and if and how these factors varied depending upon if a student took PLTW courses, attended a …
Understanding Preferred Leg Stiffness And Layered Control Strategies For Locomotion, Zhuohua H. Shen
Understanding Preferred Leg Stiffness And Layered Control Strategies For Locomotion, Zhuohua H. Shen
Open Access Dissertations
Despite advancement in the field of robotics, current legged robots still cannot achieve the kind of locomotion stability animals and humans have. In order to develop legged robots with greater stability, we need to better understand general locomotion dynamics and control principles. Here we demonstrate that a mathematical modeling approach could greatly enable the discovery and understanding of general locomotion principles. ^ It is found that animal leg stiffness when scaled by its weight and leg length falls in a narrow region between 7 and 27. Rarely in biology does such a universal preference exist. It is not known completely …