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2011

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The Structural Basis Of Flaviviridae Interaction With Antibodies And Receptors, Vincent Luca Jan 2011

The Structural Basis Of Flaviviridae Interaction With Antibodies And Receptors, Vincent Luca

All Theses and Dissertations (ETDs)

Flaviviridae are a family of enveloped, positive-stranded RNA viruses responsible for a variety of diseases including encephalitis, hemorrhagic fever and hepatocellular carcinoma. The envelope: E) proteins that coat the outer surface of these viruses provide the molecular machinery that drives receptor interaction and membrane fusion. The assignment of biological functions to specific structural elements of these E proteins has proven crucial to the understanding of viral entry into host cells. Clearance is dependent upon the presence of neutralizing antibodies that are able to disrupt several stages of this process. Given their fundamental role in the viral life cycle, we sought …

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Egfr Signaling Regulates Synaptic Connectivity Via Gurken, Sarah Naylor Jan 2011

Egfr Signaling Regulates Synaptic Connectivity Via Gurken, Sarah Naylor

All Theses and Dissertations (ETDs)

The synapse is the essential unit of neural function. It is critical to understand how synapses form during development, how they are maintained throughout the life of an organism, and how their structure and function are affected by neural activity. An understanding of these aspects of synapses will likely provide insight into the etiology of neurodevelopmental disorders such as autism, mental retardation or epilepsy. To identify novel regulators of synaptic development, I screened for mutants with defects in synaptic morphology and growth at the Drosophila larval neuromuscular junction: NMJ). My screen identified several mutants with defects in various aspects of …

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Quantitative Assessment Of Lung Microstructure In Healthy Mice Using An Mr-Based 3he Lung Morphometry Technique, Emir Osmanagic Jan 2011

Quantitative Assessment Of Lung Microstructure In Healthy Mice Using An Mr-Based 3he Lung Morphometry Technique, Emir Osmanagic

All Theses and Dissertations (ETDs)

Recently developed in our laboratory the MRI-based technique - 3He Lung Morphometry - is a unique tool allowing in vivo measurements of lung microstructural parameters such as alveolar volume, surface-to-volume ratio and alveolar density. These parameters are commonly used by lung physiologists and pathologists but were previously available only from invasive biopsy studies. 3He Lung Morphometry was originally developed for human studies but there is a need to expand it for studies of small animals like mice and rats that are used to advance our knowledge of lung physiology in health and disease and for development of drugs. Such an …

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Design, Synthesis And Characterization Of Lipidated Pna-Peptide Conjugates As Potentialtherapeutic And Diagnostic Reagents, Yinyin Song Jan 2011

Design, Synthesis And Characterization Of Lipidated Pna-Peptide Conjugates As Potentialtherapeutic And Diagnostic Reagents, Yinyin Song

All Theses and Dissertations (ETDs)

Peptide Nucleic Acids: PNAs), are an ideal choice for antisense and antigene tools and probes because of their stability and high binding affinity, but have limited application as therapeutic and diagnostic agents because of poor membrane permeability. To increase membrane permeability, we conjugated hydrophobic lipids or phospholipid molecules and hydrophilic cell penetrating peptides to the N and C terminus of PNAs, and studied their physical and biological properties. After solid-phase automated synthesis, PNA-CPPs: TAT/Arg9) were coupled with lipids or phospholipids before cleavage from the support and then purified by HPLC. The conjugates were characterized by UV-vis and MALDI, and by …

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The Role Of The Membrane Proximal Region Of The M2 Cytoplasmic Tail In Virus Replication, Shaun Stewart Jan 2011

The Role Of The Membrane Proximal Region Of The M2 Cytoplasmic Tail In Virus Replication, Shaun Stewart

All Theses and Dissertations (ETDs)

Influenza A virus encodes M2, a proton channel that has been shown to be important during virus entry and assembly. The primary aim of this thesis was to investigate the role of the membrane proximal region, residues 46-69, of the M2 cytoplasmic tail during virus replication. A cholesterol recognition/interaction amino consensus: CRAC) motif, previously identified in the membrane proximal region of M2 in some influenza A virus strains, was suggested to play a role in virus replication by mediating incorporation of M2 into budding virus particles. Alteration or completion of the M2 CRAC motif in two different recombinant virus strains …

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Development Of Thymic Natural Killer Cells From Double Negative 1 Thymocyte Precursors, Claudia Vargas Jan 2011

Development Of Thymic Natural Killer Cells From Double Negative 1 Thymocyte Precursors, Claudia Vargas

All Theses and Dissertations (ETDs)

While there has been much progress in defining the specificity and function of natural killer: NK) cells, their differentiation has not been fully elucidated. Previous studies of thymocyte development in vitro indicate that double negative: CD4&minusCD8&minus, DN) thymocytes can develop into cells with NK cell markers, but these cells have not been well characterized. Moreover, a subpopulation of NK cells which requires an intact thymus, i.e, thymic NK cells, has been described with selective expression of CD127 although their origin and differentiation are also poorly understood. Herein, we generated and characterized NK cells differentiating from thymic DN precursors. We enriched …

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The Expression Pattern And Localization Of Linc Complex Components During Mouse Retina Development, Gregory Peebles Jan 2011

The Expression Pattern And Localization Of Linc Complex Components During Mouse Retina Development, Gregory Peebles

All Theses and Dissertations (ETDs)

No abstract provided.

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The Role Of Fas With Fas Ligand Interaction In Herpetci Stromal Keratitis (Hsk), Hamideh Zakeri Jan 2011

The Role Of Fas With Fas Ligand Interaction In Herpetci Stromal Keratitis (Hsk), Hamideh Zakeri

All Theses and Dissertations (ETDs)

No abstract provided.

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Bi-Harmonic Atomic Force Microscopy, Santosh R. Kodandarama Jan 2011

Bi-Harmonic Atomic Force Microscopy, Santosh R. Kodandarama

Masters Theses

"In tapping mode atomic force microscopy, surface features are measured indirectly via the amplitude of the tapping cantilever. A change in surface profile is detectable only if it results in an amplitude change that is significant enough to be measured by the optics. Previous works have focused on improving sensitivity through the system's Q-factor, either by changing physical cantilever properties or using feedback control, but those approaches undesirably slow down the dynamic response. In this work we take a novel approach to sensitivity amplification by reshaping the tapping trajectory. By shaping the trajectory so that the probe spends a greater …

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How It Began: The Rise Of The Women's Suffrage Movement In Britain, Shihui Yun Jan 2011

How It Began: The Rise Of The Women's Suffrage Movement In Britain, Shihui Yun

All Theses and Dissertations (ETDs)

No abstract provided.

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Generating Muscle Driven Arm Movements Using Reinforcement Learning, Alex S. Broad Jan 2011

Generating Muscle Driven Arm Movements Using Reinforcement Learning, Alex S. Broad

All Computer Science and Engineering Research

This project focuses on using Reinforcement Learning to optimize arm dynamics through muscle control for desired trajectories. The goal of this project was to create a tool that can be used to gain a better understanding of the arm’s muscles and collect information that is useful in many other disciplines such as biomechanics, anthropology, medicine and robotics. I developed biologically realistic models of primate arm's using Stanford’s SimTK software, an open-source tool for modeling musculoskeletal structures. I then made use of Differential Dynamic Programming in order to generate novel movements from first principles and optimize motion over a specified trajectory. …

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Role Of Hyperglycemia, Hypoglycemia, And Glucose Transporter 4 On Brain Glucose Sensing, Counterregulation, And Neuronal Viability, Erwin Puente Jan 2011

Role Of Hyperglycemia, Hypoglycemia, And Glucose Transporter 4 On Brain Glucose Sensing, Counterregulation, And Neuronal Viability, Erwin Puente

All Theses and Dissertations (ETDs)

As glucose is the main fuel source for the brain and a major nutrient for peripheral tissues, the brain must sense and respond to changes in blood glucose in order to sustain its own nutritional requirements and maintain whole body energy homeostasis. Disruption of brain glucose sensing results in impaired glucose tolerance, a hallmark in the pathogenesis of diabetes, as well as increased risk of severe hypoglycemia as occurs with insulin therapy. Thus, understanding how the brain senses and responds to changes in glucose is particularly important to individuals with diabetes. Experiments in this thesis investigated: 1) the role of …

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Dynamic Measurement Of Soluble Human Aβ In A Combined Microdialysis-Experimental Traumatic Brain Injury Mouse Model, Katherine Schwetye Jan 2011

Dynamic Measurement Of Soluble Human Aβ In A Combined Microdialysis-Experimental Traumatic Brain Injury Mouse Model, Katherine Schwetye

All Theses and Dissertations (ETDs)

The amyloid-β peptide: Aβ) plays a central pathophysiological role in Alzheimer's disease, but little is known about its dynamics in the brain's extracellular space. A recent microdialysis-based study in human patients with severe brain injuries found that extracellular Aβ dynamics correlate with changes in neurological status. Because neurological status is generally diminished following injury, this correlation suggests that extracellular Aβ is reduced relative to baseline. However, human studies cannot assess pre-injury Aβ levels, very early post-injury Aβ levels, nor the relationship between extracellular Aβ and total tissue levels. Therefore, we developed a mouse model that combines experimental TBI with microdialysis …

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Opposing Crosstalk Between Rho1 And Cdc42 In Epithelial Morphogenesis, Steve Warner Jan 2011

Opposing Crosstalk Between Rho1 And Cdc42 In Epithelial Morphogenesis, Steve Warner

All Theses and Dissertations (ETDs)

Epithelial cells line all surfaces of the body exposed to external environments where they perform critical roles for maintaining homeostasis. In addition, epithelial cells are implicated in several disease processes and are the most common cell type implicated in cancer. Therefore, understanding the regulation of epithelial cell development and function has important implications for adult homeostasis and disease states. The Rho family of small GTPases functions in a wide array of cellular processes in epithelial cells. However, in mammals Rho subfamilies have multiple members, often with overlapping roles, complicating the precise determination of Rho protein function in epithelial cells, especially …

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Specific Roles Of Macaque Parietal Regions In Making Saccades And Reaches, Eric Yttri Jan 2011

Specific Roles Of Macaque Parietal Regions In Making Saccades And Reaches, Eric Yttri

All Theses and Dissertations (ETDs)

A principle task of our brain is to guide movements, includng saccade: fast eye movements) and reaches towards things that we see. Regions in the parietal cortex such as LIP and PRR are active during visually-guided movements. Neurons in these areas respond differentially for saccades versus reaches, but in most parietal areas there is some response: in single unit recording as well as in fMRI imaging) with either type of movement. This raises an important question. What is the functional significance of the neuronal activity in parietal areas? Recording and imaging studies can only show correlations; causal roles must be …

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Mass Spectrometry-Based Structural Proteomics: Bottom-Up Protein Footprinting And Top-Down Native Electrospray Of Protein Assemblies, Hao Zhang Jan 2011

Mass Spectrometry-Based Structural Proteomics: Bottom-Up Protein Footprinting And Top-Down Native Electrospray Of Protein Assemblies, Hao Zhang

All Theses and Dissertations (ETDs)

Converting gene-sequence information into functional information about a protein is a major challenge of post-genomic biology. Proteins have a variety of functions from serving as catalysts to acting as structural components; all these functions are closely related to protein structure. The first step to understand protein function is often a structural study of that protein. Two major approaches, NMR spectroscopy and X-ray crystallography, can provide an atomic-level, 3D structural model of a protein. The applications of these high resolution approaches, however, are limited by protein size, conformational flexibility, and aggregation propensity. To obtain complementary structural information about proteins, a variety …

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Clinical Interpretation Of Novel Copy Number Variations, Clifton Carey Jan 2011

Clinical Interpretation Of Novel Copy Number Variations, Clifton Carey

All Theses and Dissertations (ETDs)

Copy Number Variations: CNVs) are a significant source of human genetic diversity and are believed to be responsible for a wide variety of phenotypic variation. Recent advances in microarray-based genomic hybridization techniques have facilitated CNV analysis as a viable diagnostic technique in the clinic, and several public databases of well-characterized CNVs are being compiled, but a standard for interpreting uncharacterized CNVs has yet to emerge. This thesis examines the clinical interpretation of uncharacterized CNVs as a multiple instance binary classification problem. We analyze the current state of clinical techniques, then present and test several novel statistical approaches to the problem.

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Exploring The Potential Of Inkjet Printing For The Fabrication Of Tissue Test Systems, Vidya Seshadri Jan 2011

Exploring The Potential Of Inkjet Printing For The Fabrication Of Tissue Test Systems, Vidya Seshadri

All Theses

Animal models and two-dimensional assays involved in drug testing, vaccine development and basic scientific discovery are not an accurate representation of the human body; hence there is a need to develop new bench top methodologies which are better suited to yield information about in vivo behavior. There is a paucity of reliable in vitro-derived information regarding the reasons for the cause and progression of diseases. These concerns have lead to the development of three-dimensional systems which can facilitate improved understanding of disease etiology and also can bridge the path to the clinic.
The long term goal, beyond the scope of …

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Cloning, Expression Analysis, And Transformation Vector Construction Of Dam Homologs In Peach And Poplar, Yuhui Xie Jan 2011

Cloning, Expression Analysis, And Transformation Vector Construction Of Dam Homologs In Peach And Poplar, Yuhui Xie

All Theses

Genetic fine mapping and sequencing of the EVG locus in peach [Prunus persica (L.) Batsch] identified six tandem arrayed Dormancy-Associated MADS-box (DAM) genes as candidates for regulating growth cessation and terminal bud formation in the non-dormant evergrowing (evg) mutant. Since the mutant is lacking expression of six genes in the mapped locus, further functional analysis is needed to narrow the list of gene candidates for the non-dormant evg phenotype. Here I report three sets of experiments designed to functionally test DAM genes in peach and their homologs in a model tree, hybrid poplar.
First I constructed overexpression and knockdown vectors …

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Cortical Cartography: Mapping Functional Areas Across The Human Brain With Resting State Functional Connectivity Mri, Alexander Cohen Jan 2011

Cortical Cartography: Mapping Functional Areas Across The Human Brain With Resting State Functional Connectivity Mri, Alexander Cohen

All Theses and Dissertations (ETDs)

Human behavior and cognition are largely supported by the cerebral cortex, a structure organized at many physical scales ranging from individual neurons up to distributed systems of multiple interconnected “functional areas”. Each functional area possesses a unique combination of inputs, outputs, and internal structure, and is thought to make a distinct contribution to information processing. Thus, the study of each area's normal function, developmental trajectory, and modified responses following loss or injury may greatly enhance our understanding of cognition. Indeed, one of the: often unsaid) overarching goals of functional neuroimaging is to use differential activity between conditions to identify specific …

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Apobec-1 Complementation Factor (Acf) Binds And Regulates Multiple Rnas, Kimberly Delaney Jan 2011

Apobec-1 Complementation Factor (Acf) Binds And Regulates Multiple Rnas, Kimberly Delaney

All Theses and Dissertations (ETDs)

AU-Rich Elements: ARE) are cis-acting RNA sequences in the 3'UTRs of a wide range of transcripts that function to regulate mRNA stability, localization, and/or translation through interaction with ARE-Binding Proteins. Apobec-1 Complementation Factor: ACF) was originally identified as a co-factor in ApoB mRNA C to U editing, but has recently been implicated in regulation of mRNA stability as an ARE-Binding Protein. Here we have used tissue culture models with RNA turnover assays to show that the stability of reporters cloned upstream of the Interleukin-6: IL-6) 3'UTR or portions of the Cox-2 3'UTR is regulated by levels of ACF expression. Surprisingly, …

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Regulation Of Neutrophil Homeostasis By Chemokines Signaling Through The Cxcr2 And Cxcr4 Receptors, Kyle Eash Jan 2011

Regulation Of Neutrophil Homeostasis By Chemokines Signaling Through The Cxcr2 And Cxcr4 Receptors, Kyle Eash

All Theses and Dissertations (ETDs)

The number of neutrophils in the blood is tightly regulated to ensure adequate protection against microbial pathogens while minimizing damage to host tissue. Neutrophil homeostasis in the blood is achieved through a balance of neutrophil production, release from the bone marrow, and clearance from the circulation. Accumulating evidence suggests that chemokine signaling in the bone marrow may play a key role in maintaining neutrophil homeostasis. Based on this evidence, we developed a "tug-of-war" model in which opposing chemokine gradients, specifically release-inducing CXCR2 signals and retention-promoting CXCR4 signals, act antagonistically to regulate neutrophil release from the bone marrow. We generated mice …

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The Functions Of Autophagy Genes In Lymphocytes And Osteoclasts, Brian Miller Jan 2011

The Functions Of Autophagy Genes In Lymphocytes And Osteoclasts, Brian Miller

All Theses and Dissertations (ETDs)

Macroautophagy: herein autophagy) is a process by which cells degrade long-lived proteins and organelles. The autophagy pathway and autophagy genes have been implicated in many functions in the cell such as protecting against metabolic stress, degrading damaged organelles, and regulating vesicular trafficking. To study the role of autophagy in primary cells with important physiologic functions, we generated mice lacking essential autophagy genes in B lymphocytes, T lymphocytes, and osteoclasts. We found that the essential autophagy gene Atg5 was important for B cell development and for the maintenance of B-1a B cell numbers but not peripheral B-2 B cell numbers. In …

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Examination Of Uv-Cross-Linkable Di-Block Copolymer Strategy For Functionalized Reaction Surface On Microelectrode Arrays, Libo Hu Jan 2011

Examination Of Uv-Cross-Linkable Di-Block Copolymer Strategy For Functionalized Reaction Surface On Microelectrode Arrays, Libo Hu

All Theses and Dissertations (ETDs)

Microarrays are powerful tools for high-throughput screening of small molecule libraries. Our group is using a microelectrode array variant on these efforts that allows us to construct and screen the libraries in a rapid, cost effective fashion. In this approach, the small molecules are attached to polymer-coated microelectrodes, which can be used to detect ligand-receptor interactions as they happen by means of impedance. Impedance experiment work by monitoring the current associated with a redox couple in solution. When a protein binds a ligand on the array, it sterically prevents the redox couple from reaching the electrode surface and thus causes …

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Effects Of The Aquatic To Terrestrial Habitat Ratio On An Amphibian Predator And Its Prey, Amber Kramer Jan 2011

Effects Of The Aquatic To Terrestrial Habitat Ratio On An Amphibian Predator And Its Prey, Amber Kramer

All Theses and Dissertations (ETDs)

This dissertation explores the effects of varying the composition of aquatic and terrestrial habitats in a landscape: the aquatic to terrestrial ratio) on amphibians that use both the aquatic and terrestrial habitats during their lives. In Chapter 1, I first used meta-analysis and simulations to demonstrate that as the longevity of an amphibian increases, the elasticity of the population growth rate to perturbations in the aquatic: larval) habitat decreases. In Chapter 2, I examined the abundance of larvae of a long-lived amphibian, Ambystoma maculatum, across landscapes that varied in their aquatic to terrestrial ratios and found that larvae of this …

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Efficient Automated Planning With New Formulations, Ruoyun Huang Jan 2011

Efficient Automated Planning With New Formulations, Ruoyun Huang

All Theses and Dissertations (ETDs)

Problem solving usually strongly relies on how the problem is formulated. This fact also applies to automated planning, a key field in artificial intelligence research. Classical planning used to be dominated by STRIPS formulation, a simple model based on propositional logic. In the recently introduced SAS+ formulation, the multi-valued variables naturally depict certain invariants that are missed in STRIPS, make SAS+ have many favorable features. Because of its rich structural information SAS+ begins to attract lots of research interest. Existing works, however, are mostly limited to one single thing: to improve heuristic functions. This is in sharp contrast with the …

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Low-Impact Profiling Of Streaming, Heterogeneous Applications, Joseph Lancaster Jan 2011

Low-Impact Profiling Of Streaming, Heterogeneous Applications, Joseph Lancaster

All Theses and Dissertations (ETDs)

Computer engineers are continually faced with the task of translating improvements in fabrication process technology: i.e., Moore's Law) into architectures that allow computer scientists to accelerate application performance. As feature-size continues to shrink, architects of commodity processors are designing increasingly more cores on a chip. While additional cores can operate independently with some tasks: e.g. the OS and user tasks), many applications see little to no improvement from adding more processor cores alone. For many applications, heterogeneous systems offer a path toward higher performance. Significant performance and power gains have been realized by combining specialized processors: e.g., Field-Programmable Gate Arrays, …

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The Role Of Dsrna In Nuclear Differentiation And Remodeling In The Ciliate, Tetrahymena Thermophila, Jason Motl Jan 2011

The Role Of Dsrna In Nuclear Differentiation And Remodeling In The Ciliate, Tetrahymena Thermophila, Jason Motl

All Theses and Dissertations (ETDs)

The ciliate, Tetrahymena thermophila, like a handful of other eukaryotes, engages in massive genome reorganization known collectively as chromatin diminution. Part of this process involves large-scale DNA excision known as DNA elimination. Recent data has shown DNA elimination to be dependent on RNA interference: RNAi). Using T. thermophila, I have sought to determine the role of non-coding RNA: ncRNA) in RNAi-dependent DNA elimination through studies of DNA sequences that are to be eliminated called internal eliminated sequences: IESs) and through a conjugation-specific Dicer protein and its putative tandem dsRNA-binding motif: DSRM) protein partners. Studies of the R IES revealed the …

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Interactions Between Bmp And Canonical Wnt Signaling Regulate Critical Stages Of The Osteoblast Lifecycle, Valerie Salazar Jan 2011

Interactions Between Bmp And Canonical Wnt Signaling Regulate Critical Stages Of The Osteoblast Lifecycle, Valerie Salazar

All Theses and Dissertations (ETDs)

Skeletal development and post-natal bone homeostasis are dependent on the coordinated activity of bone-forming cells called osteoblasts and bone-resorbing cells called osteoclasts. Over 10 million people in the US currently suffer from osteoporosis, which increases the risk of low-trauma fractures and accounts for health care expenditures exceeding $14 billion per year. Osteoporosis is often treated with anti-resorptive compounds, primarily bisphosphonates, which inhibit osteoclast-mediated bone destruction. However, these drugs do not restore bone mass, which can only be accomplished by activation new bone formation, as with intermittent parathyroid hormone therapy. The development of additional bone "anabolic" therapies will require genetic and …

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Using Visual Feedback To Guide Movement: Properties Of Adaptation In Changing Environments And Parkinson's Disease, Jennifer Semrau Jan 2011

Using Visual Feedback To Guide Movement: Properties Of Adaptation In Changing Environments And Parkinson's Disease, Jennifer Semrau

All Theses and Dissertations (ETDs)

On a day-to-day basis we use visual information to guide the execution of our movements with great ease. The use of vision allows us to guide and modify our movements by appropriately transforming external sensory information into proper motor commands. Current literature characterizes the process of visuomotor adaptation, but fails to consider the incremental response to sensed errors that comprise a fully adaptive process. We aimed to understand the properties of the trial-by-trial transformation of sensed visual error into subsequent motor adaptation. In this thesis we further aimed to understand how visuomotor learning changes as a function of experienced environment …

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