Digital Commons Network^™

Genetic Analysis Of The Hippo Pathway In Mouse Liver, Li Lu

Dissertations and Theses (Open Access)

Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in Drosophila revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the balance of cell proliferation and apoptosis and results in epithelial tissue tumorigenesis. The pathway is therefore believed to be a tumor suppressor pathway. However, a corresponding role in mammals is yet to be determined. Our lab began to investigate the tumor suppression function of the potent mammalian Hippo pathway by putting floxed alleles into the mouse genome flanking the functional-domain-expressing …

Fibulin-2 Stabilizes Tumor Extracellular Matrix And Drives Malignant Progression Of Lung Adenocarcinoma, Brandi N. Baird

Dissertations and Theses (Open Access)

The ECM of epithelial carcinomas undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How tumors maintain ECM integrity in the face of dynamic biophysical forces is still largely unclear. This study addresses these deficiencies using mouse models of human lung adenocarcinoma. Spontaneous lung tumors were marked by disorganized basement membranes, dense collagen networks, and increased tissue stiffness. Metastasis-prone lung adenocarcinoma cells secreted fibulin-2 (Fbln2), a matrix glycoprotein involved in ECM supra-molecular assembly. Fibulin-2 depletion in tumor cells decreased the intra-tumoral abundance of matrix metalloproteinases and reduced collagen cross-linking and tumor compressive properties resulting in …

Simultaneous Induction Of Nkg2d And Nkg2d Ligand For Promoting Immune Surveillance By Il-12 Plus Doxorubicin Treatment, Jiemiao Hu

Dissertations and Theses (Open Access)

NKG2D (natural killer group 2, member D) and its ligands interaction in tumor microenvironment directs tumor infiltrating immune cells to recognize tumor cells, stimulate cytotoxic effector immune cells, and therefore eradicate tumor cells. IL-12, a cytokine produced by antigen presenting cells, has remarkable antitumor effect by activating innate and adaptive immunity. Doxorubicin, a commonly used chemotherapeutic agent also boosts the host antitumor immune response to cause tumor cell death. Our previous publication suggests that IL-12 plus doxorubicin enhances NKG2D function-dependent inhibition of tumor progression and promotes CD8⁺T cells infiltrating into tumors. The purpose of this study is to …

Post-Transcriptional Regulation Of Mammalian Gene Expression In Non-Coding Region Of Target Rna, Jing Lin

Dissertations and Theses (Open Access)

Tumor Suppressor Candidate 2 (TUSC2) is a novel tumor suppressor gene located in the human chromosome 3p21.3 region. TUSC2 mRNA transcripts could be detected on Northern blots in both normal lung and some lung cancer cell lines, but no endogenous TUSC2 protein could be detected in a majority of lung cancer cell lines. Mechanisms regulating TUSC2 protein expression and its inactivation in primary lung cancer cells are largely unknown. We investigated the role of the 5’- and 3’-untranslated regions (UTRs) of the TUSC2 gene in the regulation of TUSC2 protein expression. We found that two small upstream open-reading frames (uORFs) …

Prostate Cancer Stem Cells: Drug To Lerance, Experimental Reconstitution And Castration Resistance, Xin Chen

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is one of the leading malignancies affecting men in the Western world. Although tremendous effort has been made towards understanding PCa development and developing clinical treatments in the past decades, the exact mechanisms of PCa are still not clearly understood. Emerging evidence has postulated that a population of stem cell-like cells inside a tumor, termed ‘cancer stem cells (CSCs)’, may be the cells responsible for tumor initiation, progression, recurrence, metastasis and therapy resistance. Like CSC studies in other cancer types, it has been reported that PCa also contains CSCs. However, there remain several unresolved questions that need …

Induction Of Stronger And Long Lasting Vaccine Immunity To Tuberculosis, Pearl Bakhru

Dissertations and Theses (Open Access)

Tuberculosis is a major cause of death due to an infection in mankind. BCG vaccine protects against childhood tuberculosis although, it fails to protect against adult tuberculosis. BCG vaccine localizes to immature phagosomes of macrophages, and avoids lysosomal fusion, which decreases peptide antigen production. Peptides are essential for macrophage-mediated priming of CD4 and CD8 T cells respectively through MHC-II and MHC-I pathways. Furthermore, BCG reduces the expression of MHC-II in macrophages of mice after infection, through Toll-like receptor-1/2 (TLR-1/2) mediated signaling. In my first aim, I hypothesized that BCG-induced reduction of MHC-II levels in macrophages can decrease CD4 T cell …

Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu

Dissertations and Theses (Open Access)

In this dissertation, I discovered that function of TRIM24 as a co-activator

of ERα-mediated transcriptional activation is dependent on specific histone

modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first

part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated

histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.

Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of

TRIM24-regulated ERα target genes is greatly impaired. Importantly, I

demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen

responsive elements (EREs) in a time-dependent manner upon estrogen

induction, and depletion of their expression exert corresponding time-dependent

effect …

Design, Calibration, And Evaluation Of Depth-Of-Interaction-Capable Pet Detector Modules, Chad J. Bircher

Dissertations and Theses (Open Access)

High-resolution, small-bore PET systems suffer from a tradeoff between system sensitivity, and image quality degradation. In these systems long crystals allow mispositioning of the line of response due to parallax error and this mispositioning causes resolution blurring, but long crystals are necessary for high system sensitivity. One means to allow long crystals without introducing parallax errors is to determine the depth of interaction (DOI) of the gamma ray interaction within the detector module. While DOI has been investigated previously, newly available solid state photomultipliers (SSPMs) well-suited to PET applications and allow new modules for investigation. Depth of interaction in full …

Exploring The Impact Of Decreased Ampk Pathway Activity On Brain Injury Outcome, Julia L. Hill

Dissertations and Theses (Open Access)

Each year, 150 million people sustain a Traumatic Brain Injury (TBI). TBI results in life-long cognitive impairments for many survivors. One observed pathological alteration following TBI are changes in glucose metabolism. Altered glucose uptake occurs in the periphery as well as in the nervous system, with an acute increase in glucose uptake, followed by a prolonged metabolic suppression. Chronic, persistent suppression of brain glucose uptake occurs in TBI patients experiencing memory loss. Abberant post-injury activation of energy-sensing signaling cascades could result in perturbed cellular metabolism. AMP-activated kinase (AMPK) is a kinase that senses low ATP levels, and promotes efficient cell …

Cellular Uptake Of Neutrohpil Elastase Links Inflammation To Adaptive Immunity, Elizabeth A. Mittendorf

Dissertations and Theses (Open Access)

Many tumors arise from sites of inflammation providing evidence that innate immunity is a critical component in the development and progression of cancer. Neutrophils are primary mediators of the innate immune response. Upon activation, an important function of neutrophils is release of an assortment of proteins from their granules including the serine protease neutrophil elastase (NE). The effect of NE on cancer has been attributed primarily to its ability to degrade the extracellular matrix thereby promoting invasion and metastasis. Recently, it was shown that NE could be taken up by lung cancer cells leading to degradation of insulin receptor substrate-1 …

Characterization Of Selective Inhibition Of Adenylyl Cyclase Activity By Small Molecule Inhibitor Nky80, Cameron S. Brand

Dissertations and Theses (Open Access)

The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. Decreasing AC5 activity has been shown to have potential therapeutic benefit, including reduced stress on the heart, pain relief, and attenuation of morphine dependence and withdrawal behaviors. However, AC structure is well conserved, and there are currently no isoform selective AC inhibitors in clinical use.

P-site inhibitors inhibit AC directly at the catalytic site, but with an uncompetitive or noncompetitive mechanism. Due to this mechanism and nanomolar potency in cell-free systems, attempts at ligand-based drug …

Tet1: A Unique Dna Demethylase For Maintenance Of Dna Methylation Pattern, Chunlei Jin

Dissertations and Theses (Open Access)

DNA methylation at the C5 position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification of the genome and has been implicated in numerous cellular processes in mammals, including embryonic development, transcription, X chromosome inactivation, genomic imprinting and chromatin structure. Like histone modifications, DNA methylation is also dynamic and reversible. However, in contrast to well defined DNA methyltransferases, the enzymes responsible for erasing DNA methylation still remain to be studied. The ten-eleven translocation family proteins (TET1/2/3) were recently identified as Fe(II)/2-oxoglutarate (2OG)-dependent 5mC dioxygenases, which consecutively convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine both in vitro and in mammalian …

Homology Cloning, Heterologous Expression And Characterization Of A New Channelrhodopsin, Sing-Yi Hou

Dissertations and Theses (Open Access)

Channelrhodopsins are phototaxis receptors in the plasma membranes of motile unicellular algae. They function as light-gated cation channels and this channel activity has been exploited to trigger action potentials in neurons with light to control neural circuits (“optogenetics"). Four channelrhodopsins were identified in two algal species, Chlamydomonas reinhardtii and Volvox carteri, with known genome sequences; each species contains 2 channelrhodopsins, one absorbing at longer wavelengths and one at shorter wavelengths, named CrChR1 and CrChR2, respectively. Our goals are to expand knowledge of channelrhodopsin mechanisms and also to identify new channelrhodopsins from various algal species with improved properties …

Can The States Keep Secrets From The Federal Government?, Robert A. Mikos

Vanderbilt Law School Faculty Publications

States amass troves of information detailing the regulated activities of their citizens, including activities that violate federal law. Not surprisingly, the federal government is keenly interested in this information. It has ordered reluctant state officials to turn over their confidential files concerning medical marijuana, juvenile criminal history, immigration status, tax payments, and employment discrimination, among many other matters, to help enforce federal laws against private citizens. Many states have objected to these demands, citing opposition to federal policies and concerns about the costs of breaching confidences, but the lower courts have uniformly upheld the federal government’s power to commandeer information …

Intraspecific Density Dependence And A Guild Of Consumers Coexisting On One Resource, Mark A. Mcpeek

Dartmouth Scholarship

The importance of negative intraspecific density dependence to promoting species coexistence in a community is well accepted. However, such mechanisms are typically omitted from more explicit models of community dynamics. Here I analyze a variation of the Rosenzweig-MacArthur consumer–resource model that includes negative intraspecific density dependence for consumers to explore its effect on the coexistence of multiple consumers feeding on a single resource. This analysis demonstrates that a guild of multiple consumers can easily coexist on a single resource if each limits its own abundance to some degree, and stronger intraspecific density dependence permits a wider variety of consumers to …

Stranger Of The House: The Evolution Of Sensation's New Man, Laura Mogel

All Theses

While Elaine Showalter argues that the 'crisis in masculinity' occurs with the emergence of the New Woman and the fin de sicle, this thesis suggests that men, specifically here wealthy men, were in crisis long before these phenomena due to their dissolved understanding of their place and position amidst immense changes in Victorian England. An interrogation of 1860s sensation fiction, and specifically Wilkie Collins's Basil and Mary Elizabeth Braddon's Lady Audley's Secret, suggests that men grappled with their position and masculinity prior to the fin de sicle as evidenced by the heroine-prescribed social deaths of Basil and George Talboys. After …

Bioswellable Amphiphilic Copolymers, David Ingram

All Theses

The suture is one of the most commonly used medical devices, consisting of a fiber, a surgical needle and the packaging in which it is stored. The fiber itself remains after implantation for a defined time and is responsible for the approximation of the wound during the healing process. The needle merely serves to aid in insertion, and preferably has a diameter larger than the diameter of the fiber .
The 1970's marked the birth of a new family of fibrous materials for the approximation of wounds: synthetic absorbable sutures. This family has the ability to provide wound support during …

Can The Application Of A Landscape Designed Learning Environment Enhance Education?, Virginia Bailey

All Theses

There is a need for a restructuring the way that a child's learning environment is designed. Currently, the mainstream educational design process ignores the notion that children have different ways of learning. Furthermore, when there are so many distractions, how we successfully reach a child's mind has become a challenge. The current school system is structured in a manner that does not address the presence of these distractions, often causing overstimulation and inattentiveness. Designing for children should be approached in a way that all senses are engaged. Having opportunities for hands-on learning inside and outside of the classroom is important …

Ammonia Measurements And Emissions From A California Dairy Using Point And Remote Sensors, Kori D. Moore, E. Young, C. Gurell, Michael D. Wojcik, Randy S. Martin, G. E. Bingham, R. L. Pfeiffer, J. H. Prueger, J. L. Hatfield

Civil and Environmental Engineering Faculty Publications

Ammonia (NH3) is an important trace gas species in the atmosphere that can have negative impacts on human, animal, and ecosystem health. Agriculture has been identified as the largest source of NH3, specifically livestock operations. NH3 emissions from a commercial dairy in California were investigated during June 2008. Cattle were held in open-lot pens, except for young calves in hutches with shelters. Solid manure was stored in the open-lot pens. Liquid manure from feed lanes was passed through a solids settling basin and stored in a holding pond. Passive sensors and open-path Fourier transform infrared spectrometers (OP-FTIR) were deployed around …

The Effects Of 0.2 Hz Varying Latency With 20-100 Ms Varying Amplitude On Simulator Sickness In A Helmet Mounted Display, Matthew St. Pierre

All Dissertations

The relationship between the occurrence of simulator sickness (SS) and the several characteristics of latency (i.e., added latency, amplitude of latency, and frequency of latency) in a helmet-mounted display (HMD) were explored in this study. The experience of SS while using an HMD has often been attributed to system latency. These findings are typical in research where HMDs with head trackers are used. The current study explored the effects of 200 ms added constant latency, latency varying at 0.2 Hz with a constant 100 ms amplitude, and latency varying at 0.2 Hz with a 20-100 ms varying amplitude on the …

Molecular Genetics Of Nodule Number Regulation: Cloning, Characterization And Functional Studies Of The Root Determined Nodulator1 (Rdn1) Gene In Medicago Truncatula, Tessema Kassaw

All Dissertations

Nitrogen is critical to life. However, the majority of nitrogen on earth (in the atmosphere) is inert and unavailable to nearly all organisms. Metabolically diverse prokaryotes are the only organisms capable of fixing atmospheric nitrogen; rhizobia set up a symbiosis with legume plants allowing the plants to benefit from this ability. Since nodulation and the subsequent nitrogen fixation processes are energy intensive, the host plant must balance hosting of the rhizobia by limiting the number of nodules it forms through a mechanism called Autoregulation of Nodulation (AON). My study of mutants in the model legume Medicago truncatula defective in AON …

Analyses Of Consumer Perceptions, Farmer Challenges, Polyamine, And Amino Acid Content Of Organic And Conventional Fresh Produce Grown In South Carolina, Emily Steinberg

All Dissertations

Execution of the USDA organic standards led to more support for local food as distinct from organic food. The current study was conducted to examine fresh produce perceptions and purchasing decisions of S.C. consumers. Four-hundred and eight S.C. consumers were surveyed at S.C. grocery stores. More than one-third of the S.C. consumers not knowing about the 'certified S.C. grown' program suggest that the S.C. Department of Agriculture (SCDA) may want to improve the promotion of their program. Eighty-five percent of consumers indicated that they would choose local over organic. This information would be useful to local S.C. produce farmers who …

Policy Evaluation Using Cost-Benefit Analysis: Empirical Ramifications For Two Policy Issues, Elizabeth Crouch

All Dissertations

Using two distinct health policy issues my research examines the relevance and ramifications of using cost-benefit analysis (CBA) to demonstrate real-world impacts of the policies. My dissertation discusses how these two situations represent particular challenges to cost-benefit analysis. The challenges have specific implications for how scholars, agencies, and government entities should use CBA to evaluate policies. Specifically, my research finds that by separating CBA into four different approaches, a much more complete, and less assumption-laden, CBA can be accomplished.

Energy Conserving Privacy Enhancing Algorithms For Resource-Constrained Devices, Michael Groat

Computer Science ETDs

Resource-constrained devices such as wireless sensor networks, body area networks, or smart phones collect confidential and sensitive information about their users. Traditional solutions to protect these data, such as encryption, consume a significant amount of resources to be viable. In this dissertation, I present two energy efficient information collection protocols based on the notion that by relaxing the definition of privacy, such as using indistinguishability, energy use can be reduced. The first protocol, multi-dimensional negative surveys (MDNSs), protects multivariate categorical data by perturbing sensed values to something other than what was actually sensed, and transmits the perturbed values to a …

Gene Duplication And The Evolution Of Hemoglobin Isoform Differentiation In Birds, Michael T. Grispo

School of Biological Sciences: Dissertations, Theses, and Student Research

The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes: HbA (the major adult Hb isoform, with α-chain subunits encoded by the α^A-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the α^D-globin gene). The α^D-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, …

Hell On The Range: A Story Of Honor, Conscience, And The American West, Daniel J. Herman, Taunalyn F. Rutherford

BYU Studies

In the introduction to Hell on the Range, Daniel Justin Herman informs readers that his account of Arizona's Rim Country War of the 1880s is more than revisionist critique; it is self-critique. Herman, an associate professor of history at Central Washington University, is an Arizonan who, like many growing up in the western United States, was "raised on its romance," and in his youth he viewed "Arizonans--especially cowboys--[as] made of sterner, stronger stuff than people who grew up elsewhere" (xxii). His view of Mormons and Mormonism--an important undercurrent animating much of this book--was informed by his experiences as a non-Mormon …

Avian Diversity And Habitat Use On Wetland Reserve Program Lands In The Lower Missouri River Valley, Eric C. Hopps

The Prairie Naturalist

A primary objective of the Wetland Reserve Program (WRP) is to provide habitat for migratory birds throughout all seasons of the year. Comprehensive avian assessments are lacking and limit our ability to evaluate the benefits of the WRP to continental bird populations. I investigated avian species occurrence on WRP lands within the Lower Missouri River Valley (LMRV), Nebraska, USA, from March 2010 to February 2011. Ten WRP habitat types are described based on plant community assemblages and observed hydrological regimes. Estimates of avian species richness were greatest in lowland forest (n = 115), lowland woodland (n = 83) and upland …

Fish Assemblage Structure In Black Hills, South Dakota Streams, Luke D. Schultz, Sarah J. Lewis, Katie Nicole Bertrand

The Prairie Naturalist

Understanding factors structuring fish assemblages in a particular area is valuable to both sport fishery management and native species conservation. Fish assemblages in the Black Hills are unique to South Dakota because they contain economically valuable introduced salmonids as well as native species of conservation need. Our objective was to examine the relationship between fish assemblages and geomorphic and reach-scale habitat features across multiple stream reaches in the Black Hills. Canonical correspondence analysis, a direct gradient ordination analysis, indicated that factors operating at multiple spatial scales interacted to structure fish assemblages. There also was indication of segregation between native species …

Walleye Trophic Position Before And After A Gizzard Shad Extirpation, Bethany J. Bethke, Justin A. Vandehey, Mark J. Fincel, Brian D.S. Graeb, Mark T. Porath

The Prairie Naturalist

Walleye (Sander vitreus) are an ecologically and recreationally important sport fish species. Reduced growth and condition in walleye can occur when prey availability is limited. In two Nebraska reservoirs, walleye consumed gizzard shad (Dorosoma cepedianum) as their primary prey until a winterkill extirpated the gizzard shad in 2001. Because of the winterkill, walleye in the two reservoirs had to change to alternative prey items. Our objective was to determine if stable isotope analysis on archived walleye scales can be used to detect a known food web shift in two reservoir food webs. We quantified the changes …

Repudiating The Narrow Rule In Capital Sentencing, Scott W. Howe

BYU Law Review

This Article proposes a modest reform of Eighth Amendment law governing capital sentencing to spur major reform in the understanding of the function of the doctrine. The Article urges the Supreme Court to renounce a largely empty mandate known as the “narrowing” rule and the rhetoric of equality that has accompanied it. By doing so, the Court could speak more truthfully about the important but more limited function that its capital-sentencing doctrine actually pursues, which is to ensure that no person receives the death penalty who does not deserve it. The Court could also speak more candidly than it has …