Characterization Of Erbb4 Expression In Osteosarcoma, Nupur Lala

Dissertations and Theses (Open Access)

ERBB4 (Her-4) is a member of the ERBB family of Class I receptor tyrosine kinases. ERBB4 is unique within the ERBB family for alternate splicing in its juxtamembrane and cytoplasmic regions, which produces four juxtamembrane isoforms and two cytoplasmic isoforms. The cleavable juxtamembrane isoforms, Jm-a and Jm-d, can undergo proteolytic cleavage and produce an 80-kDa cytoplasmic fragment referred to as “p80,” which has been demonstrated to enhance cellular survival and malignant behavior in many solid tumors [44]. ERBB4 was almost exclusively 80 kDa in size and localized to the nucleus in primary tumors and metastases in studies characterizing ERBB4 expression …

Regulation Of The Oxidative Stress Response By Arid1a, Suet Yan Kwan

Dissertations and Theses (Open Access)

SWI/SNF is mutated in about 20% of all human cancers; in particular ARID1A is the most frequently mutated SWI/SNF subunit. ARID1A is a tumor suppressor gene, inactivating mutations in ARID1A are most frequently found in ovarian and endometrial cancers, specifically uterine corpus endometrioid carcinomas (UCEC), ovarian clear cell carcinomas (OCCC) and ovarian endometrioid carcinomas (OEC). The functional roles of ARID1A are not completely understood and there are limited therapeutic strategies that specifically target ARID1A-mutant cancers. Given that ARID1A expression is lost in cancer, ARID1A mutations cannot be targeted directly and novel therapeutic strategies are required to target ARID1A-mutant …

In Vivo Functional Significance Of Ccat2 Long Non-Coding Rna In Myelodysplastic Syndrome, Maitri Y. Shah

Dissertations and Theses (Open Access)

Long non-coding RNAs form the largest part of the mammalian non-coding transcriptome and control gene expression at various levels including chromatin modification, transcriptional and post-transcriptional processing. Although the underlying molecular mechanisms are not yet entirely understood, lncRNAs are implicated in initiation and progression of several cancers. CCAT2 is a lncRNA that spans the highly conserved 8q24 region associated with increased risk for various cancers. CCAT2 has been shown to play an important role in inducing chromosomal instability and supporting cell proliferation and cell cycle arrest. However, a causal role of CCAT2 in initiation of tumorigenesis and the importance of G/T …

Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cytotoxic lymphocytes, which play a critical role in the immune response against malignant cells and microbial infections. NK cells are equipped with activating receptors, which upon detecting ligands expressed on stressed cells induce cytolytic activity of NK cells. Stimulation of NK cell proliferation and priming of NK cytolytic capability are accomplished by cytokines, which mediate their signals mainly through JAK-STAT signaling pathway. Previously, we found that K562 cells genetically modified to express membrane bound IL-21 (mbIL-21), which predominantly activates STAT3, induce robust expansion and activation of human NK cells. Further investigations revealed role of STAT3 …

Mobilization Of Adipose Stromal Cells In Obesity And Cancer By Sparc And Its Proteolytic Isoforms, Chieh Tseng

Dissertations and Theses (Open Access)

Obesity increases cancer risk and progression as shown by epidemiologic studies. However, the underlying pathophysiology remained unclear. Adipose stromal cells (ASC) are adipose tissue-derived mesenchymal progenitors, abundant in white adipose tissue (WAT). In this study, we show that the ASC pool is expanded in obesity and is associated with promoted tumor growth. Next, by using a chimeric GFP-RFP bone marrow transplant model, we observed higher tumor infiltrating cells with ASC phenotype in obese mice compared to lean. Consistently, systemic circulating ASC frequency is six fold higher in tumor-bearing obese mice compared to lean. The tumor infiltrating cells with ASC phenotype …

Determining The Mechanisms Generating Soluble Il-15 Complexes, Scott Anthony

Dissertations and Theses (Open Access)

A diverse assortment of infectious pathogens and TLR agonists enhance the expression of Interleukin (IL)-15. Additionally, inducing lymphopenia enhances anti-tumor responses in an IL-15-dependent manner. Paradoxically, despite the limited expression of IL-15 during homeostasis, the role of IL-15 during the steady state is well-known, while its roles during inflammation and infections remain largely undefined. IL-15 uses a unique method of production and presentation to support the development and homeostasis of NK and CD8 T cells. IL-15 is produced with its high affinity IL-15Rα and this IL-15Rα/IL-15 complex is shuttled to the cell surface where it is presented in-trans or cleaved …

The Tumor Suppressor Notch Inhibits Head And Neck Squamous Cell Carcinoma (Hnscc) Tumor Growth And Progression By Modulating Proto-Oncogenes Axl And Ctnnal1 (Α-Catulin), Shhyam Moorthy, Shhyam Moorthy

Dissertations and Theses (Open Access)

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common malignancy worldwide, with roughly 300,000 cancer related deaths occurring globally each year. The survival of patients with HNSCC has not changed significantly over the past decade, leading investigators to search for promising molecular targets. To identify new treatment targets and biomarkers that could better guide therapy, we previously characterized the genomic alterations from primary HNSCC patient samples. We were among the first to discover that NOTCH1 is one of the most frequently mutated genes in this cancer type. The spectrum of inactivating NOTCH1 mutations in HNSCC suggested …

Voxel-Level Absorbed Dose Calculations With A Deterministic Grid-Based Boltzmann Solver For Nuclear Medicine And The Clinical Value Of Voxel-Level Calculations, Justin Mikell

Dissertations and Theses (Open Access)

Voxel-level absorbed dose (VLAD) is rarely calculated for nuclear medicine (NM) procedures involving unsealed sources or 90Y microspheres (YM). The current standard of practice for absorbed dose calculations in NM utilizes MIRD S-values, which 1) assume a uniform distribution in organs, 2) do not use patient specific geometry, and 3) lack a tumor model. VLADs overcome these limitations. One reason VLADs are not routinely performed is the difficulty in obtaining accurate absorbed doses in a clinically acceptable time. The deterministic grid-based Boltzmann solver (GBBS) was recently applied to radiation oncology where it was reported as fast and accurate for both …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Redirecting T Cells With Chimeric Antigen Receptors To Target Cd123+ Leukemia, Radhika Thokala

Dissertations and Theses (Open Access)

ABSTRAC

REDIRECTING T CELLS WITH CHIMERIC ANTIGEN RECEPTORS TO TARGET CD123+ LEUKEMIA

Radhika Thokala, Ph.D*

Advisory Professor: Dean Anthony Lee, M.D, Ph.D

CD123 or interleukin receptor alpha (IL-3Rα) is expressed on hematological malignancies such as acute myeloid leukemia (AML) and some acute lymphoblastic leukemia (ALL). Significantly, CD123 is over-expressed on leukemic stem cells (LSCs) compared to normal hematopoietic stem cells and thus targeting this tumor- associated antigen (TAA) provides the potential to prevent relapse. The prototyical chimeric antigen receptor (CAR) is fashioned by …

Molecular Regulation Of Vascular Calcification In Murine Models Of Atherosclerosis, Shanshan Gao

Dissertations and Theses (Open Access)

Background: Calcification occurs often in the atherosclerotic lesions of patients with coronary heart disease and animals with hypercholesterolemia, such as apolipoprotein-E deficient (ApoE-/-) mice. However, the mechanism(s) underlying the development of calcification in atherosclerosis remains unclear. ApoE acts as a lipid transporter, but also has been recognized as a potential regulator of osteogenesis. Little information is available as to whether ApoE has any direct impact on osteogenesis and calcification in vascular smooth muscle cells (VSMC). Several signal transduction pathways play a role in regulation of calcification, including the Wnt/β-catenin system and potentially GTAP, an ubiquitin-conjugating enzyme responsible for protein …

Effects Of Pharmacological And Genetic Disruption Of Chemokine Receptor Cxcr4 In B-Cell Acute Lymphoblastic Leukemia, Shubhchintan Randhawa

Dissertations and Theses (Open Access)

The CXCR4 chemokine receptor plays a pivotal role in homing and retention of B-cell Acute Lymphoblastic Leukemia cells to bone marrow niches. The bone marrow stromal cells (BMSCs) constitutively secrete the CXCR4 ligand CXCL12, thus attracting leukemia cells and protecting them from cytotoxic drugs, a mechanism that might be responsible for minimal residual disease after conventional chemotherapy against B-ALL. Indeed, in this study we observed that B-ALL cells that had migrated beneath the BMSCs were highly resistant to chemotherapeutic drugs. Inhibition of CXCR4 to disrupt this interaction presents itself as an attractive target to overcome bone marrow derived drug resistance …

Defining The Molecular Networks Necessary For Thymus Fate And Organogenesis, Kaitlin A. Reeh

Dissertations and Theses (Open Access)

The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3^rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3^rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion …

An Automated Tool For High Resolution Visualization Applied To Transient Watershed Models, Noah Robert Taylor

Theses and Dissertations

Numeric hydrologic models can aid in water resource management by providing predictive simulations of water behavior. As computers become more advanced, the models developed also become more complex using more data to represent larger areas for forecasting hydrologic behavior. Unfortunately, as the simulations use more data, the output often becomes difficult to manage and share without investing time and effort into setting up server environments or decreasing the quality of the output to compensate for an efficient and effective user experience. A proposed solution to facilitate the accessibility of massive hydrologic model output is through the web-based visualization tool developed …

Compression Bodies And Their Boundary Hyperbolic Structures, Vinh Xuan Dang

Theses and Dissertations

We study hyperbolic structures on the compression body C with genus 2 positive boundary and genus 1 negative boundary. We consider individual hyperbolic structures as well as special regions in the space of all such hyperbolic structures. We use some properties of the boundary hyperbolic structures on C to establish an interesting property of cusp shapes of tunnel number one manifolds. This extends a result of Nimershiem in [26] to the class of tunnel number one manifolds. We also establish convergence results on the geometry of compression bodies. This extends the work of Ito in [13] from the punctured-torus case …

The Role Of Documentary Film In The Emerging Social Entrepreneurial Culture, Karyn Elizabeth Daley

Theses and Dissertations

Considering the current skepticism surrounding the impact and efficacy of nonprofit and nongovernmental organizations, some believe that a unique category of innovator known as the social entrepreneur may be society’s best hope for bringing innovative, scalable, and systemic solutions to bear on the world’s most intractable problems. Social entrepreneurs, as defined by Ashoka, have a unique set of characteristics that determine not only how they move within the world of social change-making but also how they communicate their ideas and mission to the public.

This exploratory study reviewed how social entrepreneurs currently use documentary film and visual media in their …

The Nature And Function Of Professional Support Networks For Teachers Of English Language Learners, Betsy Lynn Ferguson

Theses and Dissertations

The English learner (EL) population in the United States continues to grow. To improve their pedagogy in working with this population, many educators have received training in English as a Second Language (ESL), but the gap between ELs and their native English speaking peers persists. When teachers engage as members of professional support networks, they are more likely to successfully implement the strategies learned in their ESL professional development (Echevarria, Richards-Tutor, Chinn, & Ratleff, 2011). This study considered the nature and function of the professional support network of a district's ESL-endorsed teachers. Using network theory methods, 257 teachers and other …

Configuration Scrubbing Architectures For High-Reliability Fpga Systems, Aaron Gerald Stoddard

Theses and Dissertations

Field Programmable Gate Arrays (FPGAs) are being used more frequently in space applications because of their reconfigurability and intensive processing capabilities. FPGAs in environments like space are susceptible to ionizing radiation which can cause Single Event Upsets (SEUs) in the FPGA's configuration memory. These upsets may cause the programmed user design on the FPGA to deviate from its normal behavior. Space missions cannot afford to allow important data processing applications to become corrupted due to these radiation upsets.Configuration scrubbing is an upset mitigation technique that detects and corrects upsets in an FPGA's configuration memory. Configuration scrubbing periodically monitors an FPGA's …

A Theory Of Presence: Bringing Students And Art Closer Together, Joshua T. Hobbs

Theses and Dissertations

In seeking to create a richer learning environment in a junior high art classroom, the author develops a theory of presence. Closely connected to object-centered learning, a theory of presence in the art classroom places value on students being in the presence of, interacting with, and responding to artworks, artists, and other individuals and objects from the visual arts community. The author then describes how curricular plans are influenced by this theory of presence. Using an action research methodology, the author engages in the spiral process of planning, acting, observing, and reflecting on curriculum that explores the possibilities of connecting …

Evaluating Long-Term Land Cover Changes For Malheur Lake, Oregon Using Envi And Arcgis, Ryan Joseph Woods

Theses and Dissertations

Land cover change over time can be a useful indicator of variations in a watershed, such as the patterns of drought in an area. I present a case study using remotely sensed images from Landsat satellites for over a 30-year period to generate classifications representing land cover categories, which I use to quantify land cover change in the watershed areas that contribute to Malheur, Mud, and Harney Lakes. I selected images, about every 4 to 6 years from late June to late July, in an attempt to capture the peak vegetation growth and to avoid cloud cover. Complete coverage of …

New Genres In The Art Classroom: Shifting Ideas And Identities, Alyssa Grant Ridge

Theses and Dissertations

Secondary art education programs primarily offer courses in traditional mediums like drawing, painting, sculpture, and ceramics. In addition to valuing these traditional art forms, art education research supports integrating new technologies and media in the classroom. However, the possibilities of creating an exclusively contemporary, new genres curriculum have yet to be explored. This study examines the affordances and limitations of a high school-level new genre curriculum and describes how students reacted to these new genres and how their perceptions of art, student-peer relationships, and artist identities changed over time. By introducing students to new genres, the author found students expanded …

Cooling Before Super-Eruption: No Role For Rejuvenation In The Cottonwood Wash Tuff Magma Body, Southern Great Basin Ignimbrite Province, Utah And Nevada, Keryn Tobler Ross

Theses and Dissertations

The model of rejuvenation of a near-solidus crystal mush to produce large volumes of crystal-rich magma is tested here by analyzing the mineralogical, chemical, modal, and physical characteristics of the 31.1 Ma super-eruptive (2000 km3) Cottonwood Wash Tuff. It is the oldest in a series of three so-called “monotonous intermediate” ignimbrites from the Indian Peak-Caliente volcanic field in southern Utah and Nevada. A crystal-rich (~50% Pl > Qz ≈ Hbl ≈ Bt > Mag ≈ Ilm > Cpx + Zrn + Ap+ Po) dacite (62 – 69 wt% SiO2), the Cottonwood Wash Tuff is similar in age, volume, mineralogy, crystallinity, and elemental composition …

Shaking Table Testing To Evaluate Effectiveness Of Prefabricated Vertical Drains For Liquefaction Mitigation, Caleb Robert Oakes

Theses and Dissertations

This study was designed to evaluate the ability of vertical drains to prevent liquefaction and limit associated settlement. Drain performance was investigated using full-scale tests with vertical drains in liquefiable sand using a laminar shear box with acceleration time histories applied at the base. Performance of the sand box with drains in these tests was compared with performance of the sane box without drains in previous tests. The test data was also used to create case histories which can be used for further research and calibration of computer models. Although some investigations regarding vertical drains have been performed with centrifuge …

Numerical Analysis Of Passive Force On Skewed Bridge Abutments, Zifan Guo

Theses and Dissertations

Accounting for seismic forces and thermal expansion in bridge design requires an accurate passive force-deflection relationship for the abutment wall. Current design codes make no allowance for skew effects on passive force; however, large scale field tests indicate that there is a substantial reduction in peak passive force as skew angle increases. A reduction in passive force also reduces the transverse shear resistance on the abutment. The purpose of this study is to validate three-dimensional model using PLAXIS 3D, against large scale test results performed at Brigham Young University and to develop a set of calibrated finite element models. The …

Evidences Of Critical Thinking In The Writing Of First-Year College Students, Shannon Bryn Soper

Theses and Dissertations

A healthy civil society depends on citizens who have mature critical thinking skills and a willingness to entertain opposing points of view. The development of critical thinking in young adults has long been studied, but there has been little agreement on what the attributes of critical thinking are and how to reliably assess them. While many studies have attempted to assess the critical thinking abilities of college students, none have yet measured critical thinking through using the Critical Thinking Analytic Rubric (CTAR) to assess first-year college students' writing. This study used a modified version of the CTAR rubric to investigate …

Diversification And Speciation Across Sundaland And The Philippines: The Effects Of 30 Million Years Of Eustatic Flux, Luke J. Welton

Theses and Dissertations

I highlight two squamate lineages endemic to Southeast Asia, the Asian water monitors (Varanus salvator Complex) and the Angle-headed lizards (Agamidae: Gonocephalus), and elucidate their systematic affinities and historical biogeography. My results represent novel phylogenetic inferences, with biogeographic histories and diversification events corresponding to major climatic fluctuations over the past 30 million years. Additionally, I solidify the taxonomy and systematics of the Varanus salvator Complex, and enumerate more than a dozen Gonocephalus lineages as candidate species in need of taxonomic scrutiny. Lastly, I investigate contemporary and historical patterns of dispersal throughout Sundaland, and between Sundaland and the Philippines.

Comparing The Strength Of Diagonally Non-Recursive Functions In The Absence Of Σ02 Induction, Francois G. Dorais, Jeffry L. Hirst, Paul Shafer

Dartmouth Scholarship

We prove that the statement "there is a k such that for every f there is a k-bounded diagonally non-recursive function relative to f" does not imply weak K\"onig's lemma over RCA0+BΣ02. This answers a question posed by Simpson. A recursion-theoretic consequence is that the classic fact that every k-bounded diagonally non-recursive function computes a 2-bounded diagonally non-recursive function may fail in the absence of IΣ02.

From Networked Learning To Operational Practice: Constructing And Transferring Superintendent Knowledge In A Regional Instructional Rounds Network, Timothy J. Travis

Dissertations

Instructional rounds are an emerging network structure with processes and protocols designed to develop superintendents’ knowledge and skills in leading large-scale improvement, to enable superintendents to build an infrastructure that supports the work of improvement, to assist superintendents in distributing leadership throughout their district, and to develop a cadre of educational leaders focused on developing their practice (Rallis, Tedder, Lachman, & Elmore, 2006). In a platform-learning model, learning in a superintendents’ network can be viewed as occurring both individually and collectively on an external platform outside each individual school district (Schulz & Geithner, 2010). In this phenomenological study, I explored …

Becoming American: Constructing Mexican Immigrants In Local Newspapers, Zheng Zhu

Publications and Research

Media representation of Latino immigrants has been extensively studied by scholars across diverse academic disciplines. Particular to the U.S. context, preceding scholarships pertaining to the ways in which Latinos were represented centered on the media representation of Latino immigrants either as the exotic racial other or undesirable foreigners. In light of the important role that the Mexican immigrants played in understanding the current national debate on illegal immigration and the overall historical experiences of immigrants in Washington State (WA), this study critically investigated how news articles published in WA represented Mexican immigrants. As a crucial point of departure from prior …

Consumer Assessment Of New Creative Products Across China And The United States, Eva Teruzzi

Creative Studies Graduate Student Master's Theses

This cross-cultural research investigates how consumers assess creativity in new products and if their assessment impacts desire to own. Implicit and explicit scale-based measures were tested in China and the U.S. in online consumer samples and were positively correlated. Novelty, affect and importance dimensions of creative products were tested through Horn and Salvendy’s (2006, 2009) Product Creativity Measurement (PCM) scale. Findings point to a different role of novelty in determining desirability of creative new products across-cultures.In fact, novelty and affect are key to explain desire to own in China, while affect and importance are the drivers in the U.S. Affect, …