Digital Commons Network^™

Proteasome Regulation Of Caspase-8: Significance In Cancer, Michael Vincent Fiandalo

Theses and Dissertations--Molecular and Cellular Biochemistry

Anti-tumor therapeutic strategies based on combinations of chemotherapeutic agents with a death inducing ligand such as TNF-α Related Apoptosis Inducing Ligand (TRAIL), are directed towards selective and effective cancer cell apoptosis and enhanced therapeutic response. We previously demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of initiator caspase-8. The present study investigated the functional link between caspase-8 and the proteasome, by analyzing the impact of caspase-8 ubiquitination and proteasomal degradation on the outcomes of the extrinsic apoptosis pathway in cancer cells. Caspase-8 ubiquitination status was assessed by polyubiquitin …

Structural Basis Of Substrate Recognition In Thimet Oligopeptidase And Development Of Nanoparticles For Therapeutic Enzyme Delivery, Jonathan Mark Wagner

Theses and Dissertations--Molecular and Cellular Biochemistry

Neuropeptidases are responsible for degradation of signaling peptides in the central nervous system and periphery. Some neuropeptidases have also been shown to play a role as part of the cell’s hydrolytic machinery responsible for breaking down proteins and peptides into amino acids, and these enzymes therefore influence small peptide availability for antigen presentation. A better understanding of how neuropeptidases recognize their substrates could lead to therapeutics that modulate the activity of these important enzymes. Alternatively, re-engineering these enzymes to selectively hydrolyze undesirable peptides could make them attractive as therapeutics themselves. A key question in understanding the activity of these enzymes …

Biochemical Actions Of A Novel Cis-Terpenone, Lin Zhang

Theses and Dissertations

Abstract BIOCHEMICAL ACTIONS OF A NOVEL CIS-TERPENONE By Lin Zhang, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Director: Qibing Zhou, Ph.D Assistant Professor Department of Chemistry

Quinone methides are reactive species due to their electrophilicity, and natural quinone methide analogs have broad biological activities. Based on known actions of cytochrome P450 enzymes, we hypothesized that trans-terpenones can be metabolized in cells to form a cascade of metabolite products, which may be biologically active due to the generation of quinine and quinone methide …

Supporting Informed Learners In The 21st Century, Christine S. Bruce, Hilary Hughes, Mary M. Somerville

University Libraries Librarian and Staff Articles and Papers

This article elaborates the concept of informed learning and locates it in educational, workplace, and community settings. Drawing on existing research into people’s experience of information literacy, it identifies critical experiences of informed learners in each of these three settings. It also explores the support required in educational, community, and workplace contexts, which makes informed learning possible. Recognizing strong implications for policy makers in different sectors, the article presents a set of guiding principles for developing informed learning and learners. The idea of informed learning represents and advances understandings of information literacy that incorporate the broader concept of using information …

Impact Of An Elective Course On Pharmacy Students’ Attitudes, Beliefs, And Competency Regarding Medicare Part D, Suzanne M. Galal, Rajul A. Patel, Huong K. Thai, Christine M. Phou, Mark P. Walberg, Joseph A. Woelfel, Sian M. Carr-Lopez, Emily K. Chan

School of Pharmacy Faculty Articles

Objective. To determine the impact of an elective course on pharmacy students’ perceptions, knowledge, and confidence regarding Medicare Part D, medication therapy management (MTM), and immunizations.

Design. Thirty-three pharmacy students were enrolled in a Medicare Part D elective course that included both classroom instruction and experiential training.

Assessment. Students’ self-reported confidence in and knowledge of Part D significantly improved upon course completion. End-of-course student perceptions about the relative importance of various aspects of MTM interventions and their confidence in performing MTM services significantly improved from those at the beginning of the course. Students’ confidence in performing immunizations also increased significantly …

American Society Of Interventional Pain Physicians (Asipp) Guidelines For Responsible Opioid Prescribing In Chronic Non-Cancer Pain: Part 2--Guidance., Laxmaiah Manchikanti, Salahadin Abdi, Sairam Atluri, Carl C. Balog, Ramsin M. Benyamin, Mark V. Boswell, Keith R. Brown, Brian M. Bruel, David A. Bryce, Patricia A. Burks, Allen W. Burton, Aaron K. Calodney, David L. Caraway, Kimberly A. Cash, Paul J. Christo, Kim S. Damron, Sukdeb Datta, Timothy R. Deer, Sudhir Diwan, Ike Eriator, Frank J.E. Falco, Bert Fellows, Stephanie Geffert, Christopher G. Gharibo, Scott E. Glaser, Jay S. Grider, Haroon Hameed, Mariam Hameed, Hans Hansen, Michael E. Harned, Salim M. Hayek, Adam M. Kaye

School of Pharmacy Faculty Articles

RESULTS: Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. (Evidence: good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. (Evidence: limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription …

Career Coaching Across The Curriculum: Enhancing The Career Competencies Of The 21st Century Learner, Mark W. Slomp, Kerry B. Bernes

Northwest Journal of Teacher Education

This article examines the effectiveness of a pilot project offered by members of the Faculty of Education at the University of Lethbridge entitled, ―Career Coaching Across the Curriculum: Integrating Career Development into Classroom Instruction‖. It explores whether this pilot project effectively prepares pre-service teachers to integrate career education into curriculum. It also explores whether this pilot project contributes to the attainment of important career development competencies for students in the Kindergarten-Grade 12 educational system.

The Importance Of Using Technology-Enhanced 21st Century Literacy Skills To Support Culture And Diversity In The Classroom, Sonia Isabel Lopez-Lopez, Ibtesam Hussein, Maysoun Ali

Northwest Journal of Teacher Education

Teaching in today‘s classrooms is not the same as it has been in the past; that is what teachers claim. There is a new generation of students, with new expectations and capacities, coming into the classroom. The Internet and technology in general are used everywhere to communicate and interact with others. Today, students are looking for different interactions and ways of learning in the classroom. Therefore, technology should be used not only because students are using new technologies ubiquitously outside of the classroom, but also because the use of technology can enrich students‘ understandings of diversity and culture, which can …

Lipase-Kinase Associations Involving Pld2, Jak3 And Fes That Underlie Cancer Cell Proliferation And Invasion, Qing Ye

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Phospholipase D (PLD) is an enzyme that breaks down phospholipids in the cell membrane. It has been suggested that PLD may play a role during cell proliferation and cell invasion of cancer cells. The objective of this thesis was to define new molecular signaling pathways in which PLD2 might be involved in terms of cell proliferation (first part) and cell invasion (second part). To this, I compared molecular and biochemical aspects between untransformed cell lines with highly invasive, transformed breast cancer cells. In the first part, I investigated the interaction of two tyrosine kinases with PLD2 and the effect of …

Misrepresenting Misery: Slaves, Servants, And Motives In Early Virginia, Jamin P. Riley

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Violence has frequently been connected to the history of slavery. Graphic depictions of slaveowner violence can be found in popular literature and media. The slave experience, especially in the early modern period, should instead be explained to wider public audiences in its totality. The regulation of reproductive and familial rights by slaveowners, the use of sexual punishment, and the permanence of slavery made the enslaved life truly unique, and set it apart from the experiences of other repressed elements of early modern English society, such as the poor. The creation of the slave system and the development of its regulatory …

Friedel-Crafts Acylation Studies On 3-Alkyl-1-(Phenylsulfonyl)Indoles Using Aluminum Chloride And Bismuth Triflate, Venkateswara Reddy Karrepu

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Using the traditional catalyst, aluminum chloride in stoichiometric amounts, 3-alkyl-1-(phenylsulfonyl)indoles can be regioselectively acylated under Friedel-Crafts conditions at the C-6 position along with 10% of a minor isomer at the C-5 position. Alternatively, using catalytic amounts of the green catalyst, bismuth triflate, C-2 acylation was observed. Therefore, regioselectivity can be controlled by the nature of the Lewis acid catalyst. Moreover, this is the first-time that Friedel-Crafts acylation studies were demonstrated upon 3-alkyl-1-(phenylsulfonyl)indoles.

Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs

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Immunoglobulin heavy chain (IgH) expression and Ig secretion is inhibited by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Within the IgH gene, the 3' IgH regulatory region (3'IgH RR) has been identified as a transcriptional target of TCDD. The 3'IgH RR, which in part regulates transcription of the IgH gene, is composed of four enhancers in the mouse: hs3a; hs1,2; h3b; hs4 and three enhancers in the human: hs3a; hs1,2; hs4. In humans the hs1,2 enhancer has an invariant sequence (IS) containing a DRE, NF-κB, NF1 and AP-1 binding site. Also, the enhancer has an AP1.ETS and Oct …

Exploration Of Ypel3 Response To Hormones And Ability To Induce Senescence, Joseph E. Rotsinger

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p53 activation through different cellular senescence pathways can trigger cell cycle arrest via regulation of p53 target genes. One such target gene is YPEL3 which is expressed upon binding of tumor suppressor protein p53 at its p53 binding sites (Kelley, 2010). The ability of p53 to induce YPEL3 gene expression led to the discovery that YPEL3 is one of several p53 target genes which induce cellular senescence (Kelley, 2010). Additionally YPEL3 can be regulated independently of p53 by estrogen signaling through estrogen receptor α (Tuttle, 2011). The loss of estrogen receptor α or removal of estrogen induces YPEL3 gene expression …

Effects Of Conductivity And Fish Grazing On Alkaline Phosphatase Activity Of Littoral Periphyton, Samuel A. Drerup

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Littoral periphyton plays an important role in whole lake primary production and is a substantial contributor to whole lake energy budgets in moderately deep oligotrophic lakes. Under conditions of nutrient deficiency, members of the periphyton community supplement the available nutrient pool through the production of intracellular and extracellular enzymes. These enzymes are used to convert bio-unavailable forms of nitrogen and phosphorous to forms usable by the periphyton community. In this paper, I will investigate how conductivity and fish grazing affect periphyton production and phosphorus acquisition in both field and laboratory experiments.

An Ecological Investigation Into The Effects Of Interface On Asynchronous Group Conversations, Peter Venero

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Asynchronous group communication refers to the activity of multiple people communicating when they are separated by both time and space. Online groups (OG) and email are two settings that facilitate these interactions. While both of these settings accomplish this task, they do so in slightly different ways. Email organizes all of the posts by putting the new posts on the top of the display and the older posts towards the bottom. The OG interface uses a tree structure; putting the new posts in a subordinate post relationship to a previous post. How these two technologies present the posts to the …

A Study Of Public School Employees' Adoption Behavior Regarding Technological Innovations, Kimberly S. Snyder

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Within with the five technological innovation adopter categories, there are potential technology users who resist adoption (Joseph, 2010). Using Survey Monkey™, during the 2011-12 school year non-certified public school employees in urban, suburban, and rural Midwestern areas were surveyed about their adoption patterns and their use of technology in the workplace. This non-experimental, descriptive study determined the distribution of 44 non-certified public school employees among adopter categories regarding technological innovation designed to improve workplace efficiency. This study also examined responses to determine differences among characteristics of those in each of the adoption categories. Respondents self-identified as members of only three …

The Role Of Angiotensin Converting Enzyme (Ace) 2 In A Murine Model Of Insulin Resistance And Albuminuria, Nathan Michael Weir

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Insulin resistance and kidney disease are intimately linked and both independently tied to dysregulation of the renin angiotensin system (RAS). The purpose of this research was to better investigate Angiotensin Converting Enzyme (ACE) 2 as a possible motif in the pathophysiology of these two disease processes. The project was divided into two parts. Part 1 investigated ACE2 KO mice as a model of albuminuria. Part 2 investigated how the lack of ACE2 enzyme affected glucose homeostasis and subsequent albuminuria.

Part 1: The Role of ACE2 in the Progression of Albuminuria. To determine if global loss of ACE2 leads to spontaneous …

Evaluating The Effect Of Hyporheic Exchange On Intake Temperatures Of Open-Loop Geothermal Wells In Glacigenic Outwash Aquifers, Nathan Grigsby

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Subsurface heat flow was simulated to study the effect of hyporheic exchange on groundwater intake temperatures of open-loop geothermal wells in glacigenic-outwash aquifers in the North American midcontinent. The model represents an aquifer kilometers wide, on the order of 100m thick, and directly connected to a perennial river. The aquifer has bimodal hydraulic conductivity with a geometric mean on the order of 100m/day, an effective thermal conductivity of 2.33W/mK, and specific heats on the order of 106J/(m^3 K) for water and 103J/kgK for solids. The aquifer is initially set to a temperature of 12.85 °C and the river is fixed …

Cometabolic Degradation Of Halogenated Aliphatic Hydrocarbons By Aerobic Microorganisms Naturally Associated With Wetland Plant Roots, Madelyn M. Smith

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Wetland systems provide both anaerobic (reducing) and aerobic (oxidizing) zones for the biodegradation of chlorinated aliphatic hydrocarbons (CAH). In particular, wetland plant roots provide micro-oxidizing environments for methanotrophic bacteria from the presence of methane, which is produced in anaerobic zones, and oxygen, which is brought to the subsurface by roots of wetland plants; this shows the potential for cometabolic degradation of common organic pollutants.

This study explored the natural attenuation of CAHs by methanotrophic bacteria naturally associated with roots of the common wetland plant, Carex comosa. Root microcosms were amended with varying concentrations of methane; trichloroethene; cis 1,2-dichloroethene; 1,2-dichloroethane; or …

The Japanese American Resettlement Program Of Dayton, Ohio: As Administered By The Church Federation Of Dayton And Montgomery County, 1943-1946, Paul Michael Dankovich

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In September 1942, the Church Federation of Dayton and Montgomery County (Church Federation) was established. It created a Commission on War Services that coordinated social services to the thousands of military personnel and migrant war workers who flooded into wartime Dayton. Strategically, Dayton supported the nation's defense through the presence of two Army airfields and many vital industrial facilities.

Beginning on October 1, 1942, the War Relocation Authority (WRA) permitted those of Japanese descent to leave the internment camps on indefinite leave, and resettle outside of the West Coast exclusion zones. The WRA supported this program by opening field offices …

Computational Investigations Of The Adsorption Of Molecular Hydrogen On Graphene-Based Nanopore Model, Jared Duncan

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Computational modeling using classical grand canonical Monte Carlo simulations and first-principles calculations were carried out to study the adsorption of molecular hydrogen on nanoporous carbon modeled by the slit- pore geometry. It has previously been shown that hydrogen adsorption on pristine porous carbon has dependence on pore size and that an optimum pore size, which exhibits the maximum mass uptake, exists. There have been suggestions that doping graphitic nanocarbon structures with Pd enhances their adsorption capacity. The pore-size dependence of this change in adsorption brought about by Pd and the conditions at which improvement in adsorption can occur have not …

Terahertz Time Domain Spectroscopy And Fresnel Coefficient Based Predictive Model, Justin C. Wheatcroft

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An optical material parameter predictive model that accounts for sample to air interfaces was developed. The model predicts how a terahertz time-domain spectroscopy time domain pulse will be affected as it passes through a given thickness of a material. The model assumes a homogenous, linear, isotropic dielectric or semiconductor. The inputs to the model are the real and imaginary refractive indices across the desired frequency band. Different dielectric material's optical parameters were taken from the literature and the predicted time domain pulses were shown. It was also shown that the refractive index and absorption coefficient for samples that were optically …

Suppressor Of Cytokine Signaling (Socs) 1 & 3 Expression In Hsv-1- Infected And Interferon-Γ-Treated Neuro-2a Cells, Melinda Jones

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This study examined the effects of HSV-1 infection and IFN-γ treatment on Neuro-2A cells. HSV-1 induces expression of SOCS1 and SOCS3 in infected cells, inhibiting the ability of these cells to produce the pro inflammatory, antiviral cytokine IFN-γ (Nowoslawski and Benveniste, 2011). SOCS1 and SOCS3 levels were determined in IFN-γ-treated cells, virus-infected cells, and cells that were both IFN-γ-treated and virus-infected. Results were compared with untreated, uninfected control cells. Flow cytometry data analysis showed a slight decrease in SOCS1 and SOCS3 protein levels in cells treated with IFN-γ for 6 hours compared to control cells. A significant decrease in SOCS1 …

House Dust Mite Induced Gene Expression And Cytokine Secretion By Human Dermal Fibroblasts, Jananie Rockwood

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House dust mites are a group of mites that are commonly found in homes worldwide. The three most commonly found species of house dust mites in temperate environments in the United States are Dermatophagoides farinae, Dermatophagoides pteronyssinus and Euroglyphus maynei. House dust mite allergens are strongly associated with asthma, perennial rhinitis and atopic dermatitis. Whole dust mite extracts contain both allergen and non-allergen molecules that can influence cell functions in the skin, mucous membranes of the nose and eyes, and epithelial linings of the lungs. Extracts from the three different house dust mite species contain different molecules that induce different …

Cloudvista: A Framework For Interactive Visual Cluster Exploration Of Big Data In The Cloud, Zhen Li

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With the development and deployment of ubiquitous information sensing, mobile devices,wireless sensor networks, RFID readers, simulation, and computer generated software logs, big data have become precious resources for scientific study, business intelligence, and national security. As one of the most intuitive and effective analysis methods,visual cluster analysis remains as a significant challenge for big datasets. First, existing visualization models need to be updated to process big data in parallel. Second, processing big data inevitably bring large latency, which conflicts the requirement of interactivity. In this thesis, we develop the CloudVista framework to address the common problems with data reduction methods …

The Construction Of A Plasmid For Detecting The Pathway Of Arginine Metabolism In Human Macrophages: A Real-Time Assessment Of Macrophage Polarity, Benjamin A. Holmes

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Macrophages are "first responders", innate immune system cells which quickly arrive to a site of infection and injury, consuming cell debris and foreign matter and recruiting other immune system cells to the area. While historically they have been thought to react uniformly to all challenges, the discovery of toll-like receptors has shown that macrophages actually work closely with the adaptive immune system in fine-tuning the immune response. Furthermore, it has recently been discovered that macrophages can become polarized to one of two subtypes-M1 or M2.

M1 macrophages are efficient producers of reactive oxygen species, nitrogen intermediates, and inflammatory cytokines. They …

Assessing The Drivers Of Adaptive Radiation In A Complex Of Gall Midges: A Multitrophic Perspective On Ecological Speciation, Jeremy J. Heath

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Natural enemies as selective forces maintaining and shaping morphological, physiological, and behavioral divergence in adaptive radiations have received very little attention. Until recently, the focus has been on primary resource competition as a major driver of trait divergence in adaptive radiations. Here I consider the role of natural enemies specifically in driving trait divergence in a complex of gall midges in the nominal species Asteromyia carbonifera (Diptera: Cecidomyiidae), which appears to be in the throes of an incipient adaptive radiation on its host plant, goldenrod (Solidago). This galler uses a symbiotic fungus (Botryosphaeria dothidae) as a …

Radical Reform Of Intercollegiate Athletics: Antitrust And Public Policy Implications, Stephen F. Ross

Faculty Scholarship

Universities operating major intercollegiate athletic programs are heading for, if not already in, a crisis. Corruption continues to affect major football and basketball programs, exacerbated by a failure of imagination and will in identifying and deterring corruption, and by a lack of consensus on what constitutes "corruption" when football and men's basketball stars generate millions of dollars but cannot enjoy a lifestyle commensurate with many peer students. Current levels of spending are nonsustainable at many schools. Even where intercollegiate athletic programs are sustained primarily by football and basketball revenues, otherwise visionary and questioning college presidents have yet to publicly question …

Social Movements' Emergence And Form: The Green Movement In Iran, Afsaneh J Haddadian

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Theories of social movements suggest that 'objective' changes in the structure of political opportunities and their interaction with mobilizing and framing mechanisms render a system vulnerable to mass protest. By examining the variables relevant to such interaction, this study seeks to account for the emergence and form of the 2009 Green Movement in Iran. This research uses the congruence method and process traces the movement adherents' activities, mainly their use of Information Communication Technologies, and investigates the so-called opposition leaders' activities and statements. The study argues that in accounting for emergence and form of the Green Movement, we need to …

Light-Limited Access To Fructose Alters Metabolic Function And Adipose Tissue Catecholaminergic Activity In Mice, Naima Salem Rodwan

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Consumption of high levels of fructose produces glucose intolerance, sympathetic nervous system activation, and renal dysfunction. A diet high in fructose may play a role in the worldwide epidemic of obesity and diabetes. The aim of this study was to test the hypothesis that time (light/dark) limited access to fructose influences body fat, metabolic function, and adipose tissue catecholaminergic activity in mice. Male C57BL/6 mice were given standard chow and assigned to one of three groups: Control (n=10, water 24h); FL (n=11, 10% fructose solution during 12h light period); and FD (n=10, 10% fructose solution during 12h dark period). Metabolic …