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Heparan Sulfate, A New Target For Platinum In Metastatic Tnbc, Samantha J. Katner

Theses and Dissertations

Abstract

Heparan Sulfate, A New Target for Platinum in Metastatic TNBC

Author: Samantha J. Katner, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Virginia Commonwealth University, 2018

Advisor: Dr. Nicholas Farrell, Professor, Chemistry Department

Heparan sulfate proteoglycans (HSPGs), composed of the linear polysaccharide heparan sulfate (HS) conjugated to a protein core, are located on the cell surface and extracellular matrix. The HS chains display varying degrees of sulfation, which constitutes the molecular recognition motif for many HS-protein interactions. HSPGs, associated growth factors, and heparanase promote tumor progression by facilitating invasion, angiogenesis, …

Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna

Theses and Dissertations

Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:

Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (c_p(t)) and sputum (c_s(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from c_p(t) …

The Break, Ian Gerson

Theses and Dissertations

The Break is a personal investigation into problems and possibilities of representing my specific transgender identity.

Trans as a tactic to speak about a state of forever becoming, forever in between, outside of and in opposition to dominant social norms of being.

Trans as a model for a different way of viewing and being in the world.

Can we form a different kind of horizontal shared power though a collective refusal to play into existing structures from which we have been excluded? What are the potentials for modeling other ways of being, other ways of (dis)engaging, other ways to be …

Nuclear Rupture In Progeria Expressing Cells, Kranthidhar Bathula

Theses and Dissertations

Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this …

Enhancing Adherence To Prescribed Opioids Using A Mobile-Base Application: A Pilot Study Of Feasibility In Chronic Non-Cancer Pain, Daniel M. Sop

Theses and Dissertations

In this study we present feasibility of a mobile monitoring and reporting system that would provide an accurate unbiased screening tool to systematically analyze opioid adherence in Sickle cell disease patients. In addition, the software simultaneously measures pain. The Mobile Applications Rating Scale: a new and validated tool for assessing the quality of health mobile apps for engagement, functionality, aesthetics, information quality, subjective quality, relevance and overall impact was administered post usage to evaluate the application.

A total of 28 patients were recruited to review and test the software at one sitting. The majority of the population found the application …

Graphene As A Solid-State Ligand For Palladium Catalyzed Cross-Coupling Reactions, Yuan Yang

Theses and Dissertations

Palladium-catalyzed carbon-carbon cross-coupling reactions have emerged a broadly useful, selective and widely applicable method to synthesize pharmaceutical active ingredients. As currently practiced in the pharmaceutical industry, homogeneous Pd catalysts are typically used in cross-coupling reactions. The rational development of heterogeneous catalysts for cross-coupling reactions is critical for overcoming the major drawbacks of homogeneous catalysis including difficulties in the separation, purification, and quality control process in drug production. In order to apply heterogeneous catalysis to flow reactors that may overcome this limitation, the catalyst must be strongly bound to a support, highly stable with respect to leaching, and highly active. While …

Psychick Order, Corissa Duffey

Theses and Dissertations

Preserving Psychick Order is an investigation into the subliminal, of a body processing trauma and transition. I explore how my mind and body filter memory, fear, and the impact of the past into the present. Since childhood, making dolls has been a way for me to express complex feelings, especially as they relate to dynamics between biological and found family. By tenderly modeling dolls after my own transforming physical features and mental processes, I make connections between the effects of my mind on my body and vice versa. I like to describe the resulting forms as queer monsters trying to …

Engineering Surface Properties To Modulate Inflammation And Stem Cell Recruitment Through Macrophage Activation, Kelly M. Hotchkiss

Theses and Dissertations

Biomaterials are becoming the most commonly used therapeutic method for treatment of lost or damaged tissue in the body. Metallic materials are chosen for high strength orthopaedic and dental applications. Titanium (Ti) implants are highly successful in young, healthy patients with the ability to fully integrate to surrounding tissue. However the main population requiring these corrective treatments will not be healthy or young, therefore further research into material modifications have been started to improve outcomes in compromised patients. The body’s immune system will generate a response to any implanted material, and control the final outcome. Among the first and most …

Adolescent Emotion Expression, Emotion Regulation, And Decision-Making In Social Context, Tennisha N. Riley

Theses and Dissertations

Adolescents engage in risk behaviors at an alarming rate, and particularly when they are with peers. Despite efforts to develop prevention and intervention programs, rates of risk-taking among adolescents is still relatively high. Adolescents continue to engage in physical fights and aggressive behavior, use substances such as alcohol and illicit drugs, and make decisions that impact driving and motor vehicle incidents. The regulation of emotions plays a significant role in adolescents’ decisions to engage in such risk behaviors.Examining adolescents’ emotion expression and regulation is therefore critical to identifying ways to support positive development.

This dissertation project explored important regulatory mechanisms …

Edgelands, Anne Bujold

Theses and Dissertations

Animal imagery has been part of the human effort to understand our place in the world since the beginning of recorded history. Through examining the role and use of animal imagery in the creation of cultural signals, I have developed a framework for my practice. Edgelands employs representations of feral animals as symbols for the “misfit” to emphasize the value of those who do not fit in. My experience as a woman in the field of metal work informs my material choice and process, subverting ironwork motifs and the purpose of gates and boundaries. Edgelands overlaps a series of material …

Stat3 In The Regulation Of Brown Adipocyte Differentiation, Marc Cantwell

Theses and Dissertations

Thermogenic fat is a promising target for new therapies in diabetes and obesity. Understanding how thermogenic fat develops is important to develop rational strategies to treat obesity. Previously, we have shown that Tyk2 and STAT3, part of the JAK-STAT pathway, are necessary for proper development of classical brown fat. Using primary preadipocytes isolated from newborn mice we demonstrate that STAT3 is required for differentiation and robust expression of Uncoupling Protein 1. We also confirm that STAT3 is necessary during the early induction stage of differentiation and is dispensable during the later terminal differentiation stage. Without STAT3, the brown preadipocytes have …

High-Throughput Prediction And Analysis Of Drug-Protein Interactions In The Druggable Human Proteome, Chen Wang

Theses and Dissertations

Drugs exert their (therapeutic) effects via molecular-level interactions with proteins and other biomolecules. Computational prediction of drug-protein interactions plays a significant role in the effort to improve our current and limited knowledge of these interactions. The use of the putative drug-protein interactions could facilitate the discovery of novel applications of drugs, assist in cataloging their targets, and help to explain the details of medicinal efficacy and side-effects of drugs. We investigate current studies related to the computational prediction of drug-protein interactions and categorize them into protein structure-based and similarity-based methods. We evaluate three representative structure-based predictors and develop a Protein-Drug …

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …

Big Networks: Analysis And Optimal Control, Hung The Nguyen

Theses and Dissertations

The study of networks has seen a tremendous breed of researches due to the explosive spectrum of practical problems that involve networks as the access point. Those problems widely range from detecting functionally correlated proteins in biology to finding people to give discounts and gain maximum popularity of a product in economics. Thus, understanding and further being able to manipulate/control the development and evolution of the networks become critical tasks for network scientists. Despite the vast research effort putting towards these studies, the present state-of-the-arts largely either lack of high quality solutions or require excessive amount of time in real-world …

Advanced Imaging Analysis For Predicting Tumor Response And Improving Contour Delineation Uncertainty, Rebecca N. Mahon

Theses and Dissertations

ADVANCED IMAGING ANALYSIS FOR PREDICTING TUMOR RESPONSE AND IMPROVING CONTOUR DELINEATION UNCERTAINTY

By Rebecca Nichole Mahon, MS

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2018

Major Director: Dr. Elisabeth Weiss,

Professor,

Department of Radiation Oncology

Radiomics, an advanced form of imaging analysis, is a growing field of interest in medicine. Radiomics seeks to extract quantitative information from images through use of computer vision techniques to assist in improving treatment. Early prediction of treatment response is one way of improving overall patient care. This work …

Recent Progress In The Synthesis Of Six-Membered Aminocyclitols (2008-2017), William A. Donaldson

Chemistry Faculty Research and Publications

Aminocyclitols are of interest as glucosidase inhibitors, as probes for the study of pseudoglycosyltransferases, and as potential therapeutics for the treatment of Gaucher’s disease. The synthesis of these targets was reviewed in early 2008, and the aim of this review is to cover material relevant to the synthesis of aminocyclitols since that time. While not a focus of this review, biological evaluation of compounds will be presented where it is recorded in the literature.

Allosteric Regulation Alters Carrier Domain Translocation In Pyruvate Carboxylase, Yumeng Liu, Melissa M. Budelier, Katelyn Stine, Martin St. Maurice

Biological Sciences Faculty Research and Publications

Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. The reaction occurs in two separate catalytic domains, coupled by the long-range translocation of a biotinylated carrier domain (BCCP). Here, we use a series of hybrid PC enzymes to examine multiple BCCP translocation pathways in PC. These studies reveal that the BCCP domain of PC adopts a wide range of translocation pathways during catalysis. Furthermore, the allosteric activator, acetyl CoA, promotes one specific intermolecular carrier domain translocation pathway. These results provide a basis for the ordered thermodynamic state and the enhanced carboxyl group transfer efficiency in the presence of …

Connecting Continents: Archaeology And History In The Indian Ocean World, Krish Seetah

Ohio University Press Open Access Books

In recent decades, the vast and culturally diverse Indian Ocean region has increasingly attracted the attention of anthropologists, historians, political scientists, sociologists, and other researchers. Largely missing from this growing body of scholarship, however, are significant contributions by archaeologists and consciously interdisciplinary approaches to studying the region’s past and present.

Connecting Continents addresses two important issues: how best to promote collaborative research on the Indian Ocean world, and how to shape the research agenda for a region that has only recently begun to attract serious interest from historical archaeologists. The archaeologists, historians, and other scholars who have contributed to this …

After Suffrage Comes Equal Rights? Era As The Next Logical Step, Tracy Thomas, Tracey Jean Boisseau

Con Law Center Articles and Publications

No abstract provided.

Relationship Between New Farming Practices And Chemical Use And The Consumption Of Giant Cricket (Brachytrupes Membranaceus Drury, 1770), F. O. Miantsia, F. Meutchieye, S. Niassy

All Peer-Reviewed Publications

The current work is aimed at generating information on giant crickets and the impact of commonly used pesticides on the natural population of these crickets. Data was collected based on interviews and complemented with field observations. Out of 319 respondents surveyed, 290 were aware of the use of the giant cricket as a food source, and 161 were active consumers. Regarding the availability of the giant cricket, respondents reported that the crickets' populations were diminishing because of farming practices. About 219 persons reported that commonly used herbicides harm giant crickets at different stages. This could be attributed to the scarcity …

Diapause Disruption In Cirina Butyrospermi Vuillet (Lepidoptera, Attacidae), The Shea Caterpillar, In Burkina Faso, H. B. Bama, R. A. Dabire, D. Ouattara, S. Niassy, M. N. Ba, D. Dakouo

All Peer-Reviewed Publications

The shea caterpillar Cirina butyrospermi is an important insect, highly valued as a human food item in Burkina Faso. However, its appearance is seasonal due to its univoltine cycle. This study therefore investigated the possibilities of breaking the nymphal diapause by changing the environmental factors and through the hormonal treatment of prepupae and pupae using bovine insulin and 20-hydroxyecdysone. Changes in humidity and temperature did not result in emergence, suggesting a mandatory nature of the diapause in C. butyrospermi. Injection of 20-hydroxyecdysone between 20 and 40 ng on 20 C. butyrospermi pupae resulted in 15.24 and 47.5% emergence, respectively. The …

Endophytic Colonization Of Onions Induces Resistance Against Viruliferous Thrips And Virus Replication, Alexander Mutua Muvea, Sevgan Subramanian, Nguya Kalemba Maniania, Hans Michael Poehling, Sunday Ekesi, Rainer Meyhöfer

All Peer-Reviewed Publications

In agricultural ecosystems, insect pests, pathogens, weather patterns, and reduced soil fertility pose major challenges to crop productivity and are responsible for significant yield losses worldwide. Iris yellow spot virus (IYSV) vectored by Thrips tabaci Lindeman, is a major hindrance to onion production in eastern Africa. Control measures often rely on insecticides with deleterious effects. Endophytes are one key alternative as they can play important roles in mediating induced systemic resistance. Hence, we examined the potential effect of endophytic fungus Hypocrea lixii (F3ST1) on feeding and replication of IYSV on endophyte-colonized (E+) and endophyte-free (E-) onion plants. For more precise …

Push-Pull Farming System Controls Fall Armyworm: Lessons From Africa, Zeyaur R. Khan, Jimmy O. Pittchar, Charles A.O. Midega, John A. Pickett

All Peer-Reviewed Publications

Fall armyworm (FAW) Spodoptera frugiperda invaded Africa, with the first detections being reported in Central and Western Africa in early 2016, and now affects at least 40 countries in Africa, causing up to total crop loss amounting to over $6.2 billion p.a. FAW is an invasive polyphagous pest that causes damage to economically important crops and has recently been reported in the Indian sub-continent. Effective control of FAW through use of synthetic chemical pesticides and genetically modified crops such as Bt maize faces challenges including improper use, unaffordability by smallholder farmers and development of resistance by the pest. Additionally, dispersal …

Influence Of Prolonged Dietary Experience During The Larval Stage On Novel Odour Preferences In Adults Of Noctuid Stem Borer Moths (Lepidoptera: Noctuidae), Christophe Petit, Peter Ahuya, Bruno Le Ru, Laure Kaiser-Arnauld, Myriam Harry, Paul André Calatayud

All Peer-Reviewed Publications

In Lepidoptera, larval dietary experience of volatile cues can induce adult preference for these cues. However, such induction may require several generations, depending in part on the degree of specialization of the insects. In a previous study, using species of noctuid stem borers with different diet breadths, namely the polyphagous Sesamia nonagrioides, the oligophagous Busseola fusca and monophagous Busseola nairobica, it was shown that in S. nonagrioides, one generation was enough to induce a preference for vanillin in the resulting gravid females, whereas even two generations failed to induce a response in adults of Busseola spp. In this study, we …

Haematology Of N’Dama And West African Shorthorn Cattle Herds Under Natural Trypanosoma Vivax Challenge In Ghana, Ebenezer Yaw Ganyo, Johnson N. Boampong, Daniel K. Masiga, Jandouwe Villinger, Paa Kobina Turkson

All Peer-Reviewed Publications

Background: Animal trypanosomosis is a major cause of economic loss in livestock production in Africa. A suggested control measure is to use breeds with traits of trypanotolerance. The study examines the effect of natural Trypanosoma vivax challenge on haematological parameters in two trypanotolerant cattle [N’Dama and West African Shorthorn (WASH)] herds. Methods: Trypanosoma vivax-specific primers were used to diagnose T. vivax infection in an N’Dama herd at Cape Coast in southern Ghana and a WASH herd at Chegbani in northern Ghana from May to July 2011 in a cross-sectional study. Levels of haematological parameters comprising packed cell volume (PCV), haemoglobin …

Genotypic Responses Of Brachiaria Grass (Brachiaria Spp.) Accessions To Drought Stress, Duncan Cheruiyot, Charles Aura Odhiambo Midega, Johnnie Van Den Berg, John Anthony Pickett, Zeyaur Rahman Khan

All Peer-Reviewed Publications

Background and Objective: Brachiaria, a warm season C4 grass, is rapidly gaining popularity as fodder crop in Africa where it is also used as a component of a habitat management strategy for maize stem borers. However, increasing drought limits productivity of this grass species. The aim of this study was to evaluate and select high yielding brachiaria genotypes under simulated drought conditions. Materials and Methods: The morphological and physiological performance of 18 apomictic accessions of brachiaria in simulated drought conditions in a screen house were evaluated. Plants were exposed to different watering regimes. Well-watered (control) plants were watered every 48 …

Physico-Chemical Properties Of Extruded Aquafeed Pellets Containing Black Soldier Fly (Hermetia Illucens) Larvae And Adult Cricket (Acheta Domesticus) Meals, F. G. Irungu, C. M. Mutungi, A. K. Faraj, H. Affognon, N. Kibet, C. Tanga, S. Ekesi, D. Nakimbugwe, K. K.M. Fiaboe

All Peer-Reviewed Publications

Fish farming is faced with the challenge of high cost of feeds because of the cost of high quality protein needed for formulation of the feeds. Thus, there is urgent need for alternative protein sources. The effects of substituting freshwater shrimp meal (FWSM) with black soldier fly larvae meal (BSFM) or adult cricket meal (ACM) on physico-chemical properties of hot-extruded fish feed pellets were investigated. The FWSM protein in a 26 g/100 g protein fish feed formulation was substituted at 0, 25, 50 and 75%, and moisture content of the formulated blends adjusted to 10, 20 or 30 g/100 g …

Risk Assessment And Spread Of The Potentially Invasive Ceratitis Rosa Karsch And Ceratitis Quilicii De Meyer, Mwatawala & Virgilio Sp. Nov. Using Life-Cycle Simulation Models: Implications For Phytosanitary Measures And Management, Chrysantus Mbi Tanga, Fathiya Mbarak Khamis, Henri E.Z. Tonnang, Ivan Rwomushana, Gladys Mosomtai, Samira A. Mohamed, Sunday Ekesi

All Peer-Reviewed Publications

Integrative taxonomy has resolved the species status of the potentially invasive Ceratitis rosa Karsch into two separate species with distinct ecological requirements: C. rosa “lowland type” and the newly described species Ceratitis quilicii De Meyer, Mwatawala & Virgilio sp. nov. “highland type”. Both species are tephritid pests threatening the production of horticultural crops in Africa and beyond. Studies were carried out by constructing thermal reaction norms for each life stage of both species at constant and fluctuating temperatures. Nonlinear functions were fitted to continuously model species development, mortality, longevity and oviposition to establish phenology models that were stochastically simulated to …

Public Authority Liability And The Regulation Of Nanotechnology: A European Perspective, Nina Natalia Baranowska

Canadian Journal of Law and Technology

This paper argues that in certain circumstances public authorities should be liable for regulating nanotechnology. Nanotechnology is an emerging field of technology that enables to control shape and size of various structures, devices and systems at nanometer scale on which one nanometer is equal to one-billionth of a meter. In spite of being a nascent field of science and technology, its scope of application – in the food, pharmaceuticals, cosmetics, construction, textile, electronics, and agricultural industries – is expanding rapidly. The risks associated to nanotechnology, however, and its long-term consequences are still largely unknown, particularly in regards to its health …

Routes, Locations, And Social Imaginary: A Comparative Study Of The On-Going Production Of Geographies In Somali Forced Migration, Marnie Shaffer, Giulia Ferrato, Zaheera Jinnah

All Faculty and Staff Scholarship

Drawing on the thresholds approach, a model that incorporates geography and mobility studies to understand migration from the perspective of migrants, this article examines the importance of location and route(s) in determining the journeys of Somali migrants. We use the protracted displacement of Somalis to address the process through which actual and perceived geographies are produced and reconfigured by Somali migrants on the move. In doing so, we look at how different migration paths, connected through transnational networks, influence the geographical perception of migrants at the core of any cross-border experience. Employing ethnographic fieldwork with Somalis in South Africa and …