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Positron Emission Tomography For Pre-Clinical Sub-Volume Dose Escalation, Christopher Bass
Positron Emission Tomography For Pre-Clinical Sub-Volume Dose Escalation, Christopher Bass
Theses and Dissertations
Purpose: This dissertation focuses on establishment of pre-clinical methods facilitating the use of PET imaging for selective sub-volume dose escalation. Specifically the problems addressed are 1.) The difficulties associated with comparing multiple PET images, 2.) The need for further validation of novel PET tracers before their implementation in dose escalation schema and 3.) The lack of concrete pre-clinical data supporting the use of PET images for guidance of selective sub-volume dose escalations. Methods and materials: In order to compare multiple PET images the confounding effects of mispositioning and anatomical change between imaging sessions needed to be alleviated. To mitigate the …
Intra And Extracellular Functions Of Sphingosine-1-Phosphate In Sterile Inflammation., Jessie Yester
Intra And Extracellular Functions Of Sphingosine-1-Phosphate In Sterile Inflammation., Jessie Yester
Theses and Dissertations
Sterile inflammation is a key component of a variety of diseases including, gout, arthritis, type 1 diabetes, Alzheimer’s disease and multiple sclerosis (MS). Sterile inflammation induces the recruitment of immune cells via chemokines, such as CCL5 and CXCL10. Expression of these chemokines is dependent on IRF-1. Recently the FDA has approved the use of a pro-drug, FTY720 that after phosphorylation becomes a S1P mimetic for the treatment of MS. This report describes two novel and opposing mechanisms of S1P action in sterile inflammation. First, intracellular S1P acts as a cofactor of cIAP2 that inducesIL-1-dependent K63-polyubiquitination of IRF-1, which leads to …
Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome, Julie Chan
Theses and Dissertations
Traumatic brain injury (TBI) is a worldwide epidemic as the number of victims living with the resulting cognitive and physical impairment continues to rise, principally due to limited treatment options which fail to address its multifaceted sequelae. By approaching TBI therapy from a molecular standpoint, we have the opportunity to develop a better understanding of the mechanisms which prevent effective recovery. With this information, we can move toward the identification of novel therapeutic treatments which target specific molecules to improve patient outcome following TBI. Here, we have focused on the therapeutic potential of osteopontin (OPN), an extracellular matrix (ECM) protein …
Confocal Microscopy Study Of The Embryonic Development Of The Viviparous Nemertean Prosorhochmus Americanus Reveals Larval Features Supporting Indirect Development In Hoplonemerteans, S Tyler Spindle
Theses and Dissertations
Recent studies of hoplonenemertean planuliform larvae have clarified their development and provided insight into larval evolution within the phylum. However, an assessment of viviparous development using modern techniques is lacking. To help facilitate a comprehensive comparative evaluation of developmental diversity within hoplonemerteans, we have conducted a confocal laser scanning microscopy investigation of the development in Prosorhochmus americanus, one of the few viviparous hoplonemertean species. Phalloidin staining provides evidence of a modified transitory larval epidermis, and reveals that the foregut, midgut, proboscis, central nervous system, and body wall musculature form early in development, consistent with observations for planktonic and encapsulated hoplonemertean …
The Design And Development Of A Perceptual-Based Haptic Display Device, Sohaib Akhter
The Design And Development Of A Perceptual-Based Haptic Display Device, Sohaib Akhter
Theses and Dissertations
Graphical information presented as pictures, graphs, maps, and the like are an important media for relaying knowledge and are a fundamental means of education rarely experienced by people who are blind or have a severe visual impairment. This thesis presents the design, development and testing of a multiple finger, haptic matrix dynamic display device capable of relaying graphical information through simulated textures. The design is based on user perception studies that determined which hand constraints provided the best tradeoff between simplicity of design, accuracy and time to answer. The best design was one that incorporated multiple fingers in close proximity …
A Mathematical System For Human Implantable Wound Model Studies, Salomonsky Paul-Michael
A Mathematical System For Human Implantable Wound Model Studies, Salomonsky Paul-Michael
Theses and Dissertations
Dermal wound healing involves a myriad of highly regulated and sophisticated mechanisms, which are coordinated and carried out via several specialized cell types. The dominant players involved in this process include platelets, neutrophils, macrophages and fibroblasts. These cells play a vital role in the repair of the wound by orchestrating tasks such as forming a fibrin clot to stanch blood flow, removing foreign organisms and cellular debris, depositing new collagen matrix and establishing the contractile forces which eventually bridge the void caused by the initial infraction.\\[5pt] \indent Our current understanding of these mechanisms has been primarily based upon animal models. …
Assessment Of The Drug-Drug Interaction Potential Of Anionic Components In The Diet And Herbal Medicines On Organic Anion Transporters (Slc22 Family), Li Wang
Theses and Dissertations
Numerous natural products are widely used as first-line/alternative therapeutics and dietary supplements in both western and eastern society. However, the safety and efficacy profiles for herbal products are still limited. Organic anion transporters (OATs; SLC22 family) are expressed in many barrier organs and mediate in vivo body disposition of a broad array of endogenous substances and clinically important drugs. As some dietary flavonoids and phenolic acids were previously demonstrated to interact with OATs, it is necessary to explore the potential interaction of such components found in natural products in order to avoid potential OAT-mediated drug-drug interactions (DDIs). The inhibitory effects …
Development Of Pectoral Apparatus In Ictalurid Catfish, Shweta Lahiri
Development Of Pectoral Apparatus In Ictalurid Catfish, Shweta Lahiri
Theses and Dissertations
The thesis contains two manuscripts- 1) Developmental changes in pectoral muscle fiber diameter and number in the Blue Catfish, Ictalurus furcatus and 2) Reduction in pectoral spine and girdle in domesticated Channel Catfish, Ictalurus punctatus is likely caused by the absence of fish predators. The first study showed that fiber diameter increased linearly with fish size, whereas fiber number increases non linearly with fish size in the Blue Catfish correlated with dietary shift. The second study showed shorter spines in domesticated Channel Catfish as compared to wild Channel Catfish was a result of reduction in selection pressure during domestication in …
Environmental Influences On Sex Ratio And Spatial Distribution Of Dioecious Morella Cerifera L. On A Virginia Barrier Island., Molly Hokkanen
Environmental Influences On Sex Ratio And Spatial Distribution Of Dioecious Morella Cerifera L. On A Virginia Barrier Island., Molly Hokkanen
Theses and Dissertations
For dioecious plant species, sex ratios within a population depend on multiple environmental and life history characteristics. Sex ratio is an indicator of population health and can be a predictor for genetic bottlenecking. My study established the previously unknown sex ratio for the shrub, Morella cerifera, on a Virginia barrier island. The ratio was compared with multiple environmental and reproductive traits to determine their potential influence on sex determination and/or distribution of male and female plants. Multivariate analyses were used to identify relationships between sex, sex ratio and environmental drivers. The sex ratio for M. cerifera changed depending on scale. …
A Novel Biorelevant In Vitro System To Predict The In Vivo Performance Of Oral Transmucosal Products, Poonam Delvadia
A Novel Biorelevant In Vitro System To Predict The In Vivo Performance Of Oral Transmucosal Products, Poonam Delvadia
Theses and Dissertations
In vitro dissolution, release and permeation testing is a common practice during drug product research and development. These in vitro tests, if predictive, are referred to as biorelevant tests and can play diverse roles to facilitate and expedite product development in a cost effective manner. Oral transmucosal products (OTPs) are currently tested using compendial and modified in vitro tests which may or may not be good predictors of in vivo performance due to a lack of biorelevance. A critical need for a broadly applicable and biorelevant in vitro system for OTPs has been expressed in the literature and the goal …
Code-Switching In The Classroom: Teaching The Neutral American Dialect To The 21st Century Student, Hollis Louise Casini
Code-Switching In The Classroom: Teaching The Neutral American Dialect To The 21st Century Student, Hollis Louise Casini
Theses and Dissertations
Language is a personal process, a product of not only our development, but of one’s culture. Yet in the United States, an actor must be able to speak without a detectable dialect to be competitive in the entertainment world. How can voice teachers in a multi-cultural society, train students with more attention to the individuality of the students we educate? In this thesis, I present the information I have found important in my development as a voice teacher that has influenced my approach to training actors to use the Neutral American dialect. I begin by outlining human language acquisition and …
Examining The Relationship Between High School Deviant Behavior And Substance Use In College Students., Amanda Ndemo
Examining The Relationship Between High School Deviant Behavior And Substance Use In College Students., Amanda Ndemo
UROP Posters
The main purpose of the study was to determine the relationship between deviant high school behavior and substance use, as limited to alcohol and cigarette use. Deviant behavior as analyzed was defined by symptoms of conduct disorder and alcohol and cigarette use was limited to the past 30 days of the individual’s college career. The Conduct Disorder (CD) symptoms queried in the survey included setting fires, fights and things of that nature. Deviant behavior sum scores were created based on a pattern of related behaviors and the frequency at which each occurred. Data from 2022 VCU freshman who completed the …
Exploring Electric Field-Induced Changes In Astrocyte Behavior, Doel Dhar
Exploring Electric Field-Induced Changes In Astrocyte Behavior, Doel Dhar
Theses and Dissertations
Electric fields, which are generated by the movement of charged ions across membranes, are found in all biological systems and can influence cellular components ranging from amino acids to biological macromolecules. Physiological field strengths range from 1 – 200 mV/mm, and these electric fields are especially elevated at sites of cellular growth during development and regeneration. It has previously been demonstrated that elevated electric fields induce alignment of astrocyte processes in vitro, enhancing the rate of neurite outgrowth. It is believed that electric fields of varying physiological strength affect other astrocytic responses associated with regeneration. To characterize the duration over …
Effects Of Touch Therapy As A Means Of Treatment For Autism Among Young Children, Pahul Hanjra
Effects Of Touch Therapy As A Means Of Treatment For Autism Among Young Children, Pahul Hanjra
UROP Posters
Autism causes impediments for children with the disorder that they carry as obstacles to overcome for their entire lives. Major characteristics of autism include social delays such as inhibited interaction with others, touch aversion, as well as abnormal intake of sensory information, with understated reactions or high sensitivity to external stimuli. As a result of the many inhibitions the disorder places on afflicted individuals, day-to-day life can be a struggle. The prevalence of autism spectrum disorder is increasing in the United States and the world, and the publication of the DSM-IV has broadened the definition of autism to include forms …
Phylogeography And Species Status Of Ramphogordius Sanguineus, Cora Runnels
Phylogeography And Species Status Of Ramphogordius Sanguineus, Cora Runnels
Theses and Dissertations
Ramphogordius sanguineus (Rathke 1799) is a gregarious nemertean with a worldwide distribution and found mainly on hard substrates associated with mussels, oysters and other organisms of the fouling community. Asexual reproduction occurs by spontaneous fragmentation and only anecdotal accounts of sexual reproduction exist. This is the first phylogeographic study of R. sanguineus as well as the first species delimitation analyses employing DNA markers. Analysis of the mitochondrial gene nad6 and nuclear ISSR markers showed little diversity among geographically widespread populations, but AMOVA analyses of both markers revealed moderate to high genetic differentiation. Populations from Maine and Massachusetts exhibited the highest …
Ex Vivo Reprogramming Of Tumor-Reactive Immune Cells From Fvbn202 Mice Bearing Lung Metastatic Mammary Carcinoma: An Immunotherapeutic Opportunity Revealed Against Recurrence, Charles Hall
Theses and Dissertations
Metastatic breast cancer treatment has seen few advances in recent years, yet treatment resistance continues to rise, causing disease recurrence. A pilot study was performed to determine the efficacy of ex vivo expansion and reprogramming of tumor-reactive immune cells from experimental metastatic tumor-sensitized mice. Also, phenotypic changes in tumors due to metastasis or tumor microenvironment influences were characterized. Metastatic neu+ mouse mammary carcinoma (mMMC) and its distant relapsing neu-antigen-negative variant (mANV) were investigated in FVBN202 mice. Tumor-reactive central memory CD8+ T cells and activated NK/NKT cells were successfully reprogrammed and expanded during 6-day expansion from mMMC- and/or mANV-sensitized mice, resulting …
Role Of Tyk2 In Regulating Energy Expenditure And Preventing Obesity, Vidisha Raje
Role Of Tyk2 In Regulating Energy Expenditure And Preventing Obesity, Vidisha Raje
Theses and Dissertations
Obesity develops when energy intake exceeds energy expenditure. Defect in the function of brown fat and skeletal muscle, two of the major tissues that contribute towards energy expenditure, lead to the development of obesity and metabolic syndrome. Our previous findings suggest that Tyk2 deficient mice become obese and develop the metabolic syndrome. Tyk2, which is a tyrosine kinase of the JAK-STAT signaling family, is important for optimal brown development and function. Since brown fat and skeletal muscle, both are derived from the Myf5+ lineage of mesenchymal stem cells, we also characterized the role of Tyk2 in the development and function …
Identification And Characterization Of Ethanol Responsive Genes In Acute Ethanol Behaviors In Caenorhabditis Elegans, Joseph Alaimo
Identification And Characterization Of Ethanol Responsive Genes In Acute Ethanol Behaviors In Caenorhabditis Elegans, Joseph Alaimo
Theses and Dissertations
Alcohol abuse and dependence are complex disorders that are influenced by many genetic and environmental factors. Acute behavioral responses to ethanol have predictive value for determining an individual’s long-term susceptibility to alcohol abuse and dependence. These behavioral responses are strongly influenced by genetics. Here, we have explored the role of genetic influences on acute behavioral responses to ethanol using the nematode worm, Caenorhabditis elegans. First, we explored the role of ethanol metabolism in acute behavior responses to ethanol. Natural variation in human ethanol metabolism machinery is one of the most reported and reproducible associations found to alter drinking behavior. Ethanol …
Analysis Of Humira, Electro-Acupuncture, And Pulsatile Dry Cupping On Reducing Joint Inflammation In Patients With Rheumatoid Arthritis, Natalie Noll
UROP Posters
Humira, an anti-TNF drug aimed at decreasing inflammation in Rheumatoid Arthritis patients, can cause skin diseases from a rash to skin cancer. Humira works by blocking the chemical receptor RANKL, which therefore halts the production of osteoclasts, which attack and eat bone and cartilage, causing inflammation in arthritis patient’s joints. By analyzing Humira’s effect on the human body, it can be compared against other treatments such as electro-acupuncture and pulsatile dry cupping to see if these alternative treatments can decrease inflammation in Rheumatoid Arthritis patients through blocking RANKL, and if they are safer methods for carrying out this treatment. Under …
Stray Dogs Cause Health Risks In Thailand, Kadie Brigham
Stray Dogs Cause Health Risks In Thailand, Kadie Brigham
UROP Posters
Around 120,000 stray dogs are currently roaming the streets of Thailand compared to the 67,000,000 people that currently live there. Although the stray dog population doesn't outnumber the human population, it still should be a concern of the Thai government because stray dogs have shown aggression towards people and, carry diseases and rabies that could be transferred to people causing them serious ailments. Chantapong Wasi and colleagues from the Medicine Siriraj Hospital at Mahidol Universty in Thailand estimate that within the stray dog population only about 20% of the dogs are vaccinated or sterilized. My research explores what type of …
Genetic Analysis Of Ethanol Sensitivity And Tolerance In Drosophila, Robin Chan
Genetic Analysis Of Ethanol Sensitivity And Tolerance In Drosophila, Robin Chan
Theses and Dissertations
The genetic pathways influencing alcohol abuse and dependence are poorly characterized. Many critical discoveries about the interactions between ethanol-related behaviors and genetics have been made in the fruit fly Drosophila melanogaster. Coupling the statistical power of model organism studies to human association studies bolsters the analytical efficacy of these genomic approaches. A variety of behavioral assays are available for assessing behavioral responses to ethanol in Drosophila. However, we find our previously described eRING assay is influenced by the commonly used transgenic marker mini-white. We developed a Simple Sedation Assay (SSA) that is insensitive to the effects of white and mini-white. …
Adam10 Overexpression Dysregulates Notch Signaling In Favor Of Myeloid Derived Suppressor Cell (Mdsc) Accumulation That Deferentially Modulates The Host Response Depending On Immune Stimuli And Interaction With Mast Cells., Sheinei Saleem
Theses and Dissertations
Although the physiological consequences of Notch signaling in hematopoiesis have been extensively studied, the differential effects of individual notch cleavage products remain to be elucidated. Given that a disintegrin and metalloproteinase 10 (ADAM10) is a critical regulator of Notch and that its deletion is embryonically lethal, we generated transgenic mice that overexpress ADAM10 at early stages of lymphoid and myeloid development (A10Tg). ADAM10 transgene expression alters hematopoiesis post-hematopoietic Lineage-Sca-1+c-kit+ (LSK) subset differentiation but prior to lineage commitment of progenitor populations. This results in delayed T cell development, abrogated B2 cell development, and dramatic expansion of functionally active myeloid derived suppressor …
Synthesis, Testing And Crystallographic Studies Of Allosteric Modifiers Of Hemoglobin, Tanvi Deshpande
Synthesis, Testing And Crystallographic Studies Of Allosteric Modifiers Of Hemoglobin, Tanvi Deshpande
Theses and Dissertations
The major physiological function of hemoglobin (Hb) is to bind, transport and deliver oxygen to tissues; made efficient by endogenous effectors, such as protons and 2,3-diphosphoglycerate. Synthetic allosteric effectors of Hb (AEHs) are also known to modulate Hb oxygen affinity, showing potential for the treatment of sickle cell disease (SCD) and ischemic-related diseases. In this project, AEHs which increase Hb affinity for oxygen, including derivatives of the anti-sickling compounds, 5HMF and benzaldehydes, as well as an AEH that decreases Hb affinity for oxygen, RSR-13, were synthesized for their effects on Hb oxygen binding property and their capability to release NO …
The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood
The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood
Theses and Dissertations
Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers worldwide, with a survival rate of less than 50%. A class of mutant p53, known as gain of function (GOF) mutant p53, has been found to be expressed in tumors in these patients. GOF mutant p53 not only loses the wild type tumor suppressor functions, but also gains aberrant functions that have been linked to tumorigenesis. In this current study, we utilized a model system consisting of cells derived from HNSCC tumors in order to investigate our hypothesis that GOF mutant p53 enhances, and p63 …
Cannabinoids Delta-9-Tetrahydrocannabinol (Thc) And Cp55,940 Ablate Specific Chemokine And Cytokine Inflammatory Response In Bv-2 Mouse Microglial Cells Activated With Hiv-1 Pro-Inflammatory Protein Tat, Rebecca Maddux
Theses and Dissertations
Despite the widespread use of Highly Active Anti-retroviral Therapy (HAART) to combat Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), HIV-Associated Neurocognitive Disorders (HANDs) still remain a dire issue. HIV can enter the brain through infected monocytes and infect microglia, the resident macrophages within that compartment. Due to its pro-inflammatory properties, HIV regulatory protein Tat (Transactivating protein) may play a role in the progression of neurocognitive disorders. The aim of this project was to determine whether the select cannabinoids THC and CP55,940 could ablate the inflammatory response on BV-2 mouse microglia cells caused by Tat. Within …
Identification Of Multiple Levels Of Trauma Induced Coagulopathy, Jason Newton
Identification Of Multiple Levels Of Trauma Induced Coagulopathy, Jason Newton
Theses and Dissertations
Trauma continues to be a major cause of death across the globe. While the exact causes of trauma differ greatly between the military and civilian lifestyles, the ability to stop bleeding after trauma is paramount for survival. Over the past decade coagulation research has transitioned from a classical understanding of plasma based protein coagulation to the current cell focused research. As part of this shift, platelets have become a central player in hemostasis. Unfortunately little is currently understood about how platelet function is affected by trauma. In an effort to better define platelet function during trauma and the resulting shock …
Impact Of Self-Fertilization On Fecundity, The Timing Of First Reproduction, And Population Genetic Structure: Is A Mate Worth The Wait?, Serena Caplins
Impact Of Self-Fertilization On Fecundity, The Timing Of First Reproduction, And Population Genetic Structure: Is A Mate Worth The Wait?, Serena Caplins
Theses and Dissertations
Organisms capable of self-fertilization typically exhibit two evolutionary syndromes uniting high inbreeding depression with low levels of selfing, or low inbreeding depression and high levels of selfing. This study tests for inbreeding depression in an apparent self-compatible, hermaphroditic marine nemertean worm, Prosorhochmus americanus. Fecundity and timing to first reproduction were assessed in isolated and paired worms. Isolated worms produced significantly more offspring than paired worms and did not show inbreeding avoidance. The selfing rate of natural populations was evaluated using species-specific microsatellites and is consistent with preferential selfing (mean: 0.801), though some outcrossing appears to take place. Population genetic structure …
Negotiating The Double Mandate: Mapping Ethical Conflict Experienced By Practicing Educational Leaders, Jeffrey Mcgee
Negotiating The Double Mandate: Mapping Ethical Conflict Experienced By Practicing Educational Leaders, Jeffrey Mcgee
Theses and Dissertations
The qualitative approach used in this study captured and described ethical conflict experienced by a sample of practicing educational leaders. Narrative inquiry data were collected from 42 former and current doctoral students and additional data were captured through follow-up interviews with selected participants. The major findings of the study suggest that ethical conflict is inherent in the practice of educational leadership. Such conflict is most often experienced in relation to colleagues when the ethics of justice and care collide. Leaders’ ability to mitigate conflict that is often the result of institutional and external factors is promoted by varied background and …
Structural Basis Of Dna Binding Complexes, Ninad Walavalkar
Structural Basis Of Dna Binding Complexes, Ninad Walavalkar
Theses and Dissertations
The nucleosome remodeling and deacetylase (NuRD) complex is an abundant deacetylase complex, which couples histone deacetylation and chromatin remodeling ATPase activities, and has a broad cellular and tissue distribution. Although the working model of how this complex forms and functions is not well known, we have demonstrated that the coiled-coil interaction between two proteins (MBD2 and p66α) is critical for DNA methylation dependent gene silencing in vivo. Chapter one: ‘Unique features of the anti-parallel, heterodimeric coiled-coil interaction between methyl-cytosine binding domain 2 (MBD2) homologues and p66α dictate high affinity binding’ describes this unique coiled coil interaction. Coiled-coils were studied using …
Modular Envelops, Rotem Tamir
Modular Envelops, Rotem Tamir
Theses and Dissertations
This texts in about my thesis show; Modular envelopes which was presented in the Anderson gallery at may 2013. The text speaks about my individual process of making both this particular work and art in general.