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Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic Properties Based On Physicochemical Properties Of Calcium Channel Blockers, Tafif Abdullah Al Jul 2012

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic Properties Based On Physicochemical Properties Of Calcium Channel Blockers, Tafif Abdullah Al

Theses and Dissertations

This research explored quantitative relationships (QSPKR) between different molecular descriptors and pertinent, systemic PK properties for 14 calcium channel blockers (CCB). Physicochemical properties (PC) such as molecular weight (MW), molar volume (MV), calculated logP (clogP), pKa, calculated logD7.4 (clogD), % ionized at pH 6.3 and pH 7.4, hydrogen bond donors (HBD), hydrogen bond acceptors (HBA), and number of rotatable bonds (nRot) were chosen as possible predictor variables for systemic PK properties for CCB, obtained from pertinent literature, assessing the PK of CCB after intravenous administration to healthy humans. All PC properties and molecular descriptors were computed using ACD-solubility/DB 12.01. Total …

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Towards Understanding The Mechanism Of Action Of Abused Cathinones, Rakesh Vekariya Jul 2012

Towards Understanding The Mechanism Of Action Of Abused Cathinones, Rakesh Vekariya

Theses and Dissertations

The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft into the presynaptic terminus and plays a critical role in maintaining the normal function of dopaminergic neurons. DAT is the major target of widely abused psychostimulant drugs, including cocaine and amphetamine. DAT also figures into disease states, and it is a target for therapeutic drugs. It is known that cathinone and methcathinone, β-keto analogs of amphetamine and methamphetamine, respectively, produce pharmacological actions similar to amphetamine. Cathinone and methcathinone analogs are recently gaining in popularity on the clandestine market (e.g. ‘bath salts’). Cathinone and methcathinone analogs as well as …

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Development Of Magnetic Fabrics With Tunable Hydrophobicity, Thu Ho Jul 2012

Development Of Magnetic Fabrics With Tunable Hydrophobicity, Thu Ho

Theses and Dissertations

Polystyrene (PS) fiber mats incorporating iron (Fe) particles were fabricated by electrospinning and the hydrophobicity of the resulting magnetic fabrics was investigated with and without an applied magnetic field. The results show that the hydrophobicity (as measured using water droplet contact angle) increases in the presence of a magnetic field and the hysterisis in the advancing/receding contact angle (a measure of the stickiness of the surface) decreases in the presence of a magnetic field. It is also shown that the contact angle and hysterises increase with decreasing fiber diameter and mat thickness.

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Using Next Generation Sequencing (Ngs) To Identify And Predict Micrornas (Mirnas) Potentially Affecting Schizophrenia And Bipolar Disorder, Vernell Williamson Jul 2012

Using Next Generation Sequencing (Ngs) To Identify And Predict Micrornas (Mirnas) Potentially Affecting Schizophrenia And Bipolar Disorder, Vernell Williamson

Theses and Dissertations

The last decade has seen considerable research focusing on understanding the factors underlying schizophrenia and bipolar disorder. A major challenge encountered in studying these disorders, however, has been the contribution of genetic, or etiological, heterogeneity to the so-called “missing heritability” [1-6]. Further, recent successes of large-scale genome-wide association studies (GWAS) have nonetheless seen only limited advancements in the delineation of the specific roles of implicated genes in disease pathophysiology. The study of microRNAs (miRNAs), given their ability to alter the transcription of hundreds of targeted genes, has the potential to expand our understanding of how certain genes relate to schizophrenia …

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Sex-Specific Habitat Use And Responses To Fragmentation In An Endemic Chameleon Fauna, Philip Shirk Jul 2012

Sex-Specific Habitat Use And Responses To Fragmentation In An Endemic Chameleon Fauna, Philip Shirk

Theses and Dissertations

Chameleons are an understudied taxon facing many threats, including collection for the international pet trade and habitat loss and fragmentation. A recent field study reports a highly female-biased sex ratio in the Eastern Arc Endemic Usambara three horned chameleon, Trioceros deremensis, a large, sexually dimorphic species. This species is collected for the pet trade, and local collectors report males bring a higher price because only this sex has horns. Thus, sex ratios may vary due to differential rates of survival or harvesting. Alternatively, they may simply appear to be skewed if differences in habitat use biases detection of the sexes. …

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Life History Switch Point Plasticy In Response To Pond Drying Alyers Metamorph Allometry And Jumping Performance, Julie Charbonnier Jul 2012

Life History Switch Point Plasticy In Response To Pond Drying Alyers Metamorph Allometry And Jumping Performance, Julie Charbonnier

Theses and Dissertations

Animals with complex life cycles can cope with environmental uncertainty by altering life history switch points through developmental plasticity. Pond drying is an important factor which may alter life history switch points in aquatic organisms. Many amphibians can plastically respond to changes in pond drying by emerging earlier, but few studies have examined the post-metamorphic consequences for performance. To investigate the potential carry-over effects of plasticity to pond drying, we studied the túngara frog, Physalaemus pustulosus, a tropical anuran that breeds in highly ephemeral habitats. We conducted a field study with three different water depth treatments in 60 L mesocosms …

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Role Of Fyn And Lyn In Igg-Mediate Immune Responses, Yves Falanga Jul 2012

Role Of Fyn And Lyn In Igg-Mediate Immune Responses, Yves Falanga

Theses and Dissertations

Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage and neutrophil secretion of platelet activating factor subsequent to FcγR stimulation by IgG/Ag complexes. I have investigated the contribution of Fyn and Lyn tyrosine kinases to FcγRIIb and FcγRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). I found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38 and JNK phosphorylation. Additionally, IgG XL of …

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Small Molecules As Negative Allosteric Modulators Of Alpha7 Nachrs, Osama Alwassil Jul 2012

Small Molecules As Negative Allosteric Modulators Of Alpha7 Nachrs, Osama Alwassil

Theses and Dissertations

Alpha7 Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in essential physiological functions and play a role in disorders such as Alzheimer’s disease. MD-354 (3-chlorophenylguanidine; 21), the first small–molecule negative allosteric modulator (NAM) at alpha7 nAChRs, served as a lead in developing structure–activity relationships for NAMs at a7 nAChRs. MD-354 (21) also binds at 5-HT3 receptors. Analogs of MD-354 with structural features detrimental to 5-HT3 receptor affinity were evaluated in patch-clamp recordings and an aniline N-methyl analog resulted in a more potent and selective NAM than MD-354. A new N-methyl series of compounds was synthesized in which the 3-position was replaced …

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Transferrin Binding Protein B Structure, Function, And Export In Neisseria Gonorrhoeae, Meredith L. Weck Jul 2012

Transferrin Binding Protein B Structure, Function, And Export In Neisseria Gonorrhoeae, Meredith L. Weck

Theses and Dissertations

Iron, an essential nutrient for most microorganisms, is sequestered in the host by iron-binding proteins, such as lactoferrin and transferrin. Neisseria gonorrhoeae utilizes transferrin as an iron source and its iron acquisition system is composed of two transferrin binding proteins: TbpA and TbpB. TbpA is a TonB-dependent, outer membrane transporter and TbpB is a bilobed, surface exposed lipoprotein. TbpB can distinguish between apo- and holo-transferrin which is involved in increasing the efficiency of iron uptake through the Tbps. It is anchored in the outer leaflet of the outer membrane by its lipid moiety. We aimed to identify the mechanism of …

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Behavioral Phenotyping Of The Discriminative Stimulus Properties Of The Atypical Antipsychotic Drug Clozapine In 129s2/Hsv Mice, Kevin Webster Jul 2012

Behavioral Phenotyping Of The Discriminative Stimulus Properties Of The Atypical Antipsychotic Drug Clozapine In 129s2/Hsv Mice, Kevin Webster

Theses and Dissertations

The 129S2 inbred mouse strain is often used as a background strain in the production of genetically altered mice (i.e. knockout and transgenic mice). It is important to establish the behavioral phenotype of wild-type mice before making comparisons to genetically altered mice. Also, those comparisons can assist in the evaluation and interpretation of the in vivo effects of drugs. The drug discrimination assay measures the subjective effects of drugs and provides a measure of underlying neuropharmacological mechanisms responsible for the discriminative stimulus properties of drugs. The present study established the atypical antipsychotic drug clozapine as a discriminative stimulus in male …

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Angiogenesis In Response To Varying Fiber Size In An Electrospun Scaffold In Vivo., Damien Brown Jul 2012

Angiogenesis In Response To Varying Fiber Size In An Electrospun Scaffold In Vivo., Damien Brown

Theses and Dissertations

Injury to the spinal cord results in partial or complete loss of sensory perception and motor function. After spinal cord injury (SCI), damaged tissue dies and a cavity will form. This cavity prevents the regeneration of tissue and any functional recovery. One way to address the cavity is the insertion of an electrospun scaffold that our lab has created. This provides a substrate for regenerating tissue to grow on, and it is thought that reestablishing the blood supply within the scaffold will allow cells necessary for regeneration to thrive. This could ultimately lead to meaningful recovery for patients who have …

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The Evolution Of Conservative Attitudes As A Complement To Cognitive Threat Detection Mechanisms, Russ Clay Jul 2012

The Evolution Of Conservative Attitudes As A Complement To Cognitive Threat Detection Mechanisms, Russ Clay

Theses and Dissertations

Conservatism reflects a general attitude structure characterized by a preference for traditional social practices and an aversion to uncertainty and threat. Though the social environment undoubtedly plays a role in shaping conservative attitudes, recent studies suggest that trait-level characteristics may contribute to their development as well. The present research investigated trait-level cognitive threat detection ability as a factor which may influence the development and maintenance of conservative social attitudes. A computer simulation indicated that socially conservative attitudes may function as a strategy for increasing the survival rate of an individual with poor threat detection ability living in a relatively dangerous …

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Analysis Of The Fish Community On Tidal-Freshwater Constructed Reefs, Briana Langford Jul 2012

Analysis Of The Fish Community On Tidal-Freshwater Constructed Reefs, Briana Langford

Theses and Dissertations

Constructed reefs are used successfully in marine systems to enhance spawning habitat; this study examines the effectiveness of constructed reefs in a tidal-freshwater river. Fish abundance, species diversity and richness, residency, water column position, reproductive guilds, and feeding guilds were analyzed on two constructed reefs in the tidal-freshwater James River and compared to silted regions representing the primary substrate in the river. Reefs were sampled using hydroacoustics, electroshocking, gillnetting, trawling, and egg mats. The constructed reefs had a greater proportion of fish that broadcast spawn over hard substrate and a trend of more overall individual, residential, and demersal fish. The …

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The Role Of A And B Vitamins During Orofacial Development Of Xenopus Laevis, Allyson Kennedy Jun 2012

The Role Of A And B Vitamins During Orofacial Development Of Xenopus Laevis, Allyson Kennedy

Theses and Dissertations

Orofacial anomalies make up about a third of the 120,000 birth defects each year in the United States. Children born with these abnormalities must undergo immense physical and emotional strain in order to correct the defects. In fact, about $697 million is spent every year surgically treating children with cleft lip and/or cleft palate (2011). In countries where surgery is not an option, this abnormality causes immense difficulties in eating, hearing, speech, and psychosocial development. The causes of cleft lip/palate are extremely complex. Genetics play a role in the anomaly; however, 95% of cleft palate cases are non-syndromic and likely …

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Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib Jun 2012

Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib

Theses and Dissertations

Increasingly the role of epigenetic machinery as a bridge between underlying DNA sequence and cellular phenotype is being discovered. The establishment of a myriad of unique cellular types sharing identical gene sequences in a multicellular organism gives a broad sense for the inherent role of epigenetic influence on cell differentiation. Importantly, the epigenetic mechanisms involved in establishing cell identity unsurprisingly contribute to diseased states, including cancer. Recent research continues to elucidate contributory roles of epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA regulation, in human cancers. Additionally, chromatin remodelers, such as the Nucleosome Remodeling Factor (NURF), have been …

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Mda-7/Il-24; A Promising Cancer Therapeutic Agent, Hossein Hamed Jun 2012

Mda-7/Il-24; A Promising Cancer Therapeutic Agent, Hossein Hamed

Theses and Dissertations

Glioblastoma multiforme (GBM) is an aggressive cancer that affects millions of patients per year. Conventional therapies combining chemotherapeutic agents with radiation can only extend survival by a few months; therefore, there is a dire need for an effective means of treating this deadly disease. Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), currently in the early stages of FDA pre-IND drug trials, has proven to be an effective cancer specific cytokine, able to trigger the onset of mitochondrial dysfunction and/or autophagy. GBM’s have mutations that often result in the activation of cytoprotective cell signaling pathways, preventing cancer therapeutics and even MDA-7/IL-24 treatments from being …

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Artifacts And Commingled Skeletal Remains From A Well On The Medical College Of Virginia Campus: Appendices, Douglas W. Owsley, Karin Bruwelheide, Merry Outlaw, Richard L. Jantz Jun 2012

Artifacts And Commingled Skeletal Remains From A Well On The Medical College Of Virginia Campus: Appendices, Douglas W. Owsley, Karin Bruwelheide, Merry Outlaw, Richard L. Jantz

Office of the President Documents

This is a report prepared by Douglas W. Owsley and Karin Bruwelheide, Department of Anthropology, National Museum of Natural History, Smithsonian Institution in fulfillment of the Contract Agreement between the Smithsonian Institution. The objectives of this report included identification and documentation of the bones and artifacts recovered from the well, establishing the temporal context, and interpreting the relationship of the materials to the site’s use and history as an early medical school in the city of Richmond. This report has three main sections: a review of the archival history of the school as it related to the use of the …

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Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy Jun 2012

Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy

Theses and Dissertations

UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal …

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Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane May 2012

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane

Theses and Dissertations

Mitf and Otx transcription factors have been identified as essential to the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific role in the RPE developmental pathway have not been clearly defined. The role of the two Mitf transcription factors (Mitfa and Mitfb) and two Otx transcription factors (Otx1a and Otx2) in zebrafish RPE development was explored in these experiments. The loss of Mitf activity in mitfa, mitfb, or double mitf null mutant fish lines had no effect on RPE pigmentation or development. The loss of Otx2 activity through morpholino knockdown produced a …

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An Agent Based Model Of Tumor Growth And Response To Radiotherapy, Nicole O'Neil May 2012

An Agent Based Model Of Tumor Growth And Response To Radiotherapy, Nicole O'Neil

Theses and Dissertations

An agent based model was developed to examine the growth of a tumor in a healthy cell population. Response to radiation and impact of mutation and bystander effects were studied. In the growth model, the cancer cells proliferated outward becoming invasive. The mass of cancer cells developed a necrotic core. Various treatment protocols of radiation were compared. Timing of treatments was critical to the success of therapy. The event of mutation was rare. When mutation occurred, either unsuccessful treatment or re-growth could result. Multiple rounds of radiation potentially led to increased mutation. Low levels of the bystander effect had little …

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The Antinociceptive Effects Of Alpha 7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators In Different Animal Pain Models, Kelen Freitas May 2012

The Antinociceptive Effects Of Alpha 7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators In Different Animal Pain Models, Kelen Freitas

Theses and Dissertations

The α7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly expressed in the central nervous system (CNS) and in the periphery. Positive allosteric modulators (PAMs) of the α7 increase the response to an agonist and are divided into two types depending on whether they also decrease desensitization of the receptor (type II) or not (type I). Therefore, this study aims to investigate whether the enhancement of endogenous α7 nAChR function will result in a beneficial effect in nociceptive, inflammatory and chronic neuropathic pain models. While NS1738 and PNU-120596 were not active to reduce acute thermal pain, measured by hot-plate and tail-flick …

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T-Bet-Dependent Regulation Of T Cell Responses During Trypanosoma Cruzi Infection, Dustin Cobb May 2012

T-Bet-Dependent Regulation Of T Cell Responses During Trypanosoma Cruzi Infection, Dustin Cobb

Theses and Dissertations

The human pathogen Trypanosoma cruzi is an intracellular parasite and the etiological agent of Chagas disease. Protective immune responses to T. cruzi are highly dependent on T helper 1 and CD8+ T cells which produce interferon-gamma. A deficiency in these responses has severe consequences on the ability to control infection. Our investigation into the role of the Th1 transcription factor, T-bet, during murine T. cruzi infection revealed that T-bet is required for resistance. Contrary to our expectations, T-bet was not required for the development of Th1 immunity during infection, as T-bet-deficient mice still developed interferon-gamma-producing T cells. However, T-bet was …

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Validation Of 3'-Deoxy-3'-[18f]-Fluorothymidine Positron Emission Tomography For Image-Guidance In Biologically Adaptive Radiotherapy, Marian Axente May 2012

Validation Of 3'-Deoxy-3'-[18f]-Fluorothymidine Positron Emission Tomography For Image-Guidance In Biologically Adaptive Radiotherapy, Marian Axente

Theses and Dissertations

Accelerated tumor cell repopulation during radiation therapy is one of the leading causes for low survival rates of head-and-neck cancer patients. The therapeutic effectiveness of radiotherapy could be improved by selectively targeting proliferating tumor subvolumes with higher doses of radiation. Positron emission tomography (PET) imaging with 3´-deoxy-3´-[18F]-fluorothymidine (FLT) has shown great potential as a non-invasive approach to characterizing the proliferation status of tumors. This thesis focuses on histopathological validation of FLT PET imaging specifically for image-guidance applications in biologically adaptive radiotherapy. The lack of experimental data supporting the use of FLT PET imaging for radiotherapy guidance is addressed by developing …

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Reflections Of Self, Melissa Athey May 2012

Reflections Of Self, Melissa Athey

Theses and Dissertations

I vacillate between all extremes, beauty vs. ugly, internal vs. external, micro vs. macro. It is these disparate notions that inspire what I make. We cannot ever see ourselves objectively, but does that mean we shouldn’t try? This thesis is my attempt to dissect what I created in my 2 years at Virginia Commonwealth University, my exploration of the illness within and the psychological nature of how we go about hiding our insecurities.

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Display, Baldwin Amanda May 2012

Display, Baldwin Amanda

Theses and Dissertations

I will discuss six art works that have a range of characteristics, but can all be unified through the notion of surface, both physically and conceptually. I will investigate how ideas of taste, assumption, collage, façade, figure/ground, display and value can all be seen through this lens. Much significance and symbolism is imbued in such a thin layer and I am actively aware of this as I work. The way I construct and render my subjects and the space in which they reside determines how they are viewed, perceived, considered, and judged by others.

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Synthesis And Biological Evaluation Of Second Generation Anibamine Analogues As Novel Anti-Prostate Cancer Agents, Shilpa Singh May 2012

Synthesis And Biological Evaluation Of Second Generation Anibamine Analogues As Novel Anti-Prostate Cancer Agents, Shilpa Singh

Theses and Dissertations

Prostate cancer is the most prevalent non-cutaneous cancer among men. Since the 19th century when Virchow first introduced the concept of inflammation in cancer, chemokines and their receptors have garnered a lot of interest. Chemokine receptor CCR5 has been especially implicated in many disease states and recently found to be over expressed in prostate cancer cell lines. Anibamine, a natural CCR5 antagonist discovered in 2004, has been found to have significant anti-prostate cancer activity at micromolar level. To optimize this compound and also discover a novel pharmacophore, exploration of the original structure was carried out. Significant modifications were made to …

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Reflections On Sexuality, Sensuality, And Painting, Loie Hollowell May 2012

Reflections On Sexuality, Sensuality, And Painting, Loie Hollowell

Theses and Dissertations

The written component of my thesis will take the form of an extended artist statement in which I discuss all six paintings included in my thesis exhibition. A major theme of my work is sexuality, specifically female sexuality. This thesis will begin by looking at the three miniature paintings that spearheaded the investigation of this theme. I will examine the generalized and personal feminist symbolism that these paintings contain. The two works that followed the miniatures are depictions of sexual interactions between my husband and myself. I will explain the significance of my depictions and relate them to the work …

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The Dragons In Your Dreams, Jacquelyn Walther May 2012

The Dragons In Your Dreams, Jacquelyn Walther

Theses and Dissertations

What if every craving that you ever felt stayed with you forever? Suppose facades couldn’t exist, and what should only be the deepest, densest core of a desire was formed into a mass, a body. Its will matching yours in its physical presence. I make creatures that are embodiments of emotions. In this study I mainly focus on desires and inhibitions surrounding romance. I explore anatomical structures and how material make-up can directly reflect emotional character. In this exploration, the materiality of clay allows for a thorough manipulation of the composition of the creatures. In this I am also able …

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Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen May 2012

Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen

Theses and Dissertations

Title of Dissertation: FUNCTION OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7(IGFBP7) IN HEPATOCELLULAR CARCINOMA By Dong Chen. Purpose: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring the development of innovative and effective targeted therapies. The oncogene Astrocyte Elevated Gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates Insulin-like Growth Factor Binding Protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function. Experimental Design: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarrays by real-time PCR …

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Population Based Model Of Gonorrhea And Interventions Against Increased Antibiotic Resistance, Courtney Henry May 2012

Population Based Model Of Gonorrhea And Interventions Against Increased Antibiotic Resistance, Courtney Henry

Theses and Dissertations

Gonnorrhea is an infectious sexually transmitted disease (STD) caused by the bacterium Neisseria gonorrhoeae that commonly reproduces in the reproductive tract.The Centers of Disease Control and Prevention (CDC) estimate that more than 700,000 individuals in the U.S. contract new gonorrheal infections per year. During recent years, there has been a progressive global increase of drug-resistant strains of gonorrhea. Therefore, there exists the necessity for health organizations to encourage the monitoring, research and development of innovative treatment regimens. We have developed multiple mathematical models to explore the gonorrheal disease state. The first objective of model formulation was to fit the model …

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