Digital Commons Network^™

Developing High-Density Diffuse Optical Tomography For Neuroimaging, Brian White

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Clinicians who care for brain-injured patients and premature infants desire a bedside monitor of brain function. A decade ago, there was hope that optical imaging would be able to fill this role, as it combined fMRI's ability to construct cortical maps with EEG's portable, cap-based systems. However, early optical systems had poor imaging performance, and the momentum for the technique slowed. In our lab, we develop diffuse optical tomography: DOT), which is a more advanced method of performing optical imaging. My research has been to pioneer the in vivo use of DOT for advanced neuroimaging by: 1) quantifying the advantages …

The Role Of Snail Homolog 1 In Embryonic Stem Cell Differentiation, Jennifer Gill

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During gastrulation, epiblast cells undergo an epithelial-to-mesenchymal transition: EMT) as they ingress through the primitive streak and form mesoderm. To better understand the molecular pathways of EMT during this developmental transition, we developed a model system utilizing mouse embryonic stem: ES) cells. We show that EMT occurs during ES cell differentiation and is dependent on the Wnt signaling pathway. We further show that the Wnt-dependent transcription factor Snail homolog 1: Snail) is expressed and capable of inducing EMT in differentiating ES cells. In addition to EMT, Snail accelerates differentiation, promotes mesoderm commitment, and restricts markers of primitive ectoderm and epiblast. …

Changing Perceptions Of China In 1930s America, Erin Pattison

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No abstract provided.

Novel Roles For A-Type Lamins In Maintaining Genomic Stability, Abena Redwood

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A-type lamins, key structural components of the nucleus, have been implicated in the maintenance of nuclear architecture and chromatin organization. Mutations in A-type lamins have been associated with defects in a number of nuclear processes, including DNA replication and repair, and gene transcription and silencing. In support of an important role for nuclear organization in pathogenesis, mutations in A-type lamins are associated with a wide variety of degenerative diseases which range from muscular dystrophies and lipodystrophies to premature aging syndromes. In addition, alterations in the expression of A-type lamins are associated with different cancers such as small cell lung carcinoma …

Novel Sequence-Based Method For Identifying Transcription Factor Binding Sites In Prokaryotic Genomes, Gurmukh Sahota

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Computational techniques for microbial genomic sequence analysis are becoming increasingly important. With next–generation sequencing technology and the human microbiome project underway, current sequencing capacity is significantly greater than the speed at which organisms of interest can be experimentally probed. We have developed a method that will primarily use available sequence data in order to determine prokaryotic transcription factor binding specificities. The prototypical prokaryotic transcription factor: TF) contains a helix–turn–helix: HTH) fold and bind DNA as homodimers, leading to their palindromic motif specificities. The connection between the TF and its promoter is based on the autoregulation phenomenon noticed in E. coli. …

Molecular Dissection Of Ia Channels In Cortical Pyramidal Neurons, Aaron Norris

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The rapidly activating and inactivating voltage-gated K+: Kv) current, I _A, is broadly expressed in neurons and is a key regulator of action potential repolarization, repetitive firing, back propagation: into dendrites) of action potentials, and responses to synaptic inputs. Interestingly, results from previous studies on a number of neuronal cell types, including hippocampal, cortical and spinal neurons, suggest that macroscopic I _A is composed of multiple components and that each component is likely encoded by distinct Kv channel α-subunits. The goals of the experiments presented here were to test this hypothesis and to determine the molecular identities of the …

New Mri Techniques For Nanoparticle Based Functional And Molecular Imaging, Lingzhi Hu

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Although in clinical use for several decades, magnetic resonance imaging: MRI) is undergoing a transition from a qualitative anatomical imaging tool to a quantitative technique for evaluating myriad diseases. Furthermore, MRI has made great strides as a potential tool for molecular imaging of cellular and tissue biomarkers. Of the candidate contrast agents for molecular MRI, the excellent bio-compatibility and adaptability of perfluorocarbon nanoparticles: PFC NP) has established these agents as a potent targeted imaging agent and as a functional platform for non-invasive oxygen tension sensing. Direct readout and quantification of PFC NP can be achieved with fluorine: 19F) MRI because …

Movement Function Follows Spatial Form: Coordinate System Implications For Online Visual Feedback Control Of The Hand, Justin Brooks

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Closed loop visual feedback control of the hand is essential for accurate reaching movements. Without visual signals of either the hand or target position, reaches are inaccurate and imprecise; therefore the brain uses a relative positional signal to control movements online. Previous studies suggest that movements are planned and represented in a polar coordinate system and that the dimensions, direction and extent are independently specified and processed. We were interested to find out whether there was behavioral evidence for the independent control of hand direction and extent as a movement unfolded. We asked subjects to make a reaching movement in …

Investigation Of The Structure Of Alkyne Self-Assembled Monolayers On Gold And The Development Of Matrix-Enhanced Secondary Ion Mass Spectrometry Methods, Jennifer Dertinger

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Characterization of thin films is critical to the understanding of many technological and biological processes. The focus of this dissertation is to develop methods to characterize very low concentration species present on surfaces. A reflection adsorption infrared spectroscopy: RAIRS) system was constructed and tested. The instrument comprises an Fourier transform infrared: FTIR) spectrometer, an optical pathway and a vacuum chamber. The RAIRS system is designed to investigate in situ the interaction of vapor-deposited metals and gases, such as CVD precursors, with organic thin films, and so a vacuum chamber is required. To accommodate the vacuum chamber, an external IR optical …

Young Children's Understanding Of The Relationship Between Conventionality And Communication, Kathleen R. Sullivan

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This dissertation explores children's understanding of the conventionality of language, the notion that shared knowledge of the meanings of linguistic symbols enables communication using those symbols. Three studies investigate whether monolingual children recognize that different speakers share knowledge of lexical conventions, in this case the labels for objects, independent of children's own knowledge of those labels. Further, children's ability to use evidence of shared conventional knowledge when reasoning about communicative interactions is tested using a novel third-party communication task. Results indicate that three-year-old children track consistent labeling of novel objects across different speakers, and infer underlying shared knowledge of object …

Regulation Of Toxoplasma Motility By Calcium-Dependent Protein Kinases, Sebastian Lourido

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Apicomplexans are protozoan parasites of animals, which must penetrate host cells to find a niche in which to replicate. To humans, they represent the most ubiquitous and deadliest eukaryotic pathogens, including Toxoplasma gondii and Plasmodium spp., the etiological agents of toxoplasmosis and malaria, respectively. A common mechanism enables these parasites to penetrate biological barriers and invade host cells actively, through a process termed gliding motility. This type of motility, unique to apicomplexans, relies on the directional translocation of adhesins via an actomyosin motor complex anchored in a vesicular network underlying the plasma membrane of the parasite. A variety of stimuli …

Taspase1 Is A Non-Oncogene Mediator Of Tumorigenesis And Maintenance, David Chen

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The clinical success of oncogene-targeted therapies substantiates the continued reliance of certain cancers upon the continued function of apical oncogenes involved in its genesis--a phenomenon known as "oncogene addiction." Though this shift from non-targeted, cytotoxic therapies offers new hope to patients, resistance to oncogene inactivation often remains an eventuality, and it is clear that further investigation is required to more effectively battle cancer using alternative therapeutic targets. Our studies on Taspase1: threonine aspartase 1) reveal its role in coordinating cellular proliferation and apoptosis in cancer. Loss of Taspase1 by shRNA-mediated knockdown decreased cellular proliferation in a diverse set of cancer …

Video-Rate Fluorescence Molecular Tomography For Hand-Held And Multimodal Molecular Imaging, Metasebya Solomon

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In the United States, cancer is the second leading cause of death following heart disease. Although, a variety of treatment regimens are available, cancer management is complicated by the complexity of the disease and the variability, between people, of disease progression and response to therapy. Therefore, advancements in the methods and technologies for cancer diagnosis, prognosis and therapeutic monitoring are critical to improving the treatment of cancer patients.

The development of improved imaging methods for early diagnosis of cancer and of near real-time monitoring of tumor response to therapy may improve outcomes as well as the quality of life of …

The Bosnian War And The New Great Game: A Case Study In Strategy And Diplomacy, Sarah Maurizi

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No abstract provided.

From Democracy Deficit To Liberal Political Consolidation: Foreign Assistance And Democratization In Africa, Amber Whittington

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The correlation between foreign aid and democratization has a contentious history in the field of international affairs. The paradigm that foreign aid can be used to achieve democratization in foreign political systems underscores to the centrality of democracy in Western societies. This thesis explores the relationship between foreign aid and democratization in sub-Saharan Africa.

Women War Correspondents And The Battles They Overcame To Succeed, Angela Ness

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Women war correspondents have overcome gender bias to be able to perform the same work as men in their field. This thesis looks at the history of women war correspondents starting with Margaret Bourke-White during World War II through Christine Amanpour in the 2003 Iraqi War. Through tension with the military over censure and editors for rights to work, these women's work has withstood scrutiny over the years.

China's Political Game Face, Fendy Yang

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Foreigners have long been curious about the country that so fiercely safeguards the privacy of its internal affairs, but China’s historical reputation for manifesting an aloof and uninterested attitude towards others has left many outside scholars little choice but to study and examine the country from an external perspective. However, given the continuing controversy and speculation surrounding China’s rise over the past few decades, it is imperative for scholars in this field to become more well-versed in the foundations of China’s social and cultural traditions, to reorient their theoretical approaches to reflect a more relevant perspective in their studies. Of …

The Development And Application Of The "Petraeus Doctrine" During The 2007 Iraq Troop "Surge", Luke Mccorkel

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In Spring 2007 President Bush ordered additional American troops to Iraq as part of a troop Surge to wage a counter-offensive based on the tactics of the newly developed Petraeus Doctrine. This thesis analyzes the events leading up to and surrounding the Surge and the role of the Petraeus Doctrine the successful defeat of the insurgency and strengthening the Iraqi Government and Security Forces enabling the Americans to being an orderly withdrawal. The Petraeus Doctrine did play a vital role in the defeat of the insurgency, but it was not the primary cause for the Surge’s success and merely took …

The Role Of Notch Signaling In The Pathogenesis Of Acute Promyelocytic Leukemia, Nicole Grieselhuber

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The t(15;17) translocation is found in nearly 98% of acute promyelocytic leukemia: APL, FAB subtype M3) cases and results in the fusion of the promyelocytic leukemia: PML) gene with the retinoic acid receptor alpha: RARA) gene. The fusion product, PML-RARA, encodes a functionally altered transcription factor that is the initiating event in APL. To better understand the transcriptional changes associated with APL pathogenesis, we compared the gene expression profiles of APL samples to those of other acute myeloid leukemia FAB subtypes and of enriched normal human promyelocytes. We identified a signature of genes that are specifically dysregulated in APL relative …

Orders Of Magnitude Enhancement Of Optical Nonlinear Phenomena In Subwavelength Metal-Dielectric Gratings, Daniel Ironside

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Nonlinear optical materials give rise to a multitude of phenomena that have important applications in technology and science. Due to small nonlinearities in naturally occurring materials, large optical fields are necessary to realize measurable nonlinear phenomena. The necessity of high intensity sources severely limits its use in practical applications, especially in low-powered devices. Several methods for enhancement of nonlinearity have been proposed, including use of conjugate polymers, resonators, and metallic nanoparticles. In this thesis, the nonlinear enhancement properties of subwavelength metal-dielectric gratings are explored. Enhancement in nonlinearity by several orders of magnitude is achieved, with the enhancement entirely controlled by …

Exploring The Role Of Wolbachia Endobacteria In The Biology Of Filarial Nematode Parasites, Samantha Mcnulty

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Filarial nematodes are vector borne parasitic worms that cause a variety of disfiguring and disabling diseases, including lymphatic filariasis and onchocerciasis. Many filarial species require Wolbachia endobacteria: family: Rickettsiaceae) to carry out their life cycle. Studies using antibiotics to target the endobacteria, thereby interfering with worm fertility and viability, have generated interest in using Wolbachia as an antifilarial drug target. However, the exact mechanisms underpinning this interesting mutualistic interaction are poorly understood. Wolbachia-dependence is not ubiquitous in the filarial family. Some species are able to survive in the absence of an endosymbiont. The inconsistent patterns of Wolbachia-dependence and independence seen …

Mitofusin 2 Regulated Transport Of Mitochondria Is Necessary For Axonal Integrity, Albert Misko

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The ubiquitous finding of axonal degeneration in a number of the most prevalent neuropathologies marks the importance of understanding axonal biology and the axonal self-destruct mechanism. Though our understanding of axonal degeneration remains largely incomplete, several down-steam steps of the molecular cascade have been elucidated. While this insight has emerged from models of axon degeneration following physical injury or toxic insult, a more comprehensive understanding of the upstream events may be gained from studying primary axonopathies with defined genetic causes. This dissertation aims to elucidate a molecular mechanism underlying the loss of axons in Charcot-Marie-Tooth Disease type 2A, which is …

The Role Of Autophagy And Il-17 In Bone Resorption, Carl Deselm

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Osteoclasts are essential for skeletal homeostasis: Teitelbaum, 2000). These macrophage-lineage cells function by generating a polarized microenvironment between themselves and bone wherein skeletal matrix is degraded. This resorptive compartment is isolated from the general extracellular space by an actin ring which encompasses the ruffled border, a convoluted plasma membrane structure formed by its fusion with lysosome-related vesicles containing an electrogenic H+ATPase, a chloride channel, LAMP-1, and cathepsin K. In consequence, resorption of bone reflects secretion of HCl to mobilize mineral, and cathepsin K to degrade the collagen-rich organic matrix, into the resorptive space: Stenbeck, 2002; Zhao et al., 2008). We …

Allosteric Modulation Of Metabotropic Glutamate Receptor 5 As A Treatment For Pain, Michael Montana

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Metabotropic glutamate receptor 5: mGlu5) has been suggested to play a role in the development and maintenance of chronic pain. mGlu5 is expressed at synapses throughout the pain neuraxis where it is believed to modulate the function of ion channels that underlie nociceptive transduction and transmission. Injections of mGlu5 agonists cause hypersensitivity or nocifensive behavior when administered peripherally, intrathecally, and centrally. In addition, pharmacological antagonism of mGlu5 has been suggested to be analgesic in a variety of animal pain models. Unfortunately, the selectivity of antagonists used in these studies has been called into question, suggesting that at least some of …

Edle Einfalt, Stille Größe. Winckelmann Und Seine Rezeption Durch Schiller Und Goethe, Christian Gohlke

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Die Arbeit befasst sich mit der Ästhetischen Theoriebildung der Weimarer Klassik auf der Grundlage der Rezeption der Winckelmannschen Werke durch Goethe und Schiller.

Calcium-Stimulated Adenylyl Cyclases Are Critical Modulators Of Fear Learning And Experience-Dependent Plasticity, Lindsay Wieczorek

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Stress can exacerbate psychiatric disease, often resulting in cognitive deficits. Consequently, a better understanding of what modulates stress-facilitated memory processing will help identify new targets for possible therapeutic intervention. Recent evidence suggests a role of the Ca2+-stimulated adenylyl cyclases: AC), AC1 and AC8, in modulating fear memory. Ca2+-stimulated AC activity couples neuronal activity and intracellular Ca2+ increases to the production of cAMP, and therefore, can very tightly regulate signal transduction after learning; yet, the details by which this occurs are not well understood. In this dissertation, I first investigated the temporal and regional importance of Ca2+-stimulated AC activity during different …

Applying Neural Network Models To Predict Recurrent Maltreatment In Child Welfare Cases With Static And Dynamic Risk Factors, Jennifer Marie Jolley

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Risk assessment in child welfare has a long tradition of being based on models that assume the likelihood of recurrent maltreatment is a linear function of its various predictors: Gambrill & Shlonsky, 2000). Despite repeated testing of many child, parent, family, maltreatment incident, and service delivery variables, no consistent set of findings have emerged to describe the set of risk and protective factors that best account for increases and decreases in the likelihood of recurrent maltreatment. Shifts in predictors' statistical significance, strength, and direction of effects coupled with evidence of risk assessment models' poor predictive accuracy have led to questions …

Inventing The Sculptor: Leonardo Da Vinci And The Persistence Of Myth, Emily Hanson

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No abstract provided.

Dynamic Deformation And Mechanical Properties Of Brain Tissue, Yuan Feng

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Traumatic brain injury is an important medical problem affecting millions of people. Mathematical models of brain biomechanics are being developed to simulate the mechanics of brain injury and to design protective devices. However, because of a lack of quantitative data on brain-skull boundary conditions and deformations, the predictions of mathematical models remain uncertain. The objectives of this dissertation are to develop methods and obtain experimental data that will be used to parameterize and validate models of traumatic brain injury. To that end, this dissertation first addresses the brain-skull boundary conditions by measuring human brain motion using tagged magnetic resonance imaging. …

A New Pathway Responsible For 53bp1 Loss In Breast Cancer And Laminopathies, David Alan Grotsky

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53BP1 is a tumor suppressor protein that is important in the non-homologous end joining: NHEJ) pathway for DNA double strand break repair. Mice lacking 53BP1 present with increased radiosensitivity and genomic instability and are cancer prone. Loss of 53BP1 has been implicated by our laboratory in causing genomic instability in cells that lack A-type lamins and work by others has shown that loss of 53BP1 is associated with breast cancers of the poorest prognosis - BRCA1-mutated and Triple Negative Breast Cancers: TNBC) - and contributes to their resistance to current therapies, such as PARP inhibitors: PARPi). Work in our laboratory …