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The Role Of Streptococcus Gallolyticus Subspecies Gallolyticus In Colon Cancer Development, Jennifer L. Herold

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that Streptococcus gallolyticus subsp. gallolyticus, a group D streptococci, may play a role in the development of CRC. Sg, formerly S. bovis biotype I, has been shown to be highly associated with CRC. In observing patients with either Sg bacteremia or endocarditis it was found that 25-80% of …

Concomitant Targeting Of The Mtor/Mapk Pathways: Novel Therapeutic Strategy In Subsets Of Non-Small Cell Lung Cancer, Dennis Ruder

Dissertations and Theses (Open Access)

Over the last decade, a paradigm-shift in lung cancer therapy has evolved into targeted-driven medicinal approaches. However, patients frequently relapse and develop resistance to available therapies. Herein, we utilized genomic mutation data from advanced chemorefractory non-small cell lung cancer (NSCLC) patients enrolled in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) clinical trial to characterize novel actionable genomic alterations potentially of clinical relevance. We identified RICTOR alterations (mutations, amplifications) in 17% of lung adenocarcinomas and found RICTOR expression correlates to worse overall survival. There was enrichment of MAPK pathway genetic aberrations in key oncogenes (e.g. KRAS, BRAF, …

Maguk Scaffolds Organize A Key Synaptic Complex In Horizontal Cell Processes Contacting Photoreceptors, Alejandro Vila, Ph.D.

Dissertations and Theses (Open Access)

Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. As each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes. In studies of rabbit retina, we found SAP102 and Chapsyn110 selectively localized in …

The Role Of Phosphorylation In Pam2 Motif-Containing Proteins Mediated Messenger Rna Deadenylation, Kai-Lieh Huang

Dissertations and Theses (Open Access)

Phosphorylation regulates many cellular processes. However, its role in mRNA deadenylation, a process to remove poly adenosines from the mature mRNA 3’ end tail, is unclear. The length of poly(A) tail determines mRNA stability and translation efficiency. Poly(A)-binding protein (PABP), which binds to newly synthesized poly(A) tails homogeneously and is known as a scaffold protein for PAM2 motif-containing proteins, plays a pivotal role in the shortening of poly (A) tails. This study is to examine the role of phosphorylation of PAM2 motif–containing proteins in regulating their interactions with PABP and mRNA deadenylation function.

The PAM2 motif, a region required for …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations and Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Her4 Promotes A Stem-Like Phenotype In Osteosarcoma, Rocio K. Rivera-Valentin

Dissertations and Theses (Open Access)

Metastatic disease to the lungs is the primary cause of death for patients with pediatric osteosarcoma (OS). OS has a high degree of heterogeneity and genomic instability, making understanding the pathogenesis and drivers of metastasis of this disease challenging. In an effort to explain tumoral heterogeneity, the tumor initiating cell model (TIC) states that tumors are composed of cells that form the majority of the tumor and are terminally differentiated. This model however, attributes tumorigenesis, metastasis and chemoresistance to a distinct cell population with a stem-like phenotype that can be identified using selective markers. OS appears to follow this model …

Determination Of Thermal Dose Model Parameters Using Magnetic Resonance Imaging, Christopher James Maclellan

Dissertations and Theses (Open Access)

Magnetic Resonance Temperature Imaging (MRTI) is a powerful technique for noninvasively monitoring temperature during minimally invasive thermal therapy procedures. When coupled with thermal dose models, MRTI feedback provides the clinician with a real-time estimate of tissue damage by functioning as a surrogate for post-treatment verification imaging. This aids in maximizing the safety and efficacy of treatment by facilitating adaptive control of the damaged volume during therapy. The underlying thermal dose parameters are derived from laboratory experiments that do not necessarily reflect the surrogate imaging endpoints used for treatment verification. Thus, there is interest and opportunity in deriving model parameters from …

Targeting Pd-1/Pdl-1 Signaling In The Treatment Of Osteosarcoma Lung Metastasis, Pooja Dhupkar 3012359

Dissertations and Theses (Open Access)

Osteosarcoma (OS) manifests itself as pulmonary metastasis, which is a major cause of death in OS patients. Novel treatments like immunotherapy hold promise for the treatment of OS pulmonary metastasis. However, immunosuppressive mechanisms such as binding of immune inhibitory receptor, PD-1 with PDL-1, which is upregulated in cancer cells, may cause disease relapse.

The effect of PD-1 blockade on NK cells and macrophages has not been investigated till date. The aim of this study was to determine if PD-1 blockade leads to of OS lung metastasis regression and study the role of NK cells and/or macrophages in the anti-PD-1 responses. …

Organ Specific Vascular Response To Fibrosis Affects Breast Cancer Metastatic Organotropism, Eliot S. Fletcher, Eliot S. Fletcher

Dissertations and Theses (Open Access)

The solid tumor microenvironment, pre-metastatic niche, and fibrotic environment are known to have significant biochemical and biomechanical similarities to the fibrotic environment. All have significantly increased levels of factors such as TGFβ, HIF1α, TNFα, PDGF, VEGF, FGF, interleukins and other growth factors that are known to be pro-tumorigenic. Clinical and basic science research has shown that fibrosis presents an environment that favors tumor growth, such as hepatocellular carcinoma being commonly preceded by liver cirrhosis, or bleomycin induced lung fibrosis enhancing pulmonary metastasis in mouse models of breast cancer. In addition to the evidence indicating that fibrosis enhances primary tumor growth …

Long-Term Survival In Metastatic Melanoma Patients With Leptomeningeal Disease Treated With Intrathecal Interleukin-2, Isabella C. Glitza Oliva

Dissertations and Theses (Open Access)

BACKGROUND: Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis and a paucity of effective treatment options. We assessed the safety and efficacy of intrathecal interleukin-2 (IT IL-2) in metastatic melanoma patients with LMD.

METHODS: We reviewed the outcomes of 43 consecutive metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug Study. All patients had evidence of LMD based on cerebrospinal fluid (CSF) cytology, radiology, and/or surgical pathology. IL-2 at a dose of 1.2 mIU was administered intrathecally via Ommaya reservoir up to 5 times …

Nucleotide Excision Repair, Crosslink Repair And Transcriptional Function Of Xpa In Human Cells, Mandira Mananadhar

Dissertations and Theses (Open Access)

Nucleotide excision repair (NER) in mammalian cells includes xeroderma pigmentosum group A protein (XPA) as a core factor. XPA and other NER proteins have been detected previously at some active promoters, and NER deficiency is reported to decrease activated transcription of selected genes. To determine the global extent of XPA influence on transcription, we analyzed the human transcriptome by RNA sequencing. We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage. We …

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

Dissertations and Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important …

Investigation Of Radiation Injury In The Esophagus From Definitive Chemoradiation Therapy Using Novel Imaging Biomarkers, Joshua S. Niedzielski

Dissertations and Theses (Open Access)

Radiation injury in the esophagus occurs with high frequency from the treatment of non-small cell lung cancer (NSCLC). Radiation esophagitis is an acute normal tissue toxicity that negatively affects treatment efficacy by limiting dose and potentially interrupting radiation therapy. Clinical quantification of this toxicity is typically achieved by utilizing physician grading scales, assigning complication severity on an ordinal scale of symptom presentation and/or physician chosen interventions. These criteria are subjective in nature, both from the physician assigning the grade and the patient reporting the symptom. Furthermore, radiation therapy planning guidelines for the esophagus are derived from toxicity prediction models utilizing …

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations and Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

Novel Simulation To Avoid Bias In Measurement Of Hyperpolarized Pyruvate: Demonstrated In Phantom And In Vivo, Christopher M. Walker

Dissertations and Theses (Open Access)

Dynamic nuclear polarization creates a transient hyperpolarized nuclear state that can dramatically increase the signal detected by magnetic resonance imaging. This signal increase allows real-time spectroscopic imaging of specific metabolites in vivo by magnetic resonance. Real-time imaging of both the spatial and chemical fate of hyperpolarized metabolites is showing great promise to meaningfully benefit clinical care of cancer patients. Imaging of hyperpolarized agents will have a larger clinical impact if it can function as a quantitative modality upon which clinical decisions can be made. However, quantitative measurement of hyperpolarized agents is currently difficult due to the restrictions imposed by the …

Assessing The Potential Clinical Impact Of Variable Biological Effectiveness In Proton Radiotherapy, Christopher R. Peeler Ph.D.

Dissertations and Theses (Open Access)

It has long been known that proton radiotherapy has an increased biological effectiveness compared to traditional x-ray radiotherapy. This arises from the clustered nature of DNA damage produced by the energy deposition of protons along their tracks in medium. This effect is currently quantified in clinical settings by assigning protons a relative biological effectiveness (RBE) value of 1.1 corresponding to 10% increased effectiveness compared to photon radiation. Numerous studies have shown, however, that the RBE value of protons is variable and can deviate substantially from 1.1, but experimental data on RBE and clinical evidence of its variability remains limited.

The …

Evidence For The Validity Of The Student Risk Screening Scale In Middle School: A Multilevel Confirmatory Factor Analysis, Matthew Porter Wilcox

Theses and Dissertations

The Student Risk Screening Scale—Internalizing/Externalizing (SRSS-IE) was developed to screen elementary-aged students for Emotional and Behavioral Disorders (EBD). Its use has been extended to middle schools with little evidence that it measures the same constructs as in elementary schools. Scores of a middle school population from the SRSS-IE are analyzed with Multilevel Confirmatory Factor Analysis (MCFA) to examine its factor structure, factorial invariance between females and males, and its reliability. Several MCFA models are specified, and compared, with two retained for further analysis. The first model is a single-level model with chi-square and standard errors adjusted for the clustered nature …

Policing As Administration, Christopher Slobogin

Vanderbilt Law School Faculty Publications

Police agencies should be governed by the same administrative principles that govern other agencies. This simple precept would have significant implications for regulation of police work, in particular the type of suspicionless, group searches and seizures that have been the subject of the Supreme Court's special needs jurisprudence (practices that this Article calls "panvasive"). Under administrative law principles, when police agencies create statute-like policies that are aimed at largely innocent categories of actors-as they do when administering roadblocks, inspection regimes, drug testing programs, DNA sampling programs, and data collection-they should have to engage in notice-and-comment rulemaking or a similar democratically …

Late Onset Of Pulmonary Hypertension And Sepsis In Omphalocele Infants, Joanne E. Baerg, Arul Thirumoorthi, Whitney Carlton, Shelly Haug, Andrew O. Hopper, Donna Goff, Sandhya Ramlogan, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

A subset of omphalocele infants has respiratory decompensation after the first week of life and PHN is diagnosed. Infection may initiate decompensation. In some, PHN is distinct from pulmonary hypoplasia as they oxygenate on room air for some time after birth. With aggressive treatment and follow-up, PHN can resolve. The late diagnosis of PHN in infants with omphalocele is previously unappreciated and deserves further study.

The Development Of An Immunization Training Program For Low-Income Families Within The Community, Amanda W. Cooper

DNP and Student Works

Objective: The purpose of this study was to assess knowledge levels regarding childhood immunizations among low-income parents in an effort to improve the immunization rate of 19 to 35 month old children. Design and Sample: Participants (n=36) were administered a pre- and post-test questionnaire asking for correct identification of vaccine needs of children 19 to 35 months of age. Measurements: Descriptive statistics and McNemar's test were uses to answer the PICOT question and define the sample. Intervention: A QI project using the Plan-Do-Study-Act (PDSA) cycle was implemented in a public health department care setting in Georgia to provide childhood immunization …

Immunomodulatory Effects Of Human Adipose Derived Stem Cells On Human Macrophages In Diabetic Environment, Maria Margarita Portilla

All Theses

Background: Cardiovascular Disease (CVD) is the number 1 leading cause of death in the nation, even globally [1]. By 2030, the American Heart Association projects that 43.9% of the US population will have some form of CVD [2], with more than one-half of mortality seen in the diabetic community [3]. Diabetic patients face increased inflammation, leading to vascular complications; consequently, these patients may need small-caliber grafts. Although the gold standard is represented by autologous blood vessels, these might be affected by diabetes as well. Vascular tissue engineered grafts with the addition of autologous adipose tissue-derived stem cells may be a …

Soil Organic Carbon Distribution With Depth: Implications For Ecosystem Services, Rebecca Drayton Chandler

All Theses

Most current frameworks of ecosystem services represent soil organic carbon (SOC) as a bulk/composited stock without differentiating SOC ecosystem services in the top and subsoil. This study evaluated SOC, nitrogen (N), and C/N distribution with depth in glaciated soils at the Cornell University Willsboro Research Farm in upstate New York. Soil organic carbon, N, and C/N decreased with depth in all soils sampled. The vertical distribution of SOC was examined quantitatively by soil order, soil depth class (top soil versus subsoil), and other environmentally-relevant soil and landscape variables. Top soils (A horizon) contained more variable SOC concentrations compared with the …

Predicting Culvert Deterioration Using Physical And Environmental Time-Independent Variables, Michael Wallace Stoner

All Theses

Given a database of approximately 8,000 culverts in South Carolina with varying sizes, types, configurations, and the associated ratings of different output categories, a predictive deterioration model was produced in an attempt to match the ratings of these output categories. These models used the physical culvert information given in the database of culverts and associated environmental characteristics including historical temperature, precipitation, pH, and estimated runoff coefficient as inputs for the model. The models used combinations of inputs that produced the model with the best performance measures. In addition, a separate group of models was created for each of the six …

Development Of Stable Extractive Scintillating Materials For Quantification Of Radiostrontium In Aqueous Solutions, Ayman F. Seliman

All Theses

Strontium-90 is a fission product, and it is produced with a yield of about 6%. Strontium-90 is a major radionuclide in spent nuclear fuel, high-level radioactive wastes resulting from the processing of spent nuclear fuel, and radioactive wastes associated with the operation of reactors and fuel reprocessing plants. In addition to the four stable isotopes naturally present in soil, 90Sr is present in surface soil around the world as a result of fallout from past atmospheric nuclear weapons tests. Strontium-90 is relatively mobile and can move down with percolating water to underlying layers of soil and into groundwater. The maximum …

Structural Evaluation Of Scdot Prestressed Channel Bridges, Robert Steven Gunter

All Theses

The Five Forks Bridge in Liberty, SC (Figure 7-1) is one of approximately 450 prestressed concrete channel bridges that the SCDOT oversees. Some of these channel bridges, such as the Five Forks Bridge, have unknown structural properties and flexural capacity. The Five Forks Bridge is a prestressed concrete channel bridge consisting of 33 girders that form three simple spans each 30 ft. in length. There are no formal design calculations available for some of these bridges and there are multiple prestressed strand designs that may describe the physical properties of each bridge. This project seeks to reveal the structural characteristics …

Effect Of Sourdough Fermentation Parameters On Bread Properties, Grace W. Couch

All Theses

Sourdough is the oldest form of leavening which many believe was invented by the Egyptians. Bread leavened with a sourdough culture relies on the metabolism of naturally occurring lactic acid bacteria and wild yeasts. Historically there were many ties between beer brewing and bread baking. In the fourteen and fifteen hundreds, it was discovered that brewers yeast could also be used to leaven bread. Up until the invention of commercial yeast in the nineteenth century, sourdough cultures and brewers yeast where the only bread leavening methods. By 1910, traditional sourdough was much less common because bread made with commercial yeast …

Suture Training Device With Computer Vision Based Information Acquisition, Anand Jagannathan

All Theses

Growth in surgical technology has given rise to numerous innovative methods to perform surgery and every surgery involves certain skills that have different learning curve. Due to significant growth in medical problems that involves surgery, there is a greater demand for good surgeons. Therefore there is a need to train aspiring surgeons into becoming an expert. Surgical training has undergone a drastic change in recent years with the advent of simulation based training, which allows novice surgeons to train and acquire essential surgical skills before performing an actual surgery. With the goal of objectively evaluating the level of expertise of …

Does It Take Courage To Start A Business?, Benjamin Hardy

All Theses

Courage is defined by Rate (2010) as an intentional behavior toward worthy goals involving risk. Previous research examining courage has emphasized the risk component of courage, but in large part neglected the worthy goals component. Furthermore, previous courage research has primarily examined courage as a prevention-focused behavior as a singular event. This study sought to explore courage as the pursuit of a promotion-focused goal over a long period of time. Specifically, this study examined courage in the context of starting a business. Latent/nascent entrepreneurs and actual entrepreneurs were interviewed to investigate courage and other constructs, including goal commitment and a …

Quantification Of Volatile Residuals In Polydioxanone By Gas Chromatography: Method Development, Validation And Implementation, Clayton Joseph Culbreath

All Theses

Bioresorbable polymers are increasingly utilized for implantable medical devices to avoid complications related to explant and/or long term responses to foreign materials. As with all polymeric materials, residual levels of unreacted monomer, and other volatiles, drastically affect the mechanical and chemical properties as well as the parameters required to process the material into a device. The 1,4-dioxane-2-one (PDO) monomer is a six membered ring that forms an ether-ester polymer via ring-opening polymerization (ROP) with intermediate absorption rate properties that are ideal for numerous implant situations. Developing devices using poly(1,4-dioxane-2-one) (PPDO, PDO, PDX, PPDX, or PDS) is complicated by residual levels …

Impact Of Conflict On Medical Education: A Cross-Sectional Survey Of Students And Institutions In Iraq, Ashton Barnett-Vanes, Sondus Hassounah, Marwan Shawki, Omar Abdulkadir Ismail, Chi Fung, Tara Kedia, Salman Rawaf, Azeem Majeed

Dartmouth Scholarship

Objective: This study surveyed all Iraqi medical schools and a cross-section of Iraqi medical students regarding their institutional and student experiences of medical education amidst ongoing conflict. The objective was to better understand the current resources and challenges facing medical schools, and the impacts of conflict on the training landscape and student experience, to provide evidence for further research and policy development. Setting: Deans of all Iraqi medical schools registered in the World Directory of Medical Schools were invited to participate in a survey electronically. Medical students from three Iraqi medical schools were invited to participate in a survey electronically. …