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Balagurunathan, JayakishanInvestigation of Ignition Delay Times of Conventional (JP-8) and Synthetic (S-8) Jet Fuels: A Shock Tube Study
Master of Science (M.S.), University of Dayton, 2012, Mechanical Engineering
The global depletion of petroleum-based fuels has led the world to more closely examine alternate fuels. Therefore, alternate fuels produced from feedstocks such as coal, soybeans, palm oil or switch grass through methods such as coal liquefaction, biomass gasification, and Fischer-Tropsch synthesis have been tested. Among these techniques, fuels generated using Fischer-Tropsch technologies are of interest because they produce clean burning hydrocarbons similar to those found in commercial fuels. Therefore, in this study the Fischer-Tropsch derived S-8 fuel was evaluated as a drop-in replacement for the jet fuel JP-8. The jet fuel JP-8 is comprised of n-, iso- and cyclo- alkanes as well as aromatics while the S-8 fuel is primarily comprised of n- and iso- alkanes. The composition of the fuel affects its ignition characteristics chemically and physically by either advancement or delay of time to ignition. Since this study focused on the chemical effects, the fuels were completely pre-vaporized and pre-mixed. A high pressure, high temperature heated single pulse shock tube was used for this study. The shock tube is an established experimental tool used to obtain ignition delay data behind reflected shock waves under operating conditions relevant to modern engines. The experiments were conducted over a temperature range of 1000-1600 K, a pressure of 19±2 atm, equivalence ratios of 0.5, 1 and 3, within a dwell time of 7.6±0.2 ms and an argon dilution of 93% (v/v). Ignition delay times were measured using the signal from the pressure transducer on the end plate with guidance from the optical diagnostic signal. Along with JP-8 and S-8, the ignition delay of n-heptane was also studied. N-heptane was chosen to represent the n-alkanes in the fuels for this study since it was present in both fuels and also to prove the fact that the n-alkanes were rate controlling. The results indicate that both S-8 and JP-8 fuels have similar ignition delays at corresponding equivalence ratios. The fuel-rich mixtures ignited faster at lower temperatures (<1150 K) and the fuel-lean mixtures ignited faster at higher temperatures (>1150 K). In the transition period between lower to higher temperatures (~1100-1200 K), the equivalence ratio had no significant effect on the ignition delay time. The results also show that the ignition delay time measurements of S-8 and JP-8 fuels are similar to the ignition delay of n-heptane at the equivalence ratio of Φ=0.5 and thereby indicate that the n-alkanes present in these fuels controlled the ignition under these conditions. The ignition delay results of S-8 and JP-8 at Φ=3.0 from this study were also compared to prior work (Kahandawala et al., 2008) on 2-methylheptane and n-heptane/toluene (80/20 liquid vol.%), respectively and found to be indistinguishable. This data serves to extend the gas phase ignition delay database for both JP-8 and S-8 and is the first known data taken for both these fuels at higher temperatures (>1000 K) for an equivalence ratio of 3.0 with argon as the diluent gas.

Committee:

Sukh Sidhu, Dr (Committee Chair); Philip Taylor, Dr (Committee Member); Moshan Kahandawala, Dr (Committee Member)

Subjects:

Aerospace Engineering; Aerospace Materials; Alternative Energy; Automotive Engineering; Automotive Materials; Chemical Engineering; Chemistry; Energy; Engineering; Environmental Engineering; Mechanical Engineering; Petroleum Engineering; Technology

Keywords:

Ignition delay; shock tube; S-8; JP-8; Jet fuels; Fuel characteristics; heated shock tube; Fischer-Tropsch; Alternate fuels; alkanes; synthetic fuel; fuel; iso-alkanes; jayakishan balagurunathan

Champa, Zachary J.Modulation of IL-6 and IL-8 Expression in Ovarian Cancer Cells by a Small Organic Compound
Master of Science (MS), Ohio University, 2016, Biomedical Engineering (Engineering and Technology)
Ovarian cancer ranks 5th in cancer-related deaths amongst women with 14,270 deaths in 2014 [1]. Its high mortality rate can be attributed to lack of treatment methods and the chemoresistant nature of ovarian cancer [2]. Various studies have linked high expression levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) to poor prognosis in ovarian cancer. It was hypothesized that COB-141, a small organic molecule related to methimazole, could lower these expression levels. The secretion of IL-6 and IL-8 was assayed through enzyme linked immunosorbent assays (ELISAs) and the transcriptional expression was assayed through quantitative real time polymerase chain reactions (QRTPCR) in three different ovarian cancer cell lines (CAOV-3, SKOV-3, and OVCAR-3). These techniques were used to find the compound concentration at which 50% of protein secretion or transcription was inhibited, also known as the IC50 value. All IC50 values shown are ± standard deviation of the trials. For IL-6 secretion, these values were determined to be 46.5 ± 19 µM, 30.8 ± 27 µM, and 7.65 ± 0.91 µM for the CAOV-3, SKOV-3, and OVCAR-3 cell lines respectively, and for IL-8 these values were determined to be 31.9 ± 12 µM and 15.1 ± 5.8 µM for the SKOV-3 and OVCAR-3 cell lines respectively. COB-141 induced IL-8 secretion in the CAOV-3 cell line so the IC50 measure is not applicable. For IL-6 transcription, the IC50 values were determined to be 434.0 ± 7.1 µM and 24.1 ± 7.4 µM for the SKOV-3 and OVCAR-3 cell lines respectively. Surprisingly, COB-141 had no effect on IL-6 transcription in the CAOV-3 cell line so the IC50 measure is not applicable. For IL-8 transcription, the IC50 value was found to be 8.45 ± 1.0 µM for the OVCAR-3 cell line. COB-141 had no effect on IL-8 transcription in the CAOV-3 and SKOV-3 cell lines so the IC50 measure is not applicable. An MTS assay was used to determine how COB-141 affects the mitochondrial activity of the cells. The level at which half of the mitochondrial activity was reduced, also known as the TC50 value, was determined. All TC50 values shown are ± the standard deviation of the trials. The 24 hour TC50 values from the MTS assay were found to be 217 ± 18 µM, 198 ± 25 µM, and 168 ± 85 µM for the CAOV-3, SKOV-3, and OVCAR-3 cell lines respectively. Cell proliferation was also measured using a BrdU assay and the level at which the compound reduced cell proliferation by 50%, also known as a TC50 value, was determined. These 24 hour TC50 values were found to be 731 ± 12 µM, 454 ± 59 µM, and 227 ± 120 µM for the CAOV-3, SKOV-3, and OVCAR-3 cell lines respectively. A high performance liquid chromatography (HPLC) method to detect COB-141 in acetonitrile was also investigated. It was found that COB-141 could be detected at concentrations as low as 6.25 µM which is the lowest concentration that was used in the study. To summarize, COB-141 was able to modulate IL-6 and IL-8 expression in three ovarian cancer cells lines, and this warrants further investigation on the effects of COB-141 in vivo.

Committee:

Douglas Goetz (Advisor); Monica Burdick (Committee Member); Kelly McCall (Committee Member); Stephen Bergmeier (Committee Member)

Subjects:

Biomedical Engineering

Keywords:

Interleukin 6; Interleukin 8; IL-6; IL-8; Ovarian; Cancer; Small; Organic; Compound

Hillian, Antoinette D.Interleukin-8 as a genetic modifier and pharmacologic target for cystic fibrosis pulmonary disease
Doctor of Philosophy, Case Western Reserve University, 2009, Genetics

Pulmonary disease is the most significant manifestation of cystic fibrosis (CF) and is primarily due to continuous and exaggerated inflammation stemming from an inherent dysregulation of the inflammatory processes. Specifically, airway inflammation is characterized by a disproportionate neutrophil load, high levels of neutrophilic enzymes, and excessive neutrophil chemokine expression; thus, the airway inflammation and subsequent damage is considered to be neutrophil-mediated. As interleukin-8 (IL-8) is the primary mediator for neutrophil migration and activation, the progression and maintenance of the neutrophilic inflammation is potentially due to elevated expression of IL-8. This dissertation examines how variations in the expression of IL-8 impact pulmonary disease severity.

There is considerable phenotypic variation with regards to pulmonary disease progression among CF patients. It has been suggested that the majority of the observed variation is due to genetic heterogeneity, independent of CFTR genotype. To test this hypothesis, variants in a panel of inflammatory genes were evaluated for a statistical association with lung disease severity in a CF patient population. Variants in the IL8 gene were found to associate with lung disease severity. Specifically, a functional IL-8 promoter variant was identified and shown to result in an allele specific expression difference.

To minimize damage caused by inflammation, patients are treated with anti-inflammatory drugs, including ibuprofen. High doses of ibuprofen have been shown to inhibit neutrophil migration, reduce the rate of lung function decline, and slow CF lung disease progression although the molecular mechanism has not been identified. Given its role in neutrophil recruitment and activation, IL-8 was tested as a potential molecular target of ibuprofen. In an epithelial cell line, IL-8 protein and message levels were reduced in response ibuprofen at the level of transcription. Furthermore, ibuprofen was found to correlate with reduced IL-8 message in nasal epithelium from CF patients. Therefore, it appears that the overall reduction of CF lung disease associated with ibuprofen is at least partially mediated through a decrease in IL8 expression.

Together these data suggest that alterations in the expression of interleukin-8, either through naturally occurring genetic variation or pharmacological manipulation, modify cystic fibrosis pulmonary disease phenotype.

Committee:

Mitchell Drumm, Ph.D. (Advisor); Helen Salz, Ph.D. (Committee Chair); Ronald Conlon, Ph.D. (Committee Member); Michael Konstan, M.D. (Committee Member); Tracey Bonfield, Ph.D. (Committee Member)

Subjects:

Biology; Genetics; Immunology

Keywords:

cystic fibrosis; interleukin-8; IL-8; neutrophil; ibuprofen; genetic modifier

Gadkari, Varun VA Multi-Disciplinary Investigation of Essential DNA Replication Proteins
Doctor of Philosophy, The Ohio State University, 2017, Biochemistry Program, Ohio State
An organism’s DNA is constantly under attack from various exogenous and endogenous DNA damaging agents. Thus, to assure survival, all living cells have evolved to maintain the genetic integrity of their DNA by various pathways. If left unrepaired, DNA damage sites, or “lesions” can block DNA replication by stalling DNA polymerases, the enzymes responsible for DNA replication. Ultimately, if a stalled replication fork is not rescued, the cell will undergo apoptosis. To bypass DNA lesions, organisms in all domains of life initiate a process known as Translesion DNA Synthesis (TLS). During TLS, the stalled replicative DNA polymerase is displaced by specialized Y-family DNA polymerases that are capable of efficiently bypassing various forms of DNA damage. While Y-family DNA polymerases are proficient in TLS, the fidelity of the process is a notable cause for concern. TLS mechanisms of the different Y-family DNA polymerases vary greatly, and often introduce mutations in the DNA which can lead to carcinogenesis. Thus, the activity of Y-family DNA polymerases must be strictly regulated. To this end all living organisms depend on evolutionarily conserved sliding DNA clamps which bind the DNA in a toroidal fashion, and slide along DNA during replication, serving as a scaffold for the DNA replication and repair machinery. During replication fork progression, the DNA clamp can regulate the various enzymatic activities by binding multiple proteins simultaneously as they process DNA. The overarching goal of my research has been to establish how the mechanisms of DNA replication, and TLS affect DNA clamp mediated polymerase switching (pol switching) to allow for efficient DNA replication while also preventing DNA mutagenesis. My working hypothesis is that the DNA clamp is bound to both replicative and TLS DNA polymerases at the replication fork, and that pol switching is governed by differences in DNA replication efficiency. Upon encountering a DNA lesion, replicative DNA polymerases are unable to efficiently incorporate dNTPs and continue replication. Thus, we hypothesize that the stalled replicative polymerases are exchanged in favor of Y-family DNA polymerases by DNA clamp mediated pol switching to bypass DNA lesions. After TLS, pol switching ensures that the replicative polymerase returns to the replication fork for processive, high fidelity replication. My aim was to understand the TLS mechanism to determine what parameter signals a pol switching event. I used pre-steady-state kinetics to study the TLS mechanism of Sulfolobus Solfataricus (Sso) Y-family DNA polymerase Dpo4 in response to a large helix-distorting lesion. Additionally, I used single-molecule Förster Resonance Energy Transfer (smFRET), a fluorescence based technique, to investigate how the binding of Dpo4 to DNA is affected by an oxidative DNA lesion, and further, how a templating lesion can affect nucleotide selectivity. Additionally, I used smFRET to characterize the Sso DNA clamp Proliferating Cell Nuclear Antigen, to understand the process of DNA clamp opening and closing. Collectively my research has addressed effects of DNA lesions on the DNA binding, nucleotide binding, and nucleotide incorporation by a model TLS DNA polymerase, and the nature of DNA clamp opening. These parameters, combined with previously established data will allow us to infer the mechanism of Pol switching.

Committee:

Zucai Suo, Ph.D. (Advisor); Jane Jackman, Ph.D. (Committee Member); Comert Kural, Ph.D. (Committee Member); Richard Swenson, Ph.D. (Committee Member)

Subjects:

Biochemistry

Keywords:

Sulfolobus solfataricus; Dpo4, DNA polymerase; DNA clamp; PCNA; Proliferating Cell Nuclear Antigen; 8-oxoguanine; 8-oxo-dG; DNA replication; translesion synthesis; nitrobenzanthrone; pre-steady-state kinetics; single molecule FRET; smFRET

Li, TaiBase excision repair of 7, 8-dihydro-8-oxoguanine in DNA mismatch repair proficient and mismatch repair deficient human cells
Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2007, College of Graduate Studies
Oxidative damage is one of the most common types of DNA damage and is considered a key factor in carcinogenesis. A major form of oxidative DNA lesion is 7, 8-dihydro-8-oxoguanine (8-oxoG). The plasmid p220-12-8-oxoG:A containing the 8-oxoG located on the H-Ras codon 12 was either used to directly transform DH5á and NR12397 competent cells or after the plasmid had been incubated with HeLa, DLD1, and HCT 116 nuclear extracts. The repair efficiency of different cell lines was assessed. We also demonstrated that 40 mer Ras 8-oxoG located on H-Ras codon 12 opposite to A or C incubated with HeLa, DLD1, HCT116+3, HCT116 and LoVo nuclear extracts in BER nicking assay showed cell incision ability that uncorrelated with the levels of hMYH expression in different cell lines. We propose that the 8-oxoG:A DNA lesion located on the H-Ras codon 12 is difficult to be repaired, and that the MMR protein hMutSá may interfere with the 8-oxoG:A BER repair at codon 12. And hMutLá may contribute to the MYH in BER.

Committee:

Kandace Williams (Advisor)

Subjects:

Biology, Molecular

Keywords:

H-Ras codon 12; mismatch repair deficient; 7, 8-dihydro-8-oxoguanine; mismatch repair proficient; base excision repair; human cancer cell

Shan, XiuInvestigation of mRNA oxidation in Alzheimer's disease
Doctor of Philosophy, The Ohio State University, 2005, Neuroscience
Oxidative modifications to vital cellular components have been described in association with Alzheimer’s disease (AD). Cytoplasmic RNA oxidation is a prominent feature of vulnerable neurons in AD affected regions. However, the role of RNA oxidation in the pathogenesis of AD is unknown. This dissertation examined the magnitude of oxidized mRNAs in AD, identified oxidized mRNA species, and characterized the consequence of mRNA oxidation. An immunoprecipitation method was developed to isolate, characterize and quantify oxidized mRNAs in AD brain. The data showed that 30-70% of mRNAs are oxidized in frontal cortices of AD as compared to age-matched normal control. Identification of oxidized mRNA species revealed that mRNA oxidation in AD is not random but selective. Many identified oxidized mRNA species have been implicated in the pathogenesis of AD. Quantitative analysis revealed that some mRNA species are more susceptible to oxidative damage for which the relative amounts of oxidized transcripts reach 50-70%. To understand whether oxidation of mRNAs is involved in the pathogenesis of AD, the consequence of mRNA oxidation was studied using in vitro translation system and cell lines. mRNA oxidation may have deleterious effects by interfering with normal translational process or by a toxic gain-of-function. Examination of the protein expression from oxidized mRNAs revealed that mRNA oxidation causes a decrease of protein level and associated activity, which may result from the abnormal association of polyribosomes with oxidized mRNAs during the process of translation. Furthermore, we observed that microinjection of oxidized mRNAs into neuronal cells caused cell death, suggesting that increased mRNA oxidation could be lethal to cells. Studies in primary neuronal cultures revealed that RNA oxidation is an early event far preceding cell death induced by insults associated with AD. Neurons are specifically susceptible to RNA oxidation. Some mRNA species highly oxidized in AD brain are also present in oxidized mRNA pool of oxidative insult-treated cultures. A decrease of protein level was observed to oxidized mRNA species in cultures. Taken together, these studies indicate the possibility of oxidized mRNAs to interfere with physiological functions of cells and also implicate the potential contribution of RNA oxidation in the pathogenesis of AD.

Committee:

Chien-liang Lin (Advisor)

Keywords:

Alzheimer's disease; neurodegenerative disease; neurodegeneration; oxidative stress; RNA oxidation; hydroxyl radical; 8-oxo-7;8-dihydroguanosine

Komarov, Dmitry YurievichOXIDATION OF NUCLEIC ACIDS: CHEMISTRY OF PURINE QUINONES AND DEVELOPMENT OF NOVEL PHOTOOXIDIZING AGENTS
Doctor of Philosophy (Ph.D.), Bowling Green State University, 2010, Photochemical Sciences
Chemical behavior of the oxopurines 8-oxoadenosine and 8-oxoinosine has been investigated. Purine quinones, pivotal intermediates in oxidation of oxopurines were successfully trapped and the resulting products were characterized. Formation of purine quinones was demonstrated with both chemical and photochemical oxidizing agents. Adducts formed as a result of reaction of purine quinones with nucleophiles were isolated and characterized. Pyrene dihydrodioxins have been synthesized and shown to be effective agents for release of pyrene-4,5-dione. Pyrene-4,5-dione is an effective DNA photo-oxidation agent. Pyrene dihydrodioxin incorporating a pyridinium salt as a possible internal electron trap has been shown to release pyrenequinone rapidly. Dihydrodioxins containing two pyridine and pyridinium salt moieties have been synthesized and characterized by variety of methods including 1H and 13C NMR spectroscopy. Dihydrodioxin containing two pyridine moieties was separated into D and L enantiomers via liquid chromatography on a chiral sorbent. Affinities of D and L enantiomers of these dipyridinium pyrene dihydrodioxins for nucleic acids were compared.

Committee:

R. Marshall Wilson, PhD (Advisor); Neocles B. Leontis, PhD (Committee Member); Thomas H. Kinstle, PhD (Committee Member); Warren W. McGovern, PhD (Committee Member)

Subjects:

Chemistry

Keywords:

oxopurines; 8-oxoadenosine; 8-oxoinosine; cross-linking; dihydrodioxins; photooxidizing agents; DNA intercalator

Petrey, Maria ElaineCONSTRUCTION OF THE pC5C9LZAP VECTOR FOR ANALYSIS OF ELEMENTS RESPONSIBLE FOR SHARED AND SEPARATE REGULATION OF HOXC-8 AND HOXC-6
MS, University of Cincinnati, 2001, Arts and Sciences : Biological Sciences
Hox genes play a crucial role in controlling axial patterning during embryonic development. They function as transcription factors to control a wide range of developmental processes and all contain a highly conserved sequence motif referred to as the homeobox. Comparative analysis of this homeobox DNA sequence reveals that they are highly conserved across species. One of the most striking features of Hox genes is their organization in gene clusters. Their arrangement on these clusters is directly related to their spatially restricted domains of expression along the embryonic anteroposterior axis (colinearity), as well as their timing of expression during development. The fact that Hox genes exhibit such colinearity, have overlapping expression domains, and maintain arrangement within these chromosomal clusters, suggests an organizational requirement for proper Hox gene regulation. One likely effect of this cluster organization is that cis-regulatory elements for individual Hox genes are widely scattered in the cluster and are shared between multiple genes. Hoxc-8 and Hoxc-6 are adjacent genes located 20 kb apart in the Hoxc cluster on mouse chromosome 15. The expression of these two genes overlaps with Hoxc-6 maintaining a more anterior limit of expression. It was hypothesized that the genomic region surrounding these two genes contains multiple independent and shared cis-regulatory elements. Therefore, it was the aim of this research to generate a single construct for the identification of the regulatory elements responsible for both Hoxc-8 and Hoxc-6 expression. Using homologous recombination in yeast, a 23 kb fragment of the Hoxc cluster from Hoxc-5 to Hoxc-9 was cloned into the yeast/bacteria shuttle vector, pClasper. The lacZ and human alkaline phosphatase reporter genes were subsequently introduced by homologous recombination into the coding regions of Hoxc-8 and Hoxc-6 respectively. This large reporter construct was utilized for transfection of the P19 embryonic carcinoma cell line to generate the Hoxc-8/Hoxc-6 stable cell line C5C9LZAP. The construct and stable cell line generated by this research will provide the means to identify and analyze regulatory elements required for Hoxc-8 and Hoxc-6 expression. Furthermore, since two different reporter genes were incorporated into Hoxc-8 and Hoxc-6, differential analysis of regulatory regions may be ascertained.

Committee:

Suzanne Bradshaw (Advisor)

Keywords:

HOX GENES; HOXC-8; HOXC-6; pCLASPER; HEMOLOGOUS RECOMBINATION

Gutierrez Orozco, FabiolaInfluence of Tea Catechins on the Viability, IL-8 Synthesis and Secretion, and NF-κB Activation of Gastric Epithelial AGS Cancer Cells
Master of Science, The Ohio State University, 2009, OSU Nutrition
Chronic inflammation is involved in the development of gastric cancer, the second leading cause of cancer-related death worldwide. Epidemiological evidence suggests that increased consumption of catechin rich tea may be associated with reduced risk of gastrointestinal cancers. The goal of this study was to evaluate the effects of catechin-rich extracts of green (GT) and black tea (BT) and individual tea catechins (EGC, EGCG, EGC/EGCG) on cell viability, intracellular oxidation and inflammation in the AGS gastric cancer cell line. Cell viability was measured using the MTT assay. Intracellular oxidation was evaluated using the probe dichlorofluorescin. Inflammatory markers included measurement of intracellular and secreted Interleukin 8 (IL-8) protein and the activation of nuclear factor-kappa B (NF-kB). Treatment of AGS cells (48h) with EGC, EGC/EGCG and EGCG, reduced cell viability by 36%, 31% and 19%, respectively. Interestingly, a similar reduction in cell viability (27%) was observed upon treatment of cells with BT and GT extracts. Treatment of cells with GT (1.5 mg/ml), BT (1.5 mg/ml) and EGCG (1.5 mg/ml) also inhibited cytokine-induced IL-8 production and subsequent secretion. These anti-inflammatory effects are due, in part, to a reduced activation of NF-kB in the AGS cell line. This study demonstrates a potential mechanism by which tea catechins may reduce inflammation associated with gastric cancer.

Committee:

Joshua A. Bomser, PhD (Advisor); Mark L. Failla, PhD (Committee Member); Martha A. Belury, PhD (Committee Member)

Subjects:

Food Science; Health; Nutrition

Keywords:

tea catechins; cell viability; chronic inflammation; interleukin 8; NF-kB; intracellular oxidation

Robert, Mekala DavidThe change of pore structure and particle size of coal particles in coal gasification
Master of Science (MS), Ohio University, 1981, Chemical Engineering (Engineering)

The change of pore structure and particle size of coal particles in coal gasification

Committee:

Robert Savage (Advisor)

Subjects:

Engineering, Chemical

Keywords:

Coal Gasification; Wet Sieve Analysis; Clarion - 4A; Pittsburqh No.8

Johnson, Brent E.Comparing Achievement between Traditional Public Schools and Charter Schools within the Big Eight Urban School Districts in Ohio
Doctor of Philosophy, Miami University, 2011, Educational Leadership
The purpose of this study was to investigate whether charter schools produce higher test scores than traditional public schools within the largest eight urban school districts in Ohio. With an emphasis on techniques and contexts borrowed from critical race and feminist empiricist frameworks, this study examined state test data and provides insight into charter schooling reform. The results of the overall study suggested that charter schools were not performing significantly better than traditional public schools. The few times that differences did occur,traditional public schools were outperforming their charter school counterparts.

Committee:

Nelda Cambron-McCabe, PhD (Committee Co-Chair); Sally Lloyd, PhD (Committee Co-Chair); Gerri Susan Mosley-Howard, PhD (Committee Member); William Boone, PhD (Committee Member)

Subjects:

African Americans; Education; Education Philosophy; Education Policy; Educational Evaluation; Educational Leadership; Educational Tests and Measurements; Educational Theory; Elementary Education; Gender

Keywords:

charter schools; achievement; Big 8; critical race theory; feminist empiricism; Ohio Public Schools; community schools; educational management organizations; comparing public schools

Magdic, Matthew JamesAssessment of Soil Properties in Proximity to Abandoned Oil Wells using Remote Sensing and Clay X-ray Analysis, Wood County, Ohio
Master of Science (MS), Bowling Green State University, 2016, Geology
The oil and gas booms of the late 19th century left tens of thousands of wells in Wood County, Ohio abandoned and improperly capped. This allows hydrocarbons to seep into the surrounding soil. Detection of these wells proves difficult because many of the wells are buried and their locations lost. To be able to detect the oil wells over large areas, different remote sensing techniques can be used to detect changes in soil properties caused by the presence of hydrocarbons. However, the capability of this technology depends on spatial and spectral resolution of a sensor and in situ data are often necessary. In this study, in-situ hyperspectral reflectance data and thermal imaging are used in conjunction with clay mineral X-ray diffraction analysis to identify soil properties around abandoned wells located in an agricultural area in Wood County, Ohio. This study is confirmation of previous finding and it serves to indicate uncertainties related to a limited sampling effort, and to address the importance of field sampling strategies and adequate remote sensing techniques. Non-commercial satellite based remote sensors of medium, spatial resolution, such as Landsat, are inadequate for detection of the small abandoned wells in Wood County, Ohio. In situ hyperspectral reflectance measurements, used to simulate WorldView-3 spectral and spatial resolution, suggest that this high spatial resolution commercial satellite is optimal for detecting small abandoned oil wells. It is confirmed that a spectral band ratio in the spectral range between 2.185-2.225 µm and 2.295-2.365 µm (WorldView-3 shortwave bands 6 and 8, respectively) is effective. The clay mineral X-ray diffraction analysis suggests that these changes in the spectral information occur predominately due to the hydrocarbons; clay mineral content changes in the soil did not affect the soil spectral signature to a greater extent. Thermal imaging identified higher surface temperatures in soil with higher hydrocarbon content when compared to a control site. Based on direct hydrocarbon testing results, only long chain hydrocarbons (C30+) are present in the soil, suggesting that the wells are not active and that hydrocarbons are not presently leaking from the well. Rather, the soil contamination originated in the past, most likely during drilling of the wells decades ago. The limited results in this study are suggestive for further research. More field data, including crop information are needed to support the effectiveness of remote sensing technology in similar studies. It is suggested that using high spectral resolution commercial satellites (e.g. WorldView-3) in conjunction with thermal imaging can be an optimal approach to identify the soil contamination in proximity to abandoned wells in Wood County, Ohio.

Committee:

Anita Simic (Advisor); Jeff Snyder (Committee Member); John Farver (Committee Member)

Subjects:

Geology; Remote Sensing

Keywords:

WorldView-3; hyperspectral spectroradiometer; XRD; clay minerals; hydrocarbons; thermal imaging; Landsat-8; abandoned oil and gas wells; band ratios; soil contamination; soil hydrocarbon content

Campbell, RobertTHE BURDEN OF DISEASE AMONG PATIENTS OF THE CAROLINA LUPUS STUDY: HUMANISTIC, CLINICAL AND ECONOMIC FACTORS
Doctor of Philosophy, Case Western Reserve University, 2006, Epidemiology and Biostatistics
Objectives: To quantify differences in health-related quality of life, 5-year mortality risk, and direct and indirect costs between SLE patients early in the course of disease and controls, and to assess the association, among patients, between demographic and clinical characteristics and these outcomes. Methods: Multiple dimensions of the burden of disease were measured in an inception cohort of 265 SLE patients and 355 controls. The study includes two data collection periods: the baseline study (1997-1999) and follow-up study (2001). Results: Using a previously validated 8-item short form health-related quality of life instrument (SF-8), physical component scores were 7.7 points lower (p < 0.0001), and mental component scores were 1.8 points lower (p = 0.07) in cases compared with controls, adjusting for age, sex, race, state and education. Among cases, physical component scores of the 16-29 year olds and 30-49 year olds were 5.6 and 4.1 points higher, respectively, compared with the 50 and older group. Survival rates were significantly reduced in cases: by 60 months after diagnosis, 8.7% of cases compared with 0.28% of controls had died (p<.0001). Predictors of mortality in cases included age, gender, and ethnicity, with a hazards ratio of 1.04 (95% CI 1.01, 1.06) per one-year increment in age, 2.5 (95% CI 1.0, 5.9) for males compared with females, and 2.0 (95% CI 0.89, 4.6) for African-Americans and other minorities compared with whites. Annual mean direct costs for health care was $12,375 (sd 13723) in cases compared with $3,718 (sd 6135) in controls (p <.0001); differences were also seen in the median costs ($8,008 compared with $2,207 in cases and controls, respectively). Predictors of higher costs among cases were low education level (less than high school), renal disease and serositis. Forty-seven cases (24%) compared with 8 (3%) controls reported they had stopped working because of their health, resulting in an average indirect cost of lost wages of $5113 compared to $750 in cases and controls, respectively. Conclusions: Significant differences in quality of life scores, mortality risk, direct and indirect costs demonstrate the multidimensional burden of SLE.

Committee:

Duncan Neuhauser (Advisor)

Keywords:

SF-8; health-related quality of life; mortality; direct costs; indirect costs; job loss

LI, HAOWENNonlinear Optical Studies of Potential-sensitive Dyes
Doctor of Philosophy, Case Western Reserve University, 2007, Physics
Di-8-ANEPPS and other similar potential-sensitive dyes have been extensively used to probe the electrical environment in biological membranes due to changes in its linear and nonlinear optical properties as a function of the local electric field. Ratiometric fluorescence, two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) have all been applied to study biological cell and membrane systems. Mechanism and sensitivity studies for these potential-sensitive dyes have become popular due to the increasing biological needs. In this thesis, fluorescence-free time-correlated single photon counting hyper Rayleigh scattering (TCSPC-HRS) has been used to determine the hyperpolarizability Beta. Experiment results are in agreement with quantum chemical calculations. Linear and nonlinear optical studies of di-8-ANEPPS in liquid solution have been carried out. This polarity-dependent solvent effects of linear absorption and hyper-Rayleigh scattering in solution is combined together to analyze the spectral dependence of the sensitivity to the local environment. In this thesis, a two-level model including the spectral shift, changes in transition moment, excited and ground state dipole moment difference, and spectral width is applied to study the sensitivity of di-8-ANEPPS in response to the local electric field (solvent polarity). Good agreement between the model and the measurements has been found. Studies of a di-8-ANEPPS monolayer have been tried and high resolution fluorescence near-field scanning optical microscopic (NSOM) imaging with T-Cells has been performed. Optical resolution beyond diffraction limit has been achieved.

Committee:

KENNETH SINGER (Advisor)

Keywords:

di-8-ANEPPS; hyperpolarizability; Loew; DYES

Bartling, Toni ReneeInherent Alteration of Histine Acetylation in Cell Culture Models of Cystic Fibrosis
Doctor of Philosophy, Case Western Reserve University, 2008, Genetics

There appears to be dysregulated inflammation in the cystic fibrosis (CF) airway. Inflammatory cytokines, including interleukin-8 (IL-8), are elevated in CF. The regulation of inflammatory genes involves chromatin remodeling through histone acetylation. Acetylation can be directly related to the level of transcription. Small alterations in the histone acetyl-transferase (HAT)/deacetylase (HDAC) balance could affect the transcription level from several inflammatory genes. This could have a profound effect on the initiation, duration, and resolution of an inflammatory response. Loss of tight regulation of inflammatory genes through hyperacetylation could explain some of the dysregulation of inflammatory mediators seen in CF. The CF airway is exposed to high levels of oxidative stress and oxidative stress increases histone acetylation, and inflammatory gene transcription. Loss of CFTR may even reduce protection against oxidative stress. We hypothesize that oxidative stress in CF causes increased acetylation of inflammatory gene promoters, contributing to transcriptional activity of these loci.

We have found that mRNA levels of IL8, IL6, CXCL1, CXCL2, CXCL3, and IL1 are elevated in CF epithelial cell models. The IL8 promoter is also hyperacetylated CF-model cells. The reducing agent N-acetyl- cysteine (NAC) decreases IL8 message and promoter acetylation to non-CF levels, suggesting oxidative stress contributes to IL8 expression in these models. Hydrogen peroxide treatment causes increased IL8 acetylation and mRNA in all cells, but less in the CF-model cells.

Together these data suggest a model in which cells without functional CFTR are under increased oxidative stress. Increased NF-κB activation cannot explain the elevation in IL8 expression and acetylation seen in cells deficient in CFTR. No difference was found in the expression or activity of acetyl-transferase CBP or P300, or the deacetylase HDAC1. A reduction in HDAC2 protein level and activity was observed in cells deficient in CFTR. Knocking down HDAC2 using RNAi results in exaggerated IL8 expression and promoter acetylation as seen in CFTR deficient cells. Treating CFTR deficient cells with NAC brings HDAC2 expression closer to control levels. Our data suggest that there is an intrinsic alteration in the HAT/HDAC balance in cells lacking CFTR function, and that oxidative stress is likely contributing to this alteration.

Committee:

Mitchell Drumm, PhD (Advisor); Helen Salz, PhD (Committee Chair); Ronald Conlon, PhD (Committee Member); Peter Scacheri, PhD (Committee Member); James Chmiel, MD (Committee Member)

Subjects:

Genetics

Keywords:

cystic fibrosis; acetylation; inflammation; interleukin-8; deacetylase; oxidative stress

Sander, Zachary HugoHeat Transfer, Fluid Dynamics, and Autoxidation Studies in the Jet Fuel Thermal Oxidation Tester (JFTOT)
Master of Science (M.S.), University of Dayton, 2012, Mechanical Engineering
Modern military aircraft use jet fuel as a coolant before it is burned in the combustor. Prior to combustion, dissolved O2 and other heteroatomic species react with the heated fuel to form insoluble particles and surface deposits that can impair engine performance. For safe aircraft operation, it is important to minimize jet fuel oxidation and resultant surface deposition in critical aircraft components. The Jet Fuel Thermal Oxidation Tester (JFTOT) is a thermal stability test that measures the tendency for fuel to form such deposits and delivers a pass/fail grade for each fuel tested. However, the extent of oxidation and the corresponding deposition occurring in the JFTOT is not fully understood. A JFTOT Model Mark II was modified to include a bulk outlet thermocouple measurement and a downstream oxygen sensor to measure bulk oxygen consumption. Experimental results show a direct relationship between the bulk outlet temperature and JFTOT setpoint temperature with the bulk outlet less than the setpoint temperature. Several fuels were also tested at varying setpoint temperatures with complete oxygen consumption by 320°C and a wide range of oxygen consumption from 10-85% at 260°C. Due to the complex fluid flows in the JFTOT, computational fluid dynamics (CFD) was used to model the heat transfer and fluid flow. A three-dimensional simulation showed considerable recirculation within the JFTOT due to buoyancy effects from gravity and resulted in complex residence time behavior. In addition, CFD simulations performed with a pseudo-detailed chemical kinematic mechanism showed an under prediction in both oxidation and deposition for similar fuels tested experimentally but yielded bulk outlet temperature predictions of less than 2% error. Simulations of deposition were of the right order of magnitude and matched the deposit profile of comparable experimental ellipsometry data.

Committee:

Steven S. Zabarnick, PhD (Committee Co-Chair); Jamie S. Ervin, PhD (Committee Co-Chair); James T. Edwards, PhD (Committee Member)

Subjects:

Aerospace Engineering; Chemical Engineering; Chemistry; Energy; Engineering; Fluid Dynamics; Mechanical Engineering; Petroleum Engineering

Keywords:

JFTOT;CFD; heat transfer; oxidation; autoxidation; deposition; ellipsometry; jet fuel thermal oxidation tester; oxygen consumption; FT; fischer tropsh; hrj; jp-8; jet a-1; thermal stability; fluid mechanics; astm d3241; flir; interferometry; udri

Rhodes, Audry GayleTHE EFFECTS OF JP-8 JET FUEL ON THE IMMUNE SYSTEM OF TANK ENTRY WORKERS
MS, University of Cincinnati, 2001, Medicine : Environmental Health Sciences
Jet fuel is a common occupational exposure among commercial and military maintenance workers. JP-8 jet fuel, a military formulation, has been found to have immunotoxic effects in mice but little data exists for humans. The aim of this cross-sectional study was to determine if the number of immune cells in the peripheral blood was altered among tank entry workers, a group which has been determined in previous studies to have the highest exposure to JP-8 in the U.S Air Force. A total of 123 volunteers (45 tank entry workers) from three Air Force bases participated in the study. After adjusting for a number of covariates, tank entry workers were found to have higher numbers of white blood cells (p=0.01), neutrophils (p=0.05), and monocytes (p=0.02) and no differences in the numbers of total lymphocytes, T-cells, T-helper cells, T-suppressor cells, Natural Killer cells, and B-cells when compared with a low exposure group. Tank entry workers did not show any clinical effects of the increased immune cell counts. Although there were no differences in the number of lymphocytes among study groups, further investigations are needed to evaluate the functional ability of these cells to produce lymphokines and cytokines and modulate the immune system.

Committee:

Grace Lemasters (Advisor)

Keywords:

JP-8; JET FUEL; HEALTH EFFECTS; IMMUNE SYSTEM; WHITE BLOOD CELLS

Orazbayev, AzamatOpen Shell Effects in a Microscopic Optical Potential for Elastic Scattering of Exotic Helium Isotopes
Doctor of Philosophy (PhD), Ohio University, 2013, Physics and Astronomy (Arts and Sciences)
Microscopic optical potentials taking into account the open shell structure of the halo nuclei He-6 and He-8 are derived and calculated for the first time for the elastic scattering of these nuclei from a polarized proton target. It is demonstrated that the inclusion of open shell effects leads to new terms in the optical potential. Terms associated with the scalar single particle density matrix in spin space are the same as the terms obtained for closed shell nuclei. It is shown that the single particle density matrices corresponding to vectors in spin space vanish in the case of closed shell nuclei. For the open shell nuclei He-6 and He-8, the vector in spin space can couple to spin-dependent pieces of the nucleon-nucleon interaction. This leads to additional non-zero terms in the optical potential, which are derived for the first time. In the case of He-6 and He-8, one additional central term and one additional spin-orbit term have been identified. The effect of the additional non-zero terms on the differential cross section and analyzing power is found to be small for the scattering energies between 71 and 300 MeV per nucleon. As the projectile kinetic energy increases, the differences between results calculated with the closed shell and modified optical potentials diminish. The nuclei He-6 and He-8 are described by harmonic oscillator wave functions, and the ground states are assumed to have 1s and 1p shells occupied. The higher levels of harmonic oscillator basis are excluded from consideration. Under this assumption, the harmonic oscillator wave functions do not describe the extended exponential distribution of matter specific to halo nuclei. In order to simulate exponential tails, the harmonic oscillator wave functions are replaced with exponential functions at distances greater than certain matching radii. It is found that exponential tails do not affect the observables at the considered energies. Because there are various estimations for the charge and matter radii of He-6 and He-8, the effect of varying the radii is studied. It is established that the scattering observables are sensitive to both the charge and matter radii of the target nucleus. The effect in some cases is significant and can lead to distinctly different results.

Committee:

Charlotte Elster, Prof. (Advisor); Stephen Weppner, Prof. (Committee Member); Carl Brune, Prof. (Committee Member); Klaus Himmeldirk, Prof. (Committee Member)

Subjects:

Nuclear Physics; Physics

Keywords:

Halo nuclei; Open shell effects; Microscopic optical potential; elastic scattering; shell model; Helium-6; Helium-8; differential cross section; analyzing power; scattering observables

Odhar, HasanainIdentification of novel scaffolds for Monoamine oxidase B inhibitors
MS, Kent State University, 2014, College of Arts and Sciences / School of Biomedical Sciences
Parkinsonism is a progressive neurodegenerative disease that mainly affects elderly people. The disease is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. This gradual loss of dopaminergic neurons will result in the appearance of four motor related symptoms and these are: tremor, bradykinesia, rigidity and postural imbalance. Current therapeutic approach focuses mainly on symptoms attenuation through dopamine replacement therapy. In this regard, recent drug design approaches are focused mainly on the production of multi targeted drug molecules as an attempt to generate a medication that is capable of halting or slowing down the progression of the degenerative process. Such goal can be achieved through the employment of designed multiple ligands (DMLs) strategy. MAO-B enzyme appears to be a promising target for such drug discovery approach. For our project, twenty four chemical compounds were selected (based on similarity analysis) as possible candidates for MAO-B inhibition. Structure-based virtual screening techniques (docking programs) were used to build an early impression about the binding tendency of these compounds to MAO-B crystal and bovine serum albumin (BSA) crystal. These compounds were then evaluated in vitro for their potentials to inhibit MAO isozymes and to quench peroxyl radicals. The pharmacokinetic profile for these compounds was investigated through the application of bovine serum albumin (BSA) binding assay and parallel artificial membrane permeability assay (PAMPA). Finally, a basic structure-activity relationship (SAR) study was established by comparing the structure, activity and docking images for compounds with related building blocks. As a conclusion to our SAR study, we believe that the 2-thioxo-1, 3-thiazolidin-4-one ring is essential for both MAO-B inhibition potential and radical quenching capacity. We also believe that 8-hydroxyquinoline moiety is essential for radical quenching activity; previous researches have shown that 8-hydroxyquinoline molecule can also act as a strong iron chelator. By combining 2-thioxo-1, 3-thiazolidin-4-one ring with 8-hydroxyquinoline moiety, we were able to generate two hypothetical scaffolds (scaffolds A and B). We believe that the attachment of L-alanine moiety to our design (scaffolds A and B) will enhance the selective delivery of these scaffolds into the brain. The addition of L-alanine will result in the generation of two additional scaffolds (E and F); these new scaffolds can act as good substrates to the large neutral amino acid transporter in the blood brain barrier. We believe that these scaffolds can be used for the development of a potent, selective and centrally acting MAO-B inhibitor with a possible radical quenching capacity and a promising iron chelating activity.

Committee:

Werner Geldenhuys, Ph.D. (Advisor); Altaf Darvesh, Ph.D. (Committee Member); Richard Carroll, Ph.D. (Committee Member)

Subjects:

Biomedical Research; Neurosciences; Pharmaceuticals; Pharmacology; Pharmacy Sciences

Keywords:

Parkinsonism; Monoamine oxidase; Scaffold; High throughput screening; Drug design; structure-activity relationship study; Thiazolidine; 8-hydroxyquinoline; L-alanine

Thomas, Ronald PiersonAn Investigation of the Role Education Leaders in the Academic Achievement of African American Students
Doctor of Education, Miami University, 2008, Educational Leadership

The purpose of this case study is to understand the role that K-8 principals play in improving the academic performance of African American students. I want to discover what school leaders should do to reach, understand, encourage and to motivate African American students to achieve. This case study will examine the role of leadership and how school leadership impact academic achievement of African American students.

The study will focus on three elementary principals, in an urban city in Southwest Ohio. The study's data will be collected through interviews with school principals. An intended outcome of this research is to generate discussion about African American student achievement and how K-8 principals can develop strategies that can improve the academic achievement of African American students.

Committee:

Michael Dantley, Dr. (Committee Chair); Raymond Terrell, Dr. (Committee Member); Ellen Bueschel, Dr. (Committee Member); Barbara Heuberger, Dr. (Committee Member)

Subjects:

African Americans; Education

Keywords:

Principals' role K-8 African American student achievement.

HENRY, MARKA STUDY IN FIELD VERIFICATION OF 8-VSB COVERAGE
MS, University of Cincinnati, 2001, Engineering : Electrical Engineering
The new terrestrial transmission standard for Digital Television is known as 8-VSB. The DTV-M1 is used to take actual field measurements of a stations coverage area, allowing the user to compare these results with theoretical coverage predictions that are based upon mathematical models. This document describes the main concepts behind the design of the DTV-M1, a vehicle capable of performing such tasks. Equipment considerations, equations, algorithms, and measurement procedures used in this vehicle are explored.

Committee:

Dr. James Caffery (Advisor)

Keywords:

DTV Field Measurement; 8-VSB; DTV Field Verification

THOMAS, MONICA ELISEBARRIERS AFFECTING SUCCESS IN LOCATING AFFORDABLE HOUSING WITHIN THE CINCINNATI METROPOLITAN REGION: A CASE STUDY OF CINCINNATI METROPOLITAN HOUSING AUTHORITY'S (DMHA) SECTION 8 HOUSING CHOICE VOUCHER PROGRAM
MCP, University of Cincinnati, 2002, Design, Architecture, Art, and Planning : Community Planning
The purpose of this research project was as follows: (1) to reveal obstacles/barriers that Cincinnati Metropolitan Housing Authority (CMHA) Section 8 clients have experienced in locating housing within the Cincinnati Metropolitan Region and (2) to determine whether it is possible to develop a demographic profile of successful vs. unsuccessful clients. As will be shown, the literature provides numerous reasons why households may have trouble utilizing their housing vouchers including the lack of affordable housing opportunities in tight housing markets. However, little research had been done to determine the role that these barriers play in loose housing markets. In an effort to discover the role that these barriers play in a loose housing market, I examined the barriers faced by successful and unsuccessful clients of CMHA. The methodology consisted of client interviews with fourteen successful clients and three unsuccessful clients, as well as informant interviews with six Section 8 program administrators from Cincinnati Metropolitan Housing Authority (CMHA) and Hamilton County Community Development (the other housing agency in the county offering vouchers). The main barriers and obstacles that CMHA Section 8 clients faced in searching for housing within the Cincinnati Metropolitan Region were the lack of landlords willing to rent to Section 8 clients; the lack of quality housing, neighborhoods, and schools; and both the lack of transportation to search and lack of adequate public transportation in desired neighborhoods. While successful clients experienced the same barriers as unsuccessful clients, successful clients seemed to possess greater perseverance and determination, and had a personal support network providing housing search and transportation assistance. There were two key differences between successful and unsuccessful clients with respect to demographic characteristics. Unsuccessful clients were younger and more likely to be employed. This study suggests that further research involving clients who are unsuccessful in their housing search needs to be pursued. This type of research is difficult because once these clients leave the local housing authority’s data management system, they are hard to trace. In addition, more attention should be given to the plight of Section 8 voucher holders in looser housing markets like Cincinnati. Too often it is assumed that these households face less difficulty in searching for a home. This study has shown that for a variety of reasons the challenges facing these households are still quite formidable.

Committee:

Dr. David Varady (Advisor)

Subjects:

Urban and Regional Planning

Keywords:

Section 8; housing voucher; barriers to locating; Cincinnati

Thind, Raja Mandeep SinghBRIEF CONSTANT LIGHT ACCELERATION OF NONPHOTIC CIRCADIAN PHASE SHIFTING AND REENTRAINMENT OF LD CYCLE
MS, Kent State University, 2010, College of Arts and Sciences / Department of Biological Sciences
Brief (~2 day) constant light exposure (LLb) in hamsters enhances circadian phase-resetting induced by the serotonin (5-HT) receptor agonist, 8-OH-DPAT and other nonphotic stimuli. The present study was undertaken to determine if LLb can also amplify phase-resetting responses to endogenous 5-HT and accelerate re-entrainment to large-magnitude advance and delay shifts of the light-dark (LD) cycle. Central serotonergic activity was increased by i.p. injection of L-tryptophan +/- the 5-HT reuptake inhibitor fluoxetine, followed by the efforts to study effects of short acting benzodiazepine triazolam and ethanol on the circadian phase shifting and re-entrainment to the advanced LD cycle.

Committee:

J. David Glass, PhD (Advisor); Sean Veney, PhD (Committee Member); John Johnson, PhD (Committee Member)

Subjects:

Biology; Biomedical Research

Keywords:

circadian; hamster; 8-OH-DPAT; triazolam; L-tryptophan; ethanol

Le Pommellet, Helene MarieResection of the Primary Osteosarcoma Terminates Self-seeding and Facilitates Metastasis
Master of Science, The Ohio State University, 2017, Comparative and Veterinary Medicine
Introduction: Pediatric osteosarcoma is the most common bone cancer in children. Despite aggressive surgical excision and chemotherapy, up to 80% of children die after developing metastasis, despite the absence of metastatic disease at diagnosis. Similar to numerous other cancers, surgical excision of the primary tumor is often followed by development of metastasis. The present study sought to characterize the effect that surgical excision of a primary osteosarcoma has on the subsequent development of lung metastasis. This work hypothesizes a more dynamic model of metastasis development, where circulating tumor cells enter and exit circulation in an equilibrium at both the site of the primary tumor (through the process of self-seeding) and at the metastatic niche (through the process of lung colonization). We specifically sought to identify the contributions of multiple tumor-derived cytokines and chemokines, including IL-6 and IL-8, oncostatin M, and SDF-1, based on our previous work implicating these cytokines in the biology of metastatic colonization of lung. Results: Using a murine model of metastatic osteosarcoma, we determined that surgical removal of a primary tumor caused a significant increase in the number of tumor cells within the lungs. We determined that the presence of a primary tumor could protect lungs from developing metastatic lesions when mice were inoculated with a defined number of osteosarcoma cells intravenously. In the absence of a primary tumor, circulating tumor cells preferentially migrated to the lungs. We identified significant expression of IL-6, IL-8, IL-11, Oncostatin and SDF-1 by osteosarcoma cells in culture. IL-6 and IL- 8 expression was consistently higher than that of other cytokines. All of the cytokines and chemokines tested, including IL-6, IL-8, Oncostatin and SDF-1, induced robust directional migration of osteosarcoma cells using in vitro chemotaxis assays. Conclusion: These results suggest that the presence of a primary tumor influences the migration of circulating tumor cells. Circulating tumor cells preferentially migrate to the primary tumor when present—it is the most favorable environment for growth and survival. After resection of the primary tumor, circulating tumor cells seed to the second most favorable location, the lungs, initiating the development of lung metastasis. Our data suggest that IL-6 and IL-8 likely mediate this process. Both cytokines were highly expressed in osteosarcoma cells and both were capable of inducing migration in vitro. While further work is needed to elucidate this biology in greater detail, this work already suggests that an understanding of these processes could be leveraged to design therapies that manipulate the dynamics of self-seeding and metastatic seeding to prevent and even treat pediatric osteosarcoma.

Committee:

Ryan Roberts (Advisor); Cheryl London (Committee Member); Mary McLoughlin (Committee Member)

Subjects:

Animal Sciences; Medicine; Oncology

Keywords:

pediatric osteosarcoma; osteosarcoma; IL-6; chemokine; metastasis; amputation; surgery; primary tumor; orthotopic murine model; tail vein injection; oncology; oncostatin; IL-8; IL-11; cancer

Brundage, Meghan ElizabethCLONING OF KNOWN AND NOVEL CYTOCHROME P450S IN SCUTELLARIA BAICALENIS
MS, University of Cincinnati, 2001, Arts and Sciences : Biological Sciences
Skullcap (Scutellaria baicalensis), a Chinese medicinal herb, contains several rare flavones with significant antiviral effect against HIV, influenza, and other viruses. These rare flavones differ from much more common flavones by one or two very specific hydroxylations. Although the medicinal application of these rare flavones has received recent attention, very little is known about the enzymatic pathways of their synthesis in skullcap. Previous studies of flavonoid metabolic pathways in other plants have identified specific cytochrome P450 monooxygenases as the enzymes responsible for similar oxidations. Based on the evidence from these other studies, profiling P450s in skullcap would provide much needed elucidation of these pathways. The conserved base and amino acid sequence provide the opportunity to use specific and degenerate primers to amplify partial sequences of known and novel P450s. Reported here is the successful isolation by cloning of four partial cytochrome P450 nucleotide sequences obtained from cDNA produced by reverse transcription of skullcap leaf mRNAs. Of these, one is part of the sequence for the enzyme cinnammate-4-hydroxylase. The other three are partial sequences of novel putative cytochrome P450 enzymes of as yet unknown function.

Committee:

G. Winget (Advisor)

Keywords:

SCUTELLARIA BAICALENIS; CYTOCHROME P450; FLAVONES; 6-AND 8-HYDROXYLASE; CINNAMATE 4-HYDROXYLASE

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