ETD Center Search

119 matches in the database. These are records: 1 - 30.

[1] [2] [3] [4]

1. Xanthakos, Stavra A. Prevalence and Determinants of Hepatic Steatosis in Young Adult Women.

Degree: MS, Medicine : Epidemiology (Environmental Health), 2006, University of Cincinnati

► The prevalence of nonalcoholic fatty liver disease (NAFLD) in children and young… (more)

▼ The prevalence of nonalcoholic fatty liver disease (NAFLD) in children and young adults is unknown, as population-based studies are often limited by use of serum aminotransferases as surrogate markers, lacking imaging or biopsy data to confirm NAFLD. This study determines the prevalence and determinants of NAFLD in young adult females using magnetic resonance imaging (MRI) to measure hepatic steatosis. Prevalence was hypothesized to be 15%. Methods: 278 female subjects, ages 25-27 years, were recruited from a population-based cohort. Exclusion criteria included weight >300 lbs, daily alcohol intake >20 gm/day, hepatotoxic medications, or serologic evidence of hepatitis B, C or autoimmune hepatitis. Anthropometric indices, serum lipids, insulin, glucose and aminotransferases (ALT, GGT) were measured. The hepatic fat index (HFI) was measured using a biopsy-validated MRI technique. Descriptive statistics and nonparametric tests were used, analyzing races separately to control for higher prevalence of obesity in the black females. Results: 38% of the cohort was obese (BMI > 30 kg/m2), but only 4% had abnormal ALT (>35 IU/L). Black females (N=157) had a higher prevalence of obesity (47% vs. 27%, p<0.001), abnormal waist circumference (40% vs. 25%, p=0.02), hyperinsulinemia (54% vs. 30%, p<0.001) and metabolic syndrome (10% vs. 5%, p =0.15) compared to white females. Mean HFI was 3.0 ± 2.6 (range 0 - 26) with no significant racial differences. Prevalence of abnormal HFI was 2.5%, with no significant racial differences (blacks 1.9%, whites 3.3%). BMI, waist-hip ratio, waist circumference, triglycerides, and GGT directly correlated with HFI. Of subjects with abnormal HFI, 100% were obese and hyperinsulinemic, 80% had abnormal waist circumference, but only 29% had abnormal ALT. Conclusions: Despite a high prevalence of obesity, significant hepatic steatosis is not very prevalent in young black and white adult women. Black women have a significantly higher prevalence of risk factors for NAFLD, but a strikingly low prevalence of hepatic steatosis, confirming that black race may protect against NAFLD. Shorter duration of obesity due to young age may contribute to a lower than anticipated prevalence and severity of hepatic steatosis in this population-based cohort of young adult females. Advisors/Committee Members: Heubi, Dr. James E.

Keywords: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Obesity; Magnetic Resonance Imaging

2. Xavier, Graziane de O. Motivational Teaching Strategies in a Brazilian EFL School: How Important are they and how Frequently are they used?.

Degree: Master of Arts (MA), Linguistics (Arts and Sciences), 2005, Ohio University

► For over two decades, scholars in the field of second language teaching… (more)

Subjects: Language, Linguistics

Keywords: Motivational teaching strategies; EFL/ESL Pedagogy; L2 Classroom research; EFL Teaching in Brazil; Motivational Conceptual Domains of Teaching Strategies

3. Xia, Honggang. On zeros of cubic L-functions.

Degree: Doctor of Philosophy, Mathematics, 2006, Ohio State University

► We study the distribution of zeros of cubic L-functions and obtain a… (more)

Subjects: Mathematics

Keywords: zero density theorem, large sieve

4. Xiang, Kun. The role of L-type voltage-gated calcium channels in hippocampal CA1 neuron glutamate and GABA-A receptor-mediated synaptic plasticity following chronic benzodiazepine administration.

Degree: Doctor of Philosophy in Medical Sciences (Ph.D.), College of Graduate Studies, 2007, University of Toledo Health Science Campus

► Clinicians require caution prescribing benzodiazepines for a prolonged period of time because… (more)

▼ Clinicians require caution prescribing benzodiazepines for a prolonged period of time because of the development of functional tolerance and dependence. The objective of these dissertation studies was to evaluate the role of L-type VGCC in mediating glutamate receptors and GABAA receptor functional changes in the expression of benzodiazepine tolerance and dependence following a 1-week FZP oral treatment regimen in rats. Initially, AMPA receptor-mediated mEPSC amplitude in hippocampal CA1 neurons was evaluated in rats withdrawn from 1-week FZP administration, using whole-cell electrophysiological recordings, and was found to correlate with benzodiazepine withdrawal-anxiety in rats measured using an elevated plus-maze. A compensatory role of NMDA receptor functional down-regulation was further identified as a counterbalance to AMPA receptor-mediated neuronal hyper-excitation. Following pharmacological antagonism of NMDA receptor and VGCC function, a role for regulation of L-type VGCCs, but not NMDA receptors, in mediating enhanced AMPA receptor function and benzodiazepine withdrawal anxiety was identified. Further studies concentrated on the regulation of L-type VGCC function following chronic benzodiazepine administration using whole-cell voltage-clamp method. The temporal pattern of L-type VGCC functional regulation was evaluated following chronic benzodiazepine administration. The direct concentration- and use-dependent effect of the benzodiazepines to affect L-type VGCC currents was also investigated. Based on the evidence of L-type VGCC function changes and its role in mediating AMPA receptor synaptic plasticity following chronic FZP administration, the relation between L-type VGCC and GABA receptor was further explored. Pharmacological antagonism was again applied for investigating the role of L-type VGCC in mediating GABAA receptor function using whole-cell ctrophysiological recordings of GABAA receptor-mediated currents. GABAA receptor channel kinetics and single channel conductance was evaluated after L-type VGCC antagonist application both in vivo and in vitro. In all, these studies would give the insight of an L-type VGGG-dependent Ca2+ signaling mechanism in differentially mediating specific glutamate receptors and GABAA receptor synaptic changes that are associated with benzodiazepine tolerance and dependence. To serve as the foundation for more mechanistic studies, a model of the cellular mechanisms underlying benzodiazepine tolerance and dependence was proposed in these dissertation studies based on the present findings, and on past evidence from our laboratory and others. Advisors/Committee Members: Tietz, Elizabeth.

Keywords: Benzodiazepine; L-VGCCs; Hippocampus; AMPA receptor; Dependence/Tolerance; GABA receptor

5. Xiang, Yang. Reachability, Routing and Distance Labeling Schemes in Graphs with Applications in Networks and Graph Databases.

Degree: PHD, College of Arts and Sciences / Department of Computer Science, 2009, Kent State University

► Three fundamental and related problems, with applications in networks and graph databases,… (more)

▼ Three fundamental and related problems, with applications in networks and graph databases, are the focus of this dissertation. They are: how to answer quickly whether a vertex can reach another vertex in a directed graph, using a succinct representation of the reachability information; how to route a message efficiently from a source vertex to a destination vertex and how to calculate or estimate quickly the distance between any two vertices, using very limited information stored locally at those vertices. To efficiently answer reachability queries, we introduce a novel path-tree structure to assist with the compression of transitive closure and answering reachability queries. Our path-tree generalizes the traditional tree cover approach and can produce a better compression rate for the transitive closure. We also propose a 3-hop indexing scheme with high compression rate targeting the directed graphs with higher edge-vertex ratio. In addition, we show how to effectively summarize reachability information. To efficiently route messages in a graph, we investigate three strategies of how to use a spanning tree $T$ of a graph $G$ to navigate in $G$, i.e., to move from a current vertex $x$ towards a destination vertex $y$ via a path close to optimal. We investigate advantages and limitations of these strategies on several families of graphs such as graphs with locally connected spanning trees, graphs with bounded length of largest induced cycle, graphs with bounded tree-length, and graphs with bounded hyperbolicity. For most of these families of graphs, the ancestry information from a Breadth-First-Search-tree guarantees short enough routing paths. In many cases, the obtained results are optimal up to a constant factor. Finally, we propose distance and routing labeling schemes for circle graphs and polygon graphs by constructing collective additive tree spanners. We show that the family of $n$-vertex circle graphs admits a 2-additive distance labeling scheme with $O(log^3{n})$-bit labels and $O(log{n})$ time distance decoder, and the family of $n$-vertex $k$-polygon graphs admits a 2-additive distance labeling scheme with $O(log{k}log^2{n})$-bit labels and $O(log{k})$ time distance decoder. Similar routing labeling schemes are also designed for these families of graphs. Advisors/Committee Members: Dragan, Feodor.

Subjects: Computer science

Keywords: Reachability, Routing, Distance, Labeling schemes, Graphs, Networks, Graph databases

6. Xiao, Dan. An implementation of kernelization via matchings.

Degree: Master of Science (MS), Electrical Engineering (Engineering), 2004, Ohio University

An implementation of kernelization via matchings Advisors/Committee Members: Juedes, David W.

Keywords: Kernelization; Matchings

7. Xiao, Haiyi. LOW TRANS FATTY ACID CONTAINING HYDROGENATED EDIBLE OILS.

Degree: Master of Science, Paper Science and Engineering, 2007, Miami University

► An investigation of an electrochemical process for hydrogenating edible oils at low… (more)

Keywords: Vegetable Oil, Soybean Oil, Hydrogenation, Formate, Kinetics, Model

8. Xiao, Hong. Torque and Magnetization Measurements on the Heavy Fermion Superconductor CeCoIn5.

Degree: PHD, College of Arts and Sciences / Department of Physics, 2009, Kent State University

► We performed out-of-plane torque measurements on CeCoIn5 heavy fermion single crystals. Our… (more)

Subjects: Physics

Keywords: heavy fermion, superconductivity

9. Xiao, Jin. Pharmacokinetics, pharmacodynamics, metabolism, transport, and resistance studies of a novel histone deacetylase inhibitor FK228 (FR901228, NSC630176).

Degree: Doctor of Philosophy, Pharmacy, 2004, Ohio State University

► Depsipeptide FK228 (FR901228, NSC630176), a promising histone deacetylase (HDAC) inhibitor, is currently… (more)

▼ Depsipeptide FK228 (FR901228, NSC630176), a promising histone deacetylase (HDAC) inhibitor, is currently undergoing clinical evaluation against various malignancies. Pharmacokinetic study of FK228 in the rat was first conducted with a focus on its pharmacokinetic properties and dose recovery. FK228 was found to be removed rapidly from the circulation with a total body clearance higher than the rat cardiac output, suggesting extensive metabolism in the blood. Dose recovery of FK228 was low (<15%) and there was an involvement of glutathione in FK228 elimination. Based on these results, we conducted in vitro metabolism studies, which led to identification of four glutathione conjugates and two thiols from rat and human blood incubations. Purification of these major metabolites followed by HDAC inhibition assays indicated that FK228 is a prodrug, with three major metabolites being more potent HDAC inhibitors than FK228 itself. A clinical pharmacokinetic study in AML and CLL patients was conducted. A pharmacokinetic-pharmacodynamic correlation study showed that HDAC inhibitory activity was inversely correlated with FK228 systemic exposure. This provided the first clinical evidence that FK228 was a prodrug. FK228 transport and uptake was investigated. It was found that FK228 is a substrate for both MDR1 and MRP1 by transport and cytotoxicity studies using specific inhibitors of the membrane transporters. In order to study the roles of MDR1 and MRP1 in acquired FK228 resistance, four FK228 resistant cell lines were established and characterized. We found that upregulation of MDR1, but not MRP1 or other ABC transporters, was responsible for the acquired resistance. The maintenance of acquired FK228 resistance depended on continuous drug exposure. No deregulation or impairment of the histone acetylation machinery was found. The MDR1 upregulation was further found to be via a reversible induction procedure, in which FK228 first inhibited HDACs and then caused hyperacetylation at the MDR1 promoter region to form the euchromatin structure ready for transcription. Overall, the dissertation work, involving both preclinical and clinical studies, provided valuable information of pharmacokinetics, bioactivation, transport and uptake, and resistance of the novel anticancer drug FK228. Advisors/Committee Members: Chan, Kenneth K.

Subjects: Health Sciences, Pharmacy

Keywords: FK228; depsipeptide; pharmacokinetics; pharmacodynamics; metabolism; prodrug; transport; MDR1; resistance; induction

10. Xiaojing, Li. An Investigation on Balance Switching Behavior in Credit Card Market.

Degree: Doctor of Philosophy, Economics, 2008, Ohio State University

► Research on the behavior of credit card balance switching is underdeveloped because… (more)

▼ Research on the behavior of credit card balance switching is underdeveloped because data on the phenomenon are quite limited. The few previous studies suggest that consumers' choice of accepting a low introductory interest rate and then switching a balance to it mainly depends on the APR difference and the outstanding credit card balances. This dissertation uses the Consumer Finance Monthly data with much richer information about consumers' credit history and card holding conditions to investigate several fundamental factors in balance switching. A theoretical model is developed to rationalize revolvers' decision about balance switching. An exercise of dynamic optimization is conducted to reveal the relationship between switchers' reservation rate, payment process, and the predicted duration spell. Econometric methods are used to do the empirical analysis. Two endogenous switching regression models are applied to inspect two distinct responses on the switchers' side. The accelerated lifetime model is adopted to capture the impact of the credit card debt and other relevant factors on the duration spell for holding an initial card. Last, we address the issue of unobserved heterogeneity in a structural Weibull-Gamma duration model. The two theoretical predictions in this paper are consistent with the primary findings in our empirical study. Switchers wait for an interest rate that is regarded as sufficiently low. Consumers with worse payment history have to wait longer to receive such a low rate. Our survival analysis shows that the degree of stress over the debt rather than the amount of credit card debt itself hastens consumers' switching decision. The fitted hazard rate is bell-shaped both in the accelerated lifetime model with Gamma distribution and in the structural duration model. Cardholders are most likely to switch in the window of the sixth to twelfth month staying with old cards. Our empirical findings support "adverse selection" as in Ausubel (1991). Switchers improved their debt situation right after switching. But balance switching could only bring symptomatic relief but not a credit cure. Switchers still bear a heavier burden of credit card debt in the long run. Advisors/Committee Members: Dunn, Lucia.

Subjects: Economics

Keywords: Balance Switching, Default History, Adverse Selection, Endogenous Switching Regression, Accelerated Lifetime

11. Xiao, Mingli. An Empirical Study of Using Internet-Based Desktop Videoconferencing in an EFL Setting.

Degree: Doctor of Philosophy (PhD), Instructional Technology (Education), 2007, Ohio University

► The recently developed Internet-based desktop videoconferencing as the highest level of CMC… (more)

▼ The recently developed Internet-based desktop videoconferencing as the highest level of CMC offers an authentic learning environment in which language learners can orally and visually interact with another human being in the target language, much in the same way as in a face-to-face interaction (Wang, 2004a, 2004b). The purpose of this study is to investigate the effects of interaction with native speakers via Internet-based desktop videoconferencing on EFL learners’ language proficiency in terms of fluency, accuracy and complexity, as well as examine L2 learners’ perception on using Internet-based videoconferencing to access native speakers to promote L2 learning.A control group and an experimental group were applied in this study, with 10 native-nonnative dyads participating in Internet-based desktop videoconferencing as a treatment for experimental group and10 nonnative-nonnative dyads using traditional face-to-face interaction for the control group. Ten topics were assigned to both groups and the research lasted about 10 weeks. Data collected from the two groups in Weeks 2, Week 6 and Week 10 were transcribed, coded and analyzed in terms of linguistic fluency, accuracy and complexity using doubly multivariate repeated measures of ANOVA for the statistic analysis. Follow-up questionnaires with both groups and online interviews with five of the participants in the experimental group were also conducted.The results indicated that there was a significant improvement in fluency, a slightly significant improvement in accuracy, but no improvement in complexity for the L2 learners in the experimental group. Interactional mode has a significant effect on L2 learners’ language proficiency. Using Internet-based desktop videoconferencing to talk with native speakers resulted in better performance by the participants in the experimental group than those in the control group in terms of fluency, accuracy and complexity. There was a significant interaction effect of time by interactional mode in terms of fluency, but no interaction effects were detected in terms of accuracy and complexity.Results from the participants’ follow-up questionnaires and interviews indicated that the Internet-based desktop videoconferencing creates a comfortable, spontaneous and less threatening environment for L2 learners to interact with native speakers. L2 learners have perceived great improvement in their language proficiency in terms of fluency and accuracy. Pedagogical implications, limitations of the study and recommendations for future research were also provided. Advisors/Committee Members: Franklin, Teresa J.

Subjects: Education, Curriculum and Instruction; Language, Linguistics

Keywords: Internet-based desktop videoconferencing; Second Language acquisition; fluency; accuracy; complexity; language proficiency

12. Xiao, Rui. Activation and regulation of TRP channels.

Degree: Doctor of Philosophy, Biophysics, 2008, Ohio State University

► Mammalian TRP superfamily is composed of 28 members. Based on the sequence… (more)

▼ Mammalian TRP superfamily is composed of 28 members. Based on the sequence homology and functional similarity, they are grouped into 6 subfamilies: canonical TRP (TRPC), vanilloid TRP (TRPV), melastatin TRP (TRPM), ankyrin TRP (TRPA), polycystin TRP (TRPP), and mucolipin TRP (TRPML). TRP channels display rather diverse tissue expression pattern and physiological functions. We mainly focused on three TRP channels: TRPV3 from TRPV subfamily; TRPC4 and TRPC5 from TRPC subfamily. For TRPV3, we performed three functional studies: first, we found that arachidonic acid (AA), together with other poly-unsaturated fatty acids (PUFAs), greatly potentiated TRPV3 channel function independent of its downstream metabolites or signaling pathways. Second, besides being potentiated by AA and other PUFAs, TRPV3 also displays an intrinsic unique functional property: sensitization upon prolonged or repetitive chemical or physical stimulations. We studied the molecular mechanism underlying this unique feature and found that calcium plays a critical role from both intracellular and extracellular sides. Third, a spontaneously occurring point mutation linked to rodent hair-less phenotype was mapped to Gly573 of TRPV3. We carried out detailed functional studies with G573C and G573S mutants of TRPV3, and discovered that these two point mutations cause constitutive channel activation and severe host cell death, which provides an important clue for the hairless phenotype. Moreover, we studied the activation mechanism of TRPC4 and TRPC5. Strikingly, we found that in addition to the previously identified Gq/11 signaling pathway, another commonly considered inhibitory G protein-coupled receptor, Gi/o signaling pathway, was excitatory for the activation of TRPC4 and TRPC5. In fact, compared to Gq/11, the Gi/o pathway was even stronger for the activator of TRPC4/C5. We also demonstrated the synergistic effect between these two pathways. The full activation of TRPC4/C5 appeared to require both signaling pathways, indicating that TRPC4 and TRPC5 work as coincident detectors for the two important G protein signaling pathways. We further confirmed the requirement of phospholipase C (PLC) and intracellular Ca2+ for the excitatory effect of Gi/o. More detailed studies will help us understand the precise underlying mechanism of Gi/o-induced TRPC4/C5 activation. Advisors/Committee Members: Zhu, Michael.

Subjects: Biophysics

Keywords: TRPV3, TRPC4, TRPC5, sensitization, PUFAs, Ca2+, Gq/11, Gi/o

13. Xiao, Ruiyang. The Freezing of Highly Sub-cooled H2O/D2O Droplets.

Degree: Master of Science, Environmental Science, 2008, Ohio State University

► The condensation of H2O and D2O in a supersonic Laval nozzle was… (more)

Subjects: Chemistry

Keywords: sub-cooled droplets; FTIR; supersonic nozzle

14. Xiao, Ying. A Two-dimensional Stochastic Model for Prediction of Localized Corrosion.

Degree: Master of Science (MS), Chemical Engineering (Engineering), 2004, Ohio University

► The two-dimensional (2-D) stochastic model, which describes the balance of two processes:… (more)

Keywords: Localized Corrosion; Modeling; Stochastic; Film; Carbon Steel; Prediction

15. Xiao, Zhigang. Synthesis of Functional Multilayer Coatings by Plasma Enhanced Chemical Vapor Deposition.

Degree: PhD, Engineering : Electrical Engineering, 2004, University of Cincinnati

► Silicon dioxide, silicon-containing polymer, silicon nitride, metal nitride, and germanium thin films… (more)

▼ Silicon dioxide, silicon-containing polymer, silicon nitride, metal nitride, and germanium thin films were grown by electron cyclotron resonance (ECR) microwave plasma enhanced chemical vapor deposition (PECVD), and multilayer coatings were grown for high hardness and high corrosion resistance. Silicon dioxide was grown from hexamethyldisiloxane (HMDSO), 1,3,5,7-tetramethylcyclotetrasiloxane (TOMCTS ), and octamethylcyclotetrasiloxance (OMCTS) in a oxygen plasma. The grown silicon dioxide thin films were hard and colorless. Silicon nitride was grown from hexamethyldisiloxane (HMDSO) and tetramethylsilane (TMS) in an ammonia (NH3) plasma. The silicon nitride thin films grown from HMDSO were hard and transparent while the silicon nitride thin films grown from TMS were black and hard. Silicon-containing polymer was grown from 100% OMCTS. The polymer thin films are colorless, had relatively low hardness and very good salt-fog corrosion resistance. Titanium nitride, zirconium nitride, and chromium nitride were grown from titanium (IV) isopropoxide and tetrakis(dimethylamino)titanium, zirconium 2-methyl-2-butoxide and zirconium t-butoxide, and bis(ethylbenzene)chromium in an ammonia plasma. The grown titanium nitride and zirconium nitride thin films had characteristic gold coloring and high hardness while the grown chromium nitride thin films were black gray and had high hardness. Germanium thin films were grown from tetramethylgermane (TMG) in a argon plasma. The deposited germanium films were uniform and had polished-like shining surface. X-ray photoelectron spectroscopic (XPS) analyses showed the films contained 97 % germanium atomic concentration with less than 1 % carbon, and X-ray diffraction (XRD) analyses showed the films had the crystal structure of <220>. Hard corrosion-resistant silicon-containing multilayer coatings were grown in a high-density microwave electron cyclotron resonance discharge. The multilayer coatings consist of a relatively soft silicon-containing polymer thin film as the bottom layer and a hard silicon dioxide or silicon nitride thin film as the top layer. Silicon-containing polymer thin films were grown from 100% OMCTS. Silicon dioxide and silicon nitride thin films were grown from OMCTS with O2 and HMDSO with NH3, respectively. The multilayer structures combined high surface hardnesses with good corrosion resistance, surviving 1800 to 2600 hours in an ASTM B117 salt-fog corrosion test. Multilayer coatings with a titanium nitride or zirconium nitride bottom layer and a transparent silicon-containing polymer or silicon dioxide top layer were grown in a high-density microwave electron cyclotron resonance discharge for protective or decorative coating application. The grown multilayer coatings had gold coloring and good film thickness. Advisors/Committee Members: Mantei, Dr. Thomas.

Keywords: PECVD, ECR, Multilayer Coating, Silicon Dioxide, Silicon Nitride, Silicon-Containing Polymer, TiN Thin Film, ZrN Thin Films, CrN Thin Films, Ge Thin Film, ASTM B117, and DLI

16. Xia, Ping. Adhesive functions in fibronectin's alternatively-spliced ED(a) segment.

Degree: Doctor of Philosophy, Molecular Biology and Microbiology, 1996, Case Western Reserve University

► EDa (EIIIA) is an alternatively-spliced type III homology repeat present in cellular… (more)

▼ EDa (EIIIA) is an alternatively-spliced type III homology repeat present in cellular fibronectins (cFNs) but not in plasma fibronectin (pFN). Potential adhesion-promoting activity was investigated for EDa and its two neighboring repeats III11 and III12. Recombinant protein corresponding to EDa alone promoted Balb/c 3T3 cell attachment, as did neighboring repeats III11 and III12 when tested as single repeats. Activities were even higher for recombinant proteins containing two or three repeats. While EDa alone exhibited 40-60% of the attachment activity of human pFN depending upon cell type, EDa with both neighboring repeats displayed 70-90% of pFN activity. Besides attachment, the recombinant substrata also supported limited cell spreading. 3T3 cells on the EDa substratum displayed round cell bodies with filopodia contacting the substratum. Cells on III11-EDa-III12 displayed spindle-shaped cell bodies and pseudopods in contact with the substratum. The two-repeat molecule of III11-III12 gave an intermediate response. Moreover, adhesion activities towards these recombinant proteins were oncogene-regulated: comple tely abrogated by two different ras oncogenes, unaffected by the sis oncogene, and elevated by the src oncogene aFunctional complementarity was noted between EDa recombinant molecule and pFN. Co-coating substrata with EDa and a suboptimal concentration of pFN led to increased attachment and extensive spreading of v-src-transformed 3T3 cells relative to that found on substrata of suboptimal pFN or EDa alone. This complementarity requires as little as 1 μg/ml EDa in the adsorbing mixture and displays sequence specificity for only EDa (i.e., III11 or III12 was without effect.). Furthermore, stress fibers and focal contacts were inducible on the EDa:PFN mixture, suggesting the full adhesion-promoting competence of the heterologous substrata aSynergy in promoting post-attachment adhesion responses among III11, EDa and III12 was also observed. This conclusion is supported by two lines of evidence: (a) spreading on two-repeat molecules was better than spreading on single-repeat molecules, and (b) only the three-repeat molecule was competent for inducing stress fibers and focal adhesions. Experimental evidence indicated that glycosaminoglycans did not participate in these adhesion processes; neither did β1-containing integrins. Affinity chromatography was employed to isolate the putative receptor(s) to no avail. These studies reveal a new adhesion promoting activity in fibronectin molecules whose function is more effectively presented by cFNs than pFN, which may indicate the advantage of cFNs in various physiological and pathological conditions where expression of EDa sequence is elevated. Advisors/Committee Members: Culp, Lloyd A.

Subjects: Biology, Cell

Keywords: Fibronectin's alternatively-spliced ED(a) segment

17. Xia, Qing. Online Monitoring of Aerobic Denitrification of Pseudomonas Aeruginosa by NAD(P)H Fluorescence.

Degree: Master of Science, Chemical Engineering, 2006, University of Akron

► In cystic fibrosis airway infection, Pseudomonas aeruginosa forms microaerobic biofilm and undergoes… (more)

▼ In cystic fibrosis airway infection, Pseudomonas aeruginosa forms microaerobic biofilm and undergoes significant physiological changes. It is important to understand the bacterium’s metabolism at microaerobic conditions. Continuous cultures of P. aeruginosa (ATCC 9027) maintained at different dissolved oxygen concentrations (DO) and three different dilution rates (D) were studied for the effects of DO and D on various culture properties, especially on aerobic respiration and denitrification. The DO was varied from 0 mg/L (completely anoxic condition) to 2.2 mg/L, and measured with optical sensors that could accurately determine very low DO based on oxygen-quenched luminescence. The studied dilution rates were 0.026 h-1, 0.06 h-1 and 0.13 h-1. The strain was found to perform aerobic denitrification; while the specific nitrate and nitrite reduction rates decreased with increasing DO, denitrification persisted even at relatively high DO levels (1-2.2 mg/L) at different D. In the presence of nitrate, the Monod constant for DO (i.e., the critical DO at which the specific oxygen uptake rate (OUR) is half of the maximum rate) was practically zero (< 0.001 mg/L) for this P. aeruginosa strain. Aerobic denitrification appeared to function as an electron-accepting mechanism supplementary or competitive to aerobic respiration. The shift of culture’s respiratory mechanism was also clearly detected with a fluorometer targeting at intracellular NAD(P)H, i.e., the reduced coenzymes nicotinamide adenine dinucleotides (phosphate). Comparatively, the NAD(P)H fluorescence was highest at the anoxic, denitrifying condition (NFUDN), lowest at fully aerobic conditions (NFUOX), and intermediate fluorescence (NFU) at conditions where both denitrification and aerobic respiration occurred. Representing a quantitative measure of the culture’s “fractional approach” to the fully denitrifying state, the normalized fractions (NFU - NFUOX)/(NFUDN - NFUOX) were correlated with the calculated fractions of electrons accepted by denitrification. The denitrification-accepted fractions of electrons increased with the NFU fractions: the increases were gradual at larger DO levels (DO ≥ d 0.1 mg/L), but much sharper at lower DO at three different dilution rates. The fluorescence fraction changed more rapidly than the electron fraction at very low DO levels (< 0.001 mg/L). The results demonstrated that online NAD(P)H fluorescence was a feasible technique for effective monitoring and quantitative description of the microaerobic state of microorganisms. Advisors/Committee Members: Ju, Lu-Kwang.

18. Xia, Shijing. Experimental and Computational Studies for Various Organic Systems.

Degree: Doctor of Philosophy, Chemistry, 2008, Ohio State University

► The electronic properties and the thermodynamic preferences for O2 addition to various… (more)

▼ The electronic properties and the thermodynamic preferences for O2 addition to various tetrathiatriarylmethyl (TAM)-type triarylmethyl (trityl) radicals were experimentally and theoretically investigated. The radicals' stability in the presence of O2 and biological milieu was also experimentally assessed. Results showed that H substitution on the aromatic ring affects the trityl radical's stability and may lead to substitution reactions in cellular systems. We proposed that this degradation process involves an arylperoxyl radical that can further decompose to alcohol or quinone products. Computational approaches were also being used to search for spin probes with improved stability and enhanced chemical and biological properties. A signature absorbance at 392 nm, which is generated from acetonitrile solutions of N-hydroxypyridin-2-thione in the presence of trans-stilbene, was used in competitive laser flash photolysis (LFP) experiments to determine rate constants of reactions for hydroxyl radical with sixteen different benzene derivatives. Structure-reactivity relationships for these reactions were derived. Computational studies were employed to reveal the details of these reactions. The tautomerism and photochemistry of N-hydroxypyridones (NHPs) and N-hydroxy-pyridinethiones (NHPTs) were also studied theoretically in order to find some potential radical precursors or probes for hydroxyl radical reactions with aromatics. To avoid the problems typically encountered in the measurement of rate constants of superoxide radical trapping by nitrones, a more straightforward approach, stopped-flow UV methodology, has been developed by using KO2 as a direct source of superoxide radical. The absolute rate constants for the reactions of superoxide radical anion with five different spin traps were measured experimentally. The conformational and IR spectroscopic studies of several novel capsules were studied computationally. The theoretical data rationalized the experimental results, and demonstrated, along with experimental data, that these compounds have a tendency to associate intramolecularly. The conformational dynamics and thermodynamics of a series of monovalent ureas, the synthetic divalent urea and its dimer were computationally studied using the B3LYP/6-31+G** level of theory which was validated to be a suitable method to study this system. Theoretical studies were also employed to study the radical-addition reactions of benzene with 13 radicals as well as regio- and diastereo-selectivity in the dimethyl dioxirane (DMDO) mediated epoxidation of carbohydrate-based oxepines. Advisors/Committee Members: Hadad, Christopher.

Subjects: Chemistry

Keywords: computational; experimental; radical; trityl; hydroxyl; superoxide; oxepine; urea; capsule

19. Xia, Yining. Farrell-Tate cohomology of the mapping class group.

Degree: Doctor of Philosophy, Mathematics, 1990, Ohio State University

Advisors/Committee Members: Glover, Henry.

20. Xie, Chao. Singularities in the Unphysical Complex Plane for Deep Water Waves.

Degree: Doctor of Philosophy, Mathematics, 2009, Ohio State University

► Two-dimensional free surface flows may be formulated through boundary integrals which allows… (more)

▼ Two-dimensional free surface flows may be formulated through boundary integrals which allows analytic continuation in the unphysical complex plane. For two dimensional water waves, Tanveer showed that the only form of singularity in the unphysical plane is of the square-root type. One may wonder what influence these singularities may have on the behavior of water waves. This thesis resolves some of these questions by tracking singularities in the unphysical domain and relating their close approach to the real axis with wave breaking. The main result is the direct verification of Tanveer’s singularity result. A boundary integral technique is used to simulate deep water wave motion. A spectral procedure is used to form-fit the Fourier spectrum of the curvature of the wave profile to a prescribed asymptotic expression. The form-fit provides information on the power and location of the closest singularity to the real axis. The power of the curvature singularities is found to be -3/2 when the curvature is expressed as a function of the Lagrangian variable. This singularity is associated with a pole singularity in the complex arclength plane, and is not an artifact of the parametrization. The singularity approaches the real axis when a plunging breaker occurs. For nonbreaking waves, the singularity wanders above some level in the unphysical plane. It is then established that this curvature singularity is theoretically equivalent to Tanveer’s one-half power singularity. When the surface elevation is viewed as a function of horizontal distance, a different type of singularity arises. It is a square root type singularity that takes the form of a breaking wave when it reaches the real axis of the horizontal coordinate. Nonlinear interactions among various wavelengths are considered important in random ocean waves. A particularly important nonlinear interaction is the Benjamin-Feir instability. For moderate initial amplitudes, the end-state of this instability is either wave breaking or the Fermi-Pasta-Ulam recurrence. Clearly, singularities in the unphysical domain will play a role. Starting with initial conditions that contain several singularities away from the real axis, their trajectories are studied. When breaking occurs, results show that it is one of the crests in the wave train that breaks like a plunging breaker while others remain moderately flat. One of the singularities moves close to the real axis while the other singularities stay far away. When recurrence occurs, evidence indicates that the closest singularity remains far away from the real axis for all time. The hope and the possibility is that a study of singularities in Benjamin-Feir instability may lead to insight into nonlinear wave interactions in general. Advisors/Committee Members: Baker, Gregory R.

Subjects: Fluid dynamics; Mathematics

Keywords: singularities; unphysical complex plane; water waves

21. Xie, Di. Exploring organizational learning culture, job satisfaction, motivation to learn, organizational commitment, and internal service quality in a sport organization.

Degree: Doctor of Philosophy, Physical Activity and Educational Services, 2005, Ohio State University

► Service quality plays an essential role in customer satisfaction, customer retention, customer… (more)

▼ Service quality plays an essential role in customer satisfaction, customer retention, customer loyalty, and profits (Cronin and Taylor, 1992; Schneider and Bowen, 1995). Previous research studies have examined factors that influence external customers’ perceived service quality in various fields (Carman, 1990; Cronin and Taylor, 1992; Finn and Lamb, 1991; Mangold and Babakus, 1991), but relatively few studies have focused on which factors influence employees’ service behavior and how employees perceive the way service provided by co-workers affects their own service delivery (e.g., Bitner, Booms, and Mohr, 1994). This study examines six factors that influence employees’ internal service quality level in a public sport organization in China through testing six hypotheses. The six factors are organizational learning culture, job satisfaction, motivation to learn, affective organizational commitment, continuance organizational commitment, and normative organizational commitment. A total of 370 questionnaires were distributed to employees in the State Sport General Administration of China (SSGAC). Two hundred and ninety-eight were returned, of which 6 were discarded because of missing data. Therefore, the number of usable questionnaires was 292 and the response rate was 80.5%. Correlation analysis indicated that five of the six hypotheses were supported. Hypothesis five, in which there is a negative relationship between continuance organizational commitment and internal service quality, was rejected. Hierarchical research analysis showed that motivation to learn and organizational learning culture played significant roles in predicting the dependent variable, internal service quality compared with other independent variables. Motivation to learn uniquely explained 12% and organizational learning culture uniquely explained 5% of the variance of internal service quality when the effects of the other independent variables were removed. This study has implications for human resource managers and advances the knowledge base of internal service quality in the field of sport management. Advisors/Committee Members: Fink, Janet S.

Subjects: Education, Physical

Keywords: service; service quality; organizational learning culture; satisfaction; motivation; commitment

22. Xie, Dong. Personality factors as cultural specific predictors of anxiety among mainland Chinese and Caucasian American college students.

Degree: Doctor of Philosophy, Psychology, 2004, Ohio State University

► The present study investigated the cultural specificity of a number of personality… (more)

▼ The present study investigated the cultural specificity of a number of personality constructs in predicting anxiety across 324 Mainland Chinese and 333 Caucasian American college students. The dependent variables were state and trait anxiety, and social anxiety. The personality constructs that were selected and hypothesized to be cultural-specific predictors were (a) harmony, face, family orientation, modernization, and Ah-Q mentality (Defensiveness), (b) membership, private, public, and identity collective self-esteem, (c) independent and interdependent self construal, and (d) self-oriented, other-oriented, and socially prescribe perfectionism. On between group comparisons, the results indicated that Chinese students scored higher on trait anxiety and social anxiety than Caucasian American students, with the largest effect size on social avoidance. The two groups did not differ on state anxiety. On the Chinese personality constructs, Chinese students scored higher on harmony, family orientation, and modernity. On collective self-esteem, Chinese students scored higher on public collective self-esteem but lower on membership, private, and identity collective self-esteem than Caucasian students. On self-construal, Chinese students scored higher on interdependent self-construal but lower on independent self-construal. Chinese students also scored lower on self-oriented and other-oriented perfectionism. With respect to within-group relationships, socially prescribed perfectionism was a stronger predictor of trait anxiety for Caucasian students and a stronger predictor of social anxiety for Chinese students. Self-oriented perfectionism only predicted anxiety for Caucasian students but in a negative direction. Independent self-construal predicted anxiety better for Caucasian students than for Chinese students. For collective self-esteem, membership collective self-esteem was a stronger negative predictor of anxiety for Chinese. For the selected Chinese personality constructs, harmony only predicted social avoidance positively for Chinese students. Interestingly, face was a strong predictor of almost all the anxiety measures for Caucasian students, but it did not predict any of the anxiety measures for Chinese students. These results were discussed in terms of cultural variations that reflect the influences of general social-cultural factors on the self. A differential and dynamic perspective was recommended for future research on cross-cultural relevance of personality constructs. Implications regarding counseling were also discussed in terms of providing more culturally responsive treatments of anxiety problems among college students. Advisors/Committee Members: Leong, Frederick.

23. Xie, Fang. Neuregulin Signaling and GABAA Receptor Expression in Cerebellar Granule Neurons.

Degree: Doctor of Philosophy, Pharmacology, 2006, Case Western Reserve University

► The gamma-aminobutyric acid receptor A (GABAA-R) mediates the effects of GABA, the… (more)

▼ The gamma-aminobutyric acid receptor A (GABAA-R) mediates the effects of GABA, the major inhibitory neurotransmitter in the CNS. The beta subunit of this receptor is required to confer sensitivity to GABA and thus is important for GABAA-R function. However, little is known about the regulation of this subunit in CNS. Recent studies demonstrated that neuregulin-1 (NRG), a growth and differentiation factor, selectively induces the expression of the GABAA-R beta subunit in cerebellar granule neurons. The goal of my studies has been to identify the signaling and regulatory mechanism of NRG’s effects on beta subunit expression in cerebellar granule neurons in culture. These studies have focused on the effect of NRG at the plasma membrane, its intracellular actions, and its effects in the nucleus. Our findings demonstrate that the effects of NRG on beta2 subunit polypeptide expression require activation of the ErbB4 receptor tyrosine kinase. The NRG-induced activation of ErbB4 stimulates the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3-K) and cyclin-dependent kinase-5(cdk5) pathways. All three pathways are required to mediate the effects of NRG on GABAA receptor subunit expression in cerebellar granule neurons. Our results show that postsynaptic density protein 95 (PSD-95), a scaffolding protein, facilitates NRG-induced GABAA receptor beta2 subunit expression through its association with ErbB4. In addition, cdk5 activation enhances PSD-95 phosphorylation, which promotes ErbB4-PSD-95 interaction. These studies demonstrate that NRG’s effect on GABAA receptor beta2 subunit are enhanced by recruiting the participation of proteins involved in regulating synaptic plasticity. Finally, initial studies have identified transcription factors that are downstream of the NRG-activated signaling cascades that are involved in GABAA receptor beta2 subunit expression. We found that early growth response 1 (Egr-1) is rapidly induced by NRG and lies downstream of NRG-activated MAPK and cdk5 pathways. Moreover, blockade of Egr-1 level attenuated NRG-induced GABAA receptor beta2 subunit expression. These findings suggest that Egr-1 is at least partially responsible for GABAA receptor beta2 subunit induction by NRG. The three parts of the thesis research provide new knowledge about the molecular mechanism of NRG signaling in GABAA receptor beta2 subunit expression in cerebellar granule neurons. Advisors/Committee Members: Siegel, Ruth E.

Keywords: Neuregulin; ErbB receptors; GABAA receptor; Signaling; PSD-95; Egr-1; Cerebellum

24. Xie, Fei. De Novo Design of Metalloproteins with Variant Hydrophobic Cores.

Degree: Doctor of Philosophy (Ph.D.), Photochemical Sciences, 2009, Bowling Green State University

► This work studies a series of related de novo designed luminescent Cu(I)… (more)

Subjects: Chemistry

Keywords: De novo; Metalloprotein; Copper

25. Xie, Han. Source apportionment of particulate matter 2.5 in Southeast Ohio.

Degree: Master of Science (MS), Chemical Engineering (Engineering), 2002, Ohio University

Source apportionment of particulate matter 2.5 in Southeast Ohio. Advisors/Committee Members: Young, Valerie L.

Subjects: Engineering, Chemical

Keywords: Source Apportionment; Particulate Matter 2.5; Southeast Ohio

26. Xie, Hang. Studies on sorting networks and expanders.

Degree: Master of Science (MS), Electrical Engineering (Engineering), 1998, Ohio University

► This thesis examines the explicit construction of Paterson's algorithm. In an attempt… (more)

▼ This thesis examines the explicit construction of Paterson's algorithm. In an attempt to make the algorithm more easily understood, we give the precise definitions for ε-halvers and separators, detailed explanations about some conclusions in Paterson's paper, and the pseudocode for Paterson's algorithm. The idea in Paterson's algorithm is to take an approximate partition of elements, which can be achieved in only a constant number of comparator levels, and then introduce some error-recovery structure into the sorting scheme. In Paterson's algorithm, the approximate partition is implemented with separators. The depth of the Paterson's algorithm is dependent on the depth and parameters of the separator, which is determined by the algorithm that implements it and the depth of an ε-halver. An ε-halver can be constructed through expanders using constant depth. We introduces expanders and the major research results in the area. Ramanujan graphs, which are asymptotically optimal in making the second- eigen-value as small as possible, are used to construct ε-halves. We analyze the construction of ε-halvers through matching in regular graphs. We give a very simple method to construct a balanced regular expander. The second largest eigenvalue of a graph is then used to analyze the expansion of a graph. We analyze the performances of Kahale's result and Tanner's result and point out that the Kahale's result is only effective for very small subsets of the vertices. We adopt the Tanner's result and calculate the depth of the associated ε-halver. We analyze a new kind of separator and give its depth. This separator can achieve fbetter separation without increasing its depth. Finally, we use all our results to analyze the depth of Paterson's algorithm. Through our construction, we achieve sorting networks in less than depth of 947512 log nwith the original separator and depth less than 765544 log nwith the new kind of separator. Advisors/Committee Members: Juedes, David W.

Keywords: Paterson's algorithm; error-recovery structure; [epsilon]-halver

27. Xie, Kun. Studies of E. Coli YIDC insertase during membrane protein insertion.

Degree: Doctor of Philosophy, Molecular, Cellular, and Developmental Biology, 2007, Ohio State University

► In bacteria, it has been widely recognized that SecYEG translocon is the… (more)

Subjects: Biology, Cell

28. Xie, Li. Comparative Studies on molecular mechanisms utilized by HTLV-1 and HTLV-2 in viral replication and induction of T-cell transformation.

Degree: Doctor of Philosophy, Veterinary Biosciences, 2005, Ohio State University

► Human T-cell leukemia virus (HTLV)-1 and HTLV-2 are closely related human retroviruses… (more)

▼ Human T-cell leukemia virus (HTLV)-1 and HTLV-2 are closely related human retroviruses that have similar genetic organization and biological properties. However, they display distinct pathogenicity. HTLV-1 has been identified as a causal agent for two human diseases, adult T-cell leukemia (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas HTLV-2 appears much less pathogenic without conclusive disease association. In order to understand the distinct pathogenicity between HTLV-1 and HTLV-2, studies in this dissertation manipulate viral elements in the context of full-length proviral clones, analyze their function and mechanism of action in a system closely mimicking in vivo HTLV infection, and focus on the unique strategies employed by HTLV-1 and/or HTLV-2 to replicate and induce cellular transformation, the initial stage of HTLV oncogenesis. First, our results indicate that the PDZ domain binding motif (PBM) uniquely present in HTLV-1 viral oncoprotein Tax, but absent in HTLV-2 Tax, plays a key role in HTLV-1-induced cell proliferation and genetic instability in vitro and facilitate viral spread and persistence in vivo. Next, we identified a major viral determinant of HTLV T-cell transformation tropism, the envelope, using recombinant proviral clones between HTLV-1 and HTLV-2. Lastly, viral trans-regulatory protein Rex facilitates efficient viral replication and its functional activity is regulated by phosphorylation events. A c-terminal phosphorylation domain (CTPD) has been previously described in HTLV-2 Rex. Here mutational analyses indicate that either introducing phosphomimetic amino acids into the CTPD or deletion of the CTPD can lock Rex in active state. However, HTLV-2 with Rex phosphomimetic mutants, but not HTLV-2 with Rex CTPD deletion mutants, can efficiently infect and stimulate cellular proliferation and immortalization of human primary T-cell, implying the critical role of the Rex CTPD in HTLV-2 life cycle. Overall, our studies provide important insight into the distinct molecular pathogenesis of HTLV-1 and HTLV-2. Advisors/Committee Members: Green, Patrick.

Subjects: Biology, Veterinary Science

Keywords: HTLV, viral replication, T-cell transformation, Tax, Env, Rex

29. Xie, Mian. Calcium Channel Beta Subunits and SCA6-Type Calcium Channel Alpha Subunits C-Termini Regulate Targeting and Function of Presynaptic Calcium Channels in Hippocampal Neurons.

Degree: Doctor of Philosophy, Neurosciences, 2008, Case Western Reserve University

► Ca2+ channel β subunits determine the transport and physiological properties of high… (more)

▼ Ca2+ channel β subunits determine the transport and physiological properties of high voltage activated Ca2+ channel complexes, and the poly-glutamination within the C-terminus (CT) of the P/Q-type Ca2+ channel α subunit is linked with Spinocerebellar ataxia type 6 (SCA6). In the first part of this study we analyzed the distribution of the Cavβ subunit family members in hippocampal neurons and correlated their synaptic distribution with their involvement in transmitter release. We found that exogenously expressed Cavβ4b and Cavβ2a subunits distribute in clusters and localize to synapses, while Cavβ1b and Cavβ3 are homogenously distributed. According to their localization Cavβ2a and 4b subunits modulate the synaptic plasticity of autaptic hippocampal neurons, i.e. Cavβ2a induces depression, while Cavβ4b induces paired-pulse facilitation followed by synaptic depression during longer stimuli trains. The induction of paired-pulse facilitation by Cavβ4b is correlated with a reduction in the release probability and cooperativity of the transmitter release. These results suggest that Cavβ subunits determine the gating properties of the presynaptic Ca2+ channels within the presynaptic terminal in a subunit specific manner and may be involved in the organization of the Ca2+ channel relative to the release machinery. We also examined whether the poly-glutamination of P/Q-type channel CT can increase the channel stability and induce a gradual accumulation of a CT degradation product. We demonstrated that the poly-glutaminated CT degradation product distributes in cytoplasmic aggregates in cultured neurons as found in SCA6 patients and has drastic physiological effects on synaptic function and synapse assembly. Our results show that the CTs induce a change in the Ca2+ dependence of transmitter release correlated with a reduced vesicular release probability, which causes synaptic depression during repetitive high frequency stimulations. The CT containing the SCA6 mutation also caused an increase in the number of synapses. Our results predict that CT degradation products derived from the P/Q-type channels in SCA6 patients would reduce synaptic strength in each synaptic terminal, but increased the overall synapse formation per neuron. The increased synapse formation may give a mechanistic explanation for the survival of nucleo-olivary pathways in SCA6, which is not observed in other SCAs. Advisors/Committee Members: Herlitze, Stefan.

Subjects: Biology, Neuroscience

Keywords: Calcium channel beta subunit; Spinocerebellar ataxia type 6; Hippocampal neuron; Electrophysiology

30. Xie, Mingsheng. The regulation and functional significance of phospholipase D in HL-60 cells.

Degree: Doctor of Philosophy, Physiology and Biophysics, 1992, Case Western Reserve University

► In the present work, I have characterized the regulation and functional significance… (more)

▼ In the present work, I have characterized the regulation and functional significance of the novel phospholipase D (PLD)-based signaling system utilizing HL-60 human promyelocytic leukemic cell line as a model system. In undifferentiated HL-60 cells, neither extracellular ATP (acting via P2-purinergic receptors) nor formylated peptides (FMLP) elicited significant PLD activation or increased secretion. After induction of granulocytic differentiation by dibutyryl cAMP, both ATP and FMLP induced large increases in azurophilic secretion and corresponding increases in PLD activity. Phorbol ester-induced PLD activity also increased significantly. In fully differentiated cells, FMLP was twice as efficacious as ATP in stimulating both secretion and PLD activity. FMLP- and ATP-stimulated PLD activity was significantly attenuated by pertussis toxin pretreatment. In particular, a strong correlation between PLD activation and exocytotic response was demonstrated in this intact cell study, suggesting the critical role of the PLD-based signaling pathway in regulation of secretion and other phagocytic functions. The regulation of PLD activity was further characterized in electropermeabilized HL-60 granulocytes and isolated membranes. Incubation of electropermeabilized cells with no n-hydrolyzable GTP analogs (GTP (S) and GMP-PNP) induced a sustained (near-linear for up to 60 minutes) stimulation of PLD activity. The ability of GTP (S) to stimulate this PLD activity was Mg2+-dependent and was inhibited by GDP and its nonhydrolyzable analogue, GDP (S). Inclusion of MgATP (ge0.1 mM), but not other nucleoside triphosphates, also induced a large potentiation of GTP (S) -dependent PLD activation. Significantly, this effect of ATP was not mimicked by AMP-PCP, a nonhydrolyzable ATP analog. Rather, AMP-PCP inhibited both basal and ATP-potentiated GTP (S) -dependent PLD activity. Membranes prepared from intact HL-60 granulocytes exhibited a low but detectable PLD activity. In membranes derived from beta-escin-permeabilized, GTP (S) -treated cells, and 8- to 10-fold increase in an ATP-dependent PLD activity was observed. This ATP-dependent activity was very stable and retained even after extensive washing. In the absence of ATP, the membrane-associated PLD was still catalytically inactive; maximal catalytic activity required millimolar levels of ATP and Mg2+. PLD activities in both the permeable cells and derived membranes could be observed even at very low (<1 nM) (Ca2+) although the activity was potentiated by micromolar Ca2+. Taken together, these results demonstrate that PLD activation can be clearly dissociated into two separable steps: a GTP-dependent process mediated by a GTP-binding regulatory protein and a subsequent ATP-dependent step mediated by a ATP-utilizing protein (a protein kinase?). Ca2+ also plays a modulatory role in the PLD regulation. Advisors/Committee Members: Dubyak, George R.

Keywords: regulation functional significance phospholipase D HL-60 cells

[1] [2] [3] [4]