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Weng, Yi-LanThe Cytoplasmic Adaptor Protein Caskin Participates in LAR-Mediated Motor Axon Guidance
Doctor of Philosophy, Case Western Reserve University, 2011, Neurosciences

LAR (leukocyte common-antigen-related) family receptors, members of the receptor protein tyrosine phosphatase (RPTP) superfamily, are important in the formation, plasticity, and regeneration of neuronal circuits. Considerable progress has been made in identifying LAR-interacting proteins, which form the basis for the molecular relays that underly LAR function. However, our understanding of intracellular LAR signaling in axon guidance remains fragmentary. In my thesis work, I identified a novel LAR-interacting protein, Caskin, and elucidated its role in motor axon guidance in the developing Drosophila embryo.

Drosophila caskin encodes a neuronal scaffolding protein containing two SAM domains and a conserved C-terminal region. Pan-neuronal caskin overexpression leads to vast axon guidance defects in both the CNS and in motor axons, implicating Caskin as a regulator of growth cone behavior. To define Caskin’s function in axon guidance, ethyl methanesulfonate (EMS)-induced caskin loss-of-function (LOF) mutants were generated and characterized. caskin LOF mutants exhibit motor axon guidance defects identical to Dlar LOF mutants. Further biochemical and genetic examination demonstrated Caskin interacts with Dlar via its first N-terminal SAM domain and relays LAR signaling via its conserved C-terminal region. I examined downstream signaling of Caskin in order to further understand how LAR signaling regulates the cytoskeleton. I conducted a yeast two-hybrid screen to search for potential binding partners that act through interaction with Caskin’s C-terminus. Through this screen I found several novel Caskin-interacting proteins, some of which are known to regulate the cytoskeleton.

Protein phosphorylation is important in motor axon guidance. An attractive model was previously proposed in which a common substrate, regulated by Abl kinase and LAR phosphatase, can provoke different axonal responses. Interestingly, I found that Caskin can become tyrosine phosphorylated in an Abl kinase-dependent manner and that Caskin and Abl interact genetically in the regulation of motor axon guidance. Further studies will seek to determine whether tyrosine phosphorylation is important in Caskin’s function.

Recently, PTPsigma, a LAR family member in vertebrates, was identified as a receptor for CSPGs, which are molecules that inhibit axonal regeneration. I found that interactions between Caskin and LAR are conserved in vertebrates; mouse Caskin 2 is capable of binding to LAR and PTPsigma. Taken together, my thesis work reveals a function for Caskin in LAR-mediated motor axon guidance and identifies a potential molecular target for intervention following nervous system injury.

Committee:

Gary Landreth (Committee Chair); Heather Broihier (Advisor); Lynn Landmesser (Committee Member); Susann Brady-Kalnay (Committee Member); Jocelyn McDonald (Committee Member)

Subjects:

Neurosciences

Keywords:

Caskin; LAR; Dlar; PTPsigma; axon guidance; motor axon guidance; mouse Caskin1; mouse Caskin2

Vassos, Sonya ThomasA study of attitudes toward the guidance department and the college-counseling process as a result of employing computer-assisted college selection /
Doctor of Philosophy, The Ohio State University, 1971, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Vocational guidance;Vocational guidance

Patel, Monica RajivParental Attitudes Toward Advanced Behavior Guidance Techniques used in Pediatric Dentistry
Master of Science, The Ohio State University, 2012, Dentistry
Purpose: To reexamine parental attitudes toward advanced behavior management techniques currently used in pediatric dentistry and determine how factors such as cost, urgency and amount of treatment influence parental acceptability. Methods: Parents bringing children for routine dental care viewed previously validated videotaped clinical vignettes of four advanced behavior guidance techniques: passive restraint, active restraint, general anesthesia and oral premedication (sedation). The study was conducted at both a children’s hospital setting and a suburban private pediatric dentistry office. Parents rated overall acceptance of the techniques, as well as acceptance under specified conditions using a visual analogue scale. Results: One hundred five parents completed the survey; fifty-five from children’s hospital and fifty from private practice. Overall, oral premedication (sedation) was rated as the most acceptable technique, followed (in order of decreasing acceptance) by general anesthesia, active restraint and passive restraint. As urgency, convenience and previous experience increased, parental acceptability of the technique increased. As cost of treatment increased, acceptability decreased. Acceptability rankings between the children’s hospital group and private practice group differed, as did the following demographic variables: insurance, income and race. Conclusions: The hierarchy of acceptability is changing with increasing approval of pharmacological management and decreasing approval of physical management. The healthcare delivery system, urgency, convenience, previous experience and cost all influence parental acceptability.

Committee:

Dennis McTigue, DDS, MS (Advisor); Sarat Thikkurissy, DDS, MS (Committee Member); Henry Fields, DDS, MS, MSD (Committee Member)

Subjects:

Dentistry

Keywords:

behavior guidance; parental acceptance of behavior guidance; behavior management; behavior management techniques

Miller, Michael E.The development of an improved low cost machine vision system for robotic guidance and manipulation of randomly oriented, straight edged objects
Master of Science (MS), Ohio University, 1989, Industrial and Manufacturing Systems Engineering (Engineering)

An improved feature geometry based, low-cost, machine vision software system was developed by conducting a statistical reliability study of a previously developed system, evaluating alternative methods of completing the machine vision process, developing more effective edge linking and corner detection algorithms and implementing these new algorithms into a more efficient and reliable version of the existing machine vision software. The resulting system utilizes the same machine vision hardware that was utilized by the previous machine vision software system. This hardware includes an Apple IIe microcomputer, that serves as the host computer for the machine vision system; a 4K frame buffer, that is used to capture designated areas of the image obtained by the image sensor; a General Electric TN2500 Digital Camera, that serves as the sensor; a monitor and a Microbot robotic arm that is used to pick up and move an object for demonstration purposes. The resulting system is capable of recognizing a flat surfaced, randomly positioned rectangular object that contrasts well with its background within about 11 seconds with an overall reliability of about 80%. This system is equipped with an interactive user interface that allows the system to be operated and maintained by a person with very little knowledge of computers and machine vision. The interface gives the user the capability of changing parameters that affect how the machine vision system operates. These features combined with the system’s ability to interactively output the data that is generated during the system’s operation makes this system a valuable teaching tool to demonstrate the application of machine vision to students.

Committee:

Helmut Zwahlen (Advisor)

Subjects:

Engineering, Industrial

Keywords:

Low Cost Machine Vision System; Robotic Guidance; Manipulation Randomly Oriented; Straight Edged Objects

Yip, Pui-ChiuThe role of regional guidance in optimization: The guided evolutionary simulated annealing approach
Doctor of Philosophy, Case Western Reserve University, 1993, Electrical Engineering
An efficient global optimization technique should be guided and random enough to escape from local minima. All prior optimization techniques are either gradient-guided search techniques or local random search techniques. In this dissertation, we explore the idea of regional guidance in optimization. A new efficient and parallel optimization technique with regional guidance is developed. We call the technique “Guided Evolutionary Simulated Annealing” (GESA). It is a hybrid technique involving simulated Darwinian evolution and simulated annealing. It is regionally guided – it has a mechanism of measuring the chance of getting the global optimum in many different regions, and automatically focuses the search in regions with higher chances. The search is random in local regions so it provides a stochastic way of escaping from local minima. Simulation results for functional optimization and combinatorial optimization problems using the GESA algorithm are presented. Use of the GESA technique to train networks with arbitrary connections is described and reported in this dissertation. A new iterative growing technique for 3-layer networks is proposed. The use of the growing technique with the GESA algorithm to generate additional hidden nodes during the training process is described.

Committee:

Yoh-Han Pao (Advisor)

Keywords:

regional guidance optimization evolutionary simulated annealing

Yarletts, Alan JamesA study of a comprehensive career education program : effectiveness in third and fifth grades /
Doctor of Philosophy, The Ohio State University, 1983, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Vocational guidance;Vocational education;Third grade ;Fifth grade

Silverman, MitchellThe development of vocational choice and interests in mentally retarded children /
Doctor of Philosophy, The Ohio State University, 1968, Graduate School

Committee:

Not Provided (Other)

Subjects:

Psychology

Keywords:

Children with mental disabilities;Vocational guidance

Bartlett, Willis EdwardPsychological needs and vocational maturity of manpower trainees /
Doctor of Philosophy, The Ohio State University, 1968, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Personality;Vocational guidance

Durgin, Rodney W.A model for managing career guidance programs in secondary schools of Ohio /
Doctor of Philosophy, The Ohio State University, 1974, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Vocational education--Ohio;Vocational guidance--Ohio

Seitz, Larry AllanTowards a selection and admissions model: predicting academic success in veterinary school /
Doctor of Philosophy, The Ohio State University, 1973, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Veterinary medicine--Vocational guidance;Universities and colleges--Admission

McCormick, Roger DeanThe influence of dissimilar group guidance activities upon the vocational interests of eighth grade pupils /
Doctor of Philosophy, The Ohio State University, 1969, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Vocational guidance;Vocational education;Vocational interests

Bloss, Norman FloydThe relationship between enrollment in agricultural education and the vocational maturity of secondary school students.
Doctor of Philosophy, The Ohio State University, 1972, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Agricultural education;Vocational guidance

Stockum, Larry AllenA study of guidance controllers for homing missiles /
Doctor of Philosophy, The Ohio State University, 1974, Graduate School

Committee:

Not Provided (Other)

Subjects:

Engineering

Keywords:

Guided missiles--Guidance systems

Hoop, Alyssa NRho-Family GTPase Signaling in the Nervous System: An Analysis of the C. elegans RhoGEF UNC-73
Master of Science, University of Toledo, 2014, College of Natural Sciences and Mathematics
Rho-family GTPases regulate various neuronal signaling pathways that are critical for proper nervous system development and function. Defects in these signaling pathways can cause severe behavioral phenotypes including a reduction in cognitive and intellectual abilities in humans. RhoGEFs are critical activators of Rho-family GTPase pathways. UNC-73 is an evolutionarily conserved C. elegans RhoGEF that regulates cytoskeletal rearrangement during axon guidance and modulates neurotransmission to control locomotory behavior. unc-73 encodes multiple differentially expressed isoforms, some of which contain the putative lipid binding domain, Sec14, at their N-termini. This study is an examination of UNC-73 isoform function and localization, focusing on the role of the UNC-73 Sec14 domain in the nervous system. Transgenic UNC-73 Sec14 domain expression, independent of full-length UNC-73, is localized to punctate subcellular regions in the cell bodies that may coincide with the Golgi. The transgenic animals overexpressing the UNC-73 Sec14 domain exhibit uncoordinated locomotion similar to unc-73 RhoGEF1 mutants suggesting UNC-73(Sec14) overexpression alters endogenous UNC-73 localization and/or function. Animals overexpressing UNC-73(Sec14) also develop more slowly compared to wildtype, but this phenotype may result from interference with the function of other Sec14 domain-containing proteins. These data point to the possible importance of the Sec14 domain in nervous system function and protein localization. To further characterize UNC-73 function, the unc-73c1 expression pattern was examined and a potential UNC-73C1 interaction with the Rab11 binding protein FIP-3/4 was characterized in vitro. UNC-73C1 localizes to a subset of neurons, including sensory neurons and interneurons, but not motorneurons. UNC-73C1 expression in these neurons rescues the unc-73 lethargic movement phenotype, suggesting that the role of UNC-73 in regulating locomotion rate is in upstream modulatory neurons, not in the motorneurons. Together, these results give us a better understanding of how the RhoGEF, UNC-73, functions in the nervous system and suggest new avenues for further study of UNC-73 homologs in mammals.

Committee:

Robert Steven, PhD. (Advisor); Rafael Garcia-Mata, PhD. (Committee Member); John Plenefisch, PhD. (Committee Member)

Subjects:

Biology; Molecular Biology; Neurobiology; Neurosciences

Keywords:

UNC-73; nervous system; Rho-Family GTPases; C elegans; Sec14; Secretory pathway; neurotransmission; axon guidance

Glavin, Kevin W.The Role of Distinctiveness in Assessing Vocational Personality Types
PHD, Kent State University, 2009, College of Education, Health, and Human Services / Department of Adult, Counseling, Health and Vocational Education

The purpose of this study was to examine the distinctiveness of interest inventory scores. The researcher studied the difference between scores on the Self-Directed Search (SDS) in an effort to determine when a difference between two scores represents a significant and meaningful difference. Researchers commonly use the standard error of measurement (SEM) to determine confidence intervals for individuals’ true scores. The SEM for the SDS equals eight points, which means two scores must be separated by at least eight points to be considered distinct. Over time the SEM has become known as the “rule of eight”, and practitioners use it as a guideline for interpreting SDS results. However, researchers determined the SEM from a statistical formula, and no study has empirically examined this guideline. This study examined the distinctiveness of interest inventory scores by calculating the difference between individuals’ highest two SDS scores, while comparing congruence between two concurrent measures of vocational interest, both taken from the SDS.

SDS data was collected for 2397, (1497 female and 900 male), undergraduate students enrolled in the exploratory major at a large Midwestern university between 1996 and 2002. Primary-code distinction represented the absolute difference between the top two SDS scores. Expressed vocational interest and inventoried interest were compared to determine whether or not a congruent match existed between the two. Congruence results were grouped by level of primary-code distinction in an effort to determine when distinction scores represent a meaningful difference.

Descriptive statistics suggest a positive relationship exists between primary-code distinction and congruence. Furthermore, distinction scores of four points appear to distinguish between individuals’ top two SDS scores. Logistic regression confirmed the existence of a significant positive relationship between primary-code distinction and congruence, such that a one-point increase in primary-code distinction increases the likelihood of finding congruence between expressed and inventoried interests by 8%. Using these results, the researcher concluded that the “rule of eight” should be replaced with the “guideline of four”, and that test manuals and interpretative routines for practitioners be updated to reflect this distinction.

Committee:

Mark Savickas, PhD (Committee Chair); Jason McGlothlin, PhD (Committee Member); Mark Kretovics, PhD (Committee Member)

Subjects:

Academic Guidance Counseling; Psychology; Vocational Education

Keywords:

SDS; Career, Self-Directed Search; Holland; Vocation; Career Counseling; Counseling; Vocational Psychology, Distinctiveness; Rule of Eight; Career Guidance; Vocational Personality Types; Primary-Code Distinction; Guideline of Four

Miller, Crystal M.Mmp2 regulates the matrix molecule Faulty attraction to promote motor axon targeting in Drosophila
Doctor of Philosophy, Case Western Reserve University, 2010, Neurosciences

During development, motor axons must navigate to their correct muscle targets in order to correctly wire the nervous system. The repertoire of receptors and adhesion molecules expressed on individual axons, combined with the unique milieu of extracellular cues the nerve encounters on muscle and glia, allows each axon to reach its particular destination. However, as in other developmental paradigms, guidance cues are only one aspect of the regulatory mechanism of axon pathfinding. In this thesis, I demonstrate that both proteolysis and the regulation of growth factors by an extracellular matrix molecule combine to direct nerves to their targets.

Using Drosophila as a model system, I examined the role of the two fly matrix metalloproteinases (MMPs) in axon guidance. Misexpression of either Mmp1 or Mmp2 results in an increase in bundling of motor axons. In contrast, Mmp1 and Mmp2 mutants both display loosely bundled and frayed axons, indicating that both MMPs promote fasciculation during axon guidance. The catalytic domain of these proteases is necessary for this function, implying that they must act on a substrate to affect pathfinding.

A yeast two-hybrid screen identified the structural ECM molecule Faulty attraction (Frac) as an interaction partner and potential substrate for Mmp2. Frac is expressed in the embryonic mesoderm in the path of extending axons and adjacent to Mmp2-expressing exit glia. Both frac mutant embryos and embryos overexpressing frac phenocopy Mmp2 mutant guidance defects, indicating Frac also acts in axon guidance. Lastly, overexpression of Mmp2 results in smaller Frac fragments on Western blots and abrogates in vivo accumulation of Frac protein in embryos.

These data suggest that Mmp2 cleavage of Frac promotes fasciculation during guidance in the Drosophila embryo. Frac provides more than structural support to the ECM, also modulating the spatiotemporal concentrations of growth factors. At an even higher level of regulation, Mmp2 proteolysis controls the balance of full-length versus cleaved Frac. Similar elaborate mechanisms have been uncovered in other developmental processes and it seems likely that ECM molecules like Frac, controlled by post-translation modifications, may create multiple levels of regulation for seemingly simple signaling pathways in many physiological and pathological contexts.

Committee:

Dr. Lynn Landmesser, PhD (Committee Chair); Dr. Heather T Broihier, PhD (Advisor); Dr. Peter Harte, PhD (Committee Member); Dr. Susann Brady-Kalnay, PhD (Committee Member)

Subjects:

Genetics; Neurology

Keywords:

Drosophila; motor axon; guidance; fibrillin; matrix metalloproteinase

Bhattacharya, SumitA Real-Time Bi-Directional Global Positioning System Data Link Over Internet Protocol
Master of Science (MS), Ohio University, 2005, Electrical Engineering & Computer Science (Engineering and Technology)

This research focused on the development of a prototype real-time bi-directional Differential Global Positioning System (DGPS) wherein data was passed over a radio frequency (RF) link using Internet Protocol (IP). This development is unique in that it combines; a typical DGPS architecture, where DGPS correction data are sent from a ground reference station to a mobile user; remote measurements functions typically found in remote positioning/monitoring applications; and using an IP via an ethernet interface to apply at a wide variety of RF data link frequencies.

This project demonstrated a proof of concept for an enhanced data link that would use the ethernet interface to communicate with a wireless transceiver operating at 2.4 GHz, thus providing for high data rates and also supporting additional data e.g., weather imagery, voice over IP, etc. The proof of concept was successfully demonstrated in a laboratory in Stocker Center, Ohio University. The simplified set up of the data link allowed for communication between a reference station and a user over IP via the ethernet interface. The data link supports high accuracy position solution and remote positioning of the user by the ground reference station.

Committee:

Chris Bartone (Advisor)

Keywords:

communication; navigation; surveillance; data link; guidance; internet

Chen, LeiThe role of Cdc42 and Rac1 GTPases in mammalian forebrain development
PhD, University of Cincinnati, 2006, Medicine : Molecular and Developmental Biology
Rho family GTPases are key regulators of a variety of cell functions including actin cytoskeleton organization, gene transcription, cell cycle progression and vesicle trafficking. In the mammalian neuronal system the Rho family members Cdc42 and Rac1 have been suggested to play roles in neuronal morphogenesis and synaptic transmission in a body of literature that is derived by over-expression of dominant-negative or constitutive-active mutants in cell cultures or transgenic animals. To investigate the physiologic function of Cdc42 and Rac1 in mammalian neural development, we have applied a conditional gene targeting strategy by crossbreeding Foxg1-Cre gene targeted mice with Rac1 or Cdc42 gene floxed conditional strain to achieve the deletion of each gene specifically in the telencephalon. We found that Cdc42-deletion abolishes the polarity of neuroepithelial (NE) cells. Consequently, neural progenitors were scattered throughout the entire depth of the NE, and the Cdc42-deficient telencephalon failed to bulge or separate into two cerebral hemispheres resulting in holoprosencephaly. However, neither the midline expression of Sonic hedgehog nor the dorso-ventral patterning of the telencephalon was affected by Cdc42-deletion. These results indicate that Cdc42 has an essential role in establishing the apical-basal polarity of the telencephalic NE, which is needed for the expansion and bifurcation of cerebral hemispheres. In contrast to Cdc42 deletion, Rac1 deficiency in the forebrain does not affect the polarity of NE, but does cause a profound phenotype. The Rac1 deficient embryos exhibit defects in the midline commissural axon tract formation and the tangential migration of the olfactory and cortical interneurons. Unlike previous studies using dominant-negative mutants, deletion of Rac1 did not prevent axon outgrowth or radial migration of cortical projection neurons. Interestingly, the tangential migration was not affected by the ventral telencephalon SVZ-deletion of Rac1 in Dlx5/6-Cre/Rac1loxp/null mice. These results provide strong evidence that Rac1 is important in regulating axonal projection, but is dispensable for neuritogenesis per se. Furthermore, there appears a progenitor-specific requirement of Rac1 for the subsequent migration of ventral telencepahlon-derived interneurons. In summary, the collective results of the thesis studies suggest that Cdc42 and Rac1 have important but distinct roles during mammalian forebrain development.

Committee:

Yi Zheng (Advisor)

Keywords:

Rho GTPase; forebrain; development; neuritogenesis; axon guidance; migration; polarity; patterning; holoprosencephaly

Beechy, Atlee.A conceptual framework for guidance /
Doctor of Philosophy, The Ohio State University, 1958, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Counseling in secondary education;Vocational guidance

Powell, C. Randall.Correlates of career performance of 1962 MBA graduates impacting upon the career decisions of male students contemplating study toward the MBA degree /
Doctor of Philosophy, The Ohio State University, 1973, Graduate School

Committee:

Not Provided (Other)

Subjects:

Business Administration

Keywords:

Vocational guidance;Business education

Hampl, Steven PaulStress, personal and environmental resources, and strain in adult career counseling clients /
Doctor of Philosophy, The Ohio State University, 1987, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Vocational guidance;Stress

Smith, Keith CalhounA study of the stability of career choices of West Virginia ninth-grade students over a two-year period, 1972-1974 /
Doctor of Philosophy, The Ohio State University, 1977, Graduate School

Committee:

Not Provided (Other)

Subjects:

Education

Keywords:

Ninth grade;Ocational guidance

Suzuki, MakotoThe best imperative approach to deontic discourse
Doctor of Philosophy, The Ohio State University, 2007, Philosophy
How should we understand deontic statements, for example, "Ken ought to go to bed now"? Such a statement is different from a usual descriptive statement, such as "Ken is going to bed now." The ought statement is not confirmed by the observation that he is going to bed now. What is the meaning of a deontic statement, and what, if anything, makes a deontic statement correct or incorrect? Philosophers have been asking these questions. This dissertation proposes an unconventional approach to them: the best imperative approach. The best imperative approach takes the correctness or truth of a deontic statement, for example, "Ken ought to go to bed now", to be understood in terms of the bestness of a piece of advice (instruction, order, suggestion, or demand) in the imperative mood, such as "Ken, go to bed now." This relation explains why deontic statements are intuitively similar to imperatives, peculiarly action-guiding and conduct-coordinating in many contexts. In addition, given this relation, if we understand what makes certain imperatives the best, we can also know what makes the corresponding ought statements correct. What makes an imperative the best? The prescribed action must be most conducive to a certain end, and it must also be practicable. The dissertation thus seeks a theory of conduciveness and practicability, and considers its implications for the nature and evaluation of ought statements, for example, moral ought statements. The guiding methodological idea is that the theory should account for and systematize the practice of evaluating imperatives and ought statements and our intuitions about it. Among other things, it turns out that the correctness of ought statements varies with the context they are given, but there must be some reason for the addressees to comply with correct ought statements. Further, generally speaking, the action prescribed by an ought statement is not evaluated by itself; it is rather evaluated in combination with compliance with other prescriptions. In addition, there are two different ways of evaluating practicability, one of which concerns personalized action guidance, while the other of which concerns setting up shared standards for a certain type of agents.

Committee:

Justin D'Arms (Advisor)

Subjects:

Philosophy

Keywords:

imperative; ought; best; legitimacy; the point of an imperative; the point of an ought statement; the point of moral discourse; conduciveness and teleology; practicability; the risk of failure; ought and defect; action guidance; social coordination

Salgaonkar, Vasant AnilPassive Imaging and Measurements of Acoustic Cavitation during Ultrasound Ablation
PhD, University of Cincinnati, 2009, Engineering : Biomedical Engineering

Cavitation is known to affect therapeutic ultrasound applications such as tissue ablation, where it may complicate heat deposition and make treatment control difficult. In this thesis, acoustic emissions from cavitating bubbles are measured and imaged to serve as indicators of thermal ablation progress. Cavitational acoustic emissions were measured using a 1-MHz transducer during thermal ablation of excised bovine livers with a 32-element linear array (3.1 MHz, 0.8-1.4 MPa pressure amplitude). Broadband, subharmonic and low-frequency emissions consistent with inertial, stable and vaporous cavitation respectively were observed. Broadband (r = 0.848) and low-frequency (r = 0.747) emissions exhibited statistically significant linear correlations with coagulated tissue volumes. Statistical models based on multinomial logistic regression were implemented to predict tissue temperature based on measured cavitational emission signals.

To perform spatially sensitive measurements of cavitation activity, images were created from beamformed bubble emission signals received by a diagnostic imaging array. This method was called passive cavitation imaging. Analytic models for point spread functions were developed to test this imaging method. It was implemented on a 192-element linear array (7.5 MHz) and separate images of stable and inertial cavitation activity were created in free field and tissue media, with mm-level resolution along the array azimuth. Passive cavitation imaging techniques were used to record emissions during ablation of ex vivo bovine liver with 1.1-MHz (1984 W/cm2 focal intensity) focused ultrasound. Spatial correspondence was observed between harmonic emissions and tissue lesioning, along the array azimuth. This was assessed by a statistically significant correlation (r = 0.684) and area under a receiver operating characteristics (ROC) curve (AUROC = 0.71).

The present cavitation detection and imaging techniques, implemented in this thesis to monitor ultrasound ablation, can potentially be extended to other therapeutic ultrasound procedures that are significantly influenced by cavitation.

Committee:

T. Douglas Mast, PhD (Committee Chair); Christy Holland, PhD (Committee Member); Marepalli Rao, PhD (Committee Member)

Subjects:

Biomedical Research

Keywords:

Ultrasound Ablation;Acoustic cavitation;Passive cavitation detection;High-intensity focused ultrasound;Passive cavitation imaging;guidance and control

Carver, LauraRegulation of Slit-Robo Signaling by Commissureless and Comm Family Members
Doctor of Philosophy, The Ohio State University, 2011, Molecular Genetics

The field of axon guidance is concerned with deciphering how axons use temporal and spatial cues to pattern a precise trajectory. We use the fruit fly Drosophila melanogaster to study embryonic pathway decisions that are fundamental in connecting the bilaterally symmetrical halves of the nervous system at the ventral midline. At the midline choice point, axons make a binary decision regarding whether or not to cross to the opposite side. One signaling pathway controlling midline crossing is Slit-Roundabout repulsive signaling, whereby axons expressing the Roundabout (Robo) receptor bind the midline-expressed chemorepellant ligand, Slit, and sense the midline as inhibitory. Expression of Commissureless (Comm)—and its post-translational re-localization of Robo—effectively silences Slit-Robo signaling, allowing axons to cross the midline. In addition to comm, there exist two other Comm family members: comm2 and comm3. We utilized cell culture and in vivo approaches to learn about comm2, whose spatiotemporal expression is similar to comm during embryogenesis. Like Comm, Comm2 re-localized full-length Robo in S2-based cell culture assays but required sequences in Robo’s extracellular (EC) and/or cytoplasmic (cyto) domain not required by Comm. Additionally, deletion of Comm2’s EC domain abrogated its Robo re-localization ability. In flies, both molecularly-defined deletion of Comm2 and Comm2 overexpression in wildtype had subtle phenotypes, but its expression in comm and comm,comm2 deletion backgrounds revealed a positive role in midline crossing. Interestingly, comparison of Comm2 expression in backgrounds deleted for comm, comm2, or both, revealed a possible inhibitory role for Comm2 at the midline.

We also created a series of chimeric fusion proteins among Comm family members. Analysis of these constructs supports an unexpected role for the Comm EC domain in regulating Robo. In the S2 cell culture assay, as little as the Comm EC domain was capable of transforming otherwise non-functional Comm2 and Comm3 transmembrane (TM) and cytoplasmic domains into Robo re-localizing proteins. This affect translated to Comm-like functionality when tested in vivo as well. Furthermore, although full-length Comm2 induced Robo re-localization in cell culture, the presence of its domains in various fusion proteins was unable to promote Robo re-localization. We also focused on Comm3, which has no Comm-like functionality, despite having a conserved TM domain and PY motifs. Its EC domain is not inhibitory to Robo re-localization; rather, it may lack the positive sequences present in Comm, making it a good tool to use for understanding Comm and Comm2 function. Its TM/cyto domains are, however, able to function when combined with a Comm EC domain.

Finally, we investigated the mechanism by which Comm regulates Robo, with a focus on ubiquitination of Comm and/or Robo. In contrast to other publications, we did not find a necessary role for Comm ubiquitination in Comm-mediated Robo re-localization in S2 cells or in vivo, as it behaved like wildtype Comm in both environments. On the other hand, in S2 cells, Comm less efficiently re-localized a short, lysine-free Robo construct, but some re-localization still occurred. When both were lysine-free, again, some re-localization still occurred, suggesting that ubiquitination may influence the process but is not absolute.

Committee:

Mark Seeger, PhD (Advisor); Christine Beattie, PhD (Committee Member); Amanda Simcox, PhD (Committee Member); Harald Vaessin, PhD (Committee Member)

Subjects:

Developmental Biology; Genetics; Molecular Biology; Neurobiology

Keywords:

Axon guidance; Commissureless; Roundabout; Drosophila melanogaster; neurobiology; molecular biology; genetics; developmental biology

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