Master of Environmental Science, Miami University, 2009, Environmental Sciences

Working in conjunction with Five Rivers MetroParks, I developed a potential trail layout with optional educational destinations for the Great Miami Mitigation Bank. The feasibility study took AASHTO shared use path guidelines, physical site characteristics, professional opinions, and observational study into account. A funding guide consisting of twenty different financial options was also created to assist Five Rivers MetroParks efforts toward park financing. A packet of deliverables consisting of two final maps, a disk of model park photos, a flash drive of GIS data, and two copies of the funding guide was delivered to Five Rivers MetroParks to be used at their discretion on August 7, 2008.

Committee: Dr. Sandra Woy-Hazleton PhD (Committee Chair); Dr. James Rubenstein PhD (Committee Member); Dr. David Prytherch PhD (Committee Member) Subjects: Environmental Science

Master of Environmental Science, Miami University, 2007, Environmental Sciences

This paper reports on materials available to create reused and recycled park furnishings for the Mill Creek Greenway Trail in Cincinnati, Ohio. Research was done during a summer 2005 internship with Mill Creek Restoration Project to identify materials that were available for use in the proposed Mill Creek Greenway Trail that would reflect a sustainability ethic. In other words, in what ways could furnishings for the greenway trial be created (multi-use trail, benches, signs, landscaping materials, etc) that would help protect the environmentally sensitive Mill Creek, while also reflecting and encouraging environmentalism in the Cincinnati region. Eight criteria were used when analyzing each material for possible use: proposed use for material, cost, durability, aesthetics, safety and health, sustainability and environmental impact, life cycle costs, and local, regional, state and national availability.

Committee: Sandra Woy-Hazleton (Advisor) Subjects:

Master of Science (MS), Ohio University, 2022, Geography (Arts and Sciences)

The need for understanding the impacts of off-road vehicle (ORV) usage on trail systems is widely accepted, with few studies being conducted in humid climates and even fewer examining the impacts of unauthorized user-created ORV routes. This research examines cross-trail profile measurements along authorized ORV trails and unauthorized ORV routes in southeastern Ohio over a six-month period in order to calculate erosion rates and understand how each trail type behaves throughout the riding season. Measurements from the two trail types are compared to one another in varying combinations and between data collection periods. Spatial comparisons of soil compaction and soil texture are also analyzed. Results from statistical analyses showed that there is no significant difference in erosion rates between authorized and unauthorized trail segments despite apparent differences in eroded sediments between the two trail types. The highest measured erosion rates on authorized and unauthorized segments totaled 3.65 m3/yr and 15.95 m3/yr, respectively. Few sites were found to have significant geomorphic change along the trail surface during the six-month study period. Soil compaction values were found to be greater on the trail surface compared to the trail-adjacent forest in both trail types. Soil compaction of the trail surface was not found to be statistically different between the two trail types, nor were values from the trail-adjacent forest different between the trail types. The results of this study demonstrate the need for effective management efforts that focus management efforts not only on authorized ORV trails, but also the unauthorized routes that are associated in ORV trail systems.

Committee: Dorothy Sack (Advisor) Subjects: Environmental Geology; Environmental Management; Geography; Geomorphology

Master of Arts, Miami University, 2014, Geography

The Israel National Trail and Jesus Trail are fascinating examples for geographers to look at in terms of sustainable tourism development. Interviews and participant observation conducted show that hikers and personnel along the trails are becoming more aware of issues within sustainability such as large amounts of trash and lack of water. Surveys conducted show the hikers along these trails are not doing much to be sustainable. These results can be seen from a lack of education and understanding of ecotourism along Israel's trails. Ecotourism is a fast growing sector of tourism and can offer ways to help preserve Israel's Trails environment, culture, as well as help out areas economically. By using the approach of surveys, interviews, and participant observation, this thesis examines how stakeholders perceive and address aspects of ecotourism along the Israel National Trail and Jesus Trail in Israel, focusing on the Lower Galilee and Negev Region.

Committee: Stanley Toops Dr. (Advisor); David Prytherch Dr. (Committee Member); Carl Dahlman Dr. (Committee Member) Subjects: Geography

Master of Science, The Ohio State University, 2024, Agricultural Communication, Education and Leadership

In an era with increased agricultural interest and heightened public scrutiny, the majority of the United States workforce is employed outside of agriculture and related industries and is therefore removed from knowledge of current agricultural practices. Though adults hold influence over the agriculture industry through their purchasing and voting powers, most agricultural literacy efforts have focused on K-12 education. As adults are able to choose their learning experiences, agritourism efforts are important to reaching adult populations. Currently, classifying an activity as agritourism requires it to have some direct connection to a farm, regardless of its operational status. However, when targeting adult learners, the literature recommends expanding the definition of activities. With its historical connection to agriculture and use of agricultural inputs, this study sought to understand, through the perspective of distillery employees, if the bourbon industry viewed itself as connected to the agriculture industry, integrated agriculture into its identity, presented agriculture to visitors, and if participants believed adults could learn about agriculture by engaging in tours. Through a multi-site, embedded case study, data collection included 19 distillery employee interviews from three distilleries, field observation, and records review, to explore, through reputational theory, distillery identity, constructed image, culture, and projected image. Data were analyzed using process, descriptive, and In Vivo coding, which was distilled down to themes when appropriate. Results indicate that participants viewed the bourbon industry as deeply connected to agriculture, and in many instances, a direct player in the agriculture industry. Participating distilleries had integrated agriculture into their identity and projected this in their public-facing operations. Though participants did not believe their industry fit the current definition of agritourism, they expresse (open full item for complete abstract)

Committee: Amanda Bowling (Committee Member); Annie Specht (Advisor) Subjects: Adult Education; Agriculture; Communication

Doctor of Philosophy, Case Western Reserve University, 2023, Pathology

Autoimmunity in type 1 diabetes is primarily caused by destruction of insulin producing pancreatic beta cells by cytotoxic T cells, in part due to dysfunctional T regulatory (Tregs) cells. This leads to hyperglycemia, which is a hallmark of diabetes. Adverse pathological effects of hyperglycemia include the increased posttranslational modification of cellular proteins at serine and threonine residues by the sugar N-acetylglucosamine, in a process termed O-GlcNAcylation. We found that the transcription factor nuclear factor kappaB (NF-κB) subunit c-Rel is a target for this pathologic O-GlcNAcylation at serine residue 350 in T lymphocytes. c-Rel is the major regulator of CD4+ and CD8+ T cell function and Treg development that controls autoimmunity and immunosuppression, respectively. Earlier, we found that c-Rel O-GlcNAcylation increases its transcriptional activity and the expression of pro-autoimmune cytokines in CD4+ T cells. However, the role c-Rel O-GlcNAcylation plays in Tregs and cytotoxic T cells remains elusive. Here, we describe dual mechanisms showing c-Rel O-GlcNAcylation acts as both a negative regulator in the transcription of forkhead box P3 (FOXP3) in Tregs while also a positive regulator of transcription of the cytotoxic genes, Fas Ligand (FasL) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), in cytotoxic T cells. To study more closely how O-GlcNAcylation is changing c-Rel-DNA binding, we have developed two tools – a site-specific monoclonal antibody for O-GlcNAcylated c-Rel and a peptidomimetic drug called OGC350 to block its transcriptional activity. Use of the S350 site-specific anti-O-GlcNAcylated c-Rel antibody has the potential to reveal the role of c-Rel O-GlcNAcylation in regulating T cell function in autoimmune diabetes, beyond the regulation of FOXP3 and cytotoxic genes, and can provide evidence of how OGC350 may further impact O-GlcNAc-sensitive transcription in T cells.

Committee: Pamela Wearsch (Committee Chair); Parameswaran Ramakrishnan (Advisor); Alex Huang (Committee Member); Clive Hamlin (Committee Member); George Dubyak (Committee Member) Subjects: Biochemistry; Biology; Biomedical Research; Immunology; Medicine; Molecular Biology

Master of Arts (MA), Bowling Green State University, 1960, English

Committee: Robert R. Hubach (Advisor) Subjects: American Literature

Master of Arts (MA), Bowling Green State University, 1960, English

Committee: Robert R. Hubach (Advisor) Subjects: American Literature

Master of Science (MS), Ohio University, 2020, Environmental Studies (Voinovich)

Urban stormwater runoff has become of increasing concern as urban sprawl has increased over decades. With more impervious surfaces, stormwater quickly passes into freshwater ecosystems with little to no water percolating into the soil. Even if there are not impervious surfaces, stormwater may pass over agricultural lands where nitrogen and phosphorus are easily available to flow into aquatic environments. Management plans are now using different strategies to filter out sediment and nutrients before they enter lotic or large lentic ecosystems. These small ponds or constructed wetlands have larger pieces of sediment settle before they have an opportunity to flow into a larger water body. While this has shown to be a successful and useful tool to filter out materials, horizontal (lateral) movement of water during flood events has become a concern. Species in a wetland can migrate in and out of the wetland into a lentic or lotic ecosystem, returning for refuge and breeding habits. If the wetland and larger water body become cut off they develop their own line of succession. The purpose of this study is to understand and characterize the water quality between an urban stormwater wetland and the headwaters of the Hocking River. Evaluate differences of biotic assemblages in the two water bodies and present information to the neighboring AHA! A Hands-On Adventure A Children's Museum. These goals are done by conducting: fish, invertebrate, crayfish and field parameter tests.

Committee: Natalie Kruse Daniels (Advisor); Nancy Stevens (Advisor); Kelly Johnson (Committee Chair) Subjects: Agricultural Education; Animal Sciences; Aquaculture; Aquatic Sciences; Art Education; Arts Management; Biology; Chemistry; Climate Change; Communication; Early Childhood Education; Earth; Ecology; Education; Entomology; Environmental Education; Environmental Studies; Hydrology; Industrial Arts Education; Multimedia Communications; Museum Studies; Museums; Pedagogy; Physical Education; Sustainability; Teacher Education; Teaching; Technical Communication; Urban Planning

Master of Landscape Architecture, The Ohio State University, 2020, Landscape Architecture

The Borjomi-Bakuriani region was once the center of the Soviet science of “resortology,” a system of rest and healing intimately tied to the unique physical characteristics of the alpine region. Every aspect of the landscape – climate, ecology, topography, aspect, hydrology – might be engaged to heal and restore the human body. Accessed by a specially constructed narrow-gauge railway, sanatoria complexes were interfaces between patients and the particular curative properties of this mountainous landscape. Connecting the body to this place – breathing its air, walking its relief, drinking its water – activated latent healing properties embedded in the landscape. After the collapse of the Soviet Union and the associated financial crisis, agricultural and manufacturing collectives in the Borjomi-Bakuriani region were closed and sanatoria were abandoned. Built vestiges of this once thriving system of healing dot the landscape. Spring waters are still collected at their source by the few residents who remain in the villages; the status of these waters as a source of wellness and vitality remains unchanged. While the curative properties of this landscape are understood to remain embedded in place, coherence between the ecological and cultural artifacts has been lost, and opportunities to activate these healing effects are no longer apparent to visitors. Meanwhile, illegal logging and unsustainable development in the region threaten to disrupt the unique climactic and ecological conditions that constitute this health landscape. This project proposes the design of an interpretive trail that might re-inscribe coherence to this historic human-environment system. Responding to critiques of the traditional form of interpretive trail design, it explores the potentials of new strategies that might structure the design process for more effective interpretive trails in heritage landscapes. Specifically, this project asks if cultural practices that have historically structu (open full item for complete abstract)

Committee: Katherine Jenkins (Advisor); Justin Parscher (Committee Member) Subjects: Landscape Architecture

Master of Science (MS), Ohio University, 2019, Recreation Studies (Education)

Curiosity about the motivations of thru-hikers has arisen on numerous occasions but whether that motivation changes throughout the hike has not been extensively researched, even in the social sciences. A long-distance hiker is stripped of everything during their hike, leaving only their true character. Though long-distance hiking is thought to be a positive and transformative experience, a thru-hike is not without its hardships. Ankle pain, heat exhaustion, dehydration, quarter-sized blisters, cramps, and broken gear are just some of the many reasons a person may quit a thru-hike. This begs the question, what about thru-hiking, or what is inside that individual, that allows them to continue on to the finish when everything in their mind and body is telling them to quit? Three million people hike on the Appalachian Trail each year, and last year alone over 1,100 people completed the entire trail. Although the number of people attempting the trail is increasing, the number of thru-hikers that complete the trail are falling. Long-distance hikers continue hiking because they want to finish, or because they enjoy the art of walking in nature. Simple yet profound, if hikers never finished a hike they would not be motivated to keep trying. This would result in doing the same thing over and over expecting different results. Therefore, the purpose of this study is to examine the extent to which changes in long-distance hikers' motivations can be explained through factors related to autonomy, competence, and relatedness, and understand adversities faced on the trail and how hikers overcome these challenges.

Committee: Bruce Martin PhD (Advisor); Andy Szolosi PhD (Committee Member); Holly Raffle PhD (Committee Member) Subjects: Behavioral Psychology; Behavioral Sciences; Cognitive Psychology; Environmental Education; Environmental Studies; Physical Education; Psychology; Recreation; Social Psychology; Sports Management

Honors Theses, Ohio Dominican University, 2017, Honors Theses

Indoor and recreational rock climbing has become an increasingly popular sport among children and adults. Additionally, recent research has demonstrated that active therapy, such as swimming and hippotherapy, is beneficial for children with autism. PURPOSE: To determine the effects of six weeks of rock-climbing on functional strength, spatial reasoning, and executive function for children with autism. METHODS: Seven subjects (8-14 years old, all male) completed six weeks of rock climbing at a pre-established gym. Examinations of Cognitive Trail Making Tests (CTMT) and hand grip strength were completed for all participants prior to the start of classes and after six weeks of training. For hand grip strength, three trials were completed on each hand using a standard hand grip dynamometer. The two highest results were taken and added to represent total grip strength. The CTMT was performed via directions given through the standard protocol. RESULTS: The data did not reveal any significant differences; however, there were positive trends among all variables. CONCLUSION: The research was limited by the number of subjects and variability between subjects. Even so, the positive trends suggest that more research may show significant benefits from rock-climbing. Past research evaluating adventure education, psychological benefits of rock climbing, and neurological and physiological adaptations to exercise still support the possibility of rock climbing as a viable therapy option. With continued research in rock climbing, we hope to be able to implement a different, potentially more beneficial, therapeutic modality that addresses cognitive and physical impairments commonly observed in children with autism.

Committee: John Marazita (Committee Chair); John Thistlethwaite (Advisor) Subjects: Education; Educational Psychology; Kinesiology; Psychology; Therapy

Doctor of Philosophy, The Ohio State University, 2017, Molecular, Cellular and Developmental Biology

MicroRNAs (miRNAs) are a family of small non-coding RNAs that can negatively regulate the expression of genes by sequence-selective targeting of mRNAs, leading to either mRNA degradation or translational repression. They have become recognized as key players in the development of cancer. Non-small cell lung cancer (NSCLC) is one of the leading cause of cancer-related death worldwide with a substantially low survival rate. MiRNAs have been confirmed to play roles in lung cancer development, epithelial-mesenchymal transition and response to therapy. Drug resistance is a major obstacle in cancer therapy; cancer treatment is a constant struggle against therapeutic resistance. TNF-related apoptosis-inducing ligand (TRAIL) has been studies as a therapeutic molecule that induces apoptosis in malignant cells without inducing significant toxicity in normal cells. However, several carcinomas, including lung cancer, remain resistant to TRAIL or develop resistance during therapy. MiRNAs have been implicated in increasing susceptibility or resistance to TRAIL-induced apoptosis by inhibiting key functional proteins. The mail goal of my research has been to understand the role of some key miRNAs in TRAIL resistance and tumorigenesis in NSCLC. Firstly, we study the role of miR-148a which is a well-known tumor suppressor miRNA in various cancers. We show that miR-148a is down-regulated in cells with acquired TRAIL-resistance compared with TRAIL-sensitive cells. Enforced expression of miR-148a sensitized cells to TRAIL and reduced lung tumorigenesis in vitro and in vivo through the down-modulation of matrix metalloproteinase 15 (MMP15) and Rho-associated kinase 1 (ROCK1). These findings suggest that miR-148a acts as a tumor suppressor and might have therapeutic application in the treatment of NSCLC. Next, we study the role of ribosomal S6 kinase 2 (RSK2) which is a downstream effector of the Ras-extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) (open full item for complete abstract)

Committee: Carlo Croce (Advisor) Subjects: Molecular Biology

PHD, Kent State University, 2017, College of Public Health

Introduction: Up to 29.5% of U.S. adults are physically inactive. Physical inactivity is associated with excess mortality and morbidity and may contribute an estimated $131 billion in health care expenditures annually. Exercise prescriptions and referrals are an economical solution to physical inactivity, and several health care provider associations and proposed government policy initiatives support adoption of exercise prescriptions. Yet as few as 14% of primary care providers prescribe exercise or make exercise referrals. The purpose of this pilot study is to identify provider characteristics, knowledge, perceived barriers, practices, and needs related to place-based exercise prescription and referral to exercise either at a specific location, or to an exercise professional. Methods: An 88-item questionnaire was developed and administered electronically and in paper format to alumni of a university's nurse practitioner program and two hospital systems' networks of primary care physicians and nurse practitioners. Descriptive statistics were generated regarding clinical practices related to patient exercise and providers' perceived needs related to exercise prescription and referral. Factor analysis was conducted to identify underlying constructs. Bivariate analyses were utilized to identify variables significantly related to exercise prescription and referral. A binomial logistic regression was performed to determine factors related to whether or not providers refer patients to place-based exercise. Results: Responses were received from 166 providers; 61.5% were female, 86.9% were white. Respondents' specialties were: family medicine (20.6%), internal medicine (27.8%), nurse practitioner (29.4%), and other (22.2%). Overall, 14.8% of providers prescribe exercise to at least some of their patients and 54.3% refer patients to specific exercise locations or professionals. Almost 90% ask about patient exercise, 64.3% document patient exercise, and 20.8% assess (open full item for complete abstract)

Committee: Sonia Alemagno (Committee Chair); Jeffrey Hallam (Committee Member); Jonathan VanGeest (Committee Member) Subjects: Health; Health Care; Health Sciences; Public Health; Public Policy

PHD, Kent State University, 2015, College of Education, Health and Human Services / School of Teaching, Learning and Curriculum Studies

The purpose of this study was to examine nature experiences; how these experiences in nature impact place-making and in turn are impacted by place; why someone would choose to engage in an intense nature experience (in connection with significant life experiences); how people connect to nature and what their construction of nature is; and how knowledge is generated during an informal nature experience. A naturalistic inquiry methodology was selected to explore how Appalachian Trail thru-hikers experience and connect to nature, what prior nature experiences and formative influences led them to undertake a long-term outdoor experience, and the relationships between space, place, identity, and power. To address this purpose, I collected data from 18 Appalachian Trail thru-hikers via in-depth semi-structured interviews, observation field notes, and an autoethnographic research journal. The results of this research included a number of emergent findings. The emergent themes fell into the following categories: awareness of nature, identifying as a participant or observer in nature, power over nature, power of nature, social experiences, nature experiences, learning, significant life experiences, formative influences, reasoning, relationships with nature, bounding/bordering nature, conceptions of nature, place-making, and evolving identities. The results are presented in this dissertation in support of an argument for environmental education scholars and practitioners to attend to varying constructions of nature as a space, as well as how identity shapes experience and place-making.

Committee: Lisa Borgerding PHD (Committee Co-Chair); Sara Raven PHD (Committee Co-Chair); Tricia Niesz PHD (Committee Member) Subjects: Environmental Education; Science Education

Master of Science (MS), Ohio University, 2014, Clinical Psychology (Arts and Sciences)

Questions about driving are common in dementia screening clinics; however, the specific cognitive impairments most associated with driving skills are unclear. Measures of Useful Field of View (UFOV), which are highly predictive of driving ability, are a cost-effective way of screening driving skills and are beginning to be used in driver's license bureaus; however, they are not commonly used in dementia screening clinics, where assessment is usually focused on diagnosis and detection of dementia. The purpose of the present study was to examine whether diagnostic measures of cognitive ability are related to driving risk, as assessed by UFOV. The first aim was to examine which cognitive constructs are most related to UFOV performance. Based on existing data on the UFOV, as well as prior studies of the cognitive domains most related to driving skill in healthy older adults, it was hypothesized that measures of cognitive flexibility, executive inhibition, visuospatial/ constructional skills and visual attention would be strongly associated with UFOV performance. The second aim was to examine whether a set of cognitive measures could be identified that accurately accounts for driving risk, as judged by clinical interpretation of UFOV scores. An important factor to consider for both study aims was the use of raw or demographically corrected scores. Whereas adjusting cognitive measures for age or other demographic factors is common practice in neuropsychological diagnostic assessments, research suggests that non-adjusted scores are more appropriate when predicting functional abilities. Thus, for both study aims, it was hypothesized that raw scores would be more strongly related to UFOV than adjusted scores. Data for the present study were taken from an archived dataset of 114 non- demented older adults (56 - 88) who were active drivers (42% male, with an average of college level education). Results showed that, of all cognitive constructs assessed, a measure of executive f (open full item for complete abstract)

Committee: Julie Suhr PhD (Advisor) Subjects: Clinical Psychology

Doctor of Philosophy (PhD), Wright State University, 2008, Computer Science and Engineering PhD

Grid computing is a computing model in which various resources, such as processing power, storage systems, data sources, or instruments, are interconnected by a communication infrastructure and accessible as a public utility for solving large scale resource intensive problems. Grid computing requires dynamic communication between distributed resources and high bandwidth quality assured survivable communication services. Optical fiber communication and networking with wavelength division multiplexing (WDM) provides a promising means to support the communication needs of grid computing, by offering huge capacity, relatively low latency, as well as dynamic control and allocation of bandwidth at various granularities. In this dissertation, we explore several important and challenging issues in optical WDM networks for supporting grid computing:Diverse Routing for Survivable Service: Grid computing requires survivable communication services due to the huge traffic volume involved. We study the diverse routing problem in networks with a shared risk link group (SRLGs) failure. An SRLG includes a set of optical links that are affected by a single failure in the physical layer of a WDM network. The objective is to determine a pair of SRLG-disjoint paths with the minimum total cost. Quality of Service Routing: To ensure the quality of service for grid communication, connections with bounded risk of failure and transmission delay are highly desirable. We study the multi-constrained routing problem that finds a path that guarantees the end-to-end failure risk bound in terms of total weight of SRLGs while minimizing the end-to-end transmission delay bound, or the path cost. Scheduled Service Provisioning using Light-trails: The recently proposed light-trail concept is a promising technique in WDM optical networks for supporting the grid computing traffic given light-trails' dynamic provisioning ability. We model the grid communication demands as a scheduled traffic model, in whi (open full item for complete abstract)

Committee: Bin Wang PhD (Advisor); Jack Jean PhD (Committee Member); Yong Pei PhD (Committee Member); Yuqing Chen PhD (Committee Member); Raul Ordonez PhD (Committee Member) Subjects: Computer Science

Master of Science (MS), Wright State University, 2008, Physiology and Neuroscience

Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is associated with mutations within codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC). BITC is a component of cruciferous vegetable extracts and a cell cycle inhibitor. BxPC3, MiaPaCa2, and Panc-1 human pancreatic adenocarcinoma cell lines were examined for TRAIL resistance. Our studies show BITC-induced TRAIL sensitization by the activation of caspases 8, 9 and 3 as well as their respective substrates Bid, XIAP, and PARP. Cell Death ELISA confirmed TRAIL sensitization by BITC.

Committee: Thomas Brown Ph.D. (Advisor); Nancy Bigley Ph.D. (Committee Member); Courtney Sulentic Ph.D. (Committee Member) Subjects: Biology; Cellular Biology

MS, University of Cincinnati, 2005, Engineering : Aerospace Engineering

One of the responsibilities of air traffic controllers is to maintain aircraft separation in flight. However, with growing air traffic demands, current research is investigating the possibility of delegating some of that responsibility to the cockpit. One suggested implementation of this concept is the design of a control law that will assist pilots in a stream of in-trail aircraft to maintain separation. The goal of this thesis is to develop and apply control laws that can aid in the maintenance of separation of long strings of aircraft. Automatic Dependence Surveillance – Broadcast (ADS-B) is used to communicate state vectors. The dynamics and controls of the aircraft are numerically simulated with the design of a MATLAB program. The results for the tests run show promising results. Further tests can be run to potentially optimize the control schemes chosen as well as analyze different flight trajectories.

Committee: Dr. Gary Slater (Advisor) Subjects: Engineering, Aerospace

Doctor of Philosophy, The Ohio State University, 2010, Biochemistry Program, Ohio State

Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and Africa, which is lethal in about 75% of cases. In the United States, there are 6,000-9,000 new cases of HCC per year. HCC is one of the highly chemo-resistant cancers, for which systemic treatments have been unsuccessful. The available therapies are surgical (10-20% of cases), locoregional or recently, chemical using Sorafenib, a multi-kinase inhibitor which has been shown in clinical trial to add two months to the lifespan of late stage HCC patients. To combat HCC with its assortment of genomic and cellular aberrations that occur during the progression of the disease, we have developed OSU-A9 and OSU-2S, novel small-molecule targeted agents for HCC therapy, using indole-3-carbinol (I3C) and fingolimod (FTY720) respectively, as scaffolds. In this study, we used pharmacological and molecular genetic approaches to investigate the mechanisms of action of the lead compounds of these classes (OSU-A9 and OSU-2S) and assess both the efficacy and safety in a series of preclinical studies carried out both in vitro and in vivo. OSU-A9 exhibits up to 100-fold greater in vitro efficacy relative to I3C in HCC cells and provides a considerable therapeutic advantage over I3C with respect to chemical stability. Mechanistic evidence indicates that OSU-A9 antitumor effect is mediated by blocking the Akt-NF-kB signaling network, leading to the inhibition of signaling pathways governing cell cycle progression, survival, and metastasis. Equally important , oral administration of OSU-A9 suppressed HCC xenograft tumor growth in mice without causing overt signs of toxicity. In addition, sub-toxic doses of OSU-A9 combined with the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) effectively inhibited the resistance of HCC to TRAIL-induced apoptosis. The synergistic apoptotic effect is mediated by the ability of OSU-A9 to antagonize TRAIL-activated NF-κB cell survival pathway and to upregulate death (open full item for complete abstract)

Committee: Ching-Shih Chen PhD (Advisor); Robert W. Brueggemeier PhD (Committee Member); Matthew D. Ringel MD (Committee Member); Tushar Patel MD (Committee Member) Subjects: Biochemistry; Molecular Biology; Pharmacology