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Li, JishengDevelopment of a Neural PD Controller for Quad-rotors for Rejection of Wind Disturbances
Master of Science, University of Toledo, 2016, Mechanical Engineering
UAVs have become increasingly popular around the world both in civilian and military application within the past few years. UAV applications are essentially fueled by advances in a combination of technologies, such as communication, embedded systems, processing, sensing and algorithms. This thesis focuses on the control aspect of UAVs, particularly lots of work has been carried out in this area recently. This thesis mainly focuses on the performance of control algorithms under wind disturbances. Recent works that include an adaptive controller and a PD controller are discussed. Then the thesis proposes a neural PD controller, in which the neural network is added to the outer PD control loop. A comparison between neural PD controller and PD controller under various scenarios of wind disturbances is carried out. The results show neural PD controller performs better than the PD controller in position tracking under wind disturbances.

Committee:

Manish Kumar (Committee Chair); Mohammad Elahninia (Committee Member); Abdollah Afjeh (Committee Member)

Subjects:

Mechanical Engineering

Keywords:

adaptive controller;PD controller;neural PD controller;wind disturbance

Cushman, Christopher ScottDestruction of chlorinated hydrocarbons by zero-valent zinc and bimetallic zinc reductants in bench-scale investigations
Master of Science (MS), Wright State University, 2014, Earth and Environmental Sciences
Many remediation technologies have been developed to treat extensive subsurface contamination by chlorinated hydrocarbons (CHCs). One such technology is a permeable reactive barrier (PRB), which contains reactive media that acts as an electron donor in order to reduce CHCs. Extensive effort has been placed on finding the most suitable reactive media in PRBs, with zero-valent iron (ZVI) being the most commonly utilized media. However, zero-valent zinc (ZVZ) is a promising replacement for ZVI in PRBs as it will more readily donate electrons, resulting in more rapid degradation of CHCs. In addition, amending a secondary/catalytic metal to primary metal surface can result in increased degradation kinetics and yield of dechlorinated byproducts. In this investigation, chlorinated methanes (CF and DCM), ethanes (1,1,2,2-TeCA, 1,1,2-TCA, 1,1,1-TCA, and 1,2-DCA), ethenes (PCE, TCE, cis-DCE, trans-DCE, and VC) and propanes (1,2,3-TCP and 1,2-DCP) were reduced by ZVZ and Zn bimetallic reductants. Results indicated that Cu/Zn was a more potent bimetallic reductant than Pd/Zn and Ni/Zn due to impressive CF degradation kinetics and increased yield of methane formed via direct transformation of CF to methane. Cu/Zn was used in reduction of all other compounds and did not significantly change byproduct distributions when compared to ZVZ. Reductive β-elimination was an important degradation pathway observed for chlorinated ethanes and ethenes, with reduction of chlorinated ethenes via this pathway resulting in the formation of highly reactive chlorinated acetylene intermediates, thus preventing the formation of VC. It appears that ZVI will reduce chlorinated ethenes via reductive β-elimination more readily than Zn reductants, suggesting an advantage of ZVI in the reduction of chlorinated ethenes. However, Zn reductants appear to be well suited for PRB applications at sites contaminated with 1,2,3-TCP, as reduction with Zn reductants yields fully dechlorinated byproducts via a reductive β-elimination to hydrogenolysis sequence, unlike ZVI. Cu/Zn increased degradation kinetics compared to ZVZ for all CHCs investigated, but only slight enhancement in kinetics was observed for chlorinated propanes. Increased chlorinated methane, ethane, and propane kinetics have been reported with ZVZ when compared to ZVI, thus suggesting the need to further study Cu/Zn as a potential replacement for ZVI in PRB applications.

Committee:

Abinash Agrawal, Ph.D. (Advisor); Mark Goltz, Ph.D. (Committee Member); Songlin Cheng, Ph.D. (Committee Member)

Subjects:

Chemistry; Environmental Engineering; Environmental Geology; Environmental Management; Environmental Science; Environmental Studies; Organic Chemistry; Sustainability; Water Resource Management

Keywords:

chlorinated hydrocarbons; zero-valent zinc; ZVZ; zero-valent iron; ZVI; bimetallic; reductants; copper; Cu-Zn; palladium; Pd-Zn; nickel; Ni-Zn; chlorinated methanes; chlorinated ethanes; chlorinated ethenes; chlorinated propanes; 1,2,3-TCP

Im, Hsung J.Metal Contacts to Silicon Carbide and Gallium Nitride Studied with Ballistic Electron Emission Microscopy
Doctor of Philosophy, The Ohio State University, 2001, Physics
Ultrahigh vacuum (UHV) ballistic electron emission microscopy (BEEM) is used to study at nanometer scale the phenomena associated with the Schottky barrier inhomogeneity and defect-related charge of silicon carbide (SiC) and gallium nitride (GaN). Also some results of studies of effects of UHV premetallization annealing and hydrogen exposure on Pd/SiC Schottky contacts, as well as our contribution to a study of boron segregation in annealed B-doped Si using Auger electron spectroscopy (AES) are presented. We show that BEEM can be used to probe nanometer scale spatial inhomogeneity of Schottky barrier height (SBH) and to extract information about conduction band structures of different polytypes (6H, 4H, and 15R) of SiC. We have performed the first successful BEEM measurements on SiC, from which SBHs and the energy separations of the second conduction band minima (CBM) of 4H- and 15R-SiC were extracted. Direct observation of the image force lowering of SiC Schottky barrier are presented as well. Also we used BEEM to characterize individual threading dislocations (TDs) in GaN crystals grown on sapphire substrates. Potential barrier profiles and ballistic transmittance across GaN Schottky contacts were measured across individual TDs, which subsequently were used to set a limit on possible trapped negative charges along the dislocations. In contrast to several prior studies, we find no indication of near-interface fixed negative dislocation charge at specific TD structures. We have performed a detailed study of diode nonidealities on the fabricated SiC Schottky contacts, such as large excess leakage current and deviation from thermionic emission theory. Tung and others had shown that a range of “nonideal” behaviors of Schottky diodes could be quantitatively explained by assuming a distribution of nanometer-sized interfacial “patches” of reduced SBH undergoing potential pinch-off. We extended this proposed model to calculate the microscopic barrier height distribution (BHD) for the assumed patch distributions. Our measurements indicate that the large excess current in highly nonideal diodes is most likely due to a few large defects of extrinsic origin, which were not considered in the original model. This last conclusion is consistent with a recent electron beam induced current (EBIC) study by Skromme and co-workers.

Committee:

Jonathan Pelz (Advisor)

Keywords:

BEEM; diode; Schottky; SBH; STM/BEEM; BHD; Pd/SiC

Tiwari, RohitCOMPUTATIONAL AND SYNTHETIC STUDIES ON ANTIMETABOLITES FOR ANTICANCER-, ANTIVIRAL-,AND ANTIBIOTIC DRUG DISCOVERY
Doctor of Philosophy, The Ohio State University, 2010, Pharmacy

Thymidine kinase (TK) and dihydrofolate reductase (DHFR) are two enzymes that play major roles in the salvage- and de novo pathways of DNA synthesis in many eukaryotes, prokaryotes, and viruses. Both enzymes have been exploited extensively as molecular targets for the therapy and imaging of cancer and infectious diseases. This thesis deals with three different research projects that are related to these two enzymes.

The first project focuses on the development of novel computational techniques for the structure-based design of carborane-containing therapeutics. These new methods were developed at the example of DHFR-targeting carboranyl antifolates using Autodock, Glide, FlexX, and Surflex as software platforms. Applying these new techniques, AutoDock and Glide were found to be superior to Surflex and FlexX in docking of closo-carboranyl antifolates into the active site of hDHFR. In the case nido-carboranyl antifolates, Autodock, Glide, and Surflex produced more accurate docking results than FlexX.

The second project describes the design and synthesis of a novel type of tumor imaging agents. These are 3-carboranyl thymidine analogues (3CTAs) that are labeled with iodine-125 at the carborane cluster. 3CTAs are substrates of human TK1 (hTK1) and are selectively entrapped in tumor cells through phosphorylation by this enzyme. The advantage of radiolabeling at the carborane cluster in these compounds is that boron-iodine bonds are apparently far less susceptible to cleavage than carbon-iodine bonds in conventional imaging agents, which may reduce the undesired accumulation of radioactive iodine in the thyroid and stomach The key step in the synthesis of a 125I-labelled 3CTA designated as N5-125I was a palladium catalyzed isotope exchange of cold iodine-127 with hot iodine-125 using commercially available Na125I as the radiohalogen source. Two different methods were developed for the synthesis of 127I-labelled N5 (N5-127I),the starting material in this reaction.

The third project deals with the design and synthesis of novel agents for a “combination therapy” of malignancies that are associated with the Epstein-Barr Virus (EBV). These include Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma, T/NK-cell lymphoma, and post-transplant lymphoproliferative disease. The agents were designed to selectively target EBV thymidine kinase (EBVTK) following induction of the lytic cycle of the virus within the proliferating cells. The EBV lytic cycle can be induced e.g. by DNA methyltransferase inhibitors, histone deacetylase (HDAC) inhibitors, and various chemotherapeutic agents. A small focused library of 24 compounds was synthesized for future evaluation in enzyme assay with hTK1 and EBVTK.

Committee:

Werner Tjarks (Advisor); Pui-Kai Li (Committee Member); Karl Werbovetz (Committee Member); Robert Baiocchi (Committee Member)

Subjects:

Chemistry; Organic Chemistry; Radiation

Keywords:

Carborane; Pd-catalyzed isotope exchange reaction; Halogen exchange; Iodine monochloride; Deglycosylation; Anomerization; Epstein-Barr Virus; Human thymidine kinase 1; Autodock; Glide; FlexX; Surflex; B-halogenation; radiohalogenation

Shrestha, Yuba R.Numerical Simulation of GaAsSb/InP Uni-Traveling Carrier Photodiode
MS, University of Cincinnati, 2005, Engineering : Electrical Engineering
The advent of the optical fiber amplifier has extended the distance between two repeaters and changed the role of the photodetector in an optical receiver in an optical fiber communication system. This new development enables amplification of the signal in its optical form before detection so that the photodetector must now be capable of responding to the high frequency, high power input optical signal without distortion, thereby eliminating the post detection amplification in electrical domain. The conventional p-i-n photodetector, which uses a depleted intrinsic layer as the light absorbing layer suffers from space charge buildup at high input optical power due to the slower movement of the photogenerated holes and so cannot respond adequately. A new type of photodetector, the Uni-Traveling Carrier Photodiode (UTC-PD), overcomes the limitations of the PIN by using a heavily doped p-type photoabsorption layer and a fully depleted, intrinsic wide bandgap collection layer. In the UTC-PD, photogenerated holes are the majority carrier in the absorption layer so their speed of response is determined by the dielectric relaxation time, which is normally very small (~ picoseconds). Therefore, only electrons are active carriers in an UTC-PD and as they move faster than the holes, the device response is much faster. In this thesis study, we have simulated the performance of a novel GaAsSb/InP UTC-PD as a possible replacement for the previously demonstrated InP/InGaAs UTC-PD. The study was performed using a commercial numerical device simulator ATLAS from Silvaco International for a 1.55 µm wavelength. This novel UTC-PD utilizes a p+ GaAsSb with a bandgap energy of 0.72 eV as the absorption layer and a Gaussian doping profile, n- InP as the depleted collection layer, n+ InP as the n+ contact, p+ InAlAs as the main electron blocking layer, p+ InGaAs as the p+ contact and a thin layer of p+ InGaAlAs as a spacer layer between GaAsSb absorption layer and InAlAs electron blocking layer. The simulation results for the device with a 0.2 micron thick absorption layer shows a 3 dB frequency of 41 GHz, responsivity of 0.35 A/W and quantum efficiency of 0.27. Also investigated were variations in the device’s structure and their effects on device performance.

Committee:

Dr. Kenneth Roenker (Advisor)

Keywords:

UTC-PD; Photodiode; GaAsSb/InP; Numerical Simulation

Lindenbaum, Lindsey K.Long-time Average Spectrum in Individuals with Parkinson Disease
Master of Science (MS), Bowling Green State University, 2012, Communication Disorders/Speech-Language Pathology

Various methods of acoustic analysis have been used to describe the speech deficits expressed in Parkinson disease (PD) including long-time average spectrum (LTAS) analysis. The aim of this study was to utilize specific measurements of the LTAS to generate conclusions about physiological components of voice pathology in PD relative to medication status.

Twenty-eight individuals with idiopathic PD and 10 controls were participants for this study. Each participant was recorded reading the first paragraph of the Rainbow Passage. An LTAS was generated from each reading sample and analyzed using the following measurements: Mean Spectral Energy (MSE), First Spectral Peak (FSP), spectral tilt (ST), three Spectral Slope (SS) measures (i.e., SSF0-1kHz, SS1-5kHz, and SS ratio) and spectral moments (i.e., spectral mean, spectral standard deviation, skewness, and kurtosis).

Examination of PD vs. Control comparison relative to LTAS measures indicated that individuals with PD demonstrated significantly lower (more negative) MSE, spectral mean and spectral SD and higher spectral skewness compared to control speakers. Furthermore, ST was positively correlated with Self-Rated Symptom Severity and Self-Rated Medication Effectiveness ratings for individuals with PD. The LTAS findings suggested that individuals with PD demonstrated overall decreased laryngeal muscle tension compared to control speakers. Decreased laryngeal muscle tension observed in the current study may have also been a reflection of decreased vocal fold closure. Future studies comparing the LTAS measures to perceptual measures may facilitate the evaluation of laryngeal function in PD.

Committee:

Alexander M. Goberman, PhD (Advisor); John W. Folkins, PhD (Committee Member); Ronald Scherer, PhD (Committee Member)

Subjects:

Speech Therapy

Keywords:

Parkinson Disease; PD; Long-time average spectrum; LTAS; Acoustic analysis; Medication

Thomas, Eugene M.A Meta-Analytic Investigation Examining Effective Characteristics of Professional Development in K-12 Education Since the Inception of the No Child Left Behind Act of 2002
Doctor of Education (Educational Leadership), Youngstown State University, 2013, Department of Counseling, School Psychology and Educational Leadership
Professional development is a common phrase used by public school educators to describe the training they participate in order to stay current and increase their knowledge and skills in their respective fields. School districts implement professional development for various purposes including but not limited to curriculum, pedagogy, mathematics and so forth. In various school districts professional development training has many formats. Some of these formats include attending conferences, hiring outside consultants, using existing staff, small group book studies, live sessions and online training. Often, the sessions vary from one single isolated training session to on-going multi-year training plans. Essentially, no professional development programs are identical. This dissertation analyzes current secondary data including published articles, journals, reports, dissertations, theses and studies to identify effective characteristics of professional development in traditional public schools grades K-12 since the inception the No Child Left Behind Act of 2002 hereafter referred to as NCLB. The dependent variable of student test scores is analyzed to examine what characteristics/strategies are identified as effective and to what degree. Analysis revealed that the professional development of teachers had a moderate-to-large significant effect on student achievement.

Committee:

Karen Larwin, PhD (Advisor); Robert Beebe, EdD (Committee Member); David Dees, PhD (Committee Member); Jake Protivnak, PhD (Committee Member)

Subjects:

Education; Education Policy; Educational Leadership

Keywords:

professional development; No Child Left Behind; student achievement; effective characteristics; test scores; staff training; staff development; on-line professional development; teacher training; staff training; NCLB; PD; effective practices

Ross, Martin JamesInvestigation into Catalytic Metallodrugs that Target Hepatitis C IRES RNA: Development, Characterization, and Mechanism
Doctor of Philosophy, The Ohio State University, 2015, Chemistry
Metals have been used for therapeutic purposes since the dawn of civilization including the ancient Egyptians using copper jars to sterilize their water. This use of metal and others were commonplace until the discovery of penicillin. With the discovery of penicillin, small molecules with a rational and target approach became the standard of the drug industry. Traditional drugs to this today mostly consist of organic compounds, composed primarily of carbon, hydrogen, nitrogen, oxygen, chlorine, and fluorine. The discovery of cis-platin and the advancement of our understanding of how the body works, including how our bodies handle metals, and advance techniques have created the environment for the renaissance in interest and development of bioinorganic compounds for therapeutic use. Metal complexes offer unique opportunities and properties that traditional small molecules lack. One such approach is through the development of catalytic metallodrugs which by design are able to recognize and target multiple of the same therapeutic target. This ability enable these compounds to be dose at lower dosage, sub-stoichiometric equivalents, which will lead to fewer off-targeting and side-effects. Limited preliminary studies have applied this approach towards ribonucleic acids, such as Hepatitis C IRES RNA. Hepatitis C Virus (HCV) affects over 200 million people globally which unchecked can lead to cirrhosis or liver cancer. Unfortunately, there is not a vaccine available for HCV like hepatitis A or hepatitis B. The current approach towards treatment involve cocktails, mixtures of several compounds each with a different therapeutic target. Initial reports have demonstrated the activity of the Cu-GGHYrFK, copper peptide complex, in recognition of stem-loop IIb of the HCV IRES RNA. This research starts by understanding the products and binding of Cu-GGHYrFK to stem-loop IIb (SLIIb). With the lead compound, pathways and mechanism for oxidative degradation of RNA were developed. Derivatives including the all D-configuration and all L-configuration of this peptide were synthesized to examine the importance of stereochemistry on reactivity. After this, a structure activity relationship study based upon the all L configuration was preformed to evaluate the role of each of the targeting domain amino acids on binding, reactivity, and cellular uptake. This was then continued to the first position after the Cu-GGH domain to examine catalytic properties. A series of different metal ions, Ni2+, Co3+, Pd2+, Pt2+, Au3+, were incorporated into GGHYrFK, the lead compound, to investigate the importance of the metal ion with reactivity. A further more in-depth mechanistic study was carried out with Cu-GGHYrFK with the use of heavy water, H218O to determine the source of oxygen into products of RNA degradation. The novel 5’-product, 5’-geminal diol was reported. Finally, several catalytic drugs based on reported peptides that bind stem-loop IV of the HCV IRES RNA were developed and characterized. These compounds represent a paradigm shift in therapeutic approach for the treatment of hepatitis c virus.

Committee:

Jimmy Cowan (Advisor); A. Douglas Kinghorn (Committee Member); Hannah Shafaat (Committee Member); Claudia Turro (Committee Member)

Subjects:

Chemistry

Keywords:

RNA oxidation; ATCUN; SLIIb; SLIV; HCV; IRES; 5 NTR; Cu; Ni; Pd; Pt; Au; Co;

Merrill, Elaine AliceA Mechanism-Based Model to Describe GABAA Receptor Trafficking and Benzodiazepine Pharmacoresistance during Status Epilepticus
Doctor of Philosophy (PhD), Wright State University, 2012, Biomedical Sciences PhD
Status epilepticus (SE) is a perplexing pathology involving a sudden and long disruption of the brain's normal electrical activity. The study of relevant cellular processes has been useful in identifying therapeutic targets. As a result, many novel drugs are being studied which target receptor systems involved in neuronal membrane excitability. Yet, the standard treatment for SE remains benzodiazepines (BZs), a class of GABAA agonist drugs. Unfortunately, the targeted receptors undergo a desensitization mechanism via enhanced endocytosis (receptor trafficking), leading to rapidly reduced BZ efficacy (pharmacoresistance) within minutes of seizure onset. A comprehensive understanding of the complex interplay between the anticonvulsant's pharmacokinetics and its effect during SE is still lacking. Quantitative information regarding how the trafficking mechanisms of the targeted receptor contribute to the drug's overall pharmacodynamic profile is especially important for the development and assessment of SE countermeasures. This is because the testing of seizure therapeutics can only be performed in animals. Therefore computational modeling of pharmacodynamics provides a useful approach for extrapolations to humans. This dissertation links a physiologically-based pharmacokinetic (PBPK) model for the therapeutic agent, with a cellular level pharmacodynamic (PD) model of the targeted receptors. The latter explicitly takes into accounts the targeted receptor's surface expression and disrupted trafficking during seizures and the binding of the therapeutic drug. This approach is demonstrated for the interaction of diazepam and its major active metabolite, with the GABAA receptor, the major therapeutic target. The GABAA receptor is known to be rapidly modulated during seizure activity. Hypothetically, by accounting for diazepam's pharmacokinetics and occupancy of BZ-sensitive GABAA receptors, as well as the cellular trafficking of those receptors during SE, one should be able to mathematically describe the rapid pharmacoresistance. The model developed suggests that approximately 55% occupancy of the original receptor number is required to reverse ongoing seizures. This is up from a reported 37% occupancy required to prevent seizures in the rat, when diazepam is administered just before seizure onset. The physiological basis of the model allows for extrapolation to humans and dose optimization. In addition, the modeling approach used may serve to explain why some drugs may be more or less effective than BZs in treating SE and to offer suggestions for alternative therapeutics.

Committee:

Jeffrey Gearhart, PhD (Committee Chair); James Lucot, PhD (Committee Co-Chair); Andrian Corbett, PhD (Committee Member); Gerald Alter, PhD (Committee Member); James McDougal, PhD (Committee Member)

Subjects:

Pharmacology

Keywords:

GABAA receptor; PBPK/PD modeling; receptor trafficking; status epilepticus; pharmacoresistance; benzodiazepine

Al-Mafrachi, Basheer Husham AliDetection of DDoS Attacks against the SDN Controller using Statistical Approaches
Master of Science in Computer Engineering (MSCE), Wright State University, 2017, Computer Engineering
In traditional networks, switches and routers are very expensive, complex, and inflexible because forwarding and handling of packets are in the same device. However, Software Defined Networking (SDN) makes networks design more flexible, cheaper, and programmable because it separates the control plane from the data plane. SDN gives administrators of networks more flexibility to handle the whole network by using one device which is the controller. Unfortunately, SDN faces a lot of security problems that may severely affect the network operations if not properly addressed. Threat vectors may target main components of SDN such as the control plane, the data plane, and/or the application. Threats may also target the communication among these components. Among the threats that can cause significant damages include attacks on the control plane and communication between the controller and other networks components by exploiting the vulnerabilities in the controller or communication protocols. Controllers of SDN and their communications may be subjected to different types of attacks. DDoS attacks on the SDN controller can bring the network down. In this thesis, we have studied various form of DDoS attacks against the controller of SDN. We conducted a comparative study of a set of methods for detecting DDoS attacks on the SDN controller and identifying compromised switch interfaces. These methods are sequential probability ratio test (SPRT), count-based detection (CD), percentage-based detection (PD), and entropy-based detection (ED). We implemented the detection methods and evaluated the performance of the methods using publicly available DARPA datasets. Finally, we found that SPRT is the only one that has the highest accuracy and F score and detect almost all DDoS attacks without producing false positive and false negative.

Committee:

Bin Wang, Ph.D. (Advisor); Yong Pei, Ph.D. (Committee Member); Mateen Rizki, Ph.D. (Committee Member)

Subjects:

Computer Engineering

Keywords:

SDN; Controller; DDoS attacks; SPRT; CD; PD; CUSUM; ED

Liang, DongEnvironmental and Alloying Effects on Corrosion of Metals and Alloys
Doctor of Philosophy, The Ohio State University, 2009, Materials Science and Engineering

Occupational Safety & Health Administration (OSHA) under U.S. Department of Labor released a new regulation which required a substantial reduction of the permissible exposure limit (PEL) of Cr6+ from 52 µg/m3 to 5 µg/m3 to protect the workers’ health. Ventilation of the hazardous welding fumes is difficult because manual SMAW is often used in confined spaces during ship-building process. Since the main source of fumes is the melting filler metal, therefore the aim is to develop a chromium-free filler metal for welding of SS304 as a replacement for conventional SS308 while retaining the corrosion properties.

In the first part of this project, corrosion studies were carried out on 304L stainless steel samples welded with Cr-free consumables, which were developed to minimize the concentration of chromate species in the weld fume. The corrosion properties of Ni-Cu and Ni-Cu-Pd Gas Tungsten Arc (GTA) welds and Shielded Metal Arc (SMA) welds are found to be comparable to those of welds fabricated with SS308L consumable. Due to the cost of recently-developed Ni-Cu-Pd weld consumables, efforts have been made to find a substitute for Pd using other relatively cheaper elements while retaining satisfactory corrosion and welding performance. Ru is chosen because it is the cheapest in the Platinum Group Metal. The results suggest that Ni-Cu-Ru welds exhibited comparable or even better corrosion properties than SS308L and Ni-Cu-Pd welds.

In the second part of this project, efforts are put on the connection between lab and field exposure tests because sometimes the correspondence between lab atmospheric corrosion tests (ASTM B117) and field exposures is poor as a result of differences in the critical conditions controlling chemical and electrochemical reactions on surfaces. Recent studies in atmospheric chemistry revealed the formation of reactive species from interactions between UV light, chloride aerosols and oxidizing agents such as ozone. Atmospheric corrosion can be affected by these species which might be transported long distances in the atmosphere. However, these species could be missed in ASTM B117 test.

Initial efforts focused on the effects UV radiation, O3, relative humidity (RH) on the atmospheric corrosion of bare silver. It was found that both UV and O3 are necessary for fast corrosion on bare silver and this fast corrosion reaction results from atomic oxygen generated photodegradation of O3. In the presence of UV and O3, RH has little effect on the atmospheric corrosion of bare silver. Later, focus was put on the atmospheric corrosion of silver with nanometer-sized NaCl particles deposited on the surface. O3 was found to cause corrosion of silver with NaCl particles even in the absence of UV. The enhancement of corrosion by UV is limited for Ag with NaCl particles at low ozone concentration and high RH. The corrosion rate of silver with NaCl particles is found to increase with RH. Finally, bare silver samples were exposed in salt spray chamber according to ASTM B117 up to 4 months. Very little corrosion products were detected after exposure, which is attributed to the lack of reactive species such as O and O3.

Committee:

Gerald Frankel (Advisor); Rudolph Buchheit (Committee Member); Sheikh Akbar (Committee Member); John Lippold (Committee Member); Atanas Rountev (Committee Member)

Subjects:

Materials Science

Keywords:

Chromium free welding consumable; Ni-Cu-Pd; Ni-Cu-Ru; Gas Tungsten Arc Welding (GTAW); Shielded Metal Arc Welding (SMAW); Atmospheric corrosion; Ag; Galvanostatic reduction method; NaCl particles; Thermophoretic deposition method; UV; Relative Humidity

Kang, XuProstaglandin E2 in Oxidopamine-induced Neuronal Inflammation and Injury
MS, University of Cincinnati, 2017, Pharmacy: Pharmaceutical Sciences
Cyclooxygenase-2 (COX-2) is upregulated in many neurological conditions including strokes, epilepsies, neurodegenerative diseases, brain tumors, etc., and plays a pivot role in promoting inflammatory processes within the brain that might facilitate neuronal degeneration and functional impairments. Mounting evidence from preclinical and clinical studies suggests that the pro-inflammatory actions of COX-2 are largely attributed to its major prostanoid product – prostaglandin E2 (PGE2). PGE2 is involved in a variety of physiological and pathological proceedings in the central nervous system (CNS) via activating four G-protein coupled receptors (GPCRs) – EP1, EP2, EP3 and EP4. However, which EP receptor is the culprit of PGE2-mediated neuroinflammation and neurodegeneration remains largely unclear and is presumably dependent on the brain insult types and the responding molecular and cellular components. Here, we show evidence that the COX-2, PGE2 and pro-inflammatory cytokine interlukine-1ß (IL-1ß) are substantially induced in neuronal cells – Neuro-2a (mouse) and SH-SY5Y (human) – that are treated with neurotoxin 6-hydroxydopamine (6-OHDA). Taking advantage of our recently developed novel selective EP2 antagonists – TG4-155 and TG6-10-1, we further demonstrate that EP2 receptor is the major Gas-coupled receptor that mediates PGE2-initiated cAMP-dependent signaling pathway in Neuro-2a and SH-SY5Y cells, and largely contributes to 6-OHDA-induced neurotoxicity. Furthermore, microinjection of 6-OHDA into the striatum also causes COX-2 induction in the brain followed by the upregulation of many inflammation and gliosis-associated genes such as IL-1ß, TNF-a, Iba-1 and GFAP in Sprague Dawley rats. Our results suggest that pharmacological inhibition of EP2 receptor might represent a novel strategy to prevent brain inflammation and injury in neurodegenerative diseases such as Parkinson’s disease.

Committee:

Jianxiong| Jiang, Ph.D. (Committee Chair); Gary| Gudelsky|, Ph.D. (Committee Member); Jiukuan Hao|, Ph.D. (Committee Member)

Subjects:

Pharmaceuticals

Keywords:

PGE2;EP2;PD;COX-2;Neuroinflammation;6-OHDA

Agarwal, ShirishPalladium/Magnesium Bimetallic Systems for Dechlorination of Polychlorinated Biphenyls
PhD, University of Cincinnati, 2009, Engineering : Environmental Engineering

Polychlorinated biphenyls (PCBs), a family of 209 congeners, are recalcitrant environment pollutants and suspected carcinogens prevalent in nation's surface waters, sediments and superfund sites. The threat of PCBs, current state and critical aspects of in-situ reclamation technologies that warrant research focus has been discussed. Toward this end, an effective system has been devised for PCB dechlorination by modifying magnesium (Mg) through the deposition of very small amounts of palladium (Pd). Every Pd/Mg bimetallic particle functioned as numerous nanoscale batteries generating electrons that eventually led to PCB dechlorination. Through our study, we demonstrate Mg to be a promising substrate in Pd-based bimetallic systems for PCB dechlorination. It is the first instance of relating the unique corrosion properties of Mg to distinctive advantages it offers in synthesis, storage and application of bimetallic particles in environmental systems, aspects which have been onerous in Fe-based systems. Also, Mg at a high oxidation potential of 2.37V provides a greater thermodynamic force for dechlorination. These advantages of Mg, coupled with its natural abundance, low density and cost and environmentally friendly nature further strengthen its candidature. The Pd/Mg systems were enhanced using novel techniques of nano-synthesis to obtain tailor-made bimetallic particles with small Pd islands and maximized reduction potential at drastically reduced Pd requirements.

A better understanding of the unexplored Pd/Mg systems was sought by studying their behavior in presence of naturally abundant anions such as sulfate, chloride, nitrate, hydroxide and carbonate and organic solvents that may accompany PCB contamination. While there have been studies on some of these parameters influencing corrosion of pure Mg, literature on Mg galvanically coupled with Pd remains limited. Insights on effect of initial PCB concentration and system pH on dechlorination rates were also provided.

For PCBs undergoing catalytic hydrodechlorination (HDCl), conflicting accounts occur on the reactivity of substituted chlorines and the ensuing dechlorination pathways. In order to understand these relationships, intermediates and dechlorination pathways of carefully selected 17 congeners were investigated. The preferential site of electrophilic attack and its mechanistic aspects were interpreted in terms of steric, inductive and resonance stabilization. The trends for electrophilic substitution were consistently p- > m- > o-positions indicating that more toxic ‘coplanar’ PCBs were preferentially reduced. Dechlorination rates and pathways were influenced both by inductive effect of Cl that governs the stability of the intermediates and by steric effects primarily effecting the adsorption step. In the absence of steric effects, dechlorination occurred preferentially from the less substituted phenyl ring.

Finally, we evaluated the ability of Pd/Mg to dechlorinate i) PCBs spiked in clean clays and sediments and ii) historically contaminated aged sediments (Waukegan Harbor, WHS). While i) Pd/Mg completely dechlorinated multi-component commercial PCB mixtures, and ii) active components in extraction media did not inhibit dechlorination, sulfide in WHS poisoned Pd, compromising Pd/Mg reactivity. We discuss major factors limiting Pd/Mg performance in sediments, proposing possible solutions. Recommendations to improve Mg based systems were made focusing on their nanotechnological aspects including synthesis techniques, challenges in nanoscaling Mg and potential applications in broader environmental spheres.

Committee:

Dionysios Dionysiou (Committee Chair); Souhail Al-Abed (Committee Member); George Sorial (Committee Member); Margaret Kupferle (Committee Member)

Subjects:

Environmental Engineering

Keywords:

PCBs; Dechlorination; Pd/Mg; Bimetallic; Reduction pathway; intermediates; aggressive anions; sediment; nano-synthesis; nano-scaling; sulfide poisoning

Mazi, Wafa A.FORMATION OF C-C COVALENT BOND ON THE SURFACE OF POLY (CHLOROTRIFLUOROETHYLENE) BY SUBSTITUTION
Master of Science, Miami University, 2010, Chemistry
Previous work by our group showed the poly (chlorotrifluoroethylene) can be functionalized by one electron reduction followed by radical trapping. Several new methods for such reduction were examined including Cu / phenanthroline in dimethyl sulfoxide (DMSO), NaS2O4, in DMSO, Zn/Pd in tetrahydrofuran (THF), chloro (pyridine) cobaloxime (III) with Mg in THF, and NiCl2, Mg0 or Cu/ PPh3 in dimethylformamide (DMF) or acetonitrile. The most promising systems were found to be NiCl2, Mg0/ PPh3, but the choice of trapping agent and solvent was crucial. Trapping with acrylonitrile, dihydropyran, butyl acrylate, and styrene were successful. Further reactions of styrylated PCTFE were carried out.

Committee:

Richard Taylor, Dr (Advisor); James Hershberger, Dr (Committee Member); James Cox, Dr (Committee Member); Neil Danielson, Dr (Committee Member)

Subjects:

Chemistry

Keywords:

PCTFE; NaS2O4; DMSO; Zn/Pd; NiCl2; Mg; Cu/ PPh3;acetonitrile;DMF

Banwasi, Rakshita AViews of American Versus Indian Speech Language Pathologists on Diagnosing and Treating Parkinson's Disease
Master of Arts, Miami University, 2004, Speech Pathology and Audiology
The present study investigated the role of a speech-language pathologist (SLP) in diagnosing and treating patients with Parkinson’s disease (PD). Forty SLPs from the U.S. and forty from India were selected at random from the American Speech Language Hearing Association and Indian Speech Language Hearing Association directory respectively. Participants completed a 15-minute oral survey. An initial phone call was made to determine the date and time for conducting the survey and to obtain consent. The results suggested that the American SLPs are significantly more aware of the basic facts regarding diagnosing and treating patients with PD, including specific speech and language techniques. This difference is mainly due to the greater caseload for the American SLPs and the issue of referrals of patients with PD to the Indian SLPs . Prior experience in dealing with patients with PD led to greater SLPs knowledge of diagnosing and treating PD. Most of the American SLPs obtained their knowledge about PD through workshops and continued education units while majority of the Indian SLPs relied on the internet to obtain their information on PD. Only a few of them did obtain their information through classroom education, workshops, and other resources.

Committee:

Alice Kahn (Advisor)

Keywords:

SLP; PD; SPEECH; PARKINSON; American SLPs

Addai, Obeng ARegulated Feedback Networks with Degradation
Master of Science in Mathematics, Youngstown State University, 2015, Department of Mathematics and Statistics
Pharmacokinetic and pharmacodynamic (PK/PD)-models describe and predict the time course of drug effects resulting from a certain dosage administered to an organism. PK/PD models benefit all phases of preclinical and clinical drug development. Their wider application in clinical therapy is to determine the specific dosage for a patient. In this thesis, we review several PK/PD models and investigate the time-to-peak, T, of the models. We state and prove a theorem about the uniqueness of T. The theorem considers PK/PD modes which are linear and nonlinear in the response variable. We show that if the forcing function and the response function satisfy some conditions, then there exists only one peak in the response variable. We apply this theorem to several PK/PD models which have a unique T and show that the condition of the theorem were satisfied. The theorem is also used to investigate how T changes with respect to drug dosage D for the turnover models considered.

Committee:

George Yates, PhD (Advisor); Jozsi Jalics, PhD (Committee Member); Alicia Prieto, PhD (Committee Member)

Subjects:

Applied Mathematics; Biomedical Research; Mathematics

Keywords:

uniqueness of time to peak for some PK PD models;proof of single time to peak for a nonlinear feedback network;analysis on behavior of solution for some nonlinear feedback networks

Dorand, Rodney DixonDEFINING THE ROLE OF IMMUNE THERAPY IN PEDIATRIC CNS MALIGNANCY
Doctor of Philosophy, Case Western Reserve University, 2016, Pathology
Understanding the mechanisms tumors employ to escape detection by both the innate and adaptive immune systems is imperative for developing new immune based therapeutics. Available evidence now favors the view that physiological immune surveillance by members of the innate and adaptive immune systems play an essential role in suppressing tumor development in vivo, and the failure of immune surveillance mechanisms favors tumor development and metastasis formation (1, 2). Whether it is altering cell surface markers, secreting cytokines, or even altering its genome, tumors can evolve much faster than the immune system. New and innovative approaches to cancer therapy are necessary to combat all cancer types, but especially solid tumors as current immunotherapies are more effective at targeting non-solid tumors. Even further complicating physiologic immune surveillance, tumors that develop within the central nervous system (CNS) do so behind the blood brain barrier (BBB) that can serve as an impediment to both the small molecules employed in immunotherapeutics, as well as, the infiltrating lymphocytes necessary for tumor elimination. Medulloblastoma (MB) is the most common malignant CNS neoplasm in the pediatric setting, accounting for 20% of pediatric CNS malignancies overall. It is a WHO-Grade IV primitive neuroectodermal tumor (PNET) that develops in the cerebellum and often invades into surrounding structures including the fourth ventricle and brain stem (3). While treatment modalities and, more importantly, post treatment cognitive instruction has improved outcomes, surviving patients still suffer cognitive sequelae (4). Unique to CNS neoplasms are microglia, an additional immune cell type that plays a pivotal role in normal immune surveillance of the CNS, phagocytosis, and neuroinflammation (5). Microglia reside in the brain parenchyma and help maintain the homeostatic immunosuppressive environment partially due to their expression of CX3CR1. Fractalkine (FKN) is constitutively expressed by neurons and astrocytes leading to tonic inhibition of microglial activation (6). In the presence of malignancy, FKN signaling is disrupted and we found MB can even express FKN itself. Understanding the intricacies of the FKN signaling axis may provide the key signals leading to immune suppression in the CNS in the context of malignant tumors. Furthermore, strategies that augment physiologic immune surveillance, such as the development of tumor vaccines and the addition of small molecule inhibitors, have the potential to benefit therapeutic approaches for CNS malignancies. Whether using a conventional ex vivo vaccine approach (7), or new in situ approaches centered around plant viral nanoparticles (8), vaccination strategies hold great possibilities for enhancing CNS tumor surveillance by vigorously activating the adaptive immune system. To ensure continued activation of the immune response, other therapeutic approaches focus on targeting known immune checkpoint molecules such as CTLA-4, PD-1, or PD-L1, which are expressed on the surface of either immune cells or tumors and inhibit the immune response (9, 10). Additionally, novel approaches can be employed to disrupt the very signaling mechanisms that lead to the surface expression of these immune checkpoint molecules (11). Understanding both the basics of CNS immune cell physiology and how combining targeted immunotherapy with supplemental treatment can counteract suppressive mechanisms is imperative to prevent tumor immune evasion. Enhanced immunotherapeutic approaches to malignant diseases in the CNS have the potential to produce significant increases in overall survival and better prognosis for brain tumor patients.

Committee:

Alex Huang, MD, PhD (Advisor); George Dubyak, PhD (Committee Chair); Clive Hamlin, PhD (Committee Member); Man-Sun Sy, PhD (Committee Member); Gary Landreth, PhD (Committee Member); Agne Petrosiute, MD (Committee Member)

Subjects:

Biology; Immunology; Nanotechnology; Neurobiology

Keywords:

Medulloblatsoma, Cancer Immunotherapy, Viral Nanoparticles, Immune Checkpoint, PD-L1, Cyclin Dependent Kinase-5, Organotypic Brain Slice Culture, Microglia, CX3CR1, IRF2BP2

Trivedi, ChintanIMPLEMENTATION OF AN ADVANCED CONTROLLER ON A TORSIONAL MECHANISM
Master of Science in Electrical Engineering, Cleveland State University, 2011, Fenn College of Engineering
The hardware implementation of an active disturbance rejection controller (ADRC) is presented in the thesis for a mechanical torsional plant. ADRC is a novel disturbance rejection control technique that is not completely dependent on mathematical models of physical systems. In ADRC framework external disturbances, system uncertainties, and internal dynamics of the system are estimated as a generalized disturbance by an extended state observer and the generalized disturbance is effectively canceled by a PD controller. A torsional plant represents a class of rotational systems. Its control challenges are the vibrations caused by mass imbalance, centrifugal imbalance, and the imbalance caused by the non-coincidence between the principal and geometric axes of rotating disc. In the thesis, the ADRC is applied to the torsional mechanism to control the angular speed and displacement of the rotating disc in the presences of the vibrations. Both simulation and hardware implementation results demonstrate the effectiveness of the ADRC. In addition, the hardware implementation results of the ADRC are compared with that of PD controller in terms of performance, control voltage requirement and tuning effort involved in the design process. The comparison study shows the superiority of the ADRC to PD controller.

Committee:

Dr. Lili Dong, PhD (Committee Chair); Dr. Hanz Richter, PhD (Committee Member); Dr. Wenbing Zhao, PhD (Committee Member)

Subjects:

Electrical Engineering

Keywords:

Motion Control; Torsional Plant; State Observer; PD controller

Shin, Hyeon UngCatalytic property of fiber media supported palladium containing alloy nanoparticles and electrospun ceramic fibers biodurability study
Doctor of Philosophy, University of Akron, 2016, Chemical Engineering
The nanoscale of the supporting fibers may provide enhancements such as restricting the migration of metal catalyst particles. In this work, palladium nanoparticle doped alumina fibers were electrospun into template submicron fibers. These fibers were calcined at temperatures between 650°C and 1150°C to vary the crystal structures of the calcined fibers with the Pd particle size. Higher calcination temperatures led to higher reaction temperatures from 250 to about 450°C for total conversion, indicating the effective reactivity of the fiber-supported catalysts decreased with increase in calcination temperature. Pd-Au alloy nanoparticle doped titania fibers were also fabricated using an electrospinning method and assembled into a fibrous porous medium structure by a vacuum molding process. In reactor tests, the fiber media with Pd-Au alloy nanoparticle catalyst had greater reactivity in conversion of NO and CO gases than that of fiber media with Pd monometallic catalyst alone, attributed to a lower activation energy of the Pd-Au catalyst particles. In carbon monoxide oxidation reaction tests, the results showed that the performance was optimal for a catalyst of composition Pd2Au1 molar ratio that was active at 125°C, which had higher dispersion of active components and better catalytic performance compared to monometallic particle Au/TiO2 and Pd/TiO2 fiber media. Moreover, the improved reaction activity of Pd2Au1/TiO2 fiber medium was attributed to a decreased in the activation energy. Further experiments were conducted using the electrospun ceramic fibers biodurability study. The properties of nano-sized fiber structures have attracted the attention of recent research on ceramic nanostructures as nonwoven media for applications in hazardous chemical and high temperature environments. However, health and safety concerns of micro and nano scale ceramic materials have not been fully investigated. Little is known about the physicochemical effects of the properties of small alumina fibers, including fiber sizes, surface morphologies, crystalline, phases, and surface areas with respect to submicron sized alumina fibers formed by calcination of electrospun polymeric fibers. Therefore, in this work, sub-micron sized alumina fibers were fabricated by electrospinning and calcination of a polymer template fiber. In the calcination step, different controlled temperature heating cycles were conducted to obtain fibers of different crystalline structures. Their biodurabilities were evaluated in two types of artificial lung fluids (i.e., mimicking the airway and alveolar macrophages). Though the variation in the soak temperature, their dissolution half times were not significantly affected. The solubility half-times of the alumina fibers were shortest for fibers calcined at the fastest temperature ramp rate (though soak temperature did not have an effect).

Committee:

George Chase, Dr. (Advisor); Rex D Ramsier, Dr. (Committee Member); Chelsea Monty, Dr. (Committee Member); Shing-Chung Wong, Dr. (Committee Member); Edward A Evans, Dr. (Committee Member)

Subjects:

Chemical Engineering; Environmental Science; Materials Science

Keywords:

Fiber; electrospinning; polymer; ceramic; catalytic; nanoparticle; biodurability; calcination; crystal structure; specific surface area; reaction; alloy; palladium; gold; Pd-Au; needless electrospinning

Kumar, RumitPosition, Attitude, and Fault-Tolerant Control of Tilting-Rotor Quadcopter
MS, University of Cincinnati, 2017, Engineering and Applied Science: Aerospace Engineering
The aim of this thesis is to present algorithms for autonomous control of tilt-rotor quadcopter UAV. In particular, this research work describes position, attitude and fault tolerant control in tilt-rotor quadcopter. Quadcopters are one of the most popular and reliable unmanned aerial systems because of the design simplicity, hovering capabilities and minimal operational cost. Numerous applications for quadcopters have been explored all over the world but very little work has been done to explore design enhancements and address the fault-tolerant capabilities of the quadcopters. The tilting rotor quadcopter is a structural advancement of traditional quadcopter and it provides additional actuated controls as the propeller motors are actuated for tilt which can be utilized to improve efficiency of the aerial vehicle during flight. The tilting rotor quadcopter design is accomplished by using an additional servo motor for each rotor that enables the rotor to tilt about the axis of the quadcopter arm. Tilting rotor quadcopter is a more agile version of conventional quadcopter and it is a fully actuated system. The tilt-rotor quadcopter is capable of following complex trajectories with ease. The control strategy in this work is to use the propeller tilts for position and orientation control during autonomous flight of the quadcopter. In conventional quadcopters, two propellers rotate in clockwise direction and other two propellers rotate in counter clockwise direction to cancel out the effective yawing moment of the system. The variation in rotational speeds of these four propellers is utilized for maneuvering. On the other hand, this work incorporates use of varying propeller rotational speeds along with tilting of the propellers for maneuvering during flight. The rotational motion of propellers work in sync with propeller tilts to control the position and orientation of the UAV during the flight. A PD flight controller is developed to achieve various modes of the flight. Further, the performance of the controller and the tilt-rotor design has been compared with respect to the conventional quadcopter in the presence of wind disturbances and sensor uncertainties. In this work, another novel feed-forward control design approach is presented for complex trajectory tracking during autonomous flight. Differential flatness based feed-forward position control is employed to enhance the performance of the UAV during complex trajectory tracking. By accounting for differential flatness based feed-forward control input parameters, a new PD controller is designed to achieve the desired performance in autonomous flight. The results for tracking complex trajectories have been presented by performing numerical simulations with and without environmental uncertainties to demonstrate robustness of the controller during flight. The conventional quadcopters are under-actuated systems and, upon failure of one propeller, the conventional quadcopter would have a tendency of spinning about the primary axis fixed to the vehicle as an outcome of the asymmetry in resultant yawing moment in the system. In this work, control of tilt-rotor quadcopter is presented upon failure of one propeller during flight. The tilt-rotor quadcopter is capable of handling a propeller failure and hence is a fault-tolerant system. The dynamic model of tilting-rotor quadcopter with one propeller failure is derived and a controller has been designed to achieve hovering and navigation capability. The simulation results of way point navigation, complex trajectory tracking and fault-tolerance are presented.

Committee:

Manish Kumar, Ph.D. (Committee Chair); Frank Cazaurang, Ph.D. (Committee Member); Kelly Cohen, Ph.D. (Committee Member); Rajnikant Sharma, Ph.D. (Committee Member)

Subjects:

Aerospace Materials

Keywords:

Quadcopter;Fault Tolerance;Tilt-Rotor;Differential Flatness;PD Control;Stability

Wang, WenBaculovirus Expression and Purification of Wild Type and Mutant Full-Length Human LRRK2
Master of Sciences, Case Western Reserve University, 2008, Environmental Health Science
LRRK2 is a complex 285 kD protein in which the most prevailing mutations G2019S and R1441C are linked to autosomal dominant Parkinson disease (PD). This study has established an expression and purification system to produce active recombinant proteins of the LRRK2, to examine whether the mutations alter the LRRK2 activity and what mechanism underlies the alteration. Both bacterial and baculovirus expression systems were attempted to express and purify the proteins. The active full-length LRRK2 proteins (wild type, G2019S and R1441C) were obtained via the baculovirus system. The bacterial expression system was used for expression and purification of the LRRK2 kinase domain (LRRK2-KD) (wild type and G2019S) but it displayed no activity. The purified recombinant proteins obtained via the baculovirus expression system were analyzed in kinase assays. Our preliminary estimates of Km and Vmax may provide insight regarding the mechanism of LRRK2 activation by PD-linked mutations.

Committee:

Martina L. Veigl, PhD (Committee Chair); Qingzhong Kong, PhD (Advisor); Kumar Alagramam, PhD (Committee Member); John J. Mieyal, PhD (Committee Member); David G McCoy, PhD (Committee Member)

Subjects:

Molecular Biology

Keywords:

PD; LRRK2; Baculovirus expression systems

Thota, Anil K.Biomechanical Assessment of Normal and Parkinsonian Gait in the Non-human Primate During Treadmill Locomotion
Master of Sciences, Case Western Reserve University, 2012, Biomedical Engineering
Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by death of dopamine producing cells in Substantia Nigra. Clinical symptoms of PD include both motor and non-motor symptoms. The motor symptoms are akinesia, bradykinesia, tremor, rigidity and, postural instability and gait disorder (PIGD). In advanced PD patients, PIGD may be refractory to medical treatment and leads to increased risk of fall injuries. A major limitation in studying the underlying mechanisms of PIGD is the lack of a quantitative method to objectively assess gait abnormality and postural instability. The primary aim of this thesis is to quantify the gait pattern abnormality in non-human primate (NHP) model of PD, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated NHP. Gait pattern was assessed by capturing and analyzing 3D kinematic data while NHP was walking on a modified treadmill. The primary biomechanical variables used to distinguish normal and MPTP treated gait patterns were: step cycle duration, percentage of stance phase and angular range. Angle-angle plots were analyzed to assess inter- and intra-limb co-ordination and balance.

Committee:

Jay L. Alberts, PhD (Committee Chair); Robert F. Kirsch, PhD (Committee Member); Dawn Taylor, PhD (Committee Member)

Subjects:

Biomedical Engineering

Keywords:

Parkinson's disease (PD); postural instability and gait disorder (PIGD);1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Kinematic; Biomechanics; Gait

Ciarlariello, Paul DavidIFN-Gamma-Mediated Immunoevasive Strategies in Multiple Myeloma
Doctor of Philosophy, The Ohio State University, 2016, Molecular, Cellular and Developmental Biology
Natural killer (NK) cells are a major source of interferon-γ (IFN-γ) and may play a key role in innate immunity against multiple myeloma (MM). IFN-γ abrogates MM tumor cell in vitro proliferation, however, clinical trials of recombinant IFN-γ in patients with MM showed no benefit. MM cells exhibit strategies designed to evade NK cell surveillance and lysis. Herein, we provide evidence of a novel means of MM immune evasion in which IFN-γ appears to play a reciprocal relationship between MM and NK cells. Patients with MM exhibit higher levels of serum IFN-γ levels than in the healthy setting. NK cells produce IFN-γ in response to MM cells which express functional IFN-γ receptors. Stimulation with IFN-γ leads to increased transcription and expression of the inhibitory ligands HLA-E and PD-L1 by MM cells. This effect may be overcome by interruption of the NKG2A / HLA-E interaction. Intriguingly, MM cells release extracellular vesicles (EV) which are capable of enhancing IFN-γ production of NK cell, thus describing a potential cyclic mechanism of perpetual immune detriment. Taken in total, these results suggest that MM cells subvert the favorable effects of IFN-γ to attenuate NK cell tumor-directed cytotoxicity.

Committee:

Natarajan Muthusamy (Advisor); Don Benson, Jr. (Advisor); Michael Caligiuri (Committee Member); Gregory Lesinski (Committee Member); Flavia Pichiorri (Committee Member)

Subjects:

Immunology; Molecular Biology; Oncology

Keywords:

Interferon, Multiple Myeloma, Natural Killer Cell, immune evasion, immunoevasive, HLA-E, PD-L1, Major Histocompatibility Complex ,MHC, Human Leukocyte Antigen, HLA, inhibitory receptors, extracellular vesicles, microvesicles, exosomes

Bucher, Angie MarieA Survey of Instruments to Assess Teacher Content Knowledge in Science
Master of Education (MEd), Bowling Green State University, 2009, Curriculum and Teaching
With the increasing focus on reform of the educational system in the United States, there is a need for more rigorous assessment on the effectiveness of professional development (PD) programs on both students and teachers. Throughout the years, starting with Sputnik, attention has been drawn to science reform as it is seen as the main vehicle for a more educated, technologically advanced society. This thesis attempts to compare the higher-profile instruments used to measure changes on student and teacher content knowledge as a result of PD participation. The working hypothesis is that effective PD will help teachers to become more competent in the fields that they teach by increasing their content knowledge and improving their pedagogical skills, and should ultimately increase student achievement. However, despite a significant federal and state investment on PD each year, there is really little empirical evidence to prove the connection between teacher PD and student achievement partly due to the lack of valid and reliable instrument to assess that linkage. In this report, I analyze, compare, and contrast content knowledge instrument described in the literature and that are considered scientifically rigorous. Those instruments include ATLAST, MOSART, DTAMS, Praxis, TIMSS, and PISA. The conclusion suggests that additional instruments need to be designed, tested, and utilized to ensure education continues to make progress in science reform. Furthermore, it highlights the need of a national effort to align PD programs to the national standards to facilitate the implementation of the same instruments across programs in order to accurately measure the true impact of PD in our schools.

Committee:

Emilio Duran, Dr. (Committee Chair); Lena Ballone Duran, Dr. (Committee Member); Jodi Haney, Dr. (Committee Member); Larry Graser, Mr. (Advisor)

Subjects:

Education History; Science Education; Teacher Education

Keywords:

PD; professional development; teacher content knowledge; science; instruments; assess; student achievement; evaluation; education; school reform; assessment

Zheng, QiaoyunStudy of Cancer Related Proteins: LRG-1 and PD-L1
Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, 2017, College of Sciences and Health Professions
PROJECT I: In this study, we used the proteomic method to identify a potent biomarker candidate as leucine-rich-a-2-glycoprotein-1 (LRG-1) for cancer from the urine of patients with hepatocellular carcinoma. Further screening revealed that LRG-1 was also present in the urine of patients with a wide range of cancer types and inflammation. We found that LRG-1 could be secreted outside cells as a glycosylated form. To characterize LRG-1, we systematically studied the structure and function of this protein by using chemical N-link and/or O-link glycosylation inhibitors and site-directed mutagenesis, and showed that glycosylation of LRG-1 was able to prevent its degradation by a protease although its secretion was independent on glycosylation. Interestingly, cells deficient LRG-1 migrated faster than wild types cells and the expression of Cyclooxygenase-2 (COX-2) was down-regulated in T cells after incubated with the glycosylated form of LRG-1, suggesting a role of LRG-1 in anti-inflammation. Our findings provide very useful information for developing LRG-1 as a noninvasive urinary biomarker for diagnosis of cancer and inflammatory diseases. PROJECT II: Programmed death-ligand 1 (PD-L1) on cancer cells interacts with programmed cell death protein 1(PD1) of immune cells, resulting in suppression of anti-tumor immunity. Various factors contribute to the high expression of PD-L1 in cancer cells and lead to the escaping from the immune system. Targeting the PD-L1 and PD1 pathway is a novel strategy to restore the immunity and re-activate the immune system to abolish the tumor. Currently, the main research focusing on the pathway uses antibody drugs to block the interaction between PD-L1 and PD1. There is yet no any research effort focusing on the blockade of the PD-L1 expression in cancer cells. Small molecule drugs that can downregulate the PD-L1 expression in cancer tissue have multiple advantages such as penetration of the blood brain barrier compared to antibody drugs. To search for such type of potential lead compounds, a luciferase-based reporter assay was designed, developed, and validated to identify small molecules that can manipulate the expression of PD-L1 in cancer cells. By screening 1680 small molecule compounds, several of them were found to affect the PD-L1 expression in cancer cells.

Committee:

Aimin Zhou, Ph.D. (Committee Chair); Michael Kalafatis, Ph.D. (Committee Member); Xue-Long Sun, Ph.D. (Committee Member); Nolan Holland, Ph.D. (Committee Member); Baochuan Guo, Ph.D. (Committee Member); Bin Su, Ph.D. (Other)

Subjects:

Biomedical Research; Health Sciences; Molecular Biology; Pharmacy Sciences

Keywords:

LRG-1, glycosylation, urinary biomarker, inflammation, PD-L1, reporter luciferase assay, cancer, immunotherapy

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