Master of Engineering, Case Western Reserve University, 2013, EECS - System and Control Engineering

ABBY is a mobile industrial manipulator, a mobile robot equipped with an industrial robotic arm. The goal in creating this robot was to demonstrate that a robust research platform for mobile industrial manipulation can be created quickly at low cost. This goal was achieved by leveraging commercially-available mass produced hardware and open source software. The resulting mobile manipulator incorporates a suite of commercially-available sensors and processing hardware to enable the robot to operate as an intelligent agent alongside humans. The robot demonstrated its abilities by performing simple navigation and manipulation tasks in a laboratory setting, and will soon be employed in research on autonomous kitting in industrial environments.

Committee: Gregory Lee PhD (Advisor); Murat Cavusoglu PhD (Committee Member); Roger Quinn PhD (Committee Member) Subjects: Electrical Engineering; Engineering; Industrial Engineering; Robotics; Systems Design

MS, University of Cincinnati, 2024, Engineering and Applied Science: Mechanical Engineering

Unmanned Aerial Vehicles (UAVs) have seen a rise in applications to various fields. With plenty of algorithms to support automation in UAV flights, Global Positioning System (GPS) is still the major source of position estimation. This has limited the application of UAVs to areas where GPS signal is available and strong. Thus, some other method of position estimation for the UAV is required to expand the UAV application to GPS-denied areas. Moreover, when an operator is piloting a UAV from a remote location, the operator is solely relying on the camera feed coming from the UAV to move the UAV. This camera feed gives a limited field of view of the environment, and the human operator may accidentally run the UAV into an obstacle. In this research, a method of using Hector SLAM for performing position estimation of the UAV in a GPS-denied indoor environment is presented. The Hector SLAM uses a 2D LiDAR mounted on top of the quadcopter to scan the unknown environment. Furthermore, to empower the UAV to autonomously avoid obstacles, an algorithm using Artificial Potential Field method is developed in this thesis which maneuvers the UAV away from obstacles while being piloted by a human operator. The system is developed using Robot Operating System (ROS) and PX4 autopilot. Two different ways, setpoints and attitude commands, of operating the UAV using a keyboard are implemented and compared. The algorithm has been tested in Gazebo Classic simulator and its performance is evaluated.

Committee: Manish Kumar Ph.D. (Committee Chair); David Thompson Ph.D. (Committee Member); Janet Jiaxiang Dong Ph.D. (Committee Member) Subjects: Mechanical Engineering

Master of Science, The Ohio State University, 2024, Electrical and Computer Engineering

As manufacturing techniques such as topology optimization and additive manufacturing develop, components with increasing geometric complexity are becoming more common. Thus, it is necessary to develop automated non-destructive evaluation techniques that are adaptable to various surface geometries. This project seeks to leverage robotic simulation software to virtually plan and optimize eddy current inspections of various airplane components to detect flaws while eliminating false positives. The final deliverable will be a Robot Operating System (ROS) software package that generates an optimal tool path plan based on probe output for various scan resolutions.

Committee: Michael Groeber (Advisor); Balasubramaniam Shanker (Committee Member); Matthew Cherry (Advisor); LoriAnne Groo (Committee Member) Subjects: Aerospace Engineering; Aerospace Materials; Automotive Materials; Computer Engineering; Computer Science; Electrical Engineering; Electromagnetics; Engineering; Experiments; Industrial Engineering; Materials Science; Mechanical Engineering; Robotics

PhD, University of Cincinnati, 2023, Medicine: Immunology

Cognate interaction between effector memory CD4+ T cells (TEM) and dendritic cells (DCs) induces innate inflammatory cytokine production, resulting in detrimental outcomes such as autoimmune pathology and cytokine storms. We previously established that TEM cells use TNF superfamily ligands to activate DCs, yet whether this interaction with DCs induces other cell intrinsic changes that influence inflammatory responses by DCs has never been investigated. Here we have made a surprising discovery that TEM cells trigger double-strand DNA breaks via mitochondrial ROS production in interacting DCs. Initiation of the DNA damage response in DCs leads to activation of a cGAS-independent, non-canonical STING-TRAF6-NFκB signaling axis. Consequently, STING deficient DCs display reduced NFκB activation leading to significant defects in transcriptional induction and functional production of IL-1β and IL-6 following their interaction with TEM cells, both in vitro and in vivo. The discovery of TEM cell-induced innate inflammation through DNA damage and a non-canonical STING-NFκB pathway presents this pathway as a potential target to alleviate T cell driven inflammation in autoimmunity and cytokine storms.

Committee: Chandrashekhar Pasare Ph.D. (Committee Chair); Jonathan Katz Ph.D. (Committee Member); Sing Sing Way M.D. Ph.D. (Committee Member); William Miller Ph.D. (Committee Member); Daniel Starczynowski Ph.D. (Committee Member); Leah Claire Kottyan Ph.D. (Committee Member) Subjects: Immunology

Master of Sciences, Case Western Reserve University, 2023, EECS - Computer and Information Sciences

Action entropy active sensing represents huge leaps forward in the field of active sensing. Previous papers have found that while action entropy increases the accuracy of the simulation, it also increases the time required to calculate sensing actions. The time cost can be reduced by implementing parallel processing that splits the computations over multiple cores. This can be done on a local machine and via implementation of the cloud. This paper focuses on implementing a detection and recovery mechanism for a potential cloud crash. The communication is facilitated through Docker and OpenVPN, using the ROS client-service architecture. This paper adjusts the methodology of the existing model to make it more robust to failures. The simulation results indicate that the time to recovery is feasible, and that this new structure increases the reliability of the existing model

Committee: Vincenzo Liberatore (Advisor) Subjects: Computer Science; Robotics

Doctor of Philosophy, The Ohio State University, 2023, Molecular, Cellular and Developmental Biology

The nucleus is a dynamic organelle whose nuclear envelope (NE) is composed of a double membrane with a distinct but continuous outer nuclear membrane (ONM) and inner nuclear membrane (INM). Linker of the nucleoskeleton and cytoskeleton (LINC) complexes are located at the nuclear envelope and are composed of Klarsicht/ANC-1/Syne Homology (KASH) ONM proteins and Sad1/UNC-84 (SUN) INM proteins. SUN and KASH proteins interact in the NE lumen, forming a bridge between the nucleoplasm and cytoplasm. While plants do not encode homologs of animal KASH proteins, functional analogs have been identified. The Arabidopsis thaliana WPP domain-interacting proteins (WIPs) were the first plant KASH proteins identified. These proteins interact with WPP domain-interacting tail-anchored (WIT) proteins at the ONM, and with Arabidopsis SUN proteins in the INM. Together, a LINC complex comprised of SUN, WIP, and WIT is necessary for proper vegetative nuclear movement and morphology in pollen tubes. In Arabidopsis pollen tubes, the vegetative nucleus (VN) precedes the sperm cells (SCs) and maintains a fixed distance from the pollen tube tip during growth. In pollen tubes of wip and wit mutants, the SCs precede the VN during pollen tube growth and the fixed VN distance from the tip is lost. Pollen tubes frequently fail to burst upon reception at the ovule, leading to a significant fertility defect. In vitro-induction of reactive oxygen species (ROS) has been shown previously to lead to pollen tube growth arrest and rupture in a Ca2+-dependent manner. I hypothesized that the WIT-WIP-SUN LINC complex is required for ROS-induced pollen tube rupture. I report a decrease in Ca2+-dependent ROS-induced pollen tube rupture in both wip and wit mutants. The ROS hyposensitivity correlates with an increased distance of the VN from the pollen tube tip. In addition, I report the first evidence of nuclear Ca2+ fluctuations in the VN and show that the patterns during growth and ROS-mediated pollen tube (open full item for complete abstract)

Committee: Iris Meier (Advisor); Stephen Osmani (Committee Member); Patrice Hamel (Committee Member); Anna Dobritsa (Committee Member) Subjects: Genetics; Molecular Biology; Plant Biology

Master of Science, The Ohio State University, 2023, Mechanical Engineering

This work leverages recent advances in the Robot Operating System (ROS) to design a platform capable of processing previously unknown geometries with minimal user interaction. Industry needs inspection platforms which are adaptable to multiple part families. An eddy current inspection tool was selected to prioritize design choices which accommodated micrometer-precision tool positioning when deployed on an 6-axis industrial robot. These robots offer the physical reach and flexibility required by in situ inspections at the refined control level necessary for accurate data collection. Surface scanning and reconstruction was achieved using a low-cost, commercially available stereoptic camera. Non-contact, material inspection techniques such as eddy current use electromagnetic field propagation to measure variation in electrical conductivity and magnetic permeability to detect defects. Geometry with sharp changes in topology causes magnetic variations which give improper eddy current readings. To circumvent this issue, an operator is used to interactively select inspection surfaces. This manuscript will focus on the design process and a representative deployment using a Yaskawa Motoman GP7 industrial robot. This study successfully implemented a high precision robotic inspection platform using highly configurable software controls while maintaining an easy-to-use user interface.

Committee: Michael Groeber (Advisor); Saeedeh Ziaeefard (Committee Member); Andrew Gillman (Committee Member) Subjects: Mechanical Engineering; Robotics

Master of Science, The Ohio State University, 2023, Mechanical Engineering

This research focused on reducing the fatigue elements related to on track testing of a production vehicle outfitted with an aftermarket autonomous driving package. This package consisted of Autoware.ai operating on the Robot Operating System 1 (ROS) with C++ and Python. Initial focus was understanding the basics of ROS and how to implement test scenarios in Python to characterize the control systems and dynamics of the vehicle. As understanding of the system continued to develop, test scenarios were adapted to better fit system characterization goals with identification of system configuration limits. Trends from on-track testing were identified and pared with first-order linear systems to simulate actual vehicle responses to given command inputs. Sub-models were developed and simulated in MATLAB with command inputs from on-track testing. These sub-models were converted into Python using Spyder, then uploaded into the simulation framework. Full model dynamics within the simulation framework had limited validation due to unexpected system feedback issues with Autoware. This work provides a methodology for model development with future simulation work. The existing system configuration can be altered to allow for various combinations of vehicle performance. Additionally, this work can fast track model development for other autonomous vehicle analyses.

Committee: Dennis Guenther (Advisor); Marcello Canova (Committee Member); Gary Heydinger (Advisor) Subjects: Automotive Engineering; Mechanical Engineering; Robotics; Transportation

Master of Sciences, Case Western Reserve University, 2023, Pathology

Noise-induced hearing loss (NIHL) is a major health issue with no treatment to prevent it. Loss of cochlear sensory ‘hair' cell function is one common cause of NIHL. Studies show that exposure to noise is a major cause of oxidative stress in hair cells, and the mitochondria generates reactive oxygen species (ROS) under stress. Since Szeto-Schiller (SS-31) peptide is a proven inhibitor of ROS production from the mitochondria, it was hypothesized that SS-31 treatment would prevent noise-induced loss of hair cell function. The thesis project was designed to test the hypothesis in a mouse model of NIHL. CBA/J mice exposed to 8-16 kHz noise at 98 dB SPL for 2 hours displayed hearing loss from synaptopathy (reduced hair cell-afferent synapse activity); however, SS-31 treatment initiated immediately after noise exposure prevented the noise-induced phenotype. The results support the hypothesis and highlight the potential of SS-31 to prevent NIHL in humans.

Committee: Ruben Stepanyan (Advisor); Pamela Wearsch (Committee Member); Brian McDermott (Committee Member); Neena Singh (Committee Chair) Subjects: Biomedical Research; Pathology; Pharmacology; Physiology

PhD, University of Cincinnati, 2022, Arts and Sciences: Chemistry

Reactive oxygen species (ROS) are essential to cellular function but in diseased states elevated levels cause oxidative stress. Skin cancer reported as the most prevalent type of diagnosed cancer in the world is primarily caused by ultraviolet radiation (UVR). Studies show UVR exposure leads to several damaging signaling cascades detrimental to cell survival. One mechanism of damage is the overproduction of ROS through activation of NADPH Oxidase (NOX). NOX is a family of holoenzymes comprised of several subunits required for activations. Upon unique complex assembly, NOX produce ROS such as O2.- ,H2O2, OH- which can cause oxidative damage to lipids, protein, and nucleotides. Recent literature has identified NOX1 activation after UV in skin cells. Thus, NOX1 specific inhibitors are promising candidates for prevention of skin cancers. This research examines the efficacy of novel NOX1 inhibitors designed to decrease damage after UVR exposure. Through disruptions of the binding interaction between NOX1 cytosolic subunit NOXO1 and the membrane bound CYBA peptide these inhibitors are proposed to decrease ROS production by stopping UV induced NOX1 complex activation. Using in vitro based cellular studies in primary keratinocytes inhibitor toxicity and ability to protect cell viability after UV are assessed. Additional studies using an optimized skin explant model demonstrate the ability of inhibitors to decrease cellular stress and UV induced DNA damage. Methods are evaluated for the ability to detect inhibitor modulation of direct ROS species production using glutathione and oxidate burst quantification to detect NOX1 inhibition. These studies in combination with key computation design and biophysical evaluation of CYBA-NOXO1 binding interaction produce several plausible drug candidates for further evaluation as NOX1 specific inhibition.

Committee: Pearl Tsang Ph.D. (Committee Member); Ana Luisa Kadekaro Ph.D. (Committee Member); Peng Zhang Ph.D. (Committee Member); Edward Merino Ph.D. (Committee Member); In-Kwon Kim Ph.D. (Committee Member) Subjects: Chemistry

PHD, Kent State University, 2022, College of Arts and Sciences / Department of Chemistry and Biochemistry

The rise of antimicrobial resistance (AMR), coupled with the dwindling number of lead compounds in the drug development pipeline, necessitates the search for antimicrobial agents that have mechanisms of action different from those of the conventional antibiotics to combat AMR. In this regard, metal complexes offer a unique opportunity to access certain modes of action that purely organic compounds may not be able to access. Thus far, many metals including Bi, Zn, Cu, Ag, Te and others have been investigated for such purposes, but Fe is conspicuously missing from this list. The main reason for such omission is that Fe is usually considered a bacterial growth promoter, making the design and synthesis of Fe-based antimicrobial agents seem paradoxical. Although an essential element for all forms of life including pathogenic bacteria, Fe also presents a serious risk of cytotoxicity resulting from its redox activity to trigger the production of reactive oxygen species (ROS) by the Fenton reaction. Therefore, I have begun to explore the capability of neutral octahedral Fe(III)-complexes formed with various bidentate chelating ligands containing the hard Lewis donor atoms of O and/or N to disrupt the regulation of iron uptake in bacteria, and thus delivering iron across the cell membrane for the benefit of developing iron-based antimicrobial agents. I have demonstrated that neutral Fe(III) complexes formed with the naturally occurring metal chelator hinokitiol, 8-hydroxyqunoline and tropolone have the remarkable ability, due to their high lipophilicity and the nonpolar nature, to penetrate the cell membrane of Staphylococcus aureus (SA), thus effectively bypassing the regulation of bacterial iron homeostasis, which in turn triggers the production of ROS through Fenton reaction to exhibit potent antimicrobial efficacy in SA. Furthermore, these Fe(III) complexes show an unusual ability to inhibit biofilm formation. More importantly, the development of resistance in SA toward (open full item for complete abstract)

Committee: Songping Huang (Advisor); Yaorong Zheng (Committee Member); Hao Shen (Committee Member); Min-Ho Kim (Committee Member); Wilson Chung (Committee Member) Subjects: Chemistry

MS, University of Cincinnati, 2022, Engineering and Applied Science: Mechanical Engineering

With the development of artificial intelligence and robotic technology, autonomous vehicles are becoming an important part of road traffic. By collecting and processing the data from installed sensors and cameras, autonomous vehicles navigate themselves by algorithms instead of being driven by humans. It is reported that over 90 percent of accidents are caused by human factors [1]; thus, the application of autonomous vehicles could reduce accidents significantly. In addition, autonomous technologies are based on electric vehicles system, so autonomous vehicles have higher fuel efficiency and lower carbon emission [2]. However, the popularization of autonomous vehicles requires a long period of research time, and there is still a long way to go for autonomous vehicles to replace human-driven vehicles completely. During this period, road traffic will be a mix of autonomous and human-driven vehicles, and autonomous drive technology will be developed under such situations [3]. Autonomous drive in a traffic system with mixed autonomous and human-driven vehicles requires transitioning from a simulation to a real road environment. The simulation environment is a city road sandbox model with mixed vehicles running. Test of autonomous algorithms in the early stage can be deployed to simulation to save cost and ensure safety. In this thesis, a ROS-based control method was developed to simulate a realistic human-driven vehicle used in a mixed environment. Communication algorithms and video transmission of a robotic vehicle were designed and implemented. With developed algorithms, the driver can use a simulator to drive the robotic vehicle in the city road model. For hardware, an off-the-shelf four-wheeled Raspberry Pi robotic vehicle is selected as a testing vehicle and a Logitech G29 Racing Wheel and Floor Pedals kit as the simulator. The control of the vehicle is based on ROS topic communication. The signal of the simulator of the G29 kit is extracted, (open full item for complete abstract)

Committee: Janet Jiaxiang Dong Ph.D. (Committee Member); David Thompson Ph.D. (Committee Member); Ou Ma Ph.D. (Committee Member) Subjects: Mechanical Engineering

Doctor of Philosophy, University of Toledo, 2022, Medicinal Chemistry

Ferroptosis is a recently discovered non-apoptotic cell death mechanism with potential to expand the cancer drug armamentarium. Ferroptotic agents induce accumulation of lipid ROS through inhibition of Xc-, GPX4, and other antioxidant-related proteins compromising cell membrane integrity and leading to eventual cell death. CETZOLE is a novel small molecule that exhibits hallmarks of ferroptosis. Biological studies revealed Xc- as a possible CETZOLE target whilst a parallel study shows that 2-ethynylthiazole moiety acts as the warhead of CETZOLE and targets several intracellular reductive homeostasis-related proteins, including GPX4. In this work, we conducted a structure-activity relationship study of CETZOLEs that resulted in the discovery of CETZOLE analogs as highly potent covalently-binding ferroptosis inducers. Imaging studies using a fluorescent probe showed the localization of the fluorescent probe in cell vacuoles and the nucleus. Qualitative proteomic studies using designed molecular probes indicated several significantly enriched anti-ROS proteins, to be CETZOLE targets, which were then validated by Western blotting. In our recently published work, we showed that imidazole chalcones (IPEs) initially designed as HDAC inhibitors are not classic HDAC inhibitors. However, they have better antimitotic properties characterized by the disruption of the spindle causing mitotic arrest of cancer cells. The installation of a cyclopropyl group on the -unsaturated double bond was done to evaluate the relevance of the -unsaturated double bond for cytotoxicity. Biological evaluation of cyclopropyl analogs showed a 10-fold drop in cytotoxicity, proving that the unsaturated keto-imidazole Michael acceptor is important for IPEs' cytotoxicity. Further comprehensive structure–activity relationship (SAR) studies of IPEs focusing on four major structural variations: the length of the molecule, the Michael acceptor character, the nature and substitution pattern of ri (open full item for complete abstract)

Committee: Viranga Tillekeratne (Committee Chair); William Taylor (Committee Member); Steven Peseckis (Committee Member); Jianglong Zhu (Committee Member); James Slama (Committee Member) Subjects: Biology; Cellular Biology; Chemistry

Master of Science in Electrical Engineering (MSEE), Wright State University, 2022, Electrical Engineering

Cognitive capabilities for robotic applications are furthered by developing an artificial amygdala that mimics biology. The amygdala portion of the brain is commonly understood to control mood and behavior based upon sensory inputs, motivation, and context. This research builds upon prior work in creating artificial intelligence for robotics which focused on mood-generated actions. However, recent amygdala research suggests a void in greater functionality. This work developed a computational model of an amygdala, integrated this model into a robot model, and developed a comprehensive integration of the robot for simulation, and live embodiment. The developed amygdala, instantiated in the Nengo Brain Maker environment, leveraged spiking neural networks and the semantic pointer architecture to allow the abstraction of neuron ensembles into high-level concept vocabularies. Test and validation were performed on a TurtleBot in both simulated (Gazebo) and live testing. Results were compared to a baseline model which has a simplistic, amygdala-like model. Metrics of nearest distance and nearest time were used for assessment. The amygdala model is shown to outperform the baseline in both simulations, with a 70.8% improvement in nearest distance and, 4% improvement in the nearest time, and in real applications with a 62.4% improvement in nearest distance. Notably, this performance occurred despite a five-fold increase in architecture size and complexity.

Committee: Luther Palmer III Ph.D. (Advisor); Trevor J. Bihl Ph.D. (Committee Member); Xiaodong Zhang Ph.D. (Committee Member) Subjects: Artificial Intelligence; Electrical Engineering; Robotics

Master of Science (MS), Wright State University, 2021, Pharmacology and Toxicology

In skin connective tissue, dermal fibroblasts appear to be the most prevalent cell type. They are in charge of making the extracellular matrix that makes up the skin's connective tissue, and also involved in wound healing. Moreover, they produce Insulin-like growth factor-1 (IGF-1) which helps in activation of Insulin growth factor-1 receptor (IGF-1R). This receptor helps to control cell proliferation and responses to DNA-damaging substances such as UVB radiation, reactive oxygen species (ROS), and therapeutic drugs. According to our findings, lack of IGF-1 expression in the dermis of elderly patients due to fibroblast senescence (senescence is characterized by which cells enter a condition of irreversible growth arrest after irreversibly avoiding dividing without enduring cell death) has been linked to an increased incidence of skin cancer in the epidermal keratinocyte. Our group resolved that pretreatment with creatine monohydrate and nicotinamide shows a protective effect on oxidative-stress senescence. Based on this study, the present project was designed to study the effect of creatine and nicotinamide on stress-induced reactive oxygen species (ROS) generation as a possible mechanism for their protective effects. Similarly, the present study also examined how the pro-energetics acts on senescence as a post-treatment. Using primary human dermal fibroblasts exposed to H2O2 in vitro, via ROS staining, beta-galactosidase staining, and RT-qPCR, we discovered that pre-treatment with creatine and nicotinamide reduces oxidative stress-induced ROS levels, while post-treatment with creatine or nicotinamide after H2O2 had no effect on stress-induced senescence.

Committee: Jeffrey B. Travers M.D., Ph.D. (Advisor); Michael G. Kemp Ph.D. (Committee Member); Ravi P. Sahu Ph.D. (Committee Member) Subjects: Pharmacology; Toxicology

Master of Science, University of Toledo, 2021, Mechanical Engineering

Harmful algal blooms (HABs) can be devastating to their local environment by affecting water supplies and wildlife. HAB's are often observed and measured using satellite imagery and water samples. To help prevent damage to the environment, an autonomous swarm of unmanned aerial vehicles (UAVs) and unmanned surface vehicles (USVs) can be used for locating and monitoring the harmful algae. In this study, a swarm of multiple cost-effective USVs, along with an UAV, will be developed to survey an area for HABs. Cost-effective USVs allow for a larger swarm and improving surface coverage area. To accompany the USVs, a UAV uses image processing to identify potential HABs locations, generating target areas relayed to the surface USVs for further investigation. The system functions on a centralized swarm approach with real time data transmission from the quadcopter to a designator that distributes the USV's as the quadcopter scans the area. The models are created with ROS (open source robot control system) and Gazebo (open source robot simulation package) to allow for simulation of controls as implemented on the actual robots. The simulations provide a test chamber for all control code that can be implemented on physical boats to be tested in the field for both ideal and realist effectiveness of this heterogeneous swarm environmental sensing method.

Committee: Brian Trease PhD (Committee Chair); Meysam Haghshenas PhD (Committee Member); Adam Schroeder PhD (Committee Member) Subjects: Mechanical Engineering

Doctor of Philosophy (PhD), Ohio University, 2020, Chemistry and Biochemistry (Arts and Sciences)

Mass Spectrometry (MS) has become a widely used technique for characterization and identification of both small and large molecules. This project presents a novel quantification approach, based on electrochemistry (EC) combined with mass spectrometry (MS), in which the oxidation current recorded from an electrochemistry (EC) measurement and the oxidation reaction yield from MS signal changes upon electrolysis can be used to identify chemicals. In combination with liquid chromatography (LC), the method can also be applied to complex mixture analysis. The striking advantage of such a method is that no standard compound is required. Several analyte molecules such as dopamine, norepinephrine, rutin, and glutathione were successfully identified using our method with the quantification error ranging from -3.4% to +4.6 %. Analytes in complex samples (e.g., uric acid in urine) were also accurately measured. In our experiments, a minimal amount of sample (e.g., 300 pmol of the compound) was used for quantification indicating our method is highly sensitive. The results presented here demonstrate that mass spectrometry is a powerful technique that not only can detect metabolites at low concentrations, but also can be used for capturing and characterizing the short-lived reaction intermediates due to its gentle ionization process which transfer products directly from liquid to the gas phase. By using both electrospray ionization (ESI)-MS and desorption electrospray ionization (DESI)-MS techniques, Pd (IV) and Au (III) intermediates were successfully captured and the reaction mechanism therefore was confirmed. The second study presented here is the development of novel nanoparticles to detect and scavenge ROS in living cells. Oxidative reactive oxygen species (ROS) are held in dynamic equilibrium with reducing species in living systems. When present at appropriate concentrations, ROS can have beneficial antimicrobial and anti-inflammatory effects. However, excessive ROS ca (open full item for complete abstract)

Committee: Justin Holub (Advisor); Peter Harrington (Committee Member); Travis White (Committee Member); Peter Jung (Committee Member) Subjects: Analytical Chemistry; Biochemistry; Chemistry

Master of Science in Pharmaceutical Science (MSP), University of Toledo, 2020, Pharmaceutical Sciences (Pharmacology/Toxicology)

In response to legal restrictions on methamphetamine (MA) and 3,4- methylenedioxymethamphetamine (MDMA), there has been an increase in the use of synthetic psychoactive cathinone's (SPCs). SPCs are structurally similar to MA and MDMA, sharing many of their psychostimulant properties, however, there is some question as to whether the drugs in this class share similar hyperthermic, lethal, and neurotoxic effects as MA and MDMA. While the mechanisms of action of these drugs are still being studied, clinical reports suggest that they produce hepatocellular damage, contributing to their potential lethal effects. In studies in mice and zebrafish, the Hall laboratory has shown that MA, MDMA and SPCs induce lethal effects that are associated with seizures, perhaps indicative of uncontrolled glutamatergic activation. In a series of experiments, Halpin and Yamamoto (Halpin et al., 2013; Halpin and Yamamoto, 2012) have shown that MA induces liver impairments and elevations in plasma ammonia that contribute to increased glutamatergic activity. In our own studies we have also observed that liver tissue was severely damaged by exposure to these drugs, encouraging the use of liver cells to further understand how these drugs work. In the following project different concentrations of MA and MDMA were used in order to determine the IC50 values and the mechanism of cell death. The obtained IC50 values of MA and MDMA, through MTT assay, were used to define dose ranges for subsequent studies: a concentration which would not cause any cell death (0 mM), a concentration which is below our observed IC50 (1 mM), a concentration just above the observed IC50 values (3 mM), and a concentration which would almost completely inhibit cell survival (10 mM). In order to determine the mechanism of cell death, this study included MTT assays, LDH assays, ROS assays, and Western blots, as well as data obtained through the Incucyte live cell imaging system. MTT assays determine the concentration of drug (open full item for complete abstract)

Committee: Scott Hall (Committee Chair); Terry Hinds (Committee Member); Amit Tiwari (Committee Member) Subjects: Biology; Cellular Biology; Experiments; Health Sciences; Morphology; Pharmaceuticals; Pharmacology; Pharmacy Sciences; Toxicology

PhD, University of Cincinnati, 2020, Pharmacy: Pharmaceutical Sciences

Melanoma is the deadliest form of skin cancer. Although melanoma cases represent only 4% of all skin cancers, it accounts for 80% of all skin cancer-related deaths [1]. The identification of BRAF mutants in cancer piloted a new era in the treatment of advanced melanomas. Approximately one-half of melanomas contain a BRAFT1799A transversion, encoding the constitutively active BRAF V600E oncoprotein [3]. This discovery led to the clinical development of selective ATP-competitive RAF kinase inhibitors, including vemurafenib and dabrafenib, targeting the mutant BRAF protein. Treatment of melanoma patients with BrafV600E with either BRAF inhibitor resulted in a response rate of about 50% and median progression-free survival of about 5 months [4, 5]. With the success of clinical trials [6, 7] BRAF-inhibitor and MEK-inhibitor combination therapy has become the standard of care for BRAF-mutant melanoma with response rates of ~70% and disease control in almost all patients. Despite these successes, most treated patients will eventually exhibit disease progression. The acquired resistance to these inhibitors has limited their long-term efficacy, and has stirred interest in understanding the mechanisms underlying resistance. Recent observations demonstrate that BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells. A100, identified from a library screen, is a ROS-activated prodrug that self-cyclizes into a stable bicyclic ring and causes DNA double strand breaks. We proposed to examine if ROS activated therapy will inhibit tumor growth and evade resistance to BRAF inhibitors. In this study, the BRAF inhibitor dabrafenib was used to generate resistant cell lines (A375DR, SK-MEL-24DR and WM-115DR). Furthermore, we observed that resistant cells had increased levels of the mitochondrial antioxidant enzymes superoxide dismutase 2 (SOD2) and peroxiredoxin 1 (PRDX1). We found that A100 sensitized the resistant melanoma cells to dabrafenib and induced DNA damage. C (open full item for complete abstract)

Committee: Joan Garrett Ph.D. (Committee Chair); Zalfa Abdel-Malek Ph.D. (Committee Member); Pankaj Desai Ph.D. (Committee Member); Nalinikanth Kotagiri Ph.D. (Committee Member); Timothy Phoenix Ph.D. (Committee Member) Subjects: Pharmaceuticals

Master of Sciences (Engineering), Case Western Reserve University, 2020, EECS - Electrical Engineering

Robots are ideal for work in inhospitable environments. These environments are often far away, under water, or in space, and robots operating there are susceptible to communications lag between the operator and the robot. This results in long missions, which are tedious for robot operators and hard on remote energy sources. Autonomous skills solve this problem. Using a six DOF robotic arm, a six DOF force-torque sensor, Robot Operating System (ROS), and Natural Admittance Control (NAC), skills have been developed that are stable, robust, gentle, and quick. A robot supervisor using these skills can quickly perform assembly tasks such as removing a child-proof medicine bottle cap and inserting a cylinder over a peg even under effort constraints and two second communication lag.

Committee: Wyatt Newman (Advisor); Greg Lee (Committee Member); Cenk Cavusoglu (Committee Member) Subjects: Computer Science; Electrical Engineering; Engineering; Robotics; Robots