Master of Science, The Ohio State University, 2021, Environmental Science

Beekeepers are reporting significant honey bee deaths during and after almond bloom. These losses pose a major problem for the California almond industry because of its dependence on honey bees as pollinators. This research aimed to determine if combinations of agrochemicals applied during almond bloom were a possible explanation for losses reported by beekeepers. Common agrochemical mixtures often include pesticides such as insecticides and fungicides, and pesticide adjuvants, which are added to improve the performance of pesticides. This research was performed in two separate studies which both looked at the acute effects of individual and mixture effects on adult honey bee mortality. The first study looked primarily at insecticide-fungicide mixture toxicity, however, the pesticide adjuvant Dyne-Amic was used in this first study as an introduction to pesticide adjuvant toxicity alone and in combination with pesticides. The second study focused primarily on establishing toxicities for a number of different pesticide adjuvants and later looked at the toxicity of some of these adjuvants in combination with pesticides. In both studies, a Potter Spray Tower was used to mimic the spray application route of exposure and apply widely used pesticide and pesticide adjuvant formulations at field relevant application rates to adult honey bees. Previous research has shown that combinations of fungicide and insecticide active ingredients can be more toxic than the individual pesticides. The first study aimed to test the effects of pesticides and pesticide mixtures to honey bees, using formulated pesticide products sprayed on the bees at field relevant concentrations. Insecticides tested included Altacor and Intrepid and fungicides included Tilt, Pristine, Luna Sensation and Vangard, all of which are widely used in almonds during bloom. In the first study, synergistic toxicity was observed when the fungicide Tilt (a.i. propiconazole) was applied with the insecticide Altacor (open full item for complete abstract)

Committee: Reed Johnson (Advisor); Guy Brock (Committee Member); Roman Lanno (Committee Member); Larry Phelan (Committee Member) Subjects: Entomology; Environmental Science

Master of Science (MS), Ohio University, 2019, Biomedical Engineering (Engineering and Technology)

Drug development is an ever-increasingly prominent field in the scientific community. A crucial step in the drug development process involves examining the toxicity of potential therapeutic compounds. A plethora of organic compounds have been synthesized through an ongoing drug discovery program at Ohio University. Two of these compounds have demonstrated significant promise in several models of disease. In the present study, the potential toxicity of these two compounds was evaluated via in silico and in vitro techniques.

Committee: Douglas Goetz Ph. D. (Advisor); Monica Burdick Ph. D. (Committee Member); Sumit Sharma Ph. D. (Committee Member); Robert Colvin Ph. D. (Committee Member) Subjects: Biomedical Engineering; Biomedical Research

Doctor of Philosophy, University of Toledo, 2018, Civil Engineering

This dissertation explores the eco-design concepts for emerging PV cells. By conducting life cycle assessment (LCA) method, I addressed the following questions: (1) What is the environmental impact of a scalable perovskite PV cell? (2) How important are the metal emissions from the emerging thin film devices during the use phase? (3) What are the environmental impacts and costs of the materials used in emerging PVs? These questions are addressed in the analyses presented in the Chapters two, three and four, respectively. Chapter two assesses the environmental impacts of perovskites PVs that have device structures suitable for low cost manufacturing. A structure with an inorganic hole transport layer (HTL) was developed for both solution and vacuum based processes, and an HTL-free structure with printed back contact was modeled for solution-based deposition. The environmental impact of conventional Si PV technology was used as a reference point. The environmental impacts from manufacturing of perovskite solar cells were lower than that of mono-Si. However, environmental impacts from unit electricity generated were higher than all commercial PV technology mainly because of the shorter lifetime of perovskite solar cell. The HTL-free perovskite generally had the lowest environmental impacts among the three structures studied. Solution based methods used in perovskite deposition were observed to decrease the overall electricity consumption. Organic materials used for preparing the precursors for perovskite deposition were found to cause a high marine eutrophication impact. Surprisingly, the toxicity impacts of the lead used in the formation of the absorber layer were found to be negligible. Chapter three addresses the life cycle toxicity of metals (cadmium, copper, lead, nickel, tin and zinc) that are commonly used in emerging PVs. In estimating the potential metal release, a new model that incorporates field conditions (crack size, time, glass thickness) and phy (open full item for complete abstract)

Committee: Defne Apul (Committee Chair); Michael Heben (Committee Member); Randall Ellingson (Committee Member); Constance Schall (Committee Member); Cyndee Gruden (Committee Member); Kumar Ashok (Committee Member) Subjects: Energy; Environmental Engineering

Doctor of Philosophy, The Ohio State University, 2015, Integrated Biomedical Science Graduate Program

Nanoparticles are increasingly being incorporated into common consumer products, including in foods and food packaging, for their unique properties at the nanoscale. Food-grade silica and titania are used as anti-caking and whitening agents, respectively, and these particle size distributions are composed of approximately one-third nanoparticles. Zinc oxide and silver nanoparticles can be used for their antimicrobial properties. However, little is known about the interactions of nanoparticles in the body upon ingestion. This study was performed to investigate the role of nanoparticle characteristics including surface chemistry, dissolution, and material type on toxicity to the intestinal epithelium. Only mild acute toxicity of zinc oxide nanoparticles was observed after 24-hour treatment of intestinal epithelial C2BBe1 cells based on the results of toxicity assays measuring necrosis, apoptosis, membrane damage, and mitochondrial activity. Silica and titanium dioxide nanoparticles were not observed to be toxic although all nanoparticles were internalized by cells. In vitro digestion of nanoparticles in solutions representing the stomach and intestines prior to treatment of cells did not alter nanoparticle toxicity. Long-term repeated treatment of cells weekly for 24 hours with nanoparticles did not change nanoparticle cytotoxicity or the growth rate of the treated cell populations. Thus, silica, titanium dioxide, and zinc oxide nanoparticles were found to induce little toxicity in intestinal epithelial cells. Fluorescent silica nanoparticles were synthesized as a model for silica used in foods that could be tracked in vitro and in vivo. To maintain an exterior of pure silica, a silica shell was hydrolyzed around a core particle of quantum dots or a fluorescent dye electrostatically associated with a commercial silica particle. The quantum dots used were optimized from a previously reported microwave quantum dot synthesis to a quantum yield of 40%. Characteri (open full item for complete abstract)

Committee: W. James Waldman PhD (Advisor); Prabir Dutta PhD (Committee Chair); Narasimham Parinandi PhD (Committee Member); Estelle Cormet-Boyaka PhD (Committee Member) Subjects: Biomedical Research; Nanotechnology; Toxicology

Master of Science (MS), Wright State University, 2011, Biochemistry and Molecular Biology

We describe a methodology that combines urinary metabolomics with a tissue-specific stressor administration to enhance assessment of tissue function. Kidney function in rats was mildly compromised with a sub-acute dose of D-serine and stressed with furosemide. NMR-based metabolomics analyses showed no detectable effects due to D-serine alone; but furosemide or D-serine + furosemide groups, classified separately from each other, and from control. Furosemide alone caused a ca. 2-fold increase in glucose, lactate, choline, and a 30% decrease in TCA intermediates (p≤0.05). D-serine suppressed these effects and produced a 1.7-fold increase in a p-phenolic acid-derivative of tyrosine (PAdY) relative to control (p≤0.05). The PAdY/tyrosine ratio increased 2-fold relative to rats given furosemide alone. D-serine effects were only detectable in furosemide-challenged rats, suggesting that minor disruption in kidney function, induced by low-level D-serine, is manifested by this functional metabolomics methodology. This technique may improve sensitivity for assessment of tissue function and disease

Committee: Nicholas V. Reo PhD (Advisor); MIchael L. Raymer PhD (Committee Member); Oleg Paliy PhD (Committee Member) Subjects: Biochemistry

Master of Science in Pharmaceutical Sciences, University of Toledo, 2010, Pharmaceutical Science

Ambroxol is an active metabolite of bromexine that has been proven to possess a great bronchosecretolytic effect and has been used to treat infants from 0 to 6 month and children till over 12 years of age, as well as adults. My thesis research was aimed to detect potential adverse effects of ambroxol on development using zebrafish embryos/larvae as a model and to investigate the possible involvement of the zebrafish cytosolic sulfotransferases (SULTs) in the protection against the possible adverse effects. Developing eggs at 24 hpf, 48 hpf, and 72 hpf were exposed to different concentrations (1mM, 0.5 mM, 0.25 mM, 0.125 mM, and 0.05 mM) of ambroxol in triplicate and observations were made daily for eleven consecutive days. Ambroxol induced cardiac edema and bradycardia at different stages of development in a dose-dependent manner. Enzymatic assay of purified zebrafish SULTs showed significant sulfation of ambroxol by SULT2 ST1 and SULT3 ST1, 2, 3, 4, and 5. How these SULTs may be involved in protection against the adverse effects of ambroxol remains to be clarified.

Committee: Ming-Cheh Liu PhD (Committee Chair); Frederick Williams PhD (Committee Member); Zahoor Shah PhD (Committee Member) Subjects: Pharmacology

Doctor of Philosophy, The Ohio State University, 2024, Microbiology

Bacteria can communicate with each other through the production, release, and detection of small molecules called N-acyl homoserine lactones (AHLs). In a subset of the family Enterobacteriaceae, including the well-known genera Salmonella and Escherichia, AHLs are not produced but these bacteria retain the ability to detect them through the LuxR-type protein SdiA. This strategy is referred to as eavesdropping: where one species may listen in on the communication of another. The role of SdiA-mediated eavesdropping in the lifecycle of these bacteria is unknown. To determine the function of eavesdropping, we first reviewed the available literature on SdiA. Since the initial discovery of SdiA, many studies have attempted to gain insight into its role by looking for mutant defects in various host systems, elucidating the SdiA regulon, or finding in vitro phenotypes. The literature on each topic is complex and interpretation must be measured and considerate of the methodology used. We next examined the role of Salmonella SdiA in several host systems, including house flies, mice, and plants. We also determined the SdiA regulons of Salmonella, E. coli, and Enterobacter cloacae. The house fly is a known mechanical vector of Salmonella with some evidence of a more dynamic interaction between host and bacteria. Based on the abundance of AHL synthase homologs in insect metagenomes, we hypothesized that SdiA played a role in the survival of Salmonella within house flies. After a series of experimental infections, the evidence suggests that sdiA mutants are highly advantaged over their wild-type competitor and that SdiA may have a negative effect on survival within house flies. Using a randomly barcoded transposon library (Barseq), we examined Salmonella fitness in mice that were co-infected with the AHL producing pathogen Yersinia enterocolitica. Consistent with previous reporting, sdiA and its regulon suffered no fitness defects during gastroenteritis. Finally, an experiment (open full item for complete abstract)

Committee: Brian Ahmer (Advisor); Chad Rappleye (Committee Member); Sarah Short (Committee Member); John Gunn (Committee Member) Subjects: Microbiology

MS, Kent State University, 2024, College of Arts and Sciences / Department of Computer Science

Online communities have long suffered from issues caused by a lack of accountability for participants exhibiting toxic behaviors. Difficulty with providing effective moderation, sufficiently dissuading would-be offenders, identifying problem users, and mitigating toxic activity in real-time has led to an unwelcoming environment for users. It's difficult to effectively police communication networks to provide safe environment's when participants are both anonymous and cannot be sufficiently identified as problematic. Our study employs temporal multivariate data mining and pattern analysis, and natural language processing techniques to examine organic conversations across a large collection of online gaming communities' messages. By analyzing instances of toxic behavior, arguments, and profane conversation, our objective is to identify the distinct features that characterize toxicity in digital environments. Our study analyzed conversational data extracted from four video game focused Discord communities. The dataset encompasses a rich collection of 685,432 public messages. Using the Perspective API, messages were classified against six metrics relating to toxicity. To elucidate the temporal dynamics and complex patterns of these interactions, we employed Temporal Multidimensional Scaling and utilized a Shannon Entropy Visualization method. Additionally, manual review was performed on a subset of 140,000 comments' worth of toxic events. We then leveraged BERTopic for cluster analysis to deduce related thematic concerns. For a nuanced representation of these themes, we customized the topic modeling using OpenAI's GPT-3.5 Turbo language model, enriching our understanding of the contextual underpinnings of toxicity in online gaming discourse. Our study found that toxic events occurred without warning and rapidly dissipated as the conversation went on. Toxicity is extremely rare relative to the general activity of the community and is largely contributed by eith (open full item for complete abstract)

Committee: Ruoming Jin (Advisor) Subjects: Artificial Intelligence; Computer Science

Master of Science, The Ohio State University, 2024, Chemical Engineering

A quantitative structure-activity relationship (QSAR) model relates the structure and/or physical properties of molecules to their biological activity. A good QSAR model can predict the environmental fate of molecules and assist in quickly screening chemical compounds for potential toxicity at a low cost, reducing or eliminating the need for experimental studies. The dataset used to train a QSAR model impacts performance. Often, training sets are small due to limited experimental data, causing concern over the reliability of a model's predictions. In other cases, very large training sets may increase computation time and costs. In response to these issues, this work proposes that a smaller, diverse training set of molecules can be used to build a model that performs just as well as one built on a larger training set. A structurally diverse training set of compounds is relatively uniformly spread throughout a given chemical space, increasing the chance that a new molecule is reliably predicted by a model. The dataset used to test this proposal consists of 1603 organic molecules with a molecular endpoint of ready biodegradability. ToxPrints were used as features to represent the compounds. The MaxMin algorithm, paired with either the complement of the Tanimoto coefficient or the Modified Tanimoto Coefficient, was used to select a smaller, diverse set of molecules from a randomly determined whole training set. The performance of models built on these smaller, diverse sets was compared to the performance of models built on the whole training set and on smaller, randomly selected training sets. Various sizes of the diverse and random training sets were examined. Diverse training sets that were at least 60% the size of a whole training set led to similar model performance as the whole training sets. Randomly selected training sets consistently resulted in lower model performance across all sizes. The Tanimoto and Modified Tanimoto coefficients created (open full item for complete abstract)

Committee: James Rathman (Advisor); Isamu Kusaka (Committee Member) Subjects: Chemical Engineering

Master of Science (MS), Wright State University, 2023, Biological Sciences

Although α-synuclein (α-syn) has been linked genetically and pathologically to Parkinson's disease, the mechanism by which it drives disease pathogenesis is not fully understood. When α-syn is overexpressed in yeast, it forms abnormal cytoplasmic accumulations and leads to cell death, resembling the phenotypes observed in neurons. Such yeast models have been widely used to uncover molecular mechanisms of α-syn toxicity, but the induction of α-syn relies on growing yeast in galactose, a fermentable carbon source. Yeast does not require cellular respiration when grown in galactose, thus limiting the understanding of α-syn toxicity when cellular respiration is essential for neurons. We developed a new model that expresses α-syn under the respiratory condition. We observed striking mitochondrial defects correlated with α-syn accumulation and toxicity. We also identified human and yeast genes that suppress α-syn toxicity and reduce mitochondrial damage. Our data support using a respiratory cell model to study mitochondria-associated α-syn toxicity.

Committee: Quan Zhong Ph.D. (Advisor); Lynn Hartzler Ph.D. (Committee Member); Hongmei Ren Ph.D. (Committee Member) Subjects: Biology

Master of Science (MS), Wright State University, 2023, Biological Sciences

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes the degeneration of motor neurons which leads to loss of motor function and eventual death. Over 20 genes have been implicated in ALS's pathogenesis, one being TARDBP, which codes for TDP-43. TDP-43 mislocalizes from the nucleus, accumulates, and then aggregates in the cytoplasm and is linked to cellular toxicity. We have modeled this aggregation and toxicity of TDP-43 in budding yeast. From genetic screens of human genes and their ability to modulate TDP-43 toxicity, we found 50 human genes that were able to reduce TDP-43 toxicity. 12 of these genes expressed the strongest rescue phenotype. Interestingly, these 12 genes did not lower the protein level or aggregation of TDP-43, nor did they exhibit any protein-protein interactions with TDP-43. We then investigated a possible cellular pathway that could be associated with TDP-43 toxicity and examined how our suppressors were able to reverse its effects. We identified four suppressors that were implicated in the cAMP/PKA pathway, with two of them directly downregulating it. Further analysis revealed that out of these four genes, two led to significantly increased cAMP levels compared to TDP-43 alone. We then studied a downstream target of the cAMP/PKA pathway, stress granule formation. Our observation indicated that TDP-43 not only colocalized with stress granules but also stimulated their formation.

Committee: Shulin Ju Ph.D. (Advisor); Michael Markey Ph.D. (Committee Member); Andrew Voss Ph.D. (Committee Member) Subjects: Biology; Cellular Biology; Molecular Biology

Master of Science, The Ohio State University, 2023, Environmental Science

Commercial beekeepers transport honey bees across the United States to provide pollination services to almonds and other bee-pollinated crops. Unfortunately, beekeepers have reported honey bee deaths while providing pollination services, possibly due to pesticide applications made during crop bloom. Pesticides contain both active ingredients that carry the pesticidal properties and “inert” or “other” ingredients in the formulation to improve the application properties of the pesticide. Pesticide applications are often made as “tank mixes” of multiple pesticide products, each with their own active and “inert” ingredients, and may also include spray adjuvants, which are formulations of additional “inert ingredients.” Adjuvants are intended to improve the handling or application characteristics of a pesticide application often by increasing the spreading, sticking, and penetration of pesticides through crop leaves. These “inert ingredients” that are present both as pesticide formulation components and as the “principal functioning agents” in adjuvant products do not undergo the same testing and risk assessment that is required of pesticide active ingredients and generally have no mitigation measures that prevent application onto crops during bloom at times of day when bees are foraging. This thesis consists of a literature review, a primary research study, and a research brief. The literature review suggests that the use of agricultural adjuvants and tank mix combinations of adjuvants with pesticides may be contributing to observed colony losses during almond pollination in California, highlighting a need to focus on the toxicity of these “inert ingredients” to honey bees. The research study aimed to determine toxicity of adjuvants to adult worker honey bees, both when applied alone and in adjuvant-pesticide tank mixtures for the suite of fungicides, insecticides, and adjuvants commonly applied as tank mixes to almonds during bloom. Field-relevant combinations of fo (open full item for complete abstract)

Committee: Reed Johnson (Advisor); Megan Meuti (Committee Member); Christopher Ranger (Committee Member); Robyn Wilson (Committee Member) Subjects: Entomology; Environmental Science; Toxicology

Doctor of Philosophy, The Ohio State University, 2022, Entomology

Metal contamination, resulting from industrial, mining, transportation, and incineration activities, is ubiquitous in urban and other human dominated areas and poses an understudied yet potentially impactful challenge to pollinator communities. Legacy cities, concentrated in post-industrial regions, are cities that experienced a dramatic economic decline, followed by an exodus of residents which led to an abundance of vacant infrastructure and land that is oftentimes contaminated with metals. Increasing interest in reimagining unused urban land as habitat for bees and other beneficial species has created an urgent need to identify and isolate the impacts of metal exposure on these pollinators. Bees are exposed to and accumulate metals while searching for food and resources within contaminated regions, yet, they and other organisms are readily found within contaminated landscapes despite the potential negative effects of metal exposure. Therefore, the overarching goals of this dissertation research were to determine the lethal limits of metal exposure for bees, investigate the impacts of field relevant concentrations of common urban metals on bumble bee colony health, and asses any sublethal effects of metal exposure on bumble bee foraging behavior. Focusing first on legacy cities' unique opportunities for urban bee habitat with a potential for unintended metal exposure, the first objectives of this research were to review the literature on potential metal exposure routes for pollinators, and if bees are exposed, the impacts of metals on wild bee health, fitness, and behavior (Chapter 1). My next objective was to identify if, and at what concentrations, metal exposure results in forager bee mortality and if bees bioaccumulate any metals within their bodies (Chapter 2). Next, I wanted to identify how exposure to environmentally relevant concentrations of metals arsenic, cadmium, chromium, and lead that bees encounter in cities influence overall Bombus impatiens co (open full item for complete abstract)

Committee: Frances Sivakoff (Committee Member); Roman Lanno (Committee Member); Reed Johnson (Committee Member); Mary Gardiner (Advisor) Subjects: Entomology

Master of Science (MS), Wright State University, 2022, Chemistry

Benzotriazoles are a class of contaminant of emerging concern which are commonly used as anticorrosive agents in aircraft deicer and anti-icing fluids (ADAFs). The analogues 1H-benzotriazole (BTZ), 4-methyl-1H-benzotrizole (4m-BTZ), and 5-methyl-1H-benzotriazole (5m-BTZ) are commonly found in environmental occurrence together. The two methylated isomers, collectively known as tolytriazole (TTZ), have different toxicity and stability. These contaminants are highly water soluble and resistant to biodegradation, making them persistent through water treatment. Benzotriazoles have been detected worldwide; this investigation focuses on monitoring three sites near a small airpark in Wilmington, Ohio. Two sites that receive runoff from the airpark, Lytle Creek and Indian Run, have been under investigation for decades due to documented poor water quality issues. This investigation adds to data from the two previous years documenting an increase in BTZ compounds that corresponds to an increase in activity at the airpark by an online retailer. Solid Phase Extraction (SPE) was used to isolate benzotriazoles from surface water samples. Liquid Chromatography/Mass Spectrometry (LC/MS) was used for separation and detection of analytes. Each consecutive monitoring season detected more BTZ and TTZ on average than previous seasons. The 2021 season detected TTZ from 0.346-1.785 µg/L at Indian Run. Lytle Creek yielded BTZ from 0.051-0.158 µg/L and TTZ from 1.700-51.87 µg/L. Other occurrences have detected BTZ compounds associated with airpark runoff ranging from ng/L to mg/L. Gas Chromatography/Mass Spectrometry (GC/MS) was employed to separate the two TTZ isomers that could not be separated by LC/MS. This method revealed a ratio of 41.29% 4m-BTZ and 58.71% 5m-BTZ in selected water samples, a ratio which is similar to findings in a Wisconsin study. Based on the ratios of each isomer, hazard quotients assessed most samples analyzed as low environmental risk with a few days presenting med (open full item for complete abstract)

Committee: Audrey McGowin Ph.D. (Advisor); Steven Higgins Ph.D. (Committee Member); Eric Fossum Ph.D. (Committee Member) Subjects: Analytical Chemistry; Chemistry; Environmental Science

Doctor of Philosophy, The Ohio State University, 2022, Pharmaceutical Sciences

Acute myeloid leukemia (AML) is one of the most lethal forms of hematologic malignancies with low survival rates (<8%) in patients older than 60. With FDA-approved targeted therapies and immunotherapies and advancement of sequencing techniques, the treatment strategies for AML has undergone a paradigm shift in the last decade. But because of inter- and intra-patient heterogeneity, identification of a therapy that can broadly target different subtypes of AML is very challenging. Two mutations and/or concurrent signaling abnormalities are needed to synergistically license leukemia initiation and maintenance. NAMPT is a rate-limiting NAD+ generation enzyme, involving in various functions of leukemia cells. Upon discovery of the roles of NAMPT in metabolic reprograming, small inhibitors that target NAMPT have been soon developed. In our published studies, we showed that NAMPT inhibitor, KPT-9274, was able to induce potent cytotoxicity of AML patient cells and provided survival benefit for murine models of disseminated AML. NAMPT inhibition can selectively eliminate leukemia stem cell population. Although NAMPT inhibitors demonstrated exciting preclinical properties, dose-limiting toxicities including thrombocytopenia and gastrointestinal toxicities were observed. KPT-9274 exhibited gender-dependent toxicity in kidney and anemia, highlighting the necessity of identification of synthetic lethal partners for KPT-9274 treatment. By using CRISPR screen, we were able to identify histone acetylases, HDAC8 and SIRT6, as co-essential genes with KPT-9274 treatment. HDAC8 or SIRT6 inhibition sensitized AML cell lines and primary patient cells to NAMPT inhibition. Importantly, a pan-HDAC inhibitor, AR-42, eliminated leukemia initiating cells (LICs) in vitro and in vivo in combination with KPT-9274 by altering transcriptional patterns of LICs and shutting down multiple DNA repair pathways. Understanding of cooperativity of co-mutations in driving leukemogenesis offers another me (open full item for complete abstract)

Committee: Rosa Lapalombella (Advisor); John Byrd (Committee Member); Sharyn Baker (Committee Member); Moray Campbell (Committee Member) Subjects: Bioinformatics; Cellular Biology; Molecular Biology; Pharmaceuticals; Pharmacology; Pharmacy Sciences

Doctor of Philosophy, Case Western Reserve University, 2021, EMC - Mechanical Engineering

Statistics show that many fatalities in a fire event are caused by smoke inhalation, where hot smoke injured or burned the respiratory system or toxic gases exceed the exposure limits. Certain gases in smoke only require small concentrations to be lethal to the victims. Smoke testing method using a smoke density chamber has been developed at NIST and has been used for compliance testing. However, the smoke chamber is not used as extensively for research in comparison to other standard equipment such as the cone calorimeter, nor has the burning environment been studied numerically. The numerical simulation of the burning environment can reveal the mixing of gases and the fire ventilation conditions in the enclosed chamber, thus enabling the interpretation of the measured concentrations of gases sampled from only one port. Therefore, the smoke chamber method combined with the numerical simulation via Fire Dynamics Simulator (developed by NIST) shows a potential for further research and fire hazard testing, especially if material pyrolysis is incorporated into the model in the future. For this research, two groups of materials are studied: cellulosic materials (wood), and synthetic polymeric materials. All experiments are conducted with the specimen oriented vertically or horizontally in a standard smoke density chamber at an imposed radiant heat flux of 25 kW/m2, and a Fourier transform infrared (FTIR) gas analyzer is connected to a single gas-sampling port in the smoke chamber. The relationship between the progress of the wood pyrolysis (or charring) and the production of the toxic gases in the wood smoke is studied. Black polymethylmethacrylate (PMMA) is numerically modeled with a modified global reaction, with results within reasonable agreement with the experiment. Parameters such as the heat release rate and heat of gasification which were previously only available for the cone calorimeter, is calculated within ranges reported in literature. Finally, select p (open full item for complete abstract)

Committee: Fumiaki Takahashi (Advisor); Gary Wnek (Committee Member); Ya-Ting Liao (Committee Member); James T'ien (Committee Member) Subjects: Engineering

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

Cisplatin is a DNA damage-based chemotherapeutic drug widely used to treat various types of cancers; however, the treatment's toxicity restricts its efficiency. Studies have shown that the circadian rhythm controls the DNA damage response and affects the repair pathways of cisplatin-induced DNA damage. Circadian clock modulation, therefore, has been proposed to be a potential mechanism for enhancing cisplatin tolerability. Here we used clock-enhancing molecules to evaluate the effect of pharmacological clock modulation on cisplatin cytotoxicity. Using cultured human cell lines, cisplatin cytotoxicity was found to be attenuated following treatment with circadian-enhancing molecules KS15 and SR8278. Moreover, the protein and mRNA levels of cell cycle and apoptosis regulators, as well as clock-controlled genes, were modified in response to KS15 and SR8278. Those molecules were also able to enhance cisplatin-induced DNA adducts removal and induce G1-phase cell cycle arrest. Our findings suggest that the use of circadian clock modulators has promising implications for improving cancer care and treatment outcomes.

Committee: Michael G. Kemp Ph.D. (Advisor); Ravi P. Sahu Ph.D. (Committee Member); Yong-jie Xu M.D., Ph.D. (Committee Member) Subjects: Pharmacology; Toxicology

PhD, University of Cincinnati, 2021, Engineering and Applied Science: Environmental Engineering

UV/sodium percarbonate (UV/SPC) is an emerging technology not yet been fully studied for water and wastewater treatment. The application of UV/SPC is debatable because that the Na2CO3 in SPC reacts with hydroxyl radical (HO*) to generate carbonate radical anion (CO3*-)) may undermine the oxidation efficiency of HO* based technologies. However, CO3*- has high reactivity with organic compounds of electron rich moieties. The steady state concentration of CO3*- ([CO3*-]ss) in nature waters is orders higher than that of HO* ([HO*]ss). The cost performance, stability, and safety of SPC are higher than those of liquid H2O2. Bisphenol A (BPA), a well-known endocrine disruptor with two electron rich rings, is a suitable compound for investigation of contaminant destruction in UV/SPC. Experiments on BPA transformation in UV/SPC and UV/H2O2 were conducted and compared in this study to better understand the kinetics and mechanism underlying UV/SPC, the environmental compatibility of UV/SPC treated effluents, and the potential of UV/SPC for water and wastewater treatment. Results of this study showed comparable efficiency of UV/SPC and UV/H2O2 for BPA degradation in Milli-Q water at equivalent concentration of H2O2. The actual degradation efficiency of UV/SPC for BPA removal in various field water samples demonstrated the potential of UV/SPC for treatment of effluents from membrane processes in water reuse. The impact patterns of initial concentration of oxidant, pH, common ions, and different types of natural organic matter on BPA removal in UV/SPC were similar to those in UV/H2O2 though less interferences were observed in UV/SPC. In addition to HO*, CO3*- was another reactive species contributing to the degradation of BPA in UV/SPC with a second order rate constant of 2.23× 10^8 M-1 s-1. The [CO3*-]ss and [HO*]ss in the solution of 1 mM SPC activated by 0.093 mW cm-2 UV were 2.3× 10^-12 M and 1.82 × 10^-14 M, respectively. The two orders of magnitude higher [CO3*-]ss tha (open full item for complete abstract)

Committee: Dionysios Dionysiou Ph.D. (Committee Chair); Margaret Kupferle Ph.D. (Committee Member); Mallikarjuna Nadagouda Ph.D. (Committee Member); George Sorial Ph.D. (Committee Member) Subjects: Environmental Engineering

Doctor of Philosophy, The Ohio State University, 2020, Pharmaceutical Sciences

Membrane transporters are integral proteins contributing to the cellular integrity of all tissue and cell types. The solute carrier superfamily represents the second largest family of membrane proteins, encoding for over 400 transport proteins that collectively, play a pivotal role in cellular homeostasis, including the transport of essential nutrients or ions and the removal of toxic by-products. Moreover, membrane transporters are major contributors to the pharmacokinetics of therapeutic drugs, and the tissue specific expression of uptake transporters can serve as initiating mechanisms that govern a drug's pharmacodynamic properties (e.g., efficacy and toxicity). Here, we demonstrate that the sub-family of organic cation transporters are critical mediators initiating the debilitating toxicity profiles of chemotherapeutic agents, and that the targeting of these transporters can be exploited clinically to afford protection against injury in healthy tissues without compromising therapeutic benefits.

Committee: Alex Sparreboom PhD (Advisor); Shuiying Hu PhD (Advisor); Cynthia Carnes PharmD; PhD (Committee Member); Rajgopal Govindarajan PhD (Committee Member); Maryam Lustberg MD (Committee Member); Lara Sucheston-Campbell PhD (Committee Member) Subjects: Pharmacology

Master of Science in Chemistry, Youngstown State University, 2020, Department of Chemistry

Heavy metals are natural elements found in the earth's crust which have dynamic applications in industrial, domestic, and agricultural activities. These human activities have caused their increased distribution to the environment. Science has shown some of these elements such as lead, cadmium, chromium, mercury and arsenic to be toxic to living organisms. Heavy metals are today known to cause cancer, development retardation in children, anemia, and autism, among other diseases. Currently chelation is the state-of-the-art technique in treatment of heavy metal toxicity in humans. However, despite the success stories, lack of selectivity, non-target side effects, redistribution of metals to other parts of the body and low efficiency attributable to chelators calls for alternative ways in treatment and management of heavy metals. One such approach would be the use of metal-organic frameworks (MOFs) in adsorption of heavy metals. MOFs are prepared through reaction of metal ions with multi-topic organic ligands, which assemble to form porous structures. This thesis has two sections. The first section of the document presents the in vitro adsorption capability of the selected metal-organic frameworks. We focused on two zirconium-derived MOFs, thiophene-containing (DUT-67) and non-thiophene containing (UiO-66) for adsorption of heavy metals from water, protein solutions, and Ovis aries's (sheep's) blood. The second section will address an unprecedented behavior of UiO-66 in Pb2+ adsorption. The results obtained in heavy metal adsorption (section one) shows that DUT-67 and UiO-66 have similar adsorption capabilities for Pb2+, Cd2+ and Cr3+ in water, protein solution, and blood samples. Adsorption of the selected heavy metals is noteworthy since Pb2+, Cr3+ and Cd2+ have been known to impose great risk to human health. Additionally, this report shows that these MOFs could selectively adsorb heavy metals from solution leaving behind most of the essential elements, hence reduc (open full item for complete abstract)

Committee: Douglas Genna PhD (Advisor); Nina Stourman PhD (Committee Member); Christopher Arntsen PhD (Committee Member) Subjects: Chemistry; Environmental Health; Environmental Management; Environmental Science; Materials Science; Therapy; Toxicology