PHD, Kent State University, 2018, College of Arts and Sciences / Department of Chemistry

The piwi interacting RNAs (piRNAs) are small non-coding RNAs with mostly 24-32 nucleotides in length. The piRNAs are defined by their ability to specifically bind to the PIWI proteins, a requirement for their functions. The piRNAs are involved in germline development, transposon control, transcriptional and post-transcriptional gene regulation. However, piRNA mediated post-transcriptional gene regulation in human somatic cells is not well understood. We discovered a human piRNA (piR-FTH1) that negatively regulates the FTH1 expression at the post-transcriptional level in MDA-MB 231 triple negative breast cancer cells. Furthermore, we established that piR-FTH1 knocks down the FTH1 mRNA through the piR-FTH1-HIWI-RISC pathway by using the HIWI2 and HILI proteins. We determined that FTH1 repression by piR-FTH1 increases the sensitivity of the chemotherapeutic agent Doxorubicin by a remarkable 20-fold. In a related project, we investigated the role of piRNA structure in its function. Interestingly, the piRNAs do not have any defined secondary structure. Using bioinformatics analysis, we discovered the presence of putative G-quadruplex (GQ)-forming sequences in human piRNAs that are higher in number compared to the piRNA pools of other organisms that were analyzed. Using one GQ forming human piRNA sequence (piR-48164), we showed that formation of GQ structure in the piRNA led to inhibitions of the PIWI protein binding and target gene silencing in vitro and in cellulo. These studies unraveled the role of a non- canonical secondary structure GQ in the piRNA function and added a new layer of regulation in piRNA function. It has been reported previously that after the PIWI protein degradations, piRNAs become unprotected and undergo elimination. Prior to this study, the degradation mechanism of piRNA is unknown. We found that presence of 3' methylation of piRNA prevents its degradation through the exosome mediated decay pathway. We established that XRN1 and XRN2 are two 5' (open full item for complete abstract)

Committee: Soumitra Basu (Advisor); Soumitra Basu (Committee Chair); Gail Fraizer (Committee Member); Paul Sampson (Committee Member); Sanjaya Abeysirigunawardena (Committee Member); Jennifer McDonough (Committee Member) Subjects: Biochemistry; Biomedical Research; Cellular Biology; Chemistry; Inorganic Chemistry; Molecular Biology

Doctor of Philosophy, University of Toledo, 2017, Physics

Thin film solar cells based on hybrid organic-inorganic perovskites (HOIPs) have become highly attractive over the past several years due to a high solar to electric power conversion efficiencies (PCEs). Perovskite materials based on methylammonium lead iodide (CH3NH3PbI3, MAPbI3) possess high optical absorption coefficients, long minority carrier lifetimes and diffusion lengths, and desirable optical band gaps, and carrier collection in these materials can be highly efficient when they are paired with appropriate electron and hole transport materials (ETMs and HTMs), respectively. Additionally, perovskite solar cells (PSCs) can be fabricated via a variety of solution-based routes, which are suitable for low-cost, large area manufacturing. The combination of these attributes gives PSCs an advantage over currently available commercial photovoltaic (PV) technologies. Understanding the nucleation and growth mechanisms, and controlling the grain size and crystallinity in the solution-processed fabrication of perovskite thin films are important to prepare electronic-quality materials for PV applications. We investigated the nucleation and growth mechanisms of MAPbI3 formed in a two-step solution process. To prepare the MAPbI3 films, PbI2 films were spin-coated and then were reacted with methylammonium iodide (MAI) in the isopropanol (IPA) solution at various concentrations. We showed that the conversion rate, grain size, and morphology of MAPbI3 perovskite films depend on the concentration of the MAI solution. Three distinct perovskite formation behaviors were observed at various MAI concentrations, and a tentative model was proposed to explain the reaction mechanisms. The nucleation and growth process of MAPbI3 can be significantly changed by adding divalent metal salts into the MAI solution. We showed that the incorporation of Cd2+ ions significantly improved the grain size, crystallinity, and photoexcited carrier lifetime of MAPbI3. Formation of ( (open full item for complete abstract)

Committee: Michael J. Heben Ph.D. (Committee Chair); Randy J. Ellingson Ph.D. (Committee Member); Yanfa Yan Ph.D. (Committee Member); Song Cheng Ph.D. (Committee Member); Terry P. Bigioni Ph.D. (Committee Member) Subjects: Materials Science; Physics

Doctor of Philosophy, The Ohio State University, 2017, Chemistry

Liquid microjet photoelectron spectroscopy is a state-of-the-art experimental technique that provides avenues for investigating ultrafast charge and energy transfer processes in liquid water and aqueous solutions. The emphasis of this work is placed on making contact with recent liquid microjet experiments of hydrated electrons, e-(aq), in liquid water and at the liquid-vapor interface from a computational perspective. Since its discovery nearly 55 years ago, e-(aq) has attracted significant attention from both experimental and theoretical communities due to its crucial role in radiation chemistry and its relatively elusive structure in liquid water at ambient conditions. Historically, the primary observable of hydrated electrons has been a well-characterized optical absorption spectrum, but with the advent of liquid microject spectroscopy, this has shifted to measurements of its relative binding energy below vacuum level. Some experiments utilizing this methodology have been interpreted to suggest that e-(aq) at the liquid-vapor interface is energetically dissimilar than in liquid water, and that, unlike the more strongly bound species in liquid, it can potentially undergo destructive reactions with solvated DNA molecules. A variety of computational strategies are employed to demonstrate that the spectroscopic properties of hydrated electrons in liquid water are actually quite similar to the interfacial species. To that end, mixed quantum-classical molecular dynamics simulations are performed where e-(aq) in liquid water and at the interface is described by two different one-electron pseudopotentials. These simulations suggest that the presence of e-(aq) at a liquid-vapor interface is fleeting at ambient conditions, and to experimentally distinguish it from the bulk species using standard spectroscopic techniques would be challenging. Non-equilibrium polarizable continuum models (PCMs), in conjunction with MP2 and DFT methods, are then employed to compute vertic (open full item for complete abstract)

Committee: John Herbert Ph.D. (Advisor); James Coe Ph.D. (Committee Member); Sherwin Singer Ph.D. (Committee Member); Laura Podalsky Ph.D. (Committee Member) Subjects: Chemistry; Physical Chemistry

Doctor of Philosophy, The Ohio State University, 2012, Materials Science and Engineering

The toxicity and carcinogenic nature of chromates has led to the investigation of environmentally friendly compounds that offer good corrosion resistance to AA 2024-T3. Among the candidate inhibitors are rare earth metal cationic (REM) and zinc compounds, which have received much of attention over the past two decades. A comparative study on the corrosion inhibition caused by rare earth metal cations, Ce3+, Pr3+, La3+ and Zn2+ cations on the alloy was done. Cathodic polarization showed that these inhibitor ions suppress the oxygen reduction reaction (ORR) to varying extents with Zn2+ providing the best inhibition. Pr3+ exhibited windows of concentration (100-300 ppm) in which the corrosion rate is minimum; similar to the Ce3+ cation. Scanning Electron Microscopy (SEM) studies showed that the mechanism of inhibition of the Pr3+ ion is also similar to that of the Ce3+ ion. Potentiodynamic polarization experiments after 30 min immersion time showed greatest suppression of oxygen reduction reaction in neutral chloride solutions (pH 7), which reached a maximum at a Zn2+ ion concentration of 5 mM. Anodic polarization experiments after 30 min immersion time, showed no anodic inhibition by the inhibitor in any concentration (0.1 mM – 10 mM) and at any pH. However, anodic polarization of samples immersed after longer immersion times (upto 4 days) in mildly acidic Zn2+ (pH 4) solutions showed significant reduction in anodic kinetics indicating that zinc also acts as a “slow anodic inhibitor”. In contrast to the polarization experiments, coupons exposed to inhibited acidic solutions at pH 4 showed complete suppression of dissolution of Al2CuMg particles compared to zinc-free solutions in the SEM studies. Samples exposed in pH 4 Zn2+-bearing solution exhibited highest polarization resistance which was also observed to increase with time. In deaerated solutions, the inhibition by Zn2+ at pH 4 is not observed as strongly. The ability to make the interfacial electrolyte alkaline i (open full item for complete abstract)

Committee: Rudolph G Buchheit PhD (Advisor); Gerald Frankel PhD (Committee Member); Yogeshwar Sahai PhD (Committee Member) Subjects: Aerospace Materials; Automotive Materials; Engineering; Materials Science

Master of Science, The Ohio State University, 2009, Civil Engineering

Lime sludge is a byproduct of drinking water production from the water softeningprocess. As the traditional land-based disposal of lime sludge can hardly meet the need of society in a sustainable manner, alternative treatment methods are about to be developed in order to appropriately solve the issue. Fortunately in recent decades, the emergence and development of membrane technologies has provided people with advanced ways to handle environment problems. Advances in the application of ion exchange membrane processes for material separation exhibit promise for providing new approaches for improving the sustainability of industrial operations. The objectives of this study include the investigation of the fundamental mechanism of Donnan dialysis with a cation exchange membrane and sustainable treatment of lime sludge by this method. The research was designed to evaluate the change in different ion concentrations on both sides of the Donnan cell as a function of time under a variety of experimental conditions. After understanding mechanisms of the system, Donnan dialysis was applied for the treatment of real lime sludge. Ideally, after treatment, the product could be reused as material for the water softening process and thus forms a sustainable recycling system. Initial experiments tested the process using synthetic samples and various types of acids. Based on the results, CaSO4 and HCl were chosen for further investigation. The experiments presented a high recovery of calcium cations and most of the hydrogen ions from the acid were exchanged to the other side for recovery. The results also verified Donnan equilibrium theory for this cation exchange system and provided evidence for the possible extension of the theory to more heterogeneous solids. According to the fundamental experiments with synthetic samples, the process was applied for the treatment of real lime sludge. During the kinetic experiment, an interesting phenomenon was found that the magnesium cations on (open full item for complete abstract)

Committee: John Lenhart (Advisor); Harold Walker (Committee Member); Linda Weavers (Committee Member) Subjects: Civil Engineering

MS, Kent State University, 2010, College of Arts and Sciences / Department of Chemistry

Phosphatidyl inositides (PIs) are important regulators of cell signaling. Phosphoinositide 3-kinase (PI3-K)-activated signaling plays a key role in the development of cancer. Therefore various anticancer treatments target this pathway. The aim of this work was to develop an optimized method to separate fluorescent PIPs quickly and efficiently at room temperature using CE-LIF. The reason for the development of a method capable of separating the PIPs at room temperature was that, it could be used for single cell studies. In this regard, the effect of various cations on the separation of the PIs and their seven PIP derivatives was investigated. The effect of pH, temperature, voltage, as well as other buffer mixtures were also studied. Based on this developed method, the activity of PI3-K and PTEN enzymes in NIH 3T3 cells and MDA-MB 231 cells was also studied. The bioactivity of PIPs in these cells was investigated to ascertain whether preliminary CE studies would prove that they were able to be converted inside the cells into other phosphorylated derivatives. Lipid kinases and phosphatases play active roles in cell signaling. These have serious implications in many disease states. For example, accumulation of PIP3 leads to metastatic cancers. Therefore, inhibition studies were also performed to find out whether PI3-K inhibitors were able to block the conversion of PIP2 to PIP3. This is of particular interest in cell-based assays and research involving cancer drug development.

Committee: Simon M Mwongela PhD (Advisor); Songping Huang PhD (Committee Member); Bansidhar Datta PhD (Committee Member) Subjects: Biochemistry