RESISTANCE AND DNA REPAIR MECHANISMS UNDER NITROSATIVE STRESS IN MAMMALIAN AND MICROBIAL SYSTEMS

Living organisms are exposed a nitrosative stress mediated by reactive nitrogen species (RNS) that can cause DNA damage and mutation. DNA base deamination is a typical damage occurred under nitrosative stress, which results in conversion of cytosine (C) to uracil (U), adenine (A) to hypoxanthine (I), and guanine (G) to xanthine (X) or oxanine (O). Base excision repair (BER) is an important pathway to remove deaminated DNA lesions in mammalian and microbial systems. My dissertation work concerns with genes and enzymes involved in resistance to nitrosative stress and DNA glycosylases in the BER pathway. In chapter one, I will briefly review current knowledge in these areas. In chapter two, I will present a genetic and biochemical investigation that identifies mouse thioredoxin domain-containing 5 (mTrx 5) and Escherichia coli thioredoxin 1 and thioredoxin 2 as genes that are involved in resistance to nitrosative stress. This work indicates radical scavenging as an important resistance mechanism. In chapter three, I will present an extensive biochemical, molecular modeling and molecular dynamics simulations study on deaminated repair activities in E. coli mismatch-specific uracil DNA glycoyslase (MUG). Data obtained from cell extracts and purified enzymes indicate that E. coli MUG is a robust xanthine DNA glycosylase (XDG) although it is well known as a uracil DNA glycosylase. Site-directed mutagenesis, coupled with molecular modeling and molecular dynamics simulations reveal distinct hydrogen bonding patterns in the active site of E. coli MUG, which account for the specificity differences between E. coli MUG and human thymine DNA glycosylase, as well as that between the wild type MUG and mutant MUG enzymes. In chapter four, I will describe the deaminated base repair of DNA glycosylases in archaea. Overall, these studies provide new insights on the cellular mechanisms in resistance to nitrosative stress and deaminated DNA repair mechanisms in mammalian and microbial systems

Side-View Operando Optical Microscopy Analysis of a Graphite Anode to Study Its Kinetic Hysteresis

Operando analyses have provided several breakthroughs in the construction of high-performance materials and devices, including energy storage systems. However, despite the advances in electrode engineering, the formidable issues of lithium intercalation and deintercalation kinetics cannot be investigated by using planar observations. This study concerns side-view operando observation by optical microscopy of a graphite anode based on its color changes during electrochemical lithiation. Since the graphite color varies according to the optical energy gap during lithiation and delithiation, this technique can be used to study the corresponding charge-discharge kinetics. In addition, the cell configuration uses liquid electrolytes similar to commercial cells, allowing practical application. Furthermore, this side-view observation has shown that microscale spatial variations in rate and composition control the insertion and deinsertion, revealing the kinetics throughout the whole electrode. The results of this study could enhance the fundamental understanding of the kinetics of battery materials

Spin polarization amplification within nonmagnetic semiconductors at room temperature

We demonstrate theoretically that the spin polarization of current can be electrically amplified within nonmagnetic semiconductors by exploiting the fact the spin current, compared to the charge current, is weakly perturbed by electric driving forces. As a specific example, we consider a T-shaped current branching geometry made entirely of a nonmagnetic semiconductor, where the current is injected into one of the branches (input branch) and splits into the other two branches (output branches). We show that when the input current has a moderate spin polarization, the spin polarization in one of the output branches can be higher than the spin polarization in the input branch and may reach 100% when the relative magnitudes of current-driving electric fields in the two output branches are properly tuned. The proposed amplification scheme does not use ferromagnets or magnetic fields, and does not require low temperature operation, providing an efficient way to generate a highly spin polarized current in nonmagnetic semiconductors at room temperature.Comment: 11 pages, 2 figures, to appear in Phys. Rev.

Current-induced domain wall motion in a nanowire with perpendicular magnetic anisotropy

We study theoretically the current-induced magnetic domain wall motion in a metallic nanowire with perpendicular magnetic anisotropy. The anisotropy can reduce the critical current density of the domain wall motion. We explain the reduction mechanism and identify the maximal reduction conditions. This result facilitates both fundamental studies and device applications of the current- induced domain wall motion

Management Of Accrual Components In Response To Corporate Income Tax Rate Changes: Evidence From Korea

Changes in the statutory corporate income tax rate provide firms with an opportunity to reduce their tax burden by shifting their taxable income from higher to lower tax rate years. One negative consequence of shifting taxable income across years is higher variation in book income for financial reporting purposes. Taxable income and book income are closely related in most countries, and, in general, reporting volatile book income across years is not a favorable signal to investors. This study investigates how firms shift taxable income and concurrently mitigate book income fluctuation by managing accrual components separately when the statutory income tax rate changes. Unlike prior studies, we decompose discretionary accruals into two components and examine distinctive patterns of accrual management in Korea, where book-tax conformity is high and aggressive tax avoidance is restricted. We find that firms manage book-tax accruals for taxable income shifting and manage book-only accruals to mitigate book income fluctuation. Furthermore, we find the extent of book-tax and book-only accruals management varies depending on the firms’ tax and financial reporting costs. The results of this study provide clear and compelling evidence of firms’ opportunistic accrual management behavior in response to statutory tax rate reduction

Current-Induced Magnetic Domain-Wall Motion by Spin Transfer Torque: Collective Coordinate Approach with Domain-Wall Width Variation

The spin transfer torque generated by a spin-polarized current can induce the shift of the magnetic domain-wall position. In this work, we study theoretically the current-induced domain-wall motion by using the collective coordinate approach [Gen Tatara and Hiroshi Kohno, Phys. Rev. Lett. 92, 86601 (2004)]. The approach is extended to include not only the domain-wall position and the polarization angle changes but also the domain-wall width variation. It is demonstrated that the width variation affects the critical current.Comment: 13 pages, 3 figure

The Hβ index as an age indicator of old stellar systems: The effects of horizontal-branch stars

The strength of the Hβ index is computed for the integrated spectra of model globular clusters from the evolutionary population synthesis. For the first time, these models take into account the detailed systematic variation of horizontal-branch (HB) morphology with age and metallicity. Our models show that the Hβ index is significantly affected by the presence of blue HB stars. Because of the contribution from blue HB stars, the Hβ does not monotonically decrease as metallicity increases at a given age. Instead, it reaches a maximum strength when the distribution of HB stars is centered around 9500 K, the temperature at which the Hβ index becomes strongest. Our models indicate that the strength of the Hβ index increases as much as 0.75 Å because of the presence of blue HB stars. The comparison of the recent Keck observations of the globular cluster system in the Milky Way with those in the giant elliptical galaxies NGC 1399 and M87 shows a systematic shift in the Hβ-metallicity plane. Our models suggest that this systematic difference is explained if the mean age of globular cluster systems in giant elliptical galaxies is several billion years older than the Galactic counterpart. Further observations of globular cluster systems in the external galaxies from the large ground-based telescopes and space UV facilities will enable us to clarify whether this difference is indeed due to the age difference or whether other explanations are also possible