Poly(ADP)ribose (PAR) metabolism is essential to many cellular functions, including the maintenance of genomic integrity, the regulation of cell death mechanisms, as well as the regulation of gene expression. Recent work has uncovered many new players in the expanding effort to understand PAR metabolism and its cellular impact. PARP-1, the prototypical poly(ADP)ribose polymerase, was the first to be discovered, and has since been shown to be vital in the cellular response to DNA damage. Indeed, one report demonstrating that PARP-1 activation is required for apoptosis-inducing factor (AIF) release from mitochondria uncovered a novel link between DNA damage and signaling for cell death. The events following PARP activation, leading to signaling for AIF release, however, are still poorly understood. Based on our observations, we have developed a model to explain the nuclear/mitochondrial crosstalk that occurs following PARP activation. The work presented here answers several important questions regarding the relationship between ADP-ribose metabolism and mitochondria, including the role of PAR in signaling for the release of AIF, the presence of ADP-ribose metabolism protein members in mitochondria, and mitochondrial transcriptional effects following PARP activation. This work presents several novel findings, including the first report of a mitochondrial matrix isoform of poly(ADP-ribose) glycohydrolase (PARG) as well as direct evidence of mitochondria-associated PARP activity. Furthermore, it provides evidence for a novel effect of PARP-1 activation, in the specific transcriptional upregulation of the mitochondrial gene, NADH dehydrogenase, subunit 1 (ND1). Our data is consistent with the hypothesis that uncontrolled PARP activity results in energy metabolism dysfunction and cell death. Furthermore, it supports a model in which PARP activity is required for normal transcriptional responses in mitochondria following DNA damage. In total, this report adds to the body of work outlining the roles of PARP following DNA damage recognition and activation, demonstrating that ADP-ribose metabolism plays an important role in cell death regulation by both direct and indirect means.

<p> A well characterized titanate system, Nd1_xTi03, has been studied by temperature dependent reflectance spectroscopy between 50 and 40 000 cm-1 at three different doping levels, x = 0.019, 0.046, and 0.095, which yield a Matt-Hubbard insulator, a semiconductor and a correlated metal, respectively. Two main issues are discussed regarding the optical properties of the current system. The first is the variation of the low-lying electronic structure with hole concentration. The doping-dependent optical conductivity of Nd1_xTi03 shows several obvious differences when compared to the superconducting cuprates. We observed mid-infrared absorption bands in the doped samples, suggesting that mid-gap states develop inside the Hubbard gap with hole doping in the context of a two-component model. A quantitative analysis of the spectral weight below 1.2 e V as a function of doping indicates that the evolution rate of the optical excitations below 1.2 eV is related to the electron correlation strength of the parent insulator, which has been observed in other titanates as well. The second issue addressed in this thesis is the temperature-dependent optical features of the correlated metallic sample with x = 0.095, a composition close to the metal-insulator transition at x '"'-~ 0.08. The optical conductivity shows an anomalous enhancement of spectral weight below leV, in both the Drude and midinfrared part, that develops with decreasing temperature. The dynamical mean field theory (DMFT) may explain this feature. Meanwhile, the metallic sample displays a Fermi-liquid like behavior in the low-frequency limit, which can be established from the spectra of the scattering rate as a function of both frequency and temperature. We found a good agreement between the experimental results extracted from the scattering rate and the Fermi-liquid theory. </p> / Thesis / Master of Science (MSc)

Crystal growth and characterization of few multifunctional materials with perovskite (ABX3) structure are discussed in this thesis. Efforts were made to modify the magnetic and electric behaviour of these materials by selective tuning of A, B and X components. Structural, magnetic and dielectric characterization are detailed in various chapters for doped (A and B site) rare-earth manganites and organometallic compounds with different (Chloride or formate) anions. The relevant aspects of crystal structure and its relationship with ordered ground states are discussed in the introductory chapter. A detailed review of prominent theories pertaining to magnetic and ferroelectric ordering in the literature is provided. Growth of various inorganic compounds by solid-state reaction and floating zone method as well as use of solvothermal techniques for growing organometallic compounds are discussed. Material preparation, optimization of crystal growth processes and results of characterization are addressed in various chapters. The effect of Yttrium doping on structural, magnetic and dielectric properties of rare-earth manganites (RMnO3 where R = Nd, Pr) has been investigated. Neutron diffraction studies (Pr compounds) confirm A-type antiferromagnetic structure and fall in transition temperature as the Yttrium doping level increases. Diffraction experiments in conjunction with dc magnetization and ac susceptibility studies reveal magnetic frustration in excess Yttrium dopedcompounds. When mutliglass properties of 50% B-site doped Nd2NiMnO6 were investigated, evidence of re-entrant cluster glass phase was seen probably due to presence of anti-site disorder. The relaxor-like dielectric behaviour arises from crossover of relaxation time in grain and grain boundary regions. Multiferroic behaviour of the organometallic compound (C2H5NH3)2CuCl4 as well as the ferroelectric transition were investigated in detail. The role of Hydrogen bond ordering in driving structural transitions is elucidated by low temperature dielectric and Raman studies in (C2H5NH3)2CdCl4. It was found possible to tune the magnetic and ferroelectric properties in metal formate compounds (general formula AB(HCOO)3) by selectively choosing organic cations [(CH3)2NH2+; C(NH3)3+] and transition metal ion [B = Mn, Co and Cu]. The nature of magnetic ordering and transition temperature could be altered by the transition metal ion. The effect of reorientation of organic cations which leads to ferroelectric nature is discussed using dielectric and pyroelectric data. Significant results are summarized in the chapter outlining general conclusions. Future prospects of work based on these observations are also provided. The conclusions are corroborated by detailed analysis of experimental data.