DNA Repair in Mammalian Cells: Mismatched repair: variations on a theme

Abstract.: Complementary base pairing underlies the genetic template function of the DNA double helix. Therefore, to assure faithful DNA transactions, cells must adhere to a strict application of the Watson-Crick base pairing principle.Yet, mispairing does arise in DNA, most frequently as a result of DNA polymerase errors or base damage. These mismatches need be rectified to avoid mutation. Sometimes, however, mispairing is actively induced to trigger mutagenesis. This happens in activated B-lymphocytes, where the targeted generation and processing of G·U mismatches contributes to somatic hypermutation and antibody diversification. Non-mutagenic mismatches arise in heteroduplex intermediates of homologous recombination, and their processing helps restrict homeologous recombination. Depending on the type of mismatch and the biological context of its occurrence, cells must apply appropriate strategies of repair to properly control mutagenesis. This review will illustrate conceptual and functional challenges of cellular mismatch correction on typical examples of mutagenic base-base mismatches. (Part of a Multi-author Review

Orbits in the Field of a Gravitating Magnetic Monopole

Orbits of test particles and light rays are an important tool to study the properties of space-time metrics. Here we systematically study the properties of the gravitational field of a globally regular magnetic monopole in terms of the geodesics of test particles and light. The gravitational field depends on two dimensionless parameters, defined as ratios of the characteristic mass scales present. For critical values of these parameters the resulting metric coefficients develop a singular behavior, which has profound influence on the properties of the resulting space-time and which is clearly reflected in the orbits of the test particles and light rays.Comment: 24 pages, 15 figures. Accepted for publication in GR

Thyroid Hormone-disrupting Effects and the Amphibian Metamorphosis Assay

There are continued concerns about endocrine-disrupting chemical effects, and appropriate vertebrate models for assessment of risk are a high priority. Frog tadpoles are very sensitive to environmental substances because of their habitat and the complex processes of metamorphosis regulated by the endocrine system, mainly thyroid hormones. During metamorphosis, marked alteration in hormonal factors occurs, as well as dramatic structural and functional changes in larval tissues. There are a variety of mechanisms determining thyroid hormone balance or disruption directly or indirectly. Direct-acting agents can cause changes in thyroxine synthesis and/or secretion in thyroid through effects on peroxidases, thyroidal iodide uptake, deiodinase, and proteolysis. At the same time, indirect action may result from biochemical processes such as sulfation, deiodination and glucuronidation. Because their potential to disrupt thyroid hormones has been identified as an important consideration for the regulation of chemicals, the OECD and the EPA have each established guidelines that make use of larval African clawed frogs (Xenopus laevis) and frog metamorphosis for screening and testing of potential endocrine disrupters. The guidelines are based on evaluation of alteration in the hypothalamic-pituitary-thyroid axis. One of the primary endpoints is thyroid gland histopathology. Others are mortality, developmental stage, hind limb length, snout-vent length and wet body weight. Regarding histopathological features, the guidelines include core criteria and additional qualitative parameters along with grading. Taking into account the difficulties in evaluating amphibian thyroid glands, which change continuously throughout metamorphosis, histopathological examination has been shown to be a very sensitive approach

Level Crossing Along Sphaleron Barriers

In the electroweak sector of the standard model topologically inequivalent vacua are separated by finite energy barriers, whose height is given by the sphale\-ron. For large values of the Higgs mass there exist several sphaleron solutions and the barriers are no longer symmetric. We construct paths of classical configurations from one vacuum to a neighbouring one and solve the fermion equations in the background field configurations along such paths, choosing the fermions of a doublet degenerate in mass. As in the case of light Higgs masses we observe the level crossing phenomenon also for large Higgs masses.Comment: 17 pages, latex, 10 figures in uuencoded postscript files. THU-94/0

Multisphalerons in the Weinberg-Salam Theory

We construct multisphaleron solutions in the Weinberg-Salam theory. The multisphaleron solutions carry Chern-Simons charge $n/2$, where $n$ is an integer, counting the winding of the fields in the azimuthal angle. The well-known sphaleron has $n=1$. The multisphalerons possess axial symmetry and parity reflection symmetry. We vary the Higgs mass and the mixing angle. For small $n$ the energies of the multisphalerons are on the order of $n$ times the energy of the sphaleron and their magnetic dipole moments are on the order of $n$ times the magnetic dipole moment of the sphaleron.Comment: 18 pages, latex, 17 figures in uuencoded postscript files. THU-94/1

Quantum Transport in Molecular Rings and Chains

We study charge transport driven by deformations in molecular rings and chains. Level crossings and the associated Longuet-Higgins phase play a central role in this theory. In molecular rings a vanishing cycle of shears pinching a gap closure leads, generically, to diverging charge transport around the ring. We call such behavior homeopathic. In an infinite chain such a cycle leads to integral charge transport which is independent of the strength of deformation. In the Jahn-Teller model of a planar molecular ring there is a distinguished cycle in the space of uniform shears which keeps the molecule in its manifold of ground states and pinches level crossing. The charge transport in this cycle gives information on the derivative of the hopping amplitudes.Comment: Final version. 26 pages, 8 fig

The Sphaleron Barrier in the Presence of Fermions

We calculate the minimal energy path over the sphaleron barrier in the pre\-sen\-ce of fermions, assuming that the fermions of a doublet are degenerate in mass. This allows for spherically symmetric ans\"atze for the fields, when the mixing angle dependence is neglected. While light fermions have little influence on the barrier, the presence of heavy fermions ($M_F \sim$ TeV) strongly deforms the barrier, giving rise to additional sphalerons for very heavy fermions ($M_F \sim$ 10 TeV). Heavy fermions form non-topological solitons in the vacuum sector.Comment: 19 pages, latex, 18 figures in 3 seperate uuencoded postscript files THU-93/1

Gravitating monopoles in SU(3) gauge theory

We consider the Einstein-Yang-Mills-Higgs equations for an SU(3) gauge group in a spherically symmetric ansatz. Several properties of the gravitating monopole solutions are obtained an compared with their SU(2) counterpart.Comment: 7 pages, Latex, 3 figure

Rotating black holes with equal-magnitude angular momenta in d=5 Einstein-Gauss-Bonnet theory

We construct rotating black hole solutions in Einstein-Gauss-Bonnet theory in five spacetime dimensions. These black holes are asymptotically flat, and possess a regular horizon of spherical topology and two equal-magnitude angular momenta associated with two distinct planes of rotation. The action and global charges of the solutions are obtained by using the quasilocal formalism with boundary counterterms generalized for the case of Einstein-Gauss-Bonnet theory. We discuss the general properties of these black holes and study their dependence on the Gauss-Bonnet coupling constant $\alpha$. We argue that most of the properties of the configurations are not affected by the higher derivative terms. For fixed $\alpha$ the set of black hole solutions terminates at an extremal black hole with a regular horizon, where the Hawking temperature vanishes and the angular momenta attain their extremal values. The domain of existence of regular black hole solutions is studied. The near horizon geometry of the extremal solutions is determined by employing the entropy function formalism.Comment: 25 pages, 7 figure

Inelastic scattering of protons from 6,8^{6,8}He and 7,11^{7,11}Li in a folding model approach

The proton-inelastic scattering from $^{6,8}$He and $^{7,11}$Li nuclei are studied in a folding model approach. A finite-range, momentum, density and isospin dependent nucleon-nucleon interaction (SBM) is folded with realistic density distributions of the above nuclei. The renormalization factors N$_R$ and N$_I$ on the real and volume imaginary part of the folded potentials are obtained by analyzing the respective elastic scattering data and kept unaltered for the inelastic analysis at the same energy. The form factors are generated by taking derivatives of the folded potentials and therefore required renormalizations. The $\beta$ values are extracted by fitting the p + $^{6,8}$He,$^{7,11}$Li inelastic angular distributions. The present analysis of p + $^8$He inelastic scattering to the 3.57 MeV excited state, including unpublished forward angle data (RIKEN) confirms L = 2 transition. Similar analysis of the p + $^6$He inelastic scattering angular distribution leading to the 1.8 MeV (L = 2) excited state fails to satisfactorily reproduce the data.Comment: one LaTeX file, five PostScript figure