DNMTs are required for delayed genome instability caused by radiation

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

Gravitational Chern-Simons Lagrangians and black hole entropy

We analyze the problem of defining the black hole entropy when Chern-Simons terms are present in the action. Extending previous works, we define a general procedure, valid in any odd dimensions both for purely gravitational CS terms and for mixed gauge-gravitational ones. The final formula is very similar to Wald's original formula valid for covariant actions, with a significant modification. Notwithstanding an apparent violation of covariance we argue that the entropy formula is indeed covariant.Comment: 39 page

Black-hole dynamics in BHT massive gravity

Using an exact Vaidya-type null-dust solution, we study the area and entropy laws for dynamical black holes defined by a future outer trapping horizon in (2+1)-dimensional Bergshoeff-Hohm-Townsend (BHT) massive gravity. We consider the theory admitting a degenerate (anti-)de Sitter vacuum and pure BHT gravity. It is shown that, while the area of a black hole decreases by the injection of a null dust with positive energy density in several cases, the Wald-Kodama dynamical entropy always increases.Comment: 7 pages, 1 figur

On the General Kerr/CFT Correspondence in Arbitrary Dimensions

We study conformal symmetries on the horizon of a general stationary and axisymmetric black hole. We find that there exist physically reasonable boundary conditions that uniquely determine a set of symmetry generators, which form one copy of the Virasoro algebra. For extremal black holes, Cardy's formula reproduces exactly the Bekenstein-Hawking entropy.Comment: 17 page

Membrane Paradigm and Horizon Thermodynamics in Lanczos-Lovelock gravity

We study the membrane paradigm for horizons in Lanczos-Lovelock models of gravity in arbitrary D dimensions and find compact expressions for the pressure p and viscosity coefficients \eta and \zeta of the membrane fluid. We show that the membrane pressure is intimately connected with the Noether charge entropy S_Wald of the horizon when we consider a specific m-th order Lanczos-Lovelock model, through the relation pA/T=(D-2m)/(D-2)S_Wald, where T is the temperature and A is the area of the horizon. Similarly, the viscosity coefficients are expressible in terms of entropy and quasi-local energy associated with the horizons. The bulk and shear viscosity coefficients are found to obey the relation \zeta=-2(D-3)/(D-2)\eta.Comment: v1: 13 pages, no figure. (v2): refs added, typos corrected, new subsection added on the ratio \eta/s. (v3): some clarification added, typos corrected, to appear in JHE

The Entropy for General Extremal Black Holes

We use the Kerr/CFT correspondence to calculate the entropy for all known extremal stationary and axisymmetric black holes. This is done with the help of two ansatzs that are general enough to cover all such known solutions. Considering only the contribution from the Einstein-Hilbert action to the central charge(s), we find that the entropy obtained by using Cardy's formula exactly matches with the Bekenstein-Hawking entropy.Comment: Minor corrections, section 5 refined, references added

Boundary Conditions and Unitarity: the Maxwell-Chern-Simons System in AdS_3/CFT_2

We consider the holography of the Abelian Maxwell-Chern-Simons (MCS) system in Lorentzian three-dimensional asymptotically-AdS spacetimes, and discuss a broad class of boundary conditions consistent with conservation of the symplectic structure. As is well-known, the MCS theory contains a massive sector dual to a vector operator in the boundary theory, and a topological sector consisting of flat connections dual to U(1) chiral currents; the boundary conditions we examine include double-trace deformations in these two sectors, as well as a class of boundary conditions that mix the vector operators with the chiral currents. We carefully study the symplectic product of bulk modes and show that almost all such boundary conditions induce instabilities and/or ghost excitations, consistent with violations of unitarity bounds in the dual theory.Comment: 50+1 pages, 6 figures, PDFLaTeX; v2: added references, corrected typo

New supersymmetric higher-derivative couplings: Full N=2 superspace does not count!

An extended class of N=2 locally supersymmetric invariants with higher-derivative couplings based on full superspace integrals, is constructed. These invariants may depend on unrestricted chiral supermultiplets, on vector supermultiplets and on the Weyl supermultiplet. Supersymmetry is realized off-shell. A non-renormalization theorem is proven according to which none of these invariants can contribute to the entropy and electric charges of BPS black holes. Some of these invariants may be relevant for topological string deformations.Comment: 24 pages, v2: version published in JHEP, one reference added and typos corrected, v3: reference adde

Black Hole Hair Removal: Non-linear Analysis

BMPV black holes in flat transverse space and in Taub-NUT space have identical near horizon geometries but different microscopic degeneracies. It has been proposed that this difference can be accounted for by different contribution to the degeneracies of these black holes from hair modes, -- degrees of freedom living outside the horizon. In this paper we explicitly construct the hair modes of these two black holes as finite bosonic and fermionic deformations of the black hole solution satisfying the full non-linear equations of motion of supergravity and preserving the supersymmetry of the original solutions. Special care is taken to ensure that these solutions do not have any curvature singularity at the future horizon when viewed as the full ten dimensional geometry. We show that after removing the contribution due to the hair degrees of freedom from the microscopic partition function, the partition functions of the two black holes agree.Comment: 40 pages, LaTe

Thermodynamic Geometry and Phase Transitions in Kerr-Newman-AdS Black Holes

We investigate phase transitions and critical phenomena in Kerr-Newman-Anti de Sitter black holes in the framework of the geometry of their equilibrium thermodynamic state space. The scalar curvature of these state space Riemannian geometries is computed in various ensembles. The scalar curvature diverges at the critical point of second order phase transitions for these systems. Remarkably, however, we show that the state space scalar curvature also carries information about the liquid-gas like first order phase transitions and the consequent instabilities and phase coexistence for these black holes. This is encoded in the turning point behavior and the multi-valued branched structure of the scalar curvature in the neighborhood of these first order phase transitions. We re-examine this first for the conventional Van der Waals system, as a preliminary exercise. Subsequently, we study the Kerr-Newman-AdS black holes for a grand canonical and two "mixed" ensembles and establish novel phase structures. The state space scalar curvature bears out our assertion for the first order phase transitions for both the known and the new phase structures, and closely resembles the Van der Waals system.Comment: 1 + 41 pages, LaTeX, 46 figures. Discussions, clarifications and references adde