Uniqueness of the asymptotic AdS3 geometry

We explicitly show that in (2+1) dimensions the general solution of the Einstein equations with negative cosmological constant on a neigbourhood of timelike spatial infinity can be obtained from BTZ metrics by coordinate transformations corresponding geometrically to deformations of their spatial infinity surface. Thus, whatever the topology and geometry of the bulk, the metric on the timelike extremities is BTZ.Comment: LaTeX, 8 pages, no figures, version that will appear in Class. Quant. Gra

On Holomorphic Factorization in Asymptotically AdS 3D Gravity

This paper studies aspects of ``holography'' for Euclidean signature pure gravity on asymptotically AdS 3-manifolds. This theory can be described as SL(2,C) CS theory. However, not all configurations of CS theory correspond to asymptotically AdS 3-manifolds. We show that configurations that do have the metric interpretation are parameterized by the so-called projective structures on the boundary. The corresponding asymptotic phase space is shown to be the cotangent bundle over the Schottky space of the boundary. This singles out a ``gravitational'' sector of the SL(2,C) CS theory. It is over this sector that the path integral has to be taken to obtain the gravity partition function. We sketch an argument for holomorphic factorization of this partition function.Comment: 32+1 pages, no figures; (v2) one reference added, a statement regarding priorities modified; (v3) presentational changes, an important sign mistake correcte

Holographic Protection of Chronology in Universes of the Godel Type

We analyze the structure of supersymmetric Godel-like cosmological solutions of string theory. Just as the original four-dimensional Godel universe, these solutions represent rotating, topologically trivial cosmologies with a homogeneous metric and closed timelike curves. First we focus on "phenomenological" aspects of holography, and identify the preferred holographic screens associated with inertial comoving observers in Godel universes. We find that holography can serve as a chronology protection agency: The closed timelike curves are either hidden behind the holographic screen, or broken by it into causal pieces. In fact, holography in Godel universes has many features in common with de Sitter space, suggesting that Godel universes could represent a supersymmetric laboratory for addressing the conceptual puzzles of de Sitter holography. Then we initiate the investigation of "microscopic" aspects of holography of Godel universes in string theory. We show that Godel universes are T-dual to pp-waves, and use this fact to generate new Godel-like solutions of string and M-theory by T-dualizing known supersymmetric pp-wave solutions.Comment: 35 pages, 5 figures. v2: typos corrected, references adde

Goedel, Penrose, anti-Mach: extra supersymmetries of time-dependent plane waves

We prove that M-theory plane waves with extra supersymmetries are necessarily homogeneous (but possibly time-dependent), and we show by explicit construction that such time-dependent plane waves can admit extra supersymmetries. To that end we study the Penrose limits of Goedel-like metrics, show that the Penrose limit of the M-theory Goedel metric (with 20 supercharges) is generically a time-dependent homogeneous plane wave of the anti-Mach type, and display the four extra Killings spinors in that case. We conclude with some general remarks on the Killing spinor equations for homogeneous plane waves.Comment: 20 pages, LaTeX2

Cosmology in three dimensions: steps towards the general solution

We use covariant and first-order formalism techniques to study the properties of general relativistic cosmology in three dimensions. The covariant approach provides an irreducible decomposition of the relativistic equations, which allows for a mathematically compact and physically transparent description of the 3-dimensional spacetimes. Using this information we review the features of homogeneous and isotropic 3-d cosmologies, provide a number of new solutions and study gauge invariant perturbations around them. The first-order formalism is then used to provide a detailed study of the most general 3-d spacetimes containing perfect-fluid matter. Assuming the material content to be dust with comoving spatial 2-velocities, we find the general solution of the Einstein equations with non-zero (and zero) cosmological constant and generalise known solutions of Kriele and the 3-d counterparts of the Szekeres solutions. In the case of a non-comoving dust fluid we find the general solution in the case of one non-zero fluid velocity component. We consider the asymptotic behaviour of the families of 3-d cosmologies with rotation and shear and analyse their singular structure. We also provide the general solution for cosmologies with one spacelike Killing vector, find solutions for cosmologies containing scalar fields and identify all the PP-wave 2+1 spacetimes.Comment: 35 pages, 2 figure

Clinical and molecular characterization of HER2 amplified-pancreatic cancer

<p>Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p> <p>Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p> <p>Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p> <p>Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p&gt

Chronology protection in stationary three-dimensional spacetimes

We study chronology protection in stationary, rotationally symmetric spacetimes in 2+1 dimensional gravity, focusing especially on the case of negative cosmological constant. We show that in such spacetimes closed timelike curves must either exist all the way to the boundary or, alternatively, the matter stress tensor must violate the null energy condition in the bulk. We also show that the matter in the closed timelike curve region gives a negative contribution to the conformal weight from the point of view of the dual conformal field theory. We illustrate these properties in a class of examples involving rotating dust in anti-de Sitter space, and comment on the use of the AdS/CFT correspondence to study chronology protection.Comment: 20 pages. V2: minor corrections, Outlook expanded, references added, published versio

The Seven-sphere and its Kac-Moody Algebra

We investigate the seven-sphere as a group-like manifold and its extension to a Kac-Moody-like algebra. Covariance properties and tensorial composition of spinors under $S^7$ are defined. The relation to Malcev algebras is established. The consequences for octonionic projective spaces are examined. Current algebras are formulated and their anomalies are derived, and shown to be unique (even regarding numerical coefficients) up to redefinitions of the currents. Nilpotency of the BRST operator is consistent with one particular expression in the class of (field-dependent) anomalies. A Sugawara construction is given.Comment: 22 pages. Macropackages used: phyzzx, epsf. Three epsf figure files appende

Closed Timelike Curves and Holography in Compact Plane Waves

We discuss plane wave backgrounds of string theory and their relation to Goedel-like universes. This involves a twisted compactification along the direction of propagation of the wave, which induces closed timelike curves. We show, however, that no such curves are geodesic. The particle geodesics and the preferred holographic screens we find are qualitatively different from those in the Goedel-like universes. Of the two types of preferred screen, only one is suited to dimensional reduction and/or T-duality, and this provides a ``holographic protection'' of chronology. The other type of screen, relevant to an observer localized in all directions, is constructed both for the compact and non-compact plane waves, a result of possible independent interest. We comment on the consistency of field theory in such spaces, in which there are closed timelike (and null) curves but no closed timelike (or null) geodesics.Comment: 21 pages, 3 figures, LaTe

Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures