Is the gravitational action additive?

The gravitational action is not always additive in the usual sense. We provide a general prescription for the change in action that results when different portions of the boundary of a spacetime are topologically identified. We discuss possible implications for the superposition law of quantum gravity. We present a definition of `generalized additivity' which does hold for arbitrary spacetime composition.Comment: 20 pages LaTeX file, report numbers UMD-PP 94-100 and Alberta Thy 10-9

Outcome Measures in Facioscapulohumeral Muscular Dystrophy Clinical Trials

Facioscapulohumeral muscular dystrophy (FSHD) is a debilitating muscular dystrophy with a variable age of onset, severity, and progression. While there is still no cure for this disease, progress towards FSHD therapies has accelerated since the underlying mechanism of epigenetic derepression of the double homeobox 4 (DUX4) gene leading to skeletal muscle toxicity was identified. This has facilitated the rapid development of novel therapies to target DUX4 expression and downstream dysregulation that cause muscle degeneration. These discoveries and pre-clinical translational studies have opened new avenues for therapies that await evaluation in clinical trials. As the field anticipates more FSHD trials, the need has grown for more reliable and quantifiable outcome measures of muscle function, both for early phase and phase II and III trials. Advanced tools that facilitate longitudinal clinical assessment will greatly improve the potential of trials to identify therapeutics that successfully ameliorate disease progression or permit muscle functional recovery. Here, we discuss current and emerging FSHD outcome measures and the challenges that investigators may experience in applying such measures to FSHD clinical trial design and implementation

Quasilocal Energy for a Kerr black hole

The quasilocal energy associated with a constant stationary time slice of the Kerr spacetime is presented. The calculations are based on a recent proposal \cite{by} in which quasilocal energy is derived from the Hamiltonian of spatially bounded gravitational systems. Three different classes of boundary surfaces for the Kerr slice are considered (constant radius surfaces, round spheres, and the ergosurface). Their embeddings in both the Kerr slice and flat three-dimensional space (required as a normalization of the energy) are analyzed. The energy contained within each surface is explicitly calculated in the slow rotation regime and its properties discussed in detail. The energy is a positive, monotonically decreasing function of the boundary surface radius. It approaches the Arnowitt-Deser-Misner (ADM) mass at spatial infinity and reduces to (twice) the irreducible mass at the horizon of the Kerr black hole. The expressions possess the correct static limit and include negative contributions due to gravitational binding. The energy at the ergosurface is compared with the energies at other surfaces. Finally, the difficulties involved in an estimation of the energy in the fast rotation regime are discussed.Comment: 22 pages, Revtex, Alberta-Thy-18-94. (the approximations in Section IV have been improved. To appear in Phys. Rev. D

Two-dimensional quantum-corrected black hole in a finite size cavity

We consider the gravitation-dilaton theory (not necessarily exactly solvable), whose potentials represent a generic linear combination of an exponential and linear functions of the dilaton. A black hole, arising in such theories, is supposed to be enclosed in a cavity, where it attains thermal equilibrium, whereas outside the cavity the field is in the Boulware state. We calculate quantum corrections to the Hawking temperature $T_{H}$, with the contribution from the boundary taken into account. Vacuum polarization outside the shell tend to cool the system. We find that, for the shell to be in the thermal equilibrium, it cannot be placed too close to the horizon. The quantum corrections to the mass due to vacuum polarization vanish in spite of non-zero quantum stresses. We discuss also the canonical boundary conditions and show that accounting for the finiteness of the system plays a crucial role in some theories (e.g., CGHS), where it enables to define the stable canonical ensemble, whereas consideration in an infinite space would predict instability.Comment: 21 pages. In v.2 misprints corrected. To appear in Phys. Rev.

Population structure and associated phenotypes of Salmonella enterica serovars Derby and Mbandaka overlap with host range

BACKGROUND:The Salmonella enterica serovar Derby is frequently isolated from pigs and turkeys whereas serovar Mbandaka is frequently isolated from cattle, chickens and animal feed in the UK. Through comparative genomics, phenomics and mutant construction we previously suggested possible mechanistic reasons why these serovars demonstrate apparently distinct host ranges. Here, we investigate the genetic and phenotypic diversity of these two serovars in the UK. We produce a phylogenetic reconstruction and perform several biochemical assays on isolates of S. Derby and S. Mbandaka acquired from sites across the UK between the years 2000 and 2010. RESULTS:We show that UK isolates of S. Mbandaka comprise of one clonal lineage which is adapted to proficient utilisation of metabolites found in soya beans under ambient conditions. We also show that this clonal lineage forms a biofilm at 25 °C, suggesting that this serovar maybe well adapted to survival ex vivo, growing in animal feed. Conversely, we show that S. Derby is made of two distinct lineages, L1 and L2. These lineages differ genotypically and phenotypically, being divided by the presence and absence of SPI-23 and the ability to more proficiently invade porcine jejunum derived cell line IPEC-J2. CONCLUSION:The results of this study lend support to the hypothesis that the differences in host ranges of S. Derby and S. Mbandaka are adaptations to pathogenesis, environmental persistence, as well as utilisation of metabolites abundant in their respective host environments

A real-time proximity querying algorithm for haptic-based molecular docking

Intermolecular binding underlies every metabolic and regulatory processes of the cell, and the therapeutic and pharmacological properties of drugs. Molecular docking systems model and simulate these interactions in silico and allow us to study the binding process. Haptic-based docking provides an immersive virtual docking environment where the user can interact with and guide the molecules to their binding pose. Moreover, it allows human perception, intuition and knowledge to assist and accelerate the docking process, and reduces incorrect binding poses. Crucial for interactive docking is the real-time calculation of interaction forces. For smooth and accurate haptic exploration and manipulation, force-feedback cues have to be updated at a rate of 1 kHz. Hence, force calculations must be performed within 1ms. To achieve this, modern haptic-based docking approaches often utilize pre-computed force grids and linear interpolation. However, such grids are time-consuming to pre-compute (especially for large molecules), memory hungry, can induce rough force transitions at cell boundaries and cannot be applied to flexible docking. Here we propose an efficient proximity querying method for computing intermolecular forces in real time. Our motivation is the eventual development of a haptic-based docking solution that can model molecular flexibility. Uniquely in a haptics application we use octrees to decompose the 3D search space in order to identify the set of interacting atoms within a cut-off distance. Force calculations are then performed on this set in real time. The implementation constructs the trees dynamically, and computes the interaction forces of large molecular structures (i.e. consisting of thousands of atoms) within haptic refresh rates. We have implemented this method in an immersive, haptic-based, rigid-body, molecular docking application called Haptimol_RD. The user can use the haptic device to orientate the molecules in space, sense the interaction forces on the device, and guide the molecules to their binding pose. Haptimol_RD is designed to run on consumer level hardware, i.e. there is no need for specialized/proprietary hardware