Molecular similarity of MDR inhibitors

Everyone is free to re-use the published material if proper accreditation/citation of the original publication is given. http://creativecommons.org/licences/by/3.0/The molecular similarity of multidrug resistance (MDR) inhibitors was evaluated using the point centred atom charge approach in an attempt to find some common features of structurally unrelated inhibitors. A series of inhibitors of bacterial MDR were studied and there is a high similarity between these in terms of their shape, presence and orientation of aromatic ring moieties. A comparison of the lipophilic properties of these molecules has also been conducted suggesting that this factor is important in MDR inhibition.Peer reviewe

The Geometry of Small Causal Diamonds

The geometry of causal diamonds or Alexandrov open sets whose initial and final events $p$ and $q$ respectively have a proper-time separation $\tau$ small compared with the curvature scale is a universal. The corrections from flat space are given as a power series in $\tau$ whose coefficients involve the curvature at the centre of the diamond. We give formulae for the total 4-volume $V$ of the diamond, the area $A$ of the intersection the future light cone of $p$ with the past light cone of $q$ and the 3-volume of the hyper-surface of largest 3-volume bounded by this intersection valid to ${\cal O} (\tau ^4)$. The formula for the 4-volume agrees with a previous result of Myrheim. Remarkably, the iso-perimetric ratio ${3V_3 \over 4 \pi} / ({A \over 4 \pi}) ^{3 \over 2}$ depends only on the energy density at the centre and is bigger than unity if the energy density is positive. These results are also shown to hold in all spacetime dimensions. Formulae are also given, valid to next non-trivial order, for causal domains in two spacetime dimensions. We suggest a number of applications, for instance, the directional dependence of the volume allows one to regard the volumes of causal diamonds as an observable providing a measurement of the Ricci tensor.Comment: 17 pages, no figures; Misprints in eqs.(62), (65), (66) and (81) corrected; a new note on page 13 (with 2 new equations) adde

Bohm and Einstein-Sasaki Metrics, Black Holes and Cosmological Event Horizons

We study physical applications of the Bohm metrics, which are infinite sequences of inhomogeneous Einstein metrics on spheres and products of spheres of dimension 5 <= d <= 9. We prove that all the Bohm metrics on S^3 x S^2 and S^3 x S^3 have negative eigenvalue modes of the Lichnerowicz operator and by numerical methods we establish that Bohm metrics on S^5 have negative eigenvalues too. We argue that all the Bohm metrics will have negative modes. These results imply that higher-dimensional black-hole spacetimes where the Bohm metric replaces the usual round sphere metric are classically unstable. We also show that the stability criterion for Freund-Rubin solutions is the same as for black-hole stability, and hence such solutions using Bohm metrics will also be unstable. We consider possible endpoints of the instabilities, and show that all Einstein-Sasaki manifolds give stable solutions. We show how Wick rotation of Bohm metrics gives spacetimes that provide counterexamples to a strict form of the Cosmic Baldness conjecture, but they are still consistent with the intuition behind the cosmic No-Hair conjectures. We show how the Lorentzian metrics may be created ``from nothing'' in a no-boundary setting. We argue that Lorentzian Bohm metrics are unstable to decay to de Sitter spacetime. We also argue that noncompact versions of the Bohm metrics have infinitely many negative Lichernowicz modes, and we conjecture a general relation between Lichnerowicz eigenvalues and non-uniqueness of the Dirichlet problem for Einstein's equations.Comment: 53 pages, 11 figure

Fixed Scalars and Suppression of Hawking Evaporation

For an extreme charged black hole some scalars take on a fixed value at the horizon determined by the charges alone. We call them fixed scalars. We find the absorption cross section for a low frequency wave of a fixed scalar to be proportional to the square of the frequency. This implies a strong suppression of the Hawking radiation near extremality. We compute the coefficient of proportionality for a specific model.Comment: 10 pages, late

Convection in the Earth's core driven by lateral variations in the core-mantle boundary heat flux

Moving core fluid maintains an isothermal core-mantle boundary (CMB), so lateral variations in the CMB heat flow result from mantle convection. Such variations will drive thermal winds, even if the top of the core is stably stratified. These flows may contribute to the magnetic secular variation and are investigated here using a simple, non-magnetic numerical model of the core. The results depend on the equatorial symmetry of the boundary heat flux variation. Large-scale equatorially symmetric (ES) heat flux variations at the outer surface of a rapidly rotating spherical shell drive deeply penetrating flows that are strongly suppressed in stratified fluid. Smaller-scale ES heat flux variations drive flows less dominated by rotation and so less inhibited by stratification. Equatorially anti-symmetric flux variations drive flows an order of magnitude less energetic than those driven by ES patterns but, due to the nature of the Coriolis force, are less suppressed by stratification. The response of the rotating core fluid to a general CMB heat flow pattern will then depend strongly on the subadiabatic temperature profile. Imposing a lateral heat flux variation linearly related to a model of seismic tomography in the lowermost mantle drives flow in a density stratified fluid that reproduces some features found in flows inverted from geomagnetic data

Some Comments on Gravitational Entropy and the Inverse Mean Curvature Flow

The Geroch-Wald-Jang-Huisken-Ilmanen approach to the positive energy problem to may be extended to give a negative lower bound for the mass of asymptotically Anti-de-Sitter spacetimes containing horizons with exotic topologies having ends or infinities of the form $\Sigma_g \times {\Bbb R}$, in terms of the cosmological constant. We also show how the method gives a lower bound for for the mass of time-symmetric initial data sets for black holes with vectors and scalars in terms of the mass, $|Z(Q,P)|$ of the double extreme black hole with the same charges. I also give a lower bound for the area of an apparent horizon, and hence a lower bound for the entropy in terms of the same function $|Z(Q,P)|$. This shows that the so-called attractor behaviour extends beyond the static spherically symmetric case. and underscores the general importance of the function $|Z(Q,P)|$. There are hints that higher dimensional generalizations may involve the Yamabe conjectures.Comment: 13pp. late

Extended uncertainty principle and the geometry of (anti)-de Sitter space

It has been proposed that on (anti)-de Sitter background, the Heisenberg uncertainty principle should be modified by the introduction of a term proportional to the cosmological constant. We show that this modification of the uncertainty principle can be derived straightforwardly from the geometric properties of (anti)-de Sitter spacetime. We also discuss the connection between the so-called extended generalized uncertainty principle and triply special relativity.Comment: 8 pages, plain TeX, references adde