Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

Complex Line Bundles over Simplicial Complexes and their Applications

Discrete vector bundles are important in Physics and recently found remarkable applications in Computer Graphics. This article approaches discrete bundles from the viewpoint of Discrete Differential Geometry, including a complete classification of discrete vector bundles over finite simplicial complexes. In particular, we obtain a discrete analogue of a theorem of Andr\'e Weil on the classification of hermitian line bundles. Moreover, we associate to each discrete hermitian line bundle with curvature a unique piecewise-smooth hermitian line bundle of piecewise constant curvature. This is then used to define a discrete Dirichlet energy which generalizes the well-known cotangent Laplace operator to discrete hermitian line bundles over Euclidean simplicial manifolds of arbitrary dimension

The ensemble of random Markov matrices

The ensemble of random Markov matrices is introduced as a set of Markov or stochastic matrices with the maximal Shannon entropy. The statistical properties of the stationary distribution pi, the average entropy growth rate $h$ and the second largest eigenvalue nu across the ensemble are studied. It is shown and heuristically proven that the entropy growth-rate and second largest eigenvalue of Markov matrices scale in average with dimension of matrices d as h ~ log(O(d)) and nu ~ d^(-1/2), respectively, yielding the asymptotic relation h tau_c ~ 1/2 between entropy h and correlation decay time tau_c = -1/log|nu| . Additionally, the correlation between h and and tau_c is analysed and is decreasing with increasing dimension d.Comment: 12 pages, 6 figur

A numerical study of infinitely renormalizable area-preserving maps

It has been shown in (Gaidashev et al, 2010) and (Gaidashev et al, 2011) that infinitely renormalizable area-preserving maps admit invariant Cantor sets with a maximal Lyapunov exponent equal to zero. Furthermore, the dynamics on these Cantor sets for any two infinitely renormalizable maps is conjugated by a transformation that extends to a differentiable function whose derivative is Holder continuous of exponent alpha>0. In this paper we investigate numerically the specific value of alpha. We also present numerical evidence that the normalized derivative cocycle with the base dynamics in the Cantor set is ergodic. Finally, we compute renormalization eigenvalues to a high accuracy to support a conjecture that the renormalization spectrum is real

Kink propagation in a two-dimensional curved Josephson junction

We consider the propagation of sine-Gordon kinks in a planar curved strip as a model of nonlinear wave propagation in curved wave guides. The homogeneous Neumann transverse boundary conditions, in the curvilinear coordinates, allow to assume a homogeneous kink solution. Using a simple collective variable approach based on the kink coordinate, we show that curved regions act as potential barriers for the wave and determine the threshold velocity for the kink to cross. The analysis is confirmed by numerical solution of the 2D sine-Gordon equation.Comment: 8 pages, 4 figures (2 in color

Propagating Torsion in 3D-Gravity and Dynamical Mass Generation

In this paper, fermions are minimally coupled to 3D-gravity where a dynamical torsion is introduced. A Kalb-Ramond field is non-minimally coupled to these fermions in a gauge-invariant way. We show that a 1-loop mass generation mechanism takes place for both the 2-form gauge field and the torsion. As for the fermions, no mass is dynamically generated: at 1-loop, there is only a mass shift proportional to the Yukawa coupling whenever the fermions have a non-vanishing tree-level mass.Comment: 13 pages, latex file, no figures, some corrections adde

Parametrically Excited Surface Waves: Two-Frequency Forcing, Normal Form Symmetries, and Pattern Selection

Motivated by experimental observations of exotic standing wave patterns in the two-frequency Faraday experiment, we investigate the role of normal form symmetries in the pattern selection problem. With forcing frequency components in ratio m/n, where m and n are co-prime integers, there is the possibility that both harmonic and subharmonic waves may lose stability simultaneously, each with a different wavenumber. We focus on this situation and compare the case where the harmonic waves have a longer wavelength than the subharmonic waves with the case where the harmonic waves have a shorter wavelength. We show that in the former case a normal form transformation can be used to remove all quadratic terms from the amplitude equations governing the relevant resonant triad interactions. Thus the role of resonant triads in the pattern selection problem is greatly diminished in this situation. We verify our general results within the example of one-dimensional surface wave solutions of the Zhang-Vinals model of the two-frequency Faraday problem. In one-dimension, a 1:2 spatial resonance takes the place of a resonant triad in our investigation. We find that when the bifurcating modes are in this spatial resonance, it dramatically effects the bifurcation to subharmonic waves in the case of forcing frequencies are in ratio 1/2; this is consistent with the results of Zhang and Vinals. In sharp contrast, we find that when the forcing frequencies are in ratio 2/3, the bifurcation to (sub)harmonic waves is insensitive to the presence of another spatially-resonant bifurcating mode.Comment: 22 pages, 6 figures, late

Universal renormalization-group dynamics at the onset of chaos in logistic maps and nonextensive statistical mechanics

We uncover the dynamics at the chaos threshold $\mu_{\infty}$ of the logistic map and find it consists of trajectories made of intertwined power laws that reproduce the entire period-doubling cascade that occurs for $\mu <\mu_{\infty}$. We corroborate this structure analytically via the Feigenbaum renormalization group (RG) transformation and find that the sensitivity to initial conditions has precisely the form of a $q$-exponential, of which we determine the $q$-index and the $q$-generalized Lyapunov coefficient $\lambda _{q}$. Our results are an unequivocal validation of the applicability of the non-extensive generalization of Boltzmann-Gibbs (BG) statistical mechanics to critical points of nonlinear maps.Comment: Revtex, 3 figures. Updated references and some general presentation improvements. To appear published as a Rapid communication of PR