Lattice stretching bistability and dynamic heterogeneity

A simple one-dimensional lattice model is suggested to describe the experimentally observed plateau in force-stretching diagrams for some macromolecules. This chain model involves the nearest-neighbor interaction of a Morse-like potential (required to have a saturation branch) and an harmonic second-neighbor coupling. Under an external stretching applied t o the chain ends, the intersite Morse-like potential results in the appearance of a double-well potential within each chain monomer, whereas the interaction between the second neighbors provide s a homogeneous bistable (degenerate) ground state, at least within a certain part of the chain. As a result, different conformational changes occur in the chain under the external forcing. The transition regions between these conformations are described as topological solitons. With a strong second-neighbor interaction, the solitons describe the transition between the bistable ground states. However, the key point of the model is the appearance of a heterogenous structure, when the second-neighbor coupling is sufficiently weak. In this case, a part of the chain has short bonds with a single-well potential, whereas the complementary part admits strongly stretched bonds with a double-well potential. This case allows us to explain the existence of a plateau in the force-stretching diagram for DNA and alpha-helix protein. Finally, the soliton dynamics are studied in detail.Comment: Submitted to Phys. Rev. E, 13 figure

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

Separation of variables for a lattice integrable system and the inverse problem

We investigate the relation between the local variables of a discrete integrable lattice system and the corresponding separation variables, derived from the associated spectral curve. In particular, we have shown how the inverse transformation from the separation variables to the discrete lattice variables may be factorised as a sequence of canonical transformations, following the procedure outlined by Kuznetsov.Comment: 14 pages. submitted for publicatio

Quasiperiodic Solutions of the Fibre Optics Coupled Nonlinear Schr{\"o}dinger Equations

We consider travelling periodical and quasiperiodical waves in single mode fibres, with weak birefringence and under the action of cross-phase modulation. The problem is reduced to the ``1:2:1" integrable case of the two-particle quartic potential. A general approach for finding elliptic solutions is given. New solutions which are associated with two-gap Treibich-Verdier potentials are found. General quasiperiodic solutions are given in terms of two dimensional theta functions with explicit expressions for frequencies in terms of theta constants. The reduction of quasiperiodic solutions to elliptic functions is discussed.Comment: 24 page

Fast algorithms for computing defects and their derivatives in the Regge calculus

Any practical attempt to solve the Regge equations, these being a large system of non-linear algebraic equations, will almost certainly employ a Newton-Raphson like scheme. In such cases it is essential that efficient algorithms be used when computing the defect angles and their derivatives with respect to the leg-lengths. The purpose of this paper is to present details of such an algorithm.Comment: 38 pages, 10 figure

Failed attempts to improve the reliability of the alcohol Visual Probe Task following empirical recommendations

Introduction: The Visual Probe Task (VPT) is a computerised task used to measure attentional bias to substance-related stimuli. Little research has examined the psychometric properties of the VPT, despite concerns it demonstrates poor test-retest reliability and internal consistency. These issues can reduce confidence in inferences based on VPT performance. As such, we attempted to identify parameters under which the reliability of the alcohol VPT might be improved by applying recent empirical recommendations for outlier handling, bias calculation and task design from the anxiety literature. Methods: We reanalysed data from 3 previously published studies in our laboratory and 2 newly collected data-sets. We compared tasks which presented images on the left/right of the screen to above/below, whether participants responded to the location or content of the probe, and whether general alcohol-related images or images personalised to the individual were used. In each VPT we also applied a-priori outlier removal (2 and 3 standard deviations and median absolute difference) and data-driven outlier removal (Winsorising), in addition to calculating trial-level bias scores. Results: Across all studies and tasks internal consistency and test-retest reliability of attentional bias measures were inadequate. There was no consistent improvement in internal consistency or test-retest reliability as a function of outlier removal methods. Discussion: We were unable to demonstrate adequate reliability of the alcohol VPT, which further supports observations that these tasks may not yield reliable measures. Future research should focus on improving the reliability of these tasks or abandoning them in favour of more reliable alternatives

Discovery of the spectroscopic binary nature of three bright southern Cepheids

We present an analysis of spectroscopic radial velocity and photometric data of three bright Galactic Cepheids: LR Trianguli Australis (LR TrA), RZ Velorum (RZ Vel), and BG Velorum (BG Vel). Based on new radial velocity data, these Cepheids have been found to be members of spectroscopic binary systems. The ratio of the peak-to-peak radial velocity amplitude to photometric amplitude indicates the presence of a companion for LR TrA and BG Vel. IUE spectra indicate that the companions of RZ Vel and BG Vel cannot be hot stars. The analysis of all available photometric data revealed that the pulsation period of RZ Vel and BG Vel varies monotonically, due to stellar evolution. Moreover, the longest period Cepheid in this sample, RZ Vel, shows period fluctuations superimposed on the monotonic period increase. The light-time effect interpretation of the observed pattern needs long-term photometric monitoring of this Cepheid. The pulsation period of LR TrA has remained constant since the discovery of its brightness variation. Using statistical data, it is also shown that a large number of spectroscopic binaries still remain to be discovered among bright classical Cepheids.Comment: 9 pages, 14 figure