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

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

High Q Cavity Induced Fluxon Bunching in Inductively Coupled Josephson Junctions

We consider fluxon dynamics in a stack of inductively coupled long Josephson junctions connected capacitively to a common resonant cavity at one of the boundaries. We study, through theoretical and numerical analysis, the possibility for the cavity to induce a transition from the energetically favored state of spatially separated shuttling fluxons in the different junctions to a high velocity, high energy state of identical fluxon modes.Comment: 8 pages, 5 figure

Efficient full decay inversion of MRS data with a stretched-exponential approximation of the distribution

We present a new, efficient and accurate forward modelling and inversion scheme for magnetic resonance sounding (MRS) data. MRS, also called surface-nuclear magnetic resonance (surface-NMR), is the only non-invasive geophysical technique that directly detects free water in the subsurface. Based on the physical principle of NMR, protons of the water molecules in the subsurface are excited at a specific frequency, and the superposition of signals from all protons within the excited earth volume is measured to estimate the subsurface water content and other hydrological parameters. In this paper, a new inversion scheme is presented in which the entire data set is used, and multi-exponential behaviour of the NMR signal is approximated by the simple stretched-exponential approach. Compared to the mono-exponential interpretation of the decaying NMR signal, we introduce a single extra parameter, the stretching exponent, which helps describe the porosity in terms of a single relaxation time parameter, and helps to determine correct initial amplitude and relaxation time of the signal. Moreover, compared to a multi-exponential interpretation of the MRS data, the decay behaviour is approximated with considerably fewer parameters. The forward response is calculated in an efficient numerical manner in terms of magnetic field calculation, discretization and integration schemes, which allows fast computation while maintaining accuracy. A piecewise linear transmitter loop is considered for electromagnetic modelling of conductivities in the layered half-space providing electromagnetic modelling of arbitrary loop shapes. The decaying signal is integrated over time windows, called gates, which increases the signal-to-noise ratio, particularly at late times, and the data vector is described with a minimum number of samples, that is, gates. The accuracy of the forward response is investigated by comparing a MRS forward response with responses from three other approaches outlining significant differences between the three approaches. All together, a full MRS forward response is calculated in about 20 s and scales so that on 10 processors the calculation time is reduced to about 34 s. The proposed approach is examined through synthetic data and through a field example, which demonstrate the capability of the scheme. The results of the field example agree well the information from an in-site borehole

Evolution in a Changing Environment

We propose a simple model for genetic adaptation to a changing environment, describing a fitness landscape characterized by two maxima. One is associated with “specialist” individuals that are adapted to the environment; this maximum moves over time as the environment changes. The other maximum is static, and represents “generalist” individuals not affected by environmental changes. The rest of the landscape is occupied by “maladapted” individuals. Our analysis considers the evolution of these three subpopulations. Our main result is that, in presence of a sufficiently stable environmental feature, as in the case of an unchanging aspect of a physical habitat, specialists can dominate the population. By contrast, rapidly changing environmental features, such as language or cultural habits, are a moving target for the genes; here, generalists dominate, because the best evolutionary strategy is to adopt neutral alleles not specialized for any specific environment. The model we propose is based on simple assumptions about evolutionary dynamics and describes all possible scenarios in a non-trivial phase diagram. The approach provides a general framework to address such fundamental issues as the Baldwin effect, the biological basis for language, or the ecological consequences of a rapid climate change

Classical integrable lattice models through quantum group related formalism

We translate effectively our earlier quantum constructions to the classical language and using Yang-Baxterisation of the Faddeev-Reshetikhin-Takhtajan algebra are able to construct Lax operators and associated $r$-matrices of classical integrable models. Thus new as well as known lattice systems of different classes are generated including new types of collective integrable models and canonical models with nonstandard $r$ matrices.Comment: 7 pages; Talk presented at NEEDS'93 (Gallipoli,Italy