Design, synthesis, and biological evaluation of aryl piperazines with potential as antidiabetic agents via the stimulation of glucose uptake and inhibition of NADH:ubiquinone oxidoreductase

The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose uptake compared to vehicle control and micromolar inhibition of NADH:ubiquinone oxidoreductase (IC50 = 27 μM). In vitro DMPK and in vivo PK studies are also described, where results suggest that 3a (RTC1) would not be expected to provoke adverse drug-drug interactions, yet be readily metabolised, avoid rapid excretion, with a short half-life, and have good tissue distribution. The overall results indicate that aryl piperazines, and 3a (RTC1) in particular, have potential as effective agents for the treatment of diabetes

A model for pion Delta electroproduction on the proton

We have extended a model for the $\gamma N\to \pi\pi N$ reaction to virtual photons and selected the diagrams which have a $\Delta$ in the final state. With this model we have evaluated cross sections for the virtual photon cross section as a function of $Q^2$ for different energies. The agreement found with the $\gamma_v p\to\Delta^0\pi^+$ and $\gamma_v p\to\Delta^{++}\pi^-$ reactions is good. The sensitivity of the results to $N\Delta$ transition form factors is also studied. The present reaction, selecting a particular final state, is an extra test for models of the $\gamma_{v} N\to \pi\pi N$ amplitude. The experimental measurement of the different isospin channels for this reaction are encouraged as a means to unravel the dynamics of the two pions photoproduction processes.Comment: 30 pages, 10 figures (ps files). Major changes added. To be published in Nucl. Phys.

Teaching of Energy Issues: A debate proposal for a GLobal Reorientation

The growing awareness of serious difficulties in the learning of energy issues has produced a great deal of research, most of which is focused on specific conceptual aspects. In our opinion, the difficulties pointed out in the literature are interrelated and connected to other aspects (conceptual as well as procedural and axiological), which are not sufficiently taken into account in previous research. This paper aims to carry out a global analysis in order to avoid the more limited approaches that deal only with individual aspects. From this global analysis we have outlined 24 propositions that are put forward for debate to lay the foundations for a profound reorientation of the teaching of energy topics in upper high school courses, in order to facilitate a better scientific understanding of these topics, avoid many students' misconceptions and enhance awareness of the current situation of planetary emergency

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

POSIT-ive negativity Diluting the positivity bias in marketing

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