GSK-3 protein and the heart: friend or foe?

Metabolic syndrome manifesting as obesity, insulin resistance and type 2 diabetes mellitus is currently pandemic. Each of these, in its own right, is strongly related to the development of cardiovascular disease. The cardiomyopathy associated with these disorders is characterised by curtailed glucose uptake and utilisation, elevated risk of damage after ischaemia and contractile dysfunction. Current research have indicated that the serine/threonine kinase, glycogen synthase kinase 3 (GSK-3), may play a central role in the development of all these dysfunctions. The development of new generations of inhibitors of this kinase, has renewed interest in its utilisation as therapeutic target. This review has therefore focused on the role of GSK-3 in the development of the obesity-related cardiomyopathy and has highlighted and discussed the detrimental as well as beneficial effects of the GSK-3 inhibitors that are currently available. We have discussed the different roleplayers such as the insulin signalling pathway, modulation of apoptosis and mitochondrial function, SERCA2 expression and regulation of the development of hypertrophy in the context of GSK-3 activity

Extending BEAMS to incorporate correlated systematic uncertainties

New supernova surveys such as the Dark Energy Survey, Pan-STARRS and the LSST will produce an unprecedented number of photometric supernova candidates, most with no spectroscopic data. Avoiding biases in cosmological parameters due to the resulting inevitable contamination from non-Ia supernovae can be achieved with the BEAMS formalism, allowing for fully photometric supernova cosmology studies. Here we extend BEAMS to deal with the case in which the supernovae are correlated by systematic uncertainties. The analytical form of the full BEAMS posterior requires evaluating 2^N terms, where N is the number of supernova candidates. This `exponential catastrophe' is computationally unfeasible even for N of order 100. We circumvent the exponential catastrophe by marginalising numerically instead of analytically over the possible supernova types: we augment the cosmological parameters with nuisance parameters describing the covariance matrix and the types of all the supernovae, \tau_i, that we include in our MCMC analysis. We show that this method deals well even with large, unknown systematic uncertainties without a major increase in computational time, whereas ignoring the correlations can lead to significant biases and incorrect credible contours. We then compare the numerical marginalisation technique with a perturbative expansion of the posterior based on the insight that future surveys will have exquisite light curves and hence the probability that a given candidate is a Type Ia will be close to unity or zero, for most objects. Although this perturbative approach changes computation of the posterior from a 2^N problem into an N^2 or N^3 one, we show that it leads to biases in general through a small number of misclassifications, implying that numerical marginalisation is superior.Comment: Resubmitted under married name Lochner (formally Knights). Version 3: major changes, including a large scale analysis with thousands of MCMC chains. Matches version published in JCAP. 23 pages, 8 figure

Towards the Future of Supernova Cosmology

For future surveys, spectroscopic follow-up for all supernovae will be extremely difficult. However, one can use light curve fitters, to obtain the probability that an object is a Type Ia. One may consider applying a probability cut to the data, but we show that the resulting non-Ia contamination can lead to biases in the estimation of cosmological parameters. A different method, which allows the use of the full dataset and results in unbiased cosmological parameter estimation, is Bayesian Estimation Applied to Multiple Species (BEAMS). BEAMS is a Bayesian approach to the problem which includes the uncertainty in the types in the evaluation of the posterior. Here we outline the theory of BEAMS and demonstrate its effectiveness using both simulated datasets and SDSS-II data. We also show that it is possible to use BEAMS if the data are correlated, by introducing a numerical marginalisation over the types of the objects. This is largely a pedagogical introduction to BEAMS with references to the main BEAMS papers.Comment: Replaced under married name Lochner (formally Knights). 3 pages, 2 figures. To appear in the Proceedings of 13th Marcel Grossmann Meeting (MG13), Stockholm, Sweden, 1-7 July 201

Thiamine deficiency and beriberi heart disease

No Abstract

A Frequency-Controlled Magnetic Vortex Memory

Using the ultra low damping NiMnSb half-Heusler alloy patterned into vortex-state magnetic nano-dots, we demonstrate a new concept of non-volatile memory controlled by the frequency. A perpendicular bias magnetic field is used to split the frequency of the vortex core gyrotropic rotation into two distinct frequencies, depending on the sign of the vortex core polarity $p=\pm1$ inside the dot. A magnetic resonance force microscope and microwave pulses applied at one of these two resonant frequencies allow for local and deterministic addressing of binary information (core polarity)