1,649 research outputs found
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
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 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)
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