269 research outputs found
Evidence of Strong Electron Correlations in Gamma-Iron
Single-particle excitation spectra of gamma-Fe in the paramagnetic state have
been investigated by means of the first-principles dynamical coherent potential
approximation theory which has recently been developed. It is found that the
central peak in the density of states consisting of the t2g bands is destroyed
by electron correlations, and the Mott-Hubbard type correlated bands appear.
The results indicate that the gamma-Fe can behave as correlated electrons at
high temperatures.Comment: 7 pages, 3 figures, to be published in J. Phys. Soc. Jpn. Vol.78,
No.9 (2009
State-of-the-art microscopy to understand islets of Langerhans:what to expect next?
The discovery of Langerhans and microscopic description of islets in the pancreas were crucial steps in the discovery of insulin. Over the past 150 years, many discoveries in islet biology and type 1 diabetes have been made using powerful microscopic techniques. In the past decade, combination of new probes, animal and tissue models, application of new biosensors and automation of light and electron microscopic methods and other (sub)cellular imaging modalities have proven their potential in understanding the beta cell under (patho)physiological conditions. The imaging evolution, from fluorescent jellyfish to real-time intravital functional imaging, the revolution in automation and data handling and the increased resolving power of analytical imaging techniques are now converging. Here, we review innovative approaches that address islet biology from new angles by studying cells and molecules at high spatiotemporal resolution and in live models. Broad implementation of these cellular imaging techniques will shed new light on cause/consequence of (mal)function in islets of Langerhans in the years to come
Intracellular Serotonin Modulates Insulin Secretion from Pancreatic ÎČ-Cells by Protein Serotonylation
Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion
INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes
Background
The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials.
Methods
In this context, we have developed a Master Protocol, based on the âbackboneâ of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow.
Discussion
The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers
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