889 research outputs found
Analytic Solution of the Pion-Laser Model
Brooding over bosons, wave packets and Bose - Einstein correlations, we find
that a generalization of the pion-laser model for the case of overlapping
wave-packets is analytically solvable with complete n-particle symmetrization.
The effective radius parameter of the two-particle correlation function is
reduced for low values and enlargened for high values of the mean momentum in
the rare gas limiting case, as compared to the case when multi-particle
symmetrization effects are neglected.
These results explicitly depend on the multiplicity, providing a theoretical
basis for event-by-event analysis of high energy heavy ion reactions.Comment: LaTeX, ReVTeX 3.1, 7 pages, uses 1 eps figure and epsfig.sty
(shortened version
Microcanonical Jet-fragmentation in proton-proton collisions at LHC Energy
In this paper, we show that the distribution of the longitudinal momentum
fraction of charged hadrons inside jets stemming from proton-proton
collisions at = 7 TeV center of mass energy can be described by a
statistical jet-fragmentation model. This model combines microcanonical
statistics and super-statistics induced by multiplicity fluctuations. The
resulting scale dependence of the parameters of the model turns out to be
similar to what was observed in electron-positron annihilations in Urmossy,
Barnaf\"oldi, and Bir\'o.Comment: 7 pages, 8 figure
11 beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle
OBJECTIVE: Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. \ud
RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. \ud
RESULTS: Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer insulin receptor substrate (IRS)-1. 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer IRS1 decreased and pThr Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression.\ud
CONCLUSIONS: Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11beta-HSD1 inhibition decreases pSer IRS1, increases pThr Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action
Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.
This paper was originally published in PLOS ONE (Robinson KA, Hegyi K, Hannun YA, Buse MG, Sethi JK, PLoS ONE 2014, 9(10): e108963. doi:10.1371/journal.pone.0108963).Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway.This work was supported by grants from the Biotechnology and Biological Sciences Research Council (David Phillips Fellowship, JF16994), Diabetes UK (BDA:RD06/0003237) and British Heart Foundation (PG/10/38/28359) to J.K. Sethi and also from National Institute of Diabetes and Digestive and Kidney Diseases (DK-02001) to M.G. Buse
Needs and difficulties of food businesses in the substantiation of health and nutrition claims
The food industry has been struggling with existing guidance on how to prepare health claim dossiers. Hence the EU-funded project PATHWAY-27 seeks to provide a more tailored guidance.Within this project, robust guidelines for the food industry will be developed. The guidelines will be applicable to bioactives and bioactive enriched foods in general, to facilitate health claim documentation and dossiers.Based on a questionnaire, information on the needs and difficulties of the food industry in reaching the requirements established by the national and EU authorities (EFSA) was gathered. Particular emphasis was placed on scientific, economic, technical and technological barriers
Rational Design of α-Helix-Stabilized Exendin-4 Analogues
Exendin-4 (Ex4) is a potent glucagon-like peptide-1 receptor agonist, a drug regulating the plasma glucose level of patients suffering from type 2 diabetes. The molecule’s poor solubility and its readiness to form aggregates increase the likelihood of unwanted side effects. Therefore, we designed Ex4 analogues with improved structural characteristics and better water solubility. Rational design was started from the parent 20-amino acid, well-folded Trp cage (TC) miniprotein and involved the step-by-step N-terminal elongation of the TC head, resulting in the 39-amino acid Ex4 analogue, E19. Helical propensity coupled to tertiary structure compactness was monitored and quantitatively analyzed by electronic circular dichroism and nuclear magnetic resonance (NMR) spectroscopy for the 14 peptides of different lengths. Both 15N relaxation- and diffusion-ordered NMR measurements were established to investigate the inherent mobility and self-association propensity of Ex4 and E19. Our designed E19 molecule has the same tertiary structure as Ex4 but is more helical than Ex4 under all studied conditions; it is less prone to oligomerization and has preserved biological activity. These conditions make E19 a perfect lead compound for further drug discovery. We believe that this structural study improves our understanding of the relationship between local molecular features and global physicochemical properties such as water solubility and could help in the development of more potent Ex4 analogues with improved pharmacokinetic properties
Gauge Singlet Scalars as Cold Dark Matter
In light of recent interest in minimal extensions of the Standard Model and
gauge singlet scalar cold dark matter, we provide an arXiv preprint of the
paper, published as Phys.Rev. D50 (1994) 3637, which presented the first
detailed analysis of gauge singlet scalar cold dark matter.Comment: 37 pages, 11 figures, LaTe
Partition Functions in Statistical Mechanics, Symmetric Functions, and Group Representations
Partition functions for non-interacting particles are known to be symmetric
functions. It is shown that powerful group-theoretical techniques can be used
not only to derive these relationships, but also to significantly simplify
calculation of the partition functions for particles that carry internal
quantum numbers. The partition function is shown to be a sum of one or more
group characters. The utility of character expansions in calculating the
partition functions is explored. Several examples are given to illustrate these
techniques.Comment: 16 pages of RevTe
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