Non-Gaussianity and large-scale structure in a two-field inflationary model

Single field inflationary models predict nearly Gaussian initial conditions and hence a detection of non-Gaussianity would be a signature of the more complex inflationary scenarios. In this paper we study the effect on the cosmic microwave background and on large scale structure from primordial non-Gaussianity in a two-field inflationary model in which both the inflaton and curvaton contribute to the density perturbations. We show that in addition to the previously described enhancement of the galaxy bias on large scales, this setup results in large-scale stochasticity. We provide joint constraints on the local non-Gaussianity parameter $\tilde f_{\rm NL}$ and the ratio $\xi$ of the amplitude of primordial perturbations due to the inflaton and curvaton using WMAP and SDSS data

Probing the Primordial Power Spectrum with Cluster Number Counts

We investigate how well galaxy cluster number counts can constrain the primordial power spectrum. Measurements of the primary anisotropies in the cosmic microwave background (CMB) may be limited, by the presence of foregrounds from secondary sources, to probing the primordial power spectrum at wave numbers less than about 0.30 h Mpc^{-1}. We break up the primordial power spectrum into a number of nodes and interpolate linearly between each node. This allows us to show that cluster number counts could then extend the constraints on the form of the primordial power spectrum up to wave numbers of about 0.45 h Mpc^{-1}. We estimate combinations of constraints from PLANCK and SPT primary CMB and their respective SZ surveys. We find that their constraining ability is limited by uncertainties in the mass scaling relations. We also estimate the constraint from clusters detected from a SNAP like gravitational lensing survey. As there is an unambiguous and simple relationship between the filtered shear of the lensing survey and the cluster mass, it may be possible to obtain much tighter constraints on the primordial power spectrum in this case.Comment: Clarifications added and a few minor corrections made. Matches version to appear in PR

Bayesian Calibrated Significance Levels Applied to the Spectral Tilt and Hemispherical Asymmetry

Bayesian model selection provides a formal method of determining the level of support for new parameters in a model. However, if there is not a specific enough underlying physical motivation for the new parameters it can be hard to assign them meaningful priors, an essential ingredient of Bayesian model selection. Here we look at methods maximizing the prior so as to work out what is the maximum support the data could give for the new parameters. If the maximum support is not high enough then one can confidently conclude that the new parameters are unnecessary without needing to worry that some other prior may make them significant. We discuss a computationally efficient means of doing this which involves mapping p-values onto upper bounds of the Bayes factor (or odds) for the new parameters. A p-value of 0.05 ($1.96\sigma$) corresponds to odds less than or equal to 5:2 which is below the `weak' support at best threshold. A p-value of 0.0003 ($3.6\sigma$) corresponds to odds of less than or equal to 150:1 which is the `strong' support at best threshold. Applying this method we find that the odds on the scalar spectral index being different from one are 49:1 at best. We also find that the odds that there is primordial hemispherical asymmetry in the cosmic microwave background are 9:1 at best.Comment: 5 pages. V2: clarifying comments added in response to referee report. Matches version to appear in MNRA

Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity.

Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis

Impact of Parenteral Nutrition Versus Fasting on Hepatic Bile Acid Production and Transport in a Rabbit Model of Prolonged Critical Illness

Cholestatic liver dysfunction frequently occurs during critical illness. Administration of parenteral nutrition (PN) is thought to aggravate this. Underlying mechanisms are not clear.status: publishe

The XMM Cluster Survey: a massive galaxy cluster at z = 1.45

We report the discovery of XMMXCS J2215.9-1738, a massive galaxy cluster at z=1.45, which was found in the XMM Cluster Survey. The cluster candidate was initially identified as an extended X-ray source in archival XMM data. Optical spectroscopy shows that six galaxies within a ~60" diameter region lie at z=1.45+/-0.01. Model fits to the X-ray spectra of the extended emission yield kT=7.4+2.7-1.8 keV (90% confidence); if there is an undetected central X-ray point source, then kT=6.5+2.6-1.8 keV. The bolometric X-ray luminosity is LX=4.4+0.8-0.6C 1044 ergs s-1 over a 2 Mpc radial region. The measured TX, which is the highest for any known cluster at z>1, suggests that this cluster is relatively massive for such a high redshift. The redshift of XMMXCS J2215.9-1738 is the highest currently known for a spectroscopically confirmed cluster of galaxies

The XMM Cluster Survey: The Dynamical State of XMMXCS J2215.9-1738 at z=1.457

We present new spectroscopic observations of the most distant X-ray selected galaxy cluster currently known, XMMXCS J2215.9-1738 at z=1.457, obtained with the DEIMOS instrument at the W. M. Keck Observatory, and the FORS2 instrument on the ESO Very Large Telescope. Within the cluster virial radius, as estimated from the cluster X-ray properties, we increase the number of known spectroscopic cluster members to 17 objects, and calculate the line of sight velocity dispersion of the cluster to be 580+/-140 km/s. We find mild evidence that the velocity distribution of galaxies within the virial radius deviates from a single Gaussian. We show that the properties of J2215.9-1738 are inconsistent with self-similar evolution of local X-ray scaling relations, finding that the cluster is underluminous given its X-ray temperature, and that the intracluster medium contains ~2-3 times the kinetic energy per unit mass of the cluster galaxies. These results can perhaps be explained if the cluster is observed in the aftermath of an off-axis merger. Alternatively, heating of the intracluster medium through supernovae and/or Active Galactic Nuclei activity, as is required to explain the observed slope of the local X-ray luminosity-temperature relation, may be responsible.Comment: 13 pages, 6 figures, accepted for publication in Ap

A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.

The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified IKK-ε and TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute inhibition of IKK-ε and TBK1 with amlexanox treatment increases cAMP levels in subcutaneous adipose depots of obese mice, promoting the synthesis and secretion of the cytokine IL-6 from adipocytes and preadipocytes, but not from macrophages. IL-6, in turn, stimulates the phosphorylation of hepatic Stat3 to suppress expression of genes involved in gluconeogenesis, in the process improving glucose handling in obese mice. Preliminary data in a small cohort of obese patients show a similar association. These data support an important role for a subcutaneous adipose tissue-liver axis in mediating the acute metabolic benefits of amlexanox on glucose metabolism, and point to a new therapeutic pathway for type 2 diabetes

FGF19 Regulates Cell Proliferation, Glucose and Bile Acid Metabolism via FGFR4-Dependent and Independent Pathways

Fibroblast growth factor 19 (FGF19) is a hormone-like protein that regulates carbohydrate, lipid and bile acid metabolism. At supra-physiological doses, FGF19 also increases hepatocyte proliferation and induces hepatocellular carcinogenesis in mice. Much of FGF19 activity is attributed to the activation of the liver enriched FGF Receptor 4 (FGFR4), although FGF19 can activate other FGFRs in vitro in the presence of the coreceptor βKlotho (KLB). In this report, we investigate the role of FGFR4 in mediating FGF19 activity by using Fgfr4 deficient mice as well as a variant of FGF19 protein (FGF19v) which is specifically impaired in activating FGFR4. Our results demonstrate that FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19, but is not essential for FGF19 to improve glucose and lipid metabolism in high fat diet fed mice as well as in leptin-deficient ob/ob mice. Thus, FGF19 acts through multiple receptor pathways to elicit pleiotropic effects in regulating nutrient metabolism and cell proliferation

On Perturbations in Warm Inflation

Warm inflation is an interesting possibility of describing the early universe, whose basic feature is the absence, at least in principle, of a preheating or reheating phase. Here we analyze the dynamics of warm inflation generalizing the usual slow-roll parameters that are useful for characterizing the inflationary phase. We study the evolution of entropy and adiabatic perturbations, where the main result is that for a very small amount of dissipation the entropy perturbations can be neglected and the purely adiabatic perturbations will be responsible for the primordial spectrum of inhomogeneities. Taking into account the COBE-DMR data of the cosmic microwave background anisotropy as well as the fact that the interval of inflation for which the scales of astrophysical interest cross outside the Hubble radius is about 50 e-folds before the end of inflation, we could estimate the magnitude of the dissipation term. It was also possible to show that at the end of inflation the universe is hot enough to provide a smooth transition to the radiation era.Comment: 12 pages, no figures, requires revtex4. Further explanation on the origin of the entropy perturbation, reference added and minor notation change. Version accepted for publication in Phys. Rev.