Hypoxia and muscle maintenance regulation: implications for chronic respiratory disease

PURPOSE OF REVIEW: Muscle wasting and impaired muscle oxidative metabolism are common extrapulmonary features of chronic respiratory failure (CRF) that significantly increase disease burden. This review aims to address the question whether hypoxia, an obvious consequence of this disease, actually plays a causal role in these muscle impairments. RECENT FINDINGS: In experimental models, a causal role for hypoxia in muscle atrophy and metabolic impairments has clearly been shown. Although the hypoxia-inducible factors and nuclear factor kappa B are putative mediators of these hypoxia-induced alterations, their true involvement remains to be proven. Molecular signatures of disrupted regulation of muscle mass and oxidative metabolism observed in these experimental models also have been shown in muscles of patients suffering from CRF, suggestive of but not conclusive for a causal role of hypoxia. Therapies, including but not restricted to those aimed at alleviating hypoxia, have been shown to partially but not completely restore muscle mass and oxidative capacity in CRF patients, which may imply an additive effect of nutritional modulation of substrate metabolism. SUMMARY: Although hypoxia clearly affects skeletal muscle maintenance, it remains to be confirmed whether and by which underlying molecular mechanisms hypoxia is causally involved in CRF-related muscle atrophy and impaired oxidative capacity

HST Observations of the Gravitationally Lensed Cloverleaf Broad Absorption Line QSO H1413+1143: Modeling the Lens

We investigate gravitational lens models for the quadruply-lensed Cloverleaf BAL QSO H1413+1143 based on the HST WFPC/WFPC2 astrometric and photometric data of the system by Turnshek et al. and the HST NICMOS-2 data by Falco et al. The accurate image positions and the dust-extinction-corrected relative amplifications, along with a possible detection of the lensing galaxy in the infrared, permit more accurate lens models than were previously possible. While more recent models are qualitatively consistent with the HST data, none of the previous models considered the dust-extinction-corrected relative amplifications of the image components. We use the power-law elliptical mass model to fit the HST data. We find that a single elliptical galaxy perturbed by an external shear can fit the image positions within the observational uncertainties; however, the predicted relative magnifications are only roughly consistent with the observational relative amplifications. We find that a primary galaxy combined with a secondary galaxy in the vicinity of the Cloverleaf or a cluster centered (south-)west of the Cloverleaf can fit both the image positions and relative amplifications within the observational uncertainties. We discuss future observations which could be used to test and/or further constrain lens models of the Cloverleaf.Comment: 23 pages (in aaspp.sty) including 5 tables and 3 figures, Accepted for publication in the Astrophysical Journa

Cluster Alignments and Ellipticities in LCDM Cosmology

The ellipticities and alignments of clusters of galaxies, and their evolution with redshift, are examined in the context of a Lambda-dominated cold dark matter cosmology. We use a large-scale, high-resolution N-body simulation to model the matter distribution in a light cone containing ~10^6 clusters out to redshifts of z=3. Cluster ellipticities are determined as a function of mass, radius, and redshift, both in 3D and in projection. We find strong cluster ellipticities: the mean ellipticity increases with redshift from 0.3 at z=0 to 0.5 at z=3, for both 3D and 2D ellipticities; the evolution is well-fit by e=0.33+0.05z. The ellipticities increase with cluster mass and with cluster radius; the main cluster body is more elliptical than the cluster cores, but the increase of ellipticities with redshift is preserved. Using the fitted cluster ellipsoids, we determine the alignment of clusters as a function of their separation. We find strong alignment of clusters for separations <100 Mpc/h; the alignment increases with decreasing separation and with increasing redshift. The evolution of clusters from highly aligned and elongated systems at early times to lower alignment and elongation at present reflects the hierarchical and filamentary nature of structure formation. These measures of cluster ellipticity and alignment will provide a new test of the current cosmological model when compared with upcoming cluster surveys.Comment: 29 pages including 13 figures, to appear in ApJ Jan. 2005 (corrected typos, added reference

Cluster Ellipticities as a Cosmological Probe

We investigate the dependence of ellipticities of clusters of galaxies on cosmological parameters using large-scale cosmological simulations. We determine cluster ellipticities out to redshift unity for LCDM models with different mean densities $\Omega_m$ and amplitudes of mass fluctuation $\sigma_{8,0}$. The mean ellipticity increases monotonically with redshift for all models. Larger values of $\sigma_{8,0}$, i.e., earlier cluster formation time, produce lower ellipticities. The dependence of ellipticity on $\Omega_m$ is relatively weak in the range $0.2 \leq \Omega_m \leq 0.5$ for high mass clusters. The mean ellipticity $\bar{e}(z)$ decreases linearly with the amplitude of fluctuations at the cluster redshift $z$, nearly independent of $\Omega_m$; on average, older clusters are more relaxed and are thus less elliptical. The distribution of ellipticities about the mean is approximated by a Gaussian, allowing a simple characterization of the evolution of ellipticity with redshift as a function of cosmological parameters. At $z=0$, the mean ellipticity of high mass clusters is approximated by $\bar{e}(z=0) = 0.248-0.069 \sigma_{8,0} + 0.013 \Omega_{m,0}$. This relation opens up the possibility that, when compared with future observations of large cluster samples, the mean cluster ellipticity and its evolution could be used as a new, independent tool to constrain cosmological parameters, especially the amplitude of mass fluctuations, $\sigma_{8,0}$.Comment: 16 pages, 4 figure

The velocity and mass distribution of clusters of galaxies from the CNOC1 cluster redshift survey

In the context of the CNOC1 cluster survey, redshifts were obtained for galaxies in 16 clusters. The resulting sample is ideally suited for an analysis of the internal velocity and mass distribution of clusters. Previous analyses of this dataset used the Jeans equation to model the projected velocity dispersion profile. However, the results of such an analysis always yield a strong degeneracy between the mass density profile and the velocity dispersion anisotropy profile. Here we analyze the full (R,v) dataset of galaxy positions and velocities in an attempt to break this degeneracy. We build an `ensemble cluster' from the individual clusters under the assumption that they form a homologous sequence. To interpret the data we study a one-parameter family of spherical models with different constant velocity dispersion anisotropy. The best-fit model is sought using a variety of statistics, including the overall likelihood of the dataset. Although the results of our analysis depend slightly on which statistic is used to judge the models, all statistics agree that the best-fit model is close to isotropic. This result derives primarily from the fact that the observed grand-total velocity histogram is close to Gaussian, which is not expected to be the case for a strongly anisotropic model. The best-fitting models have a mass-to-number-density ratio that is approximately independent of radius over the range constrained by the data. They also have a mass-density profile that is consistent with the dark matter halo profile advocated by Navarro, Frenk & White, in terms of both the profile shape and the characteristic scale length. This adds important new weight to the evidence that clusters do indeed follow this proposed universal mass density profile. [Abridged]Comment: 37 pages, LaTeX, with 11 PostScript figures. Accepted by the Astronomical Journal, to appear in the May 2000 issue. This replacement version contains an additional Appendix and one additional Figure with respect to the version submitted to astro-ph originall

Weak lensing surveys and the intrinsic correlation of galaxy ellipticities

We explore the possibility that an intrinsic correlation between galaxy ellipticities arising during the galaxy formation process may account for part of the shear signal recently reported by several groups engaged in weak lensing surveys. Using high resolution N-body simulations we measure the projected ellipticities of dark matter halos and their correlations as a function of pair separation. With this simplifying, but not necessarily realistic assumption (halo shapes as a proxy for galaxy shapes), we find a positive detection of correlations up to scales of at least 20 h^-1mpc (limited by the box size). The signal is not strongly affected by variations in the halo finding technique, or by the resolution of the simulations. We translate our 3d results into angular measurements of ellipticity correlation functions and shear variance which can be directly compared to observations. We also measure similar results from simulated angular surveys made by projecting our simulation boxes onto the plane of the sky and applying a radial selection function. Interestingly, the shear variance we measure is a small, but not entirely negligible fraction (from ~10-20 %) of that seen by the observational groups, and the ellipticity correlation functions approximately mimic the functional form expected to be caused by weak lensing. The amplitude depends on the width in redshift of the galaxy distribution. If photometric redshifts are used to pick out a screen of background galaxies with a small width, then the intrinsic correlation may become comparable to the weak lensing signal. Although we are dealing with simulated dark matter halos, whether there is a signal from real galaxies could be checked with a nearby sample with known redshifts.Comment: 12 pages, 11 ps figures, emulateapj.sty, submitted to Ap

The Velocity Dispersion of MS1054-03: A Massive Galaxy Cluster at High Redshift

We present results from a dynamical study of the high redshift, massive, X-ray luminous galaxy cluster MS1054--03. We significantly increase the number of confirmed cluster members by adding 20 to an existing set of twelve; using the confirmed members, we estimate MS1054--03's redshift, velocity dispersion, and mass. We find that z=0.8329 +/- 0.0017, sigma = 1170 +/- 150 km/s, and the central mass is approximately 1.9 +/- 0.5 x 10^{15} h^{-1} M_{odot} (within R=1 h^{-1} Mpc; H_0 =100h km s^{-1} Mpc^{-1}, q_0=0.5). MS1054--03 is one of a handful of high redshift (z>0.5) clusters known that also has X-ray and weak-lensing observations (Donahue et al. 1998; Luppino & Kaiser 1997); we find our dynamical mass agrees with mass estimates from both studies. The confirmation of MS1054--03 as a massive cluster at z~0.8 is consistent with an open (Omega_M~0.3) or flat, Lambda-dominated (Omega_M+Omega_{Lambda}=1) universe. In addition, we compare MS1054--03's velocity dispersion and X-ray temperature to a sample of low and intermediate redshift galaxy clusters to test for evolution in the sigma - T_x relation; we find no evidence for evolution in this relation to z~0.8.Comment: 13 pages, 3 figures, LaTex; Accepted for Publication in the Astrophysical Journa

Resveratrol and metabolic health in COPD:A proof-of-concept randomized controlled trial

Background: Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function in patients with COPD. Secondary objectives were to investigate the effect of resveratrol on adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD. Methods: In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) received resveratrol (150 mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained for metabolic and inflammatory profiling. Body composition was assessed by dual energy X-ray absorptiometry. Results: Muscle mitochondrial biogenesis regulators AMPK, SIRT1 and PGC-1 alpha as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine did not change after resveratrol supplementation. Adipose tissue inflammatory markers were unaffected by resveratrol, while markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol -0.95 +/- 1.01 kg vs placebo -0.16 +/- 0.66 kg, p = 0.049) due to a reduction in lean mass (resveratrol -1.79 +/- 1.67 kg vs 0.37 +/- 0.86 kg, p = 0.026). Conclusion: We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved