Hyaluronan: A simple polysaccharide with diverse biological functions

Hyaluronan (HA) is a linear polysaccharide with disaccharide repeats of d-glucuronic acid and N-acetyl-d-glucosamine. It is evolutionarily conserved and abundantly expressed in the extracellular matrix (ECM), on the cell surface and even inside cells. Being a simple polysaccharide, HA exhibits an astonishing array of biological functions. HA interacts with various proteins or proteoglycans to organize the ECM and to maintain tissue homeostasis. The unique physical and mechanical properties of HA contribute to the maintenance of tissue hydration, the mediation of solute diffusion through the extracellular space and the lubrication of certain tissues. The diverse biological functions of HA are manifested through its complex interactions with matrix components and resident cells. Binding of HA with cell surface receptors activates various signaling pathways, which regulate cell function, tissue development, inflammation, wound healing and tumor progression and metastasis. Taking advantage of the inherent biocompatibility and biodegradability of HA, as well as its susceptibility to chemical modification, researchers have developed various HA-based biomaterials and tissue constructs with promising and broad clinical potential. This paper illustrates the properties of HA from a matrix biology perspective by first introducing the principles underlying the biosynthesis and biodegradation of HA, as well as the interactions of HA with various proteins and proteoglycans. It next highlights the roles of HA in physiological and pathological states, including morphogenesis, wound healing and tumor metastasis. A deeper understanding of the mechanisms underlying the roles of HA in various physiological processes can provide new insights and tools for the engineering of complex tissues and tissue models

Antisense inhibition of cyclin D1 expression is equivalent to flavopiridol for radiosensitization of zebrafish embryos

Purpose: Flavopiridol, a small molecule pan-cyclin inhibitor, has been shown to enhance the radiation response of tumor cells both in vitro and in vivo. The clinical utility of flavopiridol, however, is limited by toxicity, previously attributed to pleiotropic inhibitory effects on several targets affecting multiple signal transduction pathways. Here we utilized zebrafish embryos to investigate radiosensitizing effects of flavopiridol in normal tissues. Methods and Materials: Zebrafish embryos at the 1-4 cell stage were treated with 500 nM flavopiridol or injected with 0.5 pmol antisense hydroxylprolyl-phosphono nucleic acid oligomers to reduce cyclin D1 expression, then subjected to ionizing radiation (IR) or no radiation. Results: Flavopiridol-treated embryos demonstrated a 2-fold increase in mortality following exposure to 40 Gy by 96 hours post fertilization (hpf) and developed distinct radiation-induced defects in midline development (curly-up phenotype) at higher rates when compared to embryos receiving IR only. Cyclin D1-deficient embryos had virtually identical IR sensitivity profiles when compared to embryos treated with flavopiridol. This was particularly evident for the IR-induced curly-up phenotype, which was greatly exacerbated by both flavopriridol and cyclin D1 downregulation. Conclusions: Treatment of zebrafish embryos with flavopiridol enhanced radiation sensitivity of zebrafish embryos to a degree that was very similar to that associated with downregulation of cyclin D1 expression. These results are consistent with the hypothesis that inhibition of cyclin D1 is sufficient to account for the radiosensitizing action of flavopiridol in the zebrafish embryo vertebrate model

The Atacama Cosmology Telescope: Temperature and Gravitational Lensing Power Spectrum Measurements from Three Seasons of Data

We present the temperature power spectra of the cosmic microwave background (CMB) derived from the three seasons of data from the Atacama Cosmology Telescope (ACT) at 148 GHz and 218 GHz, as well as the cross-frequency spectrum between the two channels. We detect and correct for contamination due to the Galactic cirrus in our equatorial maps. We present the results of a number of tests for possible systematic error and conclude that any effects are not significant compared to the statistical errors we quote. Where they overlap, we cross-correlate the ACT and the South Pole Telescope (SPT) maps and show they are consistent. The measurements of higher-order peaks in the CMB power spectrum provide an additional test of the Lambda CDM cosmological model, and help constrain extensions beyond the standard model. The small angular scale power spectrum also provides constraining power on the Sunyaev-Zel'dovich effects and extragalactic foregrounds. We also present a measurement of the CMB gravitational lensing convergence power spectrum at 4.6-sigma detection significance.Comment: 21 pages; 20 figures, Submitted to JCAP, some typos correcte

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure

The Atacama Cosmology Telescope: Physical Properties and Purity of a Galaxy Cluster Sample Selected via the Sunyaev-Zel'dovich Effect

We present optical and X-ray properties for the first confirmed galaxy cluster sample selected by the Sunyaev-Zel'dovich Effect from 148 GHz maps over 455 square degrees of sky made with the Atacama Cosmology Telescope. These maps, coupled with multi-band imaging on 4-meter-class optical telescopes, have yielded a sample of 23 galaxy clusters with redshifts between 0.118 and 1.066. Of these 23 clusters, 10 are newly discovered. The selection of this sample is approximately mass limited and essentially independent of redshift. We provide optical positions, images, redshifts and X-ray fluxes and luminosities for the full sample, and X-ray temperatures of an important subset. The mass limit of the full sample is around 8e14 Msun, with a number distribution that peaks around a redshift of 0.4. For the 10 highest significance SZE-selected cluster candidates, all of which are optically confirmed, the mass threshold is 1e15 Msun and the redshift range is 0.167 to 1.066. Archival observations from Chandra, XMM-Newton, and ROSAT provide X-ray luminosities and temperatures that are broadly consistent with this mass threshold. Our optical follow-up procedure also allowed us to assess the purity of the ACT cluster sample. Eighty (one hundred) percent of the 148 GHz candidates with signal-to-noise ratios greater than 5.1 (5.7) are confirmed as massive clusters. The reported sample represents one of the largest SZE-selected sample of massive clusters over all redshifts within a cosmologically-significant survey volume, which will enable cosmological studies as well as future studies on the evolution, morphology, and stellar populations in the most massive clusters in the Universe.Comment: 20 pages, 15 figures, 6 tables. Accepted for publication in ApJ. Higher resolution figures available at: http://peumo.rutgers.edu/~felipe/e-prints

The Atacama Cosmology Telescope: Extragalactic Sources at 148 GHz in the 2008 Survey

We report on extragalactic sources detected in a 455 square-degree map of the southern sky made with data at a frequency of 148 GHz from the Atacama Cosmology Telescope 2008 observing season. We provide a catalog of 157 sources with flux densities spanning two orders of magnitude: from 15 to 1500 mJy. Comparison to other catalogs shows that 98% of the ACT detections correspond to sources detected at lower radio frequencies. Three of the sources appear to be associated with the brightest cluster galaxies of low redshift X-ray selected galaxy clusters. Estimates of the radio to mm-wave spectral indices and differential counts of the sources further bolster the hypothesis that they are nearly all radio sources, and that their emission is not dominated by re-emission from warm dust. In a bright (>50 mJy) 148 GHz-selected sample with complete cross-identifications from the Australia Telescope 20 GHz survey, we observe an average steepening of the spectra between 5, 20, and 148 GHz with median spectral indices of $\alpha_{\rm 5-20} = -0.07 \pm 0.06$, $\alpha_{\rm 20-148} = -0.39 \pm0.04$, and $\alpha_{\rm 5-148} = -0.20 \pm 0.03$. When the measured spectral indices are taken into account, the 148 GHz differential source counts are consistent with previous measurements at 30 GHz in the context of a source count model dominated by radio sources. Extrapolating with an appropriately rescaled model for the radio source counts, the Poisson contribution to the spatial power spectrum from synchrotron-dominated sources with flux density less than 20 mJy is C^{\rm Sync} = (2.8 \pm 0.3) \times 10^{-6} \micro\kelvin^2.Comment: Accepted to Ap

The Atacama Cosmology Telescope: A Measurement of the Cosmic Microwave Background Power Spectrum at 148 and 218 GHz from the 2008 Southern Survey

We present measurements of the cosmic microwave background (CMB) power spectrum made by the Atacama Cosmology Telescope at 148 GHz and 218 GHz, as well as the cross-frequency spectrum between the two channels. Our results clearly show the second through the seventh acoustic peaks in the CMB power spectrum. The measurements of these higher-order peaks provide an additional test of the {\Lambda}CDM cosmological model. At l > 3000, we detect power in excess of the primary anisotropy spectrum of the CMB. At lower multipoles 500 < l < 3000, we find evidence for gravitational lensing of the CMB in the power spectrum at the 2.8{\sigma} level. We also detect a low level of Galactic dust in our maps, which demonstrates that we can recover known faint, diffuse signals.Comment: 19 pages, 13 figures. Submitted to ApJ. This paper is a companion to Hajian et al. (2010) and Dunkley et al. (2010

The Atacama Cosmology Telescope: Data Characterization and Map Making

We present a description of the data reduction and mapmaking pipeline used for the 2008 observing season of the Atacama Cosmology Telescope (ACT). The data presented here at 148 GHz represent 12% of the 90 TB collected by ACT from 2007 to 2010. In 2008 we observed for 136 days, producing a total of 1423 hours of data (11 TB for the 148 GHz band only), with a daily average of 10.5 hours of observation. From these, 1085 hours were devoted to a 850 deg^2 stripe (11.2 hours by 9.1 deg) centered on a declination of -52.7 deg, while 175 hours were devoted to a 280 deg^2 stripe (4.5 hours by 4.8 deg) centered at the celestial equator. We discuss sources of statistical and systematic noise, calibration, telescope pointing, and data selection. Out of 1260 survey hours and 1024 detectors per array, 816 hours and 593 effective detectors remain after data selection for this frequency band, yielding a 38% survey efficiency. The total sensitivity in 2008, determined from the noise level between 5 Hz and 20 Hz in the time-ordered data stream (TOD), is 32 micro-Kelvin sqrt{s} in CMB units. Atmospheric brightness fluctuations constitute the main contaminant in the data and dominate the detector noise covariance at low frequencies in the TOD. The maps were made by solving the least-squares problem using the Preconditioned Conjugate Gradient method, incorporating the details of the detector and noise correlations. Cross-correlation with WMAP sky maps, as well as analysis from simulations, reveal that our maps are unbiased at multipoles ell > 300. This paper accompanies the public release of the 148 GHz southern stripe maps from 2008. The techniques described here will be applied to future maps and data releases.Comment: 20 pages, 18 figures, 6 tables, an ACT Collaboration pape

The Atacama Cosmology Telescope: Sunyaev Zel'dovich Selected Galaxy Clusters at 148 GHz in the 2008 Survey

We report on twenty-three clusters detected blindly as Sunyaev-Zel'dovich (SZ) decrements in a 148 GHz, 455 square-degree map of the southern sky made with data from the Atacama Cosmology Telescope 2008 observing season. All SZ detections announced in this work have confirmed optical counterparts. Ten of the clusters are new discoveries. One newly discovered cluster, ACT-CL J0102-4915, with a redshift of 0.75 (photometric), has an SZ decrement comparable to the most massive systems at lower redshifts. Simulations of the cluster recovery method reproduce the sample purity measured by optical follow-up. In particular, for clusters detected with a signal-to-noise ratio greater than six, simulations are consistent with optical follow-up that demonstrated this subsample is 100% pure. The simulations further imply that the total sample is 80% complete for clusters with mass in excess of 6x10^14 solar masses referenced to the cluster volume characterized by five hundred times the critical density. The Compton y -- X-ray luminosity mass comparison for the eleven best detected clusters visually agrees with both self-similar and non-adiabatic, simulation-derived scaling laws.Comment: 13 pages, 7 figures, Accepted for publication in Ap