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

Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases.

High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52-kb intronic deletion 3'). Family members were assessed for HBM segregation with identified variants. Three-dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM (∼prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non-LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5-HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST-LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z-scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z-scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion (∼3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance.This study was supported by The Wellcome Trust and NIHR CRN (portfolio number 5163). CLG was funded by a Wellcome Trust Clinical Research Training Fellowship (080280/Z/06/Z), the EU 7th Framework Programme under grant agreement number 247642 (GEoCoDE), a British Geriatric Society travel grant, and is now funded by Arthritis Research UK (grant ref 20000). SH acknowledges Arthritis Research UK support (grant ref 19580). KESP acknowledges the support of Cambridge NIHR Biomedical Research Centre. KAW is supported by the core programme of the MRC Nutrition and Bone Health group at MRC Human Nutrition Research, funded by the UK Medical Research Council (Grant code U10590371). EM acknowledges support of the Sheffield Teaching Hospitals Foundation Trust Clinical Research Facility. The SGC is a registered charity (no. 1097737) that receives funds from AbbVie, Bayer, Boehringer Ingelheim, Genome Canada (Ontario Genomics Institute OGI- 055), GlaxoSmithKline, Janssen, Lilly Canada, Novartis Research Foundation, Ontario Ministry of Economic Development & Innovation, Pfizer, Takeda, and Wellcome Trust (092809/Z/10/Z).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.270

The Atacama Cosmology Telescope: Cosmological parameters from three seasons of data

We present constraints on cosmological and astrophysical parameters from high-resolution microwave background maps at 148 GHz and 218 GHz made by the Atacama Cosmology Telescope (ACT) in three seasons of observations from 2008 to 2010. A model of primary cosmological and secondary foreground parameters is fit to the map power spectra and lensing deflection power spectrum, including contributions from both the thermal Sunyaev-Zeldovich (tSZ) effect and the kinematic Sunyaev-Zeldovich (kSZ) effect, Poisson and correlated anisotropy from unresolved infrared sources, radio sources, and the correlation between the tSZ effect and infrared sources. The power ell^2 C_ell/2pi of the thermal SZ power spectrum at 148 GHz is measured to be 3.4 +\- 1.4 muK^2 at ell=3000, while the corresponding amplitude of the kinematic SZ power spectrum has a 95% confidence level upper limit of 8.6 muK^2. Combining ACT power spectra with the WMAP 7-year temperature and polarization power spectra, we find excellent consistency with the LCDM model. We constrain the number of effective relativistic degrees of freedom in the early universe to be Neff=2.79 +\- 0.56, in agreement with the canonical value of Neff=3.046 for three massless neutrinos. We constrain the sum of the neutrino masses to be Sigma m_nu < 0.39 eV at 95% confidence when combining ACT and WMAP 7-year data with BAO and Hubble constant measurements. We constrain the amount of primordial helium to be Yp = 0.225 +\- 0.034, and measure no variation in the fine structure constant alpha since recombination, with alpha/alpha0 = 1.004 +/- 0.005. We also find no evidence for any running of the scalar spectral index, dns/dlnk = -0.004 +\- 0.012.Comment: 26 pages, 22 figures. This paper is a companion to Das et al. (2013) and Dunkley et al. (2013). Matches published JCAP versio

What Do Unions Do for Economic Performance?

Twenty years have passed since Freeman and Medoff's What Do Unions Do? This essay assesses their analysis of how unions in the U.S. private sector affect economic performance - productivity, profitability, investment, and growth. Freeman and Medoff are clearly correct that union productivity effects vary substantially across workplaces. Their conclusion that union effects are on average positive and substantial cannot be sustained, subsequent evidence suggesting an average union productivity effect near zero. Their speculation that productivity effects are larger in more competitive environments appears to hold up, although more evidence is needed. Subsequent literature continues to find unions associated with lower profitability, as noted by Freeman and Medoff. Unions are found to tax returns stemming from market power, but industry concentration is not the source of such returns. Rather, unions capture firm quasi-rents arising from long-lived tangible and intangible capital and from firm-specific advantages. Lower profits and the union tax on asset returns leads to reduced investment and, subsequently, lower employment and productivity growth. There is little evidence that unionization leads to higher rates of business failure. Given the decline in U.S. private sector unionism, I explore avenues through which individual and collective voice might be enhanced, focusing on labor law and workplace governance defaults. Substantial enhancement of voice requires change in the nonunion sector and employer as well as worker initiatives. It is unclear whether labor unions would be revitalized or further marginalized by such an evolution

Myosin-Vb functions as a dynamic tether for peripheral endocytic compartments during transferrin trafficking

<p>Abstract</p> <p>Background</p> <p>Myosin-Vb has been shown to be involved in the recycling of diverse proteins in multiple cell types. Studies on transferrin trafficking in HeLa cells using a dominant-negative myosin-Vb tail fragment suggested that myosin-Vb was required for recycling from perinuclear compartments to the plasma membrane. However, chemical-genetic, dominant-negative experiments, in which myosin-Vb was specifically induced to bind to actin, suggested that the initial hypothesis was incorrect both in its site and mode of myosin-Vb action. Instead, the chemical-genetic data suggested that myosin-Vb functions in the actin-rich periphery as a dynamic tether on peripheral endosomes, retarding transferrin transport to perinuclear compartments.</p> <p>Results</p> <p>In this study, we employed both approaches, with the addition of overexpression of full-length wild-type myosin-Vb and switching the order of myosin-Vb inhibition and transferrin loading, to distinguish between these hypotheses. Overexpression of full-length myosin-Vb produced large peripheral endosomes. Chemical-genetic inhibition of myosin-Vb after loading with transferrin did not prevent movement of transferrin from perinuclear compartments; however, virtually all myosin-Vb-decorated particles, including those moving on microtubules, were halted by the inhibition. Overexpression of the myosin-Vb tail caused a less-peripheral distribution of early endosome antigen-1 (EEA1).</p> <p>Conclusion</p> <p>All results favored the peripheral dynamic tethering hypothesis.</p

Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics

Vascular endothelial growth factor-A (VEGF) is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120) on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188) or wild type controls (fswt) were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively) were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine kinase receptor activation. VEGF isoforms are emerging as potential biomarkers for anti-VEGF therapies. Our results reveal novel roles of individual isoforms associated with cancer growth and metastasis and highlight the importance of understanding their diverse actions

Experiments on contaminant transport from sewer infrastructure within shallow floodwater

Understanding the transport of soluble contamination in urban floodwater is an important aspect of public health risk assessment. However due to significant measurement complexity, there is a current lack of datasets to elucidate the associated relevant flow pathways, local velocity fields and turbulent diffusion processes. This paper evaluates three alternate experimental methodologies to quantify 2D contaminant transport at scales typical of shallow urban floodwater. It further provides a new open access dataset describing transport processes from an experimental scale model of floodwater under sewer surcharge conditions, featuring different geometrical and hydraulic configurations. Results show broad agreement between the different experimental techniques, with small but notable differences associated with measurement and experimental limitations. Results and datasets also demonstrate the considerable influence of hydraulic and geometrical complexity on transport processes, and sensitivity of the concentration levels in model street networks to heterogeneous flow pathways and velocity gradients

The Antimicrobial Scrub Contamination and Transmission (ASCOT) Trial: A Three-Arm, Blinded, Randomized Controlled Trial With Crossover Design to Determine the Efficacy of Antimicrobial-Impregnated Scrubs in Preventing Healthcare Provider Contamination

OBJECTIVE To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing. DESIGN We completed a 3-arm randomized controlled trial to test the efficacy of 2 types of antimicrobial-impregnated clothing compared to standard HCP clothing. Cultures were obtained from each nurse participant, the healthcare environment, and patients during each shift. The primary outcome was the change in total contamination on nurse scrubs, measured as the sum of colony-forming units (CFU) of bacteria. PARTICIPANTS AND SETTING Nurses working in medical and surgical ICUs in a 936-bed tertiary-care hospital. INTERVENTION Nurse subjects wore standard cotton-polyester surgical scrubs (control), scrubs that contained a complex element compound with a silver-alloy embedded in its fibers (Scrub 1), or scrubs impregnated with an organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion (Scrub 2). Nurse participants were blinded to scrub type and randomly participated in all 3 arms during 3 consecutive 12-hour shifts in the intensive care unit. RESULTS In total, 40 nurses were enrolled and completed 3 shifts. Analyses of 2,919 cultures from the environment and 2,185 from HCP clothing showed that scrub type was not associated with a change in HCP clothing contamination ( P =.70). Mean difference estimates were 0.118 for the Scrub 1 arm (95% confidence interval [CI], −0.206 to 0.441; P =.48) and 0.009 for the Scrub 2 rm (95% CI, −0.323 to 0.342; P =.96) compared to the control. HCP became newly contaminated with important pathogens during 19 of the 120 shifts (16%). CONCLUSIONS Antimicrobial-impregnated scrubs were not effective at reducing HCP contamination. However, the environment is an important source of HCP clothing contamination. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT 02645214 Infect Control Hosp Epidemiol 2017;38:1147–115

The Spending and Debt Response to Minimum Wage Hikes

Following a minimum wage hike, spending increases more than income, and thus debt rises, in households with minimum wage workers. The size, as well as the timing, persistence, composition, and distribution of the spending response is inconsistent with the basic certainty equivalent life cycle model. However, the response is consistent with a model where households can borrow against part of the value of their durable goods

Private Sector Union Density and the Wage Premium: Past, Present, and Future

The rise and decline of private sector unionization were among the more important features of the U.S. labor market during the twentieth century. Following a dramatic spurt in unionization after passage of the depression-era National Labor Relations Act (NLRA) of 1935, union density peaked in the mid-1950s, and then began a continuous decline. At the end of the century, the percentage of private wage and salary workers who were union members was less than 10 percent, not greatly different from union density prior to the NLRA