Dark-ages Reionization and Galaxy Formation Simulation -- XIX: Predictions of infrared excess and cosmic star formation rate density from UV observations

We present a new analysis of high-redshift UV observations using a semi-analytic galaxy formation model, and provide self-consistent predictions of the infrared excess (IRX) -- $\beta$ relations and cosmic star formation rate density. We combine the Charlot & Fall dust attenuation model with the Meraxes semi-analytic model, and explore three different parametrisations for the dust optical depths, linked to star formation rate, dust-to-gas ratio and gas column density respectively. A Bayesian approach is employed to statistically calibrate model free parameters including star formation efficiency, mass loading factor, dust optical depths and reddening slope directly against UV luminosity functions and colour-magnitude relations at z ~ 4-7. The best-fit models show excellent agreement with the observations. We calculate IRX using energy balance arguments, and find that the large intrinsic scatter in the IRX -$\beta$ plane is driven by the specific star formation rate. Additionally, the difference among the three dust models suggests a factor of two systematic uncertainty in the dust-corrected star formation rate when using the Meurer IRX - $\beta$ relation at z > 4.Comment: 15 pages, 10 figure. Accepted for publication in MNRA

The Human Cytomegalovirus Latency-Associated Gene Product Latency Unique Natural Antigen Regulates Latent Gene Expression

Human cytomegalovirus (HCMV) infection can lead to either lytic or latent infection, which is dependent on the regulation of the viral major immediate early promoter (MIEP). Suppression of the MIEP is a pre-requisite for latency and is driven by repressive epigenetic modifications at the MIEP during latent infection. However, other viral genes are expressed during latency and this is correlated with activatory epigenetic modifications at latent gene promoters. Yet the molecular basis of the differential regulation of latent and lytic gene expression by epigenetics is unclear. LUNA, a latent viral transcript, has been suggested to be important for HCMV latency and has also been shown to be important for efficient reactivation likely through its known deSUMOylase activity. Intriguingly, we and others have also observed that LUNA enhances latency-associated expression of the viral UL138 gene. Here, we show that in the absence of LUNA, the expression of multiple latency-associated transcripts is reduced during latent infection, which is correlated with a lack of activatory marks at their promoters. Interestingly, we also show that LUNA interacts with the hematopoietic transcription factor GATA-2, which has previously been shown to bind to a number of latency-associated gene promoters, and that this interaction is dependent on the deSUMOylase domain of LUNA. Finally, we show that the deSUMOylase activity of LUNA is required for the establishment and/or maintenance of an open chromatin configuration around latency-associated gene promoters. As such, LUNA plays a key role in efficient latency-associated viral gene expression and carriage of viral genome during latent carriage

A BMPR2/YY1 Signaling Axis Is Required for Human Cytomegalovirus Latency in Undifferentiated Myeloid Cells.

Human cytomegalovirus (HCMV) presents a major health burden in the immunocompromised and in stem cell transplant medicine. A lack of understanding about the mechanisms of HCMV latency in undifferentiated CD34+ stem cells, and how latency is broken for the virus to enter the lytic phase of its infective cycle, has hampered the development of essential therapeutics. Using a human induced pluripotent stem cell (iPSC) model of HCMV latency and patient-derived myeloid cell progenitors, we demonstrate that bone morphogenetic protein receptor type 2 (BMPR2) is necessary for HCMV latency. In addition, we define a crucial role for the transcription factor Yin Yang 1 (YY1) in HCMV latency; high levels of YY1 are maintained in latently infected cells as a result of BMPR2 signaling through the SMAD4/SMAD6 axis. Activation of SMAD4/6, through BMPR2, inhibits TGFbeta receptor signaling, which leads to the degradation of YY1 via induction of a cellular microRNA (miRNA), hsa-miR-29a. Pharmacological targeting of BMPR2 in progenitor cells results in the degradation of YY1 and an inability to maintain latency and renders cells susceptible to T cell killing. These data argue that BMPR2 plays a role in HCMV latency and is a new potential therapeutic target for maintaining or disrupting HCMV latency in myeloid progenitors. IMPORTANCE Understanding the mechanisms which regulate HCMV latency could allow therapeutic targeting of the latent virus reservoir from where virus reactivation can cause severe disease. We show that the BMPR2/TGFbeta receptor/YY1 signaling axis is crucial to maintain HCMV latency in undifferentiated cells and that pharmacological reduction of BMPR2 in latently infected cells leads to reactivation of the viral lytic transcription program, which renders the infected cell open to immune detection and clearance in infected individuals. Therefore, this work identifies key host-virus interactions which regulate HCMV latent infection. It also demonstrates a potential new therapeutic approach to reduce HCMV reactivation-mediated disease by the treatment of donor stem cells/organs prior to transplantation, which could have a major impact in the transplant disease setting

The Balmer decrement of SDSS galaxies

High resolution spectra are necessary to distinguish and correctly measure the Balmer emission lines due to the presence of strong metal and Balmer absorption features in the stellar continuum. This accurate measurement is necessary for use in emission line diagnostics, such as the Balmer decrement (i.e. Halpha/Hbeta), used to determine the attenuation of galaxies. Yet at high redshifts obtaining such spectra becomes costly. Balmer emission line equivalent widths are much easier to measure, requiring only low resolution spectra or even simple narrow band filters and therefore shorter observation times. However a correction for the stellar continuum is still needed for this equivalent width Balmer decrement. We present here a statistical analysis of the Sloan Digital Sky Survey Data Release 7 emission line galaxy sample, using the spectrally determined Balmer emission line fluxes and equivalent widths. Using the large numbers of galaxies available in the SDSS catalogue, we determined an equivalent width Balmer decrement including a statistically-based correction for the stellar continuum. Based on this formula, the attenuation of galaxies can now be obtained from low spectral resolution observations. In addition, this investigation also revealed an error in the Hbeta line fluxes, within the SDSS DR7 MPA/JHU catalogue, with the equivalent widths underestimated by average ~0.35A in the emission line galaxy sample. This error means that Balmer decrement determined attenuations are overestimated by a systematic 0.1 magnitudes in A_V, and future analyses of this sample need to include this correction.Comment: 10 pages, accepted MNRA

Sunyaev-Zel'dovich clusters in millennium gas simulations

Large surveys using the Sunyaev–Zel’dovich (SZ) effect to find clusters of galaxies are now starting to yield large numbers of systems out to high redshift, many of which are new dis- coveries. In order to provide theoretical interpretation for the release of the full SZ cluster samples over the next few years, we have exploited the large-volume Millennium gas cosmo- logical N-body hydrodynamics simulations to study the SZ cluster population at low and high redshift, for three models with varying gas physics. We confirm previous results using smaller samplesthattheintrinsic(spherical)Y500–M500relationhasverylittlescatter(σlog10Y ≃0.04), is insensitive to cluster gas physics and evolves to redshift 1 in accordance with self-similar expectations. Our preheating and feedback models predict scaling relations that are in excel- lent agreement with the recent analysis from combined Planck and XMM–Newton data by the Planck Collaboration. This agreement is largely preserved when r500 and M500 are derived using thehydrostaticmassproxy,YX,500,albeitwithsignificantlyreducedscatter(σlog10Y ≃0.02),a result that is due to the tight correlation between Y500 and YX,500. Interestingly, this assumption also hides any bias in the relation due to dynamical activity. We also assess the importance of projection effects from large-scale structure along the line of sight, by extracting cluster Y500 values from 50 simulated 5 × 5-deg2 sky maps. Once the (model-dependent) mean signal is subtracted from the maps we find that the integrated SZ signal is unbiased with respect to the underlying clusters, although the scatter in the (cylindrical) Y500–M500 relation increases in the preheating case, where a significant amount of energy was injected into the intergalactic medium at high redshift. Finally, we study the hot gas pressure profiles to investigate the origin of the SZ signal and find that the largest contribution comes from radii close to r500 in all cases. The profiles themselves are well described by generalized Navarro, Frenk & White profiles but there is significant cluster-to-cluster scatter. In conclusion, our results support the notion that Y500 is a robust mass proxy for use in cosmological analyses with clusters

Implementing telephone triage in general practice: a process evaluation of a cluster randomised controlled trial

Background: Telephone triage represents one strategy to manage demand for face-to-face GP appointments in primary care. However, limited evidence exists of the challenges GP practices face in implementing telephone triage. We conducted a qualitative process evaluation alongside a UK-based cluster randomised trial (ESTEEM) which compared the impact of GP-led and nurse-led telephone triage with usual care on primary care workload, cost, patient experience, and safety for patients requesting a same-day GP consultation. The aim of the process study was to provide insights into the observed effects of the ESTEEM trial from the perspectives of staff and patients, and to specify the circumstances under which triage is likely to be successfully implemented. Here we report perspectives of staff. Methods: The intervention comprised implementation of either GP-led or nurse-led telephone triage for a period of 2-3 months. A qualitative evaluation was conducted using staff interviews recruited from eight general practices (4 GP triage, 4 Nurse triage) in the UK, implementing triage as part of the ESTEEM trial. Qualitative interviews were undertaken with 44 staff members in GP triage and nurse triage practices (16 GPs, 8 nurses, 7 practice managers, 13 administrative staff). Results: Staff reported diverse experiences and perceptions regarding the implementation of telephone triage, its effects on workload, and on the benefits of triage. Such diversity were explained by the different ways triage was organised, the staffing models used to support triage, how the introduction of triage was communicated across practice staff, and by how staff roles were reconfigured as a result of implementing triage. Conclusion: The findings from the process evaluation offer insight into the range of ways GP practices participating in ESTEEM implemented telephone triage, and the circumstances under which telephone triage can be successfully implemented beyond the context of a clinical trial. Staff experiences and perceptions of telephone triage are shaped by the way practices communicate with staff, prepare for and sustain the changes required to implement triage effectively, as well as by existing practice culture, and staff and patient behaviour arising in response to the changes made. Trial registration: Current Controlled Trials ISRCTN20687662. Registered 28 May 2009

The MUSIC of Galaxy Clusters I: Baryon properties and Scaling Relations of the thermal Sunyaev-Zel'dovich Effect

We introduce the Marenostrum-MultiDark SImulations of galaxy Clusters (MUSIC) Dataset, one of the largest sample of hydrodynamically simulated galaxy clusters with more than 500 clusters and 2000 groups. The objects have been selected from two large N-body simulations and have been resimulated at high resolution using SPH together with relevant physical processes (cooling, UV photoionization, star formation and different feedback processes). We focus on the analysis of the baryon content (gas and star) of clusters in the MUSIC dataset both as a function of aperture radius and redshift. The results from our simulations are compared with the most recent observational estimates of the gas fraction in galaxy clusters at different overdensity radii. When the effects of cooling and stellar feedbacks are included, the MUSIC clusters show a good agreement with the most recent observed gas fractions quoted in the literature. A clear dependence of the gas fractions with the total cluster mass is also evident. The impact of the aperture radius choice, when comparing integrated quantities at different redshifts, is tested: the standard definition of radius at a fixed overdensity with respect to critical density is compared with a definition based on the redshift dependent overdensity with respect to background density. We also present a detailed analysis of the scaling relations of the thermal SZ (Sunyaev Zel'dovich) Effect derived from MUSIC clusters. The integrated SZ brightness, Y, is related to the cluster total mass, M, as well as, the M-Y counterpart, more suitable for observational applications. Both laws are consistent with predictions from the self-similar model, showing a very low scatter. The effects of the gas fraction on the Y-M scaling and the presence of a possible redshift dependence on the Y-M scaling relation are also explored.Comment: 22 pages, 25 figures, accepted for pubblication by MNRA

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

Lessons from using iPads to understand young children's creativity

This paper explores how iPads can be used as part of a child-centred data collection approach to understanding young children’s creativity. Evidence is presented from a pilot study about 3- to 5-year-old children’s creative play. Researchers’ reflective accounts of children’s engagement with iPad video diaries and free to use apps were logged across two early educational settings over a three-month period. Findings suggest that iPads offer a mechanism to allow children to express their creative play and to encourage involvement in the research process. However, bespoke research software to use with early years children is required to improve this process

The WiggleZ Dark Energy Survey: the growth rate of cosmic structure since redshift z=0.9

We present precise measurements of the growth rate of cosmic structure for the redshift range 0.1 < z < 0.9, using redshift-space distortions in the galaxy power spectrum of the WiggleZ Dark Energy Survey. Our results, which have a precision of around 10% in four independent redshift bins, are well-fit by a flat LCDM cosmological model with matter density parameter Omega_m = 0.27. Our analysis hence indicates that this model provides a self-consistent description of the growth of cosmic structure through large-scale perturbations and the homogeneous cosmic expansion mapped by supernovae and baryon acoustic oscillations. We achieve robust results by systematically comparing our data with several different models of the quasi-linear growth of structure including empirical models, fitting formulae calibrated to N-body simulations, and perturbation theory techniques. We extract the first measurements of the power spectrum of the velocity divergence field, P_vv(k), as a function of redshift (under the assumption that P_gv(k) = -sqrt[P_gg(k) P_vv(k)] where g is the galaxy overdensity field), and demonstrate that the WiggleZ galaxy-mass cross-correlation is consistent with a deterministic (rather than stochastic) scale-independent bias model for WiggleZ galaxies for scales k < 0.3 h/Mpc. Measurements of the cosmic growth rate from the WiggleZ Survey and other current and future observations offer a powerful test of the physical nature of dark energy that is complementary to distance-redshift measures such as supernovae and baryon acoustic oscillations.Comment: 17 pages, 11 figures, accepted for publication by MNRA