On merger bias and the clustering of quasars

We use the large catalogues of haloes available for the Millennium Simulation to test whether recently merged haloes exhibit stronger large-scale clustering than other haloes of the same mass. This effect could help to understand the very strong clustering of quasars at high redshift. However, we find no statistically significant excess bias for recently merged haloes over the redshift range 2 < z < 5, with the most massive haloes showing an excess of at most ~5%. We also consider galaxies extracted from a semianalytic model built on the Millennium Simulation. At fixed stellar mass, we find an excess bias of ~ 20-30% for recently merged objects, decreasing with increasing stellar mass. The fact that recently-merged galaxies are found in systematically more massive haloes than other galaxies of the same stellar mass accounts for about half of this signal, and perhaps more for high-mass galaxies. The weak merger bias of massive systems suggests that objects of merger-driven nature, such as quasars, do not cluster significantly differently than other objects of the same characteristic mass. We discuss the implications of these results for the interpretation of clustering data with respect to quasar duty cycles, visibility times, and evolution in the black hole-host mass relation.Comment: 10 pages, 9 figures. Submitted to MNRAS. Comments welcom

Modeling the cosmological co-evolution of supermassive black holes and galaxies: II. The clustering of quasars and their dark environment

We use semi-analytic modeling on top of the Millennium simulation to study the joint formation of galaxies and their embedded supermassive black holes. Our goal is to test scenarios in which black hole accretion and quasar activity are triggered by galaxy mergers, and to constrain different models for the lightcurves associated with individual quasar events. In the present work we focus on studying the spatial distribution of simulated quasars. At all luminosities, we find that the simulated quasar two-point correlation function is fit well by a single power-law in the range 0.5 < r < 20 h^{-1} Mpc, but its normalization is a strong function of redshift. When we select only quasars with luminosities within the range typically accessible by today's quasar surveys, their clustering strength depends only weakly on luminosity, in agreement with observations. This holds independently of the assumed lightcurve model, since bright quasars are black holes accreting close to the Eddington limit, and are hosted by dark matter haloes with a narrow mass range of a few 10^12 h^{-1} M_sun. Therefore the clustering of bright quasars cannot be used to disentangle lightcurve models, but such a discrimination would become possible if the observational samples can be pushed to significantly fainter limits. Overall, our clustering results for the simulated quasar population agree rather well with observations, lending support to the conjecture that galaxy mergers could be the main physical process responsible for triggering black hole accretion and quasar activity.Comment: 17 pages, 16 figures, to be published on MNRA

The Demography of Super-Massive Black Holes: Growing Monsters at the Heart of Galaxies

Supermassive black holes (BHs) appear to be ubiquitous at the center of all galaxies which have been observed at high enough sensitivities and resolution with the Hubble Space Telescope. Their masses are found to be tightly linked with the masses and velocity dispersions of their host galaxies. On the other hand, BHs are widely held to constitute the central engines of quasars and active galactic nuclei (AGN) in general. It is however still unclear how BHs have grown, and whether they have co-evolved with their hosts. In this Review I discuss how, in ways independent of specific models, constraints on the growth history of BHs and their host galaxies have been set by matching the statistics of local BHs to the emissivity, number density, and clustering properties of AGNs at different cosmological epochs. I also present some new results obtained through a novel numerical code which evolves the BH mass function and clustering adopting broad distributions of Eddington ratios. I finally review BH evolution in a wider cosmological context, connecting BH growth to galaxy evolution.Comment: 70 pages. New Astronomy Reviews, in pres

Defining populations of dorsal horn interneurons

No abstract available

The search for the ideal biocatalyst

While the use of enzymes as biocatalysts to assist in the industrial manufacture of fine chemicals and pharmaceuticals has enormous potential, application is frequently limited by evolution-led catalyst traits. The advent of designer biocatalysts, produced by informed selection and mutation through recombinant DNA technology, enables production of process-compatible enzymes. However, to fully realize the potential of designer enzymes in industrial applications, it will be necessary to tailor catalyst properties so that they are optimal not only for a given reaction but also in the context of the industrial process in which the enzyme is applied

Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial

BACKGROUND: No treatments have been approved for primary progressive multiple sclerosis. Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is effective in relapse-onset multiple sclerosis, but has not been assessed in primary progressive multiple sclerosis. We assessed the safety and efficacy of fingolimod in patients with primary progressive multiple sclerosis. METHODS: In INFORMS, a multicentre, double-blind, placebo-controlled parallel-group study, patients with primary progressive multiple sclerosis recruited across 148 centres in 18 countries were randomly allocated (1:1) with computer-generated blocks to receive oral fingolimod or placebo for at least 36 months and a maximum of 5 years. Patients were initially assigned to fingolimod 1·25 mg per day or placebo (cohort 1); however, after a protocol amendment on Nov 19, 2009, patients were switched in a masked manner to fingolimod 0·5 mg, whereas those on placebo continued on matching placebo. From then onwards, patients were assigned to receive fingolimod 0·5 mg/day or placebo (cohort 2). Key inclusion criteria were age 25-65 years, clinical diagnosis of primary progressive multiple sclerosis, 1 year or more of disease progression, and two of the following criteria: positive brain MRI; positive spinal cord MRI; or positive cerebrospinal fluid. Additional eligibility criteria included disease duration of 2-10 years and objective evidence of disability progression in the previous 2 years. Patients and study investigators were masked to group assignment. We used a novel primary composite endpoint based on change from baseline in Expanded Disability Status Scale (EDSS), 25' Timed-Walk Test, or Nine-Hole Peg Test to assess time to 3-month confirmed disability progression in study participants treated for at least 3 years. All randomised patients took at least one dose of study drug. The primary efficacy analysis included all patients in cohort 2 and those assigned to placebo in cohort 1. The safety analysis included all patients in cohorts 1 and 2. This study is registered with ClinicalTrials.gov, number NCT00731692. The study is now closed. FINDINGS: 970 patients were randomly assigned between Sept 3, 2008, and Aug 30, 2011 (147 to fingolimod 1·25 mg and 133 to placebo in cohort 1; 336 to fingolimod 0·5 mg and 354 to placebo in cohort 2). The efficacy analysis set (n=823) consisted of 336 patients randomly allocated to fingolimod 0·5 mg and 487 to placebo. Baseline characteristics were similar across groups and representative of a primary progressive multiple sclerosis population (48% women, mean age 48·5 years [SD 8·4], mean EDSS 4·67 [SD 1·03], 87% free of gadolinium-enhancing lesions). By end of study, 3-month confirmed disability progression had occurred in 232 and 338 patients in the fingolimod and placebo groups, respectively, resulting in Kaplan-Meier estimates of 77·2% (95% CI 71·87-82·51) of patients in the fingolimod group versus 80·3% (73·31-87·25) of patients in the placebo group (risk reduction 5·05%; hazard ratio 0·95, 95% CI 0·80-1·12; p=0·544). Safety results were generally consistent with those of studies of fingolimod in patients with relapse-onset multiple sclerosis. Lymphopenia occurred in 19 (6%) patients in the fingolimod group versus none in the placebo group, bradycardia in five (1%) versus one (<1%), and first-degree atrioventricular block in three (1%) versus six (1%). Serious adverse events occurred in 84 (25%) patients in the fingolimod group and 117 (24%) in the placebo group, including macular oedema in six (2%) versus six (1%), and basal-cell carcinoma in 14 (4%) versus nine (2%). INTERPRETATION: The anti-inflammatory effects of fingolimod did not slow disease progression in primary progressive multiple sclerosis. Therapeutic strategies for primary progressive multiple sclerosis might need different approaches to those used for relapse-onset multiple sclerosis. FUNDING: Novartis Pharma AG

Reversible Disruption of Pre-Pulse Inhibition in Hypomorphic-Inducible and Reversible CB1-/- Mice

Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes). Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout (-/-) mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1-/-) only in absence of doxycycline (Dox). In such mice, under Dox+ or vehicle, as well as in wild-type (WT) and CB1-/-, two endophenotypes motor activity (increased in animal models of schizophrenia) and pre-pulse inhibition (PPI) of startle reflex (disrupted in schizophrenia) were analyzed. Both CB1-/- and IRh-CB1-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1-/- animals, was on the contrary highly and significantly disrupted only in Dox+ IRh-CB1-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in schizophrenia and in other psychiatric disorders

Herschel-ATLAS/GAMA: What determines the far-infrared properties of radio galaxies?

We perform a stacking analysis of Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS) data in order to obtain isothermal dust temperatures and rest-frame luminosities at 250 μm (L_250), for a well-defined sample of 1599 radio sources over the H-ATLAS Phase 1/Galaxy and Mass Assembly (GAMA) area. The radio sample is generated using a combination of NRAO VLA Sky Survey data and K-band United Kingdom Infrared Telescope Deep Sky Survey–Large Area Survey data, over the redshift range 0.01 < z < 0.8. The far-infrared (FIR) properties of the sample are investigated as a function of 1.4-GHz luminosity, redshift, projected radio-source size and radio spectral index. In order to search for stellar-mass-dependent relations, we split the parent sample into those sources which are below and above 1.5 L∗_(K). After correcting for stellar mass and redshift, we find no relation between the 250-μm luminosity and the 1.4-GHz radio luminosity of radio active galactic nuclei. This implies that a galaxy's nominal radio luminosity has little or no bearing on the star formation rate (SFR) and/or dust mass content of the host system, although this does not mean that other variables (e.g. radio source size) related to the jets do not have an effect. The L_250 of both the radio detected and non-radio-detected galaxies (defined as those sources not detected at 1.4 GHz but detected in the Sloan Digital Sky Survey with r′ 30 kpc) counterparts. The higher dust temperature suggests that this may be attributed to enhanced SFRs in compact radio galaxies, but whether this is directly or indirectly due to radio activity (e.g. jet-induced or merger-driven star formation) is as yet unknown. For matched samples in L_K and g′–r′, sub-1.5 L∗_K and super-1.5 L∗_K radio-detected galaxies have 0.89±0.18 and 0.49±0.12 times the 250 μm luminosity of their non-radio-detected counterparts. Thus, while no difference in L_250 is observed in sub-1.5 L∗_K radio-detected galaxies, a strong deficit is observed in super-1.5 L∗_K radio-detected galaxies. We explain these results in terms of the hotter, denser and richer halo environments massive radio galaxies maintain and are embedded in. These environments are expected to quench the cold gas and dust supply needed for further star formation and therefore dust production. Our results indicate that all massive radio galaxies (>1.5 L∗_K) may have systematically lower FIR luminosities (∼25 per cent) than their colour-matched non-radio-detected counterparts. Finally, no relation between radio spectral index and L_250 is found for the subset of 1.4-GHz radio sources with detections at 330 MHz

Disentangling star formation and AGN activity in powerful infrared luminous radio galaxies at 1 < z < 4

© 2016 ESO. High-redshift radio galaxies present signs of both star formation and AGN activity, making them ideal candidates to investigate the connection and coevolution of AGN and star formation in the progenitors of present-day massive galaxies. We make use of a sample of 11 powerful radio galaxies spanning 1 &lt;z&lt; 4 which have complete coverage of their spectral energy distribution (SED) from UV to FIR wavelengths. Using Herschel data, we disentangle the relative contribution of the AGN and star formation by combining the galaxy evolution code PÉGASE.3 with an AGN torus model. We find that three components are necessary to reproduce the observed SEDs: an evolved and massive stellar component, a submm bright young starburst, and an AGN torus. We find that powerful radio galaxies form at very high-redshift, but experience episodic and important growth at 1 &lt;z&lt; 4 as the mass of the associated starburst varies from 5 to 50% of the total mass of the system. The properties of star formation differ from source to source, indicating no general trend of the star formation properties in the most infrared luminous high-redshift radio galaxies and no correlation with the AGN bolometric luminosity. Moreover, we find that AGN scattered light have a very limited impact on broad-band SED fitting on our sample. Finally, our analysis also suggests a wide range in origins for the observed star formation,which we partially constrain for some sources