Interpreting radiative efficiency in radio-loud AGNs

Author submitted version of unrefereed Nature Astronomy comment. Version in journal format available at https://rdcu.be/KH6WRadiative efficiency in radio-loud active galactic nuclei is governed by the accretion rate onto the central black hole rather than directly by the type of accreted matter; while it correlates with real differences in host galaxies and environments, it does not provide unambiguous information about particular objects.Non peer reviewedFinal Accepted Versio

Structure, function and mechanism of beta-barrel protein assembly in Campylobacter jejuni

Campylobacter jejuni is one of the world’s leading causes of food-mediated bacterial infection, affecting millions of people every year. BamA, a highly conserved, essential membrane protein found in C. jejuni and other Gram-negative bacteria is responsible for folding a number of essential β-barrel outer membrane proteins making it vital for survival in this pathogenic organism. Along with essential roles in basic physiological functions, such as nutrient import and export, outer membrane proteins are also found in a number of multidrug resistance and virulence mechanisms in pathogenic organisms, making them and BamA popular targets for therapeutic intervention. BamA is well characterised in model organisms, however the conversed mechanism which facilitates assembly in different species remains unclear. In this work, the biogenesis of β-barrel proteins is investigated in C. jeuni NCTC-11168. A recombinant expression system is developed and used to express recombinant CjBamA (Cj0129) in an E. coli BL21 host, followed by subsequent purification and biophysical characterisation. A pelB leader sequence is used to target the recombinant protein for outer membrane localisation, with an extended 10x-polyhistidine tag and purified by immobilised metal affinity chromatography. Secondary structure analysis is performed using synchrotron radiation circular dichroism confirming the presence of a dominant β-sheet fraction. Furthermore, bioinformatics tools are used to investigate the structure of BamA homology models and explore the structural relationships between BamA and a previously unidentified accessory BamD protein found in the Campylobacter genus

Simulating Reionization: Character and Observability

In recent years there has been considerable progress in our understanding of the nature and properties of the reionization process. In particular, the numerical simulations of this epoch have made a qualitative leap forward, reaching sufficiently large scales to derive the characteristic scales of the reionization process and thus allowing for realistic observational predictions. Our group has recently performed the first such large-scale radiative transfer simulations of reionization, run on top of state-of-the-art simulations of early structure formation. This allowed us to make the first realistic observational predictions about the Epoch of Reionization based on detailed radiative transfer and structure formation simulations. We discuss the basic features of reionization derived from our simulations and some recent results on the observational implications for the high-redshift Ly-alpha sources.Comment: 3 pages, to appear in the Proceedings of First Stars III, Santa Fe, July 2007, AIP Conference Serie

Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids

RP2 mutations cause a severe form of X-linked retinitis pigmentosa (XLRP). The mechanism of RP2-associated retinal degeneration in humans is unclear, and animal models of RP2 XLRP do not recapitulate this severe phenotype. Here, we developed gene-edited isogenic RP2 knockout (RP2 KO) induced pluripotent stem cells (iPSCs) and RP2 patient-derived iPSC to produce 3D retinal organoids as a human retinal disease model. Strikingly, the RP2 KO and RP2 patient-derived organoids showed a peak in rod photoreceptor cell death at day 150 (D150) with subsequent thinning of the organoid outer nuclear layer (ONL) by D180 of culture. Adeno-associated virus-mediated gene augmentation with human RP2 rescued the degeneration phenotype of the RP2 KO organoids, to prevent ONL thinning and restore rhodopsin expression. Notably, these data show that 3D retinal organoids can be used to model photoreceptor degeneration and test potential therapies to prevent photoreceptor cell death

Low frequency radio properties of the z>5 quasar population

Optically luminous quasars at z > 5 are important probes of super-massive black hole (SMBH) formation. With new and future radio facilities, the discovery of the brightest low-frequency radio sources in this epoch would be an important new probe of cosmic reionization through 21-cm absorption experiments. In this work, we systematically study the low-frequency radio properties of a sample of 115 known spectroscopically confirmed z > 5 quasars using the second data release of the Low Frequency Array (LOFAR) Two Metre Sky survey (LoTSS-DR2), reaching noise levels of ∼80 µJy beam−1 (at 144 MHz) over an area of ∼ 5720 deg2 . We find that 41 sources (36%) are detected in LoTSS-DR2 at > 2σ significance and we explore the evolution of their radio properties (power, spectral index, and radio loudness) as a function of redshift and rest-frame ultra-violet properties. We obtain a median spectral index of −0.29+0.10 −0.09 by stacking 93 quasars using LoTSS-DR2 and Faint Images of the Radio Sky at Twenty Centimetres (FIRST) data at 1.4 GHz, in line with observations of quasars at z < 3. We compare the radio loudness of the high-z quasar sample to a lower-z quasar sample at z ∼ 2 and find that the two radio loudness distributions are consistent with no evolution, although the low number of high-z quasars means that we cannot rule out weak evolution. Furthermore, we make a first order empirical estimate of the z = 6 quasar radio luminosity function, which is used to derive the expected number of high-z sources that will be detected in the completed LoTSS survey. This work highlights the fact that new deep radio observations can be a valuable tool in selecting high-z quasar candidates for follow-up spectroscopic observations by decreasing contamination of stellar dwarfs and reducing possible selection biases introduced by strict colour cuts

Galaxy And Mass Assembly (GAMA): The 325 MHz Radio Luminosity Function of AGN and Star Forming Galaxies

Measurement of the evolution of both active galactic nuclei (AGN) and star-formation in galaxies underpins our understanding of galaxy evolution over cosmic time. Radio continuum observations can provide key information on these two processes, in particular via the mechanical feedback produced by radio jets in AGN, and via an unbiased dust-independent measurement of star-formation rates. In this paper we determine radio luminosity functions at 325 MHz for a sample of AGN and star-forming galaxies by matching a 138 deg sq. radio survey conducted with the Giant Metrewave Radio Telescope (GMRT), with optical imaging and redshifts from the Galaxy And Mass Assembly (GAMA) survey. We find that the radio luminosity function at 325 MHz for star-forming galaxies closely follows that measured at 1.4 GHz. By fitting the AGN radio luminosity function out to $z = 0.5$ as a double power law, and parametrizing the evolution as ${\Phi} \propto (1 + z)^{k}$ , we find evolution parameters of $k = 0.92 \pm 0.95$ assuming pure density evolution and $k = 2.13 \pm 1.96$ assuming pure luminosity evolution. We find that the Low Excitation Radio Galaxies are the dominant population in space density at lower luminosities. Comparing our 325 MHz observations with radio continuum imaging at 1.4 GHz, we determine separate radio luminosity functions for steep and flat-spectrum AGN, and show that the beamed population of flat-spectrum sources in our sample can be shifted in number density and luminosity to coincide with the unbeamed population of steep-spectrum sources, as is expected in the orientation based unification of AGN

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Population screening for colorectal cancer: the implications of an ageing population

Population screening for colorectal cancer (CRC) has recently commenced in the United Kingdom supported by the evidence of a number of randomised trials and pilot studies. Certain factors are known to influence screening cost-effectiveness (e.g. compliance), but it remains unclear whether an ageing population (i.e. demographic change) might also have an effect. The aim of this study was to simulate a population-based screening setting using a Markov model and assess the effect of increasing life expectancy on CRC screening cost-effectiveness. A Markov model was constructed that aimed, using a cohort simulation, to estimate the cost-effectiveness of CRC screening in an England and Wales population for two timescales: 2003 (early cohort) and 2033 (late cohort). Four model outcomes were calculated; screened and non-screened cohorts in 2003 and 2033. The screened cohort of men and women aged 60 years were offered biennial unhydrated faecal occult blood testing until the age of 69 years. Life expectancy was assumed to increase by 2.5 years per decade. There were 407 552 fewer people entering the model in the 2033 model due to a lower birth cohort, and population screening saw 30 345 fewer CRC-related deaths over the 50 years of the model. Screening the 2033 cohort cost £96 million with cost savings of £43 million in terms of detection and treatment and £28 million in palliative care costs. After 30 years of follow-up, the cost per life year saved was £1544. An identical screening programme in an early cohort (2003) saw a cost per life year saved of £1651. Population screening for CRC is costly but enables cost savings in certain areas and a considerable reduction in mortality from CRC. This Markov simulation suggests that the cost-effectiveness of population screening for CRC in the United Kingdom may actually be improved by rising life expectancies

MIGHTEE: Are giant radio galaxies more common than we thought?

We report the discovery of two new giant radio galaxies (GRGs) using the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) survey. Both GRGs were found within a ∼1 deg2 region inside the COSMOS field. They have redshifts of z = 0.1656 and z = 0.3363 and physical sizes of 2.4 Mpc and 2.0 Mpc, respectively. Only the cores of these GRGs were clearly visible in previous high resolution VLA observations, since the diffuse emission of the lobes was resolved out. However, the excellent sensitivity and uv coverage of the new MeerKAT telescope allowed this diffuse emission to be detected. The GRGs occupy an unpopulated region of radio power – size parameter space. Based on a recent estimate of the GRG number density, the probability of finding two or more GRGs with such large sizes at z < 0.4 in a ∼1 deg2 field is only 2.7 × 10−6, assuming Poisson statistics. This supports the hypothesis that the prevalence of GRGs has been significantly underestimated in the past due to limited sensitivity to low surface brightness emission. The two GRGs presented here may be the first of a new population to be revealed through surveys like MIGHTEE which provide exquisite sensitivity to diffuse, extended emission