The first high-redshift changing-look quasars

We report on three redshift $z>2$ quasars with dramatic changes in their C IV emission lines, the first sample of changing-look quasars (CLQs) at high redshift. This is also the first time the changing-look behaviour has been seen in a high-ionisation emission line. SDSS J1205+3422, J1638+2827, and J2228+2201 show interesting behaviour in their observed optical light curves, and subsequent spectroscopy shows significant changes in the C IV broad emission line, with both line collapse and emergence being displayed on rest-frame timescales of $\sim$240-1640 days. These are rapid changes, especially when considering virial black hole mass estimates of $M_{\rm BH} > 10^{9} M_{\odot}$ for all three quasars. Continuum and emission line measurements from the three quasars show changes in the continuum-equivalent width plane with the CLQs seen to be on the edge of the full population distribution, and showing indications of an intrinsic Baldwin effect. We put these observations in context with recent state-change models, and note that even in their observed low-state, the C IV CLQs are generally above $\sim$5\% in Eddington luminosity.Comment: 12 pages, 7 figures, 4 tables. All data, analysis code and text are fully available at: github.com/d80b2t/CIV_CLQs. Comments, questions and suggestions welcome and encourage

The first high-redshift changing-look quasars

We report on three redshift z > 2 quasars with dramatic changes in their C IV emission lines, the first sample of changing-look quasars (CLQs) at high redshift. This is also the first time the changing-look behaviour has been seen in a high-ionization emission line. SDSS J1205+3422, J1638+2827, and J2228 + 2201 show interesting behaviour in their observed optical light curves, and subsequent spectroscopy shows significant changes in the C IV broad emission line, with both line collapse and emergence being displayed on rest-frame time-scales of ∼240–1640 d. These are rapid changes, especially when considering virial black hole mass estimates of M_(BH) > 10⁹M⊙ for all three quasars. Continuum and emission line measurements from the three quasars show changes in the continuum-equivalent width plane with the CLQs seen to be on the edge of the full population distribution, and showing indications of an intrinsic Baldwin effect. We put these observations in context with recent state-change models, and note that even in their observed low-state, the C IV CLQs are generally above ∼5 per cent in Eddington luminosity

Spectroscopy of QUBRICS quasar candidates: 1672 new redshifts and a Golden Sample for the Sandage Test of the Redshift Drift

The QUBRICS (QUasars as BRIght beacons for Cosmology in the Southern hemisphere) survey aims at constructing a sample of the brightest quasars with z>~2.5, observable with facilities in the Southern Hemisphere. QUBRICS makes use of the available optical and IR wide-field surveys in the South and of Machine Learning techniques to produce thousands of bright quasar candidates of which only a few hundred have been confirmed with follow-up spectroscopy. Taking advantage of the recent Gaia Data Release 3, which contains 220 million low-resolution spectra, and of a newly developed spectral energy distribution fitting technique, designed to combine the photometric information with the Gaia spectroscopy, it has been possible to measure 1672 new secure redshifts of QUBRICS candidates, with a typical uncertainty $\sigma_z = 0.02$. This significant progress of QUBRICS brings it closer to (one of) its primary goals: providing a sample of bright quasars at redshift 2.5 < z < 5 to perform the Sandage test of the cosmological redshift drift. A Golden Sample of seven quasars is presented that makes it possible to carry out this experiment in about 1500 hours of observation in 25 years, using the ANDES spectrograph at the 39m ELT, a significant improvement with respect to previous estimates.Comment: 11 pages, 10 figures, accepted for publication in MNRA

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Niche-specific regulation of central metabolic pathways in a fungal pathogen

To establish an infection, the pathogen Candida albicans must assimilate carbon and grow in its mammalian host. This fungus assimilates six-carbon compounds via the glycolytic pathway, and two-carbon compounds via the glyoxylate cycle and gluconeogenesis. We address a paradox regarding the roles of these central metabolic pathways in C. albicans pathogenesis: the glyoxylate cycle is apparently required for virulence although glyoxylate cycle genes are repressed by glucose at concentrations present in the bloodstream. Using GFP fusions, we confirm that glyoxylate cycle and gluconeogenic genes in C. albicans are repressed by physiologically relevant concentrations of glucose, and show that these genes are inactive in the majority of fungal cells infecting the mouse kidney. However, these pathways are induced following phagocytosis by macrophages or neutrophils. In contrast, glycolytic genes are not induced following phagocytosis and are expressed in infected kidney. Mutations in all three pathways attenuate the virulence of this fungus, highlighting the importance of central carbon metabolism for the establishment of C. albicans infections. We conclude that C. albicans displays a metabolic program whereby the glyoxylate cycle and gluconeogenesis are activated early, when the pathogen is phagocytosed by host cells, while the subsequent progression of systemic disease is dependent upon glycolysis

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

Introduction: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30– 40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc- PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis: This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination: Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals.Alicia Calderone, Wendy Stevens, David Prior, Harshal Nandurkar, Eli Gabbay, Susanna M Proudman, Trevor Williams, David Celermajer, Joanne Sahhar, Peter K K Wong, Vivek Thakkar, Nathan Dwyer, Jeremy Wrobel, Weng Chin, Danny Liew, Margaret Staples, Rachelle Buchbinder, Mandana Nikpou

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

Electron-beam Calibration of Aerogel Tiles for the HELIX RICH Detector

The HELIX cosmic-ray detector is a balloon-borne instrument designed to measure the flux of light isotopes in the energy range from 0.2 GeV/n to beyond 3 GeV/n. It will rely on a ring-imaging Cherenkov (RICH) detector for particle identification at energies greater than 1 GeV/n and will use aerogel tiles with refractive index near 1.15 as the radiator. To achieve the performance goals of the experiment it is necessary to know the refractive index and its position dependence over the lateral extent of the tiles to a precision of O(10$^{-4}). In this paper we describe the apparatus and methods developed to calibrate the HELIX tiles in an electron beam, in order to meet this requirement.Comment: 27 pages and 16 figures. Accepted for publication in Nuclear Instruments and Methods