A DETAILED PHOTOMETRIC AND SPECTROSCOPIC STUDY OF THE 2011 OUTBURST OF THE RECURRENT NOVA T Pyxidis FROM 0.8 TO 250 DAYS AFTER DISCOVERY

We investigated the optical light curve of T Pyx during its 2011 outburst through compiling a database of Solar Mass Ejection Imager (SMEI) and AAVSO observations. The SMEI light curve, providing unprecedented detail covering t=1.5-49 days post-discovery, was divided into four phases based on the idealised nova optical light curve; the initial rise (1.5-3.3 days), the pre-maximum halt (3.3-13.3 days), the final rise (14.7-27.9 days), and the early decline (27.9 days - -). The SMEI light curve contains a strongly detected period of 1.44_0.05 days during the pre-maximum halt phase. These oscillations resemble those found in recent TNR models arising from instabilities in the expanding envelope. No spectral variations that mirror the light curve periodicity were found however. The marked dip at t_22-24 days just before light curve maximum at t=27.9 days may represent the same (shorter duration) phenomenon seen in other novae observed by SMEI and present in some model light curves. The spectra from the 2m Liverpool Telescope and SMARTS 1.5m telescope were obtained from t=0.8-80.7 and 155.1-249.9 days, covering the major phases of development. The nova was observed very early in its rise where a distinct high velocity ejection phase was evident with derived Vej_4000 km

Spectroscopic and Photometric Development of T Pyxidis (2011) from 0.8 to 250 Days After Discovery

We investigated the optical light curve of T Pyx during its 2011 outburst through compiling a database of SMEI and AAVSO observations. The SMEI light curve, providing unprecedented detail with high cadence data during t=1.5-49 days post-discovery, was divided into four phases based on the idealised nova optical light curve; the initial rise, the pre-maximum halt (or the 'plateau'), the final rise, and the early decline. Variation in the SMEI light curve reveals a strongly detected period of 1.44\pm0.04 days before the visual maximum. The spectra from the LT and SMARTS telescopes were investigated during t=0.8-80.7 and 155.1-249.9 days. The nova was observed very early in its rise and a distinct high velocity ejection phase was evident. A marked drop and then gradual increase in derived ejection velocities were present. Here we propose two different stages of mass loss, a short-lived phase occurring immediately after outburst followed by a more steadily evolving and higher mass loss phase. The overall spectral development follows that typical of a Classical Nova and comparison to the photometric behaviour reveals consistencies with the simple evolving pseudo-photosphere model of the nova outburst. The optical spectra are also compared to X-ray and radio light curves. Weak [Fe X] 6375A emission was marginally detected before the rise in X-ray emission. The middle of the plateau in the X-ray light curve is coincident with the appearance of high ionization species detected in optical spectra and the peak of the high frequency radio flux

Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein

Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study

BACKGROUND: The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer. METHODS: A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR=ANC/(WBC−ANC). A high dNLR was defined using a cut-off value of ⩾2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan–Meier method. Comparison between groups was performed using Cox regression. RESULTS: A total of 1630 patients were assigned to the continuous (N=815) or intermittent (N=815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR=1.70; 95% CI=1.52–1.90; P<0.001). The estimate of the hazard ratio did not alter substantially (HR=1.54) after adjusting for treatment, tumour status, number of metastatic sites, alkaline phosphate and platelet count. CONCLUSIONS: Derived neutrophil to lymphocyte ratio is strongly prognostic for survival in the COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy

An 800-million-solar-mass black hole in a significantly neutral Universe at redshift 7.5

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120+0641 at z=7.09 has remained the only one known at z>7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10+092838.61 (hereafter J1342+0928) at redshift z=7.54. This quasar has a bolometric luminosity of 4e13 times the luminosity of the Sun and a black hole mass of 8e8 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old---just five percent of its current age---reinforces models of early black-hole growth that allow black holes with initial masses of more than about 1e4 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman alpha emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342+0928 is neutral. We derive a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.Comment: Updated to match the final journal versio

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

The role of glacier mice in the invertebrate colonisation of glacial surfaces: the moss balls of the Falljökull, Iceland

Glacier surfaces have a surprisingly complex ecology. Cryoconite holes contain diverse invertebrate communities while other invertebrates, such as Collembola often graze on algae and windblown dead organic on the glacier surface. Glacier mice (ovoid unattached moss balls) occur on some glaciers worldwide. Studies of these glacier mice have concentrated on their occurrence and mode of formation. There are no reports of the invertebrate communities. But, such glacier mice may provide a suitable favourable habitat and refuge for a variety of invertebrate groups to colonise the glacier surface. Here we describe the invertebrate fauna of the glacier mice (moss balls) of the Falljökull, Iceland. The glacier mice were composed of Racomitrium sp. and varied in size from 8.0 to 10.0 cm in length. All glacier mice studied contained invertebrates. Two species of Collembola were present. Pseudisotoma sensibilis (Tullberg, 1876) was numerically dominant with between 12 and 73 individuals per glacier mouse while Desoria olivacea (Tullberg, 1871) occurred but in far lower numbers. Tardigrada and Nematoda had mean densities of approximately 200 and 1,000 respectively. No Acari, Arachnida or Enchytraeidae were observed which may be related to the difficulty these groups have in colonizing the glacier mice. We suggest that glacier mice provide an unusual environmentally ameliorated microhabitat for an invertebrate community dwelling on a glacial surface. The glacier mice thereby enable an invertebrate fauna to colonise an otherwise largely inhospitable location with implications for carbon flow in the system

Visual parameter optimisation for biomedical image processing

Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships between input and output. Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by integrating input and output, and by supporting exploration of their relationships. We discuss its application to a colour deconvolution technique for stained histology images and show how it enabled a domain expert to identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying assumption about the algorithm. Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs in biomedical image processing that is not supported by previous analysis software. The analysis supported by our method is not feasible with conventional trial-and-error approaches