The 2011 Eruption of the Recurrent Nova T Pyxidis; the Discovery, the Pre-eruption Rise, the Pre-eruption Orbital Period, and the Reason for the Long Delay

We report the discovery by M. Linnolt on JD 2455665.7931 (UT 2011 April 14.29) of the sixth eruption of the recurrent nova T Pyxidis. This discovery was made just as the initial fast rise was starting, so with fast notification and response by observers worldwide, the entire initial rise was covered (the first for any nova), and with high time resolution in three filters. The speed of the rise peaked at 9 mag/day, while the light curve is well fit over only the first two days by a model with a uniformly expanding sphere. We also report the discovery by R. Stubbings of a pre-eruption rise starting 18 days before the eruption, peaking 1.1 mag brighter than its long-time average, and then fading back towards quiescence 4 days before the eruption. This unique and mysterious behavior is only the fourth known anticipatory rise closely spaced before a nova eruption. We present 19 timings of photometric minima from 1986 to February 2011, where the orbital period is fast increasing with P/dot{P}=313,000 yrs. From 2008-2011, T Pyx had a small change in this rate of increase, so that the orbital period at the time of eruption was 0.07622950+-0.00000008 days. This strong and steady increase of the orbital period can only come from mass transfer, for which we calculate a rate of 1.7-3.5x10^-7 Mo/yr. We report 6116 magnitudes between 1890 and 2011, for an average B=15.59+-0.01 from 1967-2011, which allows for an eruption in 2011 if the blue flux is nearly proportional to the accretion rate. The ultraviolet-optical-infrared spectral energy distribution is well fit by a power law with flux proportional to nu^1.0, although the narrow ultraviolet region has a tilt with a fit of \nu^{1/3}. We prove that most of the T Pyx light is not coming from a disk, or any superposition of blackbodies, but rather is coming from some nonthermal source.Comment: ApJ submitted, 62 pages, 8 figures; much added data, updated analysi

A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours

Purpose: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials. Experimental design: Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules. Results: Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma. Conclusions: WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly

The Resolved Structure and Dynamics of an Isolated Dwarf Galaxy: A VLT and Keck Spectroscopic Survey of WLM

We present spectroscopic data for 180 red giant branch stars in the isolated dwarf irregular galaxy WLM. Observations of the Calcium II triplet lines in spectra of RGB stars covering the entire galaxy were obtained with FORS2 at the VLT and DEIMOS on Keck II allowing us to derive velocities, metallicities, and ages for the stars. With accompanying photometric and radio data we have measured the structural parameters of the stellar and gaseous populations over the full galaxy. The stellar populations show an intrinsically thick configuration with $0.39 \leq q_{0} \leq 0.57$. The stellar rotation in WLM is measured to be $17 \pm 1$ km s$^{-1}$, however the ratio of rotation to pressure support for the stars is $V/\sigma \sim 1$, in contrast to the gas whose ratio is seven times larger. This, along with the structural data and alignment of the kinematic and photometric axes, suggests we are viewing WLM as a highly inclined oblate spheroid. Stellar rotation curves, corrected for asymmetric drift, are used to compute a dynamical mass of $4.3\pm 0.3\times10^{8}$M$_{\odot}$ at the half light radius ($r_{h} = 1656 \pm 49$ pc). The stellar velocity dispersion increases with stellar age in a manner consistent with giant molecular cloud and substructure interactions producing the heating in WLM. Coupled with WLM's isolation, this suggests that the extended vertical structure of its stellar and gaseous components and increase in stellar velocity dispersion with age are due to internal feedback, rather than tidally driven evolution. These represent some of the first observational results from an isolated Local Group dwarf galaxy which can offer important constraints on how strongly internal feedback and secular processes modulate SF and dynamical evolution in low mass isolated objects.Comment: 14 Pages, 17 figures, 3 tables. Accepted for publication in Ap

Small non-coding RNA CjNC110 influences motility, autoagglutination, AI-2 localization, and chicken colonization in Campylobacter jejuni

Small non-coding RNAs are involved in many important physiological functions in pathogenic microorganisms. Previous studies have identified the presence of non-coding RNAs in the major zoonotic pathogen Campylobacter jejuni, however, few have been functionally characterized to date. CjNC110 is a conserved ncRNA in C. jejuni, located downstream of the luxS gene which is responsible for the production of the quorum-sensing molecule autoinducer-2 (AI-2). In this study, we utilized strand specific high-throughput RNAseq to identify potential targets or interactive partners of CjNC110 in a sheep abortion clone of C. jejuni. This data was utilized to focus further phenotypic evaluation of the role of CjNC110 in growth, motility, autoagglutination, quorum sensing, and chicken colonization in C. jejuni. Inactivation of the CjNC110 ncRNA led to a statistically significant decrease in autoagglutination ability as well as increased motility when compared to wild-type. Extracellular AI-2 detection was decreased in ΔCjNC110, however, intracellular AI-2 accumulation was significantly increased with a concurrent increase in LuxS expression, suggesting a key role of CjNC110 in modulating the transport of AI-2. Notably, ΔCjNC110 also showed a significant defect in the ability to colonize chickens. Complementation of CjNC110 restored all phenotypic changes back to wild-type levels. The collective results of the phenotypic and transcriptomic changes observed in our data provide valuable insights into the pathobiology of C. jejuni sheep abortion clone and strongly suggest that CjNC110 plays an important role in regulation of energy taxis, flagellar glycosylation, cellular communication via quorum sensing, and chicken colonization in this important zoonotic pathogen

An impact assessment for urban stormwater use

The adoption of stormwater collection and use for a range of non-potable applications requires that the perceived risks, particularly those associated with public health, are addressed. Pollutant impacts have been assessed using E. coli and a scoring system on a scale of 0 to 5 to identify the magnitude of impacts and also the likelihood of exposure to stormwater during different applications. Combining these identifies that low or medium risks are generally predicted except for domestic car washing and occupational irrigation of edible raw food crops where the predicted high risk would necessitate the introduction of remedial action

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

Phlorotannin-Rich Ascophyllum nodosum Seaweed Extract Inhibits Influenza Infection

Seaweed-derived compounds are a renewable resource utilised in the manufacturing and food industry. This study focuses on an enriched seaweed extract (ESE) isolated from Ascophyllum nodosum. The ESE was screened for antiviral activity by plaque reduction assays against influenza A/Puerto Rico/8/1934 H1N1 (PR8), A/X-31 H3N2 (X31) and A/England/195/2009 H1N1 (Eng195), resulting in the complete inhibition of infection. Time of addition assays and FACS analysis were used to help determine the modes of action. The therapeutic potential of ESE was then explored using differentiated human bronchiole epithelial cells at the air–liquid interphase and a murine model challenged with IAV. The data indicates that ESE primarily interacts directly with virions, reducing mean virus–cell binding by 79.3% with 0.01 mg/mL ESE. Interestingly, ESE also inhibits the early and late stages of the influenza A lifecycle when treatment occurs after cell binding. This inhibitory effect appears to reduce the internalisation of the virus and the release of progeny virus by targeting neuraminidase activity, with IC50 values of 0.5 μg/mL for X31, 3.2 μg/mL for Eng195 and 12.8 μg/mL for PR8. The intranasal administration of 5 mg/kg ESE in mice infected with IAV reduced the viral load in lung tissue. ESE may be a promising broad-acting antiviral agent in the treatment of influenza infections