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

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

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

Inclusive Masculinities in a Working-Class Sixth Form in Northeast England

This research examines the construction of masculinity among a group of working-class boys aged sixteen to nineteen in the northeast of England. Drawing on data collected from a six-week ethnography with boys in a religious (Christian) sixth form college, this study documents how only a small minority of these boys embodied the orthodox archetype of masculinity that has traditionally been associated with working-class youth. Instead, the great majority of participants adopted attitudes and behaviors that can be categorized as a set of inclusive masculinities: They espoused positive attitudes toward homosexuality, engaged in physical tactility and emotional intimacy, and used homosexually themed language without the intent to wound or marginalize other boys. These findings pose a considerable challenge to dominant narratives on working-class masculinities; narratives that must now be reconfigured to account for the proliferation of inclusive masculinities among working-class youth