Impact of tumour histological subtype on chemotherapy outcome in advanced oesophageal cancer.

AIM: To investigate the impact of histology on outcome in advanced oesophageal cancer treated with first-line fluoropyrimidine-based chemotherapy. METHODS: Individual patient data were pooled from three randomised phase III trials of fluoropyrimidine-based chemotherapy ± platinum/anthracycline in patients with advanced, untreated gastroesophageal adenocarcinoma or squamous cell carcinoma (SCC) randomised between 1994 and 2005. The primary endpoint was overall survival of oesophageal cancer patients according to histology. Secondary endpoints were response rates and a toxicity composite endpoint. RESULTS: Of the total 1836 randomised patients, 973 patients (53%) were eligible (707 patients with gastric cancer were excluded), 841 (86%) had adenocarcinoma and 132 (14%) had SCC. There was no significant difference in survival between patients with adenocarcinoma and SCC, with median overall survivals of 9.5 mo vs 7.6 mo (HR = 0.85, 95%CI: 0.70-1.03, P = 0.09) and one-year survivals of 38.8% vs 28.2% respectively. The overall response rate to chemotherapy was 44% for adenocarcinoma vs 33% for SCC (P = 0.01). There was no difference in the frequency of the toxicity composite endpoint between the two groups. CONCLUSION: There was no significant difference in survival between adenocarcinoma and SCC in patients with advanced oesophageal cancer treated with fluoropyrimidine-based chemotherapy despite a trend for worse survival and less chemo-sensitivity in SCC. Tolerance to treatment was similar in both groups. This analysis highlights the unmet need for SCC-specific studies in advanced oesophageal cancer and will aid in the design of future trials of targeted agents

The structural properties of full-length annexin A11

Annexin A11 (ANXA11) is a calcium-dependent phospholipid-binding protein belonging to the annexin protein family and implicated in the neurodegenerative amyotrophic lateral sclerosis. Structurally, ANXA11 contains a conserved calcium-binding C-terminal domain common to all annexins and a putative intrinsically unfolded N-terminus specific for ANXA11. Little is known about the structure and functions of this region of the protein. By analogy with annexin A1, it was suggested that residues 38 to 59 within the ANXA11 N-terminus could form a helical region that would be involved in interactions. Interestingly, this region contains residues that, when mutated, may lead to clinical manifestations. In the present study, we have studied the structural features of the full-length protein with special attention to the N-terminal region using a combination of biophysical techniques which include nuclear magnetic resonance and small angle X-ray scattering. We show that the N-terminus is intrinsically disordered and that the overall features of the protein are not markedly affected by the presence of calcium. We also analyzed the 38–59 helix hypothesis using synthetic peptides spanning both the wild-type sequence and clinically relevant mutations. We show that the peptides have a remarkable character typical of a native helix and that mutations do not alter the behaviour suggesting that they are required for interactions rather than being structurally important. Our work paves the way to a more thorough understanding of the ANXA11 functions

A role for fast rhythmic bursting neurons in cortical gamma oscillations in vitro

Basic cellular and network mechanisms underlying gamma frequency oscillations (30–80 Hz) have been well characterized in the hippocampus and associated structures. In these regions, gamma rhythms are seen as an emergent property of networks of principal cells and fast-spiking interneurons. In contrast, in the neocortex a number of elegant studies have shown that specific types of principal neuron exist that are capable of generating powerful gamma frequency outputs on the basis of their intrinsic conductances alone. These fast rhythmic bursting (FRB) neurons (sometimes referred to as "chattering" cells) are activated by sensory stimuli and generate multiple action potentials per gamma period. Here, we demonstrate that FRB neurons may function by providing a large-scale input to an axon plexus consisting of gap-junctionally connected axons from both FRB neurons and their anatomically similar counterparts regular spiking neurons. The resulting network gamma oscillation shares all of the properties of gamma oscillations generated in the hippocampus but with the additional critical dependence on multiple spiking in FRB cells

The Calibration and Data Products of the Galaxy Evolution Explorer

We describe the calibration status and data products pertaining to the GR2 and GR3 data releases of the Galaxy Evolution Explorer (GALEX). These releases have identical pipeline calibrations that are significantly improved over the GR1 data release. GALEX continues to survey the sky in the Far Ultraviolet (FUV, ~154 nm) and Near Ultraviolet (NUV, ~232 nm) bands, providing simultaneous imaging with a pair of photon counting, microchannel plate, delay line readout detectors. These 1.25 degree field-of-view detectors are well-suited to ultraviolet observations because of their excellent red rejection and negligible background. A dithered mode of observing and photon list output pose complex requirements on the data processing pipeline, entangling detector calibrations and aspect reconstruction algorithms. Recent improvements have achieved photometric repeatability of 0.05 and 0.03 mAB in the FUV and NUV, respectively. We have detected a long term drift of order 1% FUV and 6% NUV over the mission. Astrometric precision is of order 0.5" RMS in both bands. In this paper we provide the GALEX user with a broad overview of the calibration issues likely to be confronted in the current release. Improvements are likely as the GALEX mission continues into an extended phase with a healthy instrument, no consumables, and increased opportunities for guest investigations.Comment: Accepted to the ApJS (a special GALEX issue

Ongoing Formation of Bulges and Black Holes in the Local Universe: New Insights from GALEX

We analyze a volume-limited sample of massive bulge-dominated galaxies with data from both the Sloan Digital Sky Survey and the Galaxy Evolution Explorer (GALEX) satellite. The galaxies have central velocity dispersions greater than 100 km/s and stellar surface mass densities that lie above the value where galaxies transition from actively star forming to passive systems. The sample is limited to redshifts 0.03<z<0.07. At these distances, the SDSS spectra sample the light from the bulge-dominated central regions of the galaxies. The GALEX NUV data provide high sensitivity to low rates of global star formation in these systems. Our sample of bulge-dominated galaxies exhibits a much larger dispersion in NUV-r colour than in optical g-r colour. Nearly all of the galaxies with bluer NUV-r colours are AGN. Both GALEX images and SDSS colour profiles demonstrate that the excess UV light is associated with an extended disk. We find that galaxies with red outer regions almost never have a young bulge or a strong AGN. Galaxies with blue outer regions have bulges and black holes that span a wide range in age and accretion rate. Galaxies with young bulges and strongly accreting black holes almost always have blue outer disks. Our suggested scenario is one in which the source of gas that builds the bulge and black hole is a low mass reservoir of cold gas in the disk.The presence of this gas is a necessary, but not sufficient condition for bulge and black hole growth. Some mechanism must transport this gas inwards in a time variable way. As the gas in the disk is converted into stars, the galaxies will turn red, but further gas infall can bring them back into the blue NUV-r sequence.(Abridged)Comment: 34 pages, 16 figures. Accepted for the GALEX special issue of ApJ

Large-Scale Spatial Cross-Calibration of Hinode/SOT-SP and SDO/HMI

We investigate the cross-calibration of the Hinode/SOT-SP and SDO/HMI instrument meta-data, specifically the correspondence of the scaling and pointing information. Accurate calibration of these datasets gives the correspondence needed by inter-instrument studies and learning-based magnetogram systems, and is required for physically-meaningful photospheric magnetic field vectors. We approach the problem by robustly fitting geometric models on correspondences between images from each instrument's pipeline. This technique is common in computer vision, but several critical details are required when using scanning slit spectrograph data like Hinode/SOT-SP. We apply this technique to data spanning a decade of the Hinode mission. Our results suggest corrections to the published Level 2 Hinode/SOT-SP data. First, an analysis on approximately 2,700 scans suggests that the reported pixel size in Hinode/SOT-SP Level 2 data is incorrect by around 1%. Second, analysis of over 12,000 scans show that the pointing information is often incorrect by dozens of arcseconds with a strong bias. Regression of these corrections indicates that thermal effects have caused secular and cyclic drift in Hinode/SOT-SP pointing data over its mission. We offer two solutions. First, direct co-alignment with SDO/HMI data via our procedure can improve alignments for many Hinode/SOT-SP scans. Second, since the pointing errors are predictable, simple post-hoc corrections can substantially improve the pointing. We conclude by illustrating the impact of this updated calibration on derived physical data products needed for research and interpretation. Among other things, our results suggest that the pointing errors induce a hemispheric bias in estimates of radial current density.Comment: Under revisions at ApJ

Clustering Properties of restframe UV selected galaxies I: the correlation length derived from GALEX data in the local Universe

We present the first measurements of the angular correlation function of galaxies selected in the far (1530 A) and near (2310 A) Ultraviolet from the GALEX survey fields overlapping SDSS DR5 in low galactic extinction regions. The area used covers 120 sqdeg (GALEX - MIS) down to magnitude AB = 22, yielding a total of 100,000 galaxies. The mean correlation length is ~ 3.7 \pm 0.6 Mpc and no significant trend is seen for this value as a function of the limiting apparent magnitude or between the GALEX bands. This estimate is close to that found from samples of blue galaxies in the local universe selected in the visible, and similar to that derived at z ~ 3 for LBGs with similar rest frame selection criteria. This result supports models that predict anti-biasing of star forming galaxies at low redshift, and brings an additional clue to the downsizing of star formation at z<1.Comment: Accepted for publication in GALEX Special ApJs, December 200

Clustering Properties of restframe UV selected galaxies II: Migration of Star Formation sites with cosmic time from GALEX and CFHTLS

We analyze the clustering properties of ultraviolet selected galaxies by using GALEX-SDSS data at z<0.6 and CFHTLS deep u' imaging at z=1. These datasets provide a unique basis at z< 1 which can be directly compared with high redshift samples built with similar selection criteria. We discuss the dependence of the correlation function parameters (r0, delta) on the ultraviolet luminosity as well as the linear bias evolution. We find that the bias parameter shows a gradual decline from high (b > 2) to low redshift (b ~ 0.79^{+0.1}_{-0.08}). When accounting for the fraction of the star formation activity enclosed in the different samples, our results suggest that the bulk of star formation migrated from high mass dark matter halos at z>2 (10^12 < M_min < 10^13 M_sun, located in high density regions), to less massive halos at low redshift (M_min < 10^12 M_sun, located in low density regions). This result extends the ``downsizing'' picture (shift of the star formation activity from high stellar mass systems at high z to low stellar mass at low z) to the dark matter distribution.Comment: Accepted for Publication in the Special GALEX Ap. J. Supplement, December 2007 Version with full resolution fig1 available at http://taltos.pha.jhu.edu/~sebastien/papers/Galex_p2.ps.g

First measurement of the Gerasimov-Drell-Hearn integral for Hydrogen from 200 to 800 MeV

A direct measurement of the helicity dependence of the total photoabsorption cross section on the proton was carried out at MAMI (Mainz) in the energy range 200 < E_gamma < 800 MeV. The experiment used a 4$\pi$ detection system, a circularly polarized tagged photon beam and a frozen spin target. The contributions to the Gerasimov-Drell-Hearn sum rule and to the forward spin polarizability $\gamma_0$ determined from the data are 226 \pm 5 (stat)\pm 12(sys) \mu b and -187 \pm 8 (stat)\pm 10(sys)10^{-6} fm^4, respectively, for 200 < E_\gamma < 800 MeV.Comment: 6 pages, 3 figures, 3 table