Testing small molecule analogues of acanthocheilonema viteae immunomodulator ES-62 against clinically relevant allergens

ES-62 is a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that protects against ovalbumin (OVA)-induced airway hyper-responsiveness in mice by virtue of covalently attached anti-inflammatory phosphorylcholine (PC) residues. We have recently generated a library of Small Molecule Analogues (SMAs) of ES-62 based around its active PC moiety as a starting point in novel drug development for asthma, and isolated two compounds - termed 11a and 12b – that mirror ES-62’s protective effects. In the present study we have moved away from OVA, a model allergen, to test the two SMAs against two clinically relevant allergens – house dust mite (HDM) and cockroach allergen (CR) extract. We show that whereas both SMAs offer some protection against development of lung allergic responses to CR, in particular reducing eosinophil infiltration, only SMA 12b is effective in protecting against eosinophil-dependent HDM-induced allergy. These data therefore suggest that helminth molecule-induced protection against model antigens may not necessarily translate to clinically relevant antigens. Nevertheless, in the present study we have managed to demonstrate that it is possible to produce synthetic drug-like molecules based on a parasitic worm product that show therapeutic potential with respect to asthma resulting from known triggers in humans

XMM−NewtonXMM-Newton Ω\Omega project: III. Gas mass fraction shape in high redshift clusters

We study the gas mass fraction, $f\_{\rm gas},$ behavior in $XMM-Newton$ $\Omega$ project. The typical $f\_{\rm gas}$ shape of high redshift galaxy clusters follows the global shape inferred at low redshift quite well. This result is consistent with the gravitational instability picture leading to self similar structures for both the dark and baryonic matter. However, the mean $f\_{\rm gas} in distant clusters shows some differences to local ones, indicating a departure from strict scaling. This result is consistent with the observed evolution in the luminosity-temperature relation. We quantitatively investigate this departure from scaling laws. Within the local sample we used, a moderate but clear variation of the amplitude of the gas mass fraction with temperature is found, a trend that weakens in the outer regions. These variations do not explain departure from scaling laws of our distant clusters. An important implication of our results is that the gas fraction evolution, a test of the cosmological parameters, can lead to biased values when applied at radii smaller than the virial radius. From our$XMM$ clusters, the apparent gas fraction at the virial radius is consistent with a non-evolving universal value in a high matter density model and not with a concordance.Comment: Accepted, A&A, in pres

The XMM-Newton Ω\Omega Project

The abundance of high-redshift galaxy clusters depends sensitively on the matter density \OmM and, to a lesser extent, on the cosmological constant $\Lambda$. Measurements of this abundance therefore constrain these fundamental cosmological parameters, and in a manner independent and complementary to other methods, such as observations of the cosmic microwave background and distance measurements. Cluster abundance is best measured by the X-ray temperature function, as opposed to luminosity, because temperature and mass are tightly correlated, as demonstrated by numerical simulations. Taking advantage of the sensitivity of XMM-Newton, our Guaranteed Time program aims at measuring the temperature of the highest redshift (z>0.4) SHARC clusters, with the ultimate goal of constraining both \OmM and $\Lambda$.Comment: To appear in the Proceedings of the XXI Moriond Conference: Galaxy Clusters and the High Redshift Universe Observed in X-rays, edited by D. Neumann, F. Durret, & J. Tran Thanh Va

XMM-Newton observations of the Galactic Supernova Remnant CTB 109 (G109.1-1.0)

We present the analysis of the X-ray Multi-Mirror Mission (XMM-Newton) European Photon Imaging Camera (EPIC) data of the Galactic supernova remnant (SNR) CTB 109 (G109.1-1.0). CTB 109 is associated with the anomalous X-ray pulsar (AXP) 1E 2259+586 and has an unusual semi-circular morphology in both the X-ray and the radio, and an extended X-ray bright interior region known as the `Lobe'. The deep EPIC mosaic image of the remnant shows no emission towards the west where a giant molecular cloud complex is located. No morphological connection between the Lobe and the AXP is found. We find remarkably little spectral variation across the remnant given the large intensity variations. All spectra of the shell and the Lobe are well fitted by a single-temperature non-equilibrium ionization model for a collisional plasma with solar abundances (kT = 0.5 - 0.7 keV, tau = n_e t = 1 - 4 x 10^11 s cm^-3, N_H = 5 - 7 x 10^21 cm^-2). There is no indication of nonthermal emission in the Lobe or the shell. We conclude that the Lobe originated from an interaction of the SNR shock wave with an interstellar cloud. Applying the Sedov solution for the undisturbed eastern part of the SNR, and assuming full equilibration between the electrons and ions behind the shock front, the SNR shock velocity is derived as v_s = 720 +/- 60 km s^-1, the remnant age as t = (8.8 +/- 0.9) x 10^3 d_3 yr, the initial energy as E_0 = (7.4 +/- 2.9) x 10^50 d_3^2.5 ergs, and the pre-shock density of the nuclei in the ambient medium as n_0 = (0.16 +/- 0.02) d_3^-0.5 cm^-3, at an assumed distance of D = 3.0 d_3 kpc. Assuming CTB 109 and 1E 2259+586 are associated, these values constrain the age and the environment of the progenitor of the SNR and the pulsar.Comment: Accepted for publication in ApJ. 9 figures. Figs. 1 + 2 are in color (fig1.jpg, fig2.jpg

X-ray Sources in the Hubble Deep Field Detected by Chandra

We present first results from an X-ray study of the Hubble Deep Field North (HDF-N) and its environs obtained using 166 ks of data collected by the Advanced CCD Imaging Spectrometer (ACIS) on board the Chandra X-ray Observatory. This is the deepest X-ray observation ever reported, and in the HDF-N itself we detect six X-ray sources down to a 0.5--8 keV flux limit of 4E-16 erg cm^-2 s^-1. Comparing these sources with objects seen in multiwavelength HDF-N studies shows positional coincidences with the extremely red object NICMOS J123651.74 +621221.4, an active galactic nucleus (AGN), three elliptical galaxies, and one nearby spiral galaxy. The X-ray emission from the ellipticals is consistent with that expected from a hot interstellar medium, and the spiral galaxy emission may arise from a `super-Eddington' X-ray binary or ultraluminous supernova remnant. Four of the X-ray sources have been detected at radio wavelengths. We also place X-ray upper limits on AGN candidates found in the HDF-N, and we present the tightest constraints yet on X-ray emission from the SCUBA submillimeter source population. None of the 10 high-significance submillimeter sources reported in the HDF-N and its vicinity is detected with Chandra ACIS. These sources appear to be dominated by star formation or have AGN with Compton-thick tori and little circumnuclear X-ray scattering.Comment: 11 pages, ApJ, in press, also available from http://www.astro.psu.edu/users/niel/hdf/hdf-chandra.htm

Gamma Ray Large Area Space Telescope (GLAST) Balloon Flight Data Handling Overview

The GLAST Balloon Flight Engineering Model (BFEM) represents one of 16 towers that constitute the Large Area Telescope (LAT), a high-energy (>20 MeV) gamma-ray pair-production telescope being built by an international partnership of astrophysicists and particle physicists for a satellite launch in 2006. The prototype tower consists of a Pb/Si pair-conversion tracker (TKR), a CsI hodoscopic calorimeter (CAL), an anti-coincidence detector (ACD) and an autonomous data acquisition system (DAQ). The self-triggering capabilities and performance of the detector elements have been previously characterized using positron, photon and hadron beams. External target scintillators were placed above the instrument to act as sources of hadronic showers. This paper provides a comprehensive description of the BFEM data-reduction process, from receipt of the flight data from telemetry through event reconstruction and background rejection cuts. The goals of the ground analysis presented here are to verify the functioning of the instrument and to validate the reconstruction software and the background-rejection scheme.Comment: 5 pages, 4 figures, to be published in IEEE Transacations on Nuclear Science, August 200

The XMM–NEWTON Ω Project: I. The X-ray luminosity – temperature relation at z>0.4

We describe XMM-Newton Guaranteed Time observations of a sample of eight high redshift (0.45 < z < rvirial) bolometric luminosities, performed β-model fits to the radial surface profiles and made spectral fits to a single temperature isothermal model. We describe data analysis techniques that pay particular attention to background mitigation. We have also estimated temperatures and luminosities for two known clusters (Abell 2246 and RXJ1325.0-3814), and one new high redshift cluste r candidate (XMMU J084701.8 +345117), that were detected o ff-axis. Characterizing the L x − Tx relation as L x = L 6 ( T 6keV ) α , we find L 6 = 15 . 9 + 7 . 6 − 5 . 2 × 1044erg s − 1 and α =2.7 ±0.4 for an Ω Λ = 0 . 0 , Ω M = 1 .0, H0 = 50 km s − 1 Mpc − 1 cosmology at a typical redshift z ∼ 0 .55. Comparing with the low redshift study by Markevitch, 1998, we find α to be in agreement, and assuming L x − Tx to evolve as (1 + z ) A , we find A =0.68 ±0.26 for the same cosmology and A = 1 .52 + 0 .26 − 0 .27 for an Ω Λ = 0 . 7 , Ω M = 0 . 3 cosmology. Our A values are very similar to those found previously by Vikhlinin et al., 2002 using a compilation of Chandra observations of 0 .39 < z < 1 .26 clusters. We conclude that there is now evidence from both XMM-Newton and Chandra for an evolutionary trend in the L x − Tx relation. This evolution is significantly below the level expected from the predictions of the self-similar model for an Ω Λ = 0 . 0 , Ω M = 1 .0, cosmology, but consistent with self-similar model in an Ω Λ = 0 . 7 , Ω M = 0 . 3 cosmology. Our observations lend support to the robustness and completeness of the SHARC and 160SD surveys

Constraints on the distribution of absorption in the X-ray selected AGN population found in the 13H XMM-Newton/Chandra deep field

We present an analysis of the X-ray properties of sources detected in the 13H XMM-Newton deep (200ks) field. In order to constrain the absorbed AGN population, we use extensive Monte Carlo simulations to directly compare the X-ray colours of observed sources with those predicted by several model distributions. We have tested the simplest form of the AGN unified scheme, whereby the intrinsic XLF of absorbed AGN is set to be the same as that of their unabsorbed brethren, coupled with various model distributions of absorption. The best fitting of these models sets the fraction of AGN with absorbing column NH, proportional to (logNH)^8. We have also tested two extensions to the unified scheme: an evolving absorption scenario, and a luminosity dependent model distribution. Both of these provide poorer matches to the observed X-ray colour distributions than the best fitting simple unified model. We find that a luminosity dependent density evolution XLF reproduces poorly the 0.5-2 keV source counts seen in the 13H field. Field to field variations could be the cause of this disparity. Computing the simulated X-ray colours with a simple absorbed power-law + reflection spectral model is found to over-predict, by a factor of two, the fraction of hard sources that are completely absorbed below 0.5 keV, implying that an additional source of soft-band flux must be present for a number of the absorbed sources. Finally, we show that around 40% of the 13H sample are expected to be AGN with NH>10^22 cm^-2.Comment: 13 pages, 9 figures, Accepted for publication in MNRA

Multi-layer coating development for XEUS

Graded depth multi-layer coatings have the potential to optimise the performance of X-ray reflective surfaces for improved energy response. A study of deposition techniques on silicon substrates representative of the XEUS High Performance Pore Optics (HPO) technology has been carried out. Measurements at synchrotron radiation facilities have been used to confirm the excellent performance improvements achievable with Mo/Si and W/Si multilayers. Future activities that will be necessary to implement such coatings in the HPO assembly sequence are highlighted. Further coating developments that may allow an optimisation of the XEUS effective area in light of potential changes to science requirements and telescope configurations are also identified. Finally an initial measurement of effects of radiation damage within the multilayers is reported