On the Putative Detection of z>0 X-ray Absorption Features in the Spectrum of Markarian 421

In a series of papers, Nicastro et al. have reported the detection of z>0 OVII absorption features in the spectrum of Mrk421 obtained with the Chandra Low Energy Transmission Grating Spectrometer (LETGS). We evaluate this result in the context of a high quality spectrum of the same source obtained with the Reflection Grating Spectrometer (RGS) on XMM-Newton. The data comprise over 955ks of usable exposure time and more than 26000 counts per 50 milliAngstrom at 21.6 Angstroms. We concentrate on the spectrally clean region (21.3 < lambda < 22.5 Angstroms) where sharp features due to the astrophysically abundant OVII may reveal an intervening, warm--hot intergalactic medium (WHIM). We do not confirm detection of any of the intervening systems claimed to date. Rather, we detect only three unsurprising, astrophysically expected features down to the Log(N_i)~14.6 (3 sigma) sensitivity level. Each of the two purported WHIM features is rejected with a statistical confidence that exceeds that reported for its initial detection. While we can not rule out the existence of fainter, WHIM related features in these spectra, we suggest that previous discovery claims were premature. A more recent paper by Williams et al. claims to have demonstrated that the RGS data we analyze here do not have the resolution or statistical quality required to confirm or deny the LETGS detections. We show that our careful analysis resolves the issues encountered by Williams et al. and recovers the full resolution and statistical quality of the RGS data. We highlight the differences between our analysis and those published by Williams et al. as this may explain our disparate conclusions.Comment: 19 pages/7 figures/4 tables. 060424 submitted to ApJ 060522 re-submitted following ApJ reques

SImulator of GAlaxy Millimetre/submillimetre Emission (SIGAME): CO emission from massive z=2 main-sequence galaxies

We present SIGAME (SImulator of GAlaxy Millimetre/submillimetre Emission), a new numerical code designed to simulate the 12CO rotational line emission spectrum of galaxies. Using sub-grid physics recipes to post-process the outputs of smoothed particle hydrodynamics (SPH) simulations, a molecular gas phase is condensed out of the hot and partly ionized SPH gas. The gas is subjected to far-UV radiation fields and cosmic ray ionization rates which are set to scale with the local star formation rate volume density. Level populations and radiative transport of the CO lines are solved with the 3-D radiative transfer code LIME. We have applied SIGAME to cosmological SPH simulations of three disc galaxies at z=2 with stellar masses in the range ~(0.5-2)x10^11 Msun and star formation rates ~40-140 Msun/yr. Global CO luminosities and line ratios are in agreement with observations of disc galaxies at z~2 up to and including J=3-2 but falling short of the few existing J=5-4 observations. The central 5 kpc regions of our galaxies have CO 3-2/1-0 and 7-6/1-0 brightness temperature ratios of ~0.55-0.65 and ~0.02-0.08, respectively, while further out in the disc the ratios drop to more quiescent values of ~0.5 and <0.01. Global CO-to-H2 conversion (alpha_CO) factors are ~=1.5 Msun*pc^2/(K km s/1), i.e. ~2-3 times below typically adopted values for disc galaxies, and alpha_CO increases with radius, in agreement with observations of nearby galaxies. Adopting a top-heavy Giant Molecular Cloud (GMC) mass spectrum does not significantly change the results. Steepening the GMC density profile leads to higher global line ratios for J_up>=3 and CO-to-H2 conversion factors [~=3.6 Msun*pc^2/(K km/s)].Comment: 28 pages, 20 figures. Accepted for Publication in MNRAS. Substantial revisions from the previous version, including tests with model galaxies similar to the Milky Way. Improved figures and added table

Increased CNV-Region Deletions in Mild Cognitive Impairment (MCI) and Alzheimer\u27s Disease (AD) Subjects in the ADNI Sample

We investigated the genome-wide distribution of CNVs in the Alzheimer\u27s disease (AD) Neuroimaging Initia- tive (ADNI) sample (146 with AD, 313 with Mild Cognitive Impairment (MCI), and 181 controls). Comparison of single CNVs between cases (MCI and AD) and controls shows overrepresentation of large hetero- zygous deletions in cases (p-value b 0.0001). The analysis of CNV-Regions identifies 44 copy number variable loci of heterozygous deletions, with more CNV-Regions among affected than controls (p = 0.005). Seven of the 44 CNV-Regions are nominally significant for association with cognitive impairment. We validated and con- firmed our main findings with genome re-sequencing of selected patients and controls. The functional pathway analysis of the genes putatively affected by deletions of CNV-Regions reveals enrichment of genes implicated in axonal guidance, cell–cell adhesion, neuronal morphogenesis and differentiation. Our findings support the role of CNVs in AD, and suggest an association between large deletions and the development of cognitive impairment

Focal Plane Metrology for the LSST Camera

Meeting the science goals for the Large Synoptic Survey Telescope (LSST) translates into a demanding set of imaging performance requirements for the optical system over a wide (3.5{sup o}) field of view. In turn, meeting those imaging requirements necessitates maintaining precise control of the focal plane surface (10 {micro}m P-V) over the entire field of view (640 mm diameter) at the operating temperature (T {approx} -100 C) and over the operational elevation angle range. We briefly describe the hierarchical design approach for the LSST Camera focal plane and the baseline design for assembling the flat focal plane at room temperature. Preliminary results of gravity load and thermal distortion calculations are provided, and early metrological verification of candidate materials under cold thermal conditions are presented. A detailed, generalized method for stitching together sparse metrology data originating from differential, non-contact metrological data acquisition spanning multiple (non-continuous) sensor surfaces making up the focal plane, is described and demonstrated. Finally, we describe some in situ alignment verification alternatives, some of which may be integrated into the camera's focal plane

Bayesian Methods for Exoplanet Science

Exoplanet research is carried out at the limits of the capabilities of current telescopes and instruments. The studied signals are weak, and often embedded in complex systematics from instrumental, telluric, and astrophysical sources. Combining repeated observations of periodic events, simultaneous observations with multiple telescopes, different observation techniques, and existing information from theory and prior research can help to disentangle the systematics from the planetary signals, and offers synergistic advantages over analysing observations separately. Bayesian inference provides a self-consistent statistical framework that addresses both the necessity for complex systematics models, and the need to combine prior information and heterogeneous observations. This chapter offers a brief introduction to Bayesian inference in the context of exoplanet research, with focus on time series analysis, and finishes with an overview of a set of freely available programming libraries.Comment: Invited revie

A Sensitive Tg Assay or rhTSH Stimulated Tg: What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the follow-up of DTC. Additionally the value of imaging techniques for the localization of recurrences was evaluated. We included 121 disease free patients in long-term follow-up for DTC (median 10 years, range 1–34). Tg during thyroid hormone suppression therapy (Tg-on) and rhTSH stimulated Tg were measured with a sensitive Tg assay. Patients with rhTSH stimulated Tg ≥1.0 ng/ml underwent imaging with neck ultrasound, FDG-PET and post therapy 131I WBS. Sensitive Tg measurement resulted in 3 patients with Tg-on ≥1.0 ng/ml, recurrence could be localized in 2 of them. RhTSH stimulation resulted in Tg ≥1.0 ng/ml in another 17 of 118 patients. Recurrence could be localized in only 1 additional patient (1 out of 118 patients). Recurrence was localized by neck ultrasound in 1 of 3, by FDG-PET in 2 of 3 and by post therapy 131I WBS in 2 of 3 patients. In the detection of recurrences in DTC, rhTSH stimulation had very limited additional value in comparison to Tg-on measurement with a sensitive Tg assay. We consider this too low to justify rhTSH stimulation in all patients during long-term follow up. Neck ultrasound, FDG-PET and post therapy 131I WBS showed complementary value in localization of disease, but were only positive in a small fracture of all procedures

SNR 1E 0102.2-7219 as an X-ray calibration standard in the 0.5−1.0 keV bandpass and its application to the CCD instruments aboard Chandra , Suzaku , Swift and XMM-Newton

Context. The flight calibration of the spectral response of charge-coupled device (CCD) instruments below 1.5 keV is difficult in general because of the lack of strong lines in the on-board calibration sources typically available. This calibration is also a function of time due to the effects of radiation damage on the CCDs and/or the accumulation of a contamination layer on the filters or CCDs. Aims. We desire a simple comparison of the absolute effective areas of the current generation of CCD instruments onboard the following observatories: Chandra ACIS-S3, XMM-Newton (EPIC-MOS and EPIC-pn), Suzaku XIS, and Swift XRT and a straightforward comparison of the time-dependent response of these instruments across their respective mission lifetimes. Methods. We have been using 1E 0102.2-7219, the brightest supernova remnant in the Small Magellanic Cloud, to evaluate and modify the response models of these instruments. 1E 0102.2-7219 has strong lines of O, Ne, and Mg below 1.5 keV and little or no Fe emission to complicate the spectrum. The spectrum of 1E 0102.2-7219 has been well-characterized using the RGS gratings instrument on XMM-Newton and the HETG gratings instrument on Chandra. As part of the activities of the International Astronomical Consortium for High Energy Calibration (IACHEC), we have developed a standard spectral model for 1E 0102.2-7219 and fit this model to the spectra extracted from the CCD instruments. The model is empirical in that it includes Gaussians for the identified lines, an absorption component in the Galaxy, another absorption component in the SMC, and two thermal continuum components with different temperatures. In our fits, the model is highly constrained in that only the normalizations of the four brightest lines/line complexes (the O vii Heα triplet, O viii Lyα line, the Ne ix Heα triplet, and the Ne x Lyα line) and an overall normalization are allowed to vary, while all other components are fixed. We adopted this approach to provide a straightforward comparison of the measured line fluxes at these four energies. We have examined these measured line fluxes as a function of time for each instrument after applying the most recent calibrations that account for the time-dependent response of each instrument. Results. We performed our effective area comparison with representative, early mission data when the radiation damage and contamination layers were at a minimum, except for the XMM-Newton EPIC-pn instrument which is stable in time. We found that the measured fluxes of the O vii Heαr line, the O viii Lyα line, the Ne ix Heαr line, and the Ne x Lyα line generally agree to within ±10% for all instruments, with 38 of our 48 fitted normalizations within ± 10% of the IACHEC model value. We then fit all available observations of 1E 0102.2-7219 for the CCD instruments close to the on-axis position to characterize the time dependence in the 0.5−1.0 keV band. We present the measured line normalizations as a function of time for each CCD instrument so that the users may estimate the uncertainty in their measured line fluxes for the epoch of their observations

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV