Modeling and Analysis Generic Interface for eXternal numerical codes (MAGIX)

The modeling and analysis generic interface for external numerical codes (MAGIX) is a model optimizer developed under the framework of the coherent set of astrophysical tools for spectroscopy (CATS) project. The MAGIX package provides a framework of an easy interface between existing codes and an iterating engine that attempts to minimize deviations of the model results from available observational data, constraining the values of the model parameters and providing corresponding error estimates. Many models (and, in principle, not only astrophysical models) can be plugged into MAGIX to explore their parameter space and find the set of parameter values that best fits observational/experimental data. MAGIX complies with the data structures and reduction tools of ALMA (Atacama Large Millimeter Array), but can be used with other astronomical and with non-astronomical data.Comment: 12 pages, 15 figures, 2 tables, paper is also available at http://www.aanda.org/articles/aa/pdf/forth/aa20063-12.pd

Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: Genetic reclassification and correlation with clinical features

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder predisposing to predominantly colorectal cancer (CRC) and endometrial cancer frequently due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2 and also MSH6 in families seen to demonstrate an excess of endometrial cancer. As a consequence, tumors in HNPCC reveal alterations in the length of simple repetitive genomic sequences like poly-A, poly-T, CA or GT repeats (microsatellites) in at least 90% of the cases. Aim of the Study: The study cohort consisted of 25 HNPCC index patients ( 19 Amsterdam positive, 6 Bethesda positive) who revealed a microsatellite stable (MSS) - or low instable (MSI-L) - tumor phenotype with negative mutation analysis for the MMR genes MLH1 and MSH2. An extended marker panel (BAT40, D10S197, D13S153, D18S58, MYCL1) was analyzed for the tumors of these patients with regard to three aspects. First, to reconfirm the MSI-L phenotype found by the standard panel; second, to find minor MSIs which might point towards an MSH6 mutation, and third, to reconfirm the MSS status of hereditary tumors. The reconfirmation of the MSS status of tumors not caused by mutations in the MMR genes should allow one to define another entity of hereditary CRC. Their clinical features were compared with those of 150 patients with sporadic CRCs. Results: In this way, 17 MSS and 8 MSI-L tumors were reclassified as 5 MSS, 18 MSI-L and even 2 MSI-H ( high instability) tumors, the last being seen to demonstrate at least 4 instable markers out of 10. Among all family members, 87 malignancies were documented. The mean age of onset for CRCs was the lowest in the MSI-H-phenotyped patients with 40.5 +/- 4.9 years (vs. 47.0 +/- 14.6 and 49.8 +/- 11.9 years in MSI-L- and MSS-phenotyped patients, respectively). The percentage of CRC was the highest in families with MSS-phenotyped tumors (88%), followed by MSI-L-phenotyped ( 78%) and then by MSI-H-phenotyped (67%) tumors. MSS tumors were preferentially localized in the distal colon supposing a similar biologic behavior like sporadic CRC. MSH6 mutation analysis for the MSI-L and MSI-H patients revealed one truncating mutation for a patient initially with an MSS tumor, which was reclassified as MSI-L by analyzing the extended marker panel. Conclusion: Extended microsatellite analysis serves to evaluate the sensitivity of the reference panel for HNPCC detection and permits phenotype confirmation or upgrading. Additionally, it confirms the MSS status of hereditary CRCs not caused by the common mutations in the MMR genes and provides hints to another entity of hereditary CRC. Copyright (C) 2004 S. Karger AG, Basel

Probing MHD Shocks with high-J CO observations: W28F

Context. Observing supernova remnants (SNRs) and modelling the shocks they are associated with is the best way to quantify the energy SNRs re-distribute back into the Interstellar Medium (ISM). Aims. We present comparisons of shock models with CO observations in the F knot of the W28 supernova remnant. These comparisons constitute a valuable tool to constrain both the shock characteristics and pre-shock conditions. Methods. New CO observations from the shocked regions with the APEX and SOFIA telescopes are presented and combined. The integrated intensities are compared to the outputs of a grid of models, which were combined from an MHD shock code that calculates the dynamical and chemical structure of these regions, and a radiative transfer module based on the 'large velocity gradient' (LVG) approximation. Results. We base our modelling method on the higher J CO transitions, which unambiguously trace the passage of a shock wave. We provide fits for the blue- and red-lobe components of the observed shocks. We find that only stationary, C-type shock models can reproduce the observed levels of CO emission. Our best models are found for a pre-shock density of 104 cm-3, with the magnetic field strength varying between 45 and 100 {\mu}G, and a higher shock velocity for the so-called blue shock (\sim25 km s-1) than for the red one (\sim20 km s-1). Our models also satisfactorily account for the pure rotational H2 emission that is observed with Spitzer.Comment: 8 pages, 6 figures, 1 table, accepted for A&A SOFIA/GREAT Special Issu

First 230 GHz VLBI Fringes on 3C 279 using the APEX Telescope

We report about a 230 GHz very long baseline interferometry (VLBI) fringe finder observation of blazar 3C 279 with the APEX telescope in Chile, the phased submillimeter array (SMA), and the SMT of the Arizona Radio Observatory (ARO). We installed VLBI equipment and measured the APEX station position to 1 cm accuracy (1 sigma). We then observed 3C 279 on 2012 May 7 in a 5 hour 230 GHz VLBI track with baseline lengths of 2800 M$\lambda$ to 7200 M$\lambda$ and a finest fringe spacing of 28.6 micro-arcseconds. Fringes were detected on all baselines with SNRs of 12 to 55 in 420 s. The correlated flux density on the longest baseline was ~0.3 Jy/beam, out of a total flux density of 19.8 Jy. Visibility data suggest an emission region <38 uas in size, and at least two components, possibly polarized. We find a lower limit of the brightness temperature of the inner jet region of about 10^10 K. Lastly, we find an upper limit of 20% on the linear polarization fraction at a fringe spacing of ~38 uas. With APEX the angular resolution of 230 GHz VLBI improves to 28.6 uas. This allows one to resolve the last-photon ring around the Galactic Center black hole event horizon, expected to be 40 uas in diameter, and probe radio jet launching at unprecedented resolution, down to a few gravitational radii in galaxies like M 87. To probe the structure in the inner parsecs of 3C 279 in detail, follow-up observations with APEX and five other mm-VLBI stations have been conducted (March 2013) and are being analyzed.Comment: accepted for publication in A&

Deuterated formaldehyde in rho Ophiuchi A

From mapping observations of H2CO, HDCO, and D2CO, we have determined how the degree of deuterium fractionation changes over the central 3'x3' region of rho Oph A. The multi-transition data of the various H2CO isotopologues, as well as from other molecules (e.g., CH3OH and N2D+) present in the observed bands, were analysed using both the standard type rotation diagram analysis and, in selected cases, a more elaborate method of solving the radiative transfer for optically thick emission. In addition to molecular column densities, the analysis also estimates the kinetic temperature and H2 density. Toward the SM1 core in rho Oph A, the H2CO deuterium fractionation is very high. In fact, the observed D2CO/HDCO ratio is 1.34+/-0.19, while the HDCO/H2CO ratio is 0.107+/-0.015. This is the first time, to our knowledge, that the D2CO/HDCO abundance ratio is observed to be greater than 1. The kinetic temperature is in the range 20-30 K in the cores of rho Oph A, and the H2 density is (6-10)x10^5 cm-3. We estimate that the total H2 column density toward the deuterium peak is (1-4)x10^23 cm-2. As depleted gas-phase chemistry is not adequate, we suggest that grain chemistry, possibly due to abstraction and exchange reactions along the reaction chain H2CO -> HDCO -> D2CO, is at work to produce the very high deuterium levels observed.Comment: 17 pages, 11 figures, accepted for publication in Astronomy & Astrophysic

CHAMP+ observations of warm gas in M17 SW

Since the main cooling lines of the gas phase are important tracers of the interstellar medium in Galactic and extragalactic sources, proper and detailed understanding of their emission, and the ambient conditions of the emitting gas, is necessary for a robust interpretation of the observations. With high resolution (7"-9") maps (~3x3 pc^2) of mid-J molecular lines we aim to probe the physical conditions and spatial distribution of the warm (50 to few hundred K) and dense gas (n(H_2)>10^5 cm^-3) across the interface region of M17 SW nebula. We have used the dual color multiple pixel receiver CHAMP+ on APEX telescope to obtain a 5'.3x4'.7 map of the J=6-5 and J=7-6 transitions of 12CO, the 13CO J=6-5 line, and the {^3P_2}-{^3P_1} 370 um fine-structure transition of [C I] in M17 SW. LTE and non-LTE radiative transfer models are used to constrain the ambient conditions. The warm gas extends up to a distance of ~2.2 pc from the M17 SW ridge. The 13CO J=6-5 and [C I] 370 um lines have a narrower spatial extent of about 1.3 pc along a strip line at P.A=63 deg. The structure and distribution of the [C I] {^3P_2}-{^3P_1} 370 um map indicate that its emission arises from the interclump medium with densities of the order of 10^3 cm^-3. The warmest gas is located along the ridge of the cloud, close to the ionization front. An LTE approximation indicates that the excitation temperature of the embedded clumps goes up to ~120 K. The non-LTE model suggests that the kinetic temperature at four selected positions cannot exceed 230 K in clumps of density n(H_2)~5x10^5 cm^-3, and that the warm T_k>100 K and dense (n(H_2)>10^4 cm^-3) gas traced by the mid-J 12CO lines represent just about 2% of the bulk of the molecular gas. The clump volume filling factor ranges between 0.04 and 0.11 at these positions.Comment: Accepted for publication in Astronomy and Astrophysics, 12 pages, 10 figures, 1 tabl

A rotating molecular jet in Orion

We present CO(2-1), $^{13}$CO(2-1), CO(6-5), CO(7-6), and SO(6$_5-5_4$) line observations made with the {\it IRAM 30 m} and {\it APEX} radiotelescopes and the {\it Submillimeter Array} toward the highly collimated and extended southwest lobe of the bipolar outflow {\it Ori-S6} located in the Orion South region. We report, for all these lines, the detection of velocity asymmetries about the flow axis, with velocity differences roughly on the order of 1 km s$^{-1}$ over distances of about 5000 AU, 4 km s$^{-1}$ over distances of about 2000 AU, and close to the source of between 7 and 11 km s$^{-1}$ over smaller scales of about 1000 AU. We interpret these velocity differences as a signature of rotation but also discuss some alternatives which we recognize as unlikely in view of the asymmetries' large downstream continuation. This rotation across the {\it Ori-S6} outflow is observed out to (projected) distances beyond 2.5 $\times$ 10$^4$ AU from the flow's presumed origin. Comparison of our large-scale and small-scale observations suggests the rotational velocity to decline not faster than 1/R with distance R from the axis; in the innermost few arcsecs an increase of rotational velocity with R is even indicated. The magnetic field lines threading the inner rotating CO shell may well be anchored in a disk of radius $\sim$ 50 AU; the field lines further out need a more extended rotating base.Comment: Accepted by Astronomy and Astrophysic

Clinical and Functional Characterization of a Patient Carrying a Compound Heterozygous Pericentrin Mutation and a Heterozygous IGF1 Receptor Mutation

Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration

An epigenetic reprogramming strategy to re-sensitize radioresistant prostate cancer cells

Radiotherapy is a mainstay of curative prostate cancer treatment, but risks of recurrence after treatment remain significant in locally advanced disease. Given that tumor relapse can be attributed to a population of cancer stem cells (CSC) that survives radiotherapy, analysis of this cell population might illuminate tactics to personalize treatment. However, this direction remains challenging given the plastic nature of prostate cancers following treatment. We show here that irradiating prostate cancer cells stimulates a durable upregulation of stem cell markers that epigenetically reprogram these cells. In both tumorigenic and radioresistant cell populations, a phenotypic switch occurred during a course of radiotherapy that was associated with stable genetic and epigenetic changes. Specifically, we found that irradiation triggered histone H3 methylation at the promoter of the CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), stimulating its gene transcription. Inhibiting this methylation event triggered apoptosis, promoted radiosensitization, and hindered tumorigenicity of radioresistant prostate cancer cells. Overall, our results suggest that epigenetic therapies may restore the cytotoxic effects of irradiation in radioresistant CSC populations

Sunyaev-Zel'dovich Effect Observations of the Bullet Cluster (1E 0657-56) with APEX-SZ

We present observations of the Sunyaev-Zel'dovich effect (SZE) in the Bullet cluster (1E 0657--56) using the APEX-SZ instrument at 150 GHz with a resolution of 1 arcmin. The main results are maps of the SZE in this massive, merging galaxy cluster. The cluster is detected with 23 sigma significance within the central 1 arcmin radius of the source position. The SZE map has a broadly similar morphology to that in existing X-ray maps of this system, and we find no evidence for significant contamination of the SZE emission by radio or IR sources. In order to make simple quantitative comparisons with cluster gas models derived from X-ray observations, we fit our data to an isothermal elliptical beta model, despite the inadequacy of such a model for this complex merging system. With an X-ray derived prior on the power-law index, beta = 1.04 +0.16 -0.10, we find a core radius r_c =142 +/- 18 arcsec, an axial ratio of 0.889 +/- 0.072, and a central temperature decrement of -771 +/- 71 micro-K_CMB, including a +/-5.5% flux calibration uncertainty. Combining the APEX-SZ map with a map of projected electron surface density from Chandra X-ray observations, we determine the mass-weighted temperature of the cluster gas to be T_mg=10.8 +/- 0.9 keV, significantly lower than some previously reported X-ray spectroscopic temperatures. Under the assumption of an isothermal cluster gas distribution in hydrostatic equilibrium, we compute the gas mass fraction for prolate and oblate spheroidal geometries and find it to be consistent with previous results from X-ray and weak lensing observations. This work is the first result from the APEX-SZ experiment, and represents the first reported scientific result from observations with a large array of multiplexed superconducting transition-edge sensor bolometers.Comment: 17 pages, 5 figures, accepted for publication in the Astrophysical Journal. Changes in v2: Modified in response to referee comments. Also, improvements in the analysis pipeline and flux calibration result in modification of the maps and model fit parameters. Calibration section and X-ray comparison sections are significantly modifie