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

Validation of core competencies during residency training in anaesthesiology

Background and goal: Curriculum development for residency training is increasingly challenging in times of financial restrictions and time limitations. Several countries have adopted the CanMEDS framework for medical education as a model into their curricula of specialty training. The purpose of the present study was to validate the competency goals, as derived from CanMEDS, of the Department of Anaesthesiology and Intensive Care Medicine of the Berlin Charité University Medical Centre, by conducting a staff survey. These goals for the qualification of specialists stipulate demonstrable competencies in seven areas: expert medical action, efficient collaboration in a team, communications with patients and family, management and organisation, lifelong learning, professional behaviour, and advocacy of good health. We had previously developed a catalogue of curriculum items based on these seven core competencies. In order to evaluate the validity of this catalogue, we surveyed anaesthetists at our department in regard to their perception of the importance of each of these items. In addition to the descriptive acquisition of data, it was intended to assess the results of the survey to ascertain whether there were differences in the evaluation of these objectives by specialists and registrars

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&

Therapeutic Implications of GIPC1 Silencing in Cancer

GIPC1 is a cytoplasmic scaffold protein that interacts with numerous receptor signaling complexes, and emerging evidence suggests that it plays a role in tumorigenesis. GIPC1 is highly expressed in a number of human malignancies, including breast, ovarian, gastric, and pancreatic cancers. Suppression of GIPC1 in human pancreatic cancer cells inhibits in vivo tumor growth in immunodeficient mice. To better understand GIPC1 function, we suppressed its expression in human breast and colorectal cancer cell lines and human mammary epithelial cells (HMECs) and assayed both gene expression and cellular phenotype. Suppression of GIPC1 promotes apoptosis in MCF-7, MDA-MD231, SKBR-3, SW480, and SW620 cells and impairs anchorage-independent colony formation of HMECs. These observations indicate GIPC1 plays an essential role in oncogenic transformation, and its expression is necessary for the survival of human breast and colorectal cancer cells. Additionally, a GIPC1 knock-down gene signature was used to interrogate publically available breast and ovarian cancer microarray datasets. This GIPC1 signature statistically correlates with a number of breast and ovarian cancer phenotypes and clinical outcomes, including patient survival. Taken together, these data indicate that GIPC1 inhibition may represent a new target for therapeutic development for the treatment of human cancers

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

The sub-mm J=6-5 line of 13CO in Orion

We present a fully sampled map covering the Orion Hot Core and dense molecular ridge, in the sub-millimeter J=6-5 rotational transition of 13CO, at 0.45 mm with a resolution of 13 arcsec and 0.5 km s^-1. The map covers 3 arc min by 2arc min . The profile centered on the Hot Core peaks at 8.5 km s^-1 and has a peak intensity of 40 K, corrected antenna temperature. It shows line wings from 30 km s^-1 to -20 km s^-1. The map of intensity, integrated from 0 to +18 km s^-1, shows a prominent maximum <5 arcsec from the center of the Orion Hot Core. The FWHP is 3 arcsec, larger than the regions containing complex molecules. Single dish measurements of lines from the J=2-1 or J=1-0 transitions of CO isotopes show no such distinct maximum. Correcting for optical depth 1.5 in the J=6-5 line of 13CO, and assuming that the level populations are thermalized at 150 K, the beam averaged column density between 0 to +18 km s^-1 is N(13CO )=6.8 10^17 cm^-2 and N(CO)=5.2 10^19 cm-2. When combined with published dust emission data, the CO/ H2 number ratio is 2 {\cdot} 10^-5, a factor of ~5 lower than the canonical value, 10^-4. For the Orion South and Orion Ridge region, the column density of CO is <25% of that found for the Hot Core but CO/H2 ratios are similar. Models of Photodissociation Regions, PDRs, predict that CO lines from PDRs are only marginally optically thick. Thus our map traces warm and dense molecular gas rather than PDRs.Comment: 23 pages total, including 5 figure

The ALMA Interferometric Pipeline Heuristics

We describe the calibration and imaging heuristics developed and deployed in the ALMA interferometric data processing pipeline, as of ALMA Cycle 9. The pipeline software framework is written in Python, with each data reduction stage layered on top of tasks and toolkit functions provided by the Common Astronomy Software Applications package. This framework supports a variety of tasks for observatory operations, including science data quality assurance, observing mode commissioning, and user reprocessing. It supports ALMA and VLA interferometric data along with ALMA and NRO45m single dish data, via different stages and heuristics. In addition to producing calibration tables, calibrated measurement sets, and cleaned images, the pipeline creates a WebLog which serves as the primary interface for verifying the data quality assurance by the observatory and for examining the contents of the data by the user. Following the adoption of the pipeline by ALMA Operations in 2014, the heuristics have been refined through annual development cycles, culminating in a new pipeline release aligned with the start of each ALMA Cycle of observations. Initial development focused on basic calibration and flagging heuristics (Cycles 2-3), followed by imaging heuristics (Cycles 4-5), refinement of the flagging and imaging heuristics with parallel processing (Cycles 6-7), addition of the moment difference analysis to improve continuum channel identification (2020 release), addition of a spectral renormalization stage (Cycle 8), and improvement in low SNR calibration heuristics (Cycle 9). In the two most recent Cycles, 97% of ALMA datasets were calibrated and imaged with the pipeline, ensuring long-term automated reproducibility. We conclude with a brief description of plans for future additions, including self-calibration, multi-configuration imaging, and calibration and imaging of full polarization data.Comment: accepted for publication by Publications of the Astronomical Society of the Pacific, 65 pages, 20 figures, 10 tables, 2 appendice

Revisiting the shocks in BHR71: new observational constraints and H2O predictions for Herschel

During the formation of a star, material is ejected along powerful jets that impact the ambient material. This outflow phenomenon plays an important role in the regulation of star formation. Understanding the associated shocks and their energetic effects is therefore essential to the study of star formation. We present comparisons of shock models with observations of H$_2$ and SiO emission in the bipolar outflow BHR71, and predict water emission, under the basic assumption that the emission regions of the considered species coincide, at the resolution of currently available observations. New SiO observations from APEX are presented, and combined with \textit{Spitzer} and ground-based observations of H$_2$ to constrain shock models. The shock regions associated with targeted positions in the molecular outflow are studied by means of a 1D code that generates models of the propagation of stationary shock waves, and approximations to non-stationary ones. The SiO emission in the inner part of the outflow is concentrated near the apex of the corresponding bow-shock that is also seen in the pure rotational transitions of H$_2$. Simultaneous modelling is possible for H$_2$ and SiO and leads to constraints on the silicon pre-shock distribution on the grain mantles and/or cores. The best-fitting models are found to be of the non-stationary type, but the degeneracy of the solutions is still large. Pre-shock densities of 10$^4$ and 10$^5$ cm$^{-3}$ are investigated, and the associated best-model candidates have rather low velocity (respectively, 20-30 and 10-15 km s$^{-1}$) and are not older than 1000 years. We provide emission predictions for water, focusing on the brightest transitions, to be observed with the PACS and HIFI instruments of the \textit{Herschel} Telescope.Comment: 22 pages (12 text + 10 appendix), 8 figures, 8 tables (4 text + 4 appendix). Abstract has been amended to fullfill arxiv requirement