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

The inhomogeneous ISM toward PKS1830-211 SW - A detailed view on molecular gas at a look-back time of 7.5 Gyr

Based on measurements with the Effelsberg 100-m telescope, a multi-line study of molecular species is presented toward the south-western source of the gravitational lens system PKS 1830-211, which is by far the best known target to study molecular gas in absorption at intermediate redshift. Determining line parameters and optical depths and performing Large Velocity Gradient radiative transfer calculations, the aims of this study are (1) to evaluate physical parameters of the absorbing foreground gas at z~0.89, in particular its homogeneity, and (2) to monitor the spectroscopic time variability caused by fluctuations of the z~2.5 background continuum source. We find, that the gas is quite inhomogeneous with n(H2)~2 x 10^3 cm^-3 for most molecular species but with higher values for H2CO and lower ones for SO. Measuring the CS J=1-0 transition during a time interval of more than a decade, from 2001 to 2012, the peak absorption depth of the line remains approximately constant, while the line shape undergoes notable variations. Covering the time between 1996 and 2013, CS, HCO+, and CH3OH data indicate maximal integrated optical depths in ~2001 and 2011/2012. This is compatible with a ~10 yr periodicity, which, however, needs confirmation by substantially longer time monitoring. Comparing molecular abundances with those of different types of Galactic and nearby extragalactic clouds we find that the observed cloud complex does not correspond to one particular type but to a variety of cloud types with more diffuse and denser components as can be expected for an observed region with a transverse linear scale of several parsec and a likely larger depth along the line-of-sight. A tentative detection of Galactic absorption in the c-C3H2 1(10)-1(01) line at 18.343 GHz is also reported.Comment: Accepted for publication in A&A, 11 pages, 10 figures, 4 table

The inhomogeneous ISM toward PKS 1830–211 SW: A detailed view of molecular gas at a look-back time of 7.5 Gyr

Based on measurements with the Effelsberg 100-m telescope, a multiline study of molecular species is presented toward the southwestern source of the gravitational lens system PKS 1830–211, which is by far the best known target for studying molecular gas in absorption at intermediate redshift. Determining line parameters and optical depths and performing large velocity gradient radiative transfer calculations, the aims of this study are (1) to evaluate physical parameters of the absorbing foreground gas at z ~ 0.89, in particular its homogeneity; and (2) to monitor the spectroscopic time variability caused by fluctuations in the z ~ 2.5 background continuum source. We find, that the gas is quite inhomogeneous with n(H2) ~ 2 × 103 cm-3 for most molecular species but with higher values for H2CO and lower ones for SO. Measuring the CS J = 1 ← 0 transition during a time interval of more than a decade, from 2001 to 2012, the peak absorption depth of the line remains approximately constant, while the line shape undergoes notable variations. Covering the time between 1996 and 2013, CS, HCO+, and CH3OH data indicate maximum integrated optical depths in ~2001 and 2011/2012. This is compatible with a ~10 yr periodicity, which, however, needs confirmation by substantially longer time monitoring. Comparing molecular abundances with those of different types of Galactic and nearby extragalactic clouds we find that the observed cloud complex does not correspond to one particular type but to a variety of cloud types with more diffuse and denser components as can be expected for an observed region with a transverse linear scale of several parsec and a likely greater depth along the line of sight. A tentative detection of Galactic absorption in the c-C3H2 110−101 line at 18.343 GHz is also reported

Presence of the transmembrane protein neuropilin in cytokine-induced killer cells

Background/Aim: Cytokine-induced killer (CIK) cells are a heterogenous population of immune cells showing promising applications in immunotherapeutic cancer treatment. Neuropilin (NRP) proteins have been proven to play an important role in cancer development and prognosis. In this study, CIK cells were tested for expression of NRPs, transmembrane proteins playing a role in the proliferation and survival of cancer cells. Materials and Methods: CIK cells were analyzed at different time points via flow cytometry and quantitative real-time polymerase chain reaction for neuropilin expression. Results: Phenotyping results showed CIK cells having developed properly, and low levels of NRP2 were detected. On the other hand, no NRP1 expression was found. Two cancer cell lines were tested by flow cytometry: A549 cells expressed NRP1 and NRP2; U251-MG cells expressed high amounts of NRP2. CIK cell showed low levels of NRP2 expression on day 14. Conclusion: The presence of NRP2, but not NRP1, was shown for CIK cells. Recognizing NRP2 in CIK cells might help to improve CIK cell cytotoxicity

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&

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

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

Dense gas in nearby galaxies XVI. The nuclear starburst environment in NGC4945

A multi-line millimeter-wave study of the nearby starburst galaxy NGC 4945 has been carried out using the Swedish-ESO Submillimeter Telescope (SEST). The study covers the frequency range from 82 GHz to 354 GHz and includes 80 transitions of 19 molecules. 1.3 mm continuum data of the nuclear source are also presented. A large number of molecular species indicate the presence of a prominent high density interstellar gas component characterized by $n_{\rm H_2}\sim10^5$ cm$^{-3}$. Abundances of molecular species are calculated and compared with abundances observed toward the starburst galaxies NGC 253 and M 82 and galactic sources. Apparent is an `overabundance' of HNC in the nuclear environment of NGC 4945. While the HNC/HCN $J$=1--0 line intensity ratio is $\sim$0.5, the HNC/HCN abundance ratio is $\sim$1. While HCN is subthermally excited ($T_{\rm ex}\sim$8 K), CN is even less excited ($T_{\rm ex}\sim$3--4 K), indicating that it arises from a less dense gas component and that its $N$=2--1 line can be optically thin even though its $N$=1--0 emission is moderately optically thick. Overall, fractional abundances of NGC 4945 suggest that the starburst has reached a stage of evolution that is intermediate between those observed in NGC 253 and M 82. Carbon, nitrogen, oxygen and sulfur isotope ratios are also determined. Within the limits of uncertainty, carbon and oxygen isotope ratios appear to be the same in the nuclear regions of NGC 4945 and NGC 253. High $^{18}$O/$^{17}$O, low $^{16}$O/$^{18}$O and $^{14}$N/$^{15}$N and perhaps also low $^{32}$S/$^{34}$S ratios appear to be characteristic properties of a starburst environment in which massive stars have had sufficient time to affect the isotopic composition of the surrounding interstellar medium.Comment: 26 pages, 16 figures, accepted bt A&