2,217 research outputs found

    Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival

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    MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over-or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics

    An Absolute Flux Density Measurement of the Supernova Remnant Casseopia A at 32 GHz

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    We report 32 GHz absolute flux density measurements of the supernova remnant Cas A, with an accuracy of 2.5%. The measurements were made with the 1.5-meter telescope at the Owens Valley Radio Observatory. The antenna gain had been measured by NIST in May 1990 to be 0.505±0.007mKJy0.505 \pm 0.007 \frac{{\rm mK}}{{\rm Jy}}. Our observations of Cas A in May 1998 yield Scas,1998=194±5JyS_{cas,1998} = 194 \pm 5 {\rm Jy}. We also report absolute flux density measurements of 3C48, 3C147, 3C286, Jupiter, Saturn and Mars.Comment: 30 pages, 4 figures; accepted for publication by AJ. Revised systematic error budget, corrected typos, and added reference

    Marine latitude/altitude OH distributions: Comparison of Pacific Ocean observations with models

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    Reported here are tropical/subtropical Pacific basin OH observational data presented in a latitude/altitude geographical grid. They cover two seasons of the year (spring and fall) that reflect the timing of NASA's PEM-Tropics A (1996) and B (1999) field programs. Two different OH sensors were used to collect these data, and each instrument was mounted on a different aircraft platform (i.e., NASA's P-3B and DC-8). Collectively, these chemical snapshots of the central Pacific have revealed several interesting trends. Only modest decreases (factors of 2 to 3) were found in the levels of OH with increasing altitude (0-12 km). Similarly, only modest variations were found (factors of 1.5 to 3.5) when the data were examined as a function of latitude (30° N to 30° S). Using simultaneously recorded data for CO, O3, H2O, NO, and NMHCs, comparisons with current models were also carried out. For three out of four data subsets, the results revealed a high level of correspondence. On average, the box model results agreed with the observations within a factor of 1.5. The comparison with the three-dimensional model results was found to be only slightly worse. Overall, these results suggest that current model mechanisms capture the major photochemical processes controlling OH quite well and thus provide a reasonably good representation of OH levels for tropical marine environments. They also indicate that the two OH sensors employed during the PEM-Tropics B study generally saw similar OH levels when sampling a similar tropical marine environment. However, a modest altitude bias appears to exist between these instruments. More rigorous instrument intercomparison activity would therefore seem to be justified. Further comparisons of model predictions with observations are also recommended for nontropical marine environments as well as those involving highly elevated levels of reactive non-methane hydrocarbons. Copyright 2001 by the American Geophysical Union

    Can Protostellar Jets Drive Supersonic Turbulence in Molecular Clouds?

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    Jets and outflows from young stellar objects are proposed candidates to drive supersonic turbulence in molecular clouds. Here, we present the results from multi-dimensional jet simulations where we investigate in detail the energy and momentum deposition from jets into their surrounding environment and quantify the character of the excited turbulence with velocity probability density functions. Our study include jet--clump interaction, transient jets, and magnetised jets. We find that collimated supersonic jets do not excite supersonic motions far from the vicinity of the jet. Supersonic fluctuations are damped quickly and do not spread into the parent cloud. Instead subsonic, non-compressional modes occupy most of the excited volume. This is a generic feature which can not be fully circumvented by overdense jets or magnetic fields. Nevertheless, jets are able to leave strong imprints in their cloud structure and can disrupt dense clumps. Our results question the ability of collimated jets to sustain supersonic turbulence in molecular clouds.Comment: 33 pages, 18 figures, accepted by ApJ, version with high resolution figures at: http://www.ita.uni-heidelberg.de/~banerjee/publications/jet_paper.pd

    Chandra and XMM-Newton observations of the merging cluster of galaxies PLCK G036.7+14.9

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    We present Chandra and XMM-Newton observations of PLCK G036.7+14.9 from the Chandra-Planck Legacy Program. The high resolution X-ray observations reveal two close subclusters, G036N and G036S, which were not resolved by previous ROSAT, optical, or recent Planck observations. We perform detailed imaging and spectral analyses and use a simplified model to study the kinematics of this system. The basic picture is that PLCK G036.7+14.9 is undergoing a major merger (mass ratio close to unity) between the two massive subclusters, with the merger largely along the line-of-sight and probably at an early stage. G036N hosts a small, moderate cool-core, while G036S has at most a very weak cool-core in the central 40 kpc region. The difference in core cooling times is unlikely to be caused by the ongoing merger disrupting a pre-existing cool-core in G036S. G036N also hosts an unresolved radio source in the center, which may be heating the gas if the radio source is extended. The Planck derived mass is higher than the X-ray measured mass of either subcluster, but is lower than the X-ray measured mass of the whole cluster, due to the fact that Planck does not resolve PLCK G036.7+14.9 into subclusters and interprets it as a single cluster. This mass discrepancy could induce significant bias to the mass function if such previously unresolved systems are common in the Planck cluster sample. High resolution X-ray observations are necessary to identify the fraction of such systems and correct such a bias for the purpose of precision cosmological studies.Comment: 23 pages, 8 figures (low resolution) with additional 12 figures in the Appendix, accepted for publication in Ap
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