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

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

Characterization of the Millimeter-Wave Polarization of Centaurus A with QUaD

Centaurus (Cen) A represents one of the best candidates for an isolated, compact, highly polarized source that is bright at typical cosmic microwave background (CMB) experiment frequencies. We present measurements of the 4 degree by 2 degree region centered on Cen A with QUaD, a CMB polarimeter whose absolute polarization angle is known to 0.5 degrees. Simulations are performed to assess the effect of misestimation of the instrumental parameters on the final measurement and systematic errors due to the field's background structure and temporal variability from Cen A's nuclear region are determined. The total (Q, U) of the inner lobe region is (1.00 +/- 0.07 (stat.) +/- 0.04 (sys.), -1.72 +/- 0.06 +/- 0.05) Jy at 100 GHz and (0.80 +/- 0.06 +/- 0.06, -1.40 +/- 0.07 +/- 0.08) Jy at 150 GHz, leading to polarization angles and total errors of -30.0 +/- 1.1 degrees and -29.1 +/- 1.7 degrees. These measurements will allow the use of Cen A as a polarized calibration source for future millimeter experiments.Comment: 9 pages, 8 figures, v2 matches version published in Ap

First season QUaD CMB temperature and polarization power spectra

QUaD is a bolometric CMB polarimeter sited at the South Pole, operating at frequencies of 100 and 150 GHz. In this paper we report preliminary results from the first season of operation (austral winter 2005). All six CMB power spectra are presented derived as cross spectra between the 100 and 150 GHz maps using 67 days of observation in a low foreground region of approximately 60 deg^2. These data are a small fraction of the data acquired to date. The measured spectra are consistent with the ΛCDM cosmological model. We perform jackknife tests that indicate that the observed signal has negligible contamination from instrumental systematics. In addition, by using a frequency jackknife we find no evidence for foreground contamination

Scientific optimization of a ground-based CMB polarization experiment

We investigate the science goals achievable with the upcoming generation of ground-based Cosmic Microwave Background polarization experiments and calculate the optimal sky coverage for such an experiment including the effects of foregrounds. We find that with current technology an E-mode measurement will be sample-limited, while a B-mode measurement will be detector-noise-limited. We conclude that a 300 sq deg survey is an optimal compromise for a two-year experiment to measure both E and B-modes, and that ground-based polarization experiments can make an important contribution to B-mode surveys. Focusing on one particular experiment, QUaD, a proposed bolometric polarimeter operating from the South Pole, we find that a ground-based experiment can make a high significance measurement of the acoustic peaks in the E-mode spectrum, and will be able to detect the gravitational lensing signal in the B-mode spectrum. Such an experiment could also directly detect the gravitational wave component of the B-mode spectrum if the amplitude of the signal is close to current upper limits. We also investigate how a ground-based experiment can improve constraints on the cosmological parameters. We estimate that by combining two years of QUaD data with the four-year WMAP data, an optimized ground-based polarization experiment can improve constraints on cosmological parameters by a factor of two. If the foreground contamination can be reduced, the measurement of the tensor-to-scalar ratio can be improved by up to a factor of six over that obtainable from WMAP alone.Comment: 17 pages, 11 figures replaced with version accepted by MNRA

Signal yields, energy resolution, and recombination fluctuations in liquid xenon

This work presents an analysis of monoenergetic electronic recoil peaks in the dark-matter-search and calibration data from the first underground science run of the Large Underground Xenon (LUX) detector. Liquid xenon charge and light yields for electronic recoil energies between 5.2 and 661.7 keV are measured, as well as the energy resolution for the LUX detector at those same energies. Additionally, there is an interpretation of existing measurements and descriptions of electron-ion recombination fluctuations in liquid xenon as limiting cases of a more general liquid xenon re- combination fluctuation model. Measurements of the standard deviation of these fluctuations at monoenergetic electronic recoil peaks exhibit a linear dependence on the number of ions for energy deposits up to 661.7 keV, consistent with previous LUX measurements between 2-16 keV with $^3$H. We highlight similarities in liquid xenon recombination for electronic and nuclear recoils with a comparison of recombination fluctuations measured with low-energy calibration data.Comment: 11 pages, 12 figures, 3 table