253 research outputs found
The particle-in-cell model for ab initio thermodynamics: implications for the elastic anisotropy of the Earth's inner core
We assess the quantitative accuracy of the particle-in-cell (PIC)
approximation used in recent ab initio predictions of the thermodynamic
properties of hexagonal-close-packed iron at the conditions of the Earth's
inner core. The assessment is made by comparing PIC predictions for a range of
thermodynamic properties with the results of more exact calculations that avoid
the PIC approximation. It is shown that PIC gives very accurate results for
some properties, but that it gives an incorrect treatment of anharmonic lattice
vibrations. In addition, our assessment does not support recent PIC-based
predictions that the hexagonal c/a ratio increases strongly with increasing
temperature, and we point out that this casts doubt on a proposed
re-interpretation of the elastic anisotropy of the inner core.Comment: 25 pages, 9 figures, submitted to Physics of the Earth and Planetary
Interior
The axial ratio of hcp iron at the conditions of the Earth's inner core
We present ab initio calculations of the high-temperature axial c/a ratio of
hexagonal-close-packed (hcp) iron at Earth's core pressures, in order to help
interpret the observed seismic anisotropy of the inner core. The calculations
are based on density functional theory, which is known to predict the
properties of high-pressure iron with good accuracy. The temperature dependence
of c/a is determined by minimising the Helmholtz free energy at fixed volume
and temperature, with thermal contributions due to lattice vibrations
calculated using harmonic theory. Anharmonic corrections to the harmonic
predictions are estimated from calculations of the thermal average stress
obtained from ab initio molecular dynamics simulations of hcp iron at the
conditions of the inner core. We find a very gradual increase of axial ratio
with temperature. This increase is much smaller than found in earlier
calculations, but is in reasonable agreement with recent high-pressure,
high-temperature diffraction measurements. This result casts doubt on an
earlier interpretation of the seismic anisotropy of the inner core
Clinical and molecular characterization of HER2 amplified-pancreatic cancer
<p>Background:
Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p>
<p>Methods:
HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p>
<p>Results:
An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p>
<p>Conclusions:
HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p>
The rms-flux relations in different branches in Cyg X-2
In this paper, the rms-flux (root mean square-flux) relation along the
Z-track of the bright Z-Source Cyg X-2 is analyzed using the observational data
of Rossi X-ray Timing Explorer (RXTE). Three types of rms-flux relations, i.e.
positive, negative, and 'arch'-like correlations are found in different
branches. The rms is positively correlated with flux in normal branch (NB), but
anti-correlated in the vertical horizontal branch (VHB). The rms-flux relation
shows an 'arch'-like shape in the horizontal branch (HB). We also try to
explain this phenomenon using existing models.Comment: Accepted for publication in Astrophysics & Space Scienc
ZFOURGE catalogue of AGN candidates: an enhancement of 160-Όm-derived star formation rates in active galaxies to z  = 3.2
We investigate active galactic nuclei (AGN) candidates within the FourStar Galaxy Evolution Survey (ZFOURGE) to determine the impact they have on star formation in their host galaxies. We first identify a population of radio, X-ray, and infrared-selected AGN by cross-matching the deep Ks-band imaging of ZFOURGE with overlapping multiwavelength data. From this, we construct a mass-complete (log(Mâ/MâMâ/Mâ) â„9.75), AGN luminosity limited sample of 235 AGN hosts over z = 0.2â3.2. We compare the rest-frame U â V versus V â J (UVJ) colours and specific star formation rates (sSFRs) of the AGN hosts to a mass-matched control sample of inactive (non-AGN) galaxies. UVJ diagnostics reveal AGN tend to be hosted in a lower fraction of quiescent galaxies and a higher fraction of dusty galaxies than the control sample. Using 160 ÎŒm Herschel PACS data, we find the mean specific star formation rate of AGN hosts to be elevated by 0.34 ± 0.07 dex with respect to the control sample across all redshifts. This offset is primarily driven by infrared-selected AGN, where the mean sSFR is found to be elevated by as much as a factor of âŒ5. The remaining population, comprised predominantly of X-ray AGN hosts, is found mostly consistent with inactive galaxies, exhibiting only a marginal elevation. We discuss scenarios that may explain these findings and postulate that AGN are less likely to be a dominant mechanism for moderating galaxy growth via quenching than has previously been suggested
Neutron scattering search for static magnetism in oxygen ordered YBa2Cu3O6.5
We present elastic and inelastic neutron scattering results on highly oxygen
ordered YBa2Cu3O6.5 ortho-II. We find no evidence for the presence of ordered
magnetic moments to a sensitivity of 0.003 Bohr magnetons, an order of
magnitude smaller than has been suggested in theories of orbital or
d-density-wave (DDW) currents. The absence of sharp elastic peaks, shows that
the d-density-wave phase is not present, at least for the superconductor with
the doping of 6.5 and the ordered ortho-II structure. We cannot exclude the
possibility that a broad peak may exist with extremely short-range DDW
correlations. For less ordered or more doped crystals it is possible that
disorder may lead to static magnetism. We have also searched for the large
normal state spin gap that is predicted to exist in an ordered DDW phase.
Instead of a gap we find that the Q-correlated spin susceptibility persists to
the lowest energies studied, 6 meV. Our results are compatible with the
coexistence of superconductivity with orbital currents, but only if they are
dynamic, and exclude a sharp phase transition to an ordered d-density-wave
phase.Comment: 6 pages 4 figures RevTex Submitted to Phys Rev B January 23, 200
Rascall: Rapid (Ra) screening (Sc) of RNA-seq data for prognostically significant genomic alterations in acute lymphoblastic leukaemia (ALL)
RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, integrating RNA-seq in a clinical setting requires rapid detection and accurate reporting of clinically relevant alterations. Here we present RaScALL, an implementation of the k-mer based variant detection tool km, capable of identifying more than 100 prognostically significant lesions observed in ALL, including gene fusions, single nucleotide variants and focal gene deletions. We compared genomic alterations detected by RaScALL and those reported by alignment-based de novo variant detection tools in a study cohort of 180 Australian patient samples. Results were validated using 100 patient samples from a published North American cohort. RaScALL demonstrated a high degree of accuracy for reporting subtype defining genomic alterations. Gene fusions, including difficult to detect fusions involving EPOR and DUX4, were accurately identified in 98% of reported cases in the study cohort (n = 164) and 95% of samples (n = 63) in the validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants PAX5 p.P80R (n = 12) and IKZF1 p.N159Y (n = 4). Intragenic IKZF1 deletions resulting in aberrant transcript isoforms were also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches. The application of RaScALL enables rapid identification and reporting of previously identified genomic alterations of known clinical relevance.Jacqueline Rehn, Chelsea Mayoh, Susan L Heatley, Barbara J McClure, Laura N Eadie, Caitlin Schutz, David T Yeung, Mark J Cowley, James Breen, Deborah L Whit
The SCUBA-2 Cosmology Legacy Survey: ALMA resolves the bright-end of the submillimeter number counts
We present high-resolution 870 ÎŒm Atacama Large Millimeter/sub-millimeter Array (ALMA) continuum maps of 30 bright sub-millimeter sources in the UKIDSS UDS field. These sources are selected from deep, 1 degree2 850 ÎŒm maps from the SCUBA-2 Cosmology Legacy Survey, and are representative of the brightest sources in the field (median = 8.7 ± 0.4 mJy). We detect 52 sub-millimeter galaxies (SMGs) at >4Ï significance in our 30 ALMA maps. In of the ALMA maps the single-dish source comprises a blend of â„2 SMGs, where the secondary SMGs are Ultra-luminous Infrared Galaxies (ULIRGs) with 1012 . The brightest SMG contributes on average of the single-dish flux density, and in the ALMA maps containing â„2 SMGs the secondary SMG contributes of the integrated ALMA flux. We construct source counts and show that multiplicity boosts the apparent single-dish cumulative counts by 20% at S870 > 7.5 mJy, and by 60% at S870 > 12 mJy. We combine our sample with previous ALMA studies of fainter SMGs and show that the counts are well-described by a double power law with a break at 8.5 ± 0.6 mJy. The break corresponds to a luminosity of ~6 Ă 1012 or a star formation rate (SFR) of ~103 . For the typical sizes of these SMGs, which are resolved in our ALMA data with = 1.2 ± 0.1 kpc, this yields a limiting SFR density of ~100 yrâ1 kpcâ2 Finally, the number density of S870 2 mJy SMGs is 80 ± 30 times higher than that derived from blank-field counts. An over-abundance of faint SMGs is inconsistent with line-of-sight projections dominating multiplicity in the brightest SMGs, and indicates that a significant proportion of these high-redshift ULIRGs are likely to be physically associated
Introme accurately predicts the impact of coding and noncoding variants on gene splicing, with clinical applications
Predicting the impact of coding and noncoding variants on splicing is challenging, particularly in non-canonical splice sites, leading to missed diagnoses in patients. Existing splice prediction tools are complementary but knowing which to use for each splicing context remains difficult. Here, we describe Introme, which uses machine learning to integrate predictions from several splice detection tools, additional splicing rules, and gene architecture features to comprehensively evaluate the likelihood of a variant impacting splicing. Through extensive benchmarking across 21,000 splice-altering variants, Introme outperformed all tools (auPRC: 0.98) for the detection of clinically significant splice variants. Introme is available at https://github.com/CCICB/introme .Patricia J. Sullivan, Velimir Gayevskiy, Ryan L. Davis, Marie Wong, Chelsea Mayoh, Amali Mallawaarachchi, Yvonne Hort, Mark J. McCabe, Sarah Beecroft, Matilda R. Jackson, Peer Arts, Andrew Dubowsky, Nigel Laing, Marcel E. Dinger, Hamish S. Scott, Emily Oates, Mark Pinese, and Mark J. Cowle
A Binary Lensing Event Toward the LMC: Observations and Dark Matter Implications
The MACHO collaboration has recently analyzed 2.1 years of photometric data
for about 8.5 million stars in the Large Magellanic Cloud (LMC). This analysis
has revealed 8 candidate microlensing events and a total microlensing optical
depth of . This significantly
exceeds the number of events (1.1) and the microlensing optical depth predicted
from known stellar populations: , but it is
consistent with models in which about half of the standard dark halo mass is
composed of Machos of mass \sim 0.5 \msun. One of these 8 events appears to
be a binary lensing event with a caustic crossing that is partially resolved
which allows us to estimate the distance to the lenses. If the source star is
not a short period binary star, then we show that the lens system is very
likely to reside in the LMC. However, if we assume that the optical depth for
LMC-LMC lensing is large enough to account for our entire lensing signal, then
the binary event does not appear to be consistent with lensing of a single LMC
source star by a binary residing in the LMC. Thus, while the binary lens may
indeed reside in the LMC, there is no indication that most of the lenses reside
in the LMC.Comment: 5 pages, 3 postscript figures included; To appear in the Proceedings
of the Dark Matter '96 Conference held in Santa Monica, CA, Feb., 199
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