160 research outputs found
The TRENDS High-Contrast Imaging Survey. VI. Discovery of a Mass, Age, and Metallicity Benchmark Brown Dwarf
The mass and age of substellar objects are degenerate parameters leaving the
evolutionary state of brown dwarfs ambiguous without additional information.
Theoretical models are normally used to help distinguish between old, massive
brown dwarfs and young, low mass brown dwarfs but these models have yet to be
properly calibrated. We have carried out an infrared high-contrast imaging
program with the goal of detecting substellar objects as companions to nearby
stars to help break degeneracies in inferred physical properties such as mass,
age, and composition. Rather than using imaging observations alone, our targets
are pre-selected based on the existence of dynamical accelerations informed
from years of stellar radial velocity (RV) measurements. In this paper, we
present the discovery of a rare benchmark brown dwarf orbiting the nearby
( pc), solar-type (G9V) star HD 4747 ([Fe/H]=)
with a projected separation of only AU (
0.6"). Precise Doppler measurements taken over 18 years reveal the companion's
orbit and allow us to place strong constraints on its mass using dynamics (). Relative photometry (,
, ) indicates that HD 4747 B is
most-likely a late-type L-dwarf and, if near the L/T transition, an intriguing
source for studying cloud physics, variability, and polarization. We estimate a
model-dependent mass of for an age of
Gyr based on gyrochronology. Combining astrometric measurements with RV data,
we calculate the companion dynamical mass () and orbit
() directly. As a new mass, age, and metallicity benchmark, HD
4747 B will serve as a laboratory for precision astrophysics to test
theoretical models that describe the emergent radiation of brown dwarfs.Comment: Accepted to Ap
Evidence for the Direct Detection of the Thermal Spectrum of the Non-Transiting Hot Gas Giant HD 88133 b
We target the thermal emission spectrum of the non-transiting gas giant HD
88133 b with high-resolution near-infrared spectroscopy, by treating the planet
and its host star as a spectroscopic binary. For sufficiently deep summed flux
observations of the star and planet across multiple epochs, it is possible to
resolve the signal of the hot gas giant's atmosphere compared to the brighter
stellar spectrum, at a level consistent with the aggregate shot noise of the
full data set. To do this, we first perform a principal component analysis to
remove the contribution of the Earth's atmosphere to the observed spectra.
Then, we use a cross-correlation analysis to tease out the spectra of the host
star and HD 88133 b to determine its orbit and identify key sources of
atmospheric opacity. In total, six epochs of Keck NIRSPEC L band observations
and three epochs of Keck NIRSPEC K band observations of the HD 88133 system
were obtained. Based on an analysis of the maximum likelihood curves calculated
from the multi-epoch cross correlation of the full data set with two
atmospheric models, we report the direct detection of the emission spectrum of
the non-transiting exoplanet HD 88133 b and measure a radial projection of the
Keplerian orbital velocity of 40 15 km/s, a true mass of
1.02, a nearly face-on orbital inclination of
15, and an atmosphere opacity structure at high
dispersion dominated by water vapor. This, combined with eleven years of radial
velocity measurements of the system, provides the most up-to-date ephemeris for
HD 88133.Comment: 9 pages, 6 figures; accepted for publication in Ap
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Exploratory Analysis of Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study
Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP).
We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson = 0.59, 32 cm, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54) compared with a median time to nadir of 84 d (IQR 42-116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07-0.67, = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%-92%) and 88% specificity (95% CI 64%-99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort.
In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.This work was supported by Cancer Research UK Grant numbers: A15601 (JDB), A11906 (NR), A20240 (NR), A18072 (JDB). JDB was supported by the National Institute for Health Research Cambridge Biomedical Research Centre. CAP was supported in part by the Academy of Medical Sciences, the Wellcome Trust, British Heart Foundation and Arthritis Research UK
Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in theJAK3gene
High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene wasTP53(97% mutation frequency) followed byBRCA1(10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, afterBRCA1,JAK3was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-basedin vitrofunctional assay and identified a novel gain-of-function mutation in the kinase domain ofJAK3(p.T1022I). Importantly, p.T1022IJAK3mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entireJAK3coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening ofCDK12in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency ofJAK3andCDK12mutations in a large well characterized cohort. Although p.T1022IJAK3mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation ofCDK12mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency.ISSN:1932-620
RADIAL VELOCITY MONITORING OFKEPLERHEARTBEAT STARS
Heartbeat stars (HB stars) are a class of eccentric binary stars with close periastron passages. The characteristic photometric HB signal evident in their light curves is produced by a combination of tidal distortion, heating, and Doppler boosting near orbital periastron. Many HB stars continue to oscillate after periastron and along the entire orbit, indicative of the tidal excitation of oscillation modes within one or both stars. These systems are among the most eccentric binaries known, and they constitute astrophysical laboratories for the study of tidal effects. We have undertaken a radial velocity (RV) monitoring campaign of Kepler HB stars in order to measure their orbits. We present our first results here, including a sample of 22 Kepler HB systems, where for 19 of them we obtained the
Keplerian orbit and for 3 other systems we did not detect a statistically significant RV variability. Results presented here are based on 218 spectra obtained with the Keck/HIRES spectrograph during the 2015 Kepler observing season, and they have allowed us to obtain the largest sample of HB stars with orbits measured using a single instrument, which roughly doubles the number of HB stars with an RV measured orbit. The 19 systems measured here have orbital periods from 7 to 90 days and eccentricities from 0.2 to 0.9. We show that HB stars draw the upper envelope of the eccentricity–period distribution. Therefore, HB stars likely represent a population of stars currently undergoing high eccentricity migration via tidal orbital circularization, and they will allow for new tests
of high eccentricity migration theories
Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.
BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA. RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 μg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients. CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs
Evidence for the Direct Detection of the Thermal Spectrum of the Non-Transiting Hot Gas Giant HD 88133 b
We target the thermal emission spectrum of the non-transiting gas giant HD 88133 b with high-resolution near-infrared spectroscopy, by treating the planet and its host star as a spectroscopic binary. For sufficiently deep summed flux observations of the star and planet across multiple epochs, it is possible to resolve the signal of the hot gas giant's atmosphere compared to the brighter stellar spectrum, at a level consistent with the aggregate shot noise of the full data set. To do this, we first perform a principal component analysis to remove the contribution of the Earth's atmosphere to the observed spectra. Then, we use a cross-correlation analysis to tease out the spectra of the host star and HD 88133 b to determine its orbit and identify key sources of atmospheric opacity. In total, six epochs of Keck NIRSPEC L-band observations and three epochs of Keck NIRSPEC K-band observations of the HD 88133 system were obtained. Based on an analysis of the maximum likelihood curves calculated from the multi-epoch cross-correlation of the full data set with two atmospheric models, we report the direct detection of the emission spectrum of the non-transiting exoplanet HD 88133 b and measure a radial projection of the Keplerian orbital velocity of 40 ± 15 km s^(−1), a true mass of 1.02^(+0.61)_(-0.28)M_J, a nearly face-on orbital inclination of 15^(+6o)_(-5), and an atmosphere opacity structure at high dispersion dominated by water vapor. This, combined with 11 years of radial velocity measurements of the system, provides the most up-to-date ephemeris for HD 88133
Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene
We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8x10(-3)). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin. We estimated mutation prevalence for each gene and tested for associations with disease risk. Mutations were identified in both cases and controls in all genes except MAD2L2, where we found no evidence of mutations in controls. In FANCM we observed a higher mutation frequency in HGSOC cases compared to controls (29/3,107 cases, 0.96 percent; 13/3,368 controls, 0.38 percent; P = 0.008) with little evidence for association with other subtypes (6/1,491, 0.40 percent; P = 0.82). The relative risk of HGSOC associated with deleterious FANCM mutations was estimated to be 2.5 (95% CI 1.3 - 5.0; P = 0.006). In summary, whole exome sequencing of EOC cases with large-scale replication in case-control studies has identified FANCM as a likely novel susceptibility gene for HGSOC, with mutations associated with a moderate increase in risk. These data may have clinical implications for risk prediction and prevention approaches for high-grade serous ovarian cancer in the future and a significant impact on reducing disease mortality
New System for the Acceleration of the Airflow in Wind Turbines
Background: This patent is based on the wind industry technology called Diffuser Augmented Wind Turbines (DAWTs). This technology consists of a horizontal axis wind turbine, which is housed inside a duct with diverging section in the direction of the free air stream. In this paper, a review of preceding patents related to this technology is carried out.
Objective: This paper presents an innovative patent to improve the performance of horizontal axis wind turbines. In particular, this system is aimed at improving the performance of those turbines that otherwise might not be installed due to the low wind resource existing at certain locations.
Methods: The most innovative elements of this patent are: (1) the semi-spherical grooves, which are mechanized on the surface of the two diffusers in order to guarantee a more energetic boundary layer; (2) the coaxial diffuser, which is located downwind following the first diffuser in order to increase the suction effect on the air mass close to the inlet; (3) the coaxial rings located around the first diffuser outlet, which are used to deflect the external airflow toward the turbine wake; and (4), the selforientating system to orientate the system by the prevailing wind direction.
Results: An application of the patent for increasing the power generated by a horizontal axis wind turbine with three blades is presented. The patent is designed and its performance is evaluated by using a Computational Fluid Dynamics code. The numerical results show that this system rises the airflow going through the rotor of the turbine.
Conclusion: The patented device is an original contribution aimed at enabling a more profitable installation of wind turbines in places where the wind resource is insufficient because of the wind shear caused both by the proximity of the earth and the obstacles on the earth surface.This work was supported by the OASIS Research Project that was cofinanced by CDTI (Spanish Science and Innovation Ministry) and developed with the Spanish companies: Iridium, OHL Concesiones, Abertis, Sice, Indra, Dragados, OHL, Geocisa, GMV, Asfaltos Augusta, Hidrofersa, Eipsa, PyG, CPS, AEC and Torre de Comares Arquitectos S.L and 16 research centres. The authors also acknowledge the partial funding with FEDER funds under the Research Project FC-15-GRUPIN14-004. Finally, we also thank Swanson Analysis Inc. for the use of ANSYS University Research programs as well as the Workbench simulation environment
Populations of planets in multiple star systems
Astronomers have discovered that both planets and binaries are abundant
throughout the Galaxy. In combination, we know of over 100 planets in binary
and higher-order multi-star systems, in both circumbinary and circumstellar
configurations. In this chapter we review these findings and some of their
implications for the formation of both stars and planets. Most of the planets
found have been circumstellar, where there is seemingly a ruinous influence of
the second star if sufficiently close (<50 AU). Hosts of hot Jupiters have been
a particularly popular target for binary star studies, showing an enhanced rate
of stellar multiplicity for moderately wide binaries (>100 AU). This was
thought to be a sign of Kozai-Lidov migration, however recent studies have
shown this mechanism to be too inefficient to account for the majority of hot
Jupiters. A couple of dozen circumbinary planets have been proposed around both
main sequence and evolved binaries. Around main sequence binaries there are
preliminary indications that the frequency of gas giants is as high as those
around single stars. There is however a conspicuous absence of circumbinary
planets around the tightest main sequence binaries with periods of just a few
days, suggesting a unique, more disruptive formation history of such close
stellar pairs.Comment: Invited review chapter, accepted for publication in "Handbook of
Exoplanets", ed. H. Deeg & J. A. Belmont
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