The majority of insecticidescurrently in use are organophosphorus, carbamate, and synthetic pyrethroid compounds. Organophosphorus insecticides (OPs) produce toxicity by inhibiting the cholinesterase ...enzymes in the nervous system. Monitoring of acetylcholinesterase (AChE) inhibition has been widely used in terrestrial and freshwater aquatic systems as an indicator of OP exposure and effects. This review describes the use of AChE inhibition as a biomarker in the estuarine environment, discusses the relationship between AChE inhibition and other manifestations of OP toxicity, and highlights areas where additional research is needed. A variety of studies with estuarine fish have suggested that brain AChE inhibition levels of >70% are associated with mortality in most species. Selected species, however, appear capable of tolerating much higher levels (>90%) of brain inhibition. Sublethal effects on stamina have been reported for some estuarine fish in association with brain AChE inhibition levels as low as 50%. Most studies suggest, however, that these effects are observed only when brain AChE inhibition is at near‐lethal levels. A number of field studies have successfully used AChE inhibition in fish as a biomarker in the estuarine environment. The use of AChE inhibition as a biomarker in estuarine invertebrates has been less well studied. Although AChE inhibition has been measured in the tissues of a variety of invertebrate species following OP exposure, the relationship between AChE inhibition and lethality is less distinct. Additional work is needed in both fish and invertebrates to better explain species‐specific differences in the relationship between AChE inhibition and mortality and to investigate other physiological perturbations associated with AChE inhibition.
BACKGROUND AND AIMS: Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures. The aim of this study was to examine whether daily ...supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease. METHODS AND RESULTS: A double blind, randomised, placebo-controlled trial. Participants aged ≤ 70 years with a history of vascular disease were randomised to receive 6 months of daily oral 100mcg vitamin K2 (MK7 subtype) or matching placebo with outcomes measured at 0, 3 and 6 months. The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months. Secondary outcomes included carotid-radial pulse wave velocity, augmentation index, blood pressure, carotid intima-media thickness, C-reactive protein, B-type natriuretic peptide, cholesterol and desphospho-uncarboxylated matrix Gla protein levels. Handgrip strength and the Short Physical Performance Battery assessed physical function, while postural sway was measured using a 3-dimensional force platform. RESULTS: 80 participants were randomised, mean age 77 (SD 5) years; 44/80 were male. Vitamin K levels rose in the intervention arm compared to placebo (+48 pg/ml vs −6 pg/ml, p=0.03) at 6 months. Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months (−130 SD 117 pmol/L vs +13 SD 180 pmol/L, p<0.001). No change was seen in endothelial function (between group difference −0.3% 95%CI −1.3 to 0.8, p=0.62). A modest, non-significant improvement in pulse wave velocity was seen in the vitamin K group (−0.8m/s 95%CI −1.8 to 0.3, p=0.15) while all other vascular and physical function outcomes unchanged. CONCLUSIONS: Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease.
The Herschel Spectral and Photometric REceiver (SPIRE) instrument consists of an imaging photometric camera and an imaging Fourier Transform Spectrometer (FTS), both operating over a frequency range ...of ∼450–1550 GHz. In this paper, we briefly review the FTS design, operation, and data reduction, and describe in detail the approach taken to relative calibration (removal of instrument signatures) and absolute calibration against standard astronomical sources. The calibration scheme assumes a spatially extended source and uses the Herschel telescope as primary calibrator. Conversion from extended to point-source calibration is carried out using observations of the planet Uranus. The model of the telescope emission is shown to be accurate to within 6 per cent and repeatable to better than 0.06 per cent and, by comparison with models of Mars and Neptune, the Uranus model is shown to be accurate to within 3 per cent. Multiple observations of a number of point-like sources show that the repeatability of the calibration is better than 1 per cent, if the effects of the satellite absolute pointing error (APE) are corrected. The satellite APE leads to a decrement in the derived flux, which can be up to ∼10 per cent (1 σ) at the high-frequency end of the SPIRE range in the first part of the mission, and ∼4 per cent after Herschel operational day 1011. The lower frequency range of the SPIRE band is unaffected by this pointing error due to the larger beam size. Overall, for well-pointed, point-like sources, the absolute flux calibration is better than 6 per cent, and for extended sources where mapping is required it is better than 7 per cent.
Abstract
We present a strongly interacting quadruple system associated with the K2 target EPIC 220204960. The K2 target itself is a Kp = 12.7-mag star at Teff ≃ 6100 K, which we designate as ‘B-N’ ...(blue northerly image). The host of the quadruple system, however, is a Kp ≃ 17-mag star with a composite M-star spectrum, which we designate as ‘R-S’ (red southerly image). With a 3.2-arcsec separation and similar radial velocities and photometric distances, ‘B-N’ is likely physically associated with ‘R-S’, making this a quintuple system, but that is incidental to our main claim of a strongly interacting quadruple system in ‘R-S’. The two binaries in ‘R-S’ have orbital periods of 13.27 and 14.41 d, respectively, and each has an inclination angle of ≳89°. From our analysis of radial-velocity (RV) measurements, and of the photometric light curve, we conclude that all four stars are very similar with masses close to 0.4 M⊙. Both of the binaries exhibit significant eclipse-timing variations where those of the primary and secondary eclipses ‘diverge’ by 0.05 d over the course of the 80-d observations. Via a systematic set of numerical simulations of quadruple systems consisting of two interacting binaries, we conclude that the outer orbital period is very likely to be between 300 and 500 d. If sufficient time is devoted to RV studies of this faint target, the outer orbit should be measurable within a year.
Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), ...leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.
A systematic programme of calibration observations was carried out to monitor the performance of the Spectral and Photometric Imaging REceiver (SPIRE) Fourier Transform Spectrometer (FTS) instrument ...on board the Herschel Space Observatory. Observations of planets (including the prime point-source calibrator, Uranus), asteroids, line sources, dark sky and cross-calibration sources were made in order to monitor repeatability and sensitivity, and to improve FTS calibration. We present a complete analysis of the full set of calibration observations and use them to assess the performance of the FTS. Particular care is taken to understand and separate out the effect of pointing uncertainties, including the position of the internal beam steering mirror for sparse observations in the early part of the mission. The repeatability of spectral-line centre positions is <5 km s−1, for lines with signal-to-noise ratios >40, corresponding to <0.5–2.0 per cent of a resolution element. For spectral-line flux, the repeatability is better than 6 per cent, which improves to 1–2 per cent for spectra corrected for pointing offsets. The continuum repeatability is 4.4 per cent for the SPIRE Long Wavelength spectrometer (SLW) band and 13.6 per cent for the SPIRE Short Wavelength spectrometer (SSW) band, which reduces to ∼1 per cent once the data have been corrected for pointing offsets. Observations of dark sky were used to assess the sensitivity and the systematic offset in the continuum, both of which were found to be consistent across the FTS-detector arrays. The average point-source calibrated sensitivity for the centre detectors is 0.20 and 0.21 Jy 1σ; 1 h, for SLW and SSW. The average continuum offset is 0.40 Jy for the SLW band and 0.28 Jy for the SSW band.
We present the discovery of HD 221416 b, the first transiting planet identified by the Transiting Exoplanet Survey Satellite (TESS) for which asteroseismology of the host star is possible. HD 221416 ...b (HIP 116158, TOI-197) is a bright (V = 8.2 mag), spectroscopically classified subgiant that oscillates with an average frequency of about 430 Hz and displays a clear signature of mixed modes. The oscillation amplitude confirms that the redder TESS bandpass compared to Kepler has a small effect on the oscillations, supporting the expected yield of thousands of solar-like oscillators with TESS 2 minute cadence observations. Asteroseismic modeling yields a robust determination of the host star radius (R = 2.943 0.064 R ), mass (M = 1.212 0.074 M ), and age (4.9 1.1 Gyr), and demonstrates that it has just started ascending the red-giant branch. Combining asteroseismology with transit modeling and radial-velocity observations, we show that the planet is a "hot Saturn" (Rp = 9.17 0.33 R⊕) with an orbital period of ∼14.3 days, irradiance of F = 343 24 F⊕, and moderate mass (Mp = 60.5 5.7 M⊕) and density ( p = 0.431 0.062 g cm−3). The properties of HD 221416 b show that the host-star metallicity-planet mass correlation found in sub-Saturns (4-8 R⊕) does not extend to larger radii, indicating that planets in the transition between sub-Saturns and Jupiters follow a relatively narrow range of densities. With a density measured to ∼15%, HD 221416 b is one of the best characterized Saturn-size planets to date, augmenting the small number of known transiting planets around evolved stars and demonstrating the power of TESS to characterize exoplanets and their host stars using asteroseismology.
Genome Project Standards in a New Era of Sequencing Chain, P. S. G.; Grafham, D. V.; Fulton, R. S. ...
Science (American Association for the Advancement of Science),
10/2009, Letnik:
326, Številka:
5950
Journal Article
Recenzirano
Odprti dostop
More detailed sequence standards that keep up with revolutionary sequencing technologies will aid the research community in evaluating data.
For over a decade, genome sequences have adhered to only ...two standards that are relied on for purposes of sequence analysis by interested third parties (
1
,
2
). However, ongoing developments in revolutionary sequencing technologies have resulted in a redefinition of traditional whole-genome sequencing that requires reevaluation of such standards. With commercially available 454 pyrosequencing (followed by Illumina, SOLiD, and now Helicos), there has been an explosion of genomes sequenced under the moniker “draft”; however, these can be very poor quality genomes (due to inherent errors in the sequencing technologies, and the inability of assembly programs to fully address these errors). Further, one can only infer that such draft genomes may be of poor quality by navigating through the databases to find the number and type of reads deposited in sequence trace repositories (and not all genomes have this available), or to identify the number of contigs or genome fragments deposited to the database. The difficulty in assessing the quality of such deposited genomes has created some havoc for genome analysis pipelines and has contributed to many wasted hours. Exponential leaps in raw sequencing capability and greatly reduced prices have further skewed the time- and cost-ratios of draft data generation versus the painstaking process of improving and finishing a genome. The result is an ever-widening gap between drafted and finished genomes that only promises to continue (see the figure, page 236); hence, there is an urgent need to distinguish good from poor data sets.
It is important to explore the diversity of characteristics of low-mass, low-density planets to understand the nature and evolution of this class of planets. We present a homogeneous analysis of 12 ...new and 9 previously published broad-band photometric observations of the Uranus-sized extrasolar planet GJ 3470b, which belongs to the growing sample of sub-Jovian bodies orbiting M dwarfs. The consistency of our analysis explains some of the discrepancies between previously published results and provides updated constraints on the planetary parameters. Our data are also consistent with previous transit observations of this system. The physical properties of the transiting system can only be constrained as well as the host star is characterized, so we provide new spectroscopic measurements of GJ 3470 from 0.33 to 2.42 μm to aid our analysis. We find R
* = 0.48 ± 0.04 R⊙, M
* = 0.51 ± 0.06 M⊙, and T
eff = 3652 ± 50K for GJ 3470, along with a rotation period of 20.70 ± 0.15 d and an R-band amplitude of 0.01 mag, which is small enough that current transit measurements should not be strongly affected by stellar variability. However, to report definitively whether stellar activity has a significant effect on the light curves, this requires future multiwavelength, multi-epoch studies of GJ 3470. We also present the most precise orbital ephemeris for this system: T
o
= 2455983.70472 ± 0.00021BJDTDB, P = 3.336 6487
$^{+0.000\,0043}_{-0.000\,0033}$
d, and we see no evidence for transit timing variations greater than 1 min. Our reported planet to star radius ratio is 0.076 42 ± 0.000 37. The physical parameters of this planet are R
p = 3.88 ± 0.32 R⊕ and M
p = 13.73 ± 1.61 M⊕. Because of our revised stellar parameters, the planetary radius we present is smaller than previously reported values. We also perform a second analysis of the transmission spectrum of the entire ensemble of transit observations to date, supporting the existence of an H2-dominated atmosphere exhibiting a strong Rayleigh scattering slope.
PDF
