We present observations of the possible short GRB 180418A in γ-rays, X-rays, and in the optical. Early optical photometry with the TAROT and RATIR instruments shows a bright peak ( 14.2 AB mag) ...between T + 28 and T + 90 s that we interpret as the signature of a reverse shock. Later observations can be modeled by a standard forward shock model and show no evidence of a jet break, allowing us to constrain the jet collimation to θj > 7°. Using deep late-time optical observations, we place an upper limit of r > 24 AB mag on any underlying host galaxy. The detection of the afterglow in the Swift UV filters constrains the GRB redshift to z < 1.3 and places an upper bound on the γ-ray isotropic equivalent energy Eγ,iso < 3 × 1051 erg. The properties of this GRB (e.g., duration, hardness ratio, energy, and environment) lie at the intersection between short and long bursts, and we cannot conclusively identify its type. We estimate that the probability that it is drawn from the population of short GRBs is 10%-30%.
ABSTRACT
We derive limits on any electromagnetic counterpart to the compact binary merger S190814bv, whose parameters are consistent with the merger of a black hole and a neutron star. We present ...observations with the new wide-field optical imager DDOTI and also consider Swift/BAT observations reported by Palmer et al. We show that Swift/BAT would have detected a counterpart with similar properties to a typical on-axis short GRB at the 98 per cent confidence level, whereas our DDOTI observations only rule out such a counterpart at the 27 per cent confidence level. Neither has sufficient sensitivity to rule out an off-axis counterpart like GW 170817. We compare the efficiency of Swift/BAT and DDOTI for future observations, and show that DDOTI is likely to be about twice as efficient as Swift/BAT for off-axis events up to about 100 Mpc.
Increasing the intensity to which high power laser pulses are focused has opened up new research possibilities, including promising new approaches to particle acceleration and phenomena such as high ...field quantum electrodynamics. Whilst the intensity achievable with a laser pulse of a given power can be increased via tighter focusing, the focal spot profile also plays an important role in the interaction physics. Here we show that the spatial-intensity distribution, and specifically the ratio of the intensity in the peak of the laser focal spot to the halo surrounding it, is important in the interaction of ultraintense laser pulses with solid targets. By comparing proton acceleration measurements from foil targets irradiated with by a near-diffraction-limited wavelength scale focal spot and larger F-number focusing, we find that this spatial-intensity contrast parameter strongly influences laser energy coupling to fast electrons. We find that for multi-petawatt pulses, spatial-intensity contrast is potentially as important as temporal-intensity contrast.
The objective of this study was to compare circulating progesterone (P4) profiles and pregnancies per AI (P/AI) in lactating dairy cows bred by timed artificial insemination (TAI) following ...Ovsynch-56 after 2 different presynchronization protocols: Double-Ovsynch (DO) or Presynch-Ovsynch (PS). Our main hypothesis was that DO would increase fertility in primiparous cows, but not in multiparous cows. Within each herd (n=3), lactating dairy cows (n=1,687; 778 primiparous, 909 multiparous) were randomly assigned to DO n=837; GnRH-7d-PGF2α-3d-GnRH-7d-Ovsynch-56 (GnRH-7d-PGF2α-56h-GnRH-16hTAI) or PS (n=850; PGF2α-14d-PGF2α-12d-Ovsynch-56). In 1 herd, concentrations of P4 were determined at the first GnRH (GnRH1) of Ovsynch-56 and at d 11 after TAI (n=739). In all herds, pregnancy was diagnosed by palpation per rectum at 39 d. In 1 herd, the incidence of late embryo loss was determined at 74d, and data were available on P/AI at the subsequent second service. Presynchronization with DO reduced the percentage of animals with low P4 concentrations (<0.50ng/mL) at GnRH1 of Ovsynch-56 (5.4 vs. 25.3%, DO vs. PS). A lesser percentage of both primiparous and multiparous cows treated with DO had low P4 concentrations at GnRH1 of Ovsynch-56 (3.3 vs. 19.7%, DO vs. PS primiparous; and 8.8 vs. 31.9%, DO vs. PS multiparous). Presynchronization with DO improved P/AI at the first postpartum service (46.3 vs. 38.2%, DO vs. PS). Statistically, a fertility improvement could be detected for primiparous cows treated with DO (52.5 vs. 42.3%, DO vs. PS, primiparous), but only a tendency could be detected in multiparous cows (40.3 vs. 34.3%, DO vs. PS, multiparous), consistent with our original hypothesis. Presynchronization treatment had no effect on the incidence of late embryo loss after first service (8.5 vs. 5.5%, DO vs. PS). A lower body condition score increased the percentage of cows with low P4 at GnRH1 of Ovsynch-56 and reduced fertility to the TAI. In addition, P4 concentration at d 11 after TAI was reduced by DO. The method of presynchronization at first service had no effect on P/AI at the subsequent second service (34.7 vs. 36.5%, DO vs. PS). Thus, presynchronization with DO induced cyclicity in most anovular cows and improved fertility compared with PS, suggesting that DO could be a useful reproductive management protocol for synchronizing first service in commercial dairy herds.
We report the discovery of eight new giant planets, and updated orbits for four known planets, orbiting dwarf and subgiant stars using the CORALIE, HARPS, and MIKE instruments as part of the ...Calan-Hertfordshire Extrasolar Planet Search. The planets have masses in the range 1.1-5.4 M sub( J)'s, orbital periods from 40 to 2900 d, and eccentricities from 0.0 to 0.6. They include a double-planet system orbiting the most massive star in our sample (HD147873), two eccentric giant planets (HD128356b and HD154672b), and a rare 14 Herculis analogue (HD224538b). We highlight some population correlations from the sample of radial velocity detected planets orbiting nearby stars, including the mass function exponential distribution, confirmation of the growing body of evidence that low-mass planets tend to be found orbiting more metal-poor stars than giant planets, and a possible period-metallicity correlation for planets with masses >0.1 M sub( J), based on a metallicity difference of 0.16 dex between the population of planets with orbital periods less than 100 d and those with orbital periods greater than 100 d.
During neuronal development, the formation of neural circuits requires developing axons to traverse a diverse cellular and molecular environment to establish synaptic contacts with the appropriate ...postsynaptic partners. Essential to this process is the ability of developing axons to navigate guidance molecules presented by specialized populations of cells. These cells partition the distance traveled by growing axons into shorter intervals by serving as intermediate targets, orchestrating the arrival and departure of axons by providing attractive and repulsive guidance cues. The floor plate in the central nervous system (CNS) is a critical intermediate target during neuronal development, required for the extension of commissural axons across the ventral midline. In this review, we begin by giving a historical overview of the ventral commissure and the evolutionary purpose of decussation. We then review the axon guidance studies that have revealed a diverse assortment of midline guidance cues, as well as genetic and molecular regulatory mechanisms required for coordinating the commissural axon response to these cues. Finally, we examine the contribution of dysfunctional axon guidance to neurological diseases.
ABSTRACT The rate of image acquisition in modern synoptic imaging surveys has already begun to outpace the feasibility of keeping astronomers in the real-time discovery and classification loop. Here ...we present the inner workings of a framework, based on machine-learning algorithms, that captures expert training and ground-truth knowledge about the variable and transient sky to automate (1) the process of discovery on image differences, and (2) the generation of preliminary science-type classifications of discovered sources. Since follow-up resources for extracting novel science from fast-changing transients are precious, self-calibrating classification probabilities must be couched in terms of efficiencies for discovery and purity of the samples generated. We estimate the purity and efficiency in identifying real sources with a two-epoch image-difference discovery algorithm for the Palomar Transient Factory (PTF) survey. Once given a source discovery, using machine-learned classification trained on PTF data, we distinguish between transients and variable stars with a 3.8% overall error rate (with 1.7% errors for imaging within the Sloan Digital Sky Survey footprint). At >96% classification efficiency, the samples achieve 90% purity. Initial classifications are shown to rely primarily on context-based features, determined from the data itself and external archival databases. In the first year of autonomous operations of PTF, this discovery and classification framework led to several significant science results, from outbursting young stars to subluminous Type IIP supernovae to candidate tidal disruption events. We discuss future directions of this approach, including the possible roles of crowdsourcing and the scalability of machine learning to future surveys such as the Large Synoptic Survey Telescope (LSST).
Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors ...contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications.
Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values.
Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples.
Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.
•Estimation of TMB varies across different panels, with panel size, gene content and bioinformatics pipelines contributing to empirical variability.•Panel sizes greater than 667Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cutoffs used in practice.•Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays.
Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, ...and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA (dsDNA) and chromatin, respectively.
Here, we engineered a dual-active DNase with combined DNase1 and DNase1L3 activities and characterized the enzyme for its NET degrading potential in vitro. Furthermore, we produced a mouse model with transgenic expression of the dual-active DNase and analyzed body fluids of these animals for DNase1 and DNase 1L3 activities. We systematically substituted 20 amino acid stretches in DNase1 that were not conserved among DNase1 and DNase1L3 with homologous DNase1L3 sequences.
We found that the ability of DNase1L3 to degrade chromatin is embedded into three discrete areas of the enzyme's core body, not the C-terminal domain as suggested by the state-of-the-art. Further, combined transfer of the aforementioned areas of DNase1L3 to DNase1 generated a dual-active DNase1 enzyme with additional chromatin degrading activity. The dual-active DNase1 mutant was superior to native DNase1 and DNase1L3 in degrading dsDNA and chromatin, respectively. Transgenic expression of the dual-active DNase1 mutant in hepatocytes of mice lacking endogenous DNases revealed that the engineered enzyme was stable in the circulation, released into serum and filtered to the bile but not into the urine.
Therefore, the dual-active DNase1 mutant is a promising tool for neutralization of DNA and NETs with potential therapeutic applications for interference with thromboinflammatory disease states.
Previous studies suggest genome structure is largely conserved between Eucalyptus species. However, it is unknown if this conservation extends to more divergent eucalypt taxa. We performed ...comparative genomics between the eucalypt genera Eucalyptus and Corymbia. Our results will facilitate transfer of genomic information between these important taxa and provide further insights into the rate of structural change in tree genomes.
We constructed three high density linkage maps for two Corymbia species (Corymbia citriodora subsp. variegata and Corymbia torelliana) which were used to compare genome structure between both species and Eucalyptus grandis. Genome structure was highly conserved between the Corymbia species. However, the comparison of Corymbia and E. grandis suggests large (from 1-13 MB) intra-chromosomal rearrangements have occurred on seven of the 11 chromosomes. Most rearrangements were supported through comparisons of the three independent Corymbia maps to the E. grandis genome sequence, and to other independently constructed Eucalyptus linkage maps.
These are the first large scale chromosomal rearrangements discovered between eucalypts. Nonetheless, in the general context of plants, the genomic structure of the two genera was remarkably conserved; adding to a growing body of evidence that conservation of genome structure is common amongst woody angiosperms.
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