We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon ...number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.
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CMK, CTK, FMFMET, NUK, UL
Abstract
We present a study of timing properties of the accreting pulsar 2S 1417-624 observed during its 2018 outburst, based on Swift/BAT, Fermi/GBM, Insight-HXMT and NICER observations. We report a ...dramatic change of the pulse profiles with luminosity. The morphology of the profile in the range 0.2-10.0 keV switches from double to triple peaks at ∼2.5 $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$ and from triple to quadruple peaks at ∼7 $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$. The profile at high energies (25-100 keV) shows significant evolutions as well. We explain this phenomenon according to existing theoretical models. We argue that the first change is related to the transition from the sub to the super-critical accretion regime, while the second to the transition of the accretion disc from the gas-dominated to the radiation pressure-dominated state. Considering the spin-up as well due to the accretion torque, this interpretation allows to estimate the magnetic field self-consistently at ∼7 × 1012 G.
Although reduced-intensity conditioning (RIC) and non-myeloablative (NMA)-conditioning regimens have been used for over a decade, their relative efficacy vs myeloablative (MA) approaches to ...allogeneic hematopoietic cell transplantation in patients with AML and myelodysplasia (MDS) is unknown. We compared disease status, donor, graft and recipient characteristics with outcomes of 3731 MA with 1448 RIC/NMA procedures performed at 217 centers between 1997 and 2004. The 5-year univariate probabilities and multivariate relative risk outcomes of relapse, TRM, disease-free survival (DFS) and OS are reported. Adjusted OS at 5 years was 34, 33 and 26% for MA, RIC and NMA transplants, respectively. NMA conditioning resulted in inferior DFS and OS, but there was no difference in DFS and OS between RIC and MA regimens. Late TRM negates early decreases in toxicity with RIC and NMA regimens. Our data suggest that higher regimen intensity may contribute to optimal survival in patients with AML/MDS, suggesting roles for both regimen intensity and graft vs leukemia in these diseases. Prospective studies comparing regimens are needed to confirm this finding and determine the optimal approach to patients who are eligible for either MA or RIC/NMA conditioning.
The human transcriptome annotation is regarded as one of the most complete of any eukaryotic species. However, limitations in sequencing technologies have biased the annotation toward multi-exonic ...protein coding genes. Accurate high-throughput long read transcript sequencing can now provide additional evidence for rare transcripts and genes such as mono-exonic and non-coding genes that were previously either undetectable or impossible to differentiate from sequencing noise.
We developed the Transcriptome Annotation by Modular Algorithms (TAMA) software to leverage the power of long read transcript sequencing and address the issues with current data processing pipelines. TAMA achieved high sensitivity and precision for gene and transcript model predictions in both reference guided and unguided approaches in our benchmark tests using simulated Pacific Biosciences (PacBio) and Nanopore sequencing data and real PacBio datasets. By analyzing PacBio Sequel II Iso-Seq sequencing data of the Universal Human Reference RNA (UHRR) using TAMA and other commonly used tools, we found that the convention of using alignment identity to measure error correction performance does not reflect actual gain in accuracy of predicted transcript models. In addition, inter-read error correction can cause major changes to read mapping, resulting in potentially over 6 K erroneous gene model predictions in the Iso-Seq based human genome annotation. Using TAMA's genome assembly based error correction and gene feature evidence, we predicted 2566 putative novel non-coding genes and 1557 putative novel protein coding gene models.
Long read transcript sequencing data has the power to identify novel genes within the highly annotated human genome. The use of parameter tuning and extensive output information of the TAMA software package allows for in depth exploration of eukaryotic transcriptomes. We have found long read data based evidence for thousands of unannotated genes within the human genome. More development in sequencing library preparation and data processing are required for differentiating sequencing noise from real genes in long read RNA sequencing data.
ABSTRACT
We report on our analysis of the 2019 outburst of the X-ray accreting pulsar 4U 1901+03 observed with Insight-HXMT and NICER. Both spectra and pulse profiles evolve significantly in the ...decaying phase of the outburst. Dozens of flares are observed throughout the outburst. They are more frequent and brighter at the outburst peak. We find that the flares, which have a duration from tens to hundreds of seconds, are generally brighter than the persistent emission by a factor of ∼1.5. The pulse-profile shape during the flares can be significantly different from that of the persistent emission. In particular, a phase shift is clearly observed in many cases. We interpret these findings as direct evidence of changes of the pulsed beam pattern, due to transitions between the sub- and supercritical accretion regimes on a short time-scale. We also observe that at comparable luminosities the flares’ pulse profiles are rather similar to those of the persistent emission. This indicates that the accretion on the polar cap of the neutron star is mainly determined by the luminosity, i.e. the mass accretion rate.
Summary
Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated ...vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti‐lysosomal membrane protein‐2 (LAMP‐2) antibody, may have a pathogenic role in AAV. We have shown previously that anti‐LAMP‐2 antibody‐stimulated NET formation contains autoantigens and anti‐microbial peptides. The current study sought to determine whether LAMP‐2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti‐LAMP‐2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti‐LAMP‐2 antibody‐induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP‐2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti‐LAMP‐2 antibody, and this effect was attenuated by the inhibitors of autophagy 3‐methyladenine (3MA) and 2‐morpholin‐4‐yl‐8‐phenylchromen‐4‐one (LY294002). The anti‐LAMP‐2 antibody‐stimulated NET formation was unaffected by benzyloxycarbonyl‐Val‐ Ala‐Asp (OMe)‐fluoromethylketone (zVAD‐fmk) and necrostatin‐1 (Nec‐1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P = 0·0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti‐LAMP‐2 antibody. Our results provide further evidence that autophagy is involved in ANCA‐induced NET formation in human neutrophils.
The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to ...directly explore this mechanism in Plasmodium falciparum. We use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite. Such a broad targeting spectrum disrupts the biochemical landscape of the parasite and causes its death. Furthermore, using alkyne-tagged artemisinin coupled with a fluorescent dye to monitor protein binding, we show that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation. The haem derives primarily from the parasite's haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages. Our results support a unifying model to explain the action and specificity of artemisinin in parasite killing.
Electron resonant interaction with whistler mode waves is traditionally considered as one of the main drivers of radiation belt dynamics. The two main theoretical concepts available for its ...description are quasi‐linear theory of electron scattering by low‐amplitude waves and nonlinear theory of electron resonant trapping and phase bunching by intense waves. Both concepts successfully describe some aspects of wave‐particle interactions but predict significantly different timescales of relativistic electron acceleration. In this study, we investigate effects that can reduce the efficiency of nonlinear interactions and bridge the gap between the predictions of these two types of models. We examine the effects of random wave phase and frequency variations observed inside whistler mode wave packets on nonlinear interactions. Our results show that phase coherence and frequency fluctuations should be taken into account to accurately model electron nonlinear resonant acceleration and that, along with wave amplitude modulation, they may reduce acceleration rates to realistic, moderate levels.
Key Points
Chorus wave phase randomly fluctuates between subpackets inside longwave packets
Wave phase coherence significantly influences the efficiency of electron acceleration via nonlinear resonant interaction
Fluctuations of wave frequency within longwave packets similarly reduce the efficiency of nonlinear resonant electron acceleration
It has been known that electromagnetic ion cyclotron (EMIC) waves can precipitate ultrarelativistic electrons through cyclotron resonant scattering. However, the overall effectiveness of this ...mechanism has yet to be quantified, because it is difficult to obtain the global distribution of EMIC waves that usually exhibit limited spatial presence. We construct a statistical distribution of EMIC wave frequency spectra and their intensities based on Van Allen Probes measurements from September 2012 to December 2015. Our results show that as the ratio of plasma frequency over electron gyrofrequency increases, EMIC wave power becomes progressively dominated by the helium band. There is a pronounced dawn‐dusk asymmetry in the wave amplitude and the frequency spectrum. The frequency spectrum does not follow the commonly used single‐peak Gaussian function. Incorporating these realistic EMIC wave frequency spectra into radiation belt models is expected to improve the quantification of EMIC wave scattering effects in ultrarelativistic electron dynamics.
Key Points
Statistical distribution of the EMIC wave frequency spectrum is collected by using Van Allen Probes measurements
The RMS EMIC wave amplitude becomes stronger with increasing levels of geomagnetic activity
EMIC wave power is dominated by He‐band (H‐band) in high (low) fpe/fce regions
ABSTRACT
In this paper, we presented a detailed timing analysis of a prominent outburst of 4U 0115+63 detected by Insight-HXMT in 2017 August. The spin period of the neutron star was determined to be ...3.613 98 ± 0.000 02 s at MJD 57978. We measured the period variability and extract the orbital elements of the binary system. The angle of periastron evolved with a rate of $0.048^\circ \pm 0.003^\circ \rm \, yr^{-1}$. The light curves are folded to sketch the pulse profiles in different energy ranges. A multipeak structure in 1–10 keV is clearly illustrated. We introduced wavelet analysis into our data analysis procedures to study quasi-periodic oscillation (QPO) signals and perform a detailed wavelet analysis in many different energy ranges. Through the wavelet spectra, we report the discovery of a QPO at the frequency of ∼10 mHz. In addition, the X-ray light curves showed multiple QPOs in the period of ∼16–32 and ∼67–200 s. We found that the ∼100 s QPO was significant in most of the observations and energies. There exist positive relations between X-ray luminosity and their Q-factors and S-factors, while the QPO periods have no correlation with X-ray luminosity. In wavelet phase maps, we found that the pulse phase of ∼67–200 s QPO is drifting frequently while that of ∼16–32 s QPO is scarcely drifting. The dissipation of oscillations from high energy to low energy was also observed. These features of QPOs in 4U 0115+63 provide a new challenge to our understanding of their physical origins.
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