P‐glycoprotein P‐gp or the ATP‐binding cassette transporter B1 (ABCB1) is an important participant in multidrug resistance of cancer cells, yet the precise function of this arthropod transporter is ...unknown. The aim of this study was to determine the importance of P‐gp for susceptibility to insecticides in the beet armyworm (Spodoptera exigua) using clustered regularly interspaced short palindromic repeats/CRISPR‐associated 9 (CRISPR/Cas9) gene‐editing technology. We cloned an open reading frame (ORF) encoding the S. exigua P‐gp protein (SeP‐gp) predicted to display structural characteristics common to P‐gp and other insect ABCB1 transporters. A knockout line with a frame shift deletion of four nucleotides in the SeP‐gp ORF was established using the CRISPR/Cas9 gene‐editing system to test its potential role in determining susceptibility to chemical insecticides or insecticidal proteins from the bacterium Bacillus thuringiensis (Bt). Results from comparative bioassays demonstrate that knockout of SeP‐gp significantly increases susceptibility of S. exigua by around threefold to abamectin and emamectin benzoate (EB), but not to spinosad, chlorfenapyr, beta‐cypermethrin, carbosulfan indoxacarb, chlorpyrifos, phoxim, diafenthiuron, chlorfluazuron, chlorantraniliprole or two Bt toxins (Cry1Ca and Cry1Fa). Our data support an important role for SeP‐gp in susceptibility of S. exigua to abamectin and EB and imply that overexpression of SeP‐gp may contribute to abamectin and EB resistance in S. exigua.
The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
Young neutron stars (NSs) born in core-collapse explosions are promising candidates for the central engines of fast radio bursts (FRBs), since the first localized repeating burst FRB 121102 occurs in ...a star-forming dwarf galaxy similar to the host galaxies of superluminous supernovae and long gamma-ray bursts. However, FRB 180924 and FRB 190523 are localized to massive galaxies with low rates of star formation, compared with the host of FRB 121102. The offsets between the bursts and host centers are about 4 and 29 kpc for FRB 180924 and FRB 190523, respectively. These host properties are similar to those of short gamma-ray bursts (GRBs), which are produced by binary neutron star (BNS) or NS-black hole mergers. Therefore, the NSs powering FRBs may be formed in BNS mergers. In this paper, we study BNS merger rates and merger times, and predict the most likely merger locations for different types of host galaxies using the population synthesis method. We find that the BNS merger channel is consistent with the recently reported offsets of FRB 180924 and FRB 190523. The offset distribution of short GRBs is well reproduced by population synthesis using a galaxy model similar to that of GRB hosts. The event rate of FRBs (including non-repeating and repeating), is larger than those of BNS mergers and short GRBs, and requires a large fraction of observed FRBs emitting several bursts. Using curvature radiation by bunches in NS magnetospheres, we also predict the observational properties of FRBs from BNS mergers, including the dispersion measure and rotation measure. At late times (t ≥ 1 yr), the contribution to dispersion measure and rotation measure from BNS merger ejecta can be neglected.
The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal ...growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).
Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.
A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.
These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).
ABSTRACT We present preliminary results of the quasar survey in the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) first data release (DR1), which includes the pilot survey and ...the first year of the regular survey. There are 3921 quasars reliably identified, among which 1180 are new quasars discovered in the survey. These quasars are at low to median redshifts, with a highest z of 4.83. We compile emission line measurements around the H , Hβ, Mg ii, and C iv regions for the new quasars. The continuum luminosities are inferred from SDSS photometric data with model fitting, as the spectra in DR1 are non-flux-calibrated. We also compile the virial black hole mass estimates, with flags indicating the selection methods, and broad absorption line quasars. The catalog and spectra for these quasars are also available. Of the 3921 quasars, 28% are independently selected with optical-infrared colors, indicating that the method is quite promising for the completeness of the quasar survey. LAMOST DR1 and the ongoing quasar survey will provide valuable data for studies of quasars.
Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory ...(LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.
We present an empirical stellar spectra library created using spectra from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) DR5. This library represents a uniform data set ...ranging from 3750 through 8500 K in effective temperature (Teff), from −2.5 through +1.0 dex in metallicity (Fe/H), and from 0 to 5.0 dex in gravity (log g). The spectra in the library have resolutions R ∼ 1800, with well-calibrated fluxes and rest-framed wavelengths. Using a large number of red stars observed by LAMOST, we generated denser K-type templates to fill in data missing from current empirical spectral libraries, particularly the late K type. For K giants, we calibrated the spectroscopic surface gravities against the asteroseismic surface gravities. To verify the reliability of the parameters labeled for this library, we performed an internal cross-validation using a χ2 minimization method to interpolate the parameters of each individual spectrum using the remaining spectra in the library. We obtained precisions of 41 K, 0.11 dex, and 0.05 dex for Teff, log g, and Fe/H, respectively, which means the templates are labeled with correct stellar parameters. Through external comparisons, we confirmed that measurements of the stellar parameters through this library can achieve accuracies of approximately 125 K in Teff, 0.1 dex in Fe/H and 0.20 dex in log g without systematic offset. This empirical library is useful for stellar parameter measurements because it has large parameter coverage and full wavelength coverage from 3800 to 8900 .
Purpose
Tumoral calcinosis is a rare clinicopathological entity characterized by ectopic soft-tissue calcification, typically periarticular. Normophosphatemic tumoral calcinosis is seldom reported in ...East Asian populations, and the preoperative diagnosis is often elusive. This study was performed to characterize the clinical profile of normophosphatemic tumoral calcinosis and investigate the presence of the
SAMD9
gene mutation.
Methods
The clinical features, pathological examination findings, and outcomes of 19 subjects were retrospectively reviewed. All patients were analyzed for
SAMD9
gene mutation using paraffin-embedded tumoral calcinosis specimens.
Results
Nineteen subjects were analyzed (7 males, 12 females). Their mean age at surgery, mean age at symptom onset, and median disease duration was 51.9 ± 17.3 (range 7–75) years, 49.1 ± 17.2 (range 7–74) years, and 1.3 (interquartile range 0.5–3.0) years, respectively. Lesions were located in the hand in 8 (42.1%) subjects; wrist in 5 (26.3%); shoulder in 2 (10.5%); and hip, knee, buttock, and scrotum in 1 (5.3%) subject each. The lesions in 17 (89.5%) subjects were located around the joints small joints (hand and wrist) in 13 (68.4%) and large joints (shoulder, hip, and knee) in 4 (21.1%). Lesions occurred in the upper limbs in 15 (78.9%) subjects and in the lower limbs in 2 (10.5%). Multiple-lesion involvement (distal right index finger and middle finger) occurred in one (5.3%) subject. Symptoms included pain in 15 (78.9%) subjects, impaired mobility in 5 (26.3%), swelling in 5 (26.3%), numbness in 2 (10.5%), and an asymptomatic mass in 2 (10.5%). The serum inorganic phosphorus concentration was normal in all 19 subjects (mean 1.17 ± 0.15 mmol/L). The serum calcium concentration was normal in 18 subjects and low in 1. The serum alkaline phosphatase concentration was normal in all 19 subjects. Pathological examination indicated multiple nodules of calcified materials that manifested an amorphous or granular blue-purple crystal and were surrounded by proliferation of mononuclear or multinuclear macrophages, osteoclastic-like giant cells, fibroblasts, and chronic inflammatory cells. Notably, different phases of pathological manifestations were observed in the same microscopic field. During follow-up (0.5–65.0 months), no recurrence of tumoral calcinosis was observed in 18 (94.7%) subjects, but 1 subject developed in situ recurrence of an asymptomatic subcutaneous mass after 6 months postoperatively. Genetic analysis in all 19 subjects revealed no
SAMD9
gene mutations.
Conclusions
Most subjects were females and developed calcinosis in adulthood. Small joints (hand and wrist) and the upper limbs were frequently involved. The presence of different phases of pathological features in the same subject suggests that about half of the study participants had been misdiagnosed with another condition (such as gout, osteoarthritis, etc.). Complete surgical excision led to cure without recurrence during follow-up in majority of the study participants.
Warming amplification over the Arctic Pole (AP hereafter) and Third Pole (Tibetan Plateau, TP hereafter) can trigger a series of climate responses and have global consequences. Arctic amplification ...(AA) and Tibetan amplification (TA) are the most significant characteristics of climate change patterns over the two Poles. In this study, trends, mechanisms and consequences of both AA and TA are compared. Based on ERA5 reanalysis during 1979–2020, both AP and TP have undergone significant warming with an annual rate of 0.72 °C/decade and 0.34 °C/decade respectively, which exceeds the rates for the Northern Hemisphere (0.29 °C/decade) and the global means (0.19 °C/decade) over the same period. Based on 22 Coupled Model Intercomparison Project Phase 6 models, AA over the AP is warming at a rate almost four times than the global means and twice as fast over the TP. Although both AA and TA are projected to continue in the future, currently there is no consensus on the dominant mechanisms for AA or TA over the two Poles. Proposed mechanisms of AA can be divided into two types: local climate factors (sea ice-albedo feedback, Planck feedback, temperature gradient feedback, cloud feedback, and water vapor feedback); and poleward heat and moisture transport from lower latitudes (atmospheric circulation effect, ocean circulation effect, and modulation of Pacific and Atlantic SST). Consequences of AA include decline of sea ice cover, retreat of the Greenland ice sheet, permafrost degradation, accelerated disturbances in marine and terrestrial ecosystems, and influences on extreme climate events at lower latitudes. Anthropogenic greenhouse gas emission, snow/ice-albedo feedback, cloud-radiation interactions, water vapor and radiative flux feedbacks, local forcing and feedback processes, land use changes and reduction in total ozone, are generally considered to be the main mechanisms causing TA. TA has caused significant change within the atmosphere and cryosphere over the TP and its surroundings, such as changes in climate extremes, snow cover, the retreat of glaciers, and permafrost degradation. Similarities and differences of warming amplifications over the two Poles are proposed, and the relative contribution of each mechanism to the warming amplifications and how the specific consequences may compare over the two Poles remain unclear and under continuing investigation.
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