Most supermassive black holes (SMBHs) are accreting at very low levels and are difficult to distinguish from the galaxy centers where they reside. Our own Galaxy's SMBH provides an instructive ...exception, and we present a close-up view of its quiescent x-ray emission based on 3 megaseconds of Chandra observations. Although the x-ray emission is elongated and aligns well with a surrounding disk of massive stars, we can rule out a concentration of low-mass coronally active stars as the origin of the emission on the basis of the lack of predicted iron (Fe) Kα emission. The extremely weak hydrogen (H)—like Fe Kα line further suggests the presence of an outflow from the accretion flow onto the SMBH. These results provide important constraints for models of the prevalent radiatively inefficient accretion state.
The poor clinical outcome of hepatocellular carcinoma (HCC) patients is ascribed to the resistance of HCC cells to traditional treatments and tumor recurrence after curative therapies. Cancer stem ...cells (CSCs) have been identified as a small subset of cancer cells which have high capacity for self-renewal, differentiation and tumorigenesis. Recent advances in the field of liver CSCs (LCSCs) have enabled the identification of CSC surface markers and the isolation of CSC subpopulations from HCC cells. Given their central role in cancer initiation, metastasis, recurrence and therapeutic resistance, LCSCs constitute a therapeutic opportunity to achieve cure and prevent relapse of HCC. Thus, it is necessary to develop therapeutic strategies to selectively and efficiently target LCSCs. Small molecular inhibitors targeting the core stemness signaling pathways have been actively pursued and evaluated in preclinical and clinical studies. Other alternative therapeutic strategies include targeting LCSC surface markers, interrupting the CSC microenvironment, and altering the epigenetic state. In this review, we summarize the properties of CSCs in HCC and discuss novel therapeutic strategies that can be used to target LCSCs.
Fast radio bursts (FRBs) are bright radio transients with millisecond duration at cosmological distances. Since compact dark matter/objects (COs) could act as lenses and cause splitting of these ...kinds of very short duration signals, Muñoz et al. have proposed a novel method to probe COs with lensing of FRBs. In this Letter, we for the first time apply this method to real data and give constraints of the nature of COs with currently available FRB observations. We emphasize that the information from dynamic spectra of FRBs is quite necessary for identifying any lensed signals and find no echoes in the existing data. The null search gives a constraint comparable to that from galactic wide binaries, though the methods of redshift inference from the dispersion measure would impact a little. Furthermore, we make an improved forecast based on the distributions of real data for the ongoing and upcoming telescopes. Finally, we discuss the situation where one or more lensed signals will be detected. In such a case, the parameter space of COs can be pinned down very well since the lens mass can be directly determined through the observed flux ratio and time delay between split images.
We present a simple and efficient approach to evaluate the formation energy and, in particular, the ionization energy (IE) of charged defects in two-dimensional (2D) systems using the supercell ...approximation. So far, first-principles results for such systems can scatter widely due to the divergence of the Coulomb energy with vacuum dimension, denoted here as L_{z}. Numerous attempts have been made in the past to fix the problem under various approximations. Here, we show that the problem can be resolved without any such assumption, and a converged IE can be obtained by an extrapolation of the asymptotic IE expression at large L_{z} (with a fixed lateral area S) back to the value at L_{z}=0. Application to defects in monolayer boron nitride reveal that defects in 2D systems can be unexpectedly deep, much deeper than the bulk.
Paroxysmal kinesigenic dyskinesias is a paroxysmal movement disorder characterized by recurrent, brief attacks of abnormal involuntary movements induced by sudden voluntary movements. Although ...several loci, including the pericentromeric region of chromosome 16, have been linked to paroxysmal kinesigenic dyskinesias, the causative gene has not yet been identified. Here, we identified proline-rich transmembrane protein 2 (PRRT2) as a causative gene of paroxysmal kinesigenic dyskinesias by using a combination of exome sequencing and linkage analysis. Genetic linkage mapping with 11 markers that encompassed the pericentromeric of chromosome 16 was performed in 27 members of two families with autosomal dominant paroxysmal kinesigenic dyskinesias. Then, the whole-exome sequencing was performed in three patients from these two families. By combining the defined linkage region (16p12.1-q12.1) and the results of exome sequencing, we identified an insertion mutation c.649_650InsC (p.P217fsX7) in one family and a nonsense mutation c.487C>T (p.Q163X) in another family. To confirm our findings, we sequenced the exons and flanking introns of PRRT2 in another three families with paroxysmal kinesigenic dyskinesias. The c.649_650InsC (p.P217fsX7) mutation was identified in two of these families, whereas a missense mutation, c.796C>T (R266W), was identified in another family with paroxysmal kinesigenic dyskinesias. All of these mutations completely co-segregated with the phenotype in each family. None of these mutations was identified in 500 normal unaffected individuals of matched geographical ancestry. Thus, we have identified PRRT2 as the first causative gene of paroxysmal kinesigenic dyskinesias, warranting further investigations to understand the pathogenesis of this disorder.
The momentum spectrum and the number density of created electron-positron pairs in a frequency modulated laser field are investigated using the quantum kinetic equation. It is found that the momentum ...spectrum presents an obvious interference pattern. This is an imprint of the frequency modulated field on the momentum spectrum, because the momentum peaks correspond to the pair production process by absorbing different frequency component photons. Moreover, the interference effect can also be understood qualitatively by analyzing turning-point structures. The study of the pair number density shows that the number density is very sensitive to modulation parameters and can be enhanced by 2 or 3 orders of magnitude for certain modulation parameters, which may provide a new way to increase the number of created electron-positron pairs in future experiments.
Uterine cancer is the fourth most common malignancy in women, and uterine serous carcinoma is the most aggressive subtype. However, the molecular pathogenesis of uterine serous carcinoma is largely ...unknown. We analyzed the genomes of uterine serous carcinoma samples to better understand the molecular genetic characteristics of this cancer.
Whole-exome sequencing was performed on 10 uterine serous carcinomas and the matched normal blood or tissue samples. Somatically acquired sequence mutations were further verified by Sanger sequencing. The most frequent molecular genetic changes were further validated by Sanger sequencing in 66 additional uterine serous carcinomas and in nine serous endometrial intraepithelial carcinomas (the preinvasive precursor of uterine serous carcinoma) that were isolated by laser capture microdissection. In addition, gene copy number was characterized by single-nucleotide polymorphism (SNP) arrays in 23 uterine serous carcinomas, including 10 that were subjected to whole-exome sequencing.
We found frequent somatic mutations in TP53 (81.6%), PIK3CA (23.7%), FBXW7 (19.7%), and PPP2R1A (18.4%) among the 76 uterine serous carcinomas examined. All nine serous carcinomas that had an associated serous endometrial intraepithelial carcinoma had concordant PIK3CA, PPP2R1A, and TP53 mutation status between uterine serous carcinoma and the concurrent serous endometrial intraepithelial carcinoma component. DNA copy number analysis revealed frequent genomic amplification of the CCNE1 locus (which encodes cyclin E, a known substrate of FBXW7) and deletion of the FBXW7 locus. Among 23 uterine serous carcinomas that were subjected to SNP array analysis, seven tumors with FBXW7 mutations (four tumors with point mutations, three tumors with hemizygous deletions) did not have CCNE1 amplification, and 13 (57%) tumors had either a molecular genetic alteration in FBXW7 or CCNE1 amplification. Nearly half of these uterine serous carcinomas (48%) harbored PIK3CA mutation and/or PIK3CA amplification.
Molecular genetic aberrations involving the p53, cyclin E-FBXW7, and PI3K pathways represent major mechanisms in the development of uterine serous carcinoma.
We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five ...center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrts=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1) MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
Abstract
V410 Aur is a known deep and low-mass-ratio contact binary with a spectroscopically tertiary component and a visual companion. However, the physical and orbital properties of the tertiary ...are unknown. We constructed (
O
−
C
) curve with 117 new eclipse times and those collected from the literature, which shows a cyclical variation with a period of 25.44 (±1.17) yr and a projected semimajor axis of 0.0348 (±0.0021) days while it undergoes a long-term period decrease at a rate of
dP
/
dt
= −1.58 × 10
−7
daysyr
−1
. The cyclical variation is analyzed for the light-travel time effect. The minimum mass of the third body is determined as 1.39 (±0.13)
M
⊙
that is much larger than the inferred value (0.97
M
⊙
) of spectroscopic investigation, which indicates that the spectroscopically tertiary is a single-lined spectroscopic binary with an unseen component. The maximum orbital semimajor axis 6.19 (±0.67) au of the third body is determined. Gaia detected a visual companion to V410 Aur at practically the same distance from the Sun nicely confirming the physical bond. These results reveal that V410 Aur contains a single-lined spectroscopic binary with a visual companion in a quintuple stellar system. TESS photometric solutions confirmed that V410 Aur is a deep overcontact binary with a fill-out factor of 73.83(88)% where the additional light contribution is about 24.80(18)%. The continuous variations of light curves are explained by the evolution of a dark spot on the more massive component. The parabolic variation in the (
O
−
C
) curve may be caused by the mass transfer from the massive component to the less massive one in the deep overcontact binary.
Context. The Gaia mission has released the second data set (Gaia DR2), which contains parallaxes and proper motions for a large number of massive, young stars. Aims. We investigate the spiral ...structure in the solar neighborhood revealed by Gaia DR2 and compare it with that depicted by VLBI maser parallaxes. Methods. We examined three samples with different constraints on parallax uncertainty and distance errors and stellar spectral types: (1) all OB stars with parallax errors of less than 10%; (2) only O-type stars with 0.1 mas errors imposed and with parallax distance errors of less than 0.2 kpc; and (3) only O-type stars with 0.05 mas errors imposed and with parallax distance errors of less than 0.3 kpc. Results. In spite of the significant distance uncertainties for stars in DR2 beyond 1.4 kpc, the spiral structure in the solar neighborhood demonstrated by Gaia agrees well with that illustrated by VLBI maser results. The O-type stars available from DR2 extend the spiral arm models determined from VLBI maser parallaxes into the fourth Galactic quadrant, and suggest the existence of a new spur between the Local and Sagittarius arms.
PDF
