Fast radio bursts (FRBs) are millisecond-duration radio transients
of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star ...magnetospheres
or relativistic shocks far from the central energy source
. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters
or variable polarization angles in some other apparently one-off events
. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.
The hybrid approach to quantum computation simultaneously utilizes both discrete and continuous variables, which offers the advantage of higher density encoding and processing powers for the same ...physical resources. Trapped ions, with discrete internal states and motional modes that can be described by continuous variables in an infinite-dimensional Hilbert space, offer a natural platform for this approach. A nonlinear gate for universal quantum computing can be implemented with the conditional beam splitter Hamiltonian |e⟩⟨e|(aover ^^{†}bover ^+aover ^bover ^^{†}) that swaps the quantum states of two motional modes, depending on the ion's internal state. We realize such a gate and demonstrate its applications for quantum state overlap measurements, single-shot parity measurement, and generation of NOON states.
We present high-resolution (∼300 au) Atacama Large Millimeter/submillimeter Array observations of the massive young stellar object G11.92-0.61 MM 1. We resolve the immediate circumstellar environment ...of MM 1 in 1.3 mm continuum emission and CH3CN emission for the first time. The object divides into two main sources-MM 1a, which is the source of a bipolar molecular outflow, and MM 1b, located 0 57 (1920 au) to the southeast. The main component of MM 1a is an elongated continuum structure, perpendicular to the bipolar outflow, with a size of 0 141 × 0 050 (480 × 170 au). The gas kinematics toward MM 1a probed via CH3CN trace a variety of scales. The lower energy J = 12-11 K = 3 line traces extended, rotating gas within the outflow cavity, while the v8 = 1 line shows a clearly resolved Keplerian rotation signature. Analysis of the gas kinematics and dust emission shows that the total enclosed mass in MM 1a is 40 5 M (where between 2.2 and 5.8 M is attributed to the disk), while MM 1b is <0.6 M . The extreme mass ratio and orbital properties of MM 1a and MM 1b suggest that MM 1b is one of the first observed examples of the formation of a binary star via disk fragmentation around a massive young (proto)star.
Two different forms of death are commonly observed when Mycobacterium tuberculosis (Mtb)-infected macrophages die: (i) necrosis, a death modality defined by cell lysis and (ii) apoptosis, a form of ...death that maintains an intact plasma membrane. Necrosis is a mechanism used by bacteria to exit the macrophage, evade host defenses, and spread. In contrast, apoptosis of infected macrophages is associated with diminished pathogen viability. Apoptosis occurs when tumor necrosis factor activates the extrinsic death domain pathway, leading to caspase-8 activation. In addition, mitochondrial outer membrane permeabilization leading to activation of the intrinsic apoptotic pathway is required. Both pathways lead to caspase-3 activation, which results in apoptosis. We have recently demonstrated that during mycobacterial infection, cell death is regulated by the eicosanoids, prostaglandin E(2) (proapoptotic) and lipoxin (LX)A(4) (pronecrotic). Although PGE(2) protects against necrosis, virulent Mtb induces LXA(4) and inhibits PGE(2) production. Under such conditions, mitochondrial inner membrane damage leads to macrophage necrosis. Thus, virulent Mtb subverts eicosanoid regulation of cell death to foil innate defense mechanisms of the macrophage.
Abstract
In this paper, we model the chemical evolution of a 0.25 M⊙ protoplanetary disc surrounding a 1 M⊙ star that undergoes fragmentation due to self-gravity. We use smoothed particle ...hydrodynamics including a radiative transfer scheme, along with a time-dependent chemical evolution code to follow the composition of the disc and resulting fragments over approximately 4000 yr. Initially, four quasi-stable fragments are formed, of which two are eventually disrupted by tidal torques in the disc. From the results of our chemical modelling, we identify species that are abundant in the fragments (e.g. H2O, H2S, HNO, N2, NH3, OCS, SO), species that are abundant in the spiral shocks within the disc (e.g. CO, CH4, CN, CS, H2CO) and species that are abundant in the circumfragmentary material (e.g. HCO+). Our models suggest that in some fragments it is plausible for grains to sediment to the core before releasing their volatiles into the planetary envelope, leading to changes in, e.g., the C/O ratio of the gas and ice components. We would therefore predict that the atmospheric composition of planets generated by gravitational instability should not necessarily follow the bulk chemical composition of the local disc material.
The current sheet is believed to be the region of energy dissipation via magnetic reconnection in solar flares. However, its properties, for example, the dynamic process, are not fully understood. ...Here, we report a current sheet in a solar flare (SOL2017-09-10T16:06) that was clearly observed by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory as well as the EUV Imaging Spectrometer on Hinode. The high-resolution imaging and spectroscopic observations show that the current sheet is mainly visible in high-temperature (>10 MK) passbands, particularly in the Fe xxiv 192.03 line with a formation temperature of ∼18 MK. The hot Fe xxiv 192.03 line exhibits very large nonthermal velocities up to 200 km s−1 in the current sheet, suggesting that turbulent motions exist there. The largest turbulent velocity occurs at the edge of the current sheet, with some offset with the strongest line intensity. At the central part of the current sheet, the turbulent velocity is negatively correlated with the line intensity. From the line emission and turbulent features we obtain a thickness in the range of 7-11 Mm for the current sheet. These results suggest that the current sheet has internal fine and dynamic structures that may help the magnetic reconnection within it proceed efficiently.
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For studying the dynamics of a two-level system coupled to a quantum oscillator we have presented an analytical approach, the transformed rotating-wave approximation, which takes into account the ...effect of the counter-rotating terms but still keeps the simple mathematical structure of the ordinary rotating-wave approximation. We have calculated the energy levels of ground and lower-lying excited states, as well as the time-dependent quantum dynamics. It is obvious that the approach is quite simple and can be easily extended to more complicated situation. Besides, the results are compared with the numerically exact ones to show that for weak to intermediate coupling and moderate detuning our analytic calculations are quantitatively in good agreement with the exact ones.
Understanding the formation and evolution of giant planets (≥1 MJup) at wide orbital separation (≥5 AU) is one of the goals of direct imaging. Over the past 15 yr, many surveys have placed strong ...constraints on the occurrence rate of wide-orbit giants, mostly based on non-detections, but very few have tried to make a direct link with planet formation theories. In the present work, we combine the results of our previously published VLT/NaCo large program with the results of 12 past imaging surveys to constitute a statistical sample of 199 FGK stars within 100 pc, including three stars with sub-stellar companions. Using Monte Carlo simulations and assuming linear flat distributions for the mass and semi-major axis of planets, we estimate the sub-stellar companion frequency to be within 0.75–5.70% at the 68% confidence level (CL) within 20–300 AU and 0.5–75 MJup, which is compatible with previously published results. We also compare our results with the predictions of state-of-the-art population synthesis models based on the gravitational instability (GI) formation scenario with and without scattering. We estimate that in both the scattered and non-scattered populations, we would be able to detect more than 30% of companions in the 1–75 MJup range (95% CL). With the threesub-stellar detections in our sample, we estimate the fraction of stars that host a planetary system formed by GI to be within 1.0–8.6% (95% CL). We also conclude that even though GI is not common, it predicts a mass distribution of wide-orbit massive companions that is much closer to what is observed than what the core accretion scenario predicts. Finally, we associate the present paper with the release of the Direct Imaging Virtual Archive (DIVA), a public database that aims at gathering the results of past, present, and future direct imaging surveys.
This paper presents results from the phase I study of the focal adhesion kinase inhibitor GSK2256098 in patients with advanced solid tumors. The MTD was identified as 1000 mg, oral BID. Treatment ...with GSK2256098 showed a good tolerability, evidence of target engagement, and clinical activity in patients with recurrent, merlin-negative mesothelioma.
Focal adhesion kinase (FAK) is important in cancer growth, survival, invasion, and migration. The purpose of this study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the FAK inhibitor, GSK2256098, in cancer patients.
The dose of GSK2256098 was escalated, in cohorts of patients with advanced cancer, from 80 to 1500 mg, oral twice daily (BID), until the MTD was determined. Serial blood samples were obtained from all patients, and the PK was determined. Paired tumor biopsies were obtained in select patients, and the level of phospho-FAK (pFAK) was determined.
Sixty-two patients (39 males, 23 females; median age 61 y.o., range 21–84) received GSK2256098. Dose-limiting toxicities of grade 2 proteinuria (1000 mg BID), grade 2 fatigue, nausea, vomiting (1250 mg BID), and grade 3 asthenia and grade 2 fatigue (1500 mg BID) were reported with the MTD identified as 1000 mg BID. The most frequent adverse events (AEs) were nausea (76%), diarrhea (65%), vomiting (58%), and decreased appetite (47%) with the majority of AEs being grades 1–2. The PK was generally dose proportional with a geometric mean elimination half-life range of 4–9 h. At the 750, 1000, and 1500 mg BID dose levels evaluated, the pFAK, Y397 autophosphorylation site, was reduced by ∼80% from baseline. Minor responses were observed in a patient with melanoma (−26%) and three patients with mesothelioma (−13%, −15%, and −17%). In the 29 patients with recurrent mesothelioma, the median progression-free survival was 12 weeks with 95% CI 9.1, 23.4 weeks (23.4 weeks merlin negative, n = 14; 11.4 weeks merlin positive, n = 9; 10.9 weeks merlin status unknown, n = 6).
GSK2256098 has an acceptable safety profile, has evidence of target engagement at doses at or below the MTD, and has clinical activity in patients with mesothelioma, particularly those with merlin loss.
Underlying mechanisms in heart failure (HF) with preserved ejection fraction remain unknown. We investigated cardiovascular plasma biomarkers in HF with preserved ejection fraction and their ...correlation to diastolic dysfunction, functional class, pathophysiological processes, and prognosis.
In 86 stable patients with HF and EF ≥45% in the Karolinska Rennes (KaRen) biomarker substudy, biomarkers were quantified by a multiplex immunoassay. Orthogonal projection to latent structures by partial least square analysis was performed on 87 biomarkers and 240 clinical variables, ranking biomarkers associated with New York Heart Association (NYHA) Functional class and the composite outcome (all-cause mortality and HF hospitalization). Biomarkers significantly correlated with outcome were analyzed by multivariable Cox regression and correlations with echocardiographic measurements performed. The orthogonal partial least square outcome-predicting biomarker pattern was run against the Ingenuity Pathway Analysis (IPA) database, containing annotated data from the public domain. The orthogonal partial least square analyses identified 32 biomarkers correlated with NYHA class and 28 predicting outcomes. Among outcome-predicting biomarkers, growth/differentiation factor-15 was the strongest and an additional 7 were also significant in Cox regression analyses when adjusted for age, sex, and N-terminal probrain natriuretic peptide: adrenomedullin (hazard ratio per log increase 2.53), agouti-related protein; (1.48), chitinase-3-like protein 1 (1.35), C-C motif chemokine 20 (1.35), fatty acid-binding protein (1.33), tumor necrosis factor receptor 1 (2.29), and TNF-related apoptosis-inducing ligand (0.34). Twenty-three of them correlated with diastolic dysfunction (E/e') and 5 with left atrial volume index. The IPA suggested that increased inflammation, immune activation with decreased necrosis and apoptosis preceded poor outcome.
In HF with preserved ejection fraction, novel biomarkers of inflammation predict HF severity and prognosis that may complement or even outperform traditional markers, such as N-terminal probrain natriuretic peptide. These findings lend support to a hypothesis implicating global systemic inflammation in HF with preserved ejection fraction.
URL: http://www.clinicaltrials.gov; Unique identifier: NCT00774709.
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