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.
Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances
. It has long been speculated that magnetars are the engine powering ...repeating bursts from FRB sources
, but no convincing evidence has been collected so far
. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts
. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare
. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.
Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin ...of cosmological FRBs is still not settled. Here we report the detection of1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.9). These observations show irregular short-time variation ofthe Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (au; Earth-Sun distance) ofthe source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.
Background and purpose
Neutrophils, a pivotal immune responder to ischaemic brain insult, have been involved in neuroplasticity and increase after stroke. Recombinant tissue plasminogen activator ...(r‐tPA), a promising treatment improving neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile of neutrophils after r‐tPA treatment and their effect on neurological recovery after stroke are not well studied.
Methods
Cell counts of neutrophils, lymphocytes and their ratio (NLR) were measured on admission and 24 h after r‐tPA infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age 64 years). Death or major disability at 3 months after stroke was diagnosed based on the modified Rankin Scale (mRS ≥ 3) obtained by neurologists who were blinded to any hospital records. The longitudinal associations of percentage increase in neutrophils, lymphocytes and the NLR with death or major disability were examined by logistic regression adjusting for covariates including neurological deficits at baseline.
Results
Neutrophils exhibited a steeper increase after r‐tPA infusion in patients with death or major disability than in those without (P < 0.001). A 10% increase in neutrophils after r‐tPA infusion was associated with an 83% increased risk for death or major disability within 3 months after stroke onset odds ratio (OR) 1.99, P = 0.009. Increased neutrophils at 24 h after r‐tPA (OR 6.30, P < 0.001 after log transformation) but not on admission significantly predicted increased risks for death or major disability within 3 months after stroke onset. A similar phenomenon was also observed for the NLR.
Conclusions
A dynamic increase in neutrophils after stroke significantly predicts 3‐month death or major disability in acute ischaemic stroke patients receiving r‐tPA treatment.
The role that changes in DNA methylation and histone modifications have in human malignancies is poorly understood. p300 and CREB-binding protein (CBP), two distinct but highly homologous lysine ...acetyltransferases, are mutated in several cancers, suggesting their role as tumor suppressors. In the current study, we found that deletion of p300, but not CBP, markedly accelerated the leukemogenesis ofNup98-HoxD13 (NHD13) transgenic mice, an animal model that phenotypically copies human myelodysplastic syndrome (MDS). p300 deletion restored the ability of NHD13 expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew in vitro, and to expand in vivo, with an increase in stem cell symmetric self-renewal divisions and a decrease in apoptosis. Furthermore, loss of p300, but not CBP, promoted cytokine signaling, including enhanced activation of the MAPK and JAK/STAT pathways in the HSPC compartment. Altogether, our data indicate that p300 has a pivotal role in blocking the transformation of MDS to acute myeloid leukemia, a role distinct from that of CBP.
Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently ...available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers.
We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical IHC analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients.
Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.
In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).
The conductivity of a poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) film can be enhanced by more than two orders of magnitude by adding a compound with two or more polar ...groups, such as ethylene glycol, meso‐erythritol (1,2,3,4‐tetrahydroxybutane), or 2‐nitroenthanol, to an aqueous solution of PEDOT:PSS. The mechanism for this conductivity enhancement is studied, and a new mechanism proposed. Raman spectroscopy indicates an effect of the liquid additive on the chemical structure of the PEDOT chains, which suggests a conformational change of PEDOT chains in the film. Both coil and linear conformations or an expanded‐coil conformation of the PEDOT chains may be present in the untreated PEDOT:PSS film, and the linear or expanded‐coil conformations may become dominant in the treated PEDOT:PSS film. This conformational change results in the enhancement of charge‐carrier mobility in the film and leads to an enhanced conductivity. The high‐conductivity PEDOT:PSS film is ideal as an electrode for polymer optoelectronic devices. Polymer light‐emitting diodes and photovoltaic cells fabricated using such high‐conductivity PEDOT:PSS films as the anode exhibit a high performance, close to that obtained using indium tin oxide as the anode.
The conductivity of poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films is enhanced by the addition of ethylene glycol, meso‐erythritol, or 2‐nitroethanol, which change the conformation of the PEDOT chains. High‐performance polymer light‐emitting diodes (see Figure) and solar cells using enhanced PEDOT:PSS films as the anode are demonstrated.
Coal combustion will continue to be a major component of energy production in the foreseeable future, owing to its abundance in China. A primary challenge will be to seek ways to utilize the coal ...resources in an environmentally acceptable manner. This paper presents the coal combustion scenario and its related air pollution in China. Some commonly used technologies for removing the pollutants from coal combustion had been introduced after comparison of its utilization efficiency, engineering investment-, and operation expense. In order to cost-effectively reduce the pollutant emission, it is necessary to enhance the coal utilization efficiency by implementing large-scale advanced technologies and increasing the coal-washing rate. There is dire need for indigenously developed techniques for the pollution control to reduce the engineering cost. The development of low-cost, low water-consuming flue gas desulfurization technologies, low-cost technologies for reducing NO
x emission, and low-cost advanced technologies for inhalable particle emission control, must be predominantly paid attention.
The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We ...analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones activating signaling pathways such as FLT3 or RAS or biallelically perturbing TP53. Single-cell studies highlighted the polyclonal nature of intratumoral resistance mechanisms in some cases. Among cases that were primary refractory, we identified heterogeneous and sometimes divergent interval changes in leukemic clones within a single cycle of therapy, highlighting the dynamic and rapid occurrence of therapeutic selection in AML. In functional studies, FLT3 internal tandem duplication gain or TP53 loss conferred cross-resistance to both venetoclax and cytotoxic-based therapies. Collectively, we highlight molecular determinants of outcome with clinical relevance to patients with AML receiving venetoclax-based combination therapies.
•Adaptive resistance is often associated with TP53 abnormalities or kinase activation, particularly FLT3 internal tandem duplication.•NPM1 mutation is associated with excellent survival prospects and durable molecular remission after venetoclax-based combination therapy.
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Efficient white organic light‐emitting devices with uncomplicated architectures are fabricated employing phosphorescent platinum(II) complexes containing extended π‐conjugated cyclometalated ligands ...as a yellow‐light source, and fluorescent material 9,10‐bis‐(β‐naphthyl)‐anthrene as a blue‐light source. Peak external quantum (power) efficiencies of 11.8 % (18.4 lm W–1) are demonstrated (see figure).
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