In superconductors, electrons are paired and condensed into the ground state. An impurity can break the electron pairs into quasiparticles with energy states inside the superconducting gap. The ...characteristics of such in-gap states reflect accordingly the properties of the superconducting ground state. A zero-energy in-gap state is particularly noteworthy, because it can be the consequence of non-trivial pairing symmetry or topology. Here we use scanning tunnelling microscopy/spectroscopy to demonstrate that an isotropic zero-energy bound state with a decay length of ∼10 Å emerges at each interstitial iron impurity in superconducting Fe(Te,Se). More noticeably, this zero-energy bound state is robust against a magnetic field up to 8 T, as well as perturbations by neighbouring impurities. Such a spectroscopic feature has no natural explanation in terms of impurity states in superconductors with s-wave symmetry, but bears all the characteristics of the Majorana bound state proposed for topological superconductors, indicating that the superconducting state and the scattering mechanism of the interstitial iron impurities in Fe(Te,Se) are highly unconventional.
A new methodology based on tensor algebra that uses a higher order singular value decomposition to perform three-dimensional voxel reconstruction from a series of temporal images obtained using ...dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is proposed. Principal component analysis (PCA) is used to robustly extract the spatial and temporal image features and simultaneously de-noise the datasets. Tumour segmentation on enhanced scaled (ES) images performed using a fuzzy C-means (FCM) cluster algorithm is compared with that achieved using the proposed tensorial framework. The proposed algorithm explores the correlations between spatial and temporal features in the tumours. The multi-channel reconstruction enables improved breast tumour identification through enhanced de-noising and improved intensity consistency. The reconstructed tumours have clear and continuous boundaries; furthermore the reconstruction shows better voxel clustering in tumour regions of interest. A more homogenous intensity distribution is also observed, enabling improved image contrast between tumours and background, especially in places where fatty tissue is imaged. The fidelity of reconstruction is further evaluated on the basis of five new qualitative metrics. Results confirm the superiority of the tensorial approach. The proposed reconstruction metrics should also find future applications in the assessment of other reconstruction algorithms.
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large ...cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
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•Gut microbiomes of 98 mothers and their infants during the first year of life was assessed•Cessation of breast-feeding drives the maturation of the infant gut microbiome•Shifts in signature species demonstrate nonrandom transitions in the infants’ gut•Changes in nutrient and xenobiotic metabolism mark maturation of the gut microbiome
Bäckhed et al. assessed the gut microbiomes of 98 Swedish mothers and their infants during the first year of life. Cessation of breast-feeding was identified as a major factor in determining gut microbiota maturation, with distinct shifts in signature species being hallmarks of its functional maturation.
Abstract
The Cosmic Ray Energetics And Mass for the International Space Station (ISS-CREAM) experiment successfully recorded data for 539 days from 2017 August to 2019 February. We report the energy ...spectrum of cosmic-ray protons from the ISS-CREAM experiment at energies from 1.60 × 10
3
to 6.55 × 10
5
GeV. The measured spectrum deviates from a single power law. A smoothly broken power-law fit to the data, including statistical and systematic uncertainties, shows the spectral index change at 9.0 × 10
3
GeV from 2.57 ± 0.03 to 2.82 ± 0.02 with a significance of greater than 3
σ
. This bump-like structure is consistent with a spectral softening recently reported by the balloon-borne CREAM, DAMPE, and NUCLEON, but ISS-CREAM extends measurements to higher energies.
In order to enhance the experience of learning, many educators applied learning analytics in a classroom, the major principle of learning analytics is targeting at-risk student and given timely ...intervention according to the results of student behavior analysis. However, when researchers applied machine learning to train a risk identifying model, the reason which affected the performance of the model was overlooked. This study collected seven datasets within three universities located in Taiwan and Japan and listed performance metrics of risk identification model after fed data into eight classification methods. U1, U2, and U3 were used to denote the three universities, which have three, two, and two cases of datasets (learning logs), respectively. According to the results of this study, the factors influencing the predictive performance of classification methods are the number of significant features, the number of categories of significant features, and Spearman correlation coefficient values. In U1 dataset case 1.3 and U2 dataset case 2.2, the numbers of significant features, numbers of categories of significant features, and Spearman correlation coefficient values for significant features were all relatively high, which is the main reason why these datasets were able to perform classification with high predictive ability.
The Atlantic thermohaline circulation (THC) is an important part of the earth’s climate system. Previous research has shown large uncertainties in simulating future changes in this critical system. ...The simulated THC response to idealized freshwater perturbations and the associated climate changes have been intercompared as an activity of World Climate Research Program (WCRP) Coupled Model Intercomparison Project/Paleo-Modeling Intercomparison Project(CMIP/PMIP) committees. This intercomparison among models ranging from the earth system models of intermediate complexity (EMICs) to the fully coupled atmosphere–ocean general circulation models (AOGCMs) seeks to document and improve understanding of the causes of the wide variations in the modeled THC response. The robustness of particular simulation features has been evaluated across the model results. In response to 0.1-Sv (1 Sv ≡ 10⁶ m³ s−1) freshwater input in the northern North Atlantic, the multimodel ensemble mean THC weakens by 30% after 100 yr. All models simulate some weakening of the THC, but no model simulates a complete shutdown of the THC. The multimodel ensemble indicates that the surface air temperature could present a complex anomaly pattern with cooling south of Greenland and warming over the Barents and Nordic Seas. The Atlantic ITCZ tends to shift southward. In response to 1.0-Sv freshwater input, the THC switches off rapidly in all model simulations. A large cooling occurs over the North Atlantic. The annual mean Atlantic ITCZ moves into the Southern Hemisphere. Models disagree in terms of the reversibility of the THC after its shutdown. In general, the EMICs and AOGCMs obtain similar THC responses and climate changes with more pronounced and sharper patterns in the AOGCMs.
We report ferromagnetism in carbon-doped ZnO. Our first-principles calculations based on density functional theory predicted a magnetic moment of 2.02 mu(B) per carbon when carbon substitutes oxygen ...in ZnO, and an ferromagnetic coupling among magnetic moments of the carbon dopants. The theoretical prediction was confirmed experimentally. C-doped ZnO films deposited by pulsed-laser deposition showed ferromagnetism with Curie temperatures higher than 400 K. The measured magnetic moment based on the content of carbide in the films (1.5-3.0) mu(B) per carbon was in agreement with the theoretical prediction. The magnetism is due to the Zn-C system in the ZnO environment.
A matched filter technique is applied to the Planck all-sky Compton y-parameter map to measure the thermal Sunyaev-Zel'dovich (tSZ) effect produced by galaxy groups of different halo masses selected ...from large redshift surveys in the low-z universe. Reliable halo mass estimates are available for all of the groups, which allows us to bin groups of similar halo masses to investigate how the tSZ effect depends on halo mass over a large mass range. Filters are simultaneously matched for all groups to minimize projection effects. We find that the integrated y-parameter and the hot gas content it implies are consistent with the predictions of the universal pressure profile model only for massive groups above , but much lower than the model prediction for low-mass groups. The halo mass dependence found is in good agreement with the predictions of a set of simulations that include strong active galactic nucleus feedback, but simulations including only supernova feedback significantly overpredict the hot gas contents in galaxy groups. Our results suggest that hot gas in galaxy groups is either effectively ejected or in phases much below the virial temperatures of the host halos.
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.
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