Spatially clustered type I interferon responses at injury borderzones.

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmacytoid-dendritic-cell-depleted mice did not. Interferons blunted the protective matricellular programs and contractile function of borderzone fibroblasts, and increased vulnerability to pathological remodelling. In mice that died after myocardial infarction, IFNIC colonies were immediately adjacent to sites of ventricular rupture, while mice lacking IFNICs were protected from rupture and exhibited improved survival3. Together, these results reveal a pathological borderzone niche characterized by a cardiomyocyte-initiated innate immune response. We suggest that selective inhibition of IRF3 activation in non-immune cells could limit ischaemic cardiomyopathy while avoiding broad immunosuppression.

700,000 years of tropical Andean glaciation.

Our understanding of the climatic teleconnections that drove ice-age cycles has been limited by a paucity of well-dated tropical records of glaciation that span several glacial-interglacial intervals. Glacial deposits offer discrete snapshots of glacier extent but cannot provide the continuous records required for detailed interhemispheric comparisons. By contrast, lakes located within glaciated catchments can provide continuous archives of upstream glacial activity, but few such records extend beyond the last glacial cycle. Here a piston core from Lake Junín in the uppermost Amazon basin provides the first, to our knowledge, continuous, independently dated archive of tropical glaciation spanning 700,000 years. We find that tropical glaciers tracked changes in global ice volume and followed a clear approximately 100,000-year periodicity. An enhancement in the extent of tropical Andean glaciers relative to global ice volume occurred between 200,000 and 400,000 years ago, during sustained intervals of regionally elevated hydrologic balance that modified the regular approximately 23,000-year pacing of monsoon-driven precipitation. Millennial-scale variations in the extent of tropical Andean glaciers during the last glacial cycle were driven by variations in regional monsoon strength that were linked to temperature perturbations in Greenland ice cores1; these interhemispheric connections may have existed during previous glacial cycles.

Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

iBT-Net: an incremental broad transformer network for cancer drug response prediction.

In modern precision medicine, it is an important research topic to predict cancer drug response. Due to incomplete chemical structures and complex gene features, however, it is an ongoing work to design efficient data-driven methods for predicting drug response. Moreover, since the clinical data cannot be easily obtained all at once, the data-driven methods may require relearning when new data are available, resulting in increased time consumption and cost. To address these issues, an incremental broad Transformer network (iBT-Net) is proposed for cancer drug response prediction. Different from the gene expression features learning from cancer cell lines, structural features are further extracted from drugs by Transformer. Broad learning system is then designed to integrate the learned gene features and structural features of drugs to predict the response. With the capability of incremental learning, the proposed method can further use new data to improve its prediction performance without retraining totally. Experiments and comparison studies demonstrate the effectiveness and superiority of iBT-Net under different experimental configurations and continuous data learning.

Highly structured slow solar wind emerging from an equatorial coronal hole.

During the solar minimum, when the Sun is at its least active, the solar wind1,2 is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvénic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind3 of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain4; theories and observations suggest that they may originate at the tips of helmet streamers5,6, from interchange reconnection near coronal hole boundaries7,8, or within coronal holes with highly diverging magnetic fields9,10. The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfvén-wave turbulence11,12, heating by reconnection in nanoflares13, ion cyclotron wave heating14 and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe15 at 36 to 54 solar radii that show evidence of slow Alfvénic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities10,16 that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind.

Phase 1b/2a randomized study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with chronic hepatitis B.

BACKGROUND AND AIM: The induction of effective CD8+ T cells is thought to play a critical role in the functional cure of chronic hepatitis B (CHB). Additionally, the use of checkpoint inhibitors is being evaluated to overcome T cell dysfunction during CHB. APPROACH AND RESULTS: A chimpanzee adenoviral vector (ChAdOx1-HBV) and a Modified vaccinia Ankara boost (MVA-HBV) encoding the inactivated polymerase, core, and S region from a consensus genotype C HBV were studied. The trial enrolled 55 patients with virally-suppressed CHB virus infection and HBsAg <4,000 IU/mL Group 1 received MVA-HBV intramuscularly (IM) on Day 0 and 28, Group 2 received ChAdOx1-HBV on Day 0/MVA-HBV on Day 28 (VTP-300), Group 3 received VTP-300 + low-dose nivolumab (LDN) on Day 28, and Group 4 received VTP-300 plus LDN with both injections. VTP-300 alone and in combination with LDN was well tolerated with no treatment-related serious adverse events. Reductions of HBsAg were demonstrated in the VTP-300 group 2: 3 of 18 patients with starting HBsAg < 50 IU/ml had durable log10 declines > 0.7 log10 2 months post last-dose. Group 3 (N=18) had reductions in HBsAg of 0.76 log10 and 0.80 log10 3 (p<0.001) at 2 and 7 months post last dose. Two developed persistent non-detectable HBsAg levels. CD4+ and CD8+ antigen-specific T cell responses were generated and there was a correlation between IFN-y ELISpot response and HBsAg decline in Group 2. CONCLUSIONS: VTP-300 induced CD4+ and CD8+ T cells and lowered HBsAg in a subset of patients with baseline values below 100 IU/ml. The addition of LDN resulted in significant reduction in surface antigen. VTP-300 is a promising immunotherapeutic to move forward alone or in combination therapies. IMPACT AND IMPLICATIONS: The induction of potent, durable CD8+ T cells may be critical to achieving a functional cure in chronic hepatitis B virus infection. A prime-boost immunotherapeutic consisting of an adenoviral-vector encoding hepatitis B antigens followed by a pox virus boost was shown to induce CD8+ T cells and to lower HBsAg in CHB patients, either alone or more impactfully when administered in conjunction with a checkpoint inhibitor. The use of immunotherapeutics CLINTRIALS: NCT047789.

Excited-Band Coherent Delocalization for Improved Optical Lattice Clock Performance.

We implement coherent delocalization as a tool for improving the two primary metrics of atomic clock performance: systematic uncertainty and instability. By decreasing atomic density with coherent delocalization, we suppress cold-collision shifts and two-body losses. Atom loss attributed to Landau-Zener tunneling in the ground lattice band would compromise coherent delocalization at low trap depths for our ^{171}Yb atoms; hence, we implement for the first time delocalization in excited lattice bands. Doing so increases the spatial distribution of atoms trapped in the vertically oriented optical lattice by ∼7 times. At the same time, we observe a reduction of the cold-collision shift by 6.5(8) times, while also making inelastic two-body loss negligible. With these advantages, we measure the trap-light-induced quenching rate and natural lifetime of the ^{3}P_{0} excited state as 5.7(7)×10^{-4} E_{r}^{-1} s^{-1} and 19(2) s, respectively.

Measurements of Normalized Differential Cross Sections of Inclusive η Production in e

Using data samples collected with the BESIII detector operating at the BEPCII storage ring, the cross section of the inclusive process e^{+}e^{-}→η+X, normalized by the total cross section of e^{+}e^{-}→hadrons, is measured at eight center-of-mass energy points from 2.0000 to 3.6710 GeV. These are the first measurements with momentum dependence in this energy region. Our measurement shows a significant discrepancy compared to the existing fragmentation functions. To address this discrepancy, a new QCD analysis is performed at the next-to-next-to-leading order with hadron mass corrections and higher twist effects, which can explain both the established high-energy data and our measurements reasonably well.

First Study of Antihyperon-Nucleon Scattering Λ[over ¯]p→Λ[over ¯]p and Measurement of Λp→Λp Cross Section.

Using (10.087±0.044)×10^{9} J/ψ events collected with the BESIII detector at the BEPCII storage ring, the processes Λp→Λp and Λ[over ¯]p→Λ[over ¯]p are studied, where the Λ/Λ[over ¯] baryons are produced in the process J/ψ→ΛΛ[over ¯] and the protons are the hydrogen nuclei in the cooling oil of the beam pipe. Clear signals are observed for the two reactions. The cross sections in -0.9≤cosθ_{Λ/Λ[over ¯]}≤0.9 are measured to be σ(Λp→Λp)=(12.2±1.6_{stat}±1.1_{syst}) and σ(Λ[over ¯]p→Λ[over ¯]p)=(17.5±2.1_{stat}±1.6_{syst}) mb at the Λ/Λ[over ¯] momentum of 1.074 GeV/c within a range of ±0.017 GeV/c, where the θ_{Λ/Λ[over ¯]} are the scattering angles of the Λ/Λ[over ¯] in the Λp/Λ[over ¯]p rest frames. Furthermore, the differential cross sections of the two reactions are also measured, where there is a slight tendency of forward scattering for Λp→Λp, and a strong forward peak for Λ[over ¯]p→Λ[over ¯]p. We present an approach to extract the total elastic cross sections by extrapolation. The study of Λ[over ¯]p→Λ[over ¯]p represents the first study of antihyperon-nucleon scattering, and these new measurements will serve as important inputs for the theoretical understanding of the (anti)hyperon-nucleon interaction.

First Measurement of the Decay Asymmetry in the Pure W-Boson-Exchange Decay Λ_{c}

Based on 4.4 fb^{-1} of e^{+}e^{-} annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure W-boson-exchange decay Λ_{c}^{+}→Ξ^{0}K^{+} is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be α_{Ξ^{0}K^{+}}=0.01±0.16(stat)±0.03(syst). This result reflects the noninterference effect between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes has two solutions, which are δ_{p}-δ_{s}=-1.55±0.25(stat)±0.05(syst) rad or 1.59±0.25(stat)±0.05(syst) rad.

Determination of the Σ

Based on data samples collected with the BESIII detector at the BEPCII collider, the process e^{+}e^{-}→Σ^{+}Σ[over ¯]^{-} is studied at center-of-mass energies sqrt[s]=2.3960, 2.6454, and 2.9000 GeV. Using a fully differential angular description of the final state particles, both the relative magnitude and phase information of the Σ^{+} electromagnetic form factors in the timelike region are extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ=-0.67±0.29(stat)±0.18(syst) at sqrt[s]=2.3960 GeV, ΔΦ=55°±19°(stat)±14°(syst) at sqrt[s]=2.6454 GeV, and 78°±22°(stat)±9°(syst) at sqrt[s]=2.9000 GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.

Observation of D_{s}

By analyzing 7.33 fb^{-1} of e^{+}e^{-} annihilation data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector, we report the observation of the semileptonic decay D_{s}^{+}→η^{'}µ^{+}ν_{µ}, with a statistical significance larger than 10σ, and the measurements of the D_{s}^{+}→ηµ^{+}ν_{µ} and D_{s}^{+}→η^{'}µ^{+}ν_{µ} decay dynamics for the first time. The branching fractions of D_{s}^{+}→ηµ^{+}ν_{µ} and D_{s}^{+}→η^{'}µ^{+}ν_{µ} are determined to be (2.235±0.051_{stat}±0.052_{syst})% and (0.801±0.055_{stat}±0.028_{syst})%, respectively, with precision improved by factors of 6.0 and 6.6 compared to the previous best measurements. Combined with the results for the decays D_{s}^{+}→ηe^{+}ν_{e} and D_{s}^{+}→η^{'}e^{+}ν_{e}, the ratios of the decay widths are examined both inclusively and in several ℓ^{+}ν_{ℓ} four-momentum transfer ranges. No evidence for lepton flavor universality violation is found within the current statistics. The products of the hadronic form factors f_{+,0}^{η^{(')}}(0) and the c→s Cabibbo-Kobayashi-Maskawa matrix element |V_{cs}| are determined. The results based on the two-parameter series expansion are f_{+,0}^{η}(0)|V_{cs}|=0.452±0.010_{stat}±0.007_{syst} and f_{+,0}^{η^{'}}(0)|V_{cs}|=0.504±0.037_{stat}±0.012_{syst}, which help to constrain present models on f_{+,0}^{η^{(')}}(0). The forward-backward asymmetries are determined to be ⟨A_{FB}^{η}⟩=-0.059±0.031_{stat}±0.005_{syst} and ⟨A_{FB}^{η^{'}}⟩=-0.064±0.079_{stat}±0.006_{syst} for the first time, which are consistent with the theoretical calculation.

Investigation of the ΔI=1/2 Rule and Test of CP Symmetry through the Measurement of Decay Asymmetry Parameters in Ξ

Using (10087±44)×10^{6} J/ψ events collected with the BESIII detector, numerous Ξ^{-} and Λ decay asymmetry parameters are simultaneously determined from the process J/ψ→Ξ^{-}Ξ[over ¯]^{+}→Λ(pπ^{-})π^{-}Λ[over ¯](n[over ¯]π^{0})π^{+} and its charge-conjugate channel. The precisions of α_{Λ0} for Λ→nπ^{0} and α[over ¯]_{Λ0} for Λ[over ¯]→n[over ¯]π^{0} compared to world averages are improved by factors of 4 and 1.7, respectively. The ratio of decay asymmetry parameters of Λ→nπ^{0} to that of Λ→pπ^{-}, ⟨α_{Λ0}⟩/⟨α_{Λ-}⟩, is determined to be 0.873±0.012_{-0.010}^{+0.011}, where the first and the second uncertainties are statistical and systematic, respectively. The ratio is smaller than unity more than 5σ, which signifies the existence of the ΔI=3/2 transition in Λ for the first time. Besides, we test for CP symmetry in Ξ^{-}→Λπ^{-} and in Λ→nπ^{0} with the best precision to date.

Observation of Significant Flavor-SU(3) Breaking in the Kaon Wave Function at 12

We present cross sections for the reaction e^{+}e^{-}→K_{S}^{0}K_{L}^{0} at center-of-mass energies ranging from 3.51 to 4.95 GeV using data samples collected in the BESIII experiment, corresponding to a total integrated luminosity of 26.5 fb^{-1}. The ratio of neutral-to-charged kaon form factors at large momentum transfers (12

Observation of D

We perform for the first time an amplitude analysis of the decay D^{+}→K_{S}^{0}π^{+}η and report the observation of the decay D^{+}→K_{S}^{0}a_{0}(980)^{+} using 2.93 fb^{-1} of e^{+}e^{-} collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector. As the only W-annihilation-free decay among D to a_{0}(980) pseudoscalar, D^{+}→K_{S}^{0}a_{0}(980)^{+} is the ideal decay in extracting the contributions of the W-emission amplitudes involving a_{0}(980) and to study the final-state interactions. The absolute branching fraction of D^{+}→K_{S}^{0}π^{+}η is measured to be (1.27±0.04_{stat}±0.03_{syst})%. The branching fractions of intermediate processes D^{+}→K_{S}^{0}a_{0}(980)^{+} with a_{0}(980)^{+}→π^{+}η and D^{+}→π^{+}K[over ¯]_{0}^{*}(1430)^{0} with K[over ¯]_{0}^{*}(1430)^{0}→K_{S}^{0}η are measured to be (1.33±0.05_{stat}±0.04_{syst})% and (0.14±0.03_{stat}±0.01_{syst})%, respectively.

Precise Measurement of Born Cross Sections for e

Using data samples collected with the BESIII detector at the BEPCII collider at center-of-mass energies ranging from 3.80 to 4.95 GeV, corresponding to an integrated luminosity of 20 fb^{-1}, a measurement of Born cross sections for the e^{+}e^{-}→D^{0}D[over ¯]^{0} and D^{+}D^{-} processes is presented with unprecedented precision. Many clear peaks in the line shape of e^{+}e^{-}→D^{0}D[over ¯]^{0} and D^{+}D^{-} around the mass range of G(3900), ψ(4040), ψ(4160), Y(4260), and ψ(4415), etc., are foreseen. These results offer crucial experimental insights into the nature of hadron production in the open-charm region.

Coupled-Channel Analysis of the χ_{c1}(3872) Line Shape with BESIII Data.

We perform a study of the χ_{c1}(3872) line shape using the data samples of e^{+}e^{-}→γχ_{c1}(3872), χ_{c1}(3872)→D^{0}D[over ¯]^{0}π^{0}, and π^{+}π^{-}J/ψ collected with the BESIII detector. The effects of the coupled channels and the off-shell D^{*0} are included in the parametrization of the line shape. The line shape mass parameter is obtained to be M_{X}=(3871.63±0.13_{-0.05}^{+0.06}) MeV. Two poles are found on the first and second Riemann sheets corresponding to the D^{*0}D[over ¯]^{0} branch cut. The pole location on the first sheet is much closer to the D^{*0}D[over ¯]^{0} threshold than the other, and is determined to be 7.04±0.15_{-0.08}^{+0.07} MeV above the D^{0}D[over ¯]^{0}π^{0} threshold with an imaginary part -0.19±0.08_{-0.19}^{+0.14} MeV.

Observation of the Anomalous Shape of X(1840) in J/ψ→γ3(π

Using a sample of (10087±44)×10^{6} J/ψ events, which is about 45 times larger than that was previously analyzed, a further investigation on the J/ψ→γ3(π^{+}π^{-}) decay is performed. A significant distortion at 1.84 GeV/c^{2} in the line shape of the 3(π^{+}π^{-}) invariant mass spectrum is observed for the first time, which could be resolved by two overlapping resonant structures, X(1840) and X(1880). The new state X(1880) is observed with a statistical significance larger than 10σ. The mass and width of X(1880) are determined to be 1882.1±1.7±0.7 MeV/c^{2} and 30.7±5.5±2.4 MeV, respectively, which indicates the existence of a pp[over ¯] bound state.

Observation of Seven Astrophysical Tau Neutrino Candidates with IceCube.

We report on a measurement of astrophysical tau neutrinos with 9.7 yr of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ν_{τ} events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ν_{τ} energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π^{±}/K^{±} decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ν_{τ} astrophysical neutrinos. Thus, we rule out the absence of astrophysical ν_{τ} at the 5σ level. The measured astrophysical ν_{τ} flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations.

Observation of Structures in the Processes e

We present measurements of the Born cross sections for the processes e^{+}e^{-}→ωχ_{c1} and ωχ_{c2} at center-of-mass energies sqrt[s] from 4.308 to 4.951 GeV. The measurements are performed with data samples corresponding to an integrated luminosity of 11.0 fb^{-1} collected with the BESIII detector operating at the Beijing Electron Positron Collider storage ring. Assuming the e^{+}e^{-}→ωχ_{c2} signals come from a single resonance, the mass and width are determined to be M=(4413.6±9.0±0.8) MeV/c^{2} and Γ=(110.5±15.0±2.9) MeV, respectively, which is consistent with the parameters of the well-established resonance ψ(4415). In addition, we also use one single resonance to describe the e^{+}e^{-}→ωχ_{c1} line shape and determine the mass and width to be M=(4544.2±18.7±1.7) MeV/c^{2} and Γ=(116.1±33.5±1.7) MeV, respectively. The structure of this line shape, observed for the first time, requires further understanding.