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Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia–reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia–reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau–iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.

Most forecasts predict an annual airline traffic growth rate between 4.5 and 5 in the foreseeable future. To sustain that growth, the environmental impact of aircraft cannot be ignored. Future aircraft must have much better fuel economy, dramatically less greenhouse gas emissions and noise, in addition to better performance. Many technical breakthroughs must take place to achieve the aggressive environmental goals set up by governments in North America and Europe. One of these breakthroughs will be physics-based, highly accurate and efficient computational fluid dynamics and aeroacoustics tools capable of predicting complex flows over the entire flight envelope and through an aircraft engine, and computing aircraft noise. Some of these flows are dominated by unsteady vortices of disparate scales, often highly turbulent, and they call for higher-order methods. As these tools will be integral components of a multi-disciplinary optimization environment, they must be efficient to impact design. Ultimately, the accuracy, efficiency, robustness, scalability and geometric flexibility will determine which methods will be adopted in the design process. This article explores these aspects and identifies pacing items.

Since there have been individual reports of persistent haze–fog events in January 2013 in central-eastern China, questions on factors causing the drastic differences in changes in 2013 from changes in adjacent years have been raised. Changes in major chemical components of aerosol particles over the years also remain unclear. The extent of meteorological factors contributing to such changes is yet to be determined. The study intends to present the changes in daily based major water-soluble constituents, carbonaceous species, and mineral aerosol in PM10 at 13 stations within different haze regions in China from 2006 to 2013, which are associated with specific meteorological conditions that are highly related to aerosol pollution (parameterized as an index called Parameter Linking Aerosol Pollution and Meteorological Elements – PLAM). No obvious changes were found in annual mean concentrations of these various chemical components and PM10 in 2013, relative to 2012. By contrast, wintertime mass of these components was quite different. In Hua Bei Plain (HBP), sulfate, organic carbon (OC), nitrate, ammonium, element carbon (EC), and mineral dust concentrations in winter were approximately 43, 55, 28, 23, 21, and 130 μg m−3, respectively; these masses were approximately 2 to 4 times higher than those in background mass, which also exhibited a decline during 2006 to 2010 and then a rise till 2013. The mass of these concentrations and PM10, except minerals, respectively, increased by approximately 28 to 117 % and 25 % in January 2013 compared with that in January 2012. Thus, persistent haze–fog events occurred in January 2013, and approximately 60 % of this increase in component concentrations from 2012 to 2013 can be attributed to severe meteorological conditions in the winter of 2013. In the Yangtze River Delta (YRD) area, winter masses of these components, unlike HBP, have not significantly increase since 2010; PLAM were also maintained at a similar level without significant changes. In the Pearl River Delta (PRD) area, the regional background concentrations of the major chemical components were similar to those in the YRD, accounting for approximately 60–80 % of those in HBP. Since 2010, a decline has been found for winter concentrations, which can be partially attributable to persistently improving meteorological conditions and emission cutting with an emphasis on coal combustion in this area. In addition to the scattered and centralized coal combustion for heating, burning biomass fuels contributed to the large increase in concentrations of carbonaceous aerosol in major haze regions in winter, except in the PRD. No obvious changes were found for the proportions of each chemical components of PM10 from 2006 to 2013. Among all of the emissions recorded in chemical compositions in 2013, coal combustion was still the largest anthropogenic source of aerosol pollution in various areas in China, with a higher sulfate proportion of PM10 in most areas of China, and OC was normally ranked third. PM10 concentrations increased by approximately 25 % in January of 2013 relative to 2012, which caused persistent haze–fog events in HBP; emissions also reduced by approximately 35 % in Beijing and its vicinity (BIV) in late autumn of 2014, thereby producing the Asia Pacific Economic Cooperation (APEC) blue (extremely good air quality); thus, one can expect that the persistent haze–fog events would be reduced significantly in the BIV, if approx. one-third of the 2013 winter emissions were reduced, which can also be viewed as the upper limit of atmospheric aerosol pollution capacity in this area.

Three-dimensional (3D) topological Dirac semimetals (TDSs) represent an unusual state of quantum matter that can be viewed as \"3D graphene.\" In contrast to 2D Dirac fermions in graphene or on the surface of 3D topological insulators, TDSs possess 3D Dirac fermions in the bulk. By investigating the electronic structure of Na3Bi with angle-resolved photoemission spectroscopy, we detected 3D Dirac fermions with linear dispersions along all momentum directions. Furthermore, we demonstrated the robustness of 3D Dirac fermions in Na3Bi against in situ surface doping. Our results establish Na3Bi as a model system for 3D TDSs, which can serve as an ideal platform for the systematic study of quantum phase transitions between rich topological quantum states.

A state of matter known as a three-dimensional Dirac semimetal has latterly garnered significant theoretical and experimental attention. Using angle-resolved photoelectron spectroscopy, it is shown that Cd 3 As 2 is an experimental realization of a three-dimensional Dirac semimetal that is stable at ambient conditions. Three-dimensional (3D) topological Dirac semimetals (TDSs) are a recently proposed state of quantum matter 1 , 2 , 3 , 4 , 5 , 6 that have attracted increasing attention in physics and materials science. A 3D TDS is not only a bulk analogue of graphene; it also exhibits non-trivial topology in its electronic structure that shares similarities with topological insulators. Moreover, a TDS can potentially be driven into other exotic phases (such as Weyl semimetals 1 , 7 , axion insulators 1 , 4 and topological superconductors 8 , 9 ), making it a unique parent compound for the study of these states and the phase transitions between them. Here, by performing angle-resolved photoemission spectroscopy, we directly observe a pair of 3D Dirac fermions in Cd 3 As 2 , proving that it is a model 3D TDS. Compared with other 3D TDSs, for example, β-cristobalite BiO 2 (ref.  3 ) and Na 3 Bi (refs  4 , 5 ), Cd 3 As 2 is stable and has much higher Fermi velocities. Furthermore, by in situ doping we have been able to tune its Fermi energy, making it a flexible platform for exploring exotic physical phenomena.

This study was performed to investigate incidence, causes and factors influencing mortality after haploidentical hematopoietic stem cell transplantation (HSCT) and to compare differences between haploidentical HSCT and HLA-identical sibling HSCT. From January 2000 to June 2011, 1411 patients with acute leukemia or myelodysplastic syndrome were included in this study. Of these patients, 571 received HLA-identical sibling HSCT and 840 received haploidentical HSCT. The cumulative incidence of overall mortality and transplant-related mortality (TRM) after haploidentical HSCT was higher than those after HLA-identical sibling HSCT (38.7% vs 33.3%, P =0.012 and 27.5% vs 19.9%, P =0.002), but the incidence of relapse-related mortality (RRM) did not differ between the two groups (15.6% vs 16.7%, P =0.943). A multivariate analysis suggested that high-risk disease status and haploidentical HSCT correlated with a higher incidence of overall mortality ( P< 0.0001, hazard ratio=1.911 and P =0.019, hazard ratio=1.249); in addition, in haploidentical HSCT, only high-risk disease status correlated with a higher incidence of overall mortality ( P< 0.0001, hazard ratio=1.845). Our study suggested that haploidentical HSCT provided a higher incidence of overall mortality and TRM but the same incidence of RRM compared with HLA-identical sibling HSCT. Therefore, HLA-identical sibling HSCT remains the first choice, but haploidentical HSCT is available for patients without an HLA-identical sibling donor.

Exploring the mechanical response of rock joint subjected to dynamic shear load is essential for revealing the mechanism of dynamic disasters in jointed rock masses. Using an impact-induced direct-shear method, a series of dynamic shear experiments were conducted on artificial granite joints with regularly undulating interface. The dynamic friction coefficient of joint was first obtained from planar jointed granite specimens before the dynamic shear strength and shear displacement of the regularly undulating joints were tested. During the test, the effects of normal stress and shear rate were both considered. The results show that when the shear velocity ranges from 1 to 9 m/s, the dynamic friction coefficient of the planar joint is negatively correlated with shear velocity, and decreases by at least 50% compared with that under quasi-static condition. The rate dependence of shear strength appears opposite for granite joints with undulating angles of 11.3° and 26.6°, respectively. A shear strength model for rock joint with an undulating angle of 11.3° is then suggested based on the test results. During impact shear sliding, the maximum shear displacement of the joint is linearly negatively related to the initial normal stress. While, non-driven sliding may occur under low normal stress and high impact velocity, which leads to a large magnitude of shear slip.HighlightsThe shear strength and shear displacement of rock joints are tested with shear rate ranging from 1 to 9 m/s.The rate dependence of shear strength appears opposite for rock joints with sharp and gentle undulation and a shear strength model is suggested.Besides impact-driven sliding, the non-driven sliding may also occur in the joint under low normal stress and high impact velocity.

The outward transport of plasma and magnetic fluxes in the gas giant magnetospheres is balanced with a return flow of flux tubes emptied through magnetic reconnection. Evidence of interchange motions between inward and outward moving flux tubes have long been reported around Jupiter and Saturn. Although amply documented at Saturn, the lack of useable low energy plasma data has prevented the analysis of their plasma properties at Jupiter. The Juno data sets allow us to characterize the plasma populations inside nine interchange events at Jupiter between M‐shells 5 and 10. We confirm that they are strongly depleted in heavy ions and low energy protons and electrons, but filled with higher energy protons and electrons. We model the pitch‐angle distribution of trapped electrons through adiabatic transport and estimate that the reported flux tubes were likely isotropic between M‐shells 11 and 35. The observed features bear strong similarities with their Kronian counterparts.

High-order methods have demonstrated orders of magnitude reduction in computational cost for large eddy simulation (LES) over low-order methods in the past decade. Most such simulations are wall-resolved implicit LES (ILES) without an explicit sub-grid scale (SGS) model. The use of high-order ILES for severely under-resolved LES such as wall-modeled LES (WMLES) often runs into robustness and accuracy issues due to the low dissipation embedded in these methods. In the present study, we investigate the performance of several popular SGS models, the static Smagorinsky model, the wall-adapting local eddy-viscosity (WALE) model and the Vreman model, to improve the robustness and accuracy of under-resolved LES using high-order methods. The models are implemented in the high-order unstructured grid LES solver called hpMusic based on the discontinuous flux reconstruction method. The length scales in these SGS models are calibrated using the direct numerical simulation (DNS) database for the turbulent channel flow problem. The Vreman model has been found to produce the most accurate and consistent results with a proper choice of the length scale for WMLES.

Interfacial solute clustering is an essential step preceding grain boundary (GB) precipitation. Both states, i.e., clusters and precipitates, alter the mechanical, chemical, and corrosion properties of materials. Continuum models cannot capture the atomic details of these phenomena, specifically of the transition from clustering to precipitation. We thus use the structural phase-field crystal (XPFC) model to study the compositional and structural evolution during GB clustering in Al–Cu alloys. The results show that the compositional evolution is dominated by solute segregation to lattice defects at the very beginning and then by confined spinodal decomposition along the GBs. The latter leads to a steep increase in the concentration and then the formation of disordered clusters. This structure acts as a precursor for phase nucleation, just like the decomposed solid solution, and Guinier–Preston zones are the precursors of the thermodynamically stable Al2Cu phase in the interior of grains. Two modes of spinodal decomposition are found. (a) On low-angle tilt GBs, spinodal decomposition occurs at the dislocations that constitute the GB. (b) On high-angle tilt GBs, spinodal decomposition takes place inside the entire GB plane. In either case, the structural transition from the disordered low-dimensional precursor states to an ordered phase state takes place following the compositional enrichment. These results shed light on atomic-scale early-stage GB decomposition and precipitation processes in Al–Cu alloys and enrich our knowledge about the coupling effects between compositional and structural evolution during GB phase transformation phenomena.