Extracellular DNA traps promote thrombosis Fuchs, Tobias A.; Brill, Alexander; Duerschmied, Daniel ...
Proceedings of the National Academy of Sciences - PNAS,
09/2010, Letnik:
107, Številka:
36
Journal Article
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Neutrophil extracellular traps (NETs) are part of the innate immune response to infections. NETs are a meshwork of DNA fibers comprising histones and antimicrobial proteins. Microbes are immobilized ...in NETs and encounter a locally high and lethal concentration of effector proteins. Recent studies show that NETs are formed inside the vasculature in infections and noninfectious diseases. Here we report that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation. NETs perfused with blood caused platelet adhesion, activation, and aggregation. DNase or the anticoagulant heparin dismantled the NET scaffold and prevented thrombus formation. Stimulation of platelets with purified histones was sufficient for aggregation. NETs recruited red blood cells, promoted fibrin deposition, and induced a red thrombus, such as that found in veins. Markers of extracellular DNA traps were detected in a thrombus and plasma of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced thrombosis. Our observations indicate that NETs are a previously unrecognized link between inflammation and thrombosis and may further explain the epidemiological association of infection with thrombosis.
At the atomic-cluster scale, pure boron is markedly similar to carbon, forming simple planar molecules and cage-like fullerenes. Theoretical studies predict that two-dimensional (2D) boron sheets ...will adopt an atomic configuration similar to that of boron atomic clusters. We synthesized atomically thin, crystalline 2D boron sheets (i.e., borophene) on silver surfaces under ultrahigh-vacuum conditions. Atomic-scale characterization, supported by theoretical calculations, revealed structures reminiscent of fused boron clusters with multiple scales of anisotropic, out-of-plane buckling. Unlike bulk boron allotropes, borophene shows metallic characteristics that are consistent with predictions of a highly anisotropic, 2D metal.
In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly ...reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months.
For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval CI, 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported.
In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849 .).
ABSTRACT
We present measurements of the redshift-dependent clustering of a DESI-like luminous red galaxy (LRG) sample selected from the Legacy Survey imaging data set, and use the halo occupation ...distribution (HOD) framework to fit the clustering signal. The photometric LRG sample in this study contains 2.7 million objects over the redshift range of 0.4 < z < 0.9 over 5655 deg2. We have developed new photometric redshift (photo-z) estimates using the Legacy Survey DECam and WISE photometry, with σNMAD = 0.02 precision for LRGs. We compute the projected correlation function using new methods that maximize signal-to-noise ratio while incorporating redshift uncertainties. We present a novel algorithm for dividing irregular survey geometries into equal-area patches for jackknife resampling. For a five-parameter HOD model fit using the MultiDark halo catalogue, we find that there is little evolution in HOD parameters except at the highest redshifts. The inferred large-scale structure bias is largely consistent with constant clustering amplitude over time. In an appendix, we explore limitations of Markov chain Monte Carlo fitting using stochastic likelihood estimates resulting from applying HOD methods to N-body catalogues, and present a new technique for finding best-fitting parameters in this situation. Accompanying this paper, we have released the Photometric Redshifts for the Legacy Surveys catalogue of photo-z’s obtained by applying the methods used in this work to the full Legacy Survey Data Release 8 data set. This catalogue provides accurate photometric redshifts for objects with z < 21 over more than 16 000 deg2 of sky.
Triosephosphate isomerase (TPI) is best known as a glycolytic enzyme that interconverts the 3-carbon sugars dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). TPI is an essential ...enzyme that is required for the catabolism of DHAP and a net yield of ATP from anaerobic glucose metabolism. Loss of TPI function results in the recessive disease TPI Deficiency (TPI Df). Recently, numerous lines of evidence suggest the TPI protein has other functions beyond glycolysis, a phenomenon known as moonlighting or gene sharing. Here we review the numerous functions ascribed to TPI, including recent findings of a nuclear role of TPI implicated in cancer pathogenesis and chemotherapy resistance.
We perform a semi-automated search for strong gravitational lensing systems in the 9000 deg2 Dark Energy Camera Legacy Survey (DECaLS), part of the Dark Energy Spectroscopic Instrument Legacy Imaging ...Surveys. The combination of the depth and breadth of these surveys are unparalleled at this time, making them particularly suitable for discovering new strong gravitational lensing systems. We adopt the deep residual neural network architecture developed by Lanusse et al. for the purpose of finding strong lenses in photometric surveys. We compile a training sample that consists of known lensing systems in the Legacy Surveys and the Dark Energy Survey as well as non-lenses in the footprint of DECaLS. In this paper we show the results of applying our trained neural network to the cutout images centered on galaxies typed as ellipticals in DECaLS. The images that receive the highest scores (probabilities) are visually inspected and ranked. Here we present 335 candidate strong lensing systems, identified for the first time.
Achieving the goals of the U.S. Department of Energy (DOE) Sunshot initiative requires (1) higher operating temperatures for concentrating solar power (CSP) plants to increase theoretical efficiency, ...and (2) effective thermal energy storage (TES) strategies to ensure dispatchability. Current inorganic salt-based TES systems in large-scale CSP plants generally employ molten nitrate salts for energy storage, but nitrate salts are limited in application to lower temperatures—generally, below 600°C. These materials are sufficient for parabolic trough power plants, but they are inadequate for use at higher temperatures. At the higher operating temperatures achievable in solar power tower-type CSP plants, chloride salts are promising candidates for application as TES materials, owing to their thermal stability and generally lower cost compared to nitrate salts.
In light of this, a recent study was conducted, which included a preliminary survey of chloride salts and binary eutectic systems that show promise as high temperature TES media. This study provided some basic information about the salts, including phase equilibria data and estimates of latent heat of fusion for some of the eutectics. Cost estimates were obtained through a review of bulk pricing for the pure salts among various vendors.
This review paper updates that prior study, adding data for additional salt eutectic systems obtained from the literature. Where possible, data are obtained from the thermodynamic database software, FactSage. Radiative properties are presented, as well, since at higher temperatures, thermal radiation becomes a significant mode of heat transfer. Material compatibility for inorganic salts is another important consideration (e.g., with regard to piping and/or containment), so a summary of corrosion studies with various materials is also presented. Lastly, cost data for these systems are presented, allowing for meaningful comparison among these systems and other materials for TES applications. Because chloride salts may be employed as either sensible heat storage in the molten phase or as sensible and latent heat thermal energy storage (LHTES) as phase change materials (PCMs), cost of the candidate salt systems are presented on a cost per unit mass basis (sensible heat storage application) and a cost per unit latent heat of fusion basis (latent heat storage application). A total of 133 chloride salt systems were investigated.
Abstract
We have conducted a search for new strong gravitational lensing systems in the Dark Energy Spectroscopic Instrument Legacy Imaging Surveys’ Data Release 8. We use deep residual neural ...networks, building on previous work presented by Huang et al. These surveys together cover approximately one-third of the sky visible from the Northern Hemisphere, reaching a
z
-band AB magnitude of ∼22.5. We compile a training sample that consists of known lensing systems as well as non-lenses in the Legacy Surveys and the Dark Energy Survey. After applying our trained neural networks to the survey data, we visually inspect and rank images with probabilities above a threshold. Here we present 1210 new strong lens candidates.
We present the first results from an ongoing survey for damped Lyman-α systems (DLAs) in the spectra of z > 2 quasars observed in the course of the Baryon Oscillation Spectroscopic Survey (BOSS), ...which is part of the Sloan Digital Sky Survey (SDSS) III. Our full (non-statistical) sample, based on Data Release 9, comprises 12 081 systems with log N(H i) ≥ 20, out of which 6839 have log N(H i) ≥ 20.3. This is the largest DLA sample ever compiled, superseding that from SDSS-II by a factor of seven. Using a statistical sub-sample and estimating systematics from realistic mock data, we probe the N(H i) distribution at ⟨z⟩ = 2.5. Contrary to what is generally believed, the distribution extends beyond 1022 cm-2 with a moderate slope of index ≈−3.5. This result matches the opacity-corrected distribution observed at z = 0 surprisingly well. The cosmological mass density of neutral gas in DLAs is found to be \hbox{$\omegagdla \approx 10^{-3}$}ΩgDLA≈10-3, evolving only mildly over the past 12 billion years.
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