Biallelic mutations in IRF8 impair human NK cell maturation and function

Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8–/–, but not Irf8+/–, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense

Measurement of the W±Z boson pair-production cross section in pp collisions at √s=13TeV with the ATLAS detector

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Neutrophils can Promote Clotting via FXI and Impact Clot Structure via Neutrophil Extracellular Traps in a Distinctive Manner in vitro

Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role of neutrophils or NETs on clot structure, formation and dissolution was studied with a combination of confocal microscopy, turbidity and permeation experiments. Factor (F)XII, FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects. We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous. In conclusion, NETs accelerate clotting and contribute to the formation of a denser, more lysis resistant clot architecture. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI

Measurement of single top-quark production in association with a W boson in the single-lepton channel at \sqrt{s} = 8\,\text {TeV} with the ATLAS detector

The production cross-section of a top quark in association with a W boson is measured using proton–proton collisions at \sqrt{s} = 8\,\text {TeV}. The dataset corresponds to an integrated luminosity of 20.2\,\text {fb}^{-1}, and was collected in 2012 by the ATLAS detector at the Large Hadron Collider at CERN. The analysis is performed in the single-lepton channel. Events are selected by requiring one isolated lepton (electron or muon) and at least three jets. A neural network is trained to separate the tW signal from the dominant t{\bar{t}} background. The cross-section is extracted from a binned profile maximum-likelihood fit to a two-dimensional discriminant built from the neural-network output and the invariant mass of the hadronically decaying W boson. The measured cross-section is \sigma _{tW} = 26 \pm 7\,\text {pb}, in good agreement with the Standard Model expectation

Measurements of electroweak Wjj production and constraints on anomalous gauge couplings with the ATLAS detector

Measurements of the electroweak production of a W boson in association with two jets at high dijet invariant mass are performed using root s = 7 and 8 TeV proton-proton collision data produced by the Large Hadron Collider, corresponding respectively to 4.7 and 20.2 fb(-1) of integrated luminosity collected by the ATLAS detector. The measurements are sensitive to the production of a W boson via a triple-gauge-boson vertex and include both the fiducial and differential cross sections of the electroweak process

Random flows and diagnostics of turbulence in the high latitude cirrus

Aims. We present an analysis of the exceptionally turbulent velocity field in the high Galactic latitude cirrus cloud MBM 3. As in the other translucent clouds in our study (MBM 16 and MBM 40), there is no evidence for internal star formation. However, the large scale velocity variation in this cloud is more pronounced. Methods. We have mapped the cloud in (CO)-C-12 and (CO)-C-13 (1-0) at high spatial (0.03 pc) and velocity (0.06 km s(-1)) resolution. We constructed several velocity probability density functions (PDFs), estimated the turbulent transfer rate, and analyzed the linewidths as a function of the size of randomly chosen regions within the cloud. Results. We find strong shear flows throughout the cloud that can easily power the turbulent motions. The wings of the PDFs are well approximated by a lorentzian distribution. Such distributions, related to Levy processes that are well known to be produced by correlated processes, are an unambiguous diagnostic of the turbulent intermittency. Conclusions. We find that the linewidth-size relation frequently used to indicate the role of turbulence in molecular clouds is not an unambiguous signature of its presence

Evidence of a weak galactic center magnetic field from diffuse low-frequency nonthermal radio emission

New low-frequency 74 and 330 MHz observations of the Galactic center ( GC) region reveal the presence of a large-scale (6° x 2°) diffuse source of nonthermal synchrotron emission. A minimum-energy analysis of this emission yields a total energy of ∼(φ(4/7) f(3/7)) x 10(52) ergs and a magnetic field strength of ∼ μ G (where φ is the proton to electron energy ratio and f is the filling factor of the synchrotron emitting gas). The equipartition particle energy density is 1.2(φ/f)(2/7) eV cm(-3), a value consistent with cosmic-ray data. However, the derived magnetic field is several orders of magnitude below the 1 mG field commonly invoked for the GC. With this field the source can be maintained with the supernova rate inferred from the GC star formation. Furthermore, a strong magnetic field implies an abnormally low GC cosmic-ray energy density. We conclude that the mean magnetic field in the GC region must be weak, of order 10 mG ( at least on size scales ≥ 125(n))

THE NATURE, LOCATION AND ENVIRONMENT OF SGRA EAST

Open Access. The Center of the Galaxy: Proceedings of the 136th Symposium of the International Astronomical Union, held in Los Angeles, U.S.A., July 25-29, 1988. Edited by Mark Morris. International Astronomical Union. Symposium no. 136, Kluwer Academic Publishers, Dordrecht, 1989