Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia.

Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia affecting the long bones and skull. The cause of FMD in some individuals is gain-of-function mutations in FLNA, although how these mutations result in a hyperostotic phenotype remains unknown. Approximately one half of individuals with FMD have no identified mutation in FLNA and are phenotypically very similar to individuals with FLNA mutations, except for an increased tendency to form keloid scars. Using whole-exome sequencing and targeted Sanger sequencing in 19 FMD-affected individuals with no identifiable FLNA mutation, we identified mutations in two genes-MAP3K7, encoding transforming growth factor β (TGF-β)-activated kinase (TAK1), and TAB2, encoding TAK1-associated binding protein 2 (TAB2). Four mutations were found in MAP3K7, including one highly recurrent (n = 15) de novo mutation (c.1454C>T [ p.Pro485Leu]) proximal to the coiled-coil domain of TAK1 and three missense mutations affecting the kinase domain (c.208G>C [p.Glu70Gln], c.299T>A [p.Val100Glu], and c.502G>C [p.Gly168Arg]). Notably, the subjects with the latter three mutations had a milder FMD phenotype. An additional de novo mutation was found in TAB2 (c.1705G>A, p.Glu569Lys). The recurrent mutation does not destabilize TAK1, or impair its ability to homodimerize or bind TAB2, but it does increase TAK1 autophosphorylation and alter the activity of more than one signaling pathway regulated by the TAK1 kinase complex. These findings show that dysregulation of the TAK1 complex produces a close phenocopy of FMD caused by FLNA mutations. Furthermore, they suggest that the pathogenesis of some of the filaminopathies caused by FLNA mutations might be mediated by misregulation of signaling coordinated through the TAK1 signaling complex

Current status of turbulent dynamo theory: From large-scale to small-scale dynamos

Several recent advances in turbulent dynamo theory are reviewed. High resolution simulations of small-scale and large-scale dynamo action in periodic domains are compared with each other and contrasted with similar results at low magnetic Prandtl numbers. It is argued that all the different cases show similarities at intermediate length scales. On the other hand, in the presence of helicity of the turbulence, power develops on large scales, which is not present in non-helical small-scale turbulent dynamos. At small length scales, differences occur in connection with the dissipation cutoff scales associated with the respective value of the magnetic Prandtl number. These differences are found to be independent of whether or not there is large-scale dynamo action. However, large-scale dynamos in homogeneous systems are shown to suffer from resistive slow-down even at intermediate length scales. The results from simulations are connected to mean field theory and its applications. Recent work on helicity fluxes to alleviate large-scale dynamo quenching, shear dynamos, nonlocal effects and magnetic structures from strong density stratification are highlighted. Several insights which arise from analytic considerations of small-scale dynamos are discussed.Comment: 36 pages, 11 figures, Spa. Sci. Rev., submitted to the special issue "Magnetism in the Universe" (ed. A. Balogh

Review and application of Artificial Neural Networks models in reliability analysis of steel structures

This paper presents a survey on the development and use of Artificial Neural Network (ANN) models in structural reliability analysis. The survey identifies the different types of ANNs, the methods of structural reliability assessment that are typically used, the techniques proposed for ANN training set improvement and also some applications of ANN approximations to structural design and optimization problems. ANN models are then used in the reliability analysis of a ship stiffened panel subjected to uniaxial compression loads induced by hull girder vertical bending moment, for which the collapse strength is obtained by means of nonlinear finite element analysis (FEA). The approaches adopted combine the use of adaptive ANN models to approximate directly the limit state function with Monte Carlo simulation (MCS), first order reliability methods (FORM) and MCS with importance sampling (IS), for reliability assessment. A comprehensive comparison of the predictions of the different reliability methods with ANN based LSFs and classical LSF evaluation linked to the FEA is provided

Auger Effect in the High-Resolution Ce 3d-edge Resonant Photoemission

The bulk-sensitive Ce 4$f$ spectral weights of various Ce compounds including CeFe$_2$, CeNi$_2$, and CeSi$_2$ were obtained with the resonant photoemission technique at the Ce 3d-edge. We found the lineshapes change significantly with the small change of the incident photon energy. Detailed analysis showed that this phenomenon results primarily from the Auger transition between different multiplet states of the Ce $\underline{3d_{5/2}}4f^2$ (bar denotes a hole) electronic configuration in the intermediate state of the resonant process. This tells us that extra care should be taken for the choice of the resonant photon energy when extracting Ce 4$f$ spectral weights from the Ce 3$d$-edge resonant photoemission spectra. The absorption energy corresponding to the lowest multiplet structure of the Ce $\underline{3d_{5/2}}4f^2$ configuration seems to be the logical choice.Comment: 13 pages, 5 figures, submitted to Phys. Rev.

7th Drug hypersensitivity meeting: part two

No abstract availabl

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Multiplicity dependence of inclusive J/psi production at midrapidity in pp collisions at root s=13 TeV

Measurements of the inclusive J/psi yield as a function of charged-particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 13 TeV with ALICE at the LHC are reported. The J/psi meson yield is measured at midrapidity (vertical bar y vertical bar <0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (vertical bar eta vertical bar <1) and at forward rapidity (-3.7 <eta <-1.7 and 2.8 <eta <5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/psi yield with normalized dN(ch)/d eta is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively. (C) 2020 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe