Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Environmental Effects in the Structural Parameters of Galaxies in the Coma Cluster

We have studied 116 bright galaxies from the Coma cluster brighter than $m_{r}=17$ mag. From a quantitative morphological analysis we find that the scales of the disks are smaller than those of field spiral galaxies. There is a correlation between the scale of the disks and the position of the galaxy in the cluster; no large disks are present near the center of the cluster or in high density environments. The structural parameters of the bulges are not affected by the environment. We have analyzed the distribution of blue and red objects in the cluster. For spirals there is a trend between color and position in the cluster. The bluest spiral galaxies are located at larger projected radii; they also show larger velocity dispersions than the red ones. The differences in the scale of the disks between cluster galaxies and local samples of isolated galaxies and the color distribution of the objects can be understood in terms of the harassment scenario.Comment: 39 pages, 17 figures. Accepted for publication in A

Measurements of the Electron-Helicity Dependent Cross Sections of Deeply Virtual Compton Scattering with CEBAF at 12 GeV

We propose precision measurements of the helicity-dependent and helicity independent cross sections for the ep->epg reaction in Deeply Virtual Compton Scattering (DVCS) kinematics. DVCS scaling is obtained in the limits Q^2>>Lambda_{QCD}^2, x_Bj fixed, and -\Delta^2=-(q-q')^22 GeV^2, W>2 GeV, and -\Delta^21 GeV^2. We will use our successful technique from the 5.75 GeV Hall A DVCS experiment (E00-110). With polarized 6.6, 8.8, and 11 GeV beams incident on the liquid hydrogen target, we will detect the scattered electron in the Hall A HRS-L spectrometer (maximum central momentum 4.3 GeV/c) and the emitted photon in a slightly expanded PbF_2 calorimeter. In general, we will not detect the recoil proton. The H(e,e'g)X missing mass resolution is sufficient to isolate the exclusive channel with 3% systematic precision

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Discrete Wigner function dynamics

We study the evolution of the discrete Wigner function for prime and the power of prime dimensions using the discrete version of the star-product operation. Exact and semiclassical dynamics in the limit of large dimensions are considered. © 2005 IOP Publishing Ltd

Geometrical approach to the discrete Wigner function in prime power dimensions

We analyse the Wigner function in prime power dimensions constructed on the basis of the discrete rotation and displacement operators labelled with elements of the underlying finite field. We separately discuss the case of odd and even characteristics and analyse the algebraic origin of the non-uniqueness of the representation of the Wigner function. Explicit expressions for the Wigner kernel are given in both cases. © 2006 IOP Publishing Ltd

Turbulent Inflow Generation for the Large-Eddy Simulation Technique Through Globally Neutral Buoyancy Perturbations

An ongoing challenge in broadening the adoption of the large-eddy simulation (LES) technique to practical engineering flows is the need to generate turbulent inflow conditions that can trigger and sustain the expected energy cascade of turbulence in the flow domain. Several methods for generating realistic turbulent inflow conditions have been proposed, each with strengths and weaknesses, yet the topic of turbulent inflow boundary conditions remains an active research area. We investigate the method of buoyancy perturbations by Muñoz-Esparza et al.1,2 for the turbulent channel flow case, and extend it to better simulate the expected first and second order turbulence statistics. Our results show that buoyancy perturbations can be practical for generating turbulent inflow conditions, but turbulence statistics are dependent on the specifics of the implementation