p21 (WAF1) is component of a positive feedback loop that maintains the p53 transcriptional program

The regulation of p53 activity through the MDM2 negative feedback loop is driven in part by an extrinsic ATM-pulse that maintains p53 oscillations in response to DNA damage. We report here that the p53 pathway has evolved an intrinsic positive feedback loop that is maintained by the p53-inducible gene product p21WAF1. p21-null cancer cells have defects in p53 protein turnover, reductions in MDM2-mediated degradation of p53, and reduced DNA damage-induced ubiquitination of p53. TLR3-IRF1 or ATM-dependent signaling to p53 is defective in p21-null cells and complementation of the p21 gene in p21-null cancer cells restores the p53 transcriptional response. The mechanism of p53 inactivity in p21-null cells is linked to a p53 protein equilibrium shift from chromatin into cytosolic fractions and complementation of the p21 gene into p21-null cells restores the nuclear localization of p53. A loss of p53 transcriptional function in murine B-cells heterozygous or homozygous null for p21 highlights a p21-gene dosage effect that maintains the full p53 transcriptional response. ATM inhibition results in nuclear exclusion of p53 highlighting a positive genetic interaction between ATM and p21. P21 protein oscillates in undamaged proliferating cells, and reductions of p21 protein using siRNA eliminate the DNA damage-induced p53 pulse. The p53 transcription program has evolved a negative feedback loop maintained by MDM2 that is counteracted by a positive feedback loop maintained by ATM-p21 the balance of which controls the specific activity of p53 as a transcription factor

On perfect fluid models in non-comoving observational spherical coordinates

We use null spherical (observational) coordinates to describe a class of inhomogeneous cosmological models. The proposed cosmological construction is based on the observer past null cone. A known difficulty in using inhomogeneous models is that the null geodesic equation is not integrable in general. Our choice of null coordinates solves the radial ingoing null geodesic by construction. Furthermore, we use an approach where the velocity field is uniquely calculated from the metric rather than put in by hand. Conveniently, this allows us to explore models in a non-comoving frame of reference. In this frame, we find that the velocity field has shear, acceleration and expansion rate in general. We show that a comoving frame is not compatible with expanding perfect fluid models in the coordinates proposed and dust models are simply not possible. We describe the models in a non-comoving frame. We use the dust models in a non-comoving frame to outline a fitting procedure.Comment: 8 pages, 1 figure. To appear in Phys.Rev.

Cosmological expansion and local systems: a Lema\^{i}tre-Tolman-Bondi model

We propose a Lema\^{i}tre-Tolman-Bondi system mimicking a two-body system to address the problem of the cosmological expansion versus local dynamics. This system is strongly bound but participates in the cosmic expansion and is exactly comoving with the cosmic substratum

GOALS-JWST: unveiling dusty compact sources in the merging galaxy IIZw096

Galaxie

GOALS-JWST: hidden star formation and extended PAH emission in the luminous infrared galaxy VV 114

Galaxie

GOALS-JWST: resolving the circumnuclear gas dynamics in NGC 7469 in the mid-infrared

Galaxie

GOALS-JWST: tracing AGN feedback on the star-forming interstellar medium in NGC 7469

Galaxie

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Search for strong gravity in multijet final states produced in pp collisions at √s=13 TeV using the ATLAS detector at the LHC

A search is conducted for new physics in multijet final states using 3.6 inverse femtobarns of data from proton-proton collisions at √s = 13TeV taken at the CERN Large Hadron Collider with the ATLAS detector. Events are selected containing at least three jets with scalar sum of jet transverse momenta (HT) greater than 1TeV. No excess is seen at large HT and limits are presented on new physics: models which produce final states containing at least three jets and having cross sections larger than 1.6 fb with HT > 5.8 TeV are excluded. Limits are also given in terms of new physics models of strong gravity that hypothesize additional space-time dimensions