Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

The effects of cold working on sensitization and intergranular corrosion behavior of AISI 304 stainless steel

The effects of prior cold rolling of up to an 80 pct reduction in thickness on the sensitization-desensitization behavior of Type AISI 304 stainless steel and its susceptibility to intergranular corrosion have been studied by electrochemical potentiokinetic reactivation (EPR) and Strauss-test methods. The results indicate that the prior deformation accelerated the sensitization as compared to the undeformed stainless steel. The deformed Type 304 stainless steel experienced desensitization at higher temperatures and times, and it was found to be enhanced by increased cold deformation. This could be attributed to the increased long-range chromium diffusion, possibly brought on by increasing pipe diffusion and vacancies. The role of the deformation-induced martensite (DIM) and texture, introduced by uniaxial cold rolling, on the sensitization-desensitization kinetics has also been discussed. This study could not reveal any systematic relationship between texture and the degree of sensitization (DOS) obtained. The effect of DIM on DOS seems to be pronounced at 500 °C when the steel retained significant amounts of DIM; however, the retained DIM is insignificant at higher sensitization times and temperatures

High voltage calibration method for the CMS RPC detector

The Resistive Plate Chambers (RPC) are used for muon triggers in the CMS experiment. To calibrate the high voltage working-points (WP) and identify degraded detectors due to radiation or chemical damage, a high voltage scan has been performed using 2017 data from pp collisions at a center-of-mass energy of 13 TeV. In this paper, we present the calibration method and the latest results obtained for the 2017 data. A comparison with all scans taken since 2011 is considered to investigate the stability of the detector performance in time

CMSRPC efficiency measurement using the tag-and-probe method

We measure the efficiency of CMS Resistive Plate Chamber (RPC) detectors in proton-proton collisions at the centre-of-mass energy of 13 TeV using the tag-and-probe method. A muon from a Z(0) boson decay is selected as a probe of efficiency measurement, reconstructed using the CMS inner tracker and the rest of CMS muon systems. The overall efficiency of CMS RPC chambers during the 2016-2017 collision runs is measured to be more than 96% for the nominal RPC chambers