Multipartite Nonlocal Quantum Correlations Resistant to Imperfections

We use techniques for lower bounds on communication to derive necessary conditions in terms of detector efficiency or amount of super-luminal communication for being able to reproduce with classical local hidden-variable theories the quantum correlations occurring in EPR-type experiments in the presence of noise. We apply our method to an example involving n parties sharing a GHZ-type state on which they carry out measurements and show that for local-hidden variable theories, the amount of super-luminal classical communication c and the detector efficiency eta are constrained by eta 2^(-c/n) = O(n^(-1/6)) even for constant general error probability epsilon = O(1)

Unrealistic pessimism and obsessive‐compulsive symptoms during the COVID‐19 pandemic: two longitudinal studies

OBJECTIVE: Unrealistic pessimism (UP) is an aspect of overestimation of threat (OET) that has been associated with obsessive‐compulsive disorder/symptoms (OCD/OCS). During the COVID‐19 pandemic, UP may have played an important role in the course of OCD. To investigate the relationship, we conducted two longitudinal studies assuming that higher UP predicts an increase in OCS. METHOD: In Study 1, we investigated UP in the general population (N = 1,184) at the start of the pandemic asking about overall vulnerability to infection with SARS‐CoV‐2 and UP regarding infection and outcome of severe illness. Further, OCS status (OCS+/−) was assessed at the start of the pandemic and 3 months later. In Study 2, we investigated UP in individuals with OCD (N = 268) regarding the likelihood of getting infected, recovering, or dying from an infection with SARS‐CoV‐2 at the start of the pandemic and re‐assessed OCS 3 months later. RESULTS: In Study 1, UP was higher in the OCS+ compared to the OCS− group, and estimates of a higher overall vulnerability for an infection predicted a decrease in OCS over time. UP regarding severe illness predicted an increase in symptoms over time. In Study 2, UP was found for a recovery and death after an infection with SARS‐CoV‐2, but not for infection itself. CONCLUSIONS: Exaggeration of one’s personal vulnerability rather than OET per se seems pivotal in OCD, with UP being associated with OCD/OCS+ as well as a more negative course of symptomatology over the pandemic in a nonclinical sample. PRACTITIONER POINTS: Unrealistic optimism, a bias common in healthy individuals, is thought to be a coping mechanism promoting well‐being in the face of danger or uncertainty. The current study extends findings that its inversion, unrealistic pessimism, may play an important role in obsessive‐compulsive disorder and may also be involved in the development of the disorder. This study highlights the importance that prevention programs during a pandemic should include targeting unrealistic pessimism

Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes

In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. Although occurring within the same active site, we show here that glycosylation and proteolysis occur through separable mechanisms. OGT consists of tetratricopeptide repeat (TPR) and catalytic domains, which, together with UDP-GlcNAc, are required for both glycosylation and proteolysis. Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. Thus, from a dual glycosyltransferase-protease, essentially single-activity enzymes can be engineered both in vitro and in vivo. Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. We present a model for the evolution of HCF-1 proteolysis by OGT

The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities

O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities. OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1 <sub>PRO</sub> repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1). Here, we probed the relationship between these distinct glycosylation and proteolytic activities. For proteolysis, the HCF-1 <sub>PRO</sub> repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region. We report that linkage of this HCF-1 <sub>PRO</sub> -repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor R <sub>p</sub> -αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates. Furthermore, it potentiated proteolysis of a non-HCF-1 <sub>PRO</sub> -repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue. Using serine- or glutamate-containing HCF-1 <sub>PRO</sub> -repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together. In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis. These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies

Systemic application of bone-targeting peptidoglycan hydrolases as a novel treatment approach for staphylococcal bone infection

The rising prevalence of antimicrobial resistance in S. aureus has rendered treatment of staphylococcal infections increasingly difficult, making the discovery of alternative treatment options a high priority. Peptidoglycan hydrolases, a diverse group of bacteriolytic enzymes, show high promise as such alternatives due to their rapid and specific lysis of bacterial cells, independent of antibiotic resistance profiles. However, using these enzymes for the systemic treatment of local infections, such as osteomyelitis foci, needs improvement, as the therapeutic distributes throughout the whole host, resulting in low concentrations at the actual infection site. In addition, the occurrence of intracellularly persisting bacteria can lead to relapsing infections. Here, we describe an approach using tissue-targeting to increase the local concentration of therapeutic enzymes in the infected bone. The enzymes were modified with a short targeting moiety that mediated accumulation of the therapeutic in osteoblasts and additionally enables targeting of intracellularly surviving bacteria

GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue

As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1(+) progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Glil-creER(T2)) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1(+) cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1(+) progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1(+) progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Foxl2) in response to GDX. These findings support the premise that GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13