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)

The results of test run 1A with the experimental facility "AUWARM"

The experimental facility "AUWARM" in spite of being designed for hydrogen permeation tests under steam/methane reforming conditions, was also used for studies on the hydrogen permeation under conditions of coal gasification with steam. As an-attempt, specimens were made of a tube which had been exposed in a gas generator, and tested in the facility. The experimental results indicate that in principle good oxide layers establish in a process gas typical for coal gasification with steam,whereas the original scales have probably been damaged by the sample manufacturing

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

Causes of adverse events in home mechanical ventilation: a nursing perspective

Background Adverse events (AE) are ubiquitous in home mechanical ventilation (HMV) and can jeopardise patient safety. One particular source of error is human interaction with life-sustaining medical devices, such as the ventilator. The objective is to understand these errors and to be able to take appropriate action. With a systematic analysis of the hazards associated with HMV and their causes, measures can be taken to prevent damage to patient health. Methods A systematic adverse events analysis process was conducted to identify the causes of AE in intensive home care. The analysis process consisted of three steps. 1) An input phase consisting of an expert interview and a questionnaire. 2) Analysis and categorisation of the data into a root-cause diagram to help identify the causes of AE. 3) Derivation of risk mitigation measures to help avoid AE. Results The nursing staff reported that patient transportation, suction and tracheostomy decannulation were the main factors that cause AE. They would welcome support measures such as checklists for care activities and a reminder function, for e.g. tube changes. Risk mitigation measures are given for many of the causes listed in the root-cause diagram. These include measures such as device and care competence, as well as improvements to be made by the equipment providers and manufacturers. The first step in addressing AE is transparency and an open approach to errors and near misses. A systematic error analysis can prevent patient harm through a preventive approach. Conclusion Risks in HMV were identified based on a qualitative approach. The collected data was systematically mapped onto a root-cause diagram. Using the root-cause diagram, some of the causes were analysed for risk mitigation. For manufacturers, caregivers and care services requirements for intervention offers the possibility to create a checklist for particularly risky care activities

Überblick über die neueren Arbeiten auf dem Gebiet des Wasserstoff-und Tritiumverhaltens in Hochtemperaturreaktoren

This report comprises the contributions of members of the "Institut für Reaktor-Entwicklung" (IRE) to the "Und Seminar on Hydrogen and Tritium Behaviour in High Temperature Reactors", which was held March 8, 1978, at KFA Jülich. At the beginning the problem is introduced and the investigations at IRE related to this area are presented in their context. Then follow the individual papers on the subjects mentioned. At first the experiences with the operation of the experimental facility AUWARM and the newest results in the current testing program are discussed. Therafter the model investigations with hydrogen and deuterium on the problem of hydrogen- and tritium permeation are reported and a computer program for balancing tritium in pebble-bed-HTRs is described. Last notleast the studies on the behaviour of tritium in matrix graphite and the experiments on primary coolant purification by titanium gettering are shortly communicated. The results given in this report are preliminary informations on the actual status of the current investigations

Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection

Lung infections caused by Pseudomonas aeruginosa pose a serious threat to patients suffering from, among others, cystic fibrosis, chronic obstructive pulmonary disease, or bronchiectasis, often leading to life-threatening complications. The establishment of a chronic infection is substantially related to communication between bacteria via quorum-sensing networks. In this study, we aimed to assess the role of quorum-sensing signaling molecules of the Pseudomonas quinolone signal (PQS) and to investigate the viscoelastic properties of lung tissue homogenates of PA-infected mice in a prolonged acute murine infection model. Therefore, a murine infection model was successfully established via intra-tracheal infection with alginate-supplemented Pseudomonas aeruginosa NH57388A. Rheological properties of lung homogenates were analyzed with multiple particle tracking (MPT) and quorum-sensing molecules were quantified with LC–MS/MS. Statistical analysis of bacterial load and quorum-sensing molecules showed a strong correlation between these biomarkers in infected lungs. This was accompanied by noticeable changes in the consistency of lung homogenates with increasing infection severity. Furthermore, viscoelastic properties of the lung homogenates strongly correlated with bacterial load and quorum sensing molecules. Considering the strong correlation between the viscoelasticity of lung homogenates and the aforementioned biomarkers, the viscoelastic properties of infected lungs might serve as reliable new biomarker for the evaluation of the severity of P. aeruginosa infections in murine models

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa