The brittle-to-ductile transition in cold-rolled tungsten sheets: the rate-limiting mechanism of plasticity controlling the BDT in ultrafine-grained tungsten

Conventionally produced tungsten (W) sheets are brittle at room temperature. In contrast to that, severe deformation by cold rolling transforms W into a material exhibiting room-temperature ductility with a brittle-to-ductile transition (BDT) temperature far below room temperature. For such ultrafine-grained (UFG) and dislocation-rich materials, the mechanism controlling the BDT is still the subject of ongoing debates. In order to identify the mechanism controlling the BDT in room-temperature ductile W sheets with UFG microstructure, we conducted campaigns of fracture toughness tests accompanied by a thermodynamic analysis deducing Arrhenius BDT activation energies. Here, we show that plastic deformation induced by rolling reduces the BDT temperature and also the BDT activation energy. A comparison of BDT activation energies with the trend of Gibbs energy of kink-pair formation revealed a strong correlation between both quantities. This demonstrates that out of the three basic processes, nucleation, glide, and annihilation, crack tip plasticity in UFG W is still controlled by the glide of dislocations. The glide is dictated by the mobility of the screw segments and therefore by the underlying process of kink-pair formation. Reflecting this result, a change of the rate-limiting mechanism for plasticity of UFG W seems unlikely, even at deformation temperatures well below room temperature. As a result, kink-pair formation controls the BDT in W over a wide range of microstructural length scales, from single crystals and coarse-grained specimens down to UFG microstructures

The brittle-to-ductile transition in cold-rolled tungsten sheets: Contributions of grain and subgrain boundaries to the enhanced ductility after pre-deformation

One of the key demands on tungsten (W) as designated plasma-facing material (PFM) is the capability to fulfill a structural function. Since W has refused ductilization strategies by alloying alone, the production of W materials with enhanced ductility has come into focus considering tailored microstructures. This work addresses the rolling-induced microstructural modifications of warm- and cold-deformed W sheets and is supplemented by a comprehensive fracture mechanical study as a fundament for correlations between the spatial distribution of boundaries and brittle-to-ductile transition (BDT) temperature. Here we show that an extended Hall–Petch-like relationship is well suited to describe the rolling-induced reduction in BDT temperature and moreover has the potential to reflect the anisotropic nature of the transition temperature in severely rolled W sheets. Using the data of warm- and cold-rolled W sheets and also of strongly recovered W, best description of the BDT temperature was achieved by using as microstructural variables (i) the mean spacing between boundaries which intersect with the crack front and (ii) the mean boundary spacing along the normal of the crack plane. Taking into account the similarity to recent simulative-derived relationships, our findings support the theory suggesting the stimulated dislocation nucleation at boundaries as the decisive factor for more effective shielding of the crack tip in UFG materials and, in consequence, significantly reduced BDT temperatures. Besides, this work gives strong indications that the reduction of the BDT temperature in UFG W is not related to coincidence site lattice (CSL) boundaries

The brittle-to-ductile transition in cold-rolled tungsten sheets: On the loss of room-temperature ductility after annealing and the phenomenon of 45° embrittlement

The high brittle-to-ductile transition (BDT) temperature of conventionally produced tungsten (W), challenges the design of W-based structural components. Recent studies have demonstrated the potential of cold rolling to produce W sheets, which are ductile at room temperature and exhibit a BDT temperature of 208 K. In order to assess the thermal stability of these materials, we conducted isothermal heat treatments (at 1300 K, for annealing durations between 0.1 h and 210 h) combined with studies on the evolution of mechanical properties and microstructure of a severely deformed undoped W sheet. With this work, we demonstrate the need for a stabilized microstructure before utilization of cold-rolled W in high-temperature applications can take place successfully. After annealing at 1300 K for 6 h, the material properties changed remarkably: The BDT temperature increases from 208 K to 473 K and the sharp BDT of the as-rolled condition transforms into a wide transition regime spanning over more than 200 K. This means in fact, an endangered structural integrity at room temperature. We also address the so-called phenomenon of 45° embrittlement of W sheets. Here we show that cleavage fracture in strongly textured W sheets always takes place with an inclination angle of 45° to the rolling direction, independent of the studied material condition, whether as-rolled or annealed. An in-depth study of the microstructure indicates a correlation between an increased BDT temperature caused by annealing and microstructural coarsening presumably by extended recovery. We conclude that 45° embrittlement needs to be comprehended as a combined effect of an increased spacing between grain boundaries along the crack front, leading to an increased BDT, and a high orientation density of the rotated cube component or texture components close to that, which determine the preferred crack propagation of 45° to the rolling direction

Corporate Security Responsibility: Towards a Conceptual Framework for a Comparative Research Agenda

The political debate about the role of business in armed conflicts has increasingly raised expectations as to governance contributions by private corporations in the fields of conflict prevention, peace-keeping and postconflict peace-building. This political agenda seems far ahead of the research agenda, in which the negative image of business in conflicts, seen as fuelling, prolonging and taking commercial advantage of violent conflicts,still prevails. So far the scientific community has been reluctant to extend the scope of research on ‘corporate social responsibility’ to the area of security in general and to intra-state armed conflicts in particular. As a consequence, there is no basis from which systematic knowledge can be generated about the conditions and the extent to which private corporations can fulfil the role expected of them in the political discourse. The research on positive contributions of private corporations to security amounts to unconnected in-depth case studies of specific corporations in specific conflict settings. Given this state of research, we develop a framework for a comparative research agenda to address the question: Under which circumstances and to what extent can private corporations be expected to contribute to public security

COVID-19 among heart transplant recipients in Germany: a multicenter survey

Abstract Aims Heart transplantation may represent a particular risk factor for severe coronavirus infectious disease 2019 (COVID-19) due to chronic immunosuppression and frequent comorbidities. We conducted a nation-wide survey of all heart transplant centers in Germany presenting the clinical characteristics of heart transplant recipients with COVID-19 during the first months of the pandemic in Germany. Methods and results A multicenter survey of all heart transplant centers in Germany evaluating the current status of COVID-19 among adult heart transplant recipients was performed. A total of 21 heart transplant patients with COVID-19 was reported to the transplant centers during the first months of the pandemic in Germany. Mean patient age was 58.6 ± 12.3 years and 81.0% were male. Comorbidities included arterial hypertension (71.4%), dyslipidemia (71.4%), diabetes mellitus (33.3%), chronic kidney failure requiring dialysis (28.6%) and chronic-obstructive lung disease/asthma (19.0%). Most patients received an immunosuppressive drug regimen consisting of a calcineurin inhibitor (71.4%), mycophenolate mofetil (85.7%) and steroids (71.4%). Eight of 21 patients (38.1%) displayed a severe course needing invasive mechanical ventilation. Those patients showed a high mortality (87.5%) which was associated with right ventricular dysfunction (62.5% vs. 7.7%; p = 0.014), arrhythmias (50.0% vs. none; p = 0.012), and thromboembolic events (50.0% vs. none; p = 0.012). Elevated high-sensitivity cardiac troponin T- and N-terminal prohormone of brain natriuretic peptide were significantly associated with the severe form of COVID-19 (p = 0.017 and p < 0.001, respectively). Conclusion Severe course of COVID-19 was frequent in heart transplanted patients. High mortality was associated with right ventricular dysfunction, arrhythmias, thromboembolic events, and markedly elevated cardiac biomarkers

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Cell-permeable nicotinamide adenine dinucleotides for exploration of cellular protein ADP-ribosylation

Posttranslational modifications (PTMs) greatly enhance the functional diversity of proteins, surpassing the number of gene-encoded variations. One intriguing PTM is ADP-ribosylation, which utilizes nicotinamide adenine dinucleotide (NAD+) as a substrate and is essential in cell signaling pathways regulating cellular responses. Here, we report the first cell-permeable NAD+ analogs and demonstrate their utility for investigating cellular ADP-ribosylation. Using a desthiobiotin-labelled analog for affinity enrichment of proteins that are ADP-ribosylated in living cells under oxidative stress, we identified protein targets associated with host-virus interactions, DNA damage and repair, protein biosynthesis, and ribosome biogenesis. Most of these targets have been noted in various literature sources, highlighting the potential of our probes for cellular ADP-ribosylome studies

Herzinsuffizienzprotektion bei Patienten mit Diabetes mellitus Typ 2 durch SGLT2-Inhibitoren – Evidenzlage und mögliche Mechanismen

Background!#!Renal sodium-glucose cotransporter‑2 (SGLT2) inhibitors seem to have a cardioprotective effect beyond the antidiabetic effect. The underlying mechanisms are unclear.!##!Methods!#!Selective search in PubMed with a focus on heart failure endpoints and possible mechanisms of action.!##!Results!#!During treatment with three of the substances analyzed, there were fewer hospitalizations for heart failure compared with placebo; however, the numbers needed to treat within the primary analyses were relatively high (72-117). We found that loss of weight and lowering of blood pressure were more pronounced during treatment with verum than with placebo and an association of the preventive effect with more severely impaired renal function.!##!Conclusion!#!The SGLT2 inhibitors show a moderate heart failure protective effect in diabetic patients. It is likely that a nephroprotective effect with modulation of the cardiorenal interaction is an important part of the mechanism of action but this must be substantiated in further investigations