Industrial production quantities and uses of ten engineered nanomaterials in Europe and the world

Not much is known so far about the amounts of engineered nanomaterials (ENM) that are produced but this information is crucial for environmental exposure assessment. This paper provides worldwide and Europe-wide estimates for the production and use of ten different ENM (TiO2, ZnO, FeO x , AlO x , SiO2, CeO2, Ag, quantum dots, CNT, and fullerenes) based on a survey sent to companies producing and using ENM. The companies were asked about their estimate of the worldwide or regional market and not about their company-specific production, information that they would be less likely to communicate. The study focused on the actual production quantities and not the production capacities. The survey also addressed information on distribution of the produced ENM to different product categories. The results reveal that some ENM are produced in Europe in small amounts (less than 10t/year for Ag, QDs and fullerenes). The most produced ENM is TiO2 with up to 10,000t of worldwide production. CeO2, FeO x , AlO x , ZnO, and CNT are produced between 100 and 1000t/year. The data for SiO2 cover the whole range from less than 10 to more than 10,000t/year, which is indicative of problems related to the definition of this material (is pyrogenic silica considered an ENM or not?). For seven ENM we have obtained the first estimates for their distribution to different product categories, information that also forms the base for life-cycle based exposure analysi

A 1D RCE study of factors affecting the tropical tropopause layer and surface climate

There are discrepancies between global climate models regarding the evolution of the tropical tropopause layer (TTL) and also whether changes in ozone impact the surface under climate change. We use a 1D clear-sky radiative–convective equilibrium model to determine how a variety of factors can affect the TTL and how they influence surface climate. We develop a new method of convective adjustment, which relaxes the temperature profile toward the moist adiabat and allows for cooling above the level of neutral buoyancy. The TTL temperatures in our model are sensitive to CO2 concentration, ozone profile, the method of convective adjustment, and the upwelling velocity, which is used to calculate a dynamical cooling rate in the stratosphere. Moreover, the temperature response of the TTL to changes in each of the above factors sometimes depends on the others. The surface temperature response to changes in ozone and upwelling at and above the TTL is also strongly amplified by both stratospheric and tropospheric water vapor changes. With all these influencing factors, it is not surprising that global models disagree with regard to TTL structure and evolution and the influence of ozone changes on surface temperatures. On the other hand, the effect of doubling CO2 on the surface, including just radiative, water vapor, and lapse-rate feedbacks, is relatively robust to changes in convection, upwelling, or the applied ozone profile

ErUM-Data-Hub - The Networking and Transfer Office serving Digital Transformation in Research on Universe and Matter in Germany

Research on Universe and Matter (ErUM), conducted at major infrastructures such as CERN and large observatories in collaboration with university groups, plays an important role in driving the digital transformation for the future. The German action plan "ErUM-Data" [2] promotes this transformation through the interdisciplinary networking and financial support of about 20.000 scientists. The ErUM-Data-Hub [4] serves as a central networking and transfer office to meet these ambitions. One central task is designing, organizing and performing schools and workshops for young and expert scientists in the areas of big data, deep learning, sustainable computing and many more. We present the achievements up to the first anniversary of the ErUM-Data-Hub in the German ErUM community

Effect of Finerenone on chronic kidney disease outcomes in type 2 diabetes

Background: Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown. Methods: In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively). Conclusions: In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.)

The Arabidopsis thaliana F-Box Protein FBL17 Is Essential for Progression through the Second Mitosis during Pollen Development

In fungi and metazoans, the SCF-type Ubiquitin protein ligases (E3s) play a critical role in cell cycle regulation by degrading negative regulators, such as cell cycle-dependent kinase inhibitors (CKIs) at the G1-to-S-phase checkpoint. Here we report that FBL17, an Arabidopsis thaliana F-box protein, is involved in cell cycle regulation during male gametogenesis. FBL17 expression is strongly enhanced in plants co-expressing E2Fa and DPa, transcription factors that promote S-phase entry. FBL17 loss-of-function mutants fail to undergo pollen mitosis II, which generates the two sperm cells in mature A. thaliana pollen. Nonetheless, the single sperm cell-like cell in fbl17 mutants is functional but will exclusively fertilize the egg cell of the female gametophyte, giving rise to an embryo that will later abort, most likely due to the lack of functional endosperm. Seed abortion can, however, be overcome by mutations in FIE, a component of the Polycomb group complex, overall resembling loss-of-function mutations in the A. thaliana cyclin-dependent kinase CDKA;1. Finally we identified ASK11, as an SKP1-like partner protein of FBL17 and discuss a possible mechanism how SCFFBL17 may regulate cell division during male gametogenesis

LEGaTO: towards energy-efficient, secure, fault-tolerant toolset for heterogeneous computing

LEGaTO is a three-year EU H2020 project which started in December 2017. The LEGaTO project will leverage task-based programming models to provide a software ecosystem for Made-in-Europe heterogeneous hardware composed of CPUs, GPUs, FPGAs and dataflow engines. The aim is to attain one order of magnitude energy savings from the edge to the converged cloud/HPC.Peer ReviewedPostprint (author's final draft

A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease

AIMS: To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. METHODS AND RESULTS: Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively, on Day 30) or eplerenone (25 mg every other day, increased to 25 mg once daily on Day 30, and to 50 mg once daily on Day 60) for 90 days. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to Day 90. A key exploratory endpoint was a composite clinical endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentation for worsening HF until Day 90. Mean age ranged from 69.2 to 72.5 years in different treatment groups (standard deviation 9.7–10.6 years). Decreases in NT-proBNP of >30% from baseline occurred in 37.2% of patients in the eplerenone group and 30.9, 32.5, 37.3, 38.8, and 34.2% in the 2.5→5, 5→10, 7.5→15, 10→20, and 15→20 mg finerenone groups, respectively (P = 0.42–0.88). Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred numerically less frequently in finerenone-treated patients compared with eplerenone; this difference reached nominal statistical significance in the 10→20 mg group (hazard ratio 0.56, 95% confidence interval, CI, 0.35; 0.90; nominal P = 0.02), despite the fact that this phase 2 study was not designed to detect statistical significant differences. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients, with a balanced distribution among all treatment groups. CONCLUSION: Finerenone was well tolerated and induced a 30% or greater decrease in NT-proBNP levels in a similar proportion of patients to eplerenone. The finding of reduced clinical events in the finerenone 10→20 mg group should be further explored in a large outcomes trial