Proteins from Modern and Ancient Wheat Cultivars: Impact on Immune Cells of Healthy Individuals and Patients with NCGS

In non-celiac gluten sensitivity (NCGS), the elimination of wheat results in a clear symptom improvement, but gluten has still not been proven as (the sole) trigger. Due to the increase in the prevalence of gluten-related diseases, the breeding of high-performance wheat cultivars is discussed as a trigger. To analyze the immune stimulation and signal pathways, the immune cells of healthy subjects and patients with NCGS were stimulated with gliadins from wheat, and the expression and secretion of interleukin 1ß (IL1ß) and interleukin 6 (IL6) were studied. To determine the impact of wheat breeding, the monocyte cell line THP1 and human immune cells were stimulated with gliadin, glutenin, and albumin/globulin fractions of ancient and modern cereals, and expression of inflammatory molecules was checked. Immune cells of patients with NCGS showed an increased expression of IL1ß and IL6 after stimulation with gliadins compared to immune cells of healthy controls. Gliadins caused a strong activation of P-STAT3 in immune cells of healthy controls, and inhibitors of JAK and NFκB pathways considerably reduced this response. In addition to gliadins, we further showed that glutenins and albumin/globulins from all wheat cultivars from the last century, and especially from einkorn and spelt, also markedly induced the expression of inflammatory genes in THP1 and human immune cells. There was no correlation between enhanced immune stimulation and ancient or modern cultivars. This does not support the hypothesis that modern wheat breeding is responsible for the increase in gluten-related diseases. An altered immune situation is suggested in patients with NCGS

A Novel Deep Learning Model as a Donor-Recipient Matching Tool to Predict Survival after Liver Transplantation

Background: The digital era in the field of medicine is the new here and now. Artificial intelligence has entered many fields of medicine and is recently emerging in the field of organ transplantation. Solid organs remain a scarce resource. Being able to predict the outcome after liver transplantation promises to solve one of the long-standing problems within organ transplantation. What is the perfect donor recipient match? Within this work we developed and validated a novel deep-learning-based donor-recipient allocation system for liver transplantation. Method: In this study we used data collected from all liver transplant patients between 2004 and 2019 at the university transplantation centre in Munich. We aimed to design a transparent and interpretable deep learning framework to predict the outcome after liver transplantation. An individually designed neural network was developed to meet the unique requirements of transplantation data. The metrics used to determine the model quality and its level of performance are accuracy, cross-entropy loss, and F1 score as well as AUC score. Results: A total of 529 transplantations with a total of 1058 matching donor and recipient observations were added into the database. The combined prediction of all outcome parameters was 95.8% accurate (cross-entropy loss of 0.042). The prediction of death within the hospital was 94.3% accurate (cross-entropy loss of 0.057). The overall F1 score was 0.899 on average, whereas the overall AUC score was 0.940. Conclusion: With the achieved results, the network serves as a reliable tool to predict survival. It adds new insight into the potential of deep learning to assist medical decisions. Especially in the field of transplantation, an AUC Score of 94% is very valuable. This neuronal network is unique as it utilizes transparent and easily interpretable data to predict the outcome after liver transplantation. Further validation must be performed prior to utilization in a clinical context

A blind benchmark of analysis tools to infer kinetic rate constants from single-molecule FRET trajectories

Single-molecule FRET (smFRET) is a versatile technique to study the dynamics and function of biomolecules since it makes nanoscale movements detectable as fluorescence signals. The powerful ability to infer quantitative kinetic information from smFRET data is, however, complicated by experimental limitations. Diverse analysis tools have been developed to overcome these hurdles but a systematic comparison is lacking. Here, we report the results of a blind benchmark study assessing eleven analysis tools used to infer kinetic rate constants from smFRET trajectories. We test them against simulated and experimental data containing the most prominent difficulties encountered in analyzing smFRET experiments: different noise levels, varied model complexity, non-equilibrium dynamics, and kinetic heterogeneity. Our results highlight the current strengths and limitations in inferring kinetic information from smFRET trajectories. In addition, we formulate concrete recommendations and identify key targets for future developments, aimed to advance our understanding of biomolecular dynamics through quantitative experiment-derived models

Production of Nickel‐Rich Cathodes for Lithium‐Ion Batteries from Lab to Pilot Scale under Investigation of the Process Atmosphere

The selection of an appropriate cathode active material is important for operation performance and production of high-performance lithium-ion batteries. Promising candidates are nickel-rich layered oxides like LiNi$_x$Co$_y$Mn$_z$O$_2$ (NCM, x+y+z=1) with nickel contents of ‘x’ ≥ 0.8, characterized by high electrode potential and specific capacity. However, these materials are associated with capacity fading due to their high sensitivity to moisture. Herein, two different polycrystalline NCM materials with nickel contents of 0.81 ≤ ‘x’ ≤ 0.83 and protective surface coatings are processed in dry-room atmosphere (dew point of supply air T$_D$ ≈ −65 °C) at lab scale including the slurry preparation and coating procedure. In comparison, cathodes are produced in ambient atmosphere and both variants are tested in coin cells. Moreover, processing at pilot scale in ambient atmosphere is realized successfully by continuous coating and drying of the cathodes. Relevant electrode properties such as adhesion strength, specific electrical resistance, and pore-size distribution for the individual process steps are determined, as well as the moisture uptake during calendering. Furthermore, rate capability and cycling stability are investigated in pouch cells, wherein initial specific discharge capacities of up to 190 mAh g$^{−1}$ (with regard to the cathode material mass) are achieved at 0.2C

Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Liver Transplantation Mitigates Post-Reperfusion Syndrome and Perioperative Electrolyte Shifts

(1) Background: Post-reperfusion syndrome (PRS) and electrolyte shifts (ES) represent considerable challenges during liver transplantation (LT) being associated with significant morbidity. We aimed to investigate the impact of hypothermic oxygenated machine perfusion (HOPE) on PRS and ES in LT. (2) Methods: In this retrospective study, we compared intraoperative parameters of 100 LTs, with 50 HOPE preconditioned liver grafts and 50 grafts stored in static cold storage (SCS). During reperfusion phase, prospectively registered serum parameters and vasopressor administration were analyzed. (3) Results: Twelve percent of patients developed PRS in the HOPE cohort vs. 42% in the SCS group (p = 0.0013). Total vasopressor demand in the first hour after reperfusion was lower after HOPE pretreatment, with reduced usage of norepinephrine (-26%;p = 0.122) and significant reduction of epinephrine consumption (-52%;p = 0.018). Serum potassium concentration dropped by a mean of 14.1% in transplantations after HOPE, compared to a slight decrease of 1% (p < 0.001) after SCS. The overall incidence of early allograft dysfunction (EAD) was reduced by 44% in the HOPE group (p = 0.04). (4) Conclusions: Pre-transplant graft preconditioning with HOPE results in higher hemodynamic stability during reperfusion and lower incidence of PRS and EAD. HOPE has the potential to mitigate ES by preventing hyperpotassemic complications that need to be addressed in LT with HOPE-pre-treated grafts

A novel approach towards skill-based search and services of Open Educational Resources

Ha, K.-H., Niemann, K., Schwertel, U., Holtkamp, P., Pirkkalainen, H., Börner, D. et al (2011). A novel approach towards skill-based search and services of Open Educational Resources. In E. Garcia-Barriocanal, A. Öztürk, & M. C. Okur (Eds.), Metadata and Semantics Research: 5th International Conference MTSR 2011 (pp. 312-323), Izmir, Turkey, October 12-14, 2011. Springer.Open educational resources (OER) have a high potential to address the growing need for training materials in management education and training. Today, a high number of OER in management are already available in a large number of repositories. However, users face barriers as they have to search repository by repository with different interfaces to retrieve the appropriate learning content. In addition, the use of search criteria related to skills, such as learning objectives and skill-levels is not generally supported. The European co-funded project OpenScout addresses these barriers by intelligently connecting leading European OER repositories and providing federated, skillbased search and retrieval web services. On top of this content federation the project supports users with easy-to-apply tools that will accelerate the (re-) use of open content

Neutrinos and Cosmic Rays Observed by IceCube

The core mission of the IceCube Neutrino observatory is to study the origin and propagation of cosmic rays. IceCube, with its surface component IceTop, observes multiple signatures to accomplish this mission. Most important are the astrophysical neutrinos that are produced in interactions of cosmic rays, close to their sources and in interstellar space. IceCube is the first instrument that measures the properties of this astrophysical neutrino flux, and constrains its origin. In addition, the spectrum, composition and anisotropy of the local cosmic-ray flux are obtained from measurements of atmospheric muons and showers. Here we provide an overview of recent findings from the analysis of IceCube data, and their implications on our understanding of cosmic rays.Comment: Review article, to appear in Advances in Space Research, special issue "Origins of Cosmic Rays

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029

Neutrino interferometry for high-precision tests of Lorentz symmetry with IceCube

We acknowledge the support from the following agencies: USA—US National Science Foundation–Office of Polar Programs, US National Science Foundation–Physics Division, Wisconsin Alumni Research Foundation, Center for High Throughput Computing (CHTC) at the University of Wisconsin–Madison, Open Science Grid (OSG), Extreme Science and Engineering Discovery Environment (XSEDE), US Department of Energy–National Energy Research Scientific Computing Center, Particle astrophysics research computing centre at the University of Maryland, Institute for Cyber-Enabled Research at Michigan State University and Astroparticle physics computational facility at Marquette University; Belgium—Funds for Scientific Research (FRS-FNRS and FWO), FWO Odysseus and Big Science programmes, and Belgian Federal Science Policy Office (Belspo); Germany—Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Helmholtz Alliance for Astroparticle Physics (HAP), Initiative and Networking Fund of the Helmholtz Association, Deutsches Elektronen Synchrotron (DESY), and High Performance Computing cluster of the RWTH Aachen; Sweden—Swedish Research Council, Swedish Polar Research Secretariat, Swedish National Infrastructure for Computing (SNIC), and Knut and Alice Wallenberg Foundation; Australia—Australian Research Council; Canada—Natural Sciences and Engineering Research Council of Canada, Calcul Québec, Compute Ontario, Canada Foundation for Innovation, WestGrid and Compute Canada; Denmark—Villum Fonden, Danish National Research Foundation (DNRF); New Zealand—Marsden Fund; Japan—Japan Society for Promotion of Science (JSPS) and Institute for Global Prominent Research (IGPR) of Chiba University; Korea—National Research Foundation of Korea (NRF); Switzerland—Swiss National Science Foundation (SNSF); UK—Science and Technology Facilities Council (STFC) and The Royal Society

Differential prognostic utility of adiposity measures in chronic kidney disease

Objective Adipose tissue contributes to adverse outcomes in chronic kidney disease (CKD), but there is uncertainty regarding the prognostic relevance of different adiposity measures. We analyzed the associations of neck circumference (NC), waist circumference (WC), and body mass index (BMI) with clinical outcomes in patients with mild to severe CKD. Methods The German Chronic Kidney Disease (GCKD) study is a prospective cohort study, which enrolled Caucasian adults with mild to severe CKD, defined as estimated glomerular filtration rate (eGFR): 30–60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 in the presence of overt proteinuria. Associations of NC, WC and BMI with all-cause death, major cardiovascular events (MACE: a composite of non-fatal stroke, non-fatal myocardial infarction, peripheral artery disease intervention, and cardiovascular death), kidney failure (a composite of dialysis or transplantation) were analyzed using multivariable Cox proportional hazards regression models adjusted for confounders and the Akaike information criteria (AIC) were calculated. Models included sex interactions with adiposity measures. Results A total of 4537 participants (59% male) were included in the analysis. During a 6.5-year follow-up, 339 participants died, 510 experienced MACE, and 341 developed kidney failure. In fully adjusted models, NC was associated with all-cause death in women (HR 1.080 per cm; 95% CI 1.009–1.155), but not in men. Irrespective of sex, WC was associated with all-cause death (HR 1.014 per cm; 95% CI 1.005–1.038). NC and WC showed no association with MACE or kidney failure. BMI was not associated with any of the analyzed outcomes. Models of all-cause death including WC offered the best (lowest) AIC. Conclusion In Caucasian patients with mild to severe CKD, higher NC (in women) and WC were significantly associated with increased risk of death from any cause, but BMI was not