Evaluation and Calibration of SAPS 3 in Patients with COVID-19 Admitted to Intensive Care Units

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Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer

Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is frequently overexpressed in a variety of carcinomas. This pan-carcinoma antigen has served as the target for a plethora of immunotherapies. Innovative therapeutic approaches include the use of trifunctional antibodies (trAbs) that recruit and activate different types of immune effector cells at the tumour site. The trAb catumaxomab has dual specificity for EpCAM and CD3. In patients with malignant ascites, catumaxomab significantly increased the paracentesis-free interval, corroborating the high efficacy of this therapeutic antibody. Here, we characterised the monoclonal antibody (mAb) HO-3, that is, the EpCAM-binding arm of catumaxomab. Peptide mapping indicated that HO-3 recognises a discontinuous epitope, having three binding sites in the extracellular region of EpCAM. Studies with glycosylation-deficient mutants showed that mAb HO-3 recognised EpCAM independently of its glycosylation status. High-affinity binding was not only detected for mAb HO-3, but also for the monovalent EpCAM-binding arm of catumaxomab with an excellent KD of 5.6 × 10−10 M. Furthermore, trAb catumaxomab was at least a 1000-fold more effective in eliciting the eradication of tumour cells by effector peripheral blood mononuclear cells compared with mAb HO-3. These findings suggest the great therapeutic potential of trAbs and clearly speak in favour of EpCAM-directed cancer immunotherapies

Measurements of pion/minus/ proton elastic scattering from 1.71 to 5.53 GeV/c

Negative pion proton elastic scattering differential cross sections from 1.71 to 5.53 GeV/

Force-matched embedded-atom method potential for niobium

Large-scale simulations of plastic deformation and phase transformations in alloys require reliable classical interatomic potentials. We construct an embedded-atom method potential for niobium as the first step in alloy potential development. Optimization of the potential parameters to a well-converged set of density-functional theory (DFT) forces, energies, and stresses produces a reliable and transferable potential for molecular dynamics simulations. The potential accurately describes properties related to the fitting data, and also produces excellent results for quantities outside the fitting range. Structural and elastic properties, defect energetics, and thermal behavior compare well with DFT results and experimental data, e.g., DFT surface energies are reproduced with less than 4% error, generalized stacking-fault energies differ from DFT values by less than 15%, and the melting temperature is within 2% of the experimental value.Comment: 17 pages, 13 figures, 7 table

Seasonality in Major Depressive Disorder: Effect of Sex and Age

Background: Aside from the concept of seasonal affective disorder, the evidence for a seasonal pattern (SP) of major depressive disorder (MDD) is controversial. Furthermore, the effect of sex and age is still unclear. Methods: This is a nationwide, registry-based study assessing all inpatient admissions in mental health hospitals due to MDD episodes according to ICD-10 (moderate (F32/33.1), severe (F32/33.2) and severe with psychotic features (F32/33.3)) in Austria across 14 years. Calculations were based on deviations from expected monthly admissions. Results: The sample comprised 231,824 hospitalisations (36.8% men) for MDD. A significant SP (p=0.001) in moderate and severe depressive episodes in both women and men with decreased admission rates in the summer months and December was detected. In psychotic depression a significant SP was only evidenced in women (p = 0.002, men: p = 0.291). Patients older than 55 years had a reduced SP compared to those being younger. Limitations: Only anonymised admission data of inpatient treatments were available. Hospitalization rates cannot fully be equated to the occurrence of MDD. Conclusions: The current study indicates a seasonal variation in MDD symptoms that may go beyond seasonal affective disorder. Knowledge about the predictability of depressive symptoms in patients should encourage preventive strategies

Coupled FEM-DBEM method to assess crack growth in magnet system of Wendelstein 7-X

The fivefold symmetric modular stellarator Wendelstein 7-X (W7-X) is currently under construction in Greifswald, Germany. The superconducting coils of the magnet system are bolted onto a central support ring and interconnected with five so-called lateral support elements (LSEs) per half module. After welding of the LSE hollow boxes to the coil cases, cracks were found in the vicinity of the welds that could potentially limit the allowed number N of electromagnetic (EM) load cycles of the machine. In response to the appearance of first cracks during assembly, the Stress Intensity Factors (SIFs) were calculated and corresponding crack growth rates of theoretical semi-circular cracks of measured sizes in potentially critical position and orientation were predicted using Paris’ law, whose parameters were calibrated in fatigue tests at cryogenic temperature. In this paper the Dual Boundary Element Method (DBEM) is applied in a coupled FEM-DBEM approach to analyze the propagation of multiple cracks with different shapes. For this purpose, the crack path is assessed with the Minimum Strain Energy density criterion and SIFs are calculated by the Jintegral approach. The Finite Element Method (FEM) is adopted to model, using the commercial codes Ansys or Abaqus;, the overall component whereas the submodel analysis, in the volume surrounding the cracked area, is performed by FEM (“FEM-FEM approach”) or alternatively by DBEM (“FEM-DBEM approach”). The “FEM-FEM approach” considers a FEM submodel, that is extracted from the FEM global model; the latter provide the boundary conditions for the submodel. Such approach is affected by some restrictions in the crack propagation phase, whereas, with the “FEM-DBEM approach”, the crack propagation simulation is straightforward. In this case the submodel is created in a DBEM environment with boundary conditions provided by the global FEM analysis; then the crack is introduced and a crack propagation analysis has been performed to evaluate the effects of the crack shape and of the presence of nearby cracks on the allowed number of EM load cycles