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Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions. Samples were collected from healthy donors and metastatic colorectal cancer (mCRC) patients from the FIRE-6-Avelumab phase II study. The machine learning model accurately predicted the FcγRIIIa-V158F polymorphism in 94% of samples. FF homozygous patients showed diminished cetuximab-mediated ADCC compared to VF or VV carriers. In mCRC patients, NK cell dysfunctions were evident as impaired ADCC, decreased CD16 downregulation, and reduced CD137/CD107a induction. Elevated PD1+ NK cell levels, reduced lysis of PDL1-expressing CRC cells and improved NK cell activation in combination with the PDL1-targeting avelumab indicate that the PD1-PDL1 axis contributes to impaired cetuximab-induced NK cell function. Together, these optimized assays effectively identify NK cell dysfunctions in mCRC patients and offer potential for broader application in evaluating NK cell functionality across cancers and therapeutic settings. [ABSTRACT FROM AUTHOR]

The mechanical integrity of two commercially available lithium-ion battery separators was investigated under uniaxial and biaxial loading conditions. Two dry-processed microporous films with polypropylene (PP)/polyethylene (PE)/polypropylene (PP) compositions were studied: Celgard H2010 Trilayer and Celgard Q20S1HX Ceramic-Coated Trilayer. The uniaxial tests were carried out along the machine direction (MD), transverse direction (TD), and diagonal direction (DD). In order to generate a state of in-plane biaxial tension, a pneumatic bulge test setup was prioritized over the commonly performed punch test in an attempt to eliminate the effects of contact friction. The biaxial flow stress–strain behavior of the membranes was deduced via the Panknin–Kruglov method coupled with a 3D Digital Image Correlation (DIC) technique. The findings demonstrate a high degree of in-plane anisotropy in both membranes. The ceramic coating was found to negatively affect the mechanical performance of the trilayer microporous separator, compromising its strength and stretchability, while preserving its failure mode. Derived from experimentally calibrated constitutive models, a finite element model was developed using the explicit solver OpenRadioss. The numerical model was capable of predicting the biaxial deformation of the semicrystalline membranes up until failure, showing a fairly good correlation with the experimental observations. [ABSTRACT FROM AUTHOR]

The need for higher capacity battery cells has increased significantly during the past years. Therefore, the subject of this study is to investigate the behavior of high performance 21700 Lithium-Ion cylindric battery cells under several abuse conditions, represented by high mechanical loads with different velocities and states of charge (SoC), and to develop a finite element analysis (FEA) model, using the OpenRadioss' explicit solver capabilities. The present study is focused on the investigation of the behavior of these cells under high mechanical loads with different loading velocities and different states of charge. The aim of the study is to provide a tool to predict the point of an internal short circuit in FEA, with a very good approximation. Experiments were completed using a hydraulic flat-compression test, set up at four different states of charge, 40%, 60%, 80% and 100%, and three different loading velocities of 10 mms−1, 100 mms−1 and 1000 mms−1. A homogenized FEA model is developed to predict the internal damage of the separator, which can lead to a short circuit with a possible thermal runaway under abusive load conditions. The present model, in combination with well identified material and fracture parameters, succeeded in the prediction of the mechanical behavior at various states of charge and mechanical loading conditions; it can also be used for further crashworthiness analysis within a full-car FEA model. This accurate cell model will be the first building block to optimize the protective structures of batteries in electric vehicles, and reduce their weight through a deeper understanding of their overall behavior during the different crash cases. [ABSTRACT FROM AUTHOR]

Injection molding is a common process for manufacturing thermoplastic polymers. Preconnected to fabrication, mechanically loaded parts are examined in structural simulation. A crucial prerequisite for a valid structural simulation for any material is the underlying material data. To determine this data, different phenomena must be considered such as influences of load type, strain rate, environmental conditions and in case of fiber reinforced materials the fiber orientation (FO) in the considered area. Because of rheological effects, injection molded parts often possess a non-homogeneous FO distribution. This makes it challenging to create testing plates for specimen extraction with a well-defined FO over thickness and width in the considered area. In this paper, a novel testing part is introduced with an unidirectionally oriented testable area. It shows a FO degree of more than 0.75, which has been validated with μ-CT measurement and two thermoplastic materials: polyamide and polybutylene terephthalate, both reinforced with 30 weight percent of short glass fibers. In order to resolve influences of the already addressed FO distribution in injection molded parts, tensile test specimens need to be extracted out of specially designed plates via milling and cannot be injection molded directly. Experiments were carried out to study possible effects of preparation on the mechanical properties of specimens with both materials and two milling parameter sets. The first milling parameter set creates reproducible surface roughnesses, whereas the second parameter set shows a correlation between FO and roughness value: when milling perpendicularly to the main FO lower roughnesses are reached than milling in fiber direction. Uncertainties of the normalized rupture strain from orthogonally extracted specimens seem to be larger than the values from those extracted in fiber direction. [ABSTRACT FROM AUTHOR]