Fe2-homogenization of micromorphic elasto-plastic materials

In this work, a homogenization strategy for a micromorphic–type inelastic material is presented. In the spirit of FE2, a representative volume element is attached to each macroscopic quadrature point. Due to the inherent length scale of the micromorphic continuum, size effects for inelastic behavior are obtained on RVE–level. A focus is placed on the computation of the homogenized algorithmic tangent. It is determined via sensitivity analyses with respect to the boundary conditions imposed on the RVE. Following this procedure, costly single–scale computations with dense meshes can be replaced by a robust homogenization approach with optimal convergence rates

Fe2-homogenization of micromorphic elasto-plastic materials

In this work, a homogenization strategy for a micromorphic–type inelastic material is presented. In the spirit of FE2, a representative volume element is attached to each macroscopic quadrature point. Due to the inherent length scale of the micromorphic continuum, size effects for inelastic behavior are obtained on RVE–level. A focus is placed on the computation of the homogenized algorithmic tangent. It is determined via sensitivity analyses with respect to the boundary conditions imposed on the RVE. Following this procedure, costly single–scale computations with dense meshes can be replaced by a robust homogenization approach with optimal convergence rates

Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient

Background & AimsWe report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatment options, aiming at the induction of anti-tumor T cells responses, we initiated a personalized multi-peptide vaccination, based on in-depth analysis of tumor antigens (immunopeptidome) and sequencing.MethodsTumors were characterized by immunohistochemistry, next-generation sequencing and mass spectrometry of HLA ligands.ResultsAlthough several tumor-specific neo-epitopes were predicted in silico, none could be validated by mass spectrometry. Instead, a personalized multi-peptide vaccine containing non-mutated tumor-associated epitopes was designed and applied. Immunomonitoring showed vaccine-induced T cell responses to three out of seven peptides administered. The pulmonary metastasis resected after start of vaccination showed strong immune cell infiltration and perforin positivity, in contrast to the previous lesions. The patient remains clinically healthy, without any radiologically detectable tumors since March 2013 and the vaccination is continued.ConclusionsThis remarkable clinical course encourages formal clinical studies on adjuvant personalized peptide vaccination in cholangiocarcinoma.Lay SummaryMetastatic cholangiocarcinomas, cancers that originate from the liver bile ducts, have very limited treatment options and a fatal prognosis. We describe a novel therapeutic approach in such a patient using a personalized multi-peptide vaccine. This vaccine, developed based on the characterization of the patient’s tumor, evoked detectable anti-tumor immune responses, associating with long-term tumor-free survival