A novel operando approach to analyze the structural evolution of metallic materials during friction with application of synchrotron radiation

International audienceIn this study, we describe an experimental setup and a new approach for operando investigation of structural evolution of materials during wear and friction. The setup is particularly suited for testing various friction pairs, including those in which both rubbing bodies are made of metals. The developed device allows circumventing the problems related to significant scattering of X-rays produced by metals and makes it possible using “real samples” in synchrotron beamlines operating in reflection mode. To demonstrate the capabilities of the device and the proposed new approach, an iron-based massive sample was subjected to thousands of friction cycles using a cemented carbide pin. The material was probed with synchrotron X-ray radiation within a few milliseconds after leaving the friction zone. The results of the microstructural and structural analysis, as well as results obtained from diverse mathematical models, allowed us to evaluate several features, including gradual accumulation of defects, microstructural refinement, dislocation density changes, surface layer oxidation, as well as several other phenomena caused by the dry sliding friction process. Mainly, it was possible to conclude that the process of wear occurred due to the cooperative action of oxidation and plastic deformation, which began during the first cycle of frictional interaction and was manifested in increasing the dislocation density, whose type was changed gradually during testing. The number of defects quickly reached a threshold value and subsequently fluctuated around it due to periodically repeated processes of defect accumulation and stress relaxation resulting from material wear. It was also observed that friction led to the quick formation of a mechanically mixed layer, consisting of the sample material and a mixture of two types of iron oxide – hematite and magnetite. The delamination of this layer was probably the primary wear mechanism

Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cells

Chemotherapy of soft tissue sarcomas (STS) is restricted by low chemosensitivity and multiple drug resistance (MDR). The purpose of our study was the analysis of MDR mechanism in different types of STS. We assessed the expression of ABC-transporters, MVP, YB-1, and analyzed their correlation with chemosensitivity of cancer cells. STS specimens were obtained from 70 patients without metastatic disease (2018–2020). Expression level of MDR-associated genes was estimated by qRT-PCR and cytofluorimetry. Mutations in ABC-transporter genes were captured by exome sequencing. Chemosensitivity (SI) of STS to doxorubicin (Dox), ifosfamide (Ifo), gemcitabine (Gem), and docetaxel (Doc) was analyzed in vitro. We found strong correlation in ABCB1, ABCC1, and ABCG2 expression. We demonstrated strong negative correlations in ABCB1 and ABCG2 expression with SI (Doc) and SI (Doc + Gem), and positive correlation of MVP expression with SI (Doc) and SI (Doc + Gem) in undifferentiated pleomorphic sarcoma. Pgp expression was shown in 5 out of 44 STS samples with prevalence of synovial sarcoma relapses and it is strongly correlated with SI (Gem). Mutations in MDR-associated genes were rarely found. Overall, STS demonstrated high heterogeneity in chemosensitivity that makes reasonable in vitro chemosensitivity testing to improve personalized STS therapy, and classic ABC-transporters are not obviously involved in MDR appearance. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Soft Tissue Sarcoma Study: Association of Genetic Alterations in the Apoptosis Pathways with Chemoresistance to Doxorubicin

Soft tissue sarcomas (STS) are heterogeneous cancers with more than 100 histological subtypes, different in molecular alterations, which make its personalized therapy very complex. Gold standard of chemotherapy for advanced STS includes combinations of Doxorubicin and Ifosfamide or Gemcitabine and Docetaxel. Chemotherapy is efficient for less than 50% of patients and it is followed by a fast development of drug resistance. Our study was directed to the search of genetic alterations in cancer cells associated with chemoresistance of undifferentiated pleomorphic and synovial sarcomas to the abovementioned genotoxic drugs. We analyzed chemoresistance of cancer cells in vitro using primary STS cultures and performed genetic analysis for the components of apoptotic signaling. In 27% of tumors, we revealed alterations in TP53, ATM, PIK3CB, PIK3R1, NTRK1, and CSF2RB. Cells from STS specimens with found genetic alterations were resistant to Dox, excluding the only one case when TP53 mutation resulted in the substitution Leu344Arg associated with partial oligomerization loss and did not cause total loss of TP53 function. Significant association between alterations in the components of apoptosis signaling and chemoresistance to Dox was found. Our data are important to elaborate further the therapeutic strategy for STS patients with alterations in apoptotic signaling. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

A scalable, matrix-free multigrid preconditioner for finite element discretizations of heterogeneous Stokes flow

International audienceIn this paper we describe a computational methodology that is specifically designed for studying three-dimensional geodynamic processes governed by heterogeneous visco-plastic Stokes flow. The method employs a hybrid spatial discretization consisting of a View the MathML sourceQ2-P1disc mixed finite element formulation for the Stokes problem, coupled to a material-point formulation which is used for representing material state and history-dependent variables. The applicability and practicality of this methodology is realized through the development of an efficient, scalable and robust variable viscosity Stokes preconditioner. In this work, these objectives are achieved through exploiting matrix-free operators and a geometric multigrid preconditioner employing hybrid coarse level operators, Chebyshev smoothers and hybrid Krylov coarse level solvers. The robustness and parallel efficiency of this strategy is demonstrated using an idealized geodynamic model. Lastly, we apply the new methodology to study geodynamic models of continental rifting and break-up in order to understand the diverse range of passive continental margins we observe on Earth today