Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer.

Immunotherapy has become a standard treatment in many cancers and it is based on three main therapeutic axes: immune checkpoint blockade (ICB), vaccination and adoptive cell transfer (ACT). If originally these therapies mainly focused on exploiting CD8 T cells given their role in the direct elimination of tumor cells, increasing evidence highlights the crucial role CD4 T cells play in the antitumor immune response. Indeed, these cells can profoundly modulate the tumor microenvironment (TME) by secreting different types of cytokine or by directly eliminating cancer cells. In this review, we describe how different CD4 T cell subsets can contribute to tumor immune responses during immunotherapy and the novel high-throughput immune monitoring tools that are expected to facilitate the study of CD4 T cells, at antigen-specific and single cell level, thus accelerating bench-to-bed translational research in cancer

Stress influence on high temperature oxide scale growth: modeling and investigation on a thermal barrier coating system.

International audienceIn thermal barrier coating (TBC) systems, an oxide layer develops at high temperature below the ceramic coating, leading at long term to the mechanical failure of the structure upon cooling. This study investigates a mechanism of stress-affected oxidation likely to induce the growth of a non-uniform oxide scale detrimental to the TBC lifetime. A continuum thermodynamics formulation is derived accounting for the influence of the stress and strain situation at the sharp metal/oxide phase boundary on the local oxidation kinetics. It specially includes the contributions of the large volumetric strain and the mass consumption associated with metal oxidation. A continuum mechanics/mass diffusion framework is used along with the developed formulation for the interface evolution to study the growth of an oxide layer coupled with local stress development. The implementation of the model has required the development of a specific simulation tool, based on a finite element method completed with an external routine for the phase boundary propagation. Results on an electron-beam physical vapor deposited (EB-PVD) TBC case are presented. The processes resulting in a non-uniform oxide scale growth are analyzed and the main influences are discussed

New smoothing procedures in contact mechanics

AbstractThis paper presents recent methods to improve numerical simulation of contact problems by smoothing. The main idea is to combine contact surfaces regularization with an automatic adjustment of both penalty parameter and load step. The underlying goal is to provide handle situations frequently met in an industrial context

An Ultrawideband Time Reversal-based RADAR for Microwave-range Imaging in Cluttered Media

This work presents a new RADAR prototype built for the purpose of imaging targets located in a cluttered environment. The system is capable of performing Phase Conjugation experiments in the ultrawideband [2-4] GHz. In addition, applying the D.O.R.T. method to the inter-element matrix allows us to selectively focus onto targets, hence reducing the clutter contribution. We aim to experimentally explore the use of this focusing wave into an inversion algorithm, in order to improve its robustness against noise. Before testing this idea, we show here the first results validating the prototype separately in the frame of selective focusing via the DORT method and of multistatic-multifrequency inversion

Effects of asymmetric creep-ageing behaviour on springback of AA2050-T34 after creep age forming

This study investigates the effects of asymmetric creep-ageing behaviour on springback of aluminium alloys during creep age forming (CAF) process. An Al-Cu-Li alloy, AA2050, which shows an apparent asymmetric tension and compression creep-ageing behaviour is used for investigation. Several CAF trial tests to form singly-curved AA2050 plates with different thicknesses (3, 5 and 8 mm) are carried out with a four point bending setup. Meanwhile, two sets of finite element (FE) models of corresponding processes have been developed, in which either the conventional symmetric or the new asymmetric creep-ageing behaviour of the alloy was used. The asymmetric models can well predict the shape of formed plates for thicker materials (5 and 8 mm), while symmetric models provide over-prediction of final deflections. The results from asymmetric models indicate that more creep strain is generated in the tension stressed part of the forming plate than that in the other part with compressive stresses and therefore, resulting in an asymmetric distribution of the relaxed stresses through the thickness of the forming plates after creep-ageing. After springback, both top and bottom surfaces of the formed plates show significant compressive stresses while tensile residual stresses exist in the centre of the formed plates. The work in this study helps to understand the particular springback behaviour of AA2050 with asymmetric creep-ageing behaviour in CAF, and can be used to guide future industrial applications of the alloy in the CAF process

Diagnosis of focal liver lesions from ultrasound using deep learning

PURPOSE: The purpose of this study was to create an algorithm that simultaneously detects and characterizes (benign vs. malignant) focal liver lesion (FLL) using deep learning. MATERIALS AND METHODS: We trained our algorithm on a dataset proposed during a data challenge organized at the 2018 Journées Francophones de Radiologie. The dataset was composed of 367 two-dimensional ultrasound images from 367 individual livers, captured at various institutions. The algorithm was guided using an attention mechanism with annotations made by a radiologist. The algorithm was then tested on a new data set from 177 patients. RESULTS: The models reached mean ROC-AUC scores of 0.935 for FLL detection and 0.916 for FLL characterization over three shuffled three-fold cross-validations performed with the training data. On the new dataset of 177 patients, our models reached a weighted mean ROC-AUC scores of 0.891 for seven different tasks. CONCLUSION: This study that uses a supervised-attention mechanism focused on FLL detection and characterization from liver ultrasound images. This method could prove to be highly relevant for medical imaging once validated on a larger independent cohort

DFT study of dihydrogen addition to molybdenum π-heteroaromatic complexes: a prerequisite step for the catalytic hydrodenitrogenation process

International audienceThe range of molybdenum hydride complexes that are sought to participate in the important catalytic hydrodenitrogenation process (HDN) of nitrogen containing polycyclic aromatic hydrocarbons were evaluated by DFT studies. The previously synthesized stable (η6-quinoline)Mo(PMe3)3 complex 1N, in which molybdenum is bonded to the heterocyclic ring, was chosen as a model. The hydrogenation of the quinone heterocycle, which was postulated as the initial step in the overall HDN reaction, is found to occur via three consecutive steps of the oxidative addition of dihydrogen to Mo in 1N. Successive transfer of hydrogen atoms from the metal to the heterocycle leads to the ultimate formation of the tetrahydrido molybdenum intermediate Mo(PMe3)4H413 and 2,2,3,3-tetrahydroquinoline C9H11N 14. All the involved intermediates and transition states have been fully characterized by DFT. This computational modeling of the hydrogenation of quinoline, as a part of extended HDN catalytic processes, provides a fundamental understanding of such mechanism

A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road

Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes