A crystal plasticity model for describing the anisotropic hardening behavior of steel sheets during strain-path changes

In the present study, a viscoplastic self-consistent crystal plasticity model (VPSC-RGBV), whichaccounts for various microstructural features, including the accumulation and annihilation ofdislocations due to slip activity and latent hardening originated from interactions betweengliding dislocations on different slip planes, is described. The simulation results of the VPSC-RGBV model are compared with those of a macro-mechanical distortional plasticity model, theso-called homogeneous anisotropic hardening (HAH), and experimental data pertaining to metalsundergoing complex loading histories. The differences between the simulated and experimentalresults under non-proportional loading, including 1) the stress-strain curve, 2) instantaneous r-value after strain-path change, and 3) yield surface evolution, are discussed. Finally, potentialimprovements are suggested for VPSC-RGBV model

Carrier Transport at Metal/Amorphous Hafnium–Indium–Zinc Oxide Interfaces

In this paper, the carrier transport mechanism at the metal/amorphous hafnium–indium–zinc oxide (a-HIZO) interface was investigated. The contact properties were found to be predominantly affected by the degree of interfacial reaction between the metals and a-HIZO; that is, a higher tendency to form metal oxide phases leads to excellent Ohmic contact via tunneling, which is associated with the generated donor-like oxygen vacancies. In this case, the Schottky–Mott theory is not applicable. Meanwhile, metals that do not form interfacial metal oxide, such as Pd, follow the Schottky–Mott theory, which results in rectifying Schottky behavior. The Schottky characteristics of the Pd contact to a-HIZO can be explained in terms of the barrier inhomogeneity model, which yields a mean barrier height of 1.40 eV and a standard deviation of 0.14 eV. The work function of a-HIZO could therefore be estimated as 3.7 eV, which is in good agreement with the ultraviolet photoelectron spectroscopy (3.68 eV). Our findings will be useful for establishing a strategy to form Ohmic or Schottky contacts to a-HIZO films, which will be essential for fabricating reliable high-performance electronic devices

Dynamic changes in circulating PD-1(+)CD8(+)T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer

Background: The predictive value of immune monitoring with circulating CD8(+) T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1(+) CD8(+) T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade. Methods: Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8(+) T lymphocytes was conducted using multi-colour flow cytometry. Predictive values of dynamic changes in circulating PD-1(+) CD8(+) T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with a PD-1 inhibitor (NCT03486119). Results: Circulating PD-1(+) CD8(+) T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1(+) cells among CD8(+) T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in the analysis of tumour antigen NY-ESO-1-specific CD8(+) T lymphocytes and the validation cohort. Mechanistically, PD-1 molecule expression on CD8(+) T lymphocytes suppresses the effector functions of tumour antigen-specific CD8(+) T lymphocytes. Conclusions: Dynamic changes in circulating PD-1(+) CD8(+) T lymphocytes predict clinical, and survival benefit from PD-1 blockade treatment in NSCLC, providing a useful tool to identify patient subgroups who will optimally benefit from PD-1 inhibitors. (C) 2020 Elsevier Ltd. All rights reserved.11Nsciescopu

VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers

Although immune checkpoint blockade therapies have demonstrated clinical efficacy in cancer treatment, harnessing this strategy is largely encumbered by resistance in multiple cancer settings. Here, we show that tumor-infiltrating T cells are severely exhausted in the microsatellite stable (MSS) colorectal cancer (CRC), a representative example of PD-1 blockade-resistant tumors. In MSS CRC, we found wound healing signature to be up-regulated and that T cell exhaustion is driven by vascular endothelial growth factor-A (VEGF-A). We report that VEGF-A induces the expression of transcription factor TOX in T cells to drive exhaustion-specific transcription program in T cells. Using a combination of in vitro, ex vivo, and in vivo mouse studies, we demonstrate that combined blockade of PD-1 and VEGF-A restores the antitumor functions of T cells, resulting in better control of MSS CRC tumors