Effects of temperature and grain size on phase-field-crystal deformation simulation

We performed deformation simulations of nanocrystalline structures under different temperature and grain-size conditions using the phase-field-crystal (PFC) method with an isovolumetric numerical scheme proposed by Hirouchi et al. [Development of numerical scheme for phase field crystal deformation simulation. Comput Mater Sci 2009;44:1192-7.], and we discussed the deformation behavior of bicrystalline and polycrystalline metallic materials during plastic deformation in detail. As a result, we were able to observe typical plastic deformation behavior such as the generation, annihilation and movement of dislocations as well as grain rotation and grain boundary (GB) migration depending on the grain size and temperature. It was concluded that the PFC method with the isovolumetric deformation scheme is a powerful tool for simulating polycrystalline metals, because the obtained behaviors were in qualitative agreement with the results obtained by molecular dynamics (MD) simulations and experiments.     

Static recrystallization simulations starting from predicted deformation microstructure by coupling multi-phase-field method and finite element method based on crystal plasticity

We have developed a numerical model of recrystallization taking the inhomogeneities of the plastic deformation of a polycrystalline metal into account. Here, the plastic deformation of the polycrystalline metal is simulated by the finite element method based on crystal plasticity theory and the microstructure evolution during recrystallization is simulated by the multi-phase-field method. In primary recrystallization simulations, nucleation is the most difficult problem. In the present model, the deformation microstructure is predicted from the results of a crystal plasticity finite element simulation, and spontaneous nucleation is achieved through abnormal grain growth that is enabled by introducing the misorientation dependences of grain boundary energy and mobility. As a result of simulations under three different compression strains, it is confirmed that primary recrystallization simulations depending on the amount of deformation and taking the inhomogeneities of the plastic deformation of a polycrystalline metal into consideration can be successfully performed by employing the proposed model.     

Identification of HLA-A24-restricted epitopes with high affinities to Hsp70 using peptide arrays

Heat shock protein 70 (Hsp70) family members are known as facilitators of immune responses by interacting with receptors on antigen-presenting cells leading to Hsp70-peptide uptake and antigen cross priming. Here, identification of human leukocyte antigen (HLA)-A24-restricted epitopes was achieved using peptide arrays for evaluation of their affinities to Hsp70 and HLA-A24 binding prediction tools. Using Hsp70 as the model antigen, the GYPVTNAVI and VFQHGKVEI peptides were identified as antigens. These peptides actually bound to HLA-A24 in the stabilization assay using T2-A*2402 cells, and induced a strong peptide-reactive cytotoxic T lymphocyte response in HLA-A24 transgenic mice after vaccination.     

A motif detection and classification method for peptide sequences using genetic programming

An exploration of common rules (property motifs) in amino acid sequences has been required for the design of novel sequences and elucidation of the interactions between molecules controlled by the structural or physical environment. In the present study, we developed a new method to search property motifs that are common in peptide sequence data. Our method comprises the following two characteristics: (i) the automatic determination of the position and length of common property motifs by calculating the physicochemical similarity of amino acids, and (ii) the quick and effective exploration of motif candidates that discriminates the positives and negatives by the introduction of genetic programming (GP). Our method was evaluated by two types of model data sets. First, the intentionally buried property motifs were searched in the artificially derived peptide data containing intentionally buried property motifs. As a result, the expected property motifs were correctly extracted by our algorithm. Second, the peptide data that interact with MHC class II molecules were analyzed as one of the models of biologically active peptides with buried motifs in various lengths. Twofold MHC class II binding peptides were identified with the rule using our method, compared to the existing scoring matrix method. In conclusion, our GP based motif searching approach enabled to obtain knowledge of functional aspects of the peptides without any prior knowledge.     

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6–8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.     

A Strategy for Discovering Heterochiral Bioactive Peptides by Using the OB2nP Library and SPOTs Method

d -Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead–2ⁿ-peptide (OB2ⁿP) library, which can display 2ⁿ peptide diastereomers per bead, has been developed. Through screening of the OB2ⁿP library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-β-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the μ-opioid receptor. The screening strategy enabled d -amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.     

Molecular Mechanisms to Control Post-Transplantation Hepatitis B Recurrence

Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed.     

Note: direct measurement of the point-to-point resolution for microns-thick specimens in the ultrahigh-voltage electron microscope

We report on a direct measurement method and results of the point-to-point resolution for microns-thick amorphous specimens in the ultrahigh-voltage electron microscope (ultra-HVEM). We first obtain the ultra-HVEM images of nanometer gold particles with different sizes on the top surfaces of the thick epoxy-resin specimens. Based on the Rayleigh criterion, the point-to-point resolution is then determined as the minimum distance between centers of two resolvable tangent gold particles. Some values of resolution are accordingly acquired for the specimens with different thicknesses at the accelerating voltage of 2 MV, for example, 18.5 nm and 28.4 nm for the 5 μm and 8 μm thick epoxy-resin specimens, respectively. The presented method and results provide a reliable and useful approach to quantifying and comparing the achievable spatial resolution for the thick specimens imaged in the mode of transmission electron including the scanning transmission electron microscope.