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.     

Dependence of Vacuum Electrical Breakdown Field and Field Enhancement Factor on the Number of Apertures Drilled in Small Electrodes

Dark current based on field emission current is considered to be a factor causing the vacuum electrical breakdown between multiaperture acceleration grids in the JT‐60 negative ion source. In this paper, we focus on field enhancement factor, which is a key parameter of field emission from the electrode. Vacuum breakdown testing for small‐sized electrodes simulating the multiaperture acceleration grids of the negative ion source was performed. We found the field enhancement factor and breakdown field for multiaperture electrodes, and we investigated the dependence of each parameter on the number of apertures. The results revealed that an increase in the average field enhancement factor after the end of conditioning resulting from an increase in the number of apertures led to a decrease in the dielectric strength of the multiaperture electrodes.     

Finite-dimensional adaptive control for infinite-dimensional systems

This paper deals with the design of a finite-dimensional model reference adaptive controller for a distributed parameter system. The space of inputs and the space of outputs are both one dimensional. First an input—output representation is introduced, using filtered values generated from the inputs and outputs. Next it is shown that we can design a finite-dimensional adaptive control system by a new adaptive law. The new adaptive law guarantees the existence of a large region of attraction from which all signals are bounded and the tracking error converges to a small residual set.     

Adaptive control for infinite-dimensional systems

This paper deals with the design of a model reference adaptive controller for a distributed parameter system generated by a self-adjoint operator. The space of inputs and the space of outputs are both one dimensional. After introducing input-output representations, an adaptive control system is designed for the system with unknown input function and unknown output function. The input-output equations can be expressed using filtered values generated from the inputs and outputs     

The Influence Analysis that a Phase Characteristic of the High‐Level Earthquake Gives to Vibration Response Characteristic of the 550‐kV Disconnectors

We developed the 550‐kV disconnectors that strengthened earthquake proofing by the addition of the damper unit and weight reduction of conductive part based on the damage of the 550‐kV disconnectors by the Great East Japan earthquake (March 11, 2011) and inspected the earthquake proofing performance by shake table test. In shake table test, we performed the test by the artificial seismic wave that varied in phase characteristic in addition to the test by resonance method. And, in a high‐level earthquake area, we analyzed it about the influence that a phase characteristic of the artificial seismic wave gave to stress to occur in disconnectors. As a result, it is thought that the stress to occur in disconnectors is decided by a primary natural frequency basically because a bending strain to occur to the disconnectors in the time when the resonance frequency ingredient becomes the big acceleration response value grows big. But, on a particular phase condition, it was confirmed that the bending strain to occur in disconnectors might grow big conspicuously. As for this, the possibility is thought about by influence of higher natural frequency doing superposition.     

Present Status of the Nd:YAG Thomson Scattering System Development for Time Evolution Measurement of Plasma Profile on Heliotron J

A new high repetition rate Nd:YAG Thomson scattering system is developed for the Heliotron J helical device.A main purpose of installing the new system is the temporal evolution measurement of a plasma profile for improved confinement physics such as the edge transport barrier (H-mode) or the internal transport barrier of the helical plasma.The system has 25 spatial points with ～10mm resolution.Two high repetition Nd:YAG lasers (>550mJ@ 50Hz) realize the measurement of the time evolution of the plasma profile with ～10ms time intervals.Scattered light is collected by a large concave mirror (D=800 mm,f/2.25) with a solid angle of ～100 mstr and transferred to interference filter polychromators by optical fiber bundles in a staircase form.The signal is amplified by newly designed fast preamplifiers with DC and AC output,which reduces the low frequency background noise.The signals are digitized with a multi-event QDC,fast gated integrators.The data acquisition is performed by a VME-based system operated by the CINOS.     

Description and Phylogenetic Position of Dinosaur Eggshells from the Luanchuan Area of Western Henan Province, China

Here, we examine 145 dinosaur eggshells from a new fossil locality in the Qiupa Formation (Upper Cretaceous) of the Luanchuan area in western Henan Province, China. The eggshells display elongatoolithid macro- and microstructures, including ridges and nodes on the outer surface, two ultrastrncturai layers, and an undulatory boundary between the mammiilary and continuous layers.A phylogenic analysis shows that the Luanchuan eggshells belong to the ooclade Eiongatoolithidae.Within Elongatoolithidae, the thickness ratio of the mammillary layer to the entire eggshell, and the porosity of the Luanchuan eggshells are comparable to the oogenera Macroolithus and Elongatoolithus. There is no direct evidence for the taxonomic identity of the Luanchuan eggshells;however, they were likely laid by oviraptorids based on their phyiogenetic position and their similarities with known oviraptorid eggs.