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.     

A study of decoupling with skeleton matrix in two‐degree‐of‐freedom generalized minimum variance control

There are many multi‐input multi‐output (MIMO) systems in chemical plants, and they have multiple time delays of different length in each input and output pair. This paper explains a two‐degree‐of‐freedom (2DOF) control system based on generalized minimum variance control (GMVC) for MIMO systems. It can improve the tracking performance with respect to the reference signals and the response properties for the disturbance. The states between the sampling period can be expressed by using the modified z transform to take account of multiple time delays. Additionally, a tracking controller is designed to decouple the plant. © 2011 Wiley Periodicals, Inc. Electr Eng Jpn, 176(1): 28–36, 2011; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.21046     

Development of numerical scheme for phase field crystal deformation simulation

The phase field crystal (PFC) method is anticipated as a new multiscale method, because this method can reproduce physical phenomena depending on atomic structures in metallic materials on the diffusion time scale. Although the PFC method has been applied to some phenomena, there are few studies related to evaluations of mechanical behaviors of materials by appropriate PFC simulation. In a previous work using the PFC method, tensile deformation simulations have been performed under conditions where the volume increases during plastic deformation. In this study, we developed a new numerical technique for PFC deformation simulation that can maintain a constant volume during plastic deformation. To confirm that the PFC model with the proposed technique can reproduce appropriate elastic and plastic deformations, we performed a series of deformation simulations in one and two-dimensions. In one- and two-dimensional single-crystal simulations, linear elastic responses were confirmed in a wide strain rate range. In bicrystal simulations, we could observe typical plastic deformations due to the generation, annihilation and movement of dislocations, and the interaction between the grain boundary and dislocations. Moreover, the deformation behaviors of a nanopolycrystalline structure at high temperature were simulated and the intergranular deformations caused by grain rotation and grain boundary migration were reproduced.     

A feasible core design of lead bismuth eutectic cooled CANDLE fast reactor

Among the innovative reactor concepts, CANDLE has several advantages over conventional reactor designs. However, when CANDLE is extended to long life, the clad integrity at high neutron fluence, the build-up of fission product gases, and the pressure drop for long cores pose technological challenges which have to be overcome. In this paper, we propose practically viable design procedures, such as recladding the entire fuel pins and replacement of different amounts of fuel at different radial positions, to ensure clad integrity and flat power distribution, respectively. We demonstrate the efficacy of such design procedures by calculations that are performed on a LBE CANDLE reactor. Our calculations show that for a reactor operation period of 3700 days the various reactor parameters are within the limits proposed by Japan Atomic Energy Agency (JAEA).     

Mechanical behavior of a single polymer chain in a non-solvent

Mechanical properties of a single polystyrene chain in mixtures of dioxane and methanol were measured with AFM. The effect of the solubility of the surrounding liquid on mechanical behavior of a polymer chain was examined. In good and Θ solvents, the force-extension curves exhibit a freely jointed chain (FJC)-like trend with good reproducibility. In a non-solvent, the profile of force-extension curve was dependent on the extension speed: an FJC-like nature emerged at the lower speed of 200 nm/s while saw-toothed curves were obtained at the higher speed of 2000 nm/s. The shape of saw-toothed curves varied from measurement to measurement. A force relaxation was also observed in the non-solvent under a fixed extension distance after 2000 nm/s extension. The mechanical behavior in non-solvents suggests that inhomogeneous deformation of a PS chain occurs due to reduction of the chain mobility.     

Deformation-induced martensitic transformation behavior in cold-rolled and cold-drawn type 316 stainless steels

We investigate deformation-induced martensitic transformation behavior in cold-rolled and cold-drawn specimens of type 316 stainless steel. Deformation-induced martensite preferentially nucleates at the twin boundary between the austenite matrix and a deformation twin. In the cold-rolled specimen, martensite formed at the twin boundary has a Kurdjumov–Sachs (K–S) relationship with both the austenite matrix and the deformation twin (“double K–S relationship”). In the cold-drawn specimen, two kinds of deformation twins with different twin planes are typically formed, and therefore deformation-induced martensites are formed where the deformation twin boundaries intersect: martensite thus has an imperfect “triple K–S relationship” with the austenite matrix and the two deformation twins. The complicated crystallographic orientation relationship between austenite and martensite grains strongly restricts the formation of some variants of deformation-induced martensites. Because of the difference in number of nucleation sites in the cold-drawn and cold-rolled specimens, martensitic transformation is more enhanced in the former than in the latter.     

Fracture behavior of poly(vinyl chloride)/methyl methacrylate/butadiene/styrene polymer blends

The fracture mode of poly(vinyl chloride)/methyl methacrylate/butadiene/styrene (PVC/MBS) polymer blends can change from ductile to brittle in accordance with the changes in shape of the test specimen or test conditions. Therefore, the mechanisms of impact energy absorption and the main cause of stress whitening are complicated. The following results on PVC/MBS blends were obtained by carrying out fracture experiments at different test speeds and temperatures:

• (1) The ductile/brittle fracture mode of the PVC and PVC/MBS blends can be explained by σ (the craze initiation stress)/σ_y (the shear yield initiation stress), which depends on the strain rates and temperature.
• (2) The fracture behavior of the PVC/MBS blends can be classified into the following types from the standpoints of fracture mode and whitening degree: Fracture I: ductile fracture without whitening; Fracture II: ductile fracture with whitening; and Fracture III: brittle fracture without whitening.
• (3) The following concepts can be estimated from the measurements of yield stress, specific gravity and SEM, TEM and visual observations. In Fracture I, shear yield occurs mainly. In Fracture II, both shear yield and crazing occur. In Fracture III, deformation of the rubber and local crazing occur.
• (4) The main cause of stress whitening in PVC/MBS blends is light scattering by cavities in the rubber particles.
• (5) In Fracture II, at first, crazes with cavities in the rubber particles occur. Then, shear yield occurs. Finally, crazes are healed by the heat, and only the cavities in the rubber remain.