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.     

Iron‐Catalyzed Reaction of γ‐Tocopherol with Methyl Linoleate Hydroperoxides in Solutions

γ‐Tocopherol is one of the main constituents in vegetable oils and acts as an antioxidant by trapping lipid‐peroxyl radicals. This study reports reaction products of γ‐tocopherol with lipid‐peroxyl radicals formed by iron‐catalyzed decomposition of methyl linoleate hydroperoxides (MeLOOH) in toluene and methanol solutions. The products in toluene solution were tocored, methyl (8a‐dioxy‐γ‐tocopherone)‐epoxyoctadecenoates (γT‐OO‐epoxyMeL), methyl (8a‐dioxy‐γ‐tocopherone)‐octadecadienoates (γT‐OO‐MeL), γ‐tocopherol biphenyl dimer (γTBD), γ‐tocopherol diphenylether dimer (γTED), and adducts of γ‐tocopherol dimers with the MeLOOH‐derived peroxyl radicals (γTED‐OO‐epoxyMeL, γTBD‐OO‐MeL, and γTED‐OO‐MeL). The iron‐catalyzed reaction in toluene proceeded slowly, whereas the reaction in methanol was relatively fast. The reaction products in methanol were γT‐OO‐epoxyMeL and γTED‐OO‐epoxyMeL together with tocored, γTBD, and γTED. The results indicate that the iron‐catalyzed decomposition of MeLOOH in toluene produces both epoxyperoxyl and peroxyl radicals and that the decomposition in methanol yields only the epoxyperoxyl radicals. These peroxyl radicals could react with the 8a‐carbon‐centered radical of γ‐tocopherol or its dimers.     

One-Dimensional Phonon State of 4He Films Adsorbed in Straight Nanopores

We have studied heat capacities of ⁴He adsorbed in straight nanopores 1.8, 2.2, and 2.8 nm in diameter. Heat capacities of the ⁴He fluid film on the solid layer at 0.08–0.4 K show power laws close to T in 1.8 nm pores, close to T ² in 2.8 nm pores, and a crossover from T to T ² with increasing temperature in 2.2 nm pores. These heat capacities are explained by a model assuming a phonon dispersion with continuous one-dimensional (1D) states in the axial direction and discrete energy levels in the azimuthal direction. By fitting experimental data to the model, the phonon velocity along the pore axis and the energy gap for propagation in the cross section are derived. At temperatures sufficiently lower than the energy gap, where the thermal wave length of phonons is much longer than the effective pore diameter, the ⁴He fluid films show a T-linear heat capacity of 1D phonons propagating only along the pore axis. At higher temperatures, a 1D-2D crossover of phonons occurs.      

Application of microalgae hydrolysate as a fermentation medium for microbial production of 2-pyrone 4,6-dicarboxylic acid

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Repeatedly foldable AMOLED display

In this study, a 5.9‐inch foldable active‐matrix organic light emitting diode (AMOLED) display was developed. A folding test was performed repeatedly. The display survived the folding test (100,000 folds) with a curvature radius of 2 mm. To protect an organic light emitting diode (OLED) against moisture, inorganic passivation layers are provided on the upper and lower sides of the flexible display. Using our transfer technology, high density passivation layers can be obtained. The measured water vapor transmission rate of the layer is 7 × 10^?6 g/m²?day or less, which improves OLED reliability. With these techniques, we have developed a book‐type display, which is repeatedly foldable like a book, and a tri‐fold display including a display area, which is foldable in three.     

A coarse-to-fine IP-driven registration for pose estimation from single ultrasound image

A fast registration making use of implicit polynomial (IP) models is helpful for the real-time pose estimation from single clinical free-hand Ultrasound (US) image, because it is superior in the areas such as robustness against image noise, fast registration without enquiring correspondences, and fast IP coefficient transformation. However it might lead to the lack of accuracy or failure registration.In this paper, we present a novel registration method based on a coarse-to-fine IP representation. The approach starts from a high-speed and reliable registration with a coarse (of low degree) IP model and stops when the desired accuracy is achieved by a fine (of high degree) IP model. Over the previous IP-to-point based methods our contributions are: (i) keeping the efficiency without requiring pair-wised correspondences, (ii) enhancing the robustness, and (iii) improving the accuracy. The experimental result demonstrates the good performance of our registration method and its capabilities of overcoming the limitations of unconstrained freehand ultrasound data, resulting in fast, robust and accurate registration.     

Accelerated Discovery of Potent Bioactive anti-TNFα Aptamers by Microbead-Assisted Capillary Electrophoresis (MACE)-SELEX

Dysregulation of tumor necrosis factor-α (TNFα), a pro-inflammatory cytokine, causes several diseases, making it an important therapeutic target. Here, we identified a novel DNA aptamer against human TNFα using in vitro selection, which included a high exclusion pressure process against non-binding and weak binders through microbead-assisted capillary electrophoresis (MACE) in only three rounds. Among the 15 most enriched aptamers, Apt14 exhibited the highest inhibitory activity for the interaction between TNFα and its cognate receptor in mouse L929 cells. For further improving the bioactivity of the aptamer, dimerization programed by hybridization was evaluated, resulting in the Apt14 dimer exhibited a twofold higher binding affinity and stronger inhibition compared to the monomer counterpart. Rapid identification of bioactive aptamers using MACE in combination with facile dimerization by hybridization accelerates the discovery of novel bioactive aptamers, paving the way toward replacing current monoclonal antibody therapy with the less expensive and non-immunogenic aptamer therapy.