Engineering of Lipid Nanoparticles by the Multifunctionalization of the Surface with Amino Acid Derivatives for the Neutralization of a Target Toxic Peptide

Protein affinity reagents (e.g., antibodies) are often used for basic research, diagnostics, separations, and disease therapy. Although a lot of “synthetic” protein affinity reagents have been developed as a cost-effective alternative to antibodies, their low biocompatibility is a considerable problem for clinical application. Lipid nanoparticles (LNP) represent a highly biocompatible drug delivery agent. However, little has been reported that LNP itself works as a protein affinity reagent in living animals. Here, LNP is engineered for binding to and neutralizing a target toxic peptide in living animals by multifunctionalization with amino acid derivatives. Multifunctionalized LNP (MF-LNP) is prepared using amino acid derivative-conjugated lipids. Optimized MF-LNP exhibits nanomolar affinity to the target toxic peptide and inhibits toxic peptide-dependent hemolysis and cytotoxicity. In addition, MF-LNP captures and neutralizes the toxic peptide after intravenous injection in the bloodstream; in addition, MF-LNP does not release the toxic peptide in the accumulated organ. These results reveal the potential of using LNP as a highly biocompatible protein affinity reagent such as an antidote.     

Japanese contribution to the DEMO-R&D program under the Broader Approach activities

Several technical R&D activities mainly related to the blanket materials are newly launched as a part of the Broader Approach (BA) activities, which was initiated by the EU and Japan. According to the common interests for these parties in DEMO, R&Ds on reduced activation ferritic/martensitic (RAFM) steels as structural material, SiC_f/SiC composites as a flow channel insert material and/or alternative structural material, advanced tritium breeders and neutron multipliers, and tritium technology are carried out through the BA DEMO R&D program, in order to establish the technical bases on the blanket materials and the tritium technology required for DEMO design. This paper describes overall schedule of those R&D activities and recent progress in Japan carried out by JAEA as the domestic implementing agency on BA, collaborating with Japanese universities and other research institutes.     

Cold repeated forming of compact for aluminium foam

A cold repeated forming process of compacts for producing metal foams was developed in order to strongly bond powder particles. In this process, the compact undergoes severe plastic deformation for the strong bonding of particles by repeated backward extrusion and cup compression, and thus the compact largely foams owing to the accumulation of gas released from blowing agents inside the compact during heating. The cold repeated forming process without heating is much simpler than that for the conventional hot extrusion process. The relative density of the foam was decreased by adding silicon powder to the compact, and an aluminium foam having a relative density of 0.27 was obtained using two repeats of backward extrusion and cup compression, 1.5 mass% titanium hydride powder and 4 mass% silicon powder. In addition, a one-piece foam was successively produced from the bonding of two compacts during the foaming in a die. It was found that the cold repeated forming of compacts is effective for the production of metal foams.     

Evaluation of three-dimensional effects in short deep beams using a rigid-body-spring-model

Three-dimensional (3-D) effects in short deep beams without stirrups that failed in shear were investigated experimentally and analytically. Two deep beams with a shear span to depth ratio (a/d) of 0.5 and with different beam widths were tested. The effect of beam width on load-carrying capacity, failure mode, crack pattern and 3-D behavior was investigated, and shape effect due to beam width was clarified. In addition, the beams were analyzed by the 3-D rigid-body-spring model (RBSM). RBSM is a discrete form of modeling that presents realistic behavior from cracking to failure, and 3-D RBSM is applicable to simulate 3-D behavior as well as the confinement effect of concrete. Analytical results in terms of load–displacement curves and crack pattern are compared with the experimental results. Three-dimensional deformations, strut widths and cross-sectional stress distribution are investigated analytically and compared with the experimental results to determine 3-D behavior in detail. The 3-D effects in short deep beams are clarified.     

Drug delivery from nonpeptidic α-amino acid containing polyamides

New nonpeptidic α-amino acid-based polyamides were used for drug delivery. Benzocaine was covalently linked via a spacer to N-protected poly(l-cystyl-l-cystine) and to poly(adipoyl-l-lysine). Its release by α-chymotrypsin attack was followed by UV. It was nearly quantitative within two days with l-cystine-based polyamide. Protected forms of these polyamides were used as matrices. Release of benzocaine entrapped in polyamide from (l-cystine) was controlled by diffusion. When entrapped in polyamide from (l-lysine) it was controlled by diffusion and swelling. Received: 10 January 1997/Accepted: 23 January 1997     

Characteristics of humic substances in the Kuji River waters as determined by high-performance size exclusion chromatography with fluorescence detection

Direct measurement by high-performance size exclusion chromatography with fluorescence detection was applied to the characterization of humic substances in river waters from the Kuji River system, which runs through forest hills and an agricultural plain in Japan. The monitoring wavelength of excitation 320 nm and emission 430 nm corresponds to the fluorescence maxima for aquatic fulvic acid. Chromatograms of the river waters showed four peaks; each peak position was in good agreement among these samples. Peak height ratios for the samples from the upstream Kuji River and its tributaries were different from those of the midstream and downstream sections of the Kuji River, which may reflect differences in the characteristics of humic substances and other organic materials supplied from soil to river.     

Quantum-Mechanical Properties of Protons in Solid Molecular Hydrogen at Megabar Pressures

Quantum distributions of protons in three high-pressure phases of solid molecular hydrogen are investigated by the first-principles path integral molecular dynamics (FP-PIMD) method, in which interatomic forces are calculated precisely based on the density functional theory. The distributions have entirely different symmetries from those predicted by conventional simulation with classical treatment of protons. Especially in phase II, we found that molecular rotation is hindered by quantum fluctuation of protons, having a strong resemblance to a quantum distribution of impurity muonium in crystalline silicon. The mechanism of this “quantum localization” is clarified by a detailed study of the potential energy surface for the molecular rotation.     

Calculation of thermodynamic quantities of metals and alloys by the statistical moment method

The thermodynamic properties of metals and alloys are studied using the moment method in the statistical dynamics, which allows us to take into account the anharmonicity of thermal lattice vibrations and size mismatch of constituent atoms, going beyond the quasi-harmonic approximation. Within the fourth-order moment approximation, the free energy and equilibrium lattice spacing of the binary alloys are given explicitly in terms of the effective pair potentials and the second- and fourth-order vibrational constants. The long-range order (LRO) parameter η and order-disorder transition temperatures (ODTs) T_c of binary alloys are obtained by solving the explicit transcendental equations. The numerical calculations of thermodynamic quantities for Cu₃Au and β-CuZn alloys show that the inclusion of the anharmonicity of lattice vibration plays an essentially important role in determining the phase stabilities of metals and alloys.