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.     

Cold-start performance of an ammonia-fueled spark ignition engine with an on-board fuel reformer

This work demonstrated the first-ever cold-start operation of an ammonia (NH₃)-fueled four-cylinder spark ignition engine with an on-board fuel reformer, applying autothermal reforming. In this system, an electrically heated NH₃-air mixture was provided to a reforming catalyst and approximately 3 s was found to elapse between the start of engine rotation and the onset of combustion. Stable fast idle operation in conjunction with a cold start was realized with a H₂-to-NH₃ molar ratio of 2:1. Nearly zero NH₃ emissions were achieved during cold start and fast idle until the engine warmed up, by adsorbing unburned NH₃ passing through a three-way catalyst before the catalyst was sufficiently warmed up. The NH₃ adsorption capacity of this system could be regenerated during the engine warm-up when the engine was running under lean conditions.     

Molecular Dynamics Study of Radial Corrugation in Carbon Nanotubes

Molecular dynamics simulations of multiwalled carbon nanotubes under hydrostatic pressure are performed to elucidate the novel class of radial buckling in the systems. It is revealed by all-atom simulations that the initial circular cross section transforms into a flower-like wavy configuration at critical pressure on the order of hundreds mega pascals or less. This kind of radial buckling, called radial corrugation, originates from the competition of the three relevant energies in the system: in-plane strain energy, van der Waals interaction energy between adjacent tubes, and out-of-plane bending energy. Their possible consequences for physical properties of carbon nanotubes are also discussed.     

Binding and Enhanced Binding between Key Immunity Proteins TRAF6 and TIFA

Human tumor necrosis factor receptor associated factor (TRAF)-interacting protein, with a forkhead-associated domain (TIFA), is a key regulator of NF-κB activation. It also plays a key role in the activation of innate immunity in response to bacterial infection, through heptose 1,7-bisphosphate (HBP); a metabolite of lipopolysaccharide (LPS). However, the mechanism of TIFA function is largely unexplored, except for the suggestion of interaction with TRAF6. Herein, we provide evidence for direct binding, albeit weak, between TIFA and the TRAF domain of TRAF6, and it is shown that the binding is enhanced for a rationally designed double mutant, TIFA S174Q/M179D. Enhanced binding was also demonstrated for endogenous full-length TRAF6. Furthermore, the structures of the TRAF domain complexes with the consensus TRAF-binding peptides from the C terminus of wild-type and S174Q/M179D mutant TIFA, showing salt-bridge formation between residues 177–181 of TIFA and the binding pocket residues of the TRAF domain, were solved. Taken together, the results provide direct evidence and a structural basis for the TIFA–TRAF6 interaction, and show how this important biological function can be modulated.     

Traversable Region Estimation for Mobile Robots in an Outdoor Image

This paper describes a novel method to estimate appropriate traversable regions from an outdoor scene image. The traversable regions output by the proposed method reflect the common sense of people. For example, a candidate traversable region is “a paved road somewhat distant from the side ditch.” The input to the traversable region estimation is one color image. First, category is assigned to each pixel in the image. The categorization result is then input to the region estimator. Finally, the traversable region are estimated on the input image. An important aspect of this method is the application of two score functions in region estimation process. One score function places high value on categories selected as traversable paths by subjects. The other function places high value on categories that are not selected as traversable regions but are adjacent to categories with traversable paths. A combination of these two functions produces feasible estimation results. The effectiveness of the combined score functions was evaluated by experiments and a questionnaire.     

Mammalian Cytochrome P450-Dependent Metabolism of Polychlorinated Dibenzo-p-dioxins and Coplanar Polychlorinated Biphenyls

Polychlorinated dibenzo-p-dioxins (PCDDs) and coplanar polychlorinated biphenyls (PCBs) contribute to dioxin toxicity in humans and wildlife after bioaccumulation through the food chain from the environment. The authors examined human and rat cytochrome P450 (CYP)-dependent metabolism of PCDDs and PCBs. A number of human CYP isoforms belonging to the CYP1 and CYP2 families showed remarkable activities toward low-chlorinated PCDDs. In particular, human CYP1A1, CYP1A2, and CYP1B1 showed high activities toward monoCDDs, diCDDs, and triCDDs but no detectable activity toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD). Large amino acids located at putative substrate-recognition sites and the F-G loop in rat CYP1A1 contributed to the successful metabolism of 2,3,7,8-tetraCDD. Rat, but not human, CYP1A1 metabolized 3,3'',4,4'',5-pentachlorobiphenyl (CB126) to two hydroxylated metabolites. These metabolites are probably less toxic than is CB126, due to their higher solubility. Homology models of human and rat CYP1A1s and CB126 docking studies indicated that two amino acid differences in the CB126-binding cavity were important for CB126 metabolism. In this review, the importance of CYPs in the metabolism of dioxins and PCBs in mammals and the species-based differences between humans and rats are described. In addition, the authors reveal the molecular mechanism behind the binding modes of dioxins and PCBs in the heme pocket of CYPs.     

Modeling of CO2‐Hydrate Formation at the Gas‐Water Interface in Sand Sediment

Sub‐seabed geological storage of CO₂ in the form of gas hydrate is attractive because clathrate hydrate stably exists at low temperature and high pressure, even if a fault occurs by diastrophism like a big earthquake. For the effective design of the storage system it is necessary to model the formation of CO₂‐hydrate. Here, it is assumed that the formation of gas hydrate on the interface between gas and water consists of two stages: gas diffusion through the CO₂‐hydrate film and consequent CO₂‐hydrate formation on the interface, between film and water. Also proposed is the presence of a fresh reaction interface, which is part of the interface between the gas and aqueous phases and not covered with CO₂‐hydrate. Parameters necessary to model the hydrate formation in sand sediment are derived by comparing the results of the present numerical simulations and the measurements in the literature.     

Self‐consistent electrical parameter extraction from bias dependent spectral response measurements of III‐V multi‐junction solar cells

Spectral response of multi‐junction solar cell is complicated because of the interplay between external measurement conditions such as bias light intensity, monochromatic light intensity, bias voltage, and intrinsic electrical properties of series interconnected subcells. In this paper, we report an experimental study on the bias voltage‐dependent spectral response (SR) for multi‐junction solar cell. A self‐consistent iteration loop was developed from a nonlinear least square Powell hybrid algorithm that was used for curve fitting the experimental SR versus bias voltage data of each subcell. We demonstrated for the first time that this approach enabled us to derive the electrical parameters such as dark saturation currents (J₀), shunt resistance (R_sh), series resistance (R_s), and spectra response (J_photo) for each subcell of a Ga_0.99In_0.01As/Ge dual junction solar cell with stable convergence. The accuracies of the fitting results were confirmed by the agreement between the J–V curves calculated on the basis of these parameters and the experimental J–V curve of multi‐junction solar cell measured under AM1.5 and 1 sun condition. Copyright © 2013 John Wiley & Sons, Ltd.     

Embodied Energy and Gas Emissions of Retaining Wall Structures

The embodied energy (EE) and gas emissions of four design alternatives for an embankment retaining wall system are analyzed for a hypothetical highway construction project. The airborne emissions considered are carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O), sulphur oxides (SOX), and nitrogen oxides (NOX). The process stages considered in this study are the initial materials production, transportation of construction machineries and materials, machinery operation during installation, and machinery depreciations. The objectives are (1)?to determine whether there are statistically significant differences among the structural alternatives; (2)?to understand the relative proportions of impacts for the process stages within each design; (3)?to contextualize the impacts to other aspects in life by comparing the computed EE values to household energy consumption and car emission values; and (4)?to examine the validity of the adopted EE as an environmental impact indicator through comparison with the amount of gas emissions. For the project considered in this study, the calculated results indicate that propped steel sheet pile wall and minipile wall systems have less embodied energy and gas emissions than cantilever steel tubular wall and secant concrete pile wall systems. The difference in CO2 emission for the retaining wall of 100?m length between the most and least environmentally preferable wall design is equivalent to an average 2.0?L family car being driven for 6.2?million miles (or 62 cars with a mileage of 10,000??miles/year for 10?years). The impacts in construction are generally notable and careful consideration and optimization of designs will reduce such impacts. The use of recycled steel or steel pile as reinforcement bar is effective in reducing the environmental impact. The embodied energy value of a given design is correlated to the amount of gas emissions.