Functionalization of Human Serum Albumin by Tyrosine Click

Human serum albumin (HSA) is a promising drug delivery carrier. Although covalent modification of Cys34 is a well-established method, it is desirable to develop a novel covalent modification method that targets residues other than cysteine to introduce multiple functions into a single HSA molecule. We developed a tyrosine-selective modification of HSA. Three tyrosine selective modification methods, hemin-catalyzed, horseradish peroxidase (HRP)-catalyzed, and laccase-catalyzed reactions were performed, and the modification efficiencies and modification sites of the modified HSAs obtained by these methods were evaluated and compared. We found that the laccase-catalyzed method could efficiently modify the tyrosine residue of HSA under mild reaction conditions without inducing oxidative side reactions. An average of 2.2 molecules of functional groups could be introduced to a single molecule of HSA by the laccase method. Binding site analysis using mass spectrometry suggested Y84, Y138, and Y401 as the main modification sites. Furthermore, we evaluated binding to ibuprofen and found that, unlike the conventional lysine residue modification, the inhibition of drug binding was minimal. These results suggest that tyrosine-residue selective chemical modification is a promising method for covalent drug attachment to HSA.     

Glycotechnology for decontamination of biological agents: a model study using ricin and biotin-tagged synthetic glycopolymers

Two types of biotin-tagged glycopolymers carrying lactose or glucose in clusters along the polyacrylamide backbone were prepared and subjected to decontamination analyses with the plant toxin ricin. A buffer solution containing the toxin was treated with one glycopolymer followed by streptavidin-magnetic particles. Supernatant solutions were analyzed with surface plasmon resonance and capillary electrophoresis, and revealed that the lactose glycopolymer "captured" this toxin more effectively than the glucose polymer. Free toxin was not detectable in the supernatant after treatment with the glycopolymer and magnetic particles; >99% decontamination was achieved for this potentially fatal biological toxin.     

Computer-Aided Design of Orally Bioavailable Pyrrolidine Carboxamide Inhibitors of Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis with Favorable Pharmacokinetic Profiles

We have carried out a computational structure-based design of new potent pyrrolidine carboxamide (PCAMs) inhibitors of enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (MTb). Three-dimensional (3D) models of InhA-PCAMx complexes were prepared by in situ modification of the crystal structure of InhA-PCAM1 (Protein Data Bank (PDB) entry code: 4U0J), the reference compound of a training set of 20 PCAMs with known experimental inhibitory potencies (IC₅₀^exp). First, we built a gas phase quantitative structure-activity relationships (QSAR) model, linearly correlating the computed enthalpy of the InhA-PCAM complex formation and the IC₅₀^exp. Further, taking into account the solvent effect and loss of inhibitor entropy upon enzyme binding led to a QSAR model with a superior linear correlation between computed Gibbs free energies (ΔΔG_com) of InhA-PCAM complex formation and IC₅₀^exp (pIC₅₀^exp = −0.1552·ΔΔG_com + 5.0448, R² = 0.94), which was further validated with a 3D-QSAR pharmacophore model generation (PH4). Structural information from the models guided us in designing of a virtual combinatorial library (VL) of more than 17 million PCAMs. The VL was adsorption, distribution, metabolism and excretion (ADME) focused and reduced down to 1.6 million drug like orally bioavailable analogues and PH4 in silico screened to identify new potent PCAMs with predicted IC₅₀^pre reaching up to 5 nM. Combining molecular modeling and PH4 in silico screening of the VL resulted in the proposed novel potent antituberculotic agent candidates with favorable pharmacokinetic profiles.     

Penetration Depth of Microwave into the Mixture of Goethite with Graphite Estimated by Permittivity and Conductivity

A study has been conducted to understand the penetration behavior of microwave into the mixture of goethite with carbon (C) aiming at providing an appropriate guidance to dehydrate the substances with hydroxides occasionally contained in industrial sludge. At first, it was observed that microwave could not sufficiently penetrate into the specimen with C/goethite molar ratios greater than 2, giving incomplete dehydration. To understand the penetration behavior of microwave, permittivity and conductivity were measured. Permittivity measurements were successfully made below 9 vol pct C. For carbon content greater than 8.56 vol pct C, the conductivity of the mixture abruptly increased by four orders of magnitude because of the occurrence of the conductivity percolation. Above 13.7 vol pct C close to an inflection point approximating 10 vol pct C, the mixture became sufficiently conductive. Transition from dielectric to conductive behavior occurred between 8.56 and 13.7 vol pct C. The Generalized Effective Medium approximation could satisfactorily express the variation of the conductivity values in the whole range of vol pct C measured. The penetration depth of microwave was determined by the above two measurements. It was found that penetration depth decreased with the increasing vol pct of C contained in the mixture specimen. Finally, guidance could be provided as for the blend ratio of C to treated material along with the size of a briquette or a pellet referring to the obtained relation between penetration depth and vol pct of C. Furthermore, it was proved that the numerical simulation was quite helpful to predict how microwave behaves in the mixture under given conditions.     

Development and on-orbit operation of lithium-ion pouch battery for small scientific satellite “REIMEI”

A lithium-ion battery was developed using off-the-shelf pouch cells and launched with a small scientific satellite “REIMEI.” The cells were potted with polyurethane or epoxy resin to protect the battery from vacuum in space. Preliminary experimental test results of pouch cells potted in a soft aluminum cap suggested that the cells tended to swell in vacuum, although they had been reinforced with the resins. Bread board models (BBMs), in which pouch cells were potted with resins in a hard aluminum case, were fabricated for cycle life performance tests in the laboratory. The test results indicated that the performance of epoxy-potted BBM was superior to that of the polyurethane-potted BBM. The measured cell resistance implied that the electrolyte solution leaked through the polyurethane resin, resulting in premature deterioration. The epoxy resin was used for the flight battery. The end-of-discharge-voltage (EoDV) trend of the flight battery on orbit was compared with the laboratory test results corrected based on a post-launch cycle test using a fresh cell. The corrected EoDV trend in the laboratory was in good agreement with the on-orbit trend for the early cycle period, indicating that the on-orbit battery was not inadvertently affected by conditions in space.     

Using a Water Lens for Light Concentration in Thermoelectric Generation

A water lens is employed to concentrate sunlight on the surface of a thermoelectric module in order to heat it. This water lens can change its shape flexibly and is adjustable to solar altitudes. The lens shape and light path were simulated for the cases when the light is incident at an angle to the water surface, parallel to the central axis of the half-cylindrical water lens, and when the light is focused on a plate. A condensing ratio larger than 70 is achieved when the incident light is closer to the normal of the water surface and if the optimal lens shape is maintained.     

A Self-Supported High-Entropy Metallic Glass with a Nanosponge Architecture for Efficient Hydrogen Evolution under Alkaline and Acidic Conditions

Developing highly efficient and durable electrocatalysts for hydrogen evolution reaction (HER) under both alkaline and acidic media is crucial for the future development of a hydrogen economy. However, state-of-the-art high-performance electrocatalysts recently developed are based on carbon carriers mediated by binding noble elements and their complicated processing methods are a major impediment to commercialization. Here, inspired by the high-entropy alloy concept with its inherent multinary nature and using a glassy alloy design with its chemical homogeneity and tunability, we present a scalable strategy to alloy five equiatomic elements, PdPtCuNiP, into a high-entropy metallic glass (HEMG) for HER in both alkaline and acidic conditions. Surface dealloying of the HEMG creates a nanosponge-like architecture with nanopores and embedded nanocrystals that provides abundant active sites to achieve outstanding HER activity. The obtained overpotentials at a current density of 10 mA cm⁻² are 32 and 62 mV in 1.0 m KOH and 0.5 m H₂SO₄ solutions, respectively, outperforming most currently available electrocatalysts. Density functional theory reveals that a lattice distortion and the chemical complexity of the nanocrystals lead to a strong synergistic effect on the electronic structure that further stabilizes hydrogen proton adsorption/desorption. This HEMG strategy establishes a new paradigm for designing compositionally complex alloys for electrochemical reactions.     

Robot sweep path planning with weak field constrains under large motion disturbance

The sweeping robot plans a path and moves along its prior path. In conventional studies, the target field is separated into square cells to enable the robot to sweep evenly. The prior sweep path is generated by passing all the target cells. However, an outdoor sweeping robot cannot move as expected, because the robot cannot go to the next target easily due to the uncertainty of the motion of the robot. The uncertain motion is caused by individual differences of motors, disturbances from the environment, and position error. As a result, the robot passes the same point many times and the actual path length becomes longer. In this study, we propose sweep path planning to solve this problem by decreasing the number of cells that the robot must pass. Numerical simulations are carried out to verify our method and to verify the relation among the sweeping rate and robot disturbances. Simulation results show that our method is effective enabling the robot to satisfy a sweep rate of 80% and more, even if the robot has uncertainty of movement.     

The shifting gender composition of psychology: Trends and implications for the discipline.

Psychology, along with the majority of professions and scientific disciplines, has undergone dramatic shifts in gender composition over the past two decades. These changes have prompted concern that this increased participation by women may lead to erosion in the status of these occupations. This article describes the results of a case study of psychology conducted by a subcommittee of the American Psychological Association's (APA's) Task Force on the Changing Gender Composition of Psychology to examine the discipline's changing gender composition and the factors related to these shifts. Societal and disciplinary trends are examined, along with data on the patterns of men's and women's involvement in the educational pipeline and workplace. The results provide little support for the concern over the increasing representation of women and its impact on the prestige of the discipline. Rather, they suggest that changes in the nature and status of psychology per se may be at least partly responsible for the changes in male and female participation and that the nature, magnitude, and causes of these disciplinary changes require further examination. Specific recommendations for the APA prepared by another subcommittee of the Task Force are also presented in the Appendix. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging decreases the sensitivity of the GABA carrier to propofol and etomidate

Substitution of Asn for Ser543 in the large fragment of Taq DNA polymerase (Klentaq) increases several times the efficiency of synthesis of long (over 2 kbp) DNA molecules. The difference in the DNA synthesis efficiencies by the mutant and native enzymes increased with the increase in the DNA fragment length.