The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Generalized measuring-worm algorithm: high-accuracy mapping and movement via cooperating swarm robots

Recently, many extensive studies have been conducted on robot control via self-positioning estimation techniques. In the simultaneous localization and mapping (SLAM) method, which is one approach to self-positioning estimation, robots generally use both autonomous position information from internal sensors and observed information on external landmarks. SLAM can yield higher accuracy positioning estimations depending on the number of landmarks; however, this technique involves a degree of uncertainty and has a high computational cost, because it utilizes image processing to detect and recognize landmarks. To overcome this problem, we propose a state-of-the-art method called a generalized measuring-worm (GMW) algorithm for map creation and position estimation, which uses multiple cooperating robots that serve as moving landmarks for each other. This approach allows problems of uncertainty and computational cost to be overcome, because a robot must find only a simple two-dimensional marker rather than feature-point landmarks. In the GMW method, the robots are given a two-dimensional marker of known shape and size and use a front-positioned camera to determine the marker distance and direction. The robots use this information to estimate each other’s positions and to calibrate their movement. To evaluate the proposed method experimentally, we fabricated two real robots and observed their behavior in an indoor environment. The experimental results revealed that the distance measurement and control error could be reduced to less than 3 %.     

Observation of very thin gold island films vacuum-deposited onto MoS2 surface by STM

A gold film of about half a monolayer in thickness was vacuum-deposited onto air-cleaved MoS₂ surface at room temperature at a pressure of 10^?5 Pa. Quasi-two-dimensionally grown gold islands made of several atomic layers were observed by scanning an area of 40×30 nm². The shape of them was oblate and about 20 nm in diameter. Atomic corrugations which reflect the Au(111) surface were observed. The islands were found to move and changed their shape during the microscopy.     

Improvement in impact strength of modified cardanol‐bonded cellulose thermoplastic resin by using olefin resins

Impact strength of a modified cardanol‐bonded cellulose thermoplastic resin was greatly improved by using a small amount of olefin resins. As we showed, this thermoplastic resin (3‐pentadecylphenoxy acetic acid (PAA)‐bonded cellulose diacetate (CDA): PAA‐bonded CDA) exhibited high practical properties such as bending strength, heat resistance, and water resistance. However, its impact strength was insufficient for use in durable products. We improved the impact strength of PAA‐bonded CDA by adding hydrophobic olefin resins, such as polyethylene or polypropylene, while maintaining good bending strength and breaking strain. Furthermore, the application of olefin resins also increased water resistance and fluidity. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39829.     

Improvement in impact strength of modified cardanol‐bonded cellulose thermoplastic resin by adding modified silicones

The impact strength of cellulose diacetate (CDA) bonded with a modified cardanol (3‐pentadecylphenoxy acetic acid: PAA) was greatly improved up to 9 kJ/m² by adding a relatively small amount of modified silicones while suppressing a decrease in bending strength. In our recent research, this thermoplastic resin (PAA‐bonded CDA) exhibited high rigidity, glass transition temperature, and water resistance. However, its impact strength was insufficient for use in durable products. Therefore, silicones modified with polyether, amino, and epoxy groups were investigated as possible ways to improve the impact strength. The results show that adding polyether‐modified silicone (polyether silicone) with moderate polarity relative to PAA‐bonded CDA resulted in shearing deformation greatly enhances its impact strength while maintaining other properties, including glass transition temperature (T_g), water resistance, and thermoplasticity. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40366.     

CRACK PROPAGATION BEHAVIOR AND LIFETIME PREDICTION IN ALUMINA AND ZIRCONIA

The lifetime prediction of ceramics is discussed on the basis of the relationship between stress intensity factorK1 and crack velocity ν. The effects of water environment, the cyclic loading and microstructure of material on K1-ν characteristics are studied by carrying out the crack growth tests by the double torsion (DT) method under the static andcyclic loading in both environments of air and water for alumina and zirconia. K1-ν characteristics determined by the double torsion method are used to predict time-to-failure under the cyclic loading of alumina and zirconia ceramics. The predictions agree qualitatively with the experimental results.     

Microbiological quality of fermented milk produced by repeated-batch culture

Using a starter culture containing Lactococcus lactis subsp. cremoris and Acetobacter orientalis, repeated-batch culture for fermented-milk production was carried out for 14 d. The pH decreased to approximately 4.3 and the milk solidified stably when the mixing ratio of fermented-milk to fresh milk was set at a level as high as 10%. The microbial population gradually changed as the culture progressed, and the cell densities of lactic and acetic acid bacteria finally leveled off to constant values. The quality of the fermented-milk became almost constant with respect to the changes in the cell densities of the lactic and acetic acid bacteria. Escherichia coli was then inoculated into the fermented-milk to simulate household contamination. E. coli was washed out with the progress of the repeated-batch culture, and thus showed no adverse effects on the fermented-milk production.     

Dehydration of d-glucose in high temperature water at pressures up to 80 MPa

Reaction of d-glucose in water to yield 5-hydroxymethylfurfural (5-HMF), 1,2,4-benzenetriol (BTO) and furfural was studied at high temperatures (up to 400 °C) and high pressures (up to 80 MPa) using a continuous flow reactor. Maximum temperature and pressure conditions gave maximum furfural yield. Increasing pressure from 40 to 70 and 80 MPa enhanced dehydration reactions to 5-HMF, but also enhanced hydrolysis of 5-HMF leading to the production of BTO and thus lead to lower yields of 5-HMF (below 10%). Remarkably, the dehydration reaction to 5-HMF and the hydrolysis of 5-HMF were both enhanced by the increase in water density at 400 °C.