To successfully induce tissue repair or regeneration in vivo, bioengineered constructs must possess both optimal bioactivity and mechanical strength. This is because cell interaction with the extracellular matrix (ECM) produces two different but concurrent signaling mechanisms: ligation-induced signaling, which depends on ECM biological stimuli, and traction-induced signaling, which depends on ECM mechanical stimuli. In this report, we provide a fundamental understanding of how alterations in mechanical stimuli alone, produced by varying the viscoelastic properties of our bioengineered construct, modulate phenotypic behavior at the whole-cell level. Using a physiologically relevant ECM mimic composed of hyaluronan and fibronectin, we found that adult human dermal fibroblasts modify their mechanical response in order to match substrate stiffness. More specifically, the cells on stiffer substrates had higher modulus and a more stretched and organized actin cytoskeleton (and vice versa), which translated into larger traction forces exerted on the substrate. This modulation of cellular mechanics had contrasting effects on migration and proliferation, where cells migrated faster on softer substrates while proliferating preferentially on the stiffer ones. These findings implicate substrate rigidity as a critical design parameter in the development of bioengineered constructs aimed at eliciting maximal cell and tissue function.

A calorimetric method has been investigated for the determination of the thermodynamic parameters of acid dissociations in dipolar aprotic solvents. For the dissociations of monoprotonated bases BH+ (B: aniline, pyridine, triethylamine, tributylamine, triethanolamine, 1,3-diphenylguanidine and 1,1,3,3-tetramethylguanidine) in N,N-dimethylformamide, dimethyl sulfoxide (DMSO), acetonitrile and propylene carbonate, the solutions of the bases were titrated with small volumes of a “strong acid,” trifluoromethanesulfonic acid. In each solvent, there was an approximately linear relation of unit slope between ΔH298° and ΔG298° showing that the difference in pKa between different BH+’s can mainly be attributed to the difference in the enthalpy term. As for the solvent effect on pKa, however, the entropy term seems to play an important role. A preliminary study has shown that the calorimetric method is also applicable to the dissociations of HX-type weak acids (benzoic and salicylic acids in DMSO, for example), if the dissociation equilibria are not complicated by such reactions as homoconj ugation.

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In a previous paper, we reported the N-hydroxyformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor. Despite its attraction as a potential therapeutic agent for cerebral diseases, the preparation of an injectable formulation of HET0016 was limited by its poor solubility under neutral conditions and instability under acidic conditions. The instability of HET0016 in acidic conditions is due to the N-hydroxyformamidine moiety, which is considered to be essential for the potent and selective activity seen in our previous study. The activity was maintained when the N-hydroxyformamidine moiety was replaced by an imidazole ring (3a; IC(50) = 5.7 +/- 1.0 nM), but this was associated with a loss of selectivity for cytochrome p450s (CYPs). However, other azole derivatives such as isoxazole derivative 23 (IC(50) value 38 +/- 10 nM) and pyrazole derivative 24 (IC(50) value 23 +/- 12 nM) showed potent and selective activities with improved stability.

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In this study, the effect on the fracture load of inlay-retained composite fixed partial dentures（FPDs）caused by reinforcing them with fiber-reinforced composite（FRC）in different positions was examined. Experimental FPDs were fabricated using Estenia/EG Fiber（Kuraray Medical） . Pontic reinforcement was then performed in one of the following three ways: reinforced the central area in a single line or in double straight lines, or reinforced the bottom in a curved line. The finding was that, when the area ranging from the connector to the bottom of the pontic was reinforced with FRC in a curved line, the fracture load of the FPDs tended to become higher. In addition, the FPDs fractured mainly at the veneering composite of the connector area. Based on the results of this study, it was concluded that reinforcement using FRC is effective, and that the veneering composite in the connector area needs to have sufficient strength to prevent the fractures.