Enhanced bile canaliculi formation enabling direct recovery of biliary metabolites of hepatocytes in 3D collagen gel microcavities

Analysis of biliary metabolites is essential to predict pharmacokinetics and hepatotoxicity during drug development. In this paper, we present a hepatocyte culture configuration that enables the direct recovery of bile acid that accumulates in bile canaliculi by embedding the hepatocytes in a 3D micropatterned collagen gel substrate. We investigated the formation of bile canaliculi in hepatocytes embedded in circular microcavities of various sizes and made from collagen gel. Image analyses using fluorescently labeled bile acid revealed that the area of bile canaliculi in embedded hepatocytes in a microcavity of 60 or 80 μm in diameter was enlarged when compared with other sized microcavities and those of hepatocytes cultured using conventional hepatocyte sandwich cultures. We successfully recovered bile acid from the enlarged bile canaliculi of hepatocytes cultured in microcavities using a glass capillary and quantified the amount recovered. Using our approach, the direct recovery of biliary metabolites, using hepatocyte cultures with enhanced biliary excretion and geometrically enlarged bile canaliculi, may enable accurate screening of pharmacokinetics and drug-drug interactions against drug transporters.     

Temporal electric conductivity variations of hydrogenated amorphous silicon due to high energy protons

Electric conductivity variations of undoped, n-type and p-type hydrogenated amorphous silicon (a-Si:H) thin films irradiated with various energy protons are systematically investigated. Dark conductivity (DC) and photoconductivity (PC) of the undoped samples increase at first due to proton irradiation and then decrease dramatically with increasing proton fluence. The increase in DC and PC becomes greater with increased proton energy. However, this increase is metastable and gradually decreases with time at room temperature. Similar results are observed in the n-type a-Si:H, whereas only a monotonic decrease is observed in DC and PC for the p-type samples. The increase of both DC and PC due to proton irradiation is attributed to metastable donor center generation. On further irradiation both the DC and PC decrease by the accumulation of radiation-induced defects, which act as deep traps and compensate carriers. The decrease in DC and PC becomes less pronounced as the proton energy increase and can be fitted along a universal line when the proton fluence is converted into displacement per atom (dpa).     

New approach for designing single-chain magnets: organization of chains via hydrogen bonding between nucleobases

Two one-dimensional (1D) manganese complexes, [Mn(2)(naphtmen)(2)(L)](ClO(4))·2Et(2)O·2MeOH·H(2)O (1) and [Mn(2)(naphtmen)(2)(HL)](ClO(4))(2)·MeOH (2), were synthesized by using a bridging ligand with a nucleobase moiety, 6-amino-9-β-carboxyethylpurine, and a salen-type manganese(III) dinuclear complex, [Mn(2)(naphtmen)(2)(H(2)O)(2)](ClO(4))(2) (naphtmen(2-) = N,N'-(1,1,2,2-tetramethylethylene)bis(naphthylideneiminato) dianion). In 1 and 2, the carboxylate-bridged Mn(III) dinuclear units are alternately linked by two kinds of weak Mn···O interactions into 1D chains. As a result, canted antiferromagnetic and ferromagnetic interactions are alternately present along the chains, leading to a 1D chain with non-cancellation of anisotropic spins. Since the chains connected via H-bonds between nucleobase moieties are magnetically isolated, both 1 and 2 act as single-chain magnets (SCMs). More importantly, this result shows the smaller canting angles hinder long-range ordering in favor of SCM dynamics.     

Asymptotic analysis for the eikonal equation with the dynamical boundary conditions

We study the dynamical boundary value problem for Hamilton‐Jacobi equations of the eikonal type with a small parameter. We establish two results concerning the asymptotic behavior of solutions of the Hamilton‐Jacobi equations: one concerns with the convergence of solutions as the parameter goes to zero and the other with the large‐time asymptotics of solutions of the limit equation.     

Direct search coding algorithm with reduction in computing time by simultaneous selection rule

An optimized encoding algorithm is required to produce high-quality computer-generated holograms (CGHs). For such a purpose, I have proposed that the use of the direct search algorithm (DSA) is effective for encoding the amplitude and phase in the Lohmann-type CGH. However, it takes much computation time to obtain an optimum solution by the DSA. To solve this problem, I have newly found that the simultaneous direct search algorithm (SDSA) is greatly effective for shortening the computation time for encoding the Lohmann-type CGH. As a result, the evaluation value of the reconstructed image for the SDSA is the same as that of 0.992 for the DSA. The computation time for the SDSA is drastically shortened from 3575 to 55 s for the DSA.     

The lowest metal-to-bipyridine charge-transfer excited state of [Cr(2,2′-bipyridine)(CO)4]

The DV-Xα molecular-orbital calculations have been carried out on [Crbpy(CO)₄](bpy,2,2′-bipyridine) and its electron attachment and detachment products. The one-electron attachment of [Crbpy(CO)₄] yields a complex of bipyridine anion radical, while the one-electron detachment results in ionization of the central metal atom. The lowest excited state of [Crbpy(CO)₄] is the metal-to-ligand charge-transfer (MLCT) excited state which consists of the bipyridine anion radical and the central metal ionized. The transition-state calculation predicts the lowest MLCT excited states at around 23～30×10³ cm^?1 and the lowest bipyridine (π,π^*) excitations at 36×10³ cm^?1 and 42～45×10³ cm^?1. The calculation also concludes that the MLCT excitation induces a counter migration of the other electrons not directly involved in the charge-transfer excitation. The configuration-interaction calculations predict the lowest MLCT excited singlet states at around 21～35×10³ cm^?1 and the lowest bipyridine (π, π^*) excited singlet states at 42～62×10³ cm^?1, while the emissive lowest MLCT triplet state is at 17×10³ cm^?1. The transition moments evaluated with the transition-state wavefunctions can reproduce qualitatively the observed absorption spectral profile. The intensity of the MLCT transitions is obtained from the allowed (π, π^*) transitions of coordinated bipyridine but is not due to the intrinsic transition moments of MLCT excitations.     

Asymptotic Solutions of Hamilton–Jacobi Equations with Semi-Periodic Hamiltonians

We study the long time behavior of viscosity solutions of the Cauchy problem for Hamilton–Jacobi equations in ? ⁿ . We prove that if the Hamiltonian H(x, p) is coercive and strictly convex in a mild sense in p and upper semi-periodic in x, then any solution of the Cauchy problem “converges” to an asymptotic solution for any lower semi-almost periodic initial function.     

Using a polyelectrolyte to fabricate porous polyimide nanoparticles with crater‐like pores

We have used the reprecipitation method and subsequent two‐step imidization to fabricate highly porous polyimide (PI) nanoparticles possessing crater‐like surface pores (depths, diameters: tens of nanometers) from poly(amic acid) (PAA) derivatives in the presence of poly(sodium‐4‐styrenesulfonate) (PSS) as a polyelectrolytic porogen. The porous structures arose presumably through segregative microphase separation of PAA and PSS (i.e. repulsion between PAA and PSS in the presence of a common solvent) and subsequent removal of PSS. The addition of this strong polyelectrolyte improved the degree of porosity of the resulting PI nanoparticles and allowed controllable release of the porogen. The resulting porous PI nanoparticles exhibited a high thermal stability (5% weight loss at temperature 450°C). This technique is suitable for the preparation of novel low‐k materials and their surface‐related applications. Copyright © 2008 John Wiley & Sons, Ltd.