Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis

Blood levels of the vitamin D₃ (D₃) metabolites 25-hydroxyvitamin D₃ (25(OH)D₃), 24R,25-dihydroxyvitamin D₃, and 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) are recognized indicators for the diagnosis of bone metabolism-related diseases, D₃ deficiency-related diseases, and hypercalcemia, and are generally measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using an isotope dilution method. However, other D₃ metabolites, such as 20-hydroxyvitamin D₃ and lactone D₃, also show interesting biological activities and stable isotope-labeled derivatives are required for LC-MS/MS analysis of their concentrations in serum. Here, we describe a versatile synthesis of deuterium-labeled D₃ metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D₃ (2), 25(OH)D₃-23,26-lactone (6), and 1,25(OH)₂D₃-23,26-lactone (7) were synthesized, and successfully applied as internal standards for the measurement of these compounds in pooled human serum. This is the first quantification of 1,25(OH)₂D₃-23,26-lactone (7) in human serum.     

Transient thermal stresses in fully and partly cooled circular rings

The constraint associated with the direction of the thickness of a thin photoelastic circular-ring model is experimentally proved to occur and it is compared with the theoretical result; the constraint is induced by thermal loads. The method for dealing with the constraint and for obtaining a transient thermal stress under plane-stress conditions is applied to study the thermal stress of the circular ring partly cooled from the inside cylindrical surface. It is found that the thermal stress of the fully cooled circular ring is not always greater than the partly cooled one.     

分数算子描述的黏弹性体力学问题数值方法

讨论由黎曼-刘维尔 (Riemann-Liouville)分数导数描述的黏弹性体力学问题的数 值方法. 该方法利用黎曼-刘维尔分数 导数定义中核函数的特性，并结合被积函数在单步中的逼近以及Newmark型数值法，建立 了分数导数计算公式. 算例表明，该算法具有收敛快、精度高、稳定性好和易于 应用和改进的优点. 在对动态系统的瞬态响应分析和有限元分析格式中，算法都获得了 满意的结果.     

Fabrication of L10 FePtAg nanoparticles and a study of the effect of Ag during the annealing process

L1₀ ferromagnetic phase FePt nanoparticles containing Ag atoms (FePtAg) were synthesized by means of a liquid phase process, followed by annealing. The addition of Ag to FePt nanoparticles permits annealing to be conducted at a lower temperature (350 °C). This is further accompanied by a subsequent transformation in the crystal phase from the FCC superparamagnetic phase to the FCT (L1₀) ferromagnetic phase. The effects of annealing temperature and the Ag atoms inside the nanoparticles on the magnetic properties of the FePt nanoparticles have been studied. Using electron spectroscopy for the chemical analysis (ESCA), Ag atoms in the L1₀ phase FePtAg nanoparticles were found to be localized on the surface region of the annealed nanoparticles. The Ag atoms function to inhibit the oxidation of FePt, causing the particles to become more stable and to have ferromagnetic properties.     

Inhibitory effects of a novel ascorbic derivative, disodium isostearyl 2-O-L-ascorbyl phosphate on melanogenesis

We investigated the inhibitory effects of a novel amphiphilic ascorbic derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na), synthesized from a hydrophilic ascorbic derivative, sodium-2-O-L-ascorbyl phosphate (VCP-Na), on melanogenesis in cultured human melanoma cells, normal human melanocytes, and three-dimensional cultured human skin models. Melanin synthesis in melanoma cells treated with VCP-IS-2Na at 300 muM and melanocytes treated with VCP-IS-2Na at 100 muM decreased to 23% and 52% of that in non-treated cells, respectively, and the cell viability was not affected. VCP-IS-2Na also significantly suppressed the cellular tyrosinase activity of melanoma cells and melanocytes. Melanin synthesis in human skin models was evaluated by macro- and microscopic observations of its pigmentation and quantitative measurements of melanin. Treatment of the human skin models with 1.0% VCP-IS-2Na did not inhibit cell viability, while melanin synthesis was decreased to 21% of that in the control. In contrast, L-ascorbic acid (VC) and VCP-Na did not seem to inhibit melanin synthesis and cellular tyrosinase activity. These results indicate that VCP-IS-2Na may be an effective whitening agent for the skin, and we expect the application of VCP-IS-2Na in the cosmetic industry.     

Folding transition of a single semiflexible polyelectrolyte chain through toroidal bundling of loop structures

We consider how the DNA coil-globule transition progresses via the formation of a toroidal ring structure. We formulate a theoretical model of this transition as a phenomenon in which an unstable single loop generated as a result of thermal fluctuation is stabilized through association with other loops along a polyelectrolyte chain. An essential property of the chain under consideration is that it follows a wormlike chain model. A toroidal bundle of loop structures is characterized by a radius and a winding number. The statistical properties of such a chain are discussed in terms of the free energy as a function of the fraction of unfolded segments. We also present an actual experimental observation of the coil-globule transition of single giant DNA molecules, T4 DNA (165.5 kbp), with spermidine (3+), where intrachain phase segregation appears at a NaCl concentration of more than 10 mM. Both the theory and experiments lead to two important points. First, the transition from a partially folded state to a completely folded state has the characteristics of a continuous transition, while the transition from an unfolded state to a folded state has the characteristics of a first-order phase transition. Second, the appearance of a partially folded structure requires a folded structure to be less densely packed than in the fully folded compact state.     

Pyrromethene dye sensitized photopolymer—photochemical behavior in polymer matrix and application to photoresist for printed circuit board

The photochemical behavior of the visible light initiating system that consists of a sensitizing dye, 2,6‐diethyl‐8‐phenyl‐1,3,5,7‐tetramethylpyrromethene BF₂ complex (EPP), and a photoacid generator, N‐trifluoromethylsulfonyloxy‐1,8‐naphthalimide (NIOTf), was studied mainly by means of absorption and fluorescence spectrometry not in solution but in a polymer matrix which is a closer medium to the one currently employed in the field of photoresists. Excited singlet electron transfer from EPP to NIOTf was considered as the main reaction pathway in this system. The EPP/NIOTf system was applied to a photoresist for printed circuit board with an appropriate binder polymer which contains an acetal protection group. A pattern profile of the photoresist was exceedingly affected by the amount of photogenerated acids, their diffusion, and amine in the atmosphere. Finally, by controlling exposure energy and the post‐exposure bake (PEB) process, a photoresist with a high resolution (8 µm line and space) was obtained under argon ion laser irradiation. Copyright © 2006 John Wiley & Sons, Ltd.     

Percutaneous absorption of bromhexine in rats

The percutaneous absorption of bromhexine (BH), an expectorant drug, through rat skin was examined in vitro and in vivo. BH in free base form penetrated better than the hydrochloride through the skin. When the in vitro penetration of BH was compared using Plastibase, macrogol and sucrose ester of fatty acid F-160 (DK-ester) formulations, the DK-ester formulation showed the best penetration of BH of the three. The addition of Azone (3%) or lauric acid (BH: lauric acid molar ratio, 1:1) considerably increased BH penetration to a relatively large penetration rate. The plasma levels of BH after in vivo application of the DK-ester formulation with Azone or lauric acid (0.6 g/3.8 cm2) were also higher than those after the formulation without an enhancer, and a constant plasma level (20-50 ng/ml) was obtained during the application for 48 h. However, the bioavailability was low, 2.5 and 2.7% respectively. When the amount of BH remaining in DK-ester ointment and the skin after an 18-h application was measured, the BH content in the ointment was 88.6 +/- 8.0% for the formulation without Azone and 93.7 +/- 6.9% for that with Azone. The low penetration and low bioavailability observed will thus be due to the high drug retention of the base.