Power spectrum and blood flow velocity images obtained by dual-beam backscatter laser Doppler velocimetry

We developed a micro multipoint laser Doppler velocimeter (μ-MLDV) for noninvasive in-vivo measurements of blood flow and we presented the results of demonstrations performed on experimental animals. In this paper, we investigate the validity of power spectrum analysis for determining the flow velocity and the minimum power of the semiconductor laser in the μ-MLDV. Although average velocity is generally estimated from a peak position (f _peak) in the power spectrum, the power spectrum of blood flow included an additional component in the high-frequency region. The conventional method for determining the average velocity of flows of transparent artificial fluids, which involves determining the average velocity from f _peak, is unsuitable for in-vivo measurements of blood flow. The laser power was reduced from 140 to 30mW since 30mW was the minimum power at which images of blood flow velocity in microvessels could be obtained. About 30mW (power density of 15mW/mm²) is the maximum power which can be irradiated to humans. Further reduction in the laser power is necessary before this technique can be applied to humans.     

Determination of the absolute structure of (+)-akaterpin

We describe the total synthesis and structural determination of (+)-akaterpin (1), an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). The key features of the synthetic strategy include the resolution of β,γ-unsaturated ketone (±)-2a with chiral sulfoximine 6. The absolute stereochemistry was determined by comparison of the specific optical rotation data of (+)-1 and (-)-1 with that of natural akaterpin.     

Tuning nanoscopic self‐assembly of diblock copolymer blends on a two‐dimensional interface

Spreading amphiphilic diblock copolymers on a two‐dimensional liquid interface has been observed to produce nanoscale features via self‐assembly. Here, we develop a model that incorporates the effects of polymer entanglement and surface diffusion in polymer blends to quantitatively predict the size of experimentally observed structures. Simulations show that different polymers in the blend cooperate to self‐assemble into nanoscale features of varying sizes. Characteristic nanoscopic dimensions can be tuned by adjusting two easily controllable macroscopic quantities: the blend composition and the initial surface concentration. Theoretical predictions are in agreement with experimentally measured feature dimensions. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Exploratory Study on the RNA‐Binding Structural Motifs by Library Screening Targeting pre‐miRNA‐29 a

The metabolic stream of microRNA (miRNA) production, the so‐called maturation process of miRNAs, became one of important metabolic paths for drug‐targeting to modulate the expression of genes related to a number of diseases. We carried out discovery studies on small molecules binding to the precursor of miR‐29a (pre‐miR‐29a) from a chemical library containing 41 119 compounds (AQ library) by the fluorescent indicator displacement (FID) assay using the xanthone derivative X2SdiMe as a fluorescent indicator. The FID assay provided 1075 compounds, which showed an increase of fluorescence. These compounds were subsequently submitted to a binding analysis in a surface plasmon resonance (SPR) assay on a pre‐miR‐29a immobilized surface. 21 hit compounds were identified with a good reproducibility in the binding. These compounds have not been reported to bind to RNA until now and can be classified into two groups on the basis of the kinetics in the binding. To gain more information on the motif structures that could be necessary for the binding to pre‐miR‐29a, 19 substructures were selected from the hit compounds. The substructure library (SS library) which consisted of 362 compounds was prepared from the AQ library. An SPR assay of the SS library on pre‐miR‐29a‐immobilized surface suggested that five substructures could potentially be important structural motifs to bind to pre‐miR‐29a. These studies demonstrate that the combination of FID‐based screening of chemical library and subsequent SPR assay would be one way for obtaining practical solutions for the discovery of molecules which bind to the target pre‐miRNAs.     

Interaction of recombinant human interferon-gamma with liposomes

The interaction of recombinant human interferon-gamma (IFN) with egg phosphatidylcholine liposomes was studied. IFN which binds to liposomes was dependent on the liposomal charge and pH, and a preferential binding was observed in negatively charged liposomes at pH 7.4-10. Electron-microscopic observation showed that the increased liposomal turbidity induced by IFN was due to liposomal aggregation, and the increased turbidity could be decreased by the addition of NaCl. Thus, ionic binding may participate in this interaction. But, when the incubation time was longer, the liposomal aggregation was not decreased by the addition of NaCl, and the leakage of the entrapped marker, calcein, was observed. Electron-microscopic analysis showed that this leakage resulted from the morphological change of liposomes. From these findings, ionic binding may participate in the interaction between IFN and liposomes and then develop a morphological change in negatively charged liposomes under the neutral pH condition.