Synthesis of novel 4(5)-(5-aminotetrahydropyran-2-yl)imidazole derivatives and their in vivo release of neuronal histamine measured by brain microdialysis

The (2R,5S)-trans- and (2S,5S)-cis-stereoisomers 1a and 1b of 4(5)-(5-aminotetrahydropyran-2-yl)imidazole, which have two chiral centers and adopt a stable chair conformation, were synthesized via cyclization of diol intermediates 7 using L-glutamine as the starting material. Their enantiomers, (2S,5R)-trans-1c and (2R,5R)-cis-1d, were synthesized by the same methodology from D-glutamine. Stereo isomers 1a-d were converted into cyanoguanidines 11a-d, and into N-isopropyl and N-3,3-dimethylbutyl derivatives 12a-d and 13a-d, respectively. The results of in vivo brain microdialysis of the derivatives apparently indicated that only (2S,5R)-isomers increased the release of neuronal histamine. Among the many (2S,5R)-N-alkyl derivatives, 13c (OUP-133) and 18 (OUP-153) increased histamine release to 180-190% and 180-200% of basal levels, respectively, and were found to be novel histamine H(3) antagonists.     

Symmetries of Quantum Lax Equations for the Painlevé Equations

Based on the fact that the Painlevé equations can be written as Hamiltonian systems with affine Weyl group symmetries, a canonical quantization of the Painlevé equations preserving such symmetries has been studied recently. On the other hand, since the Painlevé equations can also be described as isomonodromic deformations of certain second-order linear differential equations, a quantization of such Lax formalism is also a natural problem. In this paper, we introduce a canonical quantization of Lax equations for the Painlevé equations and study their symmetries. We also show that our quantum Lax equations are derived from Virasoro conformal field theory.     

Experimental investigation of droplet acceleration and collision in the gas phase in a microchannel

We developed a novel microfluidic system, termed a micro-droplet collider, by utilizing the spatial-temporal localized liquid energy to realize chemical processes, which achieved rapid mixing between droplets having a large volume ratio by collision. In this paper, in order to clarify the characteristics of the micro-droplet collider, dynamics of droplet acceleration, stationary motion and collision in the gas phase in a microchannel were experimentally investigated with visualized images using a microscope equipped with a high-speed camera. The maximum velocity of 450 mm s(-1) and acceleration of 1500 m s(-2) of a 1.6 nL water droplet were achieved at an air pressure of 100 kPa. Measurement results of dynamic contact angles of droplets indicated that wettability of the surface played an important role in the stability of droplet acceleration and collision. We found that the bullet droplet penetrated into the target droplet at collision, which differed from bulk scale. The deformation of the droplet was strongly suppressed by the channel structure, thus stable collision and efficient utilization of the droplet energy were possible. These results are useful for estimating the localized energy, for improving the system in order to realize extreme performance, and for extending the applications of microfluidic devices.     

Efficient biotinylation of methacryloyl-functionalized nonadherent cells for formation of cell microarrays

In order to obtain cell microarrays formed with human promyelocytic leukemia cells (HL-60), biotinylation of methacryloyl-functionalized HL-60 cells was performed via a thiol-ene reaction with thiol-terminated 4-arm poly(ethylene glycol) (PEG(4)10K-SH). Biotinylated HL-60 cells were selectively adhered onto an avidin-patterned surface with high viability.     

Highly transparent and flexible field emission devices based on single-walled carbon nanotube films

Single-walled carbon nanotubes (SWNTs) have been used successfully to fabricate highly transparent and flexible field emission displays (FEDs). Field emission measurements indicated that SWNTs films have great potential to work as building blocks for next generation transparent and flexible FEDs.     

Extremophilic Polysaccharide for Biosynthesis and Passivation of Gold Nanoparticles and Photothermal Ablation of Cancer Cells

Extremophiles are the group of organisms that are far overlooked for exploring novel biomaterials in the field of material science and bionanotechnology. Extremophilic bacterial‐sulfated exopolysaccharide, mauran (MR), is employed for the bioreduction and passivation of gold nanoparticles (AuNps) to enhance the biocompatibility of AuNps and used for photothermal ablation of cancer cells. Here, various concentrations of MR solution are tested for the reduction of HAuCl₄ solution in the presence as well as in the absence of an external reducing agent, to produce mauran‐gold nanoparticles (MRAu Nps). These biocompatible nanocomposites are treated with cancer cell lines under in vitro conditions and NIR irradiated for complete ablation. MRAu Nps‐treated cancer cells on immediate exposure to infrared radiation from a femtosecond pulse laser of operating wavelength 800 nm are subjected to hyperthermia causing cell death. Biocompatible MR stabilization could fairly reduce the cytotoxicity caused by bare AuNps during biomedical applications. Application of a biocompatible polysaccharide from extremophilic bacterial origin for reduction and passivation of AuNps and used for a biomedical purpose is known to be first of its kind in bionanofusion studies.     

Ring Opening Three-Carbon Extension of 2-Carboethoxycyclo-Alkanones with 3-Bromo-1-(p-Tolylsulfonyl)Propene

Reaction with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) of 2-[3-(p-tolylsulfonyl)-2-propenyl]-2-carboethoxycycloalkanones, derived from 2-carboethoxy-2-sodiocycloalkanones and 3-bromo-l-(p-tolylsulfonyl)propene, caused ring opening three-carbon extension in ethanol and three-carbon ring expansion in benzene to produce terminal dienes and cyclic dienes, respectively.     

Polymer-Supported Tetrabromooxomolybdate(V): A New Type of Catalyst for Oxidation by t-Butyl Hydroperoxide

Tetrabromooxomolybdate(V) was immobilized in alkylammonium cation-type polymers obtained by the reaction of poly(p-chloromethyl-styrene-co-divinylbenzene-co-styrene) (abbreviated CMS) with amines and derived from poly(p-vinylpyridine) and poly(p-vinylpyridine-co-divinylbenzene). These immobilized polymers were active catalysts for the oxidation of alcohols and epoxidation of olefins with t-butyl hydroperoxide (abbreviated t-BuOOH). Among these polymers, we could find a polymer catalyst showing specificity, which was obtained by immobilization of tetrabromooxomolybdate(V) in the polymer derived from the reaction of CMS with trimethylamine. This immobilized polymer does not catalyze epoxidation of olefins but catalyzes oxidation of alcohols with t-BuOOH. Ammonium tetrabromooxomolybdate(V) complex was stabilized by the immobilization in the polymers, and it was found that the reactivity of the active group is due to the microenvironment supplied by the polymer chain.     

Basic structure and cell culture condition of a bioartificial renal tubule on chip towards a cell-based separation microdevice

Various separation processes have been integrated in microfluidics, such as capillary electrophoresis and chromatography, on a microchip. However, it is extremely difficult to separate a complicated biological system by conventional methods. Here, we report on a feasible structure and the culture condition of human renal proximal tubule epithelial cells (RPTECs), with the aim to construct a bioartificial renal tubule on a chip. Glass microchips and a polycarbonate membrane were sealed with no leakage after a surface modification. Furthermore, matrigel was selected as an optimized extracellular matrix (ECM) for cell-proliferation on the membrane. After culturing for 5 days, RPTECs reached confluent in the chip-membrane structure, which was confirmed by nuclei staining. So far, we have constructed the basic structure and cell proliferation circumstance for the future demonstration of the RPTECs separating function. This separation microdevice has promising potential to be applied as both a unit of a circulation cell culture system and a research platform of cell biology.     

i-RUBY: a novel software for quantitative analysis of highly accurate shotgun-proteomics liquid chromatography/tandem mass spectrometry data obtained without stable-isotope labeling of proteins

We developed a novel software named i-RUBY (identification-Related qUantification-Based strategY algorithm for liquid chromatography/tandem mass spectrometry (LC/MS/MS) data) that enables us to perform fully automatic ion current-based spectral feature analysis of highly accurate data obtained by LC/MS/MS. At the 1st step, this software utilizes accurate peptide/protein identification information for peak detection and peak matching among measurements. Then, at the 2nd step, it picks yet unidentified peaks and matches them to the peaks identified at the 1st step by a linear interpolation algorithm. The analysis of human plasma externally spiked with a known amount of yeast alcohol dehydrogenase 1 showed a good linear relationship between the amount of protein spiked and the quantitative values obtained by i-RUBY analysis. Experiment using human plasma digests spiked with a mixture of known amounts of synthetic peptides derived from two yeast proteins, alcohol dehydrogenase 1 and glucose-6-phospate isomerase, showed the expansion by the 2nd step of i-RUBY of the lower quantification limits to 1/10 to 1/1000 of those reached only by identified peaks at the 1st step. Good correlations between the i-RUBY results and the amount of proteins were confirmed by the analysis of real samples, i.e., sera of normal subjects and cancer patients, by comparing quantitative values of acute-phase proteins obtained by i-RUBY analysis of LC/MS/MS data with those obtained by an immunological method using Bio-Plex. These results taken together show that i-RUBY is a useful tool for obtaining dependable quantitative information from highly accurate shotgun-proteomics LC/MS/MS data.