Stereoselective synthesis of (Z)-alkene-containing proline dipeptide mimetics

In peptides and proteins, the peptide bond between an amino acid and proline exists as an equilibrium mixture of the cis-imide and trans-imide due to the low energy barrier in their interconversion. This feature greatly influences the structure and function of the proline-containing peptides and proteins. Therefore, restricting the amide bond with an (E)- or (Z)-alkene should provide a promising method for elucidating the structure-activity relationships of the peptide and the proteins. In this report, the regio- and stereoselective synthesis of cis-alanylproline (Ala-Pro) type (Z)-alkene dipeptide mimetic is described. The key steps of this synthesis are to introduce a C3 unit onto a gamma-phosphoryloxy-alpha,beta-unsaturated-delta-lactam with an organocopper-mediated anti-S(N)2' reaction and subsequently construct a five-membered proline-like cyclic structure with an intramolecular Suzuki coupling reaction. Hydrolysis of the amide bond in the resulting bicyclic lactam yields the desired cis-Ala-Pro type (Z)-alkene dipeptide isostere. The presented synthetic methodology should be applicable to the general syntheses of other cis-aminoacylproline type (Z)-alkene dipeptide mimetics.     

Ultra-slim laminated capillary array for high-speed DNA separation

We developed a new kind of capillary array for electrophoresis by using the numerical-control (NC) wiring technique conventionally used to produce printed-circuit boards. Laminating two polyimide sheets after laying cylindrical capillaries between them according to designed geometries, we fabricated a 16-lane laminated capillary array (LCA) 9.9 cm long, 7.2 cm wide, and 0.5 mm thick in which the effective length of all capillaries was only 10.9 cm. This compact LCA thus had separation columns as short as those in capillary array electrophoresis chips fabricated by lithography techniques. Like conventional capillary arrays, it also enabled pipetting-less direct injection of analytes from sample preparation plates. Using the LCA with LIF detection and a replaceable fluid sieving matrix, we demonstrated high-speed ssDNA fragment separations. At an electric field strength of 316 V/cm, 15 fragments ranging from 50 to 500 bases were completely separated within 5.8 min in all lanes. The lane-to-lane CV of migration time was only 0.38%, and the fragment size for which the resolution per base was 0.59 was 258 +/- 15 bases (average +/-SD).     

Suppression of thiol exchange reaction in the determination of reduced-form thiols by high-performance liquid chromatography with fluorescence detection after derivatization with fluorogenic benzofurazan reagent, 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate and 4-aminosulfonyl-7-fluoro-2,1,3-benzoxadiazole

The derivatization of the reduced-form thiols with SBD-F (7-fluoro-2,1,3-benzoxadiazole-4-sulfonate) and ABD-F (4-aminosulfonyl-7-fluoro-2,1,3-benzoxadiazole) was studied. The yields of the derivatives of the reduced-form thiols (cysteine, homocysteine, reduced-form glutathione) with SBD-F at 60 degrees C for 45 min in the borate buffer (pH 9.3) were significantly decreased in the presence of the oxidized-form thiols (cystine, homocystine, oxidized-form glutathione) because of the thiol exchange reaction between the reduced-form and the oxidized-form thiols. The use of ABD-F at low temperature enabled the suppression of these thiol exchange reactions, and the recommended conditions were below 5 degrees C for 90 min in borate buffer (pH 9.3). These results suggest that ABD-F is a preferred derivatization reagent for the accurate determination of the reduced-form thiols in samples containing the oxidized-form thiols. In addition, it was also suggested that the derivatization of the reduced-form thiols should also be performed at low temperature when derivatization reagents such as o-phthalaldehyde (OPA) and monobromobimane (BrB) are used.     

Evaluation of left ventricular function with cardiac magnetic resonance imaging using Fourier fitting

The aims of this study were to investigate the applicability of Fourier fitting in the magnetic resonance (MR) evaluation of left ventricular (LV) function and to determine the optimal number of harmonics for fitting. Cine cardiac MR imaging was performed in 10 subjects, and an LV time–volume curve was generated. Fourier fitting was applied to the original curve using 1–10 harmonics, and the qualities of the time–volume curve and first-derivative curve were evaluated. LV functional parameters were calculated from curves generated with and without fitting. The quality of the original time–volume curve was good, and Fourier fitting had no substantial effect on functional parameters obtained directly from the time–volume curve such as ejection fraction. The first-derivative curve generated without fitting showed substantial artificial fluctuation. The application of Fourier fitting depressed the fluctuation and tended to decrease estimates of peak ejection rate and peak filling rate. Five or six harmonics appeared to be appropriate for obtaining a high-quality first-derivative curve. In conclusion, Fourier fitting was indicated to aid in reducing the artificial fluctuation of the first-derivative curve generated from cine cardiac MR imaging and to contribute to the evaluation of functional parameters derived from the first-derivative curve.     

Mapping of the habenulo-interpeduncular pathway in living mice using manganese-enhanced 3D MRI

This magnetic resonance imaging (MRI) study describes mapping of the habenulo-interpeduncular pathway in living mice based on manganese-induced contrast. Six hours after intracerebroventricular microinjection of MnCl2, T1-weighted 3D MRI (2.35 T) at 117 mum isotropic resolution revealed a continuous pattern of anterograde labeling from the habenula via the fasciculus retroflexus to the interpeduncular nucleus. Alternatively, the less invasive systemic administration of MnCl2 allowed for monitoring of the dynamic uptake pattern of respective neural components with even higher reproducibility across animals. Time courses covered the range from 42 min to 24 h after injection. In conclusion, manganese-enhanced MRI may open new ways for functional assessments of the habenulo-interpeduncular system in animal models with cognitive impairment.     

Lidar measurement of constituents of microparticles in air by laser-induced breakdown spectroscopy using femtosecond terawatt laser pulses

We experimentally demonstrated remote sensing of the constituents of microparticles in air by combining laser-induced breakdown spectroscopy (LIBS) and lidar, using femtosecond terawatt laser pulses. Laser pulses of 70 fs duration and 130 mJ energy generated filaments when focused at a focal length of 20 m and the pulses irradiated artificial saltwater aerosols in air at a 10 Hz pulse repetition rate. Na fluorescence was observed remotely at a distance of 16 m using a 318 mm diameter Newtonian telescope, a spectrometer, and an intensified CCD camera. These results show the possibility of remote measurement of the constituents of atmospheric particles, such as aerosols, clouds, and toxic materials, by LIBS-lidar using femtosecond terawatt laser pulses.     

Community responses to road traffic noise in Hanoi and Ho Chi Minh City

Vietnam is a developing country in southeast Asia, and its environment has been seriously affected by industrialization and urbanization. In large cities like Hanoi (northern Vietnam) and Ho Chi Minh City (southern Vietnam), noise emission from road traffic has been found to be a serious concern among general public. In 2005 and 2007, two large-scale socio-acoustic surveys of community response to road traffic noise were conducted to investigate human reactions to road traffic noise in these cities; the sample sizes were 1503 people in Hanoi and 1471 in Ho Chi Minh City. The noise exposure levels (L_den) were 70–83 dB in Hanoi and 75–83 dB in Ho Chi Minh City. Noise annoyance was estimated using standardized annoyance scales. For both cities, dose–response relationships were established between L_den and the percentage of highly annoyed respondents. Compared to annoyance responses of European people, Vietnamese were less annoyed by road traffic noise by about 5 dB. Hanoi respondents seemed to be more annoyed by noise than Ho Chi Minh City respondents. Conversation and sleep disturbances were not as serious as expected in either city. Furthermore, window orientation in the home was found to affect activity disturbances.     

Predictions and experimental studies of the tail pipe noise of an automotive muffler using a one dimensional CFD model

The tail pipe noise from a commercial automotive muffler was studied experimentally and numerically under the condition of wide open throttle acceleration in the present research. The engine was accelerated from 1000 to 6000 rpm in 30 s at the warm up condition. The transient acoustic characteristics of its exhaust muffler were predicted using one dimensional computational fluid dynamics. To validate the results of the simulation, the transient acoustic characteristics of the exhaust muffler were measured in an anechoic chamber according to the Japanese Standard (JIS D 1616). It was found that the results of simulation are in good agreement with experimental results at the 2nd order of the engine rotational frequency. At the high order of engine speed, differences between the computational and experimental results exist in the high revolution range (from 5000 to 6000 rpm at the 4th order, and from 4200 to 6000 rpm at the 6th order). According to these results, the differences were caused by the flow noise which was not considered in the simulation. Based on the theory of one dimensional CFD model, a simplified model which can provide an acceptable accuracy and save more than 90% of execution time compared with the standard model was proposed for the optimization design to meet the demand of time to market.     

Turbulence kinetic energy budget in bubbly flows in a vertical duct

Understanding turbulence kinetic energy (TKE) budget in gas–liquid two-phase bubbly flows is indispensable to develop and improve turbulence models for the bubbly flows. In this study, a molecular tagging velocimetry based on photobleaching reaction was applied to turbulent bubbly flows with sub-millimeter bubbles in a vertical square duct to examine the applicability of the k–ε models to the bubbly flows. Effects of bubbles on TKE budget are discussed and a priori tests of the standard and low Reynolds number k–ε models are carried out to examine the applicability of these models to the bubbly flows. The conclusions obtained are as follows: (1) The photobleaching molecular tagging velocimetry is of use for validating turbulence models. (2) The bubbles increase the liquid velocity gradient in the near wall region, and therefore, enhance the production and dissipation rates of TKE. (3) The k–ε models can reasonably evaluate the production rate of TKE in the bubbly flows. (4) The modulations of diffusion due to the bubbles have different characteristics from the diffusion enhancement due to shear-induced turbulence. Hence, the k–ε models fail in evaluating the diffusion rate in the near wall region in the bubbly flows. (5) The k–ε models represent the trends of the production, dissipation, and diffusion rates of ε in the bubbly flow, although more accurate experimental data are required for quantitative validation of the ε equation.     

Massless and quantized modes of kinks in the phase space of superconducting gaps

We investigated quantized modes of kinks in the phase space of superconducting gaps in a superconductor with multiple gaps. The kink is described by the sine-Gordon model in a two-gap superconductor and by the double sine-Gordon model in a three-gap superconductor. A fractional-flux vortex exists at the edge of the kink, and a fractional-flux vortex will be stable in a three-gap superconductor with time-reversal symmetry breaking. The kink and fractional-flux vortex exhibit massless modes as a sliding motion. We show further that there are one zero-energy mode (massless mode) and quantized excitation modes in kinks, which are characteristic features of multi-gap superconductors. The equation of quantized modes for the double sine-Gordon model is solved numerically. The correction to the ground-state energy is calculated based on the renormalization theory.