Synthesis of 2'-O-[2-(N-methylcarbamoyl)ethyl]ribonucleosides using oxa-Michael reaction and chemical and biological properties of oligonucleotide derivatives incorporating these modified ribonucleosides

To develop oligonucleotides containing new 2'-O-modified ribonucleosides as nucleic acid drugs, we synthesized three types of ribonucleoside derivatives modified at the 2'-hydroxyl group with 2-(methoxycarbonyl)ethyl (MOCE), 2-(N-methylcarbamoyl)ethyl (MCE), and 2-(N,N-dimethylcarbamoyl)ethyl (DMCE) groups, as key intermediates, via the oxa-Michael reaction of the appropriately protected ribonucleoside (U, C, A, and G) derivatives. Among them, the 2'-O-MCE ribonucleosides were found to be the most stable under basic conditions. To study the effects of the 2'-O-modification on the nuclease resistance of oligonucleotides incorporating the 2'-O-modified ribonucleosides and their hybridization affinities for the complementary RNA and DNA strands, 2'-O-MCE-ribonucleoside phosphoramidite derivatives were successfully synthesized and subjected to the synthesis of 2'-O-MCE-oligonucleotides and 2'-O-methyl-oligonucleotides incorporating 2'-O-MCE-ribonucleosides. The 2'-O-MCE-oligonucleotides and chimeric oligomers with 2'-O-MCE and 2'-O-methyl groups thus obtained demonstrated complementary RNA strands and much higher nuclease resistances than the corresponding 2'-O-methylated species. Finally, we incorporated the 2'-O-MCE-ribonucleosides into antisense 2'-O-methyl-oligoribonucleotides to examine their exon-skipping activities in splicing reactions related to pre-mRNA of mouse dystrophin. The exon-skipping assay of these 2'-O-methyl-oligonucleotide incorporating 2'-O-MCE-uridines showed better efficacies than the corresponding 2'-O-methylated oligoribonucleotide phosphorothioate derivatives.     

Programmed vesicle fusion triggers gene expression

The membrane properties of phospholipid vesicles can be manipulated to both regulate and initiate encapsulated biochemical reactions and networks. We present evidence for the inhibition and activation of reactions encapsulated in vesicles by the exogenous addition of charged amphiphiles. While the incorporation of cationic amphiphile exerts an inhibitory effect, complementation of additional anionic amphiphiles revitalize the reaction. We demonstrated both the simple hydrolysis reaction of β-glucuronidase and the in vitro gene expression of this enzyme from a DNA template. Furthermore, we show that two vesicle populations decorated separately with positive and negative amphiphiles can fuse selectively to supply feeding components to initiate encapsulated reactions. This mechanism could be one of the rudimentary but effective means to regulate and maintain metabolism in dynamic artificial cell models.     

Preparation, crystal structure and photoluminescence of garnet-type calcium tin titanium aluminates

Colorless and transparent single crystals of Ca₃Sn_2.2Ti_0.8Al₂O₁₂, which emit blue-white light under ultraviolet light, were prepared by heating a mixture of oxides and calcium carbonate with a calcium and aluminum-rich composition at 1500 °C. Single crystal X-ray diffraction revealed that the crystal structure is the garnet-type with a cubic cell parameter (a=12.5309(3) Å) and the space group, Ia 3¯d (R1=0.0277, wR2=0.0663, and S=1.367 for all data). The structural formula is presented as Ca₃[Sn_0.96Ti_0.04]_octa[Al_0.67Ti_0.24Sn_0.09]_tetraO₁₂. Polycrystalline solid solutions of Ca₃Sn_3−xTi_xAl₂O₁₂ were prepared by solid state reaction in air at 1370 °C with nominal titanium contents from x=0.6 to 1.4. The refined unit cell parameter decreased with increasing x. A broad blue-white emission with a peak wavelength of 465 nm was observed for the solid solutions at room temperature.     

The investigation of short-range 3He, 3H and deuteron spin structure via the measurement of the angular distributions of the analyzing power in the \vec dd \to {}^3Hen and \vec dd \to Hp reactions at 140, 200 and 270 MeV

The results on the vector A _y and tensor A _yy , A _xx and A _xz analyzing powers of the $\vec dd \to {}^3Hen$ and $\vec dd \to {}^3Hp$ reactions obtained at intermediate energies at RARF(RIKEN, Japan) are presented. The high precision experimental data are compared with the theoretical calculation within the one nucleon exchange model by using standard ³He, ³H and deuteron wave functions. The data demonstrate the sensitivity to the short-range ³He, ³H and deuteron spin structure.     

Coalescence map for bubbles in surfactant-free aqueous electrolyte solutions

Factors influencing bubble coalescence in surfactant-free aqueous electrolyte solutions are considered in this compilation of literature results. These factors include viscous and inertial thin film drainage, surface deformation, surface elasticity, mobility or otherwise of the air-water interface, and disjoining pressure. Several models from the literature are discussed, with particular attention paid to predictions of transitions between regions where behaviour is qualitatively different. The transitions are collated onto a single chart with salt concentration and bubble approach speed as the axes. This creates a map of the regions in which different mechanisms operate, giving an overall picture of bubble coalescence behaviour over a wide range of concentration and speed. Only mm-size bubbles in water and NaCl solutions are discussed in this initial effort at creating such a map. Data on bubble coalescence or non-coalescence are collected from the literature and plotted on the same map, generally aligning well with the predicted transitions and thus providing support for the theoretical reasoning that went into creating the coalescence map.     

Effects of Therapeutic Ultrasound on Intramuscular Blood Circulation and Oxygen Dynamics

Purpose: This study aimed to clarify the effects of therapeutic ultrasound on intramuscular local blood circulation (and oxygen dynamics) using near-infrared spectroscopy (NIRS). Participants: The participants were 11 healthy males. Methods: All participants performed all three trials; (1) the ultrasound (US group), (2) without powered ultrasound (placebo group), and (3) rest (control group). Ultrasound was applied at 3 MHz, 1.0 W/cm², and 100% duty cycle for 10 minutes. Evaluation index were oxygenated, deoxygenated, and total hemoglobin (Hb) concentrations in the intramuscular and skin surface temperature (SST). The experimental protocol was a total of 40 minutes, that is, 10 minutes before trial (rest), 10 minutes during the trial (ultrasound, placebo, and control), and 20 minutes after trial (rest). The NIRS and SST data collected before and after the trial were divided into 5 minutes intervals for further analysis. Results: Oxygenated and total hemoglobin levels were significantly higher in the US group than in the placebo and control groups for the 20 minutes after ultrasound (p < 0.01). The SST was significantly higher in the US group than in the control for 15 minutes after ultrasound (p < 0.05), while it was significantly lower in the placebo group than in the US and control groups for 20 minutes after the trials (p < 0.01). Conclusion: The effects of ultrasound were maintained for 20 minutes after the trial on intramuscular blood circulation and oxygen dynamics. These effects were caused by a combination of thermal and mechanical effects of the ultrasound.     

Sulfur-Containing Vinyl Monomers. XIX. Radical Polymerization of 2-Mercaptobenzothiazolyl Methacrylate

2-Mercaptobenzothiazolyl methacrylate (MBTM) was synthesized by the reaction of 2-mercaptobenzothiazole and methacrylyl chloride in tetrahydrofuran at -18°C. MBTM was found to polymerize in the presence of 2,2′-azobisisobutyronitrile (AIBN), n-BuLi, and UV light. From the kinetic studies of radical polymerization of MBTM with AIBN in benzene at 60°C, the overall activation energy was determined to be 18.9 kcal/mole, and the rate of polymerization (R) was expressed as R_p = k[AIBN]^0.5 [MBTM], where k is the overall polymerization rate constant. From these results this polymerization was confirmed to proceed via an ordinary radical mechanism. This monomer (M₂) was also copolymerized radically with styrene (M₁) at 60°C, and the resulting copolymerization parameters were determined as r₁ = 0.042, r₂ = 0.20, Q₂ = 4.09, and e₂ = 1.39. The thermal stability and the photodegradation behavior of the polymers were examined, and they were compared with those of the related polymers.     

Characterization of heat-wave propagation through laser-driven Ti-doped underdense plasma

The propagation of a laser-driven heat-wave into a Ti-doped aerogel target was investigated. The temporal evolution of the electron temperature was derived by means of Ti K-shell X-ray spectroscopy, and compared with two-dimensional radiation hydrodynamic simulations. Reasonable agreement was obtained in the early stage of the heat-wave propagation. In the later phase, laser absorption, the propagation of the heat-wave, and hydrodynamic motion interact in a complex manner, and the plasma is mostly re-heated by collision and stagnation at the target central axis.     

Multiclass Markovian fluid queues

This paper considers a multiclass Markovian fluid queue with a buffer of infinite capacity. Input rates of fluid flows in respective classes and the drain rate from the buffer are modulated by a continuous-time Markov chain with finite states. We derive the joint Laplace-Stieltjes transform for the stationary buffer contents in respective classes, assuming the FIFO service discipline. Further we develop a numerically feasible procedure to compute the joint and marginal moments of the stationary buffer contents in respective classes. Some numerical examples are then provided.     

Development of a detection tablet for a portable NO2 monitoring system.

We have already developed a HCHO monitoring system which is called FP-30. In this experiment, we have developed a NO(2) detection tablet which can be used by the monitoring system. The detection tablet for the NO(2) was constructed with the sensing paper: porous cellulose paper that contains silica gel as an adsorbent, N-1-naphthylethylenediamine dihydrochloride (NED), and glycerin. The NO(2) in sample gas was blown over and adsorbed on the surface of the sensing paper. Then the NO(2) reacted with NED, producing a yellow compound. The coloring reaction took place on the surface of the sensing paper. The degree of color change of paper from white to yellow was monitored as a function of the intensity of the reflected light (lambda = 475 nm) of an LED. The detection limit was 0.01 ppm when the sampling time was 30 min, and the flow rate of sample gas was 250 ml/min. This sensing paper process was not interfered with by acetaldehyde, acetone, alcohols, hydrocarbons, carbon monoxide or carbon dioxide. The NO(2) concentrations in the rooms of a house or school were monitored using this monitoring system and the standard chemiluminescence method. The concentrations of NO(2) monitored by both methods were within 18% of the average. This highly sensitive, selective, and handy NO(2) gas monitoring system will be widely applicable and convenient for users who are not specialists in this field.