Kinetics of the reaction of OH with methyl nitrate (223-343 K).

Rate coefficients (k4) for the reaction of hydroxyl radicals (OH) with methyl nitrate (CH3ONO2) were measured over the temperature range 232-343 K using pulsed laser photolysis to generate OH and pulsed laser-induced fluorescence to detect it in real-time and under pseudo-first-order conditions. In order to optimize the accuracy of the rate coefficients obtained, the concentration of CH3ONO2 (the reactant in excess) was measured on-line by absorption spectroscopy at 213.86 nm for which the absorption cross-section was also measured (σ213.86 = 1.65 ± 0.09 × 10-18 cm2 molecule-1). The temperature-dependent rate coefficient is described by k4(T) = 7.5 × 10-13 exp[(-1034 ± 40)/T] cm3 molecule-1 s-1 with a room temperature rate coefficient of k4(296 ± 2 K) = (2.32 ± 0.12) × 10-14 cm3 molecule-1 s-1 where the uncertainty includes the statistical error of 2σ and an estimation of the potential systematic bias of 5%. This new dataset helps to consolidate the database for this rate coefficient and to reduce uncertainty in the atmospheric lifetime of CH3ONO2. As part of this study, an approximate rate coefficient for the reaction of H-atoms with CH3ONO2 (k9) was also derived at room temperature: k9(298 K) = (1.68 ± 0.45) × 10-13 cm3 molecule-1 s-1.

Study of backspatter using high-speed video of experimental gunshots.

Backspatter is biological material that is ejected from the entry wound against the line of fire. This phenomenon was also observed in wound ballistic simulations using so called "reference cubes" (12 cm edge length, 10% gelatin, 4 °C, paint pad beneath the cover). High-speed video records from 102 experimental shots to these target models using full metal jacketed bullets in the calibers .32 auto, .38 special, 9 mm Luger and .357 Magnum were analyzed for chronology, morphological appearance and velocity of fluid ejection. Generally, a short tail splashing of surface material occurred when the bullet was penetrating the target. In 51 shots from distance (≥ 5 cm), regardless of caliber and shot range, a linear jet of fluid started in connection with the first collapse of the temporary cavity. The initial velocity of the jet was measured between 6 and 45 m/s. The jet was streaming on for about 60 to 100 ms with a stochastic deviation of ± 13° to the horizontal. Close range and contact shots showed earlier and faster (up to 330 m/s) backspatter depending on the cartridge and the gap between muzzle and target. Gaseous aerosol-like spray and cone-like spatter indicated an increasing influence of muzzle gases with decreasing shot range. Even under standardized experimental conditions, variations of backspatter were observed in near/contact shots.

Site-Specific Labeling of MicroRNA Precursors: A Structure-Activity Relationship Study.

Functionalized oligoribonucleotides are essential tools in RNA chemical biology. Various synthetic routes have been developed over recent years to conjugate functional groups to oligoribonucleotides. However, the presence of the functional group on the oligoribonucleotide backbone can lead to partial or total loss of biological function. The limited knowledge concerning the positioning of functional groups therefore represents a hurdle for the development of oligoribonucleotide chemical tools. Here we describe a systematic investigation of site-specific labeling of pre-miRNAs to identify positions for the incorporation of functional groups, in order not to hinder their processing into active mature miRNAs.

Stereochemical bias introduced during RNA synthesis modulates the activity of phosphorothioate siRNAs.

An established means of improving the pharmacokinetics properties of oligoribonucleotides (ORNs) is to exchange their phosphodiester linkages for phosphorothioates (PSs). However, this strategy has not been pursued for small interfering RNAs (siRNAs), possibly because of sporadic reports that PS siRNAs show reduced inhibitory activity. The PS group is chiral at phosphorous (Rp/Sp centres), and conventional solid-phase synthesis of PS ORNs produces a population of diastereoisomers. Here we show that the choice of the activating agent for the synthesis of a PS ORN influences the Rp/Sp ratio of PS linkages throughout the strand. Furthermore, PS siRNAs composed of ORNs with a higher fraction of Rp centres show greater resistance to nucleases in serum and are more effective inhibitors in cells than their Sp counterparts. The finding that a stereochemically biased population of ORN diastereoisomers can be synthesized and exploited pharmacologically is important because uniform PS modification of siRNAs may provide a useful compromise of their pharmacokinetics and pharmacodynamics properties in RNAi therapeutics.