Direct detection of dimethylstannylene and tetramethyldistannene in solution and the gas phase by laser flash photolysis of 1,1-dimethylstannacyclopent-3-enes

The photochemistry of 1,1-dimethyl- and 1,1,3,4-tetramethylstannacyclopent-3-ene (4a and 4b,respectively) has been studied in the gas phase and in hexane solution by steady-state and 193-nm laser flash photolysis methods. Photolysis of the two compounds results in the formation of 1,3-butadiene (from 4a) and 2,3-dimethyl-1,3-butadiene (from 4b) as the major products, suggesting that cycloreversion to yield dimethylstannylene (SnMe2) is the main photodecomposition pathway of these molecules. Indeed, the stannylene has been trapped as the Sn-H insertion product upon photolysis of 4a in hexane containing trimethylstannane. Flash photolysis of 4a in the gas phase affords a transient absorbing in the 450-520nm range that is assigned to SnMe2 by comparison of its spectrum and reactivity to those previously reported from other precursors. Flash photolysis of 4b in hexane solution affords results consistent with the initial formation of SnMe2 (lambda(max) approximate to 500 nm), which decays over similar to 10 mu s to form tetramethyldistannene (5b; lambda(max) approximate to 470 nm). The distannene decays over the next ca. 50 mu s to form at least two other longer-lived species, which are assigned to higher SnMe2 oligomers. Time-dependent DFT calculations support the spectral assignments for SnMe2 and Sn2Me4, and calculations examining the variation in bond dissociation energy with substituent (H, Me, and Ph) in disilenes, digermenes, and distannenes rule out the possibility that dimerization of SnMe2 proceeds reversibly. Addition of methanol leads to reversible reaction with SnMe2 to form a transient absorbing at lambda(max) approximate to 360 nm, which is assigned to the Lewis acid-base complex between SnMe2 and the alcohol.

Equivalent noise level generated by drilling onto the ossicular chain as measured by laser Doppler vibrometry: A temporal bone study

Background: Inadvertent drilling on the ossicular chain is one of the causes of sensorineural hearing loss (HL) that may follow tympanomastoid surgery. A high-frequency HL is most frequently observed. It is speculated that the HL is a result of vibration of the ossicular chain resembling acoustic noise trauma. It is generally considered that using a large cutting burr is more likely to cause damage than a small diamond burr. Aim: The aim was to investigate the equivalent noise level and its frequency characteristics generated by drilling onto the short process of the incus in fresh human temporal bones. Methods and Materials: Five fresh cadaveric temporal bones were used. Stapes displacement was measured using laser Doppler vibrometry during short drilling episodes. Diamond. and cutting burrs of different diameters were used. The effect of the drilling on stapes footplate displacement was compared with that generated by an acoustic signal. The equivalent noise level (dB sound pressure level equivalent [SPL eq]) was thus calculated. Results: The equivalent noise levels generated ranged from 93 to 125 dB SPL eq. For a 1-mm cutting burr, the highest equivalent noise level was 108 dB SPL eq, whereas a 2.3-mm cutting burr produced a maximal level of 125 dB SPL eq. Diamond burrs generated less noise than their cutting counterparts, with a 2.3-mm diamond burr producing a highest equivalent noise level of 102, dB SPL eq. The energy of the noise increased at the higher end of the frequency spectrum, with a 2.3-mm cutting burr producing a noise level of 105 dB SPL eq at 1 kHz and 125 dB SPL eq at 8 kHz. In contrast, the same sized diamond burr produced 96 dB SPL eq at 1 kHz and 99 dB at 8 kHz. Conclusion:This study suggests that drilling on the ossicular chain can produce vibratory force that is analogous with noise levels known to produce acoustic trauma. For the same type of burr, the larger the diameter, the greater the vibratory force, and for the same size of burr, the cutting burr creates more vibratory force than the diamond burr. The cutting burr produces greater high-frequency than lower-frequency vibratory energy.

Stratospheric heating by potential geoengineering aerosols

A fixed dynamical heating model is used to investigate the pattern of zonal-mean stratospheric temperature change resulting from geoengineering with aerosols composed of sulfate, titania, limestone and soot. Aerosol always heats the tropical lower stratosphere, but at the poles the response can be either heating, cooling, or neutral. The sign of the change in stratospheric Pole-Equator temperature difference depends on aerosol type, size and season. This has implications for modelling geoengineering impacts and the response of the stratospheric circulation.

Scattered power from non-thermal, F-region plasma observed by EISCAT—evidence for coherent echoes?

Three rapid, poleward bursts of plasma flow, observed by the U.K.-POLAR EISCAT experiment, are studied in detail. In all three cases the large ion velocities (> 1 kms−1) are shown to drive the ion velocity distribution into a non-Maxwellian form, identified by the characteristic shape of the observed spectra and the fact that analysis of the spectra with the assumption of a Maxwellian distribution leads to excessive rises in apparent ion temperature, and an anticorrelation of apparent electron and ion temperatures. For all three periods the total scattered power is shown to rise with apparent ion temperature by up to 6 dB more than is expected for an isotropic Maxwellian plasma of constant density and by an even larger factor than that expected for non-thermal plasma. The anomalous increases in power are only observed at the lower altitudes (< 300 km). At greater altitudes the rise in power is roughly consistent with that simulated numerically for homogeneous, anisotropic, non-Maxwellian plasma of constant density, viewed using the U.K.-POLAR aspect angle. The spectra at times of anomalously high power are found to be asymmetric, showing an enhancement near the downward Doppler-shifted ion-acoustic frequency. Although it is not possible to eliminate completely rapid plasma density fluctuations as a cause of these power increases, such effects cannot explain the observed spectra and the correlation of power and apparent ion temperature without an unlikely set of coincidences. The observations are made along a beam direction which is as much as 16.5° from orthogonality with the geomagnetic field. Nevertheless, some form of coherent-like echo contamination of the incoherent scatter spectrum is the most satisfactory explanation of these data.

Effect of fluid mechanical stresses and plasma constituents on aggregation of LDL

LDL aggregates when exposed to even moderate fluid mechanical stresses in the laboratory, yet its half-life in the circulation is 2-3 days, implying that little aggregation occurs. LDL may be protected from aggregation in vivo by components of plasma, or by a qualitative difference in flows. Previous studies have shown that HDL and albumin inhibit the aggregation induced by vortexing. Using a more reproducible method of inducing aggregation and assessing aggregation both spectrophotometrically and by sedimentation techniques, we showed that at physiological concentrations, albumin is the more effective inhibitor, and that aggregation is substantially but not completely inhibited in plasma. Heat denatured and fatty-acid-stripped albumin were more effective inhibitors than normal albumin, supporting the idea that hydrophobic interactions are involved. Aggregation of LDL in a model reproducing several aspects of flow in the circulation was 200-fold slower, but was still inhibited by HDL and albumin, suggesting similar mechanisms are involved. Within the sensitivity of our technique, LDL aggregation did not occur in plasma exposed to these flows.jlr Thus, as a result of the characteristics of blood flow and the inhibitory effects of plasma components, particularly albumin, LDL aggregation is unlikely to occur within the circulation.

The impact of age on the postprandial vascular response to a fish oil-enriched meal

Although chronic fish oil intervention had been shown to have a positive impact on vascular reactivity, very little is known about their acute effects during the postprandial phase. Our aim was to examine the impact of a fish oil-enriched test meal on postprandial vascular reactivity in healthy younger ( < 50 years) v. older ( ≥ 50 years) men. Vascular reactivity was measured at baseline (0 h), 2 and 4 h after the meal by laser Doppler iontophoresis and blood samples taken at 0 and 4 h for the measurement of plasma lipids, total nitrite, glucose and insulin. Acetylcholine- (ACh, endothelial-dependent vasodilator) and sodium nitroprusside (SNP, endothelial-independent vasodilator)-induced reactivities were greater at 4 h than at baseline or 2 h in the younger men (P < 0·04). These changes were not observed in the older men. Comparison of the male groups revealed significantly greater responses to ACh (P = 0·006) and SNP (P = 0·05) at 4 h in the younger compared with the older males. Postprandial NEFA concentrations were also greater at 4 h in the younger compared with the older men (P = 0·005), with no differences observed for any of the other analytes. Multiple regression analysis revealed age to be the most significant predictor of both ACh and SNP induced reactivity 4 h after the meal. In conclusion, the ingestion of a meal enriched in fish oil fatty acids was shown to improve postprandial vascular reactivity at 4 h in our younger men, with little benefit evident in our older men.

Fish oil fatty acids improve postprandial vascular reactivity in healthy men

Chronic fish oil intervention had been shown to have a positive impact on endothelial function. Although high-fat meals have often been associated with a loss of postprandial vascular reactivity, studies examining the effects of fish oil fatty acids on vascular function in the postprandial phase are limited. The aim of the present study was to examine the impact of the addition of fish oil fatty acids to a standard test meal on postprandial vascular reactivity. A total of 25 men received in a random order either a placebo oil meal (40 g of mixed fat; fatty acid profile representative of the U.K. diet) or a fish oil meal (31 g of mixed fat and 9 g of fish oil) on two occasions. Vascular reactivity was measured at baseline (0 h) and 4 h after the meal by laser Doppler iontophoresis, and blood samples were taken for the measurement of plasma lipids, total nitrite, glucose and insulin. eNOS (endothelial NO synthase) and NADPH oxidase gene expression were determined in endothelial cells after incubation with TRLs (triacylglycerol-rich lipoproteins) isolated from the plasma samples taken at 4 h. Compared with baseline, sodium nitroprusside (an endothelium-independent vasodilator)-induced reactivity (P = 0.024) and plasma nitrite levels (P = 0.001) were increased after the fish oil meal. In endothelial cells, postprandial TRLs isolated after the fish oil meal increased eNOS and decreased NADPH oxidase gene expression compared with TRLs isolated following the placebo oil meal (P <= 0.03). In conclusion, meal fatty acids appear to be an important determinant of vascular reactivity, with fish oils significantly improving postprandial endothelium-independent vasodilation.

A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects

Objective: To study the bioavailability of anthocyanins and the effects of a 20% blackcurrant juice drink on vascular reactivity, plasma antioxidant status and other CVD risk markers. Subjects/Methods: The study was a randomised, cross over, double blind, placebo controlled acute meal study. Twenty healthy volunteers (11 females 9 males) were recruited, and all subjects completed the study. Fasted volunteers consumed a 20% blackcurrant juice drink (250 ml) or a control drink following a low-flavonoid diet for the previous 72 hours. Vascular reactivity was assessed at baseline and 120 mins after juice consumption by Laser Doppler Imaging (LDI). Plasma and urine samples were collected periodically over an 8 hour period for analysis, with a final urine sample collected at 24h. The cross over was performed after a 4-week washout. Results: There were no significant effects of the 20% blackcurrant juice drink on acute measures of vascular reactivity, biomarkers of endothelial function or lipid risk factors. Consumption of the test juice caused increases in plasma vitamin C (P=0.006), and urinary anthocyanins (P<0.001). Delphinidin-3-rutinoside and cyanidin-3-rutinoside were the main anthocyanins excreted in urine with delphinidin-3-glucoside also detected. The yield of anthocyanins in urine was 0.021 ± 0.003% of the dietary intake of delphinidin glycosides and 0.009 ± 0.002 % of the dietary intake of cyanidin glycosides. Conclusions: The juice consumption did not have a significant effect on vascular reactivity. Anthocyanins were present at low concentrations in the urine, and microbial metabolites of flavonoids were detected in plasma after juice consumption.

Acute ingestion of beetroot bread increases endothelium-independent vasodilation and lowers diastolic blood pressure in healthy men: a randomized controlled trial

Dietary nitrate, from beetroot, has been reported to lower blood pressure (BP) by the sequential reduction of nitrate to nitrite and further to NO in the circulation. However, the impact of beetroot on microvascular vasodilation and arterial stiffness is unknown. In addition, beetroot is consumed by only 4.5% of the UK population, whereas bread is a staple component of the diet. Thus, we investigated the acute effects of beetroot bread (BB) on microvascular vasodilation, arterial stiffness, and BP in healthy participants. Twenty-three healthy men received 200 g bread containing 100 g beetroot (1.1 mmol nitrate) or 200 g control white bread (CB; 0 g beetroot, 0.01 mmol nitrate) in an acute, randomized, open-label, controlled crossover trial. The primary outcome was postprandial microvascular vasodilation measured by laser Doppler iontophoresis and the secondary outcomes were arterial stiffness measured by Pulse Wave Analysis and Velocity and ambulatory BP measured at regular intervals for a total period of 6 h. Plasma nitrate and nitrite were measured at regular intervals for a total period of 7 h. The incremental area under the curve (0-6 h after ingestion of bread) for endothelium-independent vasodilation was greater (P = 0.017) and lower for diastolic BP (DBP; P = 0.032) but not systolic (P = 0.99) BP after BB compared with CB. These effects occurred in conjunction with increases in plasma and urinary nitrate (P < 0.0001) and nitrite (P < 0.001). BB acutely increased endothelium-independent vasodilation and decreased DBP. Therefore, enriching bread with beetroot may be a suitable vehicle to increase intakes of cardioprotective beetroot in the diet and may provide new therapeutic perspectives in the management of hypertension.

Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics

Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs) harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs) within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.

Holocene tidal palaeochannels, Severn Estuary Levels, UK: a search for granulometric and foraminiferal criteria

Holocene tidal palaoechannels, Severn Estuary Levels, UK: a search for granulometric and foraminiferal criteria. Proceedings of the Geologists' Association, 117, 329-344. Grain-size characteristics (by laser granulometry) and foraminiferal assemblages have been established for silts accumulated in five, dissimilar tidal palaeochannels of mid or late Holocene age in the Severn Estuary Levels, representative of muddy tidal systems. For purposes of general comparison, similar data were obtained from a representative active tidal inlet in the area, but all of these channels have been subject to human interference and are not relied upon as a model for environmental interpretation. Although the palaeochannel deposits differ substantially in their bedding characteristics and stratigraphical relationships from the level-bedded salt-marsh platform and mudflat deposits with which they are associated, and although the channel environment is distinctive morphologically and hydraulically, no critical textural differences could be found between the channel deposits and the associated facies. Similarly, no foraminiferal assemblages distinctive of a tidal channel were encountered. Instead, the assemblages compare with those from mudflats and salt-marsh platforms. It is concluded that the sides of the subfossil channels carried some vegetation, as was observed to be the case in the modern inlet. An alternative approach is necessary if concealed palaeochannel deposits are to be recognized in muddy systems from limited numbers of subsurface samples. Although the palaeochannels afforded no characteristic textural signature, they yield transverse grain-size patterns pointing to coastal movements during their evolution. Concave-up trends suggest outward coastal building, whereas convex-up ones point to marsh-edge retreat.

Problems with determining the particle size distribution of chalk soil and some of their implications

Particle size distribution (psd) is one of the most important features of the soil because it affects many of its other properties, and it determines how soil should be managed. To understand the properties of chalk soil, psd analyses should be based on the original material (including carbonates), and not just the acid-resistant fraction. Laser-based methods rather than traditional sedimentation methods are being used increasingly to determine particle size to reduce the cost of analysis. We give an overview of both approaches and the problems associated with them for analyzing the psd of chalk soil. In particular, we show that it is not appropriate to use the widely adopted 8 pm boundary between the clay and silt size fractions for samples determined by laser to estimate proportions of these size fractions that are equivalent to those based on sedimentation. We present data from field and national-scale surveys of soil derived from chalk in England. Results from both types of survey showed that laser methods tend to over-estimate the clay-size fraction compared to sedimentation for the 8 mu m clay/silt boundary, and we suggest reasons for this. For soil derived from chalk, either the sedimentation methods need to be modified or it would be more appropriate to use a 4 pm threshold as an interim solution for laser methods. Correlations between the proportions of sand- and clay-sized fractions, and other properties such as organic matter and volumetric water content, were the opposite of what one would expect for soil dominated by silicate minerals. For water content, this appeared to be due to the predominance of porous, chalk fragments in the sand-sized fraction rather than quartz grains, and the abundance of fine (<2 mu m) calcite crystals rather than phyllosilicates in the clay-sized fraction. This was confirmed by scanning electron microscope (SEM) analyses. "Of all the rocks with which 1 am acquainted, there is none whose formation seems to tax the ingenuity of theorists so severely, as the chalk, in whatever respect we may think fit to consider it". Thomas Allan, FRS Edinburgh 1823, Transactions of the Royal Society of Edinburgh. (C) 2009 Natural Environment Research Council (NERC) Published by Elsevier B.V. All rights reserved.

Comparison of sample size formulae for 2x2 cross-over designs applied to bioequivalence studies

We consider the comparison of two formulations in terms of average bioequivalence using the 2 × 2 cross-over design. In a bioequivalence study, the primary outcome is a pharmacokinetic measure, such as the area under the plasma concentration by time curve, which is usually assumed to have a lognormal distribution. The criterion typically used for claiming bioequivalence is that the 90% confidence interval for the ratio of the means should lie within the interval (0.80, 1.25), or equivalently the 90% confidence interval for the differences in the means on the natural log scale should be within the interval (-0.2231, 0.2231). We compare the gold standard method for calculation of the sample size based on the non-central t distribution with those based on the central t and normal distributions. In practice, the differences between the various approaches are likely to be small. Further approximations to the power function are sometimes used to simplify the calculations. These approximations should be used with caution, because the sample size required for a desirable level of power might be under- or overestimated compared to the gold standard method. However, in some situations the approximate methods produce very similar sample sizes to the gold standard method. Copyright © 2005 John Wiley & Sons, Ltd.

An investigation of the germylene addition reaction, GeH2+C2H2: Time-resolved gas-phase kinetic studies and quantum chemical calculations of the reaction energy surface

Time resolved studies of germylene, GeH2, generated by laser flash photolysis of 3,4-dimethylgermacyclopentene-3, have been carried out to obtain rate constants for its bimolecular reaction with acetylene, C2H2. The reaction was studied in the gas-phase over the pressure range 1-100 Tort, with SF6 as bath gas, at 5 temperatures in the range 297-553 K. The reaction showed a very slight pressure dependence at higher temperatures. The high pressure rate constants (obtained by extrapolation at the three higher temperatures) gave the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1)) (-10.94 +/- 0.05) + (6.10 +/- 0.36 kJ mol(-1))/RTln10. These Arrhenius parameters are consistent with a fast reaction occurring at approximately 30% of the collision rate at 298 K. Quantum chemical calculations (both DFT and ab initio G2//B3LYP and G2//QCISD) of the GeC2H4 potential energy surface (PES), show that GeH2 + C2H2 react initially to form germirene which can isomerise to vinylgermylene with a relatively low barrier. RRKM modelling, based on a loose association transition state, but assuming vinylgermylene is the end product (used in combination with a weak collisional deactivation model) predicts a strong pressure dependence using the calculated energies, in conflict with the experimental evidence. The detailed GeC2H4 PES shows considerable complexity with ten other accessible stable minima (B3LYP level), the three most stable of which are all germylenes. Routes through this complex surface were examined in detail. The only product combination which appears capable of satisfying the (P-3) + C2H4.C2H4 was confirmed as a product by GC observed lack of a strong pressure dependence is Ge(P-3) + C2H4. C2H4 was confirmed as a product by GC analysis. Although the formation of these products are shown to be possible by singlet-triplet curve crossing during dissociation of 1-germiranylidene (1-germacyclopropylidene), it seems more likely (on thermochernical grounds) that the triplet biradical, (GeCH2CH2.)-Ge-., is the immediate product precursor. Comparisons are made with the reaction of SiH2 with C2H2.

Time-resolved gas-phase kinetic and quantum chemical studies of the reaction of silylene with oxygen

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by laser flash photolysis of phenylsilane, have been carried out to obtain rate constants for its bimolecular reaction with O-2. The reaction was studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas, at five temperatures in the range 297-600 K. The second order rate constants at 10 Torr were fitted to the Arrhenius equation: log(k/cm(3) molecule(-1) s(-1)) = (-11.08 +/- 0.04) + (1.57 +/- 0.32 kJ mol(-1))/RT ln10 The decrease in rate constant values with increasing temperature, although systematic is very small. The rate constants showed slight increases in value with pressure at each temperature, but this was scarcely beyond experimental uncertainty. From estimates of Lennard-Jones collision rates, this reaction is occurring at ca. 1 in 20 collisions, almost independent of pressure and temperature. Ab initio calculations at the G3 level backed further by multi-configurational (MC) SCF calculations, augmented by second order perturbation theory (MRMP2), support a mechanism in which the initial adduct, H2SiOO, formed in the triplet state (T), undergoes intersystem crossing to the more stable singlet state (S) prior to further low energy isomerisation processes leading, via a sequence of steps, ultimately to dissociation products of which the lowest energy pair are H2O + SiO. The decomposition of the intermediate cyclo-siladioxirane, via O-O bond fission, plays an important role in the overall process. The bottleneck for the overall process appears to be the T -> S process in H2SiOO. This process has a small spin orbit coupling matrix element, consistent with an estimate of its rate constant of 1 x 10(9) s(-1) obtained with the aid of RRKM theory. This interpretation preserves the idea that, as in its reactions in general, SiH2 initially reacts at the encounter rate with O-2. The low values for the secondary reaction barriers on the potential energy surface account for the lack of an observed pressure dependence. Some comparisons are drawn with the reactions of CH2 + O-2 and SiCl2 + O-2.