Dense mode clustering in brain maps

A mode-based clustering method is developed for identifying spatially dense clusters in brain maps. This type of clustering focuses on identifying clusters in brain maps independent of their shape or overall variance. This can be useful for both localization in terms of interpretation and for subsequent graphical analysis that might require more coherent or dense regions of interest as starting points. The method automatically does signal/noise sharpening through density mode seeking. We also discuss the problem of parameter selection with this method and propose a new method involving 2-parameter control surface, in which we show that the same cluster solution results from tradeoff of these 2 parameters (the local density k and the radius r of the spherical kernel). We benchmark the new dense mode clustering by using several artificially created data sets and brain imaging data sets from an event perception task by perturbing the data set with noise and measuring three kinds of deviation from the original cluster solution. We present benchmark results that demonstrate that the mode clustering method consistently outperforms the commonly used single-linkage clustering, k means method (centroid method) and Ward's method (variance method).     

New pseudan (2-alkyl-4(1H)-quinolinone) alkaloids from Boronia ternata var. elongata and Boronia alulata (Rutaceae)

The aerial parts of Boronia ternata var. elongata from western Australia has yielded three new 2-acyl-4(1H)-quinolinone alkaloids, characterised as 2-n-pentyl-4(1H)-quinolinone, 1-methyl-2-n-pentyl-4(1H)-quinolinone and 1-methyl-2-(1 xi-methyl)-propyl-4(1H)-quinolinone, as well as known alkaloids of this class and a furoquinoline alkaloid. Boronia alulata, from northeast Queensland, also yielded 2-n-pentyl-4(1H)-quinolinone together with the known 2-n-propyl-4(1H)-quinolinone. Both species are assigned to Boronia section Valvatae which, alone among the sections of Boronia, appears to be characterised by the presence of alkaloids.     

A modular approach to marine macrolide construction. 4. Assembly of C36-C51 and C29-C44 building blocks and evaluation of key coupling reactions targeting spongistatin 1 (altohyrtin A)

Routes have been developed for the stereocontrolled elaboration of two highly functionalized sectors of spongistatin 1. The approach to ring F takes advantage of B-alkyl Suzuki-Miyaura coupling to install the C44-C45 bond. The E-ring pyran moiety was generated by acylation of an alpha-sulfonyl carbanion, the stereogenic centers of which were incorporated by sequential asymmetric aldol reactions. [structure: see text].     

Enantioselective catalytic ring expansion of methylenecyclopropane carboxamides promoted by a chiral magnesium Lewis acid

A catalytic enantioselective ring expansion of monoactivated methylenecyclopropanes (MCP) in the presence of N-tosyl aldimines was developed using a chiral bis(oxazoline) ligand-MgI2 complex. After evaluation of ligands and optimization of the reaction conditions, the reaction has been applied to a variety of aromatic and heteroaromatic aldimines providing the corresponding trans-C2,C3-disubstituted methylenepyrrolidines in generally good yields (greater than 52%) and up to 86% ee. [reaction: see text].     

Determination of bitter orange alkaloids in dietary supplement Standard Reference Materials by liquid chromatography with atmospheric-pressure ionization mass spectrometry

A liquid chromatographic atmospheric-pressure ionization electrospray mass spectrometry (LC–API–ES–MS) method has been developed for the determination of five bitter orange alkaloids (synephrine, octopamine, n-methyltyramine, tyramine, and hordenine) in bitter orange-containing dietary supplement standard reference materials (SRMs). The materials represent a variety of natural, extracted, and processed sample matrices. Two extraction techniques were evaluated: pressurized-fluid extraction (PFE) and sonication extraction. The influence of different solvents, extraction temperatures, and pH were investigated for a plant material and a processed sample. The LC method uses a new approach for the separation of highly polar alkaloids. A fluorinated, silica-based stationary phase separated the five alkaloids and the internal standard terbutaline in less than 20 min. This method enabled the determination of the dominant alkaloid synephrine and other minor alkaloids in a variety of dietary supplement SRMs.     

Biosynthetic production of universally <Superscript>13</Superscript>C-labelled polyunsaturated fatty acids as reference materials for natural health product research

Long-chain polyunsaturated fatty acids (LCPUFA) including eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have become important natural health products with numerous proven benefits related to brain function and cardiovascular health. Not only are omega-3 fatty acids available in a plethora of dietary supplements, but they are also increasingly being incorporated as triglycerides into conventional foods, including bread, milk, yoghurt and confectionaries. Recently, transgenic oil seed crops and livestock have been developed that enhance omega-3 fatty acid content. This diverse array of matrices presents a difficult analytical challenge and is compounded further by samples generated through clinical research. Stable isotope ¹³C-labelled LCPUFA standards offer many advantages as research tools because they may be distinguished from their naturally abundant counterparts by mass spectrometry and directly incorporated as internal standards into analytical procedures. Further, ¹³C-labelled LCPUFAs are safe to use as metabolic tracers to study uptake and metabolism in humans. Currently, ¹³C-labelled LCPUFAs are expensive, available in limited supply and not in triglyceride form. To resolve these issues, marine heterotrophic microorganisms are being isolated and screened for LCPUFA production with a view to the efficient biosynthetic production of U-¹³C-labelled fatty acids using U-¹³C glucose as a carbon source. Of 37 isolates obtained, most were thraustochytrids, and either DHA or omega-6 docosapentaenoic acid (22:5n-6) were produced as the major LCPUFA. The marine protist Hyalochlorella marina was identified as a novel source of EPA and omega-3 docosapentaenoic acid (22:5n-3). As proof of principle, gram-level production of ¹³C-labelled DHA has been achieved with high chemical purity ( >99%) and high ¹³C incorporation levels (>90%), as confirmed by NMR and MS analyses. Finally, U-¹³C-DHA was enzymatically re-esterified to glycerol to yield a ¹³C-labelled tridocosahexaenoin.     

Chemical and strontium isotope characterization of rainwater in France: influence of sources and hydrogeochemical implications

Strontium isotope ratios and Ca2+, Na+, K+, Mg2+, Cl-, SO4(2-), NO3- and Sr2+ concentrations were measured in rainwater samples collected in four stations in France (Brest, Dax, Orleans and Clermont-Ferrand) over a period of 1 year. Each sample represented a monthly series of rain events. The chemical composition and the 87Sr/86Sr ratios of the rainwater samples varied considerably. Using Na concentrations as an indicator of marine origin, the proportion of marine and crustal elements was estimated from elemental ratios. Strontium isotopes were used to characterize the different sources using data from the four stations and the literature. Such sources include sea salts, crustal sources (carbonates, silicates and volcanic rocks) and anthropogenic sources (fertilizers, automobile exhausts, incinerators and urban heating).     

Effects of carrier pulse rate and stimulation site on modulation detection by subjects with cochlear implants

Most modern cochlear-implant speech processors convey speech-envelope information using amplitude-modulated pulse trains. The use of higher-rate carrier pulse trains allows more envelope detail in the signal. However, neural response properties could limit the efficacy of high-rate carriers. This study examined effects of carrier rate and stimulation site, on psychophysical modulation detection thresholds (MDTs). Both of these variables could affect the neural representation of the carrier and thus affect perception of the modulation. Twelve human subjects with cochlear implants were tested. Phase duration of symmetric biphasic pulses was modulated sinusoidally at 40 Hz. MDTs were determined for monopolar stimulation at two carrier rates [250 and 4000 pulses/s (pps)], three stimulation sites (basal, middle, and apical), and five stimulus levels (10%, 30%, 50%, 70%, and 90% of the dynamic range). MDTs were lower for 250 pps carriers than for 4000 pps carriers in 71% of the 180 cases studied. Effects of carrier rate were greatest at the apical stimulation site and effects of stimulation site on MDTs depended on carrier rate. The data suggest a distinct disadvantage to using carrier pulse rates as high as 4000 pps. Stimulation site should be considered in evaluating modulation detection ability.