Microchemistry and microstructures of hydrothermally altered shock-metamorphosed basement gneiss, Woodleigh impact structure, Southern Carnarvon Basin, Western Australia

Hydrothermally altered shock-metamorphosed gneisses consisting of relic igneous biotite-K-feldspor-Na-rich alkali feldspar - plagioclase - quartz assemblages ( accessory garnet, corundum, titanite, monazite, zircon), and showing extensive replacement by montmorillonite, illite, sericite, and to a lesser extent chlorite, calcite, epidote, zoisite and pyrite, occur in the basement core uplift of the Woodleigh impact structure, Western Australia. The rocks display extensive hydrothermal clay alteration, complicating identification of pre-hydrothermal and pre-impact textures and compositions. Analysis of quartz-hosted planar deformation features (PDFs) indicates a majority of indexed sets parallel to omega{10 (1) over bar3}, a lesser abundance of sets parallel to pi{10 (1) over bar2}, and some sets parallel to the basal plane (0001) and r,z {10 (1) over bar1}, consistent with pressures about or over 20 GPa. Feldspar-hosted FDFs form reticulate vein networks displaying checkerboard-like to irregular and serrated patterns attributable to preferential replacement of shock-damaged PDFs and/or perthitic twin lamella by clay minerals. The gneisses are pervaded by clay-dominated intergranular and intragranular veins of cryptocrystalline material that display marked departures from bulk-rock chemistry and from mineral compositions. XRD analysis identifies the cryptocrystalline components as illite - montmorillonite, illite and chlorite, while laser Raman analysis identifies high-fluorescence sub-micrometre clay assemblage, feldspar, quartz and minor mica. SEM/EDS-probe and laser-ICPMS analysis indicate low-K high-Mg clay mineral compositions consistent with montmorillonite. Quartz PDF-hosted cryptocrystalline laminae display distinct enrichments in Al, Mg, Ca and K. Altered intergranular veins and feldspar-hosted cryptocrystalline components show consistent enrichment in the relatively refractory elements (Al, Cc, Mg, Fe) and depletion in relatively volatile elements (Si, K, Na). The clay alteration retards determination whether clay-dominated vein networks represent altered shock-induced pseudotachylite veins, diaplectic zones and/or shock-damaged twin lamella, and/or result from purely mineralogical and chemical differentiation affected by hydrothermal fluids, Overall enrichment of the shocked gneiss and of the cryptocrystalline components in Mg and trace ferromagnesian elements (Ni, Cc, Cr) may be attributed alternatively to introduction of siderophile element-rich fluid from the projectile, or/and contamination of hydrothermal fluids by MgO from dolomites surrounding the basement uplift. High Ni/Co and Ni/Cr and anomalous DGE (platinum group elements) may support the former model.

Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase

3-Fluoromethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines (14, 16, and 18-22) are highly potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT). Molecular modeling studies with 3-fluoromethyl-7-(N-alkyl aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines, such as 16, suggested that the sulfonamide -NH-could form a hydrogen bond with the side chain of Lys57. However, SAR studies and analysis of the crystal structure of human PNMT (hPNMT) in complex with 7 indicated that the sulfonamide oxygens, and not the sulfonamide -NH-, formed favorable interactions with the enzyme. Thus, we hypothesized that replacement of the sulfonamide -NH-with a methylene group could result in compounds that would retain potency at PNMT and that would have increased lipophilicity, thus increasing the likelihood they will cross the blood brain barrier. A series of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines (23-30) were synthesized and evaluated for their PNMT inhibitory potency and affinity for the R2-adrenoceptor. A comparison of these compounds with their isosteric sulfonamides (14, 16, and 18-22) showed that the sulfones were more lipophilic but less potent than their corresponding sulfonamides. Sulfone 24 (hPNMT K-i = 1.3 mu M) is the most potent compound in this series and is quite selective for PNMT versus the R2-adrenoceptor, but 24 is less potent than the corresponding sulfonamide, 16 (hPNMT K-i = 0.13 mu M). We also report the crystal structure of hPNMT in complex with sulfonamide 15, from which a potential hydrogen bond acceptor within the hPNMT active site has been identified, the main chain carbonyl oxygen of Asn39. The interaction of this residue with the sulfonamide -NH-is likely responsible for much of the enhanced inhibitory potency of the sulfonamides versus the sulfones.

Mechanics of cellular adhesion to artificial artery templates

We are using polymer templates to grow artificial artery grafts in vivo for the replacement of diseased blood vessels. We have previously shown that adhesion of macrophages to the template starts the graft formation. We present a study of the mechanics of macrophage adhesion to these templates on a single cell and single bond level with optical tweezers. For whole cells, in vitro cell adhesion densities decreased significantly from polymer templates polyethylene to silicone to Tygon (167, 135, and 65 cells/mm(2)). These cell densities were correlated with the graft formation success rate (50%, 25%, and 0%). Single-bond rupture forces at a loading rate of 450 pN/s were quantified by adhesion of trapped 2-mm spheres to macrophages. Rupture force distributions were dominated by nonspecific adhesion (forces, < 40 pN). On polystyrene, preadsorption of fibronectin or presence of serum proteins in the cell medium significantly enhanced adhesion strength from a mean rupture force of 20 pN to 28 pN or 33 pN, respectively. The enhancement of adhesion by fibronectin and serum is additive (mean rupture force of 43 pN). The fraction of specific binding forces in the presence of serum was similar for polystyrene and polymethyl-methacrylate, but specific binding forces were not observed for silica. Again, we found correlation to in vivo experiments, where the density of adherent cells is higher on polystyrene than on silica templates, and can be further enhanced by fibronectin adsorption. These findings show that in vitro adhesion testing can be used for template optimization and to substitute for in-vivo experiments.

Alpha-selenoconotoxins, a new class of potent alpha(7) neuronal nicotinic receptor antagonists

Disulfide bonds are important structural motifs that play an essential role in maintaining the conformational stability of many bioactive peptides. Of particular importance are the conotoxins, which selectively target a wide range of ion channels that are implicated in numerous disease states. Despite the enormous potential of conotoxins as therapeutics, their multiple disulfide bond frameworks are inherently unstable under reducing conditions. Reduction or scrambling by thiol-containing molecules such as glutathione or serum albumin in intracellular or extracellular environments such as blood plasma can decrease their effectiveness as drugs. To address this issue, we describe a new class of selenoconotoxins where cysteine residues are replaced by selenocysteine to form isosteric and non-reducible diselenide bonds. Three isoforms of alpha-conotoxin ImI were synthesized by t-butoxycarbonyl chemistry with systematic replacement of one([ Sec(2,8)] ImI or [Sec(3,12)] ImI), or both([Sec(2,3,8,12)] ImI) disulfide bonds with a diselenide bond. Each analogue demonstrated remarkable stability to reduction or scrambling under a range of chemical and biological reducing conditions. Three-dimensional structural characterization by NMR and CD spectroscopy indicates conformational preferences that are very similar to those of native ImI, suggesting fully isomorphic structures. Additionally, full bioactivity was retained at the alpha(7) nicotinic acetylcholine receptor, with each seleno-analogue exhibiting a dose-response curve that overlaps with wild-type ImI, thus further supporting an isomorphic structure. These results demonstrate that selenoconotoxins can be used as highly stable scaffolds for the design of new drugs.

Understanding city fringe gentrification: The role of a potential investment gap

Discussion of gentrification has become ‘balkanised’ into a series of competing and intensely-held positions. The dichotomies are between economic and cultural explanations, supply-side and demand-side explanations and structural Marxist and liberal humanist views. Despite the long academic and policy interest in gentrification there is still no clear definition of what it is and why it occurs. However, almost all previous analyses see gentrification as an inner-city phenomenon and so deal with it within framework of inner-city theory and causation. This paper approaches the debate from a somewhat different position. It argues that gentrification, seen as the replacement of lower status and income households by higher status and income households, can occur outside the inner city. It uses clear cases of gentrification on the urban fringe of metropolitan Brisbane in South East Queensland, to explore mechanisms and explanations. The key to this ‘gentrification by the sea’ is a ‘potential investment gap’ between current and potential future property values, based on increasing demand for a limited locational resource – but instead of this being inner-city properties it is waterside land in a regional facing rapid population increase. The paper also draws attention to the inadequate recognition of the roles of the state and the media in previous analyses of gentrification.

Effect of anode material and cavity design on the performance of microcavity OLEDs

We report on the effect of the replacement of the conventional ITO anode with the semitransparent metallic material on the performance of microcavity OLEDs. We performed comprehensive simulations of the emission from microcavity OLEDs consisting of widely used organic materials, N,N′-di(naphthalene-1- yl)-N,N′-diphenylbenzidine (NPB) as a hole transport layer and tris (8-hydroxyquinoline) (Alq3) as emitting and electron transporting layer. Silver and LiF/Al were considered as a cathode, while metallic (Au and Ag) anode was used and simulations were performed on devices with both the metallic and conventional ITO anode. The electroluminescence emission spectra, electric field distribution inside the device, carrier density, recombination rate and exciton density were calculated as a function of the position of the emission layer. The results show that the metallic anode enhances light output and that optimum emission from a microcavity OLED is achieved when the position of the recombination region is aligned with the antinode of the standing wave inside the cavity. The microcavity OLED devices with Ag/Ag and Ag/Au mirrors were fabricated and characterized. The experimental results have been compared to the simulations and the influence of the different anode, emission region width and position on the performance of microcavity OLEDs was discussed.

Sedimentologic, petrographic, and sulfur isotope constraints on fine-grained pyrite formation at Mount Isa Mine and environs, Northwest Queensland, Australia

Fine-grained pyrite is the earliest generation of pyrite and the most abundant sulfide within the Urquhart Shale at Mount Isa, northwest Queensland. The pyrite is intimately interbanded with ore-grade Pb-Zn miner alization at the Mount Isa mine but is also abundant north and south of the mine at several stratigraphic horizons within the Urquhart Shale. Detailed sedimentologic, petrographic, and sulfur isotope studies of the Urquhart Shale, mostly north of the mine, reveal that the fine-grained pyrite (delta(34)S = -3.3 to +26.3 parts per thousand) formed by thermochemical sulfate reduction during diagenesis. The sulfate source was local sulfate evaporites, pseudo morphs of which are present throughout the Urquhart Shale (i.e., gypsum, anhydrite, and barite). Deep-burial diagenetic replacement of these evaporites resulted in sulfate-bearing ground waters which migrated parallel to bedding. Fine-grained pyrite formed where these fluids infiltrated and then interacted with carbon-rich laminated siltstones. Comparison of the sulfur isotope systematics of fine-grained pyrite and spatially associated base metal sulfides from the Mount Isa Pb-Zn and Cu orebodies indicates a common sulfur source of ultimately marine origin for all sulfide types. Different sulfur isotope ratio distributions for the various sulfides are the result of contrasting formation mechanisms and/or depositional conditions rather than differing sulfur sources. The sulfur isotope systematics of the base metal and associated iron sulfide generations are consistent with mineralization by reduced hydrothermal fluids, perhaps generated by bulk reduction of evaporite-sourced sulfate-bearing waters generated deeper in the Mount Isa Group, the sedimentary sequence which contains the Urquhart Shale. The available sulfur isotope data from the Mount Isa orebodies are consistent with either a chemically and thermally zoned, evolving Cu-Pb-Zn system, or discrete Cu and Pb-Zn mineralizing events linked by a common sulfur source.

Marine macroalgal biodiversity hotspots: why is there high species richness and endemism in southern Australian marine benthic flora?

The southern Australian marine macroalgal flora has the highest levels of species richness and endemism of any regional macroalgal flora in the world. Analyses of species composition and distributions for the southern Australian flora have identified four different floristic elements, namely the southern Australian endemic element, the widely distributed temperate element, the tropical element and a cold water element. Within the southern Australian endemic element, four species distribution patterns are apparent, thought to largely result from the Jurassic to Oligocene fragmentation of East Gondwana, the subsequent migration of Tethyan ancestors from the west Australian coast and the later invasion of high latitude Pacific species. Climatic deterioration from the late Eocene to the present is thought responsible for the replacement of the previous tropical south coast flora by an endemic temperate flora which has subsequently diversified in response to fluctuating environmental conditions, abundant rocky substrata and substantial habitat heterogeneity. High levels of endemism are attributed to Australia's long isolation and maintained, as is the high species richness, by the lack of recent mass extinction events. The warm water Leeuwin Current has had profound influence in the region since the Eocene, flowing to disperse macroalgal species onto the south coast as well as ameliorating the local environment. It is now evident that the high species richness and endemism we now observe in the southern Australian marine macroalgal flora can be attributed to a complex interaction of biogeographical, ecological and phylogenetic processes over the last 160 million years.