Report on Phase Three: The professional capabilities framework

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The petrology and geochemistry of the rossland volcanic rocks, southern British Columbia

The Rossland Volcanic Group is a dominantly clastic succession that accumulated in a back-arc sedimentary basin in Lower Jurassic time. The lava-types preserved are predominantly augite- and plagioclase-phyric basalts and low-SiO(_2) andesites, but with some localised and conspicuous ankaramitic varieties. Amphibole is a less common but significant phenocryst in basaltic and andesitic compositions. Whole-rock and primary mineral (augite and amphibole) chemical data indicate that the Rossland volcanics are of island-arc affinity. However, rather than being a normal calc-alkaline association, they compare more favourably, in some respects, with the recent, ankaramitic associations of the New Hebrides and New Georgia island-arcs. The presence of primary amphibole in the basalts, and the rare occurrence of primary biotite in one low SiO(_2) andesite, also indicate a mildly alkaline, or high-K(_2)O affinity. Comparison with the sparse data on contemporaneous (Upper Triassic/Lower Jurassic) volcanics of the Canadian Cordillera, indicates that magmatism similar to that in the Rossland area was also operative along the Upper Triassic, Nicola-Takla axis. In the Lower Durassic, the bulk of the volcanics in north-central British Columbia were somewhat different, being more evolved in nature and representing the change of the continental margin to that of an Andean type. The chemistry of the Rossland representatives indicates an upper-mantle origin for the magmas, though only rarely were unmodified partial melts extruded. Rather, as would be expected from the strongly porphyritic nature of the volcanics, mostmagmas suffered a degree of polybaric olivine fractionation(during ascent from around 30Kb) and crustal level (2-7 kb)fractionation of olivine + Cr-spinel + clinopyroxene +amphibole + Ti-magnetite + plagioclase. Metamorphism of the volcanics occurred in Middle Jurassictime, during the early phases of the Columbian orogeny. Consideration of the secondary-mineral assemblages and chemistry, indicates that a progressive regional metamoprhism affected the volcanics, varying from the prehnite-pumpellyite facies, through the greenschist, to the epidote-amphibolite facies. This gradation is from south to north and probably culminates, north of the area, in the Valhalla gneiss dome of the Shuswap complex. Oxygen isotope ((^18)o/(^16)o) data further show that during metamorphism the volcanics exchanged oxygen considerably with a pervasive hydrothermal fluid, enriching them in (^18)0 (δ(^18)0=8-11 º/oo) relative to their original magmatic values (δ(^18)0=6º/00)), The origin of the hydrothermal fluid is enigmatic, but is most probably either extremely (^18)0-enriched meteoric water or is water released during prograde metamoprhism of deeper level sediments and which percolates upwards

Report on Phase One: The social work curriculum.

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Sphingosine Kinases in B-lineage Acute Lymphoblastic Leukaemia

The work presented in this thesis examines firstly, the effects of the sphingosine like immunomodulatory drug FTY720 on B-lineage acute lymphoblastic leukaemia (ALL) cells. Secondly, the research focuses on a related area, namely, the intra-cellular enzymes called sphingosine kinases (SphKs). FTY720 resulted in cytotoxic effects and the induction of autophagy, in vitro in ALL cells. However, disparate in vivo effects were seen in Ph+ and Ph- ALL with a reduction in disease burden seen only in the former, highlighting the importance of pharmacological testing in both in vitro and in vivo settings. Sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2) are over-expressed in ALL with inhibition producing cytotoxic effects, autophagy and predominantly caspase-independent cell death. SphK1 and SphK2 gene deletion resulted in reduced leukaemia penetrance in a murine Ph+ ALL disease model and SphK2 inhibition reduced the growth of human ALL xenografts. SphK2 inhibition resulted in lower MYC gene and protein expression through reduced association of acetylated histone H3 with the MYC promoter. This establishes a completely novel insight into the interactions of SphK2 in ALL and signifies the importance of sphingolipid signalling in this aggressive malignancy

Report on Phase Two: The readiness to practise of NQSWs.

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Delivery of nascent polypeptides to the mitochondrial surface

AbstractThousands of polypeptides with diverse biochemical properties, some of which are extremely hydrophobic, are targeted from cytoplasmic ribosomes to the surface of mitochondria. Localised synthesis, as well as transient interactions with a wide array of molecular chaperones and other cytoplasmic factors, can promote productive interaction of mitochondrial proteins with the TOM complex to initiate protein import into mitochondria