The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

An integrated approach to tourism planning in a developing nation : a case study from Beloi (Timor-Leste)

In this chapter we present a case study set in Beloi, a fishing village located on Ataúro Island, 30 km across the sea from Díli, capital of Timor-Leste (East-Timor). We explore the tension between tourism development, food security and marine conservation in a developing country context. In order to better understand the relationships between the social, ecological and economic issues that arise in tourism planning we use an approach and associated methodology based on storytelling, complexity theory and concept mapping. Through testing scenarios with this methodology we hope to evaluate which trade-offs are acceptable to local people in return for the hoped-for economic boost from increased tourist visitation and associated developments.

Volcanology and petrology of submarine volcanoes of the New Hebrides island arc

The New Hebrides Island Arc, an intra-oceanic island chain in the southwest Pacific, is formed by subduction of the Indo-Australian Plate beneath the Pacific Plate. The southern end of the New Hebrides Island Arc is an ideal location to study the magmatic and tectonic interaction of an emerging island arc as this part of the island chain is less than 3 million years old. A tectonically complex island arc, it exhibits a change in relative subduction rate from ~12cm/yr to 6 cm/yr before transitioning to a left-lateral strike slip zone at its southern end. Two submarine volcanic fields, Gemini-Oscostar and Volsmar, occur at this transition from normal arc subduction to sinistral strike slip movement. Multi-beam bathymetry and dredge samples collected during the 2004 CoTroVE cruise onboard the RV Southern Surveyor help define the relationship between magmatism and tectonics, and the source for these two submarine volcanic fields. Gemini-Oscostar volcanic field (GOVF), dominated by northwest-oriented normal faults, has mature polygenetic stratovolcanoes with evidence for explosive subaqueous eruptions and homogeneous monogenetic scoria cones. Volsmar volcanic field (VVF), located 30 km south of GOVF, exhibits a conjugate set of northwest and eastwest-oriented normal faults, with two polygenetic stratovolcanoes and numerous monogenetic scoria cones. A deep water caldera provides evidence for explosive eruptions at 1500m below sea level in the VVF. Both volcanic fields are dominated by low-K island arc tholeiites and basaltic andesites with calcalkalic andesite and dacite being found only in the GOVF. Geochemical signatures of both volcanic fields continue the along-arc trend of decreasing K2O with both volcanic fields being similar to the New Hebrides central chain lavas. Lavas from both fields display a slight depletion in high field strength elements and heavy rare earth elements, and slight enrichments in large-ion lithophile elements and light rare earth elements with respect to N-MORB mantle. Sr and Nd isotope data correlate with heavy rare earth and high field strength element data to show that both fields are derived from depleted mantle. Pb isotopes define Pacific MORB mantle sources and are consistent with isotopic variation along the New Hebrides Island Arc. Pb isotopes show no evidence for sediment contamination; the subduction component enrichment is therefore a slab-derived enrichment. There is a subtle spatial variation in source chemistry which sees a northerly trend of decreasing enrichment of slab-derived fluids.