The assessment of cementitious additives used for the stabilisation/solidification of dredged harbour sediments.

This research examined the use of cementitious additives to physically and chemically stabilise dredged harbour sediments for use as fill or for land reclamation purposes. Different combinations of Cement, Stabilime, Old Cement Kiln Dust (OCKD) Diatomite and Amorphous Silica additives were used to stabilise fine dredged harbour sediments from the Nelson and Bayswater (Auckland) marina developements. The relative performance of these different additive combinations were measured in terms of unconfined compressive strength (UCS), and their ability to bind metals using the TCLP leach test. These results were then compared with those obtained using only lime or cement as the additive. This research showed that the two sediments behaved quite differently. This was predominantly due to differences in their clay content and mineralogy. Ofthe different additives, a combination of stabilime and diatomite at a ratio of 75/25 gave best strength results for the Bayswater sediment. Nelson sediment was best stabilised using cement, however, significant substitution of cement with OCKD was shown to be possible without large strength losses. Leaching of zinc, copper, lead, chromium, nickel and cadmium was measured using the TCLP leach test. For the majority of formulations tested, levels of metals leached were found to be less than 10% of their original total content. A link between the final leachate pH and the percentage of each metal leached was the most significant trend identified from the TCLP leach tests. This indicated that precipitation as hydroxides and other similar exchangeable compounds is one of the primary mechanisms binding these metals. The results from this research cannot be used directly in other applications; however, the procedures and methodologies outlined, and the conclusions that have been made, provide a good starting point for identifying a suitable additive for a particular sediment solidification/stabilisation application

Development and Characterization of Recombinant Ovine Coagulation Factor VIII

Animal models of the bleeding disorder, hemophilia A, have been an integral component of the biopharmaceutical development process and have facilitated the development of recombinant coagulation factor VIII (fVIII) products capable of restoring median survival of persons with hemophilia A to that of the general population. However, there remain several limitations to recombinant fVIII as a biotherapeutic, including invasiveness of intravenous infusion, short half-life, immunogenicity, and lack of availability to the majority of the world's population. The recently described ovine model of hemophilia A is the largest and most accurate phenocopy. Affected sheep die prematurely due to bleeding-related pathogenesis and display robust adaptive humoral immunity to non-ovine fVIII. Herein, we describe the development and characterization of recombinant ovine fVIII (ofVIII) to support further the utility of the ovine hemophilia A model. Full-length and B-domain deleted (BDD) ofVIII cDNAs were generated and demonstrated to facilitate greater biosynthetic rates than their human fVIII counterparts while both BDD constructs showed greater expression rates than the same-species full-length versions. A top recombinant BDD ofVIII producing baby hamster kidney clone was identified and used to biosynthesize raw material for purification and biochemical characterization. Highly purified recombinant BDD ofVIII preparations possess a specific activity nearly 2-fold higher than recombinant BDD human fVIII and display a differential glycosylation pattern. However, binding to the carrier protein, von Willebrand factor, which is critical for stability of fVIII in circulation, is indistinguishable. Decay of thrombin-activated ofVIIIa is 2-fold slower than human fVIII indicating greater intrinsic stability. Furthermore, intravenous administration of ofVIII effectively reverses the bleeding phenotype in the murine model of hemophilia A. Recombinant ofVIII should facilitate the maintenance of the ovine hemophilia A herd and their utilization as a relevant large animal model for the research and development of novel nucleic acid and protein-based therapies for hemophilia A