The Flotation of Niobium Oxide Minerals from Carbonatite Ores

Global niobium production is presently dominated by three operations, Araxá and Catalão (Brazil), and Niobec (Canada). Although Brazil accounts for over 90% of the world’s niobium production, a number of high grade niobium deposits exist worldwide. The advancement of these deposits depends largely on the development of operable beneficiation flowsheets. Pyrochlore, as the primary niobium mineral, is typically upgraded by flotation with amine collectors at acidic pH following a complicated flowsheet with significant losses of niobium. This research compares the typical two stage flotation flowsheet to a direct flotation process (i.e. elimination of gangue pre-flotation) with the objective of circuit simplification. In addition, the use of a chelating reagent (benzohydroxamic acid, BHA) was studied as an alternative collector for fine grained, highly disseminated pyrochlore. For the amine based reagent system, results showed that while comparable at the laboratory scale, when scaled up to the pilot level the direct flotation process suffered from circuit instability because of high quantities of dissolved calcium in the process water due to stream recirculation and fine calcite dissolution, which ultimately depressed pyrochlore. This scale up issue was not observed in pilot plant operation of the two stage flotation process as a portion of the highly reactive carbonate minerals was removed prior to acid addition. A statistical model was developed for batch flotation using BHA on carbonatite ore (0.25% Nb2O5) that could not be effectively upgraded using the conventional amine reagent scheme. Results showed that it was possible to produce a concentrate containing 1.54% Nb2O5 with 93% Nb recovery in ~15% of the original mass. Fundamental studies undertaken included FT-IR and XPS, which showed the adsorption of both the protonized amine and the neutral amine onto the surface of the pyrochlore (possibly at niobium sites as indicated by detected shifts in the Nb3d binding energy). The results suggest that the preferential flotation of pyrochlore over quartz with amines at low pH levels can be attributed to a difference in critical hemimicelle concentration (CHC) values for the two minerals. BHA was found to be absorbed on pyrochlore surfaces by a similar mechanism to alkyl hydroxamic acid. It is hoped that this work will assist in improving operability of existing pyrochlore flotation circuits and help promote the development of niobium deposits globally. Future studies should focus on investigation into specific gangue mineral depressants and inadvertent activation phenomenon related to BHA flotation of gangue minerals.

EXAMINATION OF VALPROIC ACID-INDUCED PERTURBATIONS TO DNA REPAIR, NF-ΚB SIGNALING AND CBP/P300 TRANSCRIPTIONAL CO-ACTIVATORS

Exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of congenital malformations including heart, skeletal and most frequently neural tube defects. Although the mechanisms contributing to its teratogenesis are not well understood, VPA was previously shown to increase homologous recombination (HR)-mediated DNA repair and decrease protein expression of the transcription factor NF-κB/p65. The studies in this thesis utilized in vivo and in vitro models to evaluate the expression of HR mediators, investigate the implications of decreased p65 including DNA binding and transcriptional activation, and the expression and histone acetyltransferase activity of Cbp/p300 with an aim to provide mechanistic insight into VPA-mediated alterations. The first study demonstrated that following maternal administration of VPA, mouse embryonic mRNA expression of HR mediators Rad51, Brca1 and Brca2 exhibited temporal and tissue-specific alterations. Protein expression of Rad51 was similarly altered and preceded increased cleavage of caspase-3 and PARP; indicative of apoptosis. The second study confirms previous findings of decreased total cellular p65 protein using P19 cells, but is the first to demonstrate that nuclear p65 protein is unchanged. NF-κB DNA binding was decreased following VPA exposure and maybe mediated by decreased p50 protein, which dimerizes with p65 prior to DNA binding. Transcriptional activity of NF-κB was also increased with VPA exposure which was not due to increased p65 phosphorylation at Ser276. Furthermore, the transcriptional activation capacity was unaffected by VPA exposure as combined exposure to VPA and TNFα additively increased NF-κB activity. The third study demonstrated that VPA exposure in P19 cells decreased Cbp/p300 total cellular and nuclear protein attributed primarily to ubiquitin proteasome-mediated degradation. Histone acetyltransferase (HAT) activity of p300 was decreased proportionately to nuclear protein following VPA exposure. Inhibition of Cbp/p300 HAT activity decreased p65 total cellular protein, increased caspase-3 cleavage and ROS similar to VPA exposures. Furthermore, pre-treatment with the antioxidant enzyme catalase attenuated the increase in caspase-3 cleavage, but not p65 protein. Overall, this thesis demonstrates that VPA exposure impacts the expression and activity of the transcription factor NF-κB and transcriptional co-activators/HATs Cbp/p300, which has implications for downstream VPA targets including Rad51, Brca1 and Brca2.