Bibliography: leaves 189-203. Deals with two interpretation methods, a computer program system AUTOMAG and spectral analysis, used for studying overburden thickness and density structure of the crust. The methods were applied to the Gawler Craton, Eyre Peninsula.

We studied the security of anonymized big graph data. Our main contributions include: new De-Anonymization (DA) attacks, comprehensive anonymity, utility, and de-anonymizability quantifications, and a secure graph data publishing/sharing system SecGraph. New DA Attacks. We present two novel graph DA frameworks: cold start single-phase Optimization-based DA (ODA) and De-anonymizing Social-Attribute Graphs (De-SAG). Unlike existing seed-based DA attacks, ODA does not priori knowledge. In addition, ODA’s DA results can facilitate existing DA attacks by providing more seed information. De-SAG is the first attack that takes into account both graph structure and attribute information. Through extensive evaluations leveraging real world graph data, we validated the performance of both ODA and De-SAG. Graph Anonymity, Utility, and De-anonymizability Quantifications. We developed new techniques that enable comprehensive graph data anonymity, utility, and de-anonymizability evaluation. First, we proposed the first seed-free graph de-anonymizability quantification framework under a general data model which provides the theoretical foundation for seed-free SDA attacks. Second, we conducted the first seed-based quantification on the perfect and partial de-anonymizability of graph data. Our quantification closes the gap between seed-based DA practice and theory. Third, we conducted the first attribute-based anonymity analysis for Social-Attribute Graph (SAG) data. Our attribute-based anonymity analysis together with existing structure-based de-anonymizability quantifications provide data owners and researchers a more complete understanding of the privacy of graph data. Fourth, we conducted the first graph Anonymity-Utility-De-anonymity (AUD) correlation quantification and provided close-forms to explicitly demonstrate such correlation. Finally, based on our quantifications, we conducted large-scale evaluations leveraging 100+ real world graph datasets generated by various computer systems and services. Using the evaluations, we demonstrated the datasets’ anonymity, utility, and de-anonymizability, as well as the significance and validity of our quantifications. SecGraph. We designed, implemented, and evaluated the first uniform and open-source Secure Graph data publishing/sharing (SecGraph) system. SecGraph enables data owners and researchers to conduct accurate comparative studies of anonymization/DA techniques, and to comprehensively understand the resistance/vulnerability of existing or newly developed anonymization techniques, the effectiveness of existing or newly developed DA attacks, and graph and application utilities of anonymized data.

Bibliography: leaves 189-203. / 1 v. (various pagings) : ill., maps (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Deals with two interpretation methods, a computer program system AUTOMAG and spectral analysis, used for studying overburden thickness and density structure of the crust. The methods were applied to the Gawler Craton, Eyre Peninsula. / Thesis (Ph.D.)--University of Adelaide, Dept. of Geology and Geophysics, 1993

The Impala Platinum Mines are located in the western limb of the Bushveld Complex. The economic platinum mineralization which is currently being mined at Impala Platinum occurs in the Merensky and the Upper Group 2 (UG2) Reefs. These ore bearing horizons are stratigraphically located in the Upper Critical Zone of the Bushveld Complex. Due to the variable stratigraphic distance between the UG2 Chromitite Layer and the Merensky Reef, each of these reef horizons is influenced by different geological structural features. It has been observed on several shafts that there is no direct correlation between geological structures encountered on the Merensky Reef to that seen on the UG2 Reef horizon. This observation was prevalent during the geological structural evaluation of the two reef horizons in the No. 12 Shaft area. The Merensky Reef presented itself geologically more favorable to the UG2 Chromitite Layer in terms of structural complexities. Other positive factors included global supply and demand for the resultant metals and the encouraging metal price. There was nonetheless limited trial mining of the UG2 Reef within the No. 12 Shaft area. However, as a result of unfavorable market conditions at the time and complicated geological features which would result in very low extraction rates, it was decided to temporarily cease all mining operations related to the UG2 Reef horizon in this area. It has been strongly recommended in previous geological evaluation reports that the UG2 Chromitite Layer in the No. 12 Shaft area be appraised in significant detail in order to determine the possibility of economically exploiting this mineralized horizon. Due to the current favorable economic climate for platinum group metals, it was suggested by senior management that the UG2 Chromitite Layer be re – evaluated. This dissertation discusses some of the investigative research which was conducted during this re - assessment. The project work comprised research in the following aspects, exploratory drilling, interpretation of geological structural data, grade estimation, mineral resource estimation, financial and sensitivity analyses and aspects concerning risk management. Throughout the project all the input parameters and resultant calculations related to grade, mineral resource and reserve, financial and sensitivity analyses were based on tentative estimates which reflect the author’s personal opinions and assumptions. It is not absolute data of Impala Platinum and thus does not in any way reflect the views of the company. The UG2 Chromitite Layer in the No. 12 Shaft area was benchmarked against the neighboring shafts in terms of its geological and metallurgical characteristics. It was found that regionally, the UG2 Reef displays very limited variability. The financial assessment based on average market input data and assumptions have revealed positive results with regards to general financial and marketing decisions and strategies. In the risk assessment, the high impact risks generally facing all mining companies were found to be within manageable levels. From the investigative geological research based on general business decision criteria, market averages, estimations and assumptions which are used to broadly evaluate projects in the mining industry, it has been demonstrated that it would be economically viable to mine the UG2 Chromitite Layer in the No. 12 Shaft area of Impala Platinum. / Dissertation (MSc (Earth Science Practice and Management))--University of Pretoria, 2008. / Geology / unrestricted

The production of stable solid crystalline material is an important issue in the pharmaceutical industry and the challenge to control the desired active pharmaceutical ingredient (API) with the specific chemical and physical properties has led to more development in the drug industry. Increasing the solubility and the dissolution of the drug will increase its bioavailability; therefore the solubility can be improved with the change in the preparation method. The formation of co-crystals has emerged as a new alternate to the salts, hydrates and solvate methods since the molecules that cannot be formed by the usual methods might crystallise in the form of co-crystals. Co-crystals are multicomponent crystals which can be known as supramolecules and are constructed by the non covalent bonds between the desired former and co-former. Therefore the synthon approach was utilised to design co-crystals with the specific properties, this involves the understanding of the intermolecular interactions between these synthons. These interaction forces can be directed to control the crystal packing in the design of the new crystalline solid with the desired chemical and physical properties. The most familiar synthon was the amide group with its complementary carboxylic group, in this work isonicotinamide and benzoic acid were chosen to design co-crystal and much literature exist that introduce the determination of co-crystal growth from these two compounds. The growth of co-crystals was carried out in water, ethanol and ethanol / water mixed solvent (30 - 90 % ethanol) by utilising the Cryo-Compact circulator. Co-crystals (1:1) and (2:1) were grown in ethanol and water respectively and a mixture of both phases were grown in the mixed solvent. All the phases were examined by powder X-ray diffraction (PXRD), Raman, Infrared and 1H-NMR spectroscopy. The solubility of isonicotinamide, benzoic acid, co-crystals (1:1) and (2:1) in water, ethanol and ethanol/water mixed solvent (30 - 90 % ethanol) were determined at 25 °C, 35 °C and 40 °C by utilising the React-Array Microvate. It was important to understand some of the thermodynamic factors which control the formation of these polymorphs such as the change in the enthalpy and the change in the entropy. Also it was important to study the pH behaviour during dissolution of the former, co-former and co-crystals in water, ethanol and ethanol/water mixed solvent (30 - 90 % ethanol) in-order to examine the affect of the solvent composition on the solubility and to identify if some ions were formed during the dissociation and how this could affects the formation of co-crystals. A discussion has been introduced in this research of how similar solubility of the compounds maps the formation of the typical ternary phase diagram of the mixture of 1:1 while compounds with different solubility maps the formation of skewed phase diagram as shown in section 1.6.2.3. In this project an isotherm ternary phase diagram at 20 °C and 40 °C was constructed to map the behaviour of benzoic acid and isonicotinamide and to show all possible phases formed and the regions where all phases are represented in the ternary phase diagram were determined by the slurry method. The ternary phase diagram was used to design a drawn out and cooling crystallisation at 100 cm3 solution of 50 % ethanol / water mixed solvent and a study of the impact of seeds of co-crystals 1:1 on the cooling crystallisation method.

Background: Structure-based drug repositioning has emerged as a promising alternative to conventional drug development. Regardless of the many success stories reported over the past years and the novel breakthroughs on the AI-based system AlphaFold for structure prediction, the availability of structural data for protein–drug complexes remains very limited. Whereas the chemical libraries contain millions of drug compounds, the vast majority of them do not have structures to crystallized targets,and it is, therefore, impossible to characterize their binding to targets from a structural view. However, the concept of building blocks offers a novel perspective on the structural problem. A drug compound is considered a complex of small chemical blocks or fragments, which confer the relevant properties to the drug and have a high proportion of functional groups involved in protein binding. Based on this, we propose a novel approach to expand the scope of structure-based repositioning approaches by transferring the structural knowledge from a fragment to a compound level. - Results: We fragmented over 100,000 compounds in the Protein Data Bank (PDB) and characterized the structural binding mode of 153,000 fragments to their crystallized targets. Using the fragment’s data, we were able to artificially reconstruct the binding mode of over 7,800 complexes between ChEMBL compounds and their known targets, for which no structural data is available. We proved that the conserved binding tendency of fragments, when binding to the same targets, highly influences the drug’s binding specificity and carries the key information to reconstruct full drugs binding mode. Furthermore, our approach was able to reconstruct multiple compound-target pairs at optimal thresholds and high similarity to the actual binding mode. - Conclusions: Such reconstructions are of great value and benefit structure-based drug repositioning since they automatically enlarge the technique’s scope and allow exploring the so far ‘unexplored compounds’ from a structural perspective. In general, the transfer of structural information is a promising technique that could be applied to any chemical library, to any compound that has no crystal structure available in PDB, and even to transfer any other feature that may be relevant for the drug discovery process and that due to data limitations is not yet fully available. In that sense, the results of this work document the full potential of structure-based screening even beyond PDB.

The rapid pace of scientific advances is enabling a greater understanding of diseases at the molecular level. In turn, the process for researching and developing new medicines is growing in difficulty, costs, and length as a result of the scientific, technical, and regulatory challenges related to the development process. In light of these challenges, drug repositioning, the utilization of known drugs for a new medical indication, has emerged as an increasingly important strategy for the new drug discovery. Availability of prior knowledge regarding safety, efficacy and the appropriate administration route significantly reduces the development costs and cuts down the development time resulting in less effort to successfully bring a repositioned drug to market. In another aspect, a protein’s shape is closely linked with its function; thereby, the ability to predict this structure unlocks a greater understanding of what it does and how it works. Nowadays, more than 10,000 biologically relevant protein structures are yearly released and available to the scientific community. A number suspected to triple over the following years due to the recent breakthroughs in structure prediction techniques. This work introduces a novel structure-based drug repositioning approach, exploiting the similarities of drugs’ binding mode via identification and virtual screening of interaction patterns. Such patterns are uncovered with the use of PLIP, an automated tool for the in silico detection of non-covalent interactions defining the binding mode between drugs and their protein targets. Besides, the approach has been applied to a series of case studies with tangible results: the uncovering of an antimalarial drug as potential chemoresistance treatment, the explained binding mode of ibrutinib to the target VEGR2 as potential B-cells deactivator in autoimmune diseases, and three over the counter drugs with a proved anti-trypanocidal activity as treatments for Chagas disease. Overall the structure-based approach with interaction patterns proved to be a suitable framework for identifying novel repositioning candidates. The uncovered candidates were structurally unrelated to the currently available treatments, and experimental assays successfully demonstrated their inhibitory activity on the protein targets of interest. Furthermore, the approach represents a promising option for the 'in high demand' diseases and all rare and neglected diseases for which no reliable treatment has yet been found and for which the pharmaceutical industry makes only a little investment.