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A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy, Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johannesburg, 2017. / Numerous pharmaceutical solid dosage form manufacturing techniques have emerged over the years and among them, 3D-Printing (3DP) has emerged as a highly attractive and versatile approach. 3DP is a cutting edge technology set to expand and revolutionize tablet manufacturing among various other applications in industry. The study reported in this thesis focuses on developing a humic acid-polyquaternium-10 (HA-PQ10) 3D-Printable ink for the delivery of three anti-HIV bioactives, efavirenz (EFV), tenofovir (TDF) and emtricitabine (FTC). HA was strategically employed based on its capability of entrapping both hydrophilic and hydrophobic drugs. PQ10 contributed towards the system’s swellability in aqueous media. The HA-PQ10 PEC was responsible for retarding drug release therefore it behaved as a drug reservoir. Validation of HA-PQ10 complexation was carried out by synthesizing the HA-PQ10 polyelectrolyte complex (PEC) in aqueous media at pH 6, 7 and 8. The complexation yielded fibrilla and porous PECs. The PEC formation was attributed to ionic interactions between the quaternary ammonium centres (PQ10) and carboxylic groups (HA). The PECs were determined to be amorphous in nature and exhibited good biocompatibility when tested for cytotoxicity in human adenocarcinoma cell line (Caco2). The model drug, efavirenz (EFV) was loaded into HA-PQ10 using the complexation-precipitation (C-P) technique. The resultant EFV-loaded HA-PQ10 was compared to benchtop extrudates manufactured using the extrusion-spheronization (E-S) process. Assessment of the EFV saturation solubility and intestinal permeability showed EFV solubility and permeability enhancement of 14.14±2.81% and 61.24±6.92% respectively. The properties were compared to those of a marketed comparator product. Loading RTV into the optimized HA-PQ10 further validated the solubility and permeability enhancing properties in the BCS class IV drug as well. The extrudates performed superiorly compared to the formulation synthesized by C-P. The E-S technique was utilized to optimize HA-PQ10 based on drug release and intestinal permeation enhancement. The optimal HA-PQ10 was employed for 3DP of EFV-loaded HA-PQ10 into an oral tablet formulation. It was imperative to add cellulose acetate phthalate (CAP) to enhance the 3D-Printability of the HA-PQ10. CAP made the synthesized delivery system pH responsive and drug release results showed that most of the release occurred under intestinal conditions. The EFV-loaded 3DP tablet was compared to a tablet synthesized by direct compression. 3DP was more porous, less dense and more swellable than the direct compression tablet. These remarkable differences were attributed to the tableting method. 3DP leads to the formation of solid bridges between particles as the sludge (ink) undergoes extrusion and drying process. The direct compression technique involves axial powder compaction at high pressures which force particles to interact through Van der Waals forces or hydrogen bond formation. High drug loading of EFV was achieved and the tablet was further optimized to manufacture the ‘controlled release tritherapeutic tablet’, CRTT, a fixed dose combination (FDC) consisting of EFV, TDF and FTC. In vivo studies were conducted in large white pigs and CRTT absorption was compared to a marketed FDC, Atripla®. There was sustained release of EFV, TDF and FTC from CRTT and this was validated by the long residence times determined from pharmacokinetic analysis. EFV was maintained within the therapeutic index of the drug during the 24 hour study. Through this study, 3DP proved to be a technology with potential for manufacturing novel formulations. As more research is underway in the 3DP field, it can only be appreciated that its scope of use will continue to grow and restructure pharmaceutical manufacturing processes. / LG2018

Cette thèse se concentre sur des aspects de dualités holographiques reliant une théorie gravitationnelle en trois dimensions à une théorie des champs sur le bord de cette espace, c'est-à-dire en dimensions deux. Dans le premier chapitre, nous passons en revue diverses méthodes, utilisées tout au long de la thèse, pour calculer des quantités conservées en théorie de jauge et plus particulièrement en gravitation. Ensuite, dans le deuxième chapitre, nous rappelons le cas d'école des espaces-temps localement anti-de Sitter (AdS) à trois dimensions et de leur théorie duale, les théories des champs conformes en deux dimensions. Les chapitres trois et quatre sont dédiés à la présentation d'espaces-temps non-AdS considérés dans cette thèse et de la dualité dans laquelle ils sont impliqués. Le premier s'intéresse aux espace-temps warped AdS, qui peuvent être vus comme une déformation d'AdS. Leur théorie des champs duale serait une théorie des champs conforme warped. Le second se concentre sur des solutions cosmologiques, localement plates, qui seraient duales à des théories des champs invariantes sous le groupe BMS$_3$ (groupe de symétrie des espaces asymptotiquement plats). Dans le chapitre cinq, nous révisons des notions de thermodynamique que nous utiliserons pour discuter des transitions de phase entre deux géométries appartenant au même espace des phases. Par exemple, entre l'espaces-temps AdS thermique et le trou noir localement AdS. La partie originale de la thèse traite d'abord des solutions maximalement symétriques dans n'importe quelle théorie invariante sous difféomorphisme. Nous prouvons que le calcul d'entropie gravitationnel est reproduit par le comptage asymptotique d'états dans la théorie duale. Ce travail est étendu au cas des espaces-temps warped. Nous montrons également que leur entropie du bulk et du bord sont en correspondance et ce pour toutes théories de gravitation. Ceci constitue une vérification non triviale des correspondances holographiques. Nous étudions aussi leurs transitions de phase. Finalement, nous posons les premières pierres d'une nouvelle correspondance holographique, impliquant une corde noire, en trouvant un ensemble de conditions au bord cohérent. Nous discutons également la thermodynamique des cordes noires. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Thesis advisor: Tao Li / This dissertation explores a relationship between fibered knots and Heegaard splittings in closed, connected, orientable three-manifolds. We show that a fibered knot, which has a sufficiently complicated monodromy, induces a minimal genus Heegaard splitting that is unique up to isotopy. Moreover, we show that fibered knots in the three-sphere has complexity at most 3. / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Mathematics.

Dans cette thèse, nous explorons des structures intermédiaires ainsi que le rapport entre eux et des algorithmes utilisés dans le contexte du rendu photoréaliste (RP) et non photoréaliste (RNP). Nous présentons des nouvelles structures pour le rendu et l'utilisation alternative des structures existantes. Nous présentons trois contributions principales dans les domaines RP et RNP: Nous montrons une méthode pour la génération des images stylisées noir et blanc. Notre approche est inspirée par des bandes dessinées, utilisant l'apparence et la géometrie dans une formulation d'énérgie basée sur un graphe 2D. En contrôlant les énérgies, l'utilisateur peut générer des images de differents styles et représentations. Dans le deuxième travail, nous proposons une nouvelle méthode pour la paramétrisation temporellement cohérente des lignes animées pour la texturisation. Nous introduisons une structure spatiotemporelle et une formulation d'énérgie permettant une paramétrisation globalement optimale. La formulation par une énérgie donne un contrôle important et simple sur le résultat. Finalement, nous présentons une extension sur une méthode de l'illumination globale (PBGI) utilisée dans la production de films au cours des dernières années. Notre extension effectue une compression par quantification de données générées par l'algorithme original. Le coût ni de memoire ni de temps excède considérablement celui de la méthode d'origin et permet ainsi le rendu des scènes plus grande. L'utilisateur a un contrôle facile du facteur et de la qualité de compression. Nous proposons un nombre d'extensions ainsi que des augmentations potentielles pour les méthodes présentées. / In this thesis, we explore intermediary structures and their relationship to the employed algorithms in the context of photorealistic (PR) and non-photorealistic (NPR) rendering. We present new structures for rendering as well as new uses for existing structures. We present three original contributions in the NPR and PR domain: First, we present binary shading, a method to generate stylized black and white images, inspired by comic artists, using appearance and geometry in a graph-based energy formulation. The user can control the algorithm to generate images of different styles and representations. The second work allows the temporally coherent parameterization of line animations for texturing purposes. We introduce a spatio-temporal structure over the input data and an energy formulation for a globally optimal parameterization. Similar to the work on binary shading, the energy formulation provides a an important and simple control over the output. Finally, we present an extension to Point-based Global Illumination, a method used extensively in movie production during the last years. Our work allows compressing the data generated by the original algorithm using quantification. It is memory-efficient and has only a neglegible time overhead while enabling the rendering of larger scenes. The user can easily control the strength and quality of the compression. We also propose a number of possible extensions and improvements to the methods presented in the thesis.

This study presents an index and qualitative analysis of the operations of the National Labor Relations Board in the State of Utah. The period of time under consideration is 1935 to 1965. The major source of information is the first 153 volumes of the Decisions and Orders of the National Labor Relations Board. The thesis is broken down into four parts. The first covers the evolution of the National Labor Relations Board. It outlines changes in the operations of the board as it developed up to 1964. The second part is an analysis of the influence exercised by the Board over employers in the conduct of their Labor-Management Relations in Utah as governed by the Wagner Act. The third section provides an outline of the Board's operations in administering the Taft-Hartley Act of 1947, and the amendments added by the passage of the Landrum-Griffin Act of 1959. This is primarily an analysis of the decisions and orders issued by the Board to both employers and union representatives in Utah. The fourth section is broken down into two parts: Charges filed with the Board alleging unfair labor practices; and petitions filed with the Board requesting representation elections. No attempt has been made to analyze the representation hearings.

Three Bureau of Reclamation projects, which represent a broad cross-section of the eleven total in Utah, are studied in order to shed light on the value of the invested resources to U.S. taxpayers, the people of Utah, and the local farmers. The bureau's nonmultiple-purpose projects in Utah are termed "supplemental" as opposed to "full-service" because some amount of irrigation was already in place. Recent findings from field trials of yield vs. evapotranspiration for major crops grown in the Western states were employed to assess the annual productive value of existing river water rights had the three projects not been built. Annual estimates of crop values or revenues for each project were obtained from Bureau of Reclamation publications. However, an allowance for annual crop production costs is needed in order to arrive at annual project net incomes (net benefit streams). Cost per acre data were obtained from published intermittent farm studies and reports of farm budgets beginning as early as 1910. This information was then converted to a series of trends in annual production costs by linking to reported indices of farm prices paid as reported by the USDA for the past 80 years. Projects are arbitrarily judged to be "economically efficient" if the estimated internal rate of return at least exceeds borrowing cost to the U.S. Treasury at the time that each project was built, e.g., from 3.5 to 4.5 percent. Only the Strawberry project results suggest that the borrowing rate was exceeded. The Newton project has realized a slight positive return of less than 1 percent, and the Hyrum project has realized negative returns. Thus, the economic results of the bureau's irrigation program in the state have been mixed. Claims of great benefits from water development are not substantiated by the study results. The only unambiguous beneficiaries are farmers whose included lands had very poor or no water rights prior to project construction.

This intergenerational study compared the family planning and related attitudes of females who were daughter-mother-grandmother relatives. Questionnaire responses of eighty-one subjects in twenty-seven three-generation families were analyzed regarding birth control, abortion, and population crisis attitudes. Other variables studied included Mormon orthodoxy, education, and place of residence. Except for abortion, the generations had significantly different attitudes. The oldest generation's attitudes, which were the most conservative, differed significantly when contrasted with the more similar attitudes of the middle and younger generations. Mormon orthodoxy was the most dramatically significant factor in attitude differences. Education and residence were not significant sources of attitude variance; however, there was an education and orthodoxy interaction, with low orthodoxy-high education respondents having abortion attitudes which were significantly more liberal than other respondents.

The geometry and mineralization features of small left-lateral strike-slip faults and associated fractures in Lake Edison Granodiorite of the central Sierra Nevada, California, were examined in order to model the three-dimensional structure of strike-slip faults. These faults, which are reactivated joints, were also examined to determine fault sizes, starting joint size, and evidence for fluid flow. The associated secondary fractures are usually found in the dilational quadrants of fault-tip regions. The longest fault-segment trace is 32.14 m; the longest joint trace is 22 m. The joint population length (l) is represented by a power-law distribution (l-n) and it is l-1.22. The fault-segment distributions are l-0.23~0.79, and the compiled fault-segment distribution is l-1.18. The data on fracture and fault spacing, along with the joint power-law distribution, will aid in the simulation and analysis of fault evolution. The splay-fracture traced in the faults are linear at depth and the average splay-fracture angle is 39° ± 13°. The dihedral angle of the splay plane and fault plane ranges from 20° to 65°. There is a high concentration of splay fractures near the fault. As distance increases perpendicular form the fault, the splay-fracture spacing increases and splay-fracture frequency decreases. The splay tracelength distributions have a high short tracelength concentration with a rapid decrease of long tracelengths. The maximum tracelength of multiple splay-fracture groups is restricted by their distance orthogonal to the fault trace. The three-dimensional relationship between the splay-fracture plane and fault plane can be inferred from these data. When present, mineralized quartz appears largely as lenses and few as single continuous veins along the faults. No consistent pattern exists between fault displacement and the locations and dimensions of quartz cavities. There is no visible damage zone near the fault termination or around the faults. Microstructures in the fault zone consist of cataclasites and patchy gouges, and zones of dynamically recrystallized fault walls. The three-dimensional geometry, along with quartz cavity distribution and thin section analysis, has led to the conclusion that fluid migrates vertically among the faults and fractures.

Three crosses were used to study the inheritance of the sedimentation properties in hard red winter wheat. The parents of the three crosses were the variety Delmar, and the breeding lines 217-61- 7-14 and 217 - 19- 5. Delmar has high sedimentation properties, 217-6 1-7-14 is intermediate, and 217-19-5 has very poor sedimentation qualities. Sedimentation tests were run on five replications of the parents and 300 samples of the F3 populations in each cross. A semi-micro sedimentation test (a one-fourth scale test) was run on 200 F2 plants and the F1's from each cross. The distributions from each cross were analyzed and the type of gene action and possible number of genes involved were estimated. There were two general trends apparent in the progeny of all three crosses. (1) In the F2 generation there were more low parental types than high parental types recovered. This situation was reversed in each of the F3 populations where more high parental types were recovered than the low parental types (2) All three F3means were about 10 units higher than their respective F2 means. The type of gene action appeared to be mainly additive but with some partial dominance for the high parent in each cross . Depending on the cross, from one to three genes were estimated to be functioning in the determination of the sedimentation properties.