Yes / Three dimensional printing (3DP) was used to engineer novel oral drug delivery devices, with specialised design configurations loaded with multiple actives, with applications in personalised medicine. A filament extruder was used to obtain drug-loaded - paracetamol (acetaminophen) or caffeine - filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3D printing. A multi-nozzle 3D printer enabled fabrication of capsule-shaped solid devices, containing paracetamol and caffeine, with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different from the drug in the adjacent layers; and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least squares component matching to produce false colour representations of distribution of the drugs showed clearly the areas that contain paracetamol and caffeine, and that there is a definitive separation between the drug layers. Drug release tests in biorelevant media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both drugs was simultaneous and independent of drug solubility. With the DuoCaplet design it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device, and the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods. / The full-text of this article will be released for public view at the end of the publisher embargo on 10 Oct 2016.

Master of Science / Department of Chemical Engineering / Larry E. Erickson / The reaction chemistry of uranium metal has been well documented for use in the development of nuclear fuels. The oxidation of uranium from the thermal stress of nearby combustion is different than that of a reactor environment due to the selectivity of the various competing reactions. This work extracts available information in literature and various experiments over the last 60 years to provide a critical look at the response of uranium metal to thermal stress. The oxide fume formed and the equilibrium phase shifts during the dispersal of the airborne particulate are of principal interest when determining potential consequences to the health and safety of the workers, members of the public, and the environment. The transport phenomena and reaction kinetics of the oxide fume are also discussed at various distances from the source material. Uranium is a versatile element that can form numerous compounds, of which the oxides are the forms that are most readily generated under thermal stress and also pose the largest health risk to human beings, primarily through inhalation. A general summary of uranium and the dry compounds (oxides and carbides) is provided discussing the different structures of each state. The reaction kinetics and selectivity as the oxidation progresses is discussed for typical uranium metal forms at temperatures above and below the ignition point. Characteristics of potential fires are qualified for determining thermal stress. The creation of the oxide fume is outlined followed by dispersal characteristics of the aerosol. These molecular processes are related to the release fractions of uranium under fire scenarios which are compared with available experimental data from the regulatory handbooks. A critical look at the conclusions of the handbook with recommendations for revising the existing guidelines and additional testing are made in the interest of ensuring that derived controls are appropriate to reduce the risk of accidents involving the oxidation of uranium metal.

No description available.

Diesel engine combustion has been studied during the last decades by researchers in terms of improving the performance of the engine. In order to improve the analysis of the diesel engine combustion, dimensionless parameters were used in this study. It was concluded that the newly introduced dimensionless parameters developed in this study facilitate understanding of diesel engine combustion process. A new method has been proposed to determine the values of the form factor (m) and efficiency factors (a) of the Wiebe equation. This is achieved by developing a modified form of Wiebe equation with only one constant. The modified version of Wiebe equation facilitates the determination of constants accurately, which enhances the accuracy of evaluating the burn fraction. The error induced on the burn fraction f with respect to the values of constants a and m obtained through different methods is discussed and compared. The form factor affects the burn fraction significantly compared to the efficiency factor. A new non-dimensional parameter ‘combustion burn factor (Ci)’ has been identified in the modified Wiebe equation. The burn fraction f was found to be a function of Ci only, thus the benefits of expressing heat release rate with respect to Ci have been presented. The errors associated with the determination of apparent heat release rate (AHRR) and the cumulative heat release (Cum.Hrr) from the measured cylinder pressure data and the assumed specific heat ratio (γ) was determined and compared. The γ affected the calculated AHRR more than the cylinder pressure. Overestimation of γ resulted in an underestimation of the peak value of the AHRR and vice versa, this occurred without any shift in the combustion phasing. A new methodology has been proposed to determine the instantaneous and mean value of γ for a given combustion. A two litre Ford puma Zetec diesel engine, four cylinder and 16 valves was employed to carry out this investigation. This new methodology has been applied to determine γ for a wide range of injection pressure (800 bar to 1200 bar), injection timing (9 deg BTDC to -2 deg BTDC) and engine loads at 2.7 BMEP and 5 BMEP. Standard ultra-low sulphur diesel fuel and two bio-diesels (Rapeseed Methyl Ester and Jatropha Methyl Ester) were studied in this investigation. Ignition delay is one the most important parameter that characterises the combustion and performance of diesel engines. The relation between ignition delay and combustion performance in terms of efficiency and emission was revealed by researchers. Ignition delay period measurements in diesel engine combustion along with the most used correlation for calculating ignition delay are discussed in this work. The effect of constants on accuracy in the correlation were discussed, and induced error on calculated ignition delay periods with respect to constants were calculated and compared. New techniques were proposed to calculate the constant values directly by using the experimental data. It was found that the calculated values for ignition delay using the new techniques matched well with the experimental data. These techniques can improve the accuracy of the ignition delay correlation. Also a new correlation without any constants was introduced in this work. This correlation can be used to predict ignition delay directly by using engine parameters only. The introduced correlation provides better results compared to Arrhenius type correlation presented by Wolfer. This new correlation can be used for feedback control engine combustion process.

Air contamination strongly decreases the efficiency of fluid power systems and when the allowable limits are exceeded, the performance of the system deteriorates. The hydraulic reservoir performs the function of releasing the entrained air of the hydraulic system to the surroundings. In recent years, the reservoir design has become an important task in the design of the hydraulic system due to space restrictions forcing the use of small sized reservoirs. Despite this fact, experimental results on an air release are not available. In this paper, an experimental investigation of the air release in hydraulic reservoirs is presented. A test apparatus using an optical method as well as the post-processing of the results is described. These are given in terms of an air release rate for different reservoir designs over a wide range of oil flow rates and air loads. The current study is a significant step forward in the design of fluid power systems, as it provides an experimental procedure to measure the air release in the hydraulic reservoir as well as its quantitative analysis.

<p>Acyl-carrier-protein (ACP) is the principal transporter of fatty acids, coordinating acyl-transfer among a vast network of diverse enzymes and biochemical processes. ACP association with protein partners is thought to be exceedingly transient. This paradigm has posed challenges for understanding the molecular basis for acyl-delivery and dissociation. During biosynthesis of the lipid A component (endotoxin) of lipopolysaccharides, ACP shuttles acyl-intermediates thioester-linked to its 4'-phosphopantetheine arm among four acyltransferases: LpxA, LpxD, LpxL, and LpxM. LpxA and LpxD are essential cytoplasmic enzymes, which not only provide an excellent model system to study ACP-based interaction, but also offer an important therapeutic target for development of novel antibiotics. The current dissertation reports the crystal structures of three forms of <italic>Escherichia coli</italic> ACP engaging LpxD, which represent stalled substrate and breakage products along the reaction coordinate. The structures reveal the intricate interactions at the interface that optimally position ACP for acyl-delivery and directly involve the pantetheinyl group. Conformational differences among the stalled ACPs provide the molecular basis for the association-dissociation process. An unanticipated conformational shift of 4'-phosphopantetheine groups within the LpxD catalytic chamber reveals an unprecedented role of ACP in product release. Moreover, the crystal structure of <italic>E. coli</italic> LpxA in complex with one form of ACP (holo-ACP) is presented. The structure reveals three molecules of holo-ACP localize to the C-terminal domain of the LpxA homotrimer, and shows the functional role of this domain is two-fold: ACP recognition and nucleotide binding of UDP-GlcNAc. A comparison with the LpxD:ACP complexes uncovers that ACP utilizes different surface residues for recognition even amongst closely related acyltransferases, yet still relies on "electrostatic steering" for docking to its enzyme partner. Insights gleaned from the presented structures have provided not only a better understanding of ACP interaction with acyltransferases, but also has identified the "drugable molecular landscape" for the development of novel antibiotics against infective bacteria.</p> / Dissertation

Thesis (MComm)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Tsetse flies (Glossina spp), native to mid-continental Africa, are the vectors of trypanosomes that causes human (sleeping sickness) and animal (nagana) trypanosomiasis. Vector control plays a major role in alleviating the burden of the disease. Mathematical models of tsetse population dynamics provide insights into how best to manage these control efforts. A major mark-recapture experiment, carried out in Zimbabwe, provided valuable information on tsetse population dynamics, but the analyses so far published could be improved on because not all of the information available on the marking procedure was used. We have constructed an individual-based model that follows the life of individual tsetse flies, their progeny and, in particular, the sequence of occasions on which individual flies were captured and given distinctive marks. We have access to comprehensive data from the tsetse fly mark-release-recapture experiment carried out on Antelope Island, Lake Kariba, Zimbabwe. In order to calibrate or validate the model, we model both the growth of the introduced tsetse population and the mark-recapture process. We have compared the model outputs to the original data and recommend processes that may be followed for model calibration. It is possible to construct an individual-based model that adequately models tsetse fly populations. Whereas the focus of this study has been on modelling the mark-recapture study, the individual-based model could also be used in more general settings to model the growth, and reduction in fly numbers, changes in age structure, species and gender ratios and the acquisition of trypanosome infections by individual flies. This model can thus be used to investigate the effect of various factors on tsetse fly and trypanosome, population dynamics as well as on the performance of various control techniques effecting fly mortality and disease transmission. / AFRIKAANSE OPSOMMING: Tsetsevlieë (Glossina spp), inheems aan sentraalkontinentale Afrika, is die draers van trypanosomen wat trypanosomiasis by die mens (slaapsiekte) en by diere (nagana) veroorsaak. Die beheer van draers speel 'n belangrike rol om die las wat die siekte veroorsaak, te verlig. Wiskundige modelle van tsetse bevolkingsdinamika bied insigte oor hoe om beheerpogings die beste te bestuur. 'n Belangrike merk-hervang eksperiment, wat in Zimbabwe uitgevoer is, bevat waardevolle inligting oor tsetse bevolkingsdinamika. Die ontleding daarvan, wat tot dusver gepubliseer is, kan egter verbeter word aangesien nie al die inligting beskikbaar in die merkprosedure, gebruik is nie. Ons het 'n individu-gebaseerde model saamgestel wat die lewens van individuele tsetsevlieë en hul nageslagte volg, in besonder die volgorde waarop individuele vlieë gevang en herkenbaar gemerk is. Ons het toegang tot omvattende data van die tsetsevlieg merk-vrylaat-hervang eksperiment wat uitgevoer is op Antelope Eiland, Karibadam, Zimbabwe. Ten einde die model te kalibreer of om die model se geldigheid te bevestig, modelleer ons beide die groei van die ingevoerde tsetse bevolking en die merk-hervangs metode. Ons vergelyk die modeluitsette met die oorspronklike data en beveel prosesse aan wat gevolg kan word om die model te kalibreer. Dit is moontlik om 'n individu-gebaseerde model saam te stel wat tsetsevliegbevolkings voldoende moduleer. Terwyl hierdie studie die modellering van die merk-hervang data bestudeer, kan die individueel-gebaseerde model ook gebruik word in meer algemene gevalle vir die modellering van die vermeerdering en vermindering in vlieë getalle, veranderinge in die ouderdomstruktuur, spesies en geslagverhoudings en die verwerwing van trypanosomen infeksies deur individuele vlieë. Hierdie model kan dus gebruik word om die effek te ondesoek van verskeie faktore op die tsetsevlieg en trypanosomen, populasiedinamiek sowel as die prestasie van verskillende beheertegnieke rakende vliegsterftes en siekte-oordrag.

published_or_final_version / SPACE / Master / Master of Arts

Marine seaweeds constitute one of the most productive plant systems known on Earth and a rich fauna including juvenile fish and crustaceans is dependent on the habitats they form. Human influence on marine costal ecosystems has resulted in large scale changes to the abundance and distribution of species, where species introductions constitute an obvious part. The aims of this thesis were to 1) explore how non-native seaweeds impact on ecosystem functions (primary production and decomposition), and 2) study how interactions between non-native seaweeds and native communities affect invasion success. I used a combination of laboratory assays, outdoor mesocosms and field experiments. Paper I and II revealed that the impact on ecosystem functions were substantially different depending on the identity of the invader. The highly successful non-native red alga Heterosiphonia japonica had a large effect on community productivity. Due to the rapid growth of the invader, the primary production increased by more than four times in mixed species communities with the invader compared to  communities with only native species. In contrast, the morphologically similar and equally successful non-native red alga Bonnemaisonia hamifera grew slowly and had no effect on community production. But B. hamifera produces a potent defense compound that deters native herbivores and reduces the growth of micro-organisms. As a direct or indirect effect of this chemical defense, the litter from B. hamifera decomposed considerably slower compared to native seaweed litter. Rapid growth and defense against predation are likely important in explaining how the two invaders have become successful in the invaded range. These results show that traits related to invasion success may determine impacts on native communities. Paper III shows that the rapidly growing invader H. japonica is avoided as food by native herbivores, which likely enables the invader to survive during colder seasons with sub-optimal growth conditions.  In paper IV I found that competition from the native brown alga Fucus vesiculosus decreased growth of the non-native congener Fucus evanescens. Native herbivores caused more damage to the native competitor but it did not relieve F. evanescens from competitive pressure. Several native brown algae grow in the niche of F. evanescens, which may explain why the species only is growing sparingly in the invaded range. The results indicate that competition with native seaweeds have potential to reduce the success of non-native seaweeds in the new range. In summary, this thesis shows that non-native seaweeds differ strongly in their effect on ecosystem functions. Knowledge of which traits are present among abundant non-native species and how these traits relates to different effects may enable us to gain a better understanding of invasion impacts on native communities. The thesis also highlights that competitive interactions can be of importance for invasion success in seaweed communities. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript. Paper 4: Manuscript.</p> / Alien-native trophic interactions: consequences for invasion success and ecosystem effects of invasions

Even though the role of oxidative stress in a variety of disease states is known, strategies to alleviate this oxidative stress by antioxidants have not been able to achieve clinical success. Particularly, treatment of oxidative stress by small molecule antioxidants has not received due attention because of the challenges associated with its delivery. Antioxidant polymers, where small molecule antioxidants are incorporated into the polymer backbone, are an emerging class of materials that can address some of these challenges. In this work, biodegradable polymers incorporating phenolic antioxidants in the polymer backbone were synthesized. Antioxidant polymers were then characterized for their in vitro degradation, antioxidant release and their effect on oxidative stress levels (redox state) in the cells. Trolox, a water-soluble analogue of vitamin E, was polymerized to synthesize poly(trolox ester) with 100% antioxidant content which undergoes biodegradation to release trolox. Nanoparticles of poly(trolox ester) were able to suppress oxidative stress injury induced by metal nanoparticles in an in vitro cell injury model. In another study, we polymerized polyphenolic antioxidants (e.g. curcumin, quercetin) using a modified non-free-radical polymerization poly(β-amino ester) chemistry. This synthesis scheme can be extended to all polyphenolic antioxidants and allows tuning of polymer degradation rate by choosing appropriate co-monomers from a large library of monomers available for β-amino ester chemistry. Poly(antioxidant β-amino esters) (PABAE) were synthesized and characterized for their degradation, cytotoxicity and antioxidant activity. PABAE degradation products suppressed oxidative stress levels in the cells confirming antioxidant activity of degradation products.