Composite materials have become viable alternatives to traditional engineering materials for many different product categories. Liquid transfer moulding (LTM) processes, specifically resin transfer moulding (RTM), is a cost-effective manufacturing technique for creating high performance composite parts. These parts can be tailor-made to their specific application by optimizing the properties of the textile preform. Preforms which require little or no further assembly work and are close to the shape of the final part are critical to obtaining high quality parts while simultaneously reducing labour and costs associated with other composite manufacturing techniques. One type of fabric which is well suited for near-net- shape preforms is stitched non-crimp fabrics. These fabrics offer very high in-plane strength and stiffness while also having increased resistance to delamination. Manufacturing parts from these dry preforms typically involves long-scale fluid flow through both open channels and porous fibre bundles. This thesis documents and analyzes the flow of fluid through preforms manufactured from non-crimp fabrics featuring through-thickness stitches. The objective of this research is to determine the effect of this type of stitch on the RTM injection process. All of the tests used preforms with fibre volume fractions representative of primary and secondary structural parts. A series of trials was conducted using different fibre materials, flow rates, fibre volumes fractions, and degrees of fibre consolidation. All of the trials were conducted for cases similar to RTM. Consolidation of the fibres showed improvements to both the thoroughness of the filling and to the fibre volume fraction. Experimentally determined permeability data was shown to trend well with simple models and precision of the permeability data was comparable to values presented by other authors who studied fabrics which did not feature the through-thickness stitches.

This thesis investigates the constant pressure cake filtration of interacting cellulose fibre/TiO2 (rutile) mixtures, and involved experimental studies using an automated pressure filtration apparatus. The influence of suspension composition, filtration pressure and solution environment on filtration has been discussed in relation to cake properties such as average cake porosity and specific resistance. To help interpret the filtration results, sedimentation data were also obtained. The average porosities of filter cakes formed from pure rutile and fibre suspensions in deionised water were approximately 0.6 and 0.75, respectively, and a steady and progressive increase in porosity with fibre fraction was generally observed. With filtrations at 450 kPa, the average specific cake resistances for pure fibre and rutile in deionised water were approximately 9.4x1013 and 4.2x1012 m kg-1 respectively, with the variation of specific resistance with solids composition showing a minimum. Similar trends were observed at other tested filtration pressures with suspensions in deionised water but not with filtrations of suspensions in 0.2 M NaCl and 0.1 M CaCl2 solutions. The minima in average specific cake resistance with solids composition for feeds in deionised water was attributed to rutile-fibre interactions. Abrupt transitions in cake structure were evident part way through some filtrations, and resulted in unexpected filtrate flow behaviour. This is an interesting phenomenon, and not only were the changes in cake structure relatively reproducible, but also the nature of the change could be altered by changes in filtration pressure, solids composition and/or solution environment. The study of fibre/particle binary filtration behaviour, in particular the porosity and specific cake resistance trends, were substantiated by relevant theoretical treatment and modelling analysis. With the porosity trends, an additive porosity concept seemed to represent the data better than interparticle penetration models. With the specific cake resistance trends, a semi-empirical equation was proposed which appeared to represent a wide range of binary mixture filtration data. A mathematical framework was also developed in an attempt to understand the underlying physical mechanisms which led to filter cake restructuring, and possible explanations were postulated.

Lopinavir (LPV) is a potent protease inhibitor specific for HIV-1. However, LPV has poor placental penetration due to substrate activity for efflux transporter by P-glycoprotein (P-gp). Since fatty acid transporters are highly expressed in the placenta during pregnancy, we designed fatty acid ester prodrug of lopinavir as substrates of fatty acid transporter in order to improve their uptake into placenta. Seven dicarboxylic acid esters of lopinavir have been made in our lab. The structures were characterized by 1H-NMR, 13C-NMR, LC-MS/MS, HRMS, IR and melting points. After making the prodrugs, an LC-MS/MS method with high specificity and sensitivity, as well as simultaneous quantitative analyses of lopinavir and SLPV, GLPV and DLPV in the BeWo cells methanol extraction was established and validated. The uptake of prodrugs (SLPV, GLPV and DLPV) in the BeWo cells was then determined. GLPV has the highest uptake followed by SLPV and then DLPV. The results suggest that the carbon length of the promoiety may have a positive relationship with the uptake. Ideal prodrugs should be stable before they reach placenta and can be hydrolyzed in the placenta and/or in fetal plasma. We did a series of stability and hydrolysis studies in human tissue fractions. The results showed that GLPV and SLPV were very stable in HIC, HLC and human adult plasma. DLPV was stable in HIC, HLC, but can be hydrolyzed in human adult plasma. GLPV and SLPV cannot be hydrolyzed in either human placenta or fetal plasma, while DLPV can be hydrolyzed in both human placenta and fetal plasma. Anti-HIV activities study of prodrugs was also conducted. The results showed that the EC50 of three prodrugs (GLPV, SLPV and DLPV) are 0.86 μM, 0.84 μM and 0.05 μM, which are much lower than 50 μM (The active drug criteria for this assay). It suggests that prodrugs have apparently anti-HIV activity. DLPV has comparable apparent anti-HIV activity to LPV (<0.02 μM). After incubation with CEM-SS cells for 6 days, almost half of DLPV was hydrolyzed into LPV. Therefore, the high anti-HIV potent of DLPV may be due to the anti-HIV activity of generated LPV.

Whole-cell biocatalysts are preferred in many biocatalysis applications. However, cell envelope often represents a formidable permeability barrier. As a result, reactions catalyzed by whole-cells are reportedly orders of magnitude slower than those of by their free enzyme counterparts. The present research addresses this critical issue by using membrane engineering approaches. Two E. coli strains with genetically altered outer membrane structures were used in the study, a lipopolysaccarides (LPS) mutant SM101 and a Braun's lipoprotein mutant E609L. The effects of outer membrane mutation on the permeability of substrates differing substantially in size and hydrophobicity were investigated by combining the mutant cells with model enzymes. The reduction of the outer membrane permeability barrier by these mutations led to significant accelerations (2 to 14 fold) in reaction rates of all whole-cell catalyzed reactions investigated. In the case of tetrapeptide, LPS mutation of the outer membrane can render the outer membrane completely permeable to substrate, a barrier-less condition that maximizes the reaction rate. For reaction rates of toluene dioxygenase (TDO)-catalyzed reactions, a dramatic increase of up to six fold was observed with the lipoprotein mutant for each of the three small, hydrophobic substrates tested. Mutations in either the LPS or in the Braun's lipoprotein are effective for accelerating reactions with UDP-glucose, resulting in a striking acceleration (up to 14 fold) of reaction rate. The magnitude of reaction rate acceleration was found to be dependent upon the substrate concentrations, the enzyme expression level, and on the nature of the mutations and substrates. In addition, the mutations have been demonstrated to be far more superior to common permeabilization procedures like freeze-thaw (FT) or treatment with the chelating agent EDTA (ethylene diamine tetraacetic acid). Importantly, lipoprotein mutant E609L exhibited a normal growth rate and expressed the recombinant multi-component enzyme as well as the isogenic parent. The exact nature of lpp lipoprotein mutation in E609L was further studied and deletion of lpp was successfully introduced into E. coli strain with different genetic background for whole-cell biocatalysis applications. An example was provided by introducing an lpp deletion into an E. coli O44K74 strain to achieve a higher yield for L-carnitine production. This research and the results outlined in this dissertation demonstrate a valid strategy for addressing permeability issues in whole-cell biocatalysis. The work also highlights a need for accessing substrate permeabilities in biocatalysis research and development.

Master of Science / Department of Civil Engineering / Kyle Riding / The relationship between in-place concrete strength and permeability with concrete cylinder strength and permeability with time is of interest - especially when supplementary cementitious materials (SCMs) are used. A joint research project between The University of Kansas was undergone to quantify these relationships. The permeability of concrete is directly tied to its ability to mitigate certain failure mechanisms such as corrosion and sulfate attack. The three concrete mixtures being tested by Kansas State University (KSU) vary in cementitious content as follows: (1) 100% ordinary portland cement (OPC), (2) 25% Class F fly ash (F-ash) and 75% OPC, (3) 25% Class C fly ash (C-Ash) and 75% OPC. The mixtures were also placed in three different seasons to present differing curing environmental effects. The summer slabs were cast during July and August. The fall slabs were cast in October and November. The final set of slabs were cast in March and April. Three sets of concrete specimens (lab cured, field cured and in-situ core specimens) were tested at 28, 56, 90, 180, and 360 days for strength and permeability properties. The permeability performance tests being utilized are ASTM C1202 and ASTM C642. The results have shown very desirable permeability and strength data for the mixes using blended fly ash cements. The F-ash exhibited the best high early strength and low permeability data for the summer placement season and slower strength and permeability performance at cold weather. The C-ash performed the best overall for all seasons and had the least environmental effects. The OPC performed the worst in regards to permeability and did not reach as high long term strength.

A thesis submitted to the Faculty of Engineering, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 1994. / This thesis presents the details and results of an investigation into the effects of early age curing on the durability of concrete The two main objectives of the investigation were: to develop simple test methods, applied at relatively early ages, for measuring the effects of early-age moist curing on the advance of hydration in the cover zone of concrete; to quantify the effect of early age curing on the durability performance of concretes of various strength grades and made with different binder types. [Abbreviated Abstract. Open document to view full version]

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, South Africa, in fulfilment of the requirements for the degree of Doctor of Philosophy, 2013. / The aim of the thesis is to derive group invariant, exact, approximate analytical and numerical solutions for a two-dimensional laminar, non-Newtonian pre-existing hydraulic fracture propagating in impermeable and permeable elastic media. The fracture is driven by the injection of an incompressible, viscous non-Newtonian fluid of power law rheology in which the fluid viscosity depends on the magnitude of the shear rate and on the power law index n > 0. By the application of lubrication theory, a nonlinear diffusion equation relating the half-width of the fracture to the fluid pressure is obtained. When the interface is permeable the nonlinear diffusion equation has a leak-off velocity sink term. The half-width of the fracture and the net fluid pressure are linearly related through the PKN approximation. A condition, in the form of a first order partial differential equation for the leak-off velocity, is obtained for the nonlinear diffusion equation to have Lie point symmetries. The general form of the leak-off velocity is derived. Using the Lie point symmetries the problem is reduced to a boundary value problem for a second order ordinary differential equation. The leak-off velocity is further specified by assuming that it is proportional to the fracture half-width. Only fluid injection at the fracture entry is considered. This is the case of practical importance in industry. Two exact analytical solutions are derived. In the first solution there is no fluid injection at the fracture entry while in the second solution the fluid velocity averaged over the width of the fracture is constant along the length of the fracture. For other working conditions at the fracture entry the problem is solved numerically by transforming the boundary value problem to a pair of initial value problems. The numerical solution is matched to the asymptotic solution at the fracture tip. Since the fracture is thin the fluid velocity averaged over the width of the fracture is considered. For the two analytical solutions the ratio of the averaged fluid velocity to the velocity of the fracture tip varies linearly along the fracture. For other working conditions the variation is approximately linear. Using this observation approximate analytical solutions are derived for the fracture half-width. The approximate analytical solutions are compared with the numerical solutions and found to be accurate over a wide range of values of the power-law index n and leak-off parameter β. The conservation laws for the nonlinear diffusion equation are investigated. When there is fluid leak-off conservation laws of two kinds are found which depend in which component of the conserved vector the leak-off term is included. For a Newtonian fluid two conservation laws of each kind are found. For a non-Newtonian fluid the second conservation law does not exist. The behaviour of the solutions for shear thinning, Newtonian and shear thickening fluids are qualitatively similar. The characteristic time depends on the properties of the fluid which gives quantitative differences in the solution for shear thinning, Newtonian and shear thickening fluids.

A dissertation submitted to the Faculty of Science,University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science. December 2016. / This research is concerned with the analysis of a two-dimensional Newtonian fluid-driven fracture in a permeable rock. The fluid flow in the fracture is laminar and the fracture is driven by the injection of a Newtonian fluid into it. Most of the problems in litera- ture involving fluid flow in permeable rock formation have been modeled with the use of Darcy's law. It is however known that Darcy's model breaks down for flows involv- ing high fluid velocity, such as the flow in a porous rock formation during hydraulic fracturing. The Forchheimer flow model is used to describe the non-Darcy fluid flow in the porous medium. The objective of this study is to investigate the problem of a fluid-driven fracture in a porous medium such that the flow in the porous medium is non-Darcy. Lubrication theory is applied to the system of partial di erential equations since the fracture that is considered is thin and its width slowly varies along its length. For this same reason, Perkins-Kern-Nordgren approximation is adopted. The theory of Lie group analysis of differential equations is used to solve the nonlinear coupled sys- tem of partial differential equations to obtain group invariant solutions for the fracture half-width, leak-o depth and length of the fracture. The strength of fluid leak-off at the fracture wall is classi ed into three forms, namely, weak, strong and moderate. A group invariant solution of the traveling wave form is obtained and an exact solution for the case in which there is weak fluid leak-off at the interface is found. A dimensionless parameter, F0, termed the Forchheimer number was obtained and investigated. Nu- merical results are obtained for both the case of Darcy and non-Darcy flow. Computer generated graphs are used to illustrate the analytical and numerical results. / MT2017

Rendre possible l'administration orale du docétaxel (Dtx), un puissant agent anticancéreux administré par voie intraveineuse, représente un défi important en cancérologie. Disposer de formulations administrables par voie orale, moins toxiques et mieux tolérées, représenterait une avancée majeure au plan clinique. Toutefois, plusieurs études ont montré que la très faible biodisponibilité du Dtx par voie orale résulte simultanément de : (i) sa faible solubilité aqueuse, (ii) son faible passage transépithélial au niveau intestinal, (iii) son efflux par les pompes d’efflux (P-gp) et son métabolisme par le cytochrome P450. Nous avons conçu une formulation capable de répondre simultanément à ces différents problèmes. Ainsi, nous avons tout d’abord fait appel aux cyclodextrines (CDs) pour augmenter la solubilité apparente du Dtx. La complexation du Dtx avec la méthyl-β-CD a permis d’augmenter la solubilité apparente du Dtx d’environ 5000 fois. Ce complexe a ensuite été associé à des nanoparticules(NPs) polymères composées d’un coeur de poly(cyanoacrylate d’alkyle) et recouvert en surface de chitosane thiolé afin de leur conférer des propriétés mucoadhésives et de diminuer localement le métabolisme. Ces NPs ont montré in vitro et ex vivo leur capacité à arriver intactes au niveau de l’intestin, d’y adhérer et de libérer le Dtx de manière contrôlée dans le temps, et finalement d’améliorer son absorption intestinale. Une évaluation de la toxicité de cette formulation vis-à-vis de la muqueuse intestinale suggère que l’encapsulation du Dtx dans les NPs assure une certaine protection de la muqueuse. Au final, la formulation orale proposée offre en perspective la possibilité de moduler la dose administrée, donc d’ajuster finement la posologie et finalement d’offrir au corps médical et aux patients les bénéfices d’une thérapie personnalisée. / Docetaxel (Dtx) is an anticancer drug widely used in therapy. However, severe allergic reactions and peripheral neurotoxicity are caused by the intravenous administration of the commercial formulation Taxotere®, requiring thus the oral administration of dexamethasone and antihistamine before infusion. In this context, there is an urgent need to design new orally administered Dtx formulations to reduce these side effects and improve the patient’s qualityof life. Dtx belongs to the Class IV of the Biopharmaceutical Classification System, which comprises substances with both low solubility in aqueous fluids and low apparent intestinal permeability. This represents a major drawback when foreseeing oral delivery. Moreover, Dtx has been shown to be substrate of biological transporters and/or metabolized in the intestinal barrier. We designed a formulation able to overcome these different problems. First of all, we solved the low solubility problem by using cyclodextrin (CDs). The complexation of Dtx with the Methyl-ß-CD allowed increasing the apparent solubility of the Dtx about 5000 times. This complex was then associated to polymeric core-shell nanoparticles (NPs) based on poly(isobutyl cyanoacrylate) coated with thiolated chitosan. Among the characteristics of this system, mucoadhesion properties are the most important for an oral administration. The presence of the positively charged chitosan chains, and the thiol groups at the surface allow NPs to adhere to the mucus layer. In vitro and ex vivo experiments showed that these NPs were able to ensure a time-controlled release of Dtx and to improve its absorption at the intestinal level. An evaluation of the local intestinal toxicity of this formulation suggests that the encapsulation of Dtx into polymeric NPs had a protective effect allowing a preservation of the mucosa integrity. The further step will be to confirm by in vivo studies if this kind of nanoparticles is able to enhance the bioavailability of Dtx allowing to display an anti-tumor activity.

Este trabalho tem por objetivo estudar a molhabilidade e a permeabilidade para quatro espécies de madeiras tropicais (Pinus elliottii, Araucaria angustifolia, Eucalyptus grandis e Eucalyptus citriodora). A molhabilidade é um parâmetro importante para a caracterização de diferentes espécies de madeira e, portanto, depende de fatores como o estado de limpeza da superfície da madeira, orientação das fibras, tipo de amostra (alburno ou cerne), secagem, tratamentos térmicos e químicos, rugosidade superficial, etc. Primeiramente, investigamos a molhabilidade para as quatro espécies tropicais por medida de ângulo de contato aparente para diferentes solventes na superfície da madeira As amostras foram tratadas termicamente no intervalo 100 200º C, por 8h e foi utilizado o método da gota séssil e um goniômeto. Os valores dos ângulos de contato foram maiores para as amostras submetidas aos tratamentos térmicos, indicando um aumento no caráter hidrofóbico da madeira. A técnica de ângulo de contato não foi eficiente para tratamentos térmicos superiores a 200º C, devido a sua degradação. No experimento de permeabilidade foi utilizado um fluxo de ar através das amostras com poros fechados e abertos. Foi verificado um acréscimo de 82 % na vazão para as situações de poros abertos no Eucalyptus citriodora. Nossos resultados permitem detectar mudanças consideráveis na molhabilidade e permeabilidade da madeira, sendo informações valiosas para a conservação e utilização destas madeiras. / This work aims to study wettability and permeability for tropical wood species (Pinus elliotti, Araucaria angustifolia, Eucalyptus grandis and Eucalyptus citriodora).The adhesive wettability is an important parameter for characterizing different wood species and depends on factors such as cleaning state of the wood surface, orientation of the wood fibers, type of sample (sapwood or heartwood), drying, thermal and chemical treatments, surface roughness, etc. First, we investigated the wettability of the four tropical wood species by measuring the apparent contact angles of different solvents on the wood surfaces. The samples were heat treated from 100 to 200 °C for 8 h, and the contact angles measured by the sessile drop method with a home-made goniometer. For samples heat-treated below 200 °C, higher values of contact angles were obtained, indicating a hydrophobic character for thermal treated woods. After this temperature, the wood degradation took place. For permeability experiments, a flow of air was used for wood samples with closed and open pores. An increase of 82% in flow was verified for open pores woods such as Eucalyptus citriodora. Our results allowed us to detect considerable changes on wood wettability and permeability and that are powerful information for conservation and use of these woods.