Doctor of Philosophy / Department of Biology / Brett K. Sandercock / Samantha Wisely / Anthropogenic activities and climate change have dramatically altered landscapes worldwide. The ability of species to cope and adapt to ongoing changes is likely a function of their behavior, movements, and sensitivity to fragmentation. Greater Prairie-Chickens (GPC) are a lek mating grouse native to the Great Plains Landscape Conservation Cooperative (GPLCC), for which inbreeding depression and anthropogenic avoidance are a concern. The goals of my dissertation were to: 1) identify genetic correlates of male performance which may influence population viability under current land use practices, 2) identify GPC habitat characteristics and delineate areas of critical GPC habitat necessary for GPC conservation, and 3) identify the relative importance of distance and habitat quality for maintaining genetic connectivity among spatially structured populations. First, I found male reproductive success and survival to be positively associated with genetic diversity. Using multistate modeling in Program Mark, male survival across the observed range of variation in number of alleles (15-22) increased more than fourfold from 0.17 to 0.77. Second, I found 35-40% of Kansas, and 1.5 % (11,000 Km squared) of the GPLCC, were considered high-quality lek habitats. Top performing logistic models predicting lek presence (wi=0.95) included strong effects of grassland cover and avoidance of anthropogenic disturbance. When this model was applied to putative future landscapes based on climate change and current land use trends over a 70-year period, I found a 27-40% reduction in habitat area and a 137 Km southeast shift in habitat distribution. Under equilibrium conditions we expect isolation by distance (IBD) to explain the distribution of genetic diversity. However, if the landscape restricts dispersal, then we might observe isolation by resistance (IBR). I used model selection procedures to choose among competing IBR or IBD models to explain the distribution of genetic diversity among GPC populations across Kansas and the GPLCC. IBD was never supported (R-square<0.02, P>0.09). The best models for Kansas (R2=0.69, P<0.02) and for the GPLCC (R-square=0.46, P<0.02) indicated that human-mediated landscape changes have influenced landscape permeability for dispersal. The integration of behavioral, landscape, and genetic data provided new insights on prairie-chicken ecology, and is a powerful approach for developing conservation strategies for sensitive species.

Master of Science / Department of Chemical Engineering / Mary Rezac / Polymeric membranes have been playing important roles in gas or liquid separations. Polyimide polymers are of interest due to their commercially availability along with good transport, thermal and mechanical properties. In this study, two common commercial polyimide polymers, Matrimid and P84 were blended, to combine the good transport property of Matrimid with the plasticization resistance of P84. Matrimid/P84 blend solutions ranging from 0-100 wt. % Matrimid were prepared to make blend films. Physical properties (density, d-spacing, thickness), transport properties (permeability of H2, N2, CH4, Ar, He, CO2, and gas pairs selectivity), thermal property (mass loss curves of TGA), and liquid solutes (water, methanol, toluene, butanol, 1-propanol, 2-propanol) desorption behavior were measured or characterized. Rules of changing behavior of the properties with mass fraction of Matrimid were investigated, summarized, and interpreted mathematically. As Matrimid mass fraction increases, there are more mobility and space between polymer chains, therefore there are smaller density, larger d-spacing, larger fractional free volume (FFV) and larger permeability. The selectivity-permeability relationship follows the trade-off line. Thermal mass loss curve of the blend films in air have presented intermediate characteristic with rising fraction of Matrimid compared to individual polymers. A partial-miscible behavior has been found from the correlation between permeability and FFV. The desorption behavior was found to be reasonably described by the case III model, where the diffusion rate is similar with relaxation rate of polymers.

Master of Science / Food Science Institute-- Animal Science & Industry / J. Scott Smith / Ammonia leaks in meat chilling/frozen storage or processing facilities are not uncommon. Often the meat products are packaged in polymer films that theoretically protect the product from contamination. Unfortunately, there is almost no data on whether ammonia can permeate packaging films. The objectives of this study were to evaluated meat contaminated by low levels of ammonia under frozen storage conditions (-17 ± 3[degree]C), and further evaluated the permeability of common meat packaging films including: low density polyethylene (LDPE), 3 mil Cryovac (E-2300), and 3 mil vacuum (V-PA/PE) at freezing (-17 ± 3 [degree]C) and room temperatures (21 ± 3 [degree]C). Fresh beef Semitendinosus muscles were fabricated to form 10 x 5 x 2.3 cm steaks. The packaging films were fabricated into 10 x 5 cm pouches and filled with 50 mL deionized water. The meat and the pouches were exposed in a plexiglass enclosure, contained in a freezer, to 50, 100, 250, and 500 ppm ammonia gas (85 mL/min) for exposure times of 6, 12, 24, and 48 hr. The ammonia levels in the meat samples were 34.2 (50 ppm exposure), 51.5 (100 ppm exp.), 81.1 (250 ppm exp.), and 116 ppm (500 ppm exp.), and the pH values ranged from 5.56 to 5.75 (control ranged from 5.31 to 5.43) at 48 hr. At freezing temperatures, ammonia residues remained undetected, and no differences in pH were found in the pouches. At room temperature, all pouches were slightly permeable to ammonia; the levels observed in the pouches were, 7.77 ppm (pH, 8.64) for E-2300, 5.94 ppm (pH, 8.38) for LDPE, and 0.89 ppm (pH, 7.23) for V-PA/PE at 500 ppm exposure for 48 hr (unexposed samples pH ranged from 5.49 to 6.44). The results showed that meat packaging materials have low ammonia permeability and thus protect meat products exposed to ammonia exposure during frozen storage. Moreover, meat content is low even with ammonia exposures as high as 500 ppm for up to 48 hr.

Master of Science / Department of Biochemistry / Bruce D. Schultz / John M. Tomich / Peptides based on the second transmembrane segment of the glycine receptor (M2GlyR) were made to provide a potential therapeutic treatment for cystic fibrosis (CF) and a latent absorption enhancer for drug delivery. For similarity of presentation, unique synthetic peptide sequences have been given alpha-numeric designations. Results are presented from studies focusing on four peptides. In the first study, the contributions of synthetic peptides p1171, p1172 and p1173 to net transepithelial ion transport were measured as a first step toward the goal of testing whether pore length or electrostatics of pore lining residues will affect anion transport. Peptide p1130 exhibits many attributes that make it an ideal synthetic peptide for CF treatment, but has low permselectivity for anions. Therefore, it is used as a platform for modification. Peptide p1171 is doubly substituted with diaminopropionic acid at positions T13 and T17. Peptide p1172 and p1173 are separately one and two helical turn(s) inserted into the p1130 backbone. Apical exposure of MDCK monolayers to these peptides caused a rapid increase in short circuit current (Isc), an indicator of net ion transport. The increase in Isc caused by p1172 or p1173 was accompanied by increase in transepithelial electrical conductance (gte). The electrophysiological results suggested that these modified peptides can assemble in the apical membrane of epithelial cells to form functional ion-conducting pores. Peptide NC-1059, which provides for ion transport across epithelial cells derived from many sources, was studied further to assess cellular changes that account for increased gte. NC-1059 increased Isc, gte and enhanced permeation of dextrans in a concentration dependent manner. Results from previous and current studies show that NC-1059 modulated the epithelial paracellular pathway by altering the distribution and abundance of junctional proteins. Immunoblotting and immunolabeling with confocal microscopy showed that NC-1059 induces reorganization of actin and causes a reduction in F-actin abundance in epithelial cells. The distributions were changed and cellular abundances were reduced of tight junction proteins occludin and ZO-1 and adherens junction proteins E-cadherin and β-catenin by NC-1059. These effects were largely reversed in 24 hr and fully recovered in 48 hr. Therefore, NC-1059 has the therapeutic potential to increase the efficiency of drug delivery across barrier membranes.

Master of Science / Department of Architecture / David R. Seamon / This thesis presents a redesign of Kansas City’s downtown Government District, making use of the conceptual approach provided by Responsive Environments (1985), a manual for urban design written by architects Ian Bentley and Alan Alcock, urban designers Sue McGlynn and Graham Smith, and landscape architect Paul Murrain. “Responsive environments” are those urban places, the physical settings of which maximize usability and social value by offering a wide range of day-to-day user choices within close proximity. The authors of Responsive Environments identify seven hierarchical qualities—permeability, variety, legibility, robustness, visual appropriateness, richness, and personalization—that are said to be vital in creating responsive environments within the city. Through a literature review and critique, chapters 1 and 2 of the thesis overview Responsive Environments in terms of several major theorists of urban place making, including urban theorist Bill Hillier (1984), urban critic Jane Jacobs (1961), and urban designer William Whyte (1980). In turn, chapters 3, 4, 5, and 6 investigate the practicability of Responsive Environments as an urban design approach by applying its three larger-scale qualities of permeability, variety, and legibility to the Government District, an existing urban area in downtown Kansas City, Missouri, presently underdeveloped in terms of environmental responsiveness and a strong sense of urban place. As a means to identify strengths and weaknesses of Responsive Environments, the last chapter of the thesis critiques the resulting Government District design. The thesis concludes that Responsive Environments is a valuable design approach that offers much for strengthening the quality of urban life and urban sustainability.

Thesis (MSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Fluid flow through porous media plays an important role in a variety of contexts of which filtration is one. Filtration efficiency of fibrous filters depends on the micro-structural characterization of these porous materials and is reflected in the permeability there-of. Compression of fibrous porous media has a significant effect on the permeability. Experimental data indicate that the permeability varies generally with more than an order of magnitude over the narrow porosity range in which the compression takes place. Relative to the amount of experimental studies regarding this phenomenon, there is a scarcity of geometric models in the literature that can account for the effect of compression on the permeability of a fibrous porous medium. Within the context of existing geometric porescale models based on rectangular geometry, a new model is presented and an existing model improved to predict the effect of one-dimensional compression in the streamwise direction. In addition, without compromising on a commitment to mathematical simplicity, empirical data of a non-woven fibrous porous medium was used to highlight the effect of model geometry on its predictive capability. Different mathematical expressions for the relationship between compression and porosity were considered. The permeability is expressed explicitly in terms of the fibre diameter and the compression fraction and implicitly in terms of the porosity. The porosity is incorporated through the relationship between the linear dimensions of the geometric model. The general applicability of the model(s) was validated by making use of data on airflow through a soft fibrous porous material as well as through glass and nylon fibres. The permeability predictions fall within the same order of magnitude as the experimental data. Given the mathematical simplicity of the model(s), the prediction capability is satisfactory. Attention is drawn to assumptions made and model restrictions within the analytical modelling procedure. A general predictive equation is presented for the permeability prediction in which a solid distribution factor is introduced. The proposed models serve as basis for further adaptation and refinement towards prediction capability. / AFRIKAANSE OPSOMMING: Vloei van vloeistowwe deur poreuse media speel ’n belangrike rol in ’n verskeidenheid kontekste waarvan filtrasie een is. Die filtrasie doeltreffendheid van vesel filters hang af van die mikro-strukturele karakterisering van hierdie poreuse materiale en word gereflekteer in die permeabiliteit. Kompressie van veselagtige poreuse media het ’n beduidende effek op die permeabiliteit. Eksperimentele data dui aan dat die verandering in permeabiliteit gewoonlik oor meer as ’n orde grootte strek oor die klein porositeitsinterval waarin die kompressie plaasvind. Relatief tot die aantal eksperimentele studies rakende hierdie verskynsel, is daar ’n tekort aan geometriese modelle in die literatuur wat die effek van kompressie op die permeabiliteit van veselagtige poreuse media in ag kan neem. Binne die konteks van bestaande geometriese kanaal-skaal modelle gebasseer op reghoekige geometrie, is ’n nuwe model voorgestel en ’n bestaande model verbeter om die effek van een-dimensionele kompressie in die stroomsgewyse rigting te voorspel. Sonder om die verbintenis tot wiskundige eenvoud prys te gee, is empiriese data van ’n nie-geweefde veselagtige poreuse medium gebruik om die effek van die geometrie van ’n model op sy voorspellingsvermo¨e uit te lig. Verskillende wiskundige uitdrukkings is oorweeg vir die verband tussen kompressie en porositeit. Die permeabiliteit is eksplisiet uitgedruk in terme van die veseldiameter en die kompressie breukdeel en implisiet in terme van die porositeit. Die porositeit is ge-inkorporeer deur die verhouding tussen die lineêre dimensies van die geometriese model. Die algemene toepaslikheid van die model(le) is gestaaf deur gebruik te maak van data oor lugvloei deur ’n sagte veselagtige poreuse materiaal sowel as deur glas en nylon vesels. Die voorspellings van die permeabiliteit val binne dieselfde groote orde as die eksperimentele data. Gegee die wiskundige eenvoud van die model(le), is die voorspellingsvermoë bevredigend. Aandag is gevestig op aannames wat gemaak is en modelbeperkings binne die analitiese modellerings prosedure. ’n Algemene voorspellingsvergelyking is voorgestel vir die voorspelling van die permeabiliteit waarin ’n vaste stof distribusie faktor geinkorporeer is. Die voorgestelde modelle dien as basis vir verdere aanpassing en verfyning van voorspellingsvermoë.

Eye disorders are on the rise as a result of an ageing population, an increasing obesity problem and a growth in the number of diabetic patients. Conventional ophthalmic formulations do not maintain therapeutic drug concentration in the target tissues for a long duration due to the physiological and anatomical eye barriers. Novel delivery systems such as nanoparticles have been explored to enhance the delivery of therapeutic agents to the eye. These delivery systems have in general been assessed using in-vivo animal models, despite ethical concerns for animal wellbeing. The aims of this thesis were to synthesise and characterise four amphiphilic polymers, subsequently prepare and characterise four nano sized polymeric self-assemblies loaded with triamcinolone acetonide (TA), develop an in-vitro porcine eye model and to evaluate the permeation of nano sized self-assemblies using the developed model. Four comb-shaped amphiphilic polymers (Pa5, Pa5-MPEG, Ch5 and Da10) were synthesised with a high yield (>81%) and good reproducibility. These polymers formed spontaneous positive self-assemblies in aqueous media (114-314 nm). The mean hydrodynamic diameters of the positive spontaneous self-assemblies entrapping TA were in the range of 200–334 nm loading high concentrations (455-1263 μg mL-1) of TA, much greater than the TA inherent aqueous solubility or concentrations achieved using conventional solubilisers. A porcine in-vitro eye model was developed to assess drug permeation through anterior and posterior ocular tissues. The model was partially validated using tritiated water and a series of hydrophilic markers with increasing molecular weights. The integrity of porcine ocular tissue was checked by monitoring the permeation of tritiated water to ensure the membrane intactness. Tritiated water permeation at 15 min was exploited as a potential method to normalise drug flux, as tritiated water percentage permeation at 15 min had an inverse relationship with tissue thickness (R2 = 0.66), to reduce the inherent variability between tissue samples thus increasing the accuracy of the in-vitro eye model. Four markers (fluorescein sodium salt, 4, 10 and 20 kDa FITC-dextran) were used for the purpose of investigating the effect of increasing molecular weight on ocular tissue permeability. The permeability of the markers displayed an inverse relationship and abrupt decline with Mw in terms of the permeability through scleral and corneal tissues of human and porcine and the molecular weight of the markers. The developed porcine in-vitro eye model showed good correlation with the human in-vitro model providing strong evidence it can be used to screen potential formulations before testing in-vivo. The TA loaded self-assemblies and a few chemical enhancers (glutamic acid, tween 80, chitosan, Pa5 and elevate temperature (45 °C)), selected to assist drug delivery via two routes (paracellular and transcellular), were tested using the developed in-vitro eye model. The results showed there was no marker permeation enhancement effect in porcine and human ocular tissues using chemical enhancers. In summary, a porcine in-vitro eye model was developed to assess hydrophobic and hydrophilic penetrant permeation across anterior and posterior ocular tissues. The porcine in-vitro eye model showed good correlation with the human in-vitro model providing strong evidence that the porcine in-vitro eye model can be used to screen potential formulations before testing in-vivo using the porcine model which ultimately might correlate well with the in-vivo human responses. Although TA self-assemblies did not significantly increase drug flux through human or porcine scleral tissues, it might be of interest for ophthalmic topically administered formulations due to their positive charge and small nano size.

Gut regulatory peptides, such as neuropeptides and incretins, play important roles in hunger, satiety and gastrointestinal motility, and possibly mucosal permeability. Many peptides secreted by myenteric nerves that regulate motor control are also produced in mucosal epithelial cells. Derangements in motility and mucosal permeability occur in many diseases. Current knowledge is fragmentary regarding gut peptide actions and mechanisms in motility and permeability. This thesis aimed to 1) develop probes and methods for gut permeability testing, 2) elucidate the role of neuropeptide S (NPS) in motility and permeability, 3) characterize nitrergic muscle relaxation and 4) characterize mechanisms of glucagon-like peptide 1 (GLP-1) and the drug ROSE-010 (GLP-1 analog) in motility inhibition. A rapid fluorescent permeability test was developed using riboflavin as a transcellular transport probe and the bisboronic acid 4,4'oBBV coupled to the fluorophore HPTS as a sensor for lactulose, a paracellular permeability probe. This yielded a lactulose:riboflavin ratio test. NPS induced muscle relaxation and increased permeability through NO-dependent mechanisms. Organ bath studies revealed that NPS induced NO-dependent muscle relaxation that was tetrodotoxin (TTX) sensitive. In addition to the epithelium, NPS and its receptor NPSR1 localized at myenteric nerves. Circulating NPS was too low to activate NPSR1, indicating NPS uses local autocrine/paracrine mechanisms. Nitrergic signaling inhibition by nitric oxide synthase inhibitor L-NMMA elicited premature duodenojejunal phase III contractions in migrating motility complex (MMC) in humans. L-NMMA shortened MMC cycle length, suppressed phase I and shifted motility towards phase II. Pre-treatment with atropine extended phase II, while ondansetron had no effect. Intestinal contractions were stimulated by L-NMMA, but not TTX. NOS immunoreactivity was detected in the myenteric plexus but not smooth muscle. Food-intake increased motility of human antrum, duodenum and jejunum. GLP-1 and ROSE-010 relaxed bethanechol-induced contractions in muscle strips. Relaxation was blocked by GLP-1 receptor antagonist exendin(9-39) amide, L-NMMA, adenylate cyclase inhibitor 2´5´-dideoxyadenosine or TTX. GLP-1R and GLP-2R were expressed in myenteric neurons, but not muscle. In conclusion, rapid chemistries for permeability were developed while physiological mechanisms of NPS, nitrergic and GLP-1 and ROSE-010 signaling were revealed. In the case of NPS, a tight synchrony between motility and permeability was found.

Thesis (MScMedSc (Pharmacology))--University of Stellenbosch, 2005. / In this thesis, research results are reported on the role of natural and synthetic surfactants on the in vitro permeability characteristics of various chemical compounds across porcine (buccal, bronchial, arterial, venous and rectal) and human (vaginal) tissues. The permeability flux values of the different compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin, oxytocin, zidovudine and isoniazid) were determined using a continuous flow-through diffusion system. Mean steady state flux values were compared statistically by means of a t-test at a significance level of 5% as well as an F-test using whole curve comparisons. The results indicated that the synthetic pulmonary surfactant Biopolsurf is an effective enhancer for the permeation of chemical compounds through most of the tissues tested and that molecular weight, electrostatic charge, partitioning of the molecules in surfactant and surfactant concentration play an important role in trans membrane diffusion. In addition the epithelial permeability of the different types of tissues for various chemical compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin and oxytocin) across the above tissues were compared. The results obtained showed that the permeability flux values of the compounds across porcine bronchial and human vaginal tissues were consistently similar and that porcine buccal tissue had the lowest permeability of all tissues tested. This was in agreement with previous in vitro studies. It was concluded that a wide variation in the permeability characteristics of different epithelia exists and that the pulmonary epithelium, due to its high permeability, is probably the most effective epithelium for drug delivery purposes, especially for drugs that undergo extensive gastrointestinal or hepatic first-pass metabolism.

Thesis (PhD)--University of Stellenbosch, 2003. / ENGLISH ABSTRACT: This thesis is concerned with the measurement of the complex permeability of thin round wires at radio frequencies. This is of interest as such wires are used in various applications, such as absorbing chaff. Iron and nickel alloys are also used for their good tensile properties but have an undesired electromagnetic effect which needs to be characterised. Although little work has been done in this field in recent decades it remains a relevant problem. In this thesis the advantages of accurate wide-band measurements performed by automatic network analysers are applied to the field. The measurement system is a closed coaxial transmission line with a short circuit termination. The centre conductor is the wire of interest. The surface impedance of the wire is related to complex permeability and is measured using low-loss transmission line approximations applied to half-wavelength resonances. The loss associated with complex permeability is separated from conductivity by a D.C. conductivity measurement. A full wave analysis of the coaxial mode was performed and compared to measured values. The maximum error of the propagation constant was found to be 31% at the highest frequencies and was primarily due to length uncertainties. By varying parameters expected error bands around the measured permeability were found. These bands are of the order 1 and demonstrate that the system is sufficiently robust. The measurement of the permeability of two non-magnetic wires was performed and a relative permeability of 1 was found, demonstrating the correct working of the system. A steel wire was measured and compared to measurements found in literature. The permeability dropped as frequency rose as was expected, and an acceptable comparison to other measurements was made as there is no verification standard. Thus a simple measurement system that takes advantage of calibrated automatic network analyser measurements has been developed and demonstrated to work with sufficient accuracy. / AFRIKAANSE OPSOMMING: In hierdie tesis word die meting van die komplekse permeabiliteit van dun ronde drade by radio frekwensies ondersoek. Hierdie drade word in verskeie toepassings gebruik, waaronder dié van absorberende materiale. Nikkel- en ysterallooie word ook vir hul goeie breekkrageienskappe gebruik. In laasgenoemde gevalle moet die ongewenste elektromagnetiese effekte wat voorkom, gekarakteriseer word. Hoewel baie min werk in onlangse dekades gedoen is, bly die meting van die komplekse permeabiliteit 'n relevante probleem. In hierdie tesis word die voordele van akkurate wyeband metings, soos geneem deur 'n outomatiese netwerk analiseerder, toegepas in dié veld. Die meetopstelling is 'n geslote koaksiale transmissielyn, kortgesluit aan een end. Die middel geleier is die draad van belang. Die oppervlak impedansie van die draad is verwant aan die komplekse permeabiliteit, en word gemeet deur die gebruik van lae verlies transmissielyn benaderings, soos toegepas op halfgolf resonante frekwensies. Die verlies wat met die komplekse permeabiliteit geassosieer word, word van die geleidingsvermoë onderskei deur 'n G.S. meting van die geleidingsvermoë. 'n Volgolf analise van die koaksiale mode is uitgevoer en met gemete waardes vergelyk. 'n Maksimum fout van 31% by die hoogste frekwensie is in die voortplantingskonstante gevind. Hierdie volg primêr uit onsekerhede in lengte. Deur die parameters te varieer kon 'n verwagte foutband rondom die gemete permeabiliteit gevind word. Hierdie bande is van die orde 1 waaruit volg dat die stelsel 'n genoegsame robuustheid toon. Die komplekse permeabiliteit van twee nie-magnetiese drade is gemeet en 'n relatiewe permeabiliteit van 1 is gevind. Hierdie bevestig die korrekte werking van die stelsel. 'n Staal draad is opgemeet en met gepubliseerde meetresultate vergelyk. Soos verwag, verminder die permeabiliteit met 'n verhoging in frekwensie. Hoewel geen verifiëringstandaard beskikbaar is nie, is 'n aanvaarbare vergelyking met ander metings gemaak. Die produk van die navorsing is 'n metingstelsel wat, met behulp van 'n gekalibreerde outomatiese netwerk analiseerder, aanvaarbare akkuraatheid in die meting van die komplekse permeabiliteit van dun ronde drade by radio frekwensies kan verkry.