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Unbound granular materials are generally used in road pavements as base and subbase layers. The granular materials provide load distribution through aggregate contacts to a level that can help the subgrade to withstand the applied loads. Several research studies have shown that unbound pavement layers exhibit anisotropic properties. Anisotropy is caused by the preferred orientation of aggregates and compaction forces. The result is unbound pavement layers that have higher stiffness in the vertical direction than in the horizontal direction. This behavior is not accounted for in the design and analysis procedures included in the proposed AASHTO 2002 design guide. One of the objectives of this study is to conduct a comparative analysis of flexible pavement response using different models for unbound pavement layers: linear isotropic, nonlinear isotropic, linear anisotropic and nonlinear anisotropic. Pavement response is computed using a finite element program. The computations from nonlinear isotropic and anisotropic models of unbound layers are compared to the AASHO field experimental measurements. The second objective is to analyze the influence of using isotropic and anisotropic properties for the pavement layers on the performance of flexible pavements calculated using the AASHTO 2002 models. Finally, a comprehensive sensitivity analysis of the proposed AASHTO 2002 performance models to the properties of the unbound pavement layers is conducted. The sensitivity analysis includes different types of base materials, base layer thicknesses, hot mix asphalt type and thickness, environmental conditions, and subgrade materials.

Unbound granular materials are generally used in road pavements as base and subbase layers. The granular materials provide load distribution through aggregate contacts to a level that can help the subgrade to withstand the applied loads. Several research studies have shown that unbound pavement layers exhibit anisotropic properties. Anisotropy is caused by the preferred orientation of aggregates and compaction forces. The result is unbound pavement layers that have higher stiffness in the vertical direction than in the horizontal direction. This behavior is not accounted for in the design and analysis procedures included in the proposed AASHTO 2002 design guide. One of the objectives of this study is to conduct a comparative analysis of flexible pavement response using different models for unbound pavement layers: linear isotropic, nonlinear isotropic, linear anisotropic and nonlinear anisotropic. Pavement response is computed using a finite element program. The computations from nonlinear isotropic and anisotropic models of unbound layers are compared to the AASHO field experimental measurements. The second objective is to analyze the influence of using isotropic and anisotropic properties for the pavement layers on the performance of flexible pavements calculated using the AASHTO 2002 models. Finally, a comprehensive sensitivity analysis of the proposed AASHTO 2002 performance models to the properties of the unbound pavement layers is conducted. The sensitivity analysis includes different types of base materials, base layer thicknesses, hot mix asphalt type and thickness, environmental conditions, and subgrade materials.

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: This research study investigates the influence of specimen geometry and grading curve, on the performance of a typical South African unbound granular material. The experimental design incorporates three grading curves to evaluate the influence of grading. In addition, to evaluate the influence of specimen geometry, two specimen sizes were included into the experimental design. Laboratory testing consisted of monotonic tri-axial tests to evaluate the shear performance (Cohesion and Friction Angle) and more complex short duration dynamic tri-axial tests to evaluate the load spreading ability/stiffness (Resilient Modulus) of the selected materials. In order to achieve the objectives of this study, a large tri-axial apparatus was needed that could accommodate specimens as large as 300mm ϕ * 600mm high. This would allow a full grading of large aggregate (up to 50mm particle size) to be accurately evaluated. Further development and commissioning of such a large triaxial apparatus therefore formed part of this study. The representative parent material selected for testing consisted of a G2 graded crushed Hornfels stone. The material was dried and sieved into fractions where after it was carefully reconstituted to allow for accurate control of specimen grading during specimen preparation. The three grading curves consisted of two adjusted grading curves (referred to as S19 and G19C), adjusted from the full G2 grading, and the full G2 grading itself (referred to as the Full grading curve). Material property tests, Sieve Analysis, Bulk Relative Density (BRD) and Optimum Moisture Content (OMC) tests were performed to gain an understanding of the material characteristics. Moisture-Density relationship curves were developed to identify a common Moisture Content that, for all three grading curves, would yield a common Dry Density. A Moisture Content of 4.7% was identified that would yield a Dry Density of 2340 kg/m3 for all three grading curves. This density could be achieved for both sizes of specimen preparation apparatuses without damaging material particles. Specimens were compacted using the representative vibratory hammer compaction method, sealed and left for 24 hours to allow redistribution of moisture and initial development of Cohesion. The shear parameters (Cohesion and Friction Angle) were investigated through monotonic tri-axial testing. It was found that Cohesion and Friction Angle are influenced by both grading curve and specimen geometry. Cohesion was found to reduce as the coarseness of the material grading increased (i.e. finer S19 grading yielded higher Cohesion than its coarser G19C counterpart) and the Friction Angle was found to increase with increase coarseness (i.e. finer S19 grading yielded lower Friction Angles when compared to the G19C grading). The influence of specimen geometry was also investigated. It was observed than Cohesion decreased with an increase in specimen size. Friction Angle on the other hand was found to increase with increased specimen size. From dynamic tri-axial test results, it was observed that the Resilient Modulus is influenced by both specimen geometry and grading curve. The influence of specimen geometry however is complex and no constant trend throughout the grading curves tested could be identified. Grading curve however was found to increase the Resilient Modulus for coarser gradings (i.e. coarser G19C vs finer S19). Increased large particle-to-particle contact area yields higher friction within the material specimen, resulting in lower strains induced by higher stresses, i.e. higher Resilient Modulus. It was shown, for both monotonic and dynamic tri-axial tests, that the coarser G19C grading curve yields more representative results to that of the Full grading curve when compared to the finer S19 grading. This was observed for shear and resilient performance properties. Additionally, a simple design case study yields similar trends. In conclusion, material characterisation plays an important role in the design of unbound granular materials (UGM’s). Current laboratory characterisation techniques however used adjusted gradings to limit the effects stemming from the ratio between specimen diameter and maximum particle size. This research has shown that some of the current practices do not best represent the true in-situ grading. It has been shown that both grading curve and specimen geometry influence the performance of UGM’s which, in turn, influences the design of a pavement structure. Therefore, accurate modelling of the true in-situ grading, through testing apparatuses capable of accommodating in-situ gradings, is required. / AFRIKAANSE OPSOMMING: Hierdie navorsingsstudie evalueer die invloed van proefstukgeometrie en gradering, op die gedragseienskappe van ‘n tipiese Suid Afrikaanse ongebinde granulêre aggregaat. Om die invloed van gradering te evalueer, is ‘n eksperimentele ontwerp ontwikkel wat drie materiaal graderings insluit. Verder, om die invloed van proefstukgeometrie te evalueer, is twee proefstukgroottes toegevoeg tot die eksperimentele ontwerp. Monotoniese drie-assige toetse is uitgevoer om die skuifsterkte (Kohesie en Wrywingshoek) van die materiaal te ondersoek. Addisioneel is die styfheid (Veerkragmodulus) van die materiaal ondersoek deur dinamiese drieassige toetse. Om die doelwitte van hierdie studie te bereik was ‘n groot skaalse die-assige toets apparaat benodig wat groot, 300mm ϕ * 600mm hoogte, proefstukke kan akkommodeer. So ‘n apparaat laat toe dat die volle gradering van aggregaat (tot en met 50mm korrels) akkuraat geëvalueer kan word. Daarom vorm die ontwikkeling en opstelling van so ‘n apparaat deel van hierdie studie. Die tipiese Hornfels gebreekte klip, met ‘n G2 gradering, wat ondersoek is, was gedroog en in verskeie fraksies gesif om die akkuraatheid van proefstuk voorbereiding te beheer. Die drie graderings bestaan uit twee aangepaste graderings (S19 en G19C gradering skale), aangepas vanaf die volle G2 gradering, en die vol G2 gradering homself (verwys na as die “Full” gradering skaal). Materiaal gedragstoetse, Sif Analises, Nat Gekompakteerde Relatiewe Digtheid (BRD) en Optimum Vog Inhoud (OVI) toetse, was uitgevoer om die materiaal eienskappe te ondersoek. Om ‘n gemeenskaplike Vog Inhoud en Droë Digtheid, wat vir al drie graderings geld, te vind, is Vog-Digtheid verhoudingskurwes ontwikkel. Vanaf die kurwes is identifiseer dat ‘n Vog Inhoud van 4.7% ‘n Droë Digtheid van 2340 kg/m3 vir al drie graderings sal lewer. Vibrasie kompaksie is toegepas om albei skale van proefstukke te kompakteer waarna die proefstukke vir 24 uur geseel is om vogverspreiding en ontwikkeling van Kohesie toe te laat. Monotoniese drie-assige toetse is uitgevoer om die skuifsterkte parameters (Kohesie en Wrywingshoek) te ondersoek. Die resultate het gewys dat beide gradering en proefstukgeometrie die Kohesie en Wrywinshoek beinvloed. gradering lewer hoër Kohesie waardes i.v.m. die growwer G19C gradering). Die Wrywingshoek is gevind om te verhoog soos die grofheid van die gradering verhoog (m.a.w. die fyner S19 gradering het laer Wrywingshoeke gelewer i.v.m. die growwer G19C gradering). Resultate het verder gewys dat groter proefstukke laer Kohesie en hoër Wrywingshoeke lewer. Daar kan wel gedebateer word dat variasie in materiaal die verandering van die skuifsterkte parameters gee, maar die proefstukvariasie is beperk om sodoende die invloed daarvan onopmerkbaar te maak.. Verder is die verlaging in Kohesie en verhoging in Wrywingshoek, a.g.v. ‘n vergroting in proefstuk grootte, vir albei aangepaste graderings geobserveer. Dit is ‘n moontlike aanduiding dat die verandering nie materiaal afhanklik is nie maar eerder beinvloed word deur die grens toestande tydens kompaksie. Dinamiese drie-assige toets resultate het gewys dat die Veerkragmodulus beinvloed word deur beide proefstuk geometrie en gradering. Daar is gevind dat die invloed van proefstukgeometrie kompleks is, en geen konstante verhouding, wat vir alle toets graderings geld, kon identifiseer word nie. Vir die invloed van gradering is daar gewys dat die Veerkragmodulus hoër is vir die growwer gradering (m.a.w. G19C gradering lewer hoër styfheid as S19 gradering). ‘n Verhoging in korrel-tot-korrel kontak area lewer hoër interne wrywing in die proefstuk wat bydrae tot laer vervorming by hoër spannings, m.a.w. hoër Veerkragmodulus. Baie interessant, vir beide monotoniese en dinamiese drie-assige toetse is gevind dat die growwer G19C gradering, i.v.m. die fyner S19 gradering, die ware G2 (Full) gradering beter verteenwoordig. Hierdie observasie is geldig vir beide die skuifsterkte parameters en weerstands eienskappe. Aggregaat karakterisering is ‘n belangrike deel in die ontwerp van ‘n ongebinde granulêre materiaal laag. Huidige karakterisering metodes gebruik aangepaste graderings sodat resultate nie beinvloed word deur die verhouding tussen proefstuk diameter en maksimum klipgrootte nie. Hierdie ondersoek het gevind dat van die huidige aanpassings nie die ware gradering verteenwoordig nie. Die resultate wys dat beide gradering en proefstuk geometrie die gedrag van die ongebinde granulêre materiaal beinvloed, so ook die ontwerp van ‘n padstruktuur. Daar is dus ‘n behoefte om die ware gradering te ondersoek wat slegs moontlik is met groot skaalse toets apparaat, wat groot klip korrels kan toets. Verder, indien daar ‘n verstandhouding tussen huidige (klein skaalse) toets apparaat en groot skaalse apparaat ontwikkel kan word, kan resultate aangepas word, vanaf die klein skaalse resultate, om die ware materiaal gedrag meer te verteenwoordig.

On the heels of an older generation of Romantic poets concerned with the individual’s role in creating reality, Percy Shelley defines perception as a mandatory building block for countering an external physical world that is hostile to the individual. Consequently, the question of perception, both how it is defined and how it can be influenced, plays an important role in Shelley’s works that focus on political and social change. The question of perception, as it relates to the individual and as it relates to social change, is brought to the forefront in Prometheus Unbound and his drama, The Cenci.

On the premise that examination of a poet's language can provide a valid and significant approach to the study of a work of art, this thesis proposes to make such a study of Prometheus Unbound, the major poetical work of Percy Bysshe Shelley, with specific attention to his use of color language.

Work done by several researchers reveals that unbound aggregate materials show nonlinear cross-anisotropic behavior. The incorporation of cross-anisotropic properties significantly improves the predictions of stress distribution by reducing tensile stresses computed within granular layers. Existing pavement analysis and design approaches, however, generally assume the pavement structure to be linear isotropic layered system. This assumption is motivated by the difficulties in determining cross-anisotropic resilient material properties from laboratory experiments and lack of pavement anisotropic analysis programs. Recently, the International Center for Aggregates Research (ICAR) developed a methodology to characterize unbound aggregate layers by considering stress-sensitivity and nonlinear cross-anisotropy. The ICAR model requires nine coefficients to account for stress-sensitivity and anisotropy of vertical, horizontal, and shear moduli. Unfortunately, ICAR testing protocol is time-consuming and expensive to perform and certainly do not lend themselves to routine testing. Since it is important to be able to consider the stress-sensitive and anisotropic nature of unbound granular materials, a simple procedure was proposed by accounting for the effects of aggregate gradation and shape properties in predicting the cross-anisotropic modular ratio of unbound granular materials. Variable confining pressure type repeated load triaxial tests were performed on six aggregate sources with three different gradations and three different moisture contents. The experimental results were analyzed within the framework of nonlinear cross-anisotropic elastic model in order to determine the model coefficients. Image analysis techniques were utilized to measure aggregate shape properties. The gradation and shape properties were fitted using a cumulative distribution function and nonlinear regression analysis, which is capable of capturing the complete distribution of these properties. The experimental and analytical results indicate that the vertical resilient modulus is greater than the horizontal resilient modulus and that aggregate physical properties significantly affect the anisotropic resilient behavior. Based on finite element analysis, the anisotropic resilient behavior has substantial effect on the critical pavement responses. Thus, it is extremely valuable to approximate the degree of cross-anisotropy in unbound aggregates and to use it as input in the pavement analysis programs to adequately model unbound aggregate bases for pavement design and analysis.

Unbound granular material is used in the pavement structure and usually comprises the bulk of the structural and foundation layers of a typical South African pavement. The term ‘unbound granular material’ refers to the classification of natural material, which has not been modified in any way. Various mechanistic-empirical models for the resilient response of unbound granular material have been developed over the years. However, few have incorporated important influencing parameters such as moisture or density on the basic stress-strain relationship or linked variables of the models to basic engineering properties of unbound granular material. This study builds on previous work by Theyse (2008a) and the cord modulus model developed by Theyse (2012). The Theyse (2012) model was selected to be further investigated, since it modelled the trends observed in the data realistically. The model depicts the stress dependent behaviour of unbound granular material, where an increase initial modulus is observed for increasing confinement pressure, as well as initial stress-softening with increasing stress ratio followed by stress stiffening. The model was calibrated for all bulk material samples under consideration in this thesis. The calibration process included linking variables of the model to mathematical functions that approximate the trends observed when variables were considered against level of saturation. A parametric analysis indicated that the saturation and stress-dependent cord modulus model realistically predict material behaviour. The saturation and stress-dependent cord modulus model was refined further and calibrated for crushed and natural unbound granular material. This refinement did not negatively influence the accuracy or ability to realistically predict the material behaviour. Basic material properties could be linked to predictive statistical distributions that could estimate the range of modulus values that can be expected for the material under consideration. However, the variables of the saturation and stress-dependent cord modulus model could not be linked to basic material properties due to the limit set of results available. / Thesis (PhD)--University of Pretoria, 2013. / gm2013 / Civil Engineering / unrestricted

The permeation of drugs across the blood-brain barrier (BBB) is a prerequisite for central nervous system (CNS) drug penetration. The BBB, possessing efflux transporters and tight junctions, limits drug penetration to the brain. Consequently, the discovery of novel drugs to treat CNS diseases remains problematic and is lagging behind other therapeutic areas. In vitro assays have progressed understanding of the factors that govern brain penetration. Central nervous system drug penetration is now thought to be modulated by three main processes, namely BBB permeability, active transport at the BBB and drug binding in blood and brain tissue. A more integrated approach to CNS drug discovery programmes is emerging which encompasses these processes in order to examine the rate and extent of drug brain penetration across species and improve predictions in human.A primary porcine in vitro BBB model was developed and characterised for the prediction of CNS drug permeability in vivo. Characterisation confirmed that the model exhibited physiologically realistic cell architecture, the formation of tight junction protein complexes, transcellular electrical resistance consistently >2000 Ω.cm2, functional expression the P-gp efflux transporter and ?-glutamyl transpeptidase and alkaline phosphatase activities.Transport of 12 centrally acting test drugs was investigated across four in vitro BBB models in order make comparisons between models and to generate in vitro permeability and efflux measurements. Blood-brain barrier permeability and active efflux processes are two major influences on the rate of drug penetration across the BBB. Species differences in fublood and fubrain, two prime influences on the extent of drug penetration, were investigated using equilibrium dialysis. Fraction unbound in brain was shown to be comparable across species suggesting that species differences in brain penetration could be due to variation in fublood for drugs that cross the BBB by passive diffusion, and/or species differences in transporter characteristics for drugs that are subject to active transport processes at the BBB. An in-house hybrid-PBPK rat CNS model was used to predict calculated rat Kp,uu using in vitro permeability, efflux, fublood and fubrain parameters generated during this work. The predicted Kp,uu generated using the rat CNS hybrid-PBPK model were within 3-fold of calculated Kp,uu. The rat CNS hybrid-PBPK model has potential use, as a tool for drug discovery scientists to aid the prediction of the extent of drug penetration in the early stages of drug discovery.This work has demonstrated that in vitro permeability and unbound drug fraction can be used to predict CNS drug penetration.

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