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Transmissible spongiform encephalopathy (TSE) strains are defined by their biological properties on transmission to wild-type mice, specifically by their characteristic incubation periods and patterns of vacuolar pathology (‘lesion profiles’) in the brain. Whilst a single TSE strain has been identified in variant Creutzfeldt-Jakob disease (vCJD), the phenotypic heterogeneity observed in sporadic CJD (sCJD) implies the existence of multiple strains of agent. These distinct strains are proposed to be enciphered by the different conformers of abnormal prion protein (PrP), recognised as different protease resistant PrP (PrPres) types by Western blotting (type 1 or type 2) and are thought to be substantially influenced by the different prion protein gene (PRNP) codon 129 polymorphism (MM, MV and VV). To test the relationship between disease phenotype and agent strain, this study carried out a full characterisation of the sCJD agent by primary transmission of brain tissue from 27 sCJD cases (comprising all six possible combinations of PRNP codon 129 genotype and PrPres type) in panels of wild-type mice using the standard strain typing properties of incubation period and lesion profiles, plus a full analysis of PrP in the mouse brain and the PrPres molecular subtypes present. Results were directly compared with the transmission characteristics of brain tissue from 10 vCJD cases. The characterisation of the agent strain in sCJD and vCJD was extended to include analysis of subsequent mouse-to-mouse passages. In an additional investigation, wild-type mice were experimentally challenged with a wide-range of lymphoid tissues, neural tissues and biological fluids from vCJD and sCJD patients in order to investigate the extent of peripheral involvement in CJD and to determine whether the agent is subject to any tissue-specific modifications. Analysis of all 27 sCJD sources demonstrated the existence of two strains of agent, one associated with the MM1/MV1 subgroups and the other associated with the MM2 subgroup, which could be distinguished by their transmission properties in the mice. The lack of transmission in mice challenged with VV1, MV2 and VV2 tissues provided evidence of at least one further sCJD strain. In contrast, all 10 vCJD sources resulted in consistent incubation periods and lesion profiles, suggesting that all 10 patients investigated were infected with the same strain of agent. Overall, the observation that PrPres type in sCJD and vCJD was maintained on transmission is consistent with the proposition that PrPres type plays a role in enciphering strain-specific information. Experimental transmissions from peripheral tissues extended the evidence for a peripheral infection in vCJD. However, comparison of incubation periods and lesion profiles from transmission of brain and peripheral tissues showed no evidence of tissue-specific modification in the biological properties of the agent. Furthermore, the detection of low levels of infectivity in a sCJD buffy coat sample provides supporting evidence for a peripheral involvement in sCJD. This study highlights the complex relationship between disease phenotype, PRNP codon 129 genotype, PrPres type and agent strain in sCJD and vCJD. Overall, this study confirms that multiple strains of agent are associated with sCJD, some of which successfully propagate in wild-type mice but none of which are identical to the agent responsible for vCJD. Importantly, the sCJD strains identified here by their biological properties partially correlated with the current sub-classification system for sCJD which is based on the clinical and pathological phenotype of the disease.

Detailed, accurate measurements of critical current density and resistivity to determine the upper critical field have been made on a technological NbsAl conductor in magnetic fields up to 15 T, temperatures from 4.2 K up to the critical temperature and in the strain range from -1.8% to 0.7%. The uncertainty in temperature above 4.2 K was equivalent to ± 100 mK with a stability during the measurements of < 5 mK up to a limiting current of 80 A and a typical noise level of 1 µ Vm(^-1).When B(_c2){T,ε) is defined at 5%pn, 50%pn or 95%/%pn, an empirical relation is found where and an approximate relation, holds. The Jε data were parameterised using F(_p) = J(_E)B = A(ε)[Bc(_2)](^n)b(^p)(1-b)(^9) where b = B/B(_c2)(T,ε). When B(_c2)(T,ε) is constrained to be the value at 50%pn or 95%pn, the scaling law for F(_p) breaks down such that p and q are strong functions of temperature and q is also a strong function of strain. However, when B(_c2)(T,ε) is defined at 5%pn, there is good scaling where p and q are constants independent of temperature and strain. F(_p) can also be approximated by a Kramer form where the Ginzburg-Landau constant is γ is the electronic density of states and is interpreted as the average B(_c2) for the bulk where percolative current flow occurs. The critical current density of Hot Isostatic Pressed (HIP'ed) and unHIP'ed Nb(_3)Sn Modified Jelly Roll wires has also been measured at 4.2 K. The critical current and upper critical field were decreased for the HIP'ed sample. The reduced upper critical field of the HIP'ed wire was found to be less sensitive to strain than the unHIP'ed wire. The exponent of B(_c2) in the flux pinning scaling law increased from 0.86 to 2.14 as a result of the HIP processing.

Lateral Surface Superlattices were fabricated by etching in strained InGaAs layers above a GaAs/AlGaAs 2DEG channel. These were etched both by dry plasma wet chemical etching to produce periods of l00nm, 200nm and 300nm. These superlattices were fabricated on Hall bars to allow four terminal measurement and a blanket gate was placed on top, to allow variations in the carrier concentration. The magnetoresistance effects of these superlattices were studied at varying values of gate voltage, which varies the carrier concentration and the electrostatic periodic potential and at temperatures down to 45mK in a dilution refrigerator. From the oscillations observed in the magnetoresistance traces it is possible to calculate the magnitude of the periodic potential. This showed that the etched, strained InGaAs was producing an anisotropic piezoelectric potential, along with an isotropic electrostatic potential. The variation in period allowed a study of the change of this piezoelectric potential with the period as well as a study of the interactions between the electrostatic and piezoelectric potentials. Further, at the lowest temperatures a strong interaction was observed between the Commensurability Oscillations, caused by the periodic potential, and the Shubnikov-de Haas Oscillations due to the Landau Levels. This interaction was studied as it varied with temperature and carrier concentration.

The reliability of semiconductor devices depends upon the stability of the constituent materials. Strained-layer semiconductor structures contain a layer whose lattice constant differs from the surrounding layers, resulting in a misfit strain. As dislocations are the main failure mechanism in semiconductor lasers, it is essential to establish whether the stability of these structures is affected by the lattice mismatch and the possibility of relaxation by the formation of misfit dislocations. In this thesis, dislocations in strained-layer semiconductor structures are investigated. Relaxation of strained-layer GaAs/InxGa1-xAs/GaAs heterostructures through the formation of misfit dislocations is found to occur in stages. Firstly, generation and elongation of misfit dislocations on threading dislocations during molecular beam epitaxy (MBE) growth have been demonstrated with increasing strained-layer thickness. The onset of this stage has been shown to occur at strained-layer thicknesses below those predicted by the Matthews-Blakeslee (M-B) model. The second stage of relaxation is marked by the formation of a network of 60° misfit dislocations. A third stage of relaxation has been discovered, in which pure edge (i.e. 90°) misfit dislocations are formed in addition to the existing network of 60° misfit dislocations. Different mechanisms are found to be responsible for the three stages of relaxation. The M-B model describes the transformation of threading dislocations to generate 60° misfit dislocations. As this affects individual dislocations, it results in only local relaxation. A separate mechanism, which remains unclear but is not dependent on the interactions of dislocations, dominates the formation of a 60° misfit dislocation network. The edge dislocations responsible for further relaxation of the structures are produced by vacancy-producing jogs. These protrude from pre-existing 60° dislocations and trail edge dislocation pairs as they climb. It is shown here that as-grown structures with strained-layer thicknesses below the theoretical prediction can be relaxed by the formation of a 60° dislocation network during post-growth thermal processing and bending. Thus the first two stages of relaxation are dependent on both the strained-layer thickness during fabrication, and on the temperature and applied stress of as-grown structures. Finally, dislocation motion in strained layer structures has been shown to be slower than that in unstrained structures. Thus the misfit stress acts as an additional resistant force to the displacement of atoms in non-misfit dislocations, even though it drives the formation of misfit dislocations.

Abstract: Pipelines form an integral component of the distribution network of oil and gas products, which have to be transported from production sites to markets far off where there is need for them. Pipelines thus have to traverse long distances and as any other structure are susceptible to damages with use. A common cause of damage is the mechanical damage in pipeline in the form of dents, which are caused by a host of factors ranging from, but not limited to construction errors, ground movement and third-party interactions. While some dents in a pipeline might be dormant features, some have the potential to affect the structural integrity of the pipeline thus resulting in the immediate or delayed failure of the pipeline. It becomes necessary that some measure be put in place for accessing the severity of dents in order to prioritize allocation of the resources in the implementation of management strategies. The codified stipulation of the Canadian pipeline code, CSA Z662-16, proposes the depth based criterion as a measure of the severity of dents in pipelines. History and research have however shown that this approach fails to accommodate other factors such as the localized strain and stress distribution because of the geometry of the dent, as a dent might fall below the codified deformation limits while violating the localized plastic strain or stress limits. As an alternative to the traditional depth based approach, the American Society of Mechanical Engineers Standard for gas pipelines, ASME B31.8-16, presents a set of non-mandatory closed form expressions for evaluating the strains in pipelines in a bid to generate the strain state of the dented region based on the dent profile. This technique has, however, been criticized for inaccuracies in its assumptions. Well aware of the pitfalls of existing analytical evaluation techniques for the strains in dented pipeline, some pipeline operators subscribe to the numerical modeling via Finite Element Analysis (FEA) of dents as assessment technique, a procedure regarded to be computationally demanding and resource intensive. The work presented herein is a novel technique for evaluating the strains in dented pipelines based solely on data obtained from inline inspection devices. This study discusses two ideas. The first proposes a new technique for the strain analysis of thin walled structures through a combination of B-Spline interpolation and deformation discretization. This technique allows for the evaluation of all the components of the strain tensor that defines the strain state of the dented pipeline. The second novel approach is extending the proposed technique and the existing ASME B31.8-16 equations into a three-dimensional continuum, thus allowing for a more elaborate analysis without loss in the generality of the procedure.

Abstract: Chronic wasting disease (CWD) is a contagious prion disease spreading and emerging in wild and captive Cervidae species worldwide. Prion diseases are fatal neurodegenerative disorders occurring in various mammalian species including deer, elk, sheep, cattle and humans. Central to prion pathogenesis is the PRNP gene, which encodes the cellular prion protein (PrPC), a membrane glycoprotein that is primarily expressed in the brain. The pathogenesis of prion diseases involves the misfolding of PrPC into self-replicating, strain-encoding PrPSc (PrPCWD for cervid infections) conformers termed “prions”. Single PrPC amino acid polymorphisms can influence aspects of the disease, including susceptibility, clinical presentation and pathological phenotypes. In cervids, transmission of CWD occurs within and between species expressing PRNP allelic variants. A potential consequence of prion transmission between hosts with different PrPC primary structures is the emergence of CWD strains with novel transmission properties. These studies characterize the biological effects of CWD propagation in deer expressing different PrPC molecules: I) PrPC amino acid polymorphisms H95 and S96 subjected CWD prions to selective propagation barriers that modified the spectra of PrPCWD conformers. II) Transmission of PrPCWD conformational variants resulted in the emergence of a novel CWD strain that was selected in concert with the host recipient PrPC. III) CWD transmission between deer expressing different PrPC primary structures expanded the host range of CWD. These results suggest that circulating CWD strains would diversify as transmission between different cervid PRNP genotypes occurs. Understanding the effects of PrPC polymorphisms on the properties of CWD strains could help identify key events in their replication and spread.