Dispersion of classic beta-amyloid deposits around blood vessels in Alzheimer’s disease

The spatial pattern of the classic (‘cored’) type of beta-amyloid (Abeta) deposit was studied in the upper laminae of the superior temporal gyrus in 9 cases of sporadic Alzheimer’s disease (SAD). Abeta stained tissue was counterstained with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a spatial correlation between the clusters of the classic deposits and the larger diameter (>10 micron) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (<10 micron) capillaries. In 9/11 cases, the clusters of the classic deposits were significantly larger than those of the clusters of the larger blood vessels. In addition, the density of the classic deposits declined as a negative exponential function with distance from the vertically penetrating arterioles. These results suggest that the classic Abeta deposits cluster around the larger blood vessels in the frontal cortex and that diffusion of proteins from these blood vessels could be involved in the pathogenesis of the classic deposits in SAD.

Dispersion of prion protein deposits around blood vessels in variant Creutzfeldt-Jakob disease

In variant Creutzfeldt-Jakob disease (vCJD), a disease linked to bovine spongiform encephalopathy (BSE), florid-type prion protein (PrP(sc)) deposits are aggregated around the larger diameter (> 10 µm) cerebral microvessels. Clustering of PrP(sc) deposits around blood vessels may result from blood-borne prions or be a consequence of the cerebral vasculature influencing the development of the florid deposits. To clarify the factors involved, the dispersion of the florid PrP(sc) deposits was studied around the larger diameter microvessels in the neocortex, hippocampus, and cerebellum of ten cases of vCJD. In the majority of brain regions, florid deposits were clustered around the larger diameter vessels with a mean cluster size of between 50 µm and 628 µm. With the exception of the molecular layer of the dentate gyrus, the density of the florid deposits declined as a negative exponential function of distance from a blood vessel profile suggesting that diffusion of molecules from blood vessels is a factor in the formation of the florid deposits. Diffusion of PrP(sc) directly into the brain via the microvasculature has been demonstrated in vCJD in a small number of cases. However, the distribution of the prion deposits in vCJD is more likely to reflect molecular 'chaperones' diffusing from vessels and promoting the aggregation of pre-existing PrP(sc) in the vicinity of the vessels to form florid deposits.

Systems biology approach to study permeability of paracetamol and its solid dispersion

Physiological changes that take place at cellular level are usually reflective of their level of gene expression. Different formulation excipients have an impact on physiological behavior of the exposed cells and in turn affect transporter genes, enterocyte-mediated metabolism and toxicity biomarkers. The aim of this study was to prepare solid dispersion of paracetamol and evaluate genetic changes that occur in Caco-2 cell lines during the permeability of paracetamol alone and paracetamol solid dispersion formulations. Paracetamol-PEG 8000 solid dispersion was prepared by melt fusion method and the formulation was characterised using differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Formulation of solid dispersion resulted in the conversion of crystalline drug into an amorphous form. Permeability studies showed that paracetamol absorption was higher from the solid dispersion formulation. DNA microarrays analysis was carried out in order to investigate the involvement of any efflux/uptake transporters in paracetamol or its solid dispersion permeability. Neither transporter carriers nor efflux proteins were found to be involved in the absorption of paracetamol or its PEG solid dispersion. Gene expression analysis established that paracetamol toxicity was potentially reduced upon formulation into solid dispersion when ATP binding cassette (ABC) and solute carrier transporter (SLC) genes were analyzed.

Numerically optimized implementations, mitigation and simulations of polarisation mode dispersion in real-time transmission systems

The aim of this thesis is to present numerical investigations of the polarisation mode dispersion (PMD) effect. Outstanding issues on the side of the numerical implementations of PMD are resolved and the proposed methods are further optimized for computational efficiency and physical accuracy. Methods for the mitigation of the PMD effect are taken into account and simulations of transmission system with added PMD are presented. The basic outline of the work focusing on PMD can be divided as follows. At first the widely-used coarse-step method for simulating the PMD phenomenon as well as a method derived from the Manakov-PMD equation are implemented and investigated separately through the distribution of a state of polarisation on the Poincaré sphere, and the evolution of the dispersion of a signal. Next these two methods are statistically examined and compared to well-known analytical models of the probability distribution function (PDF) and the autocorrelation function (ACF) of the PMD phenomenon. Important optimisations are achieved, for each of the aforementioned implementations in the computational level. In addition the ACF of the coarse-step method is considered separately, based on the result which indicates that the numerically produced ACF, exaggerates the value of the correlation between different frequencies. Moreover the mitigation of the PMD phenomenon is considered, in the form of numerically implementing Low-PMD spun fibres. Finally, all the above are combined in simulations that demonstrate the impact of the PMD on the quality factor (Q=factor) of different transmission systems. For this a numerical solver based on the coupled nonlinear Schrödinger equation is created which is otherwise tested against the most important transmission impairments in the early chapters of this thesis.

Surface wave techniques for the study of engineering structures and materials

A wire drive pulse echo method of measuring the spectrum of solid bodies described. Using an 's' plane representation, a general analysis of the transient response of such solids has been carried out. This was used for the study of the stepped amplitude transient of high order modes of disks and for the case where there are two adjacent resonant frequencies. The techniques developed have been applied to the measurenent of the elasticities of refractory materials at high temperatures. In the experimental study of the high order in-plane resonances of thin disks it was found that the energy travelled at the edge of the disk and this initiated the work on one dimensional Rayleigh waves.Their properties were established for the straight edge condition by following an analysis similar to that of the two dimensional case. Experiments were then carried out on the velocity dispersion of various circuits including the disk and a hole in a large plate - the negative curvature condition.Theoretical analysis established the phase and group velocities for these cases and experimental tests on aluminium and glass gave good agreement with theory. At high frequencies all velocities approach that of the one dimensional Rayleigh waves. When applied to crack detection it was observed that a signal burst travelling round a disk showed an anomalous amplitude effect. In certain cases the signal which travelled the greater distance had the greater amplitude.An experiment was designed to investigate the phenanenon and it was established that the energy travelled in two nodes with different velocities.It was found by analysis that as well as the Rayleigh surface wave on the edge, a seoond node travelling at about the shear velocity was excited and the calculated results gave reasonable agreement with the experiments.

Genomic evaluation during permeability of indomethacin and its solid dispersion

Drug resistance was first identified in cancer cells that express proteins known as multidrug resistance proteins that extrude the therapeutic agents out of the cells resulting in alteration of pharmacokinetics, tissue distribution, and pharmacodynamics of drugs. To this end studies were carried out to investigate the role of pharmacological inhibitors and pharmaceutical excipients with a primary focus on P-glycoprotein (P-gp). The aim of this study was to investigate holistic changes in transporter gene expression during permeability upon formulation of indomethacin as solid dispersion. Initial characterization studies of solid dispersion of indomethacin showed that the drug was dispersed within the carrier in amorphous form. Analysis of permeability data across Caco-2 monolayers revealed that drug absorption increased by 4-fold when reformulated as solid dispersion. The last phase of the work involved investigation of gene expression changes of transporter genes during permeability. The results showed that there were significant differences in the expression of both ATP-binding cassette (ABC) transporter genes as well as solute carrier transporter (SLC) genes suggesting that the inclusion of polyethylene glycol as well as changes in molecular form of drug from crystalline to amorphous have a significant bearing on the expression of transporter network genes resulting in differences in drug permeability. © 2011 Informa UK, Ltd.

Constructing an 'efficient frontier' of accounting journal quality

This paper reports the construction of an 'efficient frontier' of the perceived quality attributes of academic accounting journals. The analysis is based on perception data from two web-based surveys of Australasian and British academics. The research reported here contributes to the existing literature by augmenting the commonly supported single dimension of quality with an additional measure indicating the variation of perceptions of journal quality. The result of combining these factors is depicted diagrammatically in a manner that reflects the risk and return trade-off as conceptualised in the capital market model of an efficient frontier of investment opportunities. This conceptualisation of a 'market' for accounting research provides a context in which to highlight the complex issues facing academics in their roles as editors, researchers and authors. The analysis indicates that the perceptions of the so-called 'elite' US accounting journals have become unsettled particularly in Australasia, showing high levels of variability in perceived quality, while other traditionally highly ranked journals (ABR, AOS, CAR) have a more 'efficient' combination of high-quality ranking and lower dispersion of perceptions. The implications of these results for accounting academics in the context of what is often seen as a market for accounting research are discussed. © 2006 Elsevier Ltd. All rights reserved.

Experimental and theoretical characterisation of tunable fibre gratings

This thesis presents details on both theoretical and experimental aspects of UV written fibre gratings. The main body of the thesis deals with the design, fabrication and testing of telecommunication optical fibre grating devices, but also an accurate theoretical analysis of intra-core fibre gratings is presented. Since more than a decade, fibre gratings have been extensively used in the telecommunication field (as filters, dispersion compensators, and add/drop multiplexers for instance). Gratings for telecommunication should conform to very high fabrication standards as the presence of any imperfection raises the noise level in the transmission system compromising its ability of transmitting intelligible sequence of bits to the receiver. Strong side lobes suppression and high and sharp reflection profile are then necessary characteristics. A fundamental part of the theoretical and experimental work reported in this thesis is about apodisation. The physical principle of apodisation is introduced and a number of apodisation techniques, experimental results and numerical optimisation of the shading functions and all the practical parameters involved in the fabrication are detailed. The measurement of chromatic dispersion in fibres and FBGs is detailed and an estimation of its accuracy is given. An overview on the possible methods that can be implemented for the fabrication of tunable fibre gratings is given before detailing a new dispersion compensator device based on the action of a distributed strain onto a linearly chirped FBG. It is shown that tuning of second and third order dispersion of the grating can be obtained by the use of a specially designed multipoint bending rig. Experiments on the recompression of optical pulses travelling long distances are detailed for 10 Gb/s and 40 Gb/s. The characterisation of a new kind of double section LPG fabricated on a metal-clad coated fibre is reported. The fabrication of the device is made easier by directly writing the grating through the metal coating. This device may be used to overcome the recoating problems associated with standard LPGs written in step-index fibre. Also, it can be used as a sensor for simultaneous measurements of temperature and surrounding medium refractive index.

40Gbit/s single channel dispersion managed pulse propagation in standard fibre over 509km

Error free propagation of a single polarisation optical time division multiplexed 40Gbit/s dispersion managed pulse data stream over 509km has been achieved in standard (non-dispersion shifted) fibre. Dispersion compensating fibre was used after each amplifier to reduce the high local dispersion of the standard fibre. © IEE 1999.

Hydrodynamic modeling of mineral wool fiber suspensions in a two-dimensional channel flow

A consequence of a loss of coolant accident is the damage of adjacent insulation materials (IM). IM may then be transported to the containment sump strainers where water is drawn into the ECCS (emergency core cooling system). Blockage of the strainers by IM lead to an increased pressure drop acting on the operating ECCS pumps. IM can also penetrate the strainers, enter the reactor coolant system and then accumulate in the reactor pressure vessel. An experimental and theoretical study that concentrates on mineral wool fiber transport in the containment sump and the ECCS is being performed. The study entails fiber generation and the assessment of fiber transport in single and multi-effect experiments. The experiments include measurement of the terminal settling velocity, the strainer pressure drop, fiber sedimentation and resuspension in a channel flow and jet flow in a rectangular tank. An integrated test facility is also operated to assess the compounded effects. Each experimental facility is used to provide data for the validation of equivalent computational fluid dynamic models. The channel flow facility allows the determination of the steady state distribution of the fibers at different flow velocities. The fibers are modeled in the Eulerian-Eulerian reference frame as spherical wetted agglomerates. The fiber agglomerate size, density, the relative viscosity of the fluid-fiber mixture and the turbulent dispersion of the fibers all affect the steady state accumulation of fibers at the channel base. In the current simulations, two fiber phases are separately considered. The particle size is kept constant while the density is modified, which affects both the terminal velocity and volume fraction. The relative viscosity is only significant at higher concentrations. The numerical model finds that the fibers accumulate at the channel base even at high velocities; therefore, modifications to the drag and turbulent dispersion forces can be made to reduce fiber accumulation.

Autocatalytic deposition of composite coatings

The deposition and properties of electroless nickel composite coatings containing graphite, PTFE and chromium were investigated. Solutions were developed for the codeposition of graphite and chromium with electroless nickel. Solutions for the deposition of graphite contained heavy metal ions for stability, with non-ionic and anionic surfactants to provide wetting and dispersion of the particles. Stability for the codeposition of chromium particles was achieved by oxidation of the chromium. Thin oxide layers of 200 nm thick prevented initiation of the electroless reaction onto the chromium. A mechanism for the formation of electroless composite coatings was considered based on the physical adsorption of particles and as a function of the adsorption of charged surfactants and metal cations from solution. The influence of variables such as particle concentration in solution, particle size, temperature, pH, and agitation on the volume percentage of particles codeposited was studied. The volume percentage of graphite codeposited was found to increase with concentration in solution and playing rate. An increase in particle size and agitation reduced the volume percentage codeposited. The hardness of nickel-graphite deposits was found to decrease with graphite content in the as-deposited and heat treated condition. The frictional and wear properties of electroless nickel-graphite were studied and compared to those of electroless nickel-PTFE. The self-lubricating nature of both coatings was found to be dependent on the ratio of coated area to uncoated area, the size and content of lubricating material in the deposit, and the load between contacting surfaces. The mechanism of self-lubrication was considered, concluding that graphite only produced an initial lubricating surface due to the orientation of flakes, unlike PTFE, which produced true self-lubrication throughout the coating life. Heat treatment of electroless nickel chromium deposits at 850oC for 8 and 16 hours produced nickel-iron-chromium alloy deposits with a phosphorus rich surface of high hardness. Coefficients of friction and wear rates were intially moderate for the phosphorus rich layer but increased for the nickel-iron-chromium region of the coating.

Chloride resistance and durability of cement paste and concrete containing metakaolin

Metakaolin (MK), a calcined clay, was included as a partial cement replacement material, at up to 20% by weight of binder, in cement pastes and concrete, and its influence on the resistance to chloride ingress investigated. Reductions in effective chloride diffusion coefficients through hardened cement paste were obtained for binary blends and by combining OPC, MK and a second cement replacement material of pulverised fuel ash or ground granulated blast furnace slag. Steady state oxygen diffusion measurements through hardened cement pastes measured using an electrochemical cell showed that the interaction between charged species and the pore surfaces is a major factor in determining chloride diffusion rate. Rheology of the binder, particularly at high MK replacement levels, was found to have a dramatic influence on the diffusion performance of cement pastes. It was concluded that plasticising admixtures are essential for adequate dispersion of MK in cement pastes. Chloride concentration profile analysis of the concrete cylinders, exposed to sodium chloride solution for one year, was employed to obtain apparent chloride diffusion coefficients for concrete specimens. MK was found to reduce the depth of chloride penetration into concrete when compared with that of unblended mixes. Corrosion rate and corrosion potential measurements were taken on steel bars embedded in concrete exposed to a saline environment under conditions of cyclic wetting and drying. The initiation time for corrosion was found to be significantly longer for MK blended mixes than for plain OPC systems. The aggregate-paste interfacial zone of MK blended systems was investigated by steady state diffusion of chloride ions through mortar containing glass beads as model aggregate. For the model aggregate specimens tested the work confirmed the hypothesis that properties of the bulk paste are the controlling factors in ionic diffusion through mortar.

Effect of extrusion and photo-oxidation on polyethylene/clay nanocomposites

Polyethylene (a 1:1 blend of m-LLDPE and z-LLDPE) double layer silicate clay nanocomposites were prepared by melt extrusion using a twin screw extruder. Maleic anhydride grafted polyethylene (PEgMA) was used as a compatibiliser to enhance the dispersion of two organically modified monmorilonite clays (OMMT): Closite 15A (CL15) and nanofill SE 3000 (NF), and natural montmorillonite (NaMMT). The clay dispersion and morphology obtained in the extruded nanocomposite samples were fully characterised both after processing and during photo-oxidation by a number of complementary analytical techniques. The effects of the compatibiliser, the organoclay modifier (quartenary alkyl ammonium surfactant) and the clays on the behaviour of the nanocomposites during processing and under accelerated weathering conditions were investigated. X-ray diffraction, transmission electron microscopy (TEM), scanning electron microscopy (SEM), rheometry and attenuated reflectance spectroscopy (ATR-FTIR) showed that the nanocomposite structure obtained is dependent on the type of clay used, the presence or absence of a compatibiliser and the environment the samples are exposed to. The results revealed that during processing PE/clay nanocomposites are formed in the presence of the compatibiliser PEgMA giving a hybrid exfoliated and intercalated structures, while microcomposites were obtained in the absence of PEgMA; the unmodified NaMMT-containing samples showed encapsulated clay structures with limited extent of dispersion in the polymer matrix. The effect of processing on the thermal stability of the OMMT-containing polymer samples was determined by measuring the additional amount of vinyl-type unsaturation formed due to a Hoffman elimination reaction that takes place in the alkyl ammonium surfactant of the modified clay at elevated temperatures. The results indicate that OMMT is responsible for the higher levels of unsaturation found in OMMT-PE samples when compared to both the polymer control and the NaMMT-PE samples and confirms the instability of the alkyl ammonium surfactant during melt processing and its deleterious effects on the durability aspects of nanocomposite products. The photostability of the PE/clay nanocomposites under accelerated weathering conditions was monitored by following changes in their infrared signatures and mechanical properties. The rate of photo-oxidation of the compatibilised PE/PEgMA/OMMT nanocomposites was much higher than that of the PE/OMMT (in absence of PEgMA) counterparts, the polymer controls and the PE–NaMMT sample. Several factors have been observed that can explain the difference in the photo-oxidative stability of the PE/clay nanocomposites including the adverse role played by the thermal decomposition products of the alkyl ammonium surfactant, the photo-instability of PEgMA, unfavourable interactions between PEgMA and products formed in the polymer as a consequence of the degradation of the surfactant on the clay, as well as a contribution from a much higher extent of exfoliated structures, determined by TEM, formed with increasing UV-exposure times.

Optically controlled tunable dispersion compensators based on pumped fiber gratings

We demonstrate optically tunable dispersion compensators based on pumping fiber Bragg gratings made in Er/Yb codoped fiber. The tunable dispersion for a chirped grating and also a uniform-period grating was successfully demonstrated in the experiment. The dispersion of the chirped grating was tuned from 900 to 1990 ps/nm and also from -600 to -950 ps/nm in the experiment.

Analysis of powder caking in multicomponent powders using atomic force microscopy to examine particle properties

Atomic force microscopy has been used to study the surface properties of model spray dried powders. Phase imaging, nanoindentation and force modulation microscopy have differentiated between the different surface material properties of the particles, revealing a regular dispersion of soft, oil rich areas distributed across the particles' surface. Humidity and temperature cycling effects on the caking behavior of the particles have also been investigated, with significant morphology changes and onset of caking found to occur within relatively short periods of time.