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INVESTIGATING THE ROLE OF PRION PROTEIN POLYMORPHISMS ON PRION PATHOGENESISSaijo, Eri 01 January 2012 (has links)
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are lethal and infectious neurodegenerative diseases of humans and animals. The misfolding of the normal, or cellular isoform of the prion protein (PrPC) into the abnormal disease-associated isoform of PrP (PrPSc) could change the properties of PrP, consequently, PrPSc has lethal infectivity to transmit diseases. The proteinaceous infectious particle consisting mainly of PrPSc is called prion. Transmissibility of prions is strongly influenced by multiple factors including PrP polymorphisms, species barriers (PrP sequence specificity) and prion strains (conformational specificity) by unknown mechanisms. Even though the ability of prions to cross a species barrier has been recognized, the precise mechanisms of interspecies prion transmission remain unclear.
This dissertation research was conducted in order to learn more about the molecular mechanisms of conversion, propagation and transmission of PrPSc; about determinants of genetic susceptibility to infection in prion diseases; and about understanding those mechanisms, which might govern the zoonotic potential of prion diseases.
First, we investigated the transmissibility risk of multiple strains of Chronic Wasting Disease, which is a cervid TSE, with humanized transgenic mice and showed that the transmission barriers between cervid and the humanized mice are high. Next, the structural factors underlying the species barrier of prion diseases were studied using cell culture systems by systematically introducing amino acid substitutions in the regions of PrP, where the most divergences of different PrP species are recognized. Thirdly, we investigated the effects of the genetic susceptibility to prions as well as conversion kinetics and properties of PrPSc using Tg mice expressing ovine PrP polymorphism (OvPrP) at codon 136 either alanine (A) or valine (V). The templating characteristics of OvPrPSc-V136 were dominant over OvPrPSc-A136 under co-expressions of OvPrPC-A136 and OvPrPC-V136. Finally, the function of PrP was studied in relation to the pathogenesis of Alzheimer’s disease.
These studies demonstrated that the conformational compatibility between PrPC and PrPSc contributed to the conversion kinetics and species barrier. We concluded that the conformational compatibility of PrPC to PrPSc is controlled not only by the PrP sequence specificity but also by the tertiary structure of PrPC.
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HYSTERESIS IN REPOLARIZATION OF CARDIAC ACTION POTENTIALS: EFFECTS OF SPATIAL HETEROGENEITY AND SLOW REPOLARIZATION CURRENTSJing, Linyuan 01 January 2013 (has links)
Repolarization alternans, i.e. beat-to-beat variation of repolarization of action potential, is proposed as a predictor of life-threatening arrhythmias. Restitution relates repolarization duration with its previous relaxation time, i.e. diatstolic interval (DI), and is considered a dominant mechanism for alternans. Previously, we observed that different repolarization durations at the same DI during decelerating and accelerating pacing, i.e. restitution displays hysteresis, which is a measure of “cardiac memory”.
Objective of the current study was to investigate in the pig 1) the mechanism for a previously observed hysteresis type phenomenon, where alternans, once started at higher heart rate, persists even when heart rate decreases below its initiating rate, 2) regional differences in expression of hysteresis, i.e. memory in restitution in the heart, and 3) changes in restitution and memory during manipulation of an important repolarization current, the slow delayed rectifier, IKs.
Action potentials were recorded in pig ventricular tissues using microelectrodes. Regional differences were explored in endocardial and epicardial tissues from both ventricles. DIs were explicitly controlled in real time to separate restitution mechanism from non-restitution related effects. Stepwise protocols were used to explore the existence in hysteresis in alternans threshold, where DIs were held constant for each step and progressively decreased and then increased. Quantification of cardiac memory was achieved by sinusoidally changing DI protocols, which were used to investigate memory changes among myocytes from different regions of the heart and during IKs manipulation.
Results show that during stepwise protocol, hysteresis in alternans still existed, which indicates that restitution is not the only mechanism underlying the hysteresis. When comparing hysteresis obtained from sinusoidally oscillatory DIs among different regions, results show memory is expressed differently with endocardium expressing the most and epicardium the least memory. This provides important implications about the location where arrhythmia would initiate. Results also show that measures for hysteresis loops obtained by sinusoidal DI protocols decreased (increased) after enhancement (attenuation) of IKs, suggesting decreased (increased) hysteresis, i.e. memory in restitution. This effect needs to be considered during drug development.
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ATOM OPTICS, CORE ELECTRONS, AND THE VAN DER WAALS POTENTIALLonij, Vincent P. A. January 2011 (has links)
This dissertation describes new measurements of the van der Waals (vdW) potential energy for atoms near a surface. The measurements presented here were accomplished by studying diffraction a beam of atoms transmitted through a nanograting. I will describe how we improved precision by a factor of 10 over previous diffraction measurements by studying how different types of atoms interact with the same surface. As a result of this new precision, we were able to show for the first time the contribution of atomic core electrons to the atom-surface potential, and experimentally test different atomic structure calculation methods.In addition, this dissertation will describe how changing the width of the grating bars to achieve a particular "magic" grating bar width or rotating a grating to a particular "magic" angle allows us to determine both the atom-surface potential strength and the geometry of the grating. This represents an improvement over several recent studies where uncertainties in the nanograting geometry limited precision in the measurements of the vdW potential.For a complementary measurement, also discussed in this dissertation, we collaborated with the Vigue group in Toulouse, France. In this collaboration we used an atom interferometer to measure the phase shift due to transmission through a nanograting. By combining diffraction data from Tucson with interferometry data from Toulouse we improved the precision of interferometry measurements of the atom-surface potential of a single atomic species by almost a factor of 10 over previous interferometric measurements of the vdW potential. These interferometry measurements also serve to measure the shape of the vdW potential and set a limit on non-Newtonian gravitational interactions at 1-2 nm length scales.Finally, this dissertation will discuss how nanogratings with optimized geometry can improve atom interferometers, for example, with blazed gratings. We discuss next generation atom-surface potential measurements and examine new ways of analyzing diffraction data.
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CHARACTERIZATION OF CHARGE INJECTION PROCESSES OF THIN FILMS ON INDIUM TIN OXIDE ELECTRODES USING A NOVEL SPECTROELECTROCHEMICAL TECHNIQUE: POTENTIAL-MODULATED ATTENUATED TOTAL REFLECTANCE SPECTROSCOPYAraci, Zeynep January 2010 (has links)
Understanding interfacial charge injection processes is one of the key factors needed for development of efficient organic electronic devices, such as biosensors and energy conversion systems, since these processes control the electrical characteristics of these devices. Spectroelectrochemical characterization of electron transfer processes occurring at the electrode - electroactive thin film interface has been evaluated to improve our understanding of charge transfer kinetics using a novel form of electroreflectance spectroscopy, potential-modulated attenuated total reflectance (PM-ATR), which makes it possible to sensitively monitor spectroscopic changes in thin films as a function of applied potential.PM-ATR was used to evaluate three different redox-active films deposited on indium tin oxide (ITO) electrodes to investigate: i) the orientation dependence of charge transfer rates of thin films of biomolecules, ii) surface treatment and modification effects on charge transfer kinetics of conducting polymers and, iii) estimation of rates of electron injection and conduction band edge of semiconductor nanocrystalline materials.First, Prussian blue film as a model system was used successfully to examine the PM-ATR technique for determination of the charge transfer rate constant between ITO and a molecular film.Second, an anisotropic and redox active protein film, cytochrome c, was used to probe charge transfer rates with respect to molecular orientation. The electron transfer rate measured using TM polarized light was four-fold greater than that measured using TE polarized light. These data are the first to correlate a distribution of molecular orientations with a distribution of electron transfer rates in a redox-active molecular film.Third, the effects of ITO surface treatment and modification on charge transfer kinetics on a conducting polymer, poly(3,4-ethylenedioxythiophene/)/poly(styrenesulfonate) (PEDOT/PSS), were studied. The apparent interfacial charge transfer rate constant for PEDOT/PSS on ITO has been reported for the first time which cannot be measured otherwise with conventional electrochemistry due to high non-Faradaic background of PEDOT/PSS films.Fourth, PM-ATR enabled characterization of reversible redox processes between submonolayer coverages of surface-tethered, CdSe nanocrystals and ITO for the first time. Optically determined onset potentials for electron injection were used for estimation for the conduction band and valance band energies (ECB and EVB, respectively).
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Lattice potential energies and theoretical applicationsRoobottom, Helen Kay January 2000 (has links)
No description available.
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An investigation of dusty plasmasTomme, Edward B. January 2000 (has links)
No description available.
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Assessment controls on reservoir performance and the affects of granulation seam mechanics in the Bredasdorp Basin, South Africa.Schalkwyk, Hugh Je-Marco January 2006 (has links)
<p>The Bredasdorp Basin is one of the largest hydrocarbon producing blocks within Southern Africa. The E-M field is situated approximate 50 km west from the FA platform and was brought into commission due to the potential hydrocarbons it may hold. If this field is brought up to full producing capability it will extend the lifespan of the refining station in Mosselbay, situated on the south coast of South Africa, by approximately 8 to 10 years. An unexpected pressure drop within the E-M field caused the suite not to perform optimally and thus further analysis was imminent to assess and alleviate the predicament. The first step within the project was to determine what might have cause the pressure drop and thus we had to go back to cores drilled by Soekor now known as Petroleum South Africa, in the early 1980&rsquo / s.</p>
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</br>Analyses of the cores exposed a high presence of granulation seams. The granulation seams were mainly subjected within sand units within the cores. This was caused by rolling of sand grains over one another rearranging themselves due to pressure exerted through compaction and faulting, creating seal like fractures within the sand. These fractures caused these sand units to compartmentalize and prohibit flow from one on block to the next. With advance inquiry it was discovered that there was a shale unit situated within the reservoir dividing the reservoir into two main compartments. At this point it was determined to use Petrel which is windows based software for 3D visualization with a user interface based on the Windows Microsoft standards. This is easy as well as user friendly software thus the choice to go with it. The software uses shared earth modeling tool bringing about reservoir disciplines trough common data modelling. This is one of the best modelling applications in the available and it was for this reason that it was chosen to apply within the given aspects of the project A lack of data was available to model the granulation seams but with the data acquired during the core analyses it was possible to model the shale unit and factor in the influences of the granulation seams to asses the extent of compartmentalization. The core revealed a thick shale layer dividing the reservoir within two sections which was not previously noted. This shale layer act as a buffer/barrier restricting flow from the bottom to the top halve of the reservoir. This layer is thickest at the crest of the 10km² / domal closure and thins toward the confines of the E-M suite. Small incisions, visible within the 3 dimensional models could serve as a guide for possible re-entry points for future drilling. These incisions which were formed through Lowstand and Highstand systems tracts with the rise and fall of the sea level. The Bredasdorp Basin consists mainly of tilting half graben structures that formed through rifting with the break-up of Gondwanaland. The model also revealed that these faults segregate the reservoir further creating bigger compartments. The reservoir is highly compartmentalized which will explain the pressure loss within the E-M suite. The production well was drilled within one of these compartments and when the confining pressure was relieved the pressure dropped and the production decrease. As recommendation, additional wells are required to appraise the E-M structure and determine to what extent the granulation seems has affected fluid flow as well as the degree of sedimentation that could impede fluid flow. There are areas still containing untapped resources thus the recommendation for extra wells.</p>
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Development of High Capacitance Films for Electrical Energy Storage Using Electrophoretic Deposition of BaTiO3 on Ultrasonically Etched NiHarari, Berkan 13 October 2012 (has links)
High capacitance devices were developed using rapid electrophoretic deposition (EPD) of barium titanate (BaTiO3) on ultrasonically etched nickel (Ni) substrates. The microstructural and
electrical properties of films with varying thicknesses, sintering temperatures and substrate etching times were investigated to study their effect on the capacitance. Although increasing the capacitance was the primary goal, decreasing manufacturing costs and reducing environmental impact was also considered. After confirming the tetragonality and particle size of a 0.2 µm hydrothermal powder, it was dispersed in an aqueous-organic mixture of ethanol, acetone and water. A zeta potential of 50 mV was observed at the EPD pH level (6.8). Flocculation or coagulation was not likely in this situation. Therefore, mixing water with an organic solution was an effective method for reducing environmental impact while maintaining deposition quality. The presence of BaCO3 in the films was proven using X-ray diffraction. Other impurities
such as TiO2 and NiO were not detected. A significant variation in the average grain size was not observed for films with different thicknesses whereas films sintered at different temperatures displayed greater variation. A bimodal pore size distribution in the samples suggested that the powder was agglomerated after deposition due to a high deposition voltage (20 V). Rapid deposition times of 2 to 8 seconds offered a potential for cost reduction compared to longer
deposition times implemented in industry. Therefore the increased porosity was accepted. The dielectric constant of the films increased from 2900 to 6730 as the thickness increased from 17.75 µm to 47.5 µm. The dissipation factor decreased from 0.27 to 0.06 with increasing thickness. This behavior was attributed to a low dielectric constant interfacial layer and a higher dielectric leakage current at smaller thicknesses. The dielectric constant increased from 1700 to 6350 and the dissipation factor decreased from 0.23 to 0.04 as the sintering temperature increased from 1150°C to 1300°C. This was attributed to an increase in tetragonality with grain size and a decrease in porosity with sintering temperature. Finally, etching a substrate for 60 seconds increased its capacitance by 27.47% and using ultrasonic agitation further increased the capacitance by 8.75%. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2012-10-12 00:54:53.915
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Ion selectivity and membrane potential effects of two scorpion pore-forming peptides / D. ElgarElgar, Dale January 2005 (has links)
Parabutoporin (PP) and opistoporin 1 (OP1) are cation, a-helical antimicrobial peptides isolated
from the southern African scorpion species, Parabuthus schlechteri and Opistophthalmus carinatus,
respectively. Along with their antimicrobial action against bacteria and fungi, these peptides show
pore-forming properties in the membranes of mammalian cells. Pore-formation and ion selectivity in
cardiac myocytes were investigated by measuring the whole cell leak current by means of the patch
clamp technique. Pore-formation was observed as the induction of leak currents. Ion selectivity of
the pores was indicated by the shift of the reversal potential (E,,,) upon substitution of intra (K' with
CS' and CI- with aspartate) and extracellular (Na' with NMDG') ions. Results were compared with
the effect of gramicidin A used as a positive control for monovalent cation selective pores. PP and
OP I induced a fluctuating leak current and indicate non-selectivity of PP and OP1-induced pores.
An osmotic protection assay to determine estimated pore size was performed on the cardiac
myocytes. PP and OP1-induced pores had an estimate pore size of 1.38-1.78 nm in diameter.
The effect of PP and OP1 on the membrane potential (MP) of a neuroblastoma cell line and cardiac
myocytes was investigated. TMRM was used to mark the MP fluorescently and a confocal
microscope used to record the data digitally. The resting membrane potential (RMP) of the
neuroblastoma cells was calculated at -38.3 f 1.9 mV. PP (0.5 uM) and OP1 (0.5-1 uM) depolarized
the entire cell uniformly to a MP of -1 1.9 k 3.9 mV and -9.4 k 1.9 mV, respectively. This occurred
after 20-30 min of peptide exposure. In the case of the cardiac myocytes depolarization was induced
to -39.7 f 8.4 mV and -32.6 f 5.2 mV by 0.5-1 uM PP and 1.5-2.5 uM OPl, respectively. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2006.
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Adaptation of trees to the urban environment : Acacia karroo in Potchefstroom, South Africa / by Alida Yonanda PelserPelser, Alida Yonanda January 2006 (has links)
Urban open spaces are of strategic importance to the quality of life of our increasingly
urbanized society. Trees and related vegetation are planted and managed within the
communities and cities to create or add value to the busy lives of the city dwellers.
Trees in towns and cities form an important part of complex urban ecosystems and
provide significant ecosystem services and benefits for urban dwellers, for example:
reducing particulate pollution, carbon sequestration, decreasing air temperature,
decreasing water runoff, aesthetic value and an increase in human health. Trees are solarpowered
technology that can help restore balance to dysfunctional urban ecosystems.
Trees form strands in the urban fabric that connect people to nature and to each other.
The urban environment puts tremendous strain on trees by trenching, limited space for
root growth and emission of pollutants into the atmosphere, water and soil. The problem
is that the real impact of the urban environment on the trees within our community is
unknown.
The aim of this investigation was to assess the overall anthropogenic and environmental
impacts on urban trees by measuring the tree vitality of Acacia karroo using chlorophyll
fluorescence kinetics (JIP-test) and the leaf water potential using a pressure chamber.
Tree vitality was quantified as the chlorophyll fluorescence-based performance index
(PIABS)T. ree vitality measurements were also correlated with soil physical and chemical
data. In the comparative study, an urbanization gradient approach was followed in which
results of trees in rural areas were regarded as controls. The gradient approach is used
worldwide and provides a background for questions of ecological structure and function.
The urbanization gradient was quantified using the V-I-S model, based on % cover of
vegetation, impervious surface and soil. Additionally, a model to determine the monetary
value of trees in urban environments (SATAM) was tested. All this information could
eventually contribute to develop an urban tree management program for Potchefstroom. It was evident from the current study that urbanization has a negative impact on tree
vitality. The leaf water potential of a tree was, however, not necessarily negatively
impacted upon. Although trees in urban environments did not always have a high vitality
(PIABS)t, hey still played a major role in the urban environment. According to the tree
appraisal method (SATAM), some of these trees have a value of R60 000. / Thesis (M. Environmental Science (Ecological Remediation and Sustainable Utilisation))--North-West University, Potchefstroom Campus, 2007.
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