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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
281

Rorschach indicators of resilience in adolescents / I.E. Odendaal

Odendaal, Isabella Elizabeth January 2011 (has links)
The main focus of this study was to explore how personal constructions, consisting of latent and conscious schema, and obtained from a culturally sensitive interpretation of the RCS, informed the transactional resilience of Black South African adolescents. This study was motivated in view of limited knowledge available about the (i) processes that are generic to the resilience-promoting transactions of Black South African adolescents and (ii) to potentiate insight into an adolescent’s construction of personal meaning of her conscious and unconscious experiences that may not always be easily recognised in her overt behaviour or by self-report measures often used in South African resilience research. Six Black South African adolescents aged 14 to 16 years volunteered to take part in this multiple case study. The participants were identified as resilient by an advisory panel consisting of learners and educators at an English-medium school in the Vaal Triangle area. In this essentially qualitative study, qualitative data obtained from an unstructured individual interview, unstructured observations, and a follow-up interview were integrated with the data obtained from a culturally sensitive, conceptual interpretation of these Black adolescents’ Rorschach protocols. The structural, quantitative data obtained from specific indicators in Exner’s Comprehensive System were interpreted in a culturally sensitive manner and integrated with the qualitative data obtained from the Rorschach protocols. A culturally sensitive, conceptual framework for interpreting Rorschach indicators associated with adolescents’ transactional resilience was provided. These findings indicated individual and ecological protective resources well known within South African resilience research. Findings that contributed new understanding of the transactional processes associated with Black South African adolescent resilience were also obtained. Four case-specific self-reflective strategies were identified, namely, emotional stoicism, frequent introspection, honouring the past, and adopting a new identity. These selfreflective strategies served as the participants’ unique ways of compensating for their adversity-informed schema as well as encouraging them to navigate towards the sustained support of specific significant others and resilience-promoting ecological resources. The participants indicated that attachment challenges brought about repressed feelings and specific security needs, which shaped their resilience-promoting navigation and enabled them to self-knit in a resilient way. / Thesis (Ph.D. (Education))--North-West University, Vaal Triangle Campus, 2011
282

Rorschach indicators of resilience in adolescents / I.E. Odendaal

Odendaal, Isabella Elizabeth January 2011 (has links)
The main focus of this study was to explore how personal constructions, consisting of latent and conscious schema, and obtained from a culturally sensitive interpretation of the RCS, informed the transactional resilience of Black South African adolescents. This study was motivated in view of limited knowledge available about the (i) processes that are generic to the resilience-promoting transactions of Black South African adolescents and (ii) to potentiate insight into an adolescent’s construction of personal meaning of her conscious and unconscious experiences that may not always be easily recognised in her overt behaviour or by self-report measures often used in South African resilience research. Six Black South African adolescents aged 14 to 16 years volunteered to take part in this multiple case study. The participants were identified as resilient by an advisory panel consisting of learners and educators at an English-medium school in the Vaal Triangle area. In this essentially qualitative study, qualitative data obtained from an unstructured individual interview, unstructured observations, and a follow-up interview were integrated with the data obtained from a culturally sensitive, conceptual interpretation of these Black adolescents’ Rorschach protocols. The structural, quantitative data obtained from specific indicators in Exner’s Comprehensive System were interpreted in a culturally sensitive manner and integrated with the qualitative data obtained from the Rorschach protocols. A culturally sensitive, conceptual framework for interpreting Rorschach indicators associated with adolescents’ transactional resilience was provided. These findings indicated individual and ecological protective resources well known within South African resilience research. Findings that contributed new understanding of the transactional processes associated with Black South African adolescent resilience were also obtained. Four case-specific self-reflective strategies were identified, namely, emotional stoicism, frequent introspection, honouring the past, and adopting a new identity. These selfreflective strategies served as the participants’ unique ways of compensating for their adversity-informed schema as well as encouraging them to navigate towards the sustained support of specific significant others and resilience-promoting ecological resources. The participants indicated that attachment challenges brought about repressed feelings and specific security needs, which shaped their resilience-promoting navigation and enabled them to self-knit in a resilient way. / Thesis (Ph.D. (Education))--North-West University, Vaal Triangle Campus, 2011
283

Complexities of Order-Related Formal Language Extensions / Komplexiteter hos ordnings-relaterade utökningar av formella språk

Berglund, Martin January 2014 (has links)
The work presented in this thesis discusses various formal language formalisms that extend classical formalisms like regular expressions and context-free grammars with additional abilities, most relating to order. This is done while focusing on the impact these extensions have on the efficiency of parsing the languages generated. That is, rather than taking a step up on the Chomsky hierarchy to the context-sensitive languages, which makes parsing very difficult, a smaller step is taken, adding some mechanisms which permit interesting spatial (in)dependencies to be modeled. The most immediate example is shuffle formalisms, where existing language formalisms are extended by introducing operators which generate arbitrary interleavings of argument languages. For example, introducing a shuffle operator to the regular expressions does not make it possible to recognize context-free languages like anbn, but it does capture some non-context-free languages like the language of all strings containing the same number of as, bs and cs. The impact these additions have on parsing has many facets. Other than shuffle operators we also consider formalisms enforcing repeating substrings, formalisms moving substrings around, and formalisms that restrict which substrings may be concatenated. The formalisms studied here all have a number of properties in common. They are closely related to existing regular and context-free formalisms. They operate in a step-wise fashion, deriving strings by sequences of rule applications of individually limited power. Each step generates a constant number of symbols and does not modify parts that have already been generated. That is, strings are built in an additive fashion that does not explode in size (in contrast to e.g. Lindenmayer systems). All languages here will have a semi-linear Parikh image. They feature some interesting characteristic involving order or other spatial constraints. In the example of the shuffle multiple derivations are in a sense interspersed in a way that each is unaware of. All of the formalisms are intended to be limited enough to make an efficient parsing algorithm at least for some cases a reasonable goal. This thesis will give intuitive explanations of a number of formalisms fulfilling these requirements, and will sketch some results relating to the parsing problem for them. This should all be viewed as preparation for the more complete results and explanations featured in the papers given in the appendices. / Denna avhandling diskuterar utökningar av klassiska formalismer inom formella språk, till exempel reguljära uttryck och kontextfria grammatiker. Utökningarna handlar på ett eller annat sätt omordning, och ett särskilt fokus ligger på att göra utökningarna på ett sätt som dels har intressanta spatiala/ordningsrelaterade effekter och som dels bevarar den effektiva parsningen som är möjlig för de ursprungliga klassiska formalismerna. Detta står i kontrast till att ta det större steget upp i Chomsky-hierarkin till de kontextkänsliga språken, vilket medför ett svårt parsningsproblem. Ett omedelbart exempel på en sådan utökning är s.k. shuffle-formalismer. Dessa utökar existerande formalismer genom att introducera operatorer som godtyckligt sammanflätar strängar från argumentspråk. Om shuffle-operator introduceras till de reguljära uttrycken ger det inte förmågan att känna igen t.ex. det kontextfria språket anbn, men det fångar istället vissa språk som inte är kontextfria, till exempel språket som består av alla strängar som innehåller lika många a:n, b:n och c:n. Sättet på vilket dessa utökningar påverkar parsningsproblemet är mångfacetterat. Utöver dessa shuffle-operatorer tas också formalismer där delsträngar kan upprepas, formalismer där delsträngar flyttas runt, och formalismer som begränsar hur delsträngar får konkateneras upp. Formalismerna som tas upp här har dock vissa egenskaper gemensamma. De är nära besläktade med de klassiska reguljära och kontextfria formalismerna. De arbetar stegvis, och konstruerar strängar genom successiva applikationer av individuellt enkla regler. Varje steg genererar ett konstant antal symboler och modifierar inte det som redan genererats. Det vill säga, strängar byggs additivt och längden på dem kan inte explodera (i kontrast till t.ex. Lindenmayer-system). Alla språk som tas upp kommer att ha en semi-linjär Parikh-avbildning. De har någon instressant spatial/ordningsrelaterad egenskap. Exempelvis sättet på vilket shuffle-operatorer sammanflätar annars oberoende deriveringar. Alla formalismerna är tänkta att vara begränsade nog att det är resonabelt att ha effektiv parsning som mål. Denna avhandling kommer att ge intuitiva förklaring av ett antal formalismer som uppfyller ovanstående krav, och kommer att skissa en blandning av resultat relaterade till parsningsproblemet för dem. Detta bör ses som förberedande inför läsning av de mer djupgående och komplexa resultaten och förklaringarna i de artiklar som finns inkluderade som appendix.
284

Performance Improvement of Latex-based PSAs Using Polymer Microstructure Control

Qie, Lili 02 February 2011 (has links)
This thesis aims to improve the performance of latex-based pressure-sensitive adhesives (PSAs). PSA performance is usually evaluated by tack, peel strength and shear strength. Tack and peel strength characterize a PSA’s bonding strength to a substrate while shear strength reflects a PSA’s capability to resist shear deformation. In general, increasing shear strength leads to a decrease in tack and peel strength. While there are several commercial PSA synthesis methods, the two most important methods consist of either solvent-based or latex-based techniques. While latex-based PSAs are more environmentally compliant than solvent-based PSAs, they tend to have much lower shear strength, at similar tack and peel strength levels. Therefore, the goal in this thesis was to greatly improve the shear strength of latex-based PSAs at little to no sacrifice to tack and peel strength. In this study, controlling the polymer microstructure of latexes or their corresponding PSA films was used as the main method for improving the PSA performance. The research was sub-divided into four parts. First, the influence of chain transfer agent (CTA) and cross-linker on latex polymer microstructure was studied via seeded semi-batch emulsion polymerization of butyl acrylate (BA) and methyl methacrylate (MMA). Three techniques were used to produce the latexes: (1) adding CTA only, (2) adding cross-linker only, and (3) adding both CTA and cross-linker. It was found that using CTA and cross-linker simultaneously allows one to expand the range of latex microstructural possibilities. For example, latexes with similar gel contents but different Mc (molecular weight between cross-links) and Mw (molecular weight of sol polymers) could be produced if CTA and cross-linker concentration are both increased. However, for the corresponding PSAs with similar gel contents, the relationship between their polymer microstructure and performance was difficult to establish as almost all of the medium and high gel content PSAs showed very low tack and peel strength as well as extremely large shear strength readings. In the second part of this thesis, in order to improve the tack and peel strength of medium and high gel content PSAs, the monomer composition and emulsifier concentration were varied. It was found that changing the monomer mixture from BA/MMA to BA/acrylic acid (AA)/2-hydroxyethyl methacrylate (HEMA) while simultaneously decreasing emulsifier concentration dramatically improved the corresponding PSAs’ shear strength as well as tack and peel strength. The addition of polar groups to the PSA increased its cohesive strength due to the presence of strong hydrogen bonding; meanwhile, PSA films’ surface tension increased. In the third part, two series of BA/AA/HEMA latexes were generated by varying the amounts of CTA either in the absence or presence of cross-linker. The latexes produced in the absence of cross-linker exhibited significantly larger Mc and Mw compared to their counterparts with similar gel contents prepared with cross-linker. The PSAs with the larger Mc and Mw showed much larger shear strengths due to improved entanglements between the polymer chains. In the final part of the thesis, the performance of the BA/AA/HEMA PSAs was further improved by post-heating. Compared with original latex-based PSAs with similar gel contents, heat-treated PSAs showed not only significantly improved shear strengths, but also much larger tack and peel strengths. The different shear strengths were related to the PSAs’ gel structures, which were discrete in the original PSAs but continuous in the heat-treated PSAs. The improved tack and peel strengths were related to the PSA films’ surface smoothness. During the post-heating process, the PSA polymer flowed, resulting in much smoother surfaces than the original PSA films. In addition, the effect of post-heating was related to the polymer microstructure of the untreated PSAs. Decreasing the amount of very small or very big polymers or simultaneously increasing Mc and Mw could lead to post-treated PSAs with significantly better performance. Moreover, it was found that by optimizing the polymer microstructure of the original latex-based PSAs, it was possible to obtain a treated PSA with similar or even better performance than a solvent-based PSA with similar polymer microstructure. Our original objective was surpassed: in two cases, not only was shear strength greatly improved, but so were tack and peel strength due to the simultaneous modification of PSA bulk and surface properties.
285

Dynamic Composition and Management of Virtual Devices for Ad Hoc Multimedia Service Delivery

Karmouch, Eric 30 March 2011 (has links)
Pervasive computing implies the invisibility of the technology involved in providing ubiquity, such that technology is integrated into the environment and non-intrusive. In such a manner, computing and networking resources become diffused into physical environments, enabling users to exploit their provided functionalities such that functionality is distributed, enabling it to be controlled, monitored, managed, and extended beyond what it was initially designed to do. Moreover, computer awareness moves towards user-centricity, whereby systems seamlessly adapt to the characteristics, preferences, and current situations of users and their respective surrounding environments. Users exploit such functionalities in the form of a virtual device, whereby a collection of heterogeneous devices in the vicinity of the user are behaving as one single homogeneous device for the benefit of the user in solving some given task. This dissertation investigates the problem of dynamic composition and management of virtual devices for ad hoc multimedia service delivery and proposes an autonomous policy driven framework for virtual device management. The framework consists of a hierarchical structure of distributed elements, including autonomic elements, all working towards the self-management of virtual devices. The research presented in this dissertation addresses the functionalities of these components. More specifically, contributions are made towards the autonomous management of virtual devices, moving away from infrastructure based schemes with heavy user involvement to decentralized and zero touch (i.e., no user involvement) solutions. In doing so, the components and methodology behind a policy-driven autonomous framework for the dynamic discovery, selection, and composition of multimodal multi-device services are presented. The framework operates in an ad hoc network setting and introduces a Service Overlay Network (SON) based definition of a virtual device. Furthermore, device and service discovery, composition, integration, and adaptation schemes are designed for Mobile Ad hoc Network Environments (MANETs) enabling users to generate, on-the-fly, complex strong specific systems, embedding in a distributed manner, QoS models providing compositions that form the best possible virtual device at the time of need. Experimental studies are presented to demonstrate the performance of the proposed schemes.
286

Epithelial Sodium Channels in the Brain: Effect of High Salt Diet on Their Expression

Amin, Md. Shahrier 28 June 2011 (has links)
Statement of the problem: The epithelial sodium channels (ENaC) play an important role in regulation of blood pressure (BP). Although the genes are identical in Dahl salt sensitive (S) and Dahl salt resistant (R) rats, expression of ENaC subunits is increased in kidneys of S rats on high salt diet. Intracerebroventricular (icv) infusion of ENaC blocker benzamil prevents Na+ induced hypertension. It was not known whether ENaC subunits are expressed in the brain and whether or not brain ENaC plays a role in regulation of [Na+] in CNS. Hypothesis: 1. Epithelial sodium channels are expressed in the brain. 2. Expression of ENaC is increased in the kidneys and brain of Dahl S rats on high salt diet. 3. ENaC in the brain contributes to regulation of [Na+] in the CSF and brain interstitium. Methods of investigation: We studied expression and distribution of the ENaC subunits and assessed the effects of icv infusion of Na+-rich aCSF in Wistar rats or high salt diet in Dahl S rats in different areas of the brain. Function of ENaC in the choroid plexus was evaluated by studying the effects of benzamil and ouabain on Na+ transport. Major findings: In Wistar rats, both mRNA and protein of all three ENaC subunits are expressed in brain epithelia and magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nucleus. ENaC abundance is higher on the apical versus basolateral membrane of choroid cells. Benzamil decreases Na+ influx into choroid cells by 20-30% and increases CSF [Na+] by ~8 mmol/L. Na+ rich aCSF increases apical membrane expression of βENaC in the choroid cells and of α and βENaC in basolateral membrane of ependymal cells, but has no effect on neuronal ENaC. Expression of ENaC is higher in choroid cells and SON of Dahl S versus R rats and the higher expression persists on a high salt diet. High salt attenuates the ouabain blockable efflux of Na+ from choroid cells and has no effect on CSF [Na+] in Dahl R rats. In contrast, high salt does not attenuate ouabain blockable efflux of 22Na+ and CSF [Na+] increases in Dahl S. Main Conclusion: ENaC in the brain contributes to Na+ transport into the choroid cells and appear to be involved in reabsorption of Na+ from the CSF. Aberrant regulation of Na+ transport and of Na+K+ATPase activity, might contribute to increases in CSF [Na+] in Dahl S rats on high-salt diet. ENaC in magnocellular neurons may contribute to enhanced secretion of mediators such as ‘ouabain’ leading to sympathetic hyperactivity in Dahl S rats.
287

Regional neurochemical characterization of the flinders sensitive line rat with regard to gaba and cholinergic signalling pathways / P.J. van Zyl.

Van Zyl, Petrus Jurgens January 2008 (has links)
Despite their acknowledged efficacy, currently available antidepressants still demonstrate undesirable side effects, shortfalls in effectiveness and a delayed onset of action. All these agents act via monoaminergic mechanisms, although recent studies have begun to note the potential role of the cholinergic system as well as the amino acid pathways in affective isorders. It has been suggested that glutamate NMDA receptor activation may be involved in hippocampal degeneration seen in patients with depression, as well as contributing as a molecular target for the antidepressant action of known antidepressant drugs. Glutamate either separately or via the release of nitric oxide, regulates the release of various transmitters in the brain critical for affective state, e.g. monoamines (noradrenaline, dopamine), indoleamines (5HT), y-aminobutyric acid (GABA) and acetylcholine. The aim of this study was to investigate N-methyl-D-aspartate (I\IMDA) and muscarinic M1 receptor characteristics and also GABA and acetylcholine levels in a genetic animal model of depression, the Flinders Sensitive Line (FSL) rat, with respect to its control, viz. Flinders Resistant Line (FRL) rat, thereby establishing a possible role for the amino acid and cholinergic pathways in the hippocampus and frontal cortex, two brain areas implicated in depression. In addition, anxietylike behaviours were assessed using the open field and social interaction tests. A sensitive liquid chromatography tandem mass spectrometer (LC/MS/MS) method was used in the quantification of acetylcholine as well as high performance liquid chromatography with electrochemical detection (HPLG-EGD) for the quantification of GABA in the above-mentioned brain areas of FSL and FRL rats. NMDA and muscarinic M1 receptor characteristics were expressed in terms of receptor denSity (Bmax) and affinity (Kd) values and were performed using [3H]-MK801 (27.5 Gi/mmol) and quinuclidinyl benzilate (52.0 Gilmmol) for NMDA and M1 receptors, respectively. In addition, to provide evidence for face validity, behavioural assessments were routinely performed using the open field test and social interaction test. Significantly elevated levels of acetylcholine were found in the frontal cortex but with significantly reduced levels in the hippocampus of FSL rats. Cortical and hippocampal muscarinic receptor binding characteristics remained unchanged, while no differences with regard to GABA levels and NMDA receptor binding characteristics were noted in these brain areas. In concordance with studies from the literature, aversive and locomotor behaviour as measured in the open field test, provided evidence of anxiogenic behaviour in the FSL rat, evinced by significantly less social interaction than their FRL counterparts. In addition, evidence for a lack in general activity of the FSL rat in the open field was also noted. Our data therefore suggest the presence of a cholinergic dysfunction in both the frontal cortex and hippocampus of the FSL rat, although this is not accompanied by simultaneous changes in muscarinic M1 receptor binding in key limbic brain regions. Although increased cholinergic drive is a recognised characteristic of FSL rats and is representative of the model's' construct validity, we suggest that the depressive phenotype of these animals is not related to altered cholinergic activity in a single brain region, but instead involves various limbic brain regions, possibly being more dependent on opposing cholinergic deficits in the cortex and hippocampus. / Thesis (M.Sc. (Pharmacology)--North-West University, Potchefstroom Campus, 2009.
288

Ischemic profile and cardiovascular function in African men : the SABPA study / M.E. Griffiths

Griffiths, Madelein Elizabeth January 2011 (has links)
Motivation: Ischemic heart disease is the eighth leading cause of death in an African population. Silent ischemia can be defined as an ischemic episode without associated pain. The clinical significance of silent ischemia is growing and can now be considered as a risk factor in the development of coronary disease. Hypertension and associated risk factors, hypercholesterolemia and diabetes are associated with silent ischemia. Other factors such as higher pulse pressure, double product, heart rate and higher carotid intima-media thickness are also associated with silent ischemia. Urbanisation is rising in South-Africa. This new lifestyle is associated with several risk factors including: poor diets, lower physical activity levels, hypertension and increased smoking and alcohol abuse. The prevalence of stroke is high among Africans, which can be due to a higher prevalence of hypertension, diabetes and obesity. Purpose: The purpose of this study was to determine the associations between silent ischemia and cardiovascular function in African men. The focus fell on hypertension and associated risk factors, higher total cholesterol levels, and increased pulse pressure, heart rate and sub-clinical atherosclerosis. vi Methodology: This study constituted a population study in the North-West province carried out on urbanized African male teachers aged between 20-60 years. The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) sub-study consisted of a total of 80 African male volunteers. The Cardiotens apparatus was placed on each participant on the first morning. This apparatus took ambulatory blood pressure measurements as well as Electrocardiogram measurements. Hereafter, participants continued with their normal work day until 1700. After an overnight stay at the Metabolic unit of the North-West University Potchefstroom campus, the apparatus was removed at 0600. During statistical analyses, the African males were divided into groups of participants with silent ischemia (SI) and those without silent ischemia (nSI), as determined by the ambulatory electrocardiogram. Statistical analyses were performed by means of the Statistica version 10 software program. Results: In comparison with the nSI men, the SI showed the following: above normal high sensitivity C-reactive protein and glucose, higher ambulatory blood pressure, heart rate, pulse pressure, resting ST-segment depression and carotid intima-media thickness. Multiple regression analyses indicated that ambulatory silent ischemia is associated with sub-clinical atherosclerosis, possibly increasing their stroke risk. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.
289

The synthesis and characterization of diphenylacetylene containing ion channels

Moszynski, Joanne Marie 03 August 2011 (has links)
This Thesis presents the synthesis, characterization and mechanistic explorations into a series of diphenylacetylene-containing oligoester ion channels. Eighteen final compounds were synthesized and tested for ion transport activity utilizing both vesicle and planar bilayer assays. The oligomers varied in length, hydrophobicity and the nature of the aromatic moiety. Compounds incorporating a modified diphenylacetylene (‘Dip’), or a novel phenyl-extended fluorophore (‘Trip’) were made using a reliable, modular synthesis. The final compounds were prepared in a total of 5 to 11 steps from commercial materials in yields ranging from 10 to 40%. The compounds’ activity varied considerably; both highly active and completely inactive compounds were discovered. The differences in activity are controlled by structure via the influence of structural variables on the aqueous phase aggregation and the ability of the compound to insert into the bilayer membrane. These structure-activity studies uncovered two highly-active ion transporters, HO2C-Hex-Dip-Hex-Hex-OH and –OPO32- (Hex = 6-hydroxyhexanoyl) which exhibited activity almost 10-fold higher than the fully-saturated oligoesters developed in previous work. In some cases, the transport activity is initially high but declines over a period of 20-30 minutes following compound addition. This suggests that the compound slowly transitions to an environment where it cannot form active channels. In the bilayer clamp, a variety of behaviours including highly-conducting openings were observed. An apparent voltage-gated response was exhibited by one of the Trip compounds (HO2C-Trip-G(E3)-OH), a property rarely seen for synthetic ion channels. The Dip and Trip molecules exhibited environment-sensitive fluorescence. The observed Dip excimer-like emission is the second reported instance of this in solution. The Trip compounds are solvatochromic; this property was used to infer their location in the membrane. Partitioning into the membrane was followed by a blue-shifting and increased intensity of the fluorescence emission for both series of compounds. For the Trip isomers, which are significantly more emissive than the Dip molecules, this enhancement in intensity could be visualized by eye. For the Dip oligomers, the excimer emission is a broad band with variable shape and intensity; it is time-dependent under some conditions. The excimer emission has a sub-nanosecond lifetime in homogenous solution that is significantly prolonged in the presence of vesicle bilayers, in which a number of lifetimes could be detected. Both monomer and excimer emissions can be quenched by aqueous copper, the excimer emission is more efficiently quenched than is the monomer. The photophysical characteristics of these molecules allowed for a variety of experiments designed to probe their membrane partitioning and localization behaviours. The results indicate the formation of a complex mixture of interconverting monomeric and aggregate species as the compounds move from water to the bilayer. The slow evolution of the mixture is consistent with the times noted for loss of membrane activity in transport assays. From these data a new model that describes the transport process is proposed. The key feature of this model is that transport must occur via a species that forms quickly upon the mixing of the components. Possible structures of the intermediates formed are discussed. / Graduate
290

Syntaxin-1A Inhibits Cardiac ATP-Sensitive Potassium Channels by Direct Interaction with Distinct Domains within Sulphonylurea Receptor 2A Nucleotide-Binding Folds

Chao, Christin Chih Ting 13 January 2010 (has links)
KATP channels couple cell metabolic status to the membrane excitability by sensing the cytoplasmic ATP/ADP ratio. Present studies examined how conserved motifs (Walker A (WA), signature sequence (L), and Walker B (WB)) within each NBF of SUR2A bind to Syn-1A to affect its actions on cardiac KATP channels. In vitro binding experiments illustrated that Syn-1A binds cardiac SUR2A at WA and L of NBF-1 and WA, L, and WB of NBF-2. Electrophysiology experiments on stably expressing SUR2A/Kir6.2 cell-lines showed that only L and WB of NBF-1 and all three NBF-2 motifs could abrogate the inhibitory effect of Syn-1A on SUR2A/KATP channels. These results lead me to hypothesize that more independent motif in NBF-2 can bind and abrogate Syn-1A’s inhibition than NBF-1 on SUR2A/KATP channels. A corollary postulate is that Syn-1A acts as a scaffold to secure the NBF-1 and -2 in dimer conformation required for SUR2A to modulate Kir6.2 gating.

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