979 resultados para Single Site


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Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binds a 21-nucleotide myelin basic protein mRNA response element, the A2RE, and A2RE-like sequences in other localized mRNAs, and is a trans-acting factor in oligodendrocyte cytoplasmic RNA trafficking. Recombinant human hnRNPs A1 and A2 were used in a biosensor to explore interactions with A2RE and the cognate oligodeoxyribonucleotide. Both proteins have a single site that bound oligonucleotides with markedly different sequences but did not bind in the presence of heparin. Both also possess a second, specific site that bound only A2RE and was unaffected by heparin, hnRNP A2 bound A2RE in the latter site with a K-d near 50 nM, whereas the K-d for hnRNP A1 was above 10 muM. UV cross-linking assays led to a similar conclusion. Mutant A2RE sequences, that in earlier qualitative studies appeared not to bind hnRNP A2 or support RNA trafficking in oligodendrocytes, had dissociation constants above 5 muM for this protein. The two concatenated RNA recognition motifs (RRMs), but not the individual RRMs, mimicked the binding behavior of hnRNP A2. These data highlight the specificity of the interaction of A2RE with these hnRNPs and suggest that the sequence-specific A2RE-binding site on hnRNP A2 is formed by both RRMs acting in cis.

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Os avanços realizados nas técnicas cirúrgicas têm permitido que o tempo de recuperação outrora contado em dias ou até semanas tenha sido reduzido para horas, com os pacientes a saírem do hospital pelo seu próprio pé pouco tempo após a intervenção. Tal resulta numa redução do tempo de recuperação, menos desconforto para o paciente e consequente redução dos custos associados ao internamento. A redução nos tempos de recuperação é fundamentalmente devida às técnicas cirúrgicas minimamente invasivas que assentam sobretudo na utilização de instrumentos laparoscópicos. A anestesia é agora muitas vezes local ou apenas uma sedação, ficando o paciente sob efeito da anestesia durante um período menor quando comparado com as técnicas tradicionais. O desenvolvimento de dispositivos laparoscópicos que permitam ao cirurgião maior manobrabilidade associada a uma atuação simples, sem os movimentos invertidos inerentes aos instrumentos tradicionais, irão permitir realizar intervenções que outrora seriam realizadas com as técnicas tradicionais, de forma segura e menos intrusiva reduzindo o risco de complicações pós-operatórias. Os dispositivos laparoscópicos mais avançados associados a certas técnicas cirúrgicas, permitem a realização de intervenções complexas e de grande minucia através de apenas um orifício LESS (Laparoendoscopic single-site surgery), ou no caso de ser realizada com robô, R-LESS (Robotic laparoendoscopic single-site surgery); reduzindo de forma ainda mais acentuada o tempo de recuperação e o tamanho da cicatriz. O aumento da manobrabilidade dos dispositivos laparoscópicos é obtida através da inclusão de sistemas eletromecânicos relativamente complexos que tentam transpor o movimento da mão para a pinça dentro do paciente. No entanto, a adição destes sistemas podem tornar a manipulação desses dispositivos pouco intuitiva e pouco ergonómica, sobretudo se forem usados com apenas uma das mãos. Por outro lado, quando a atuação deixa de ser realizada de forma puramente mecânica e direta o cirurgião perde sensibilidade da força que está a ser exercida pelo dispositivo já que esta passa a ser efetuada através de um sistema assistido, como por exemplo motores elétricos, sistemas hidráulicos ou pneumáticos. Estes fatores resultam que a aceitação destes dispositivos pelos cirurgiões não tenha sido fácil. Para contornar este problema, o dispositivo desenvolvido para além de grande capacidade de manobra, oferece atuação natural e portabilidade. Contempla uma componente háptica de atuação hidráulica que ajudará o cirurgião a melhor perceci-onar o que se passa na ponta da pinça. Como o movimento da pinça é controlado por um sistema eletromecânico é possível escalonar a amplitude do movimento de entrada e reduzir o tremor fisiológico das mãos. A pinça e respetiva haste é convencional podendo ser usados os trocarts já existentes. Foi desenvolvido um protótipo virtual com todos os componentes necessários para um funcionamento integral. No então não foram realizados protótipos físicos de todos os componentes, nem se sabe como os diferentes módulos interagem entre si.

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1 The L6 myocyte cell line expresses high affinity receptors for calcitonin gene-related peptide (CGRP) which are coupled to activation of adenylyl cyclase. The biochemical pharmacology of these receptors has been examined by radioligand binding or adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. 2 In intact cells at 37 degrees C, human and rat alpha- and beta-CGRP all activated adenylyl cyclase with EC50s of about 1.5 nM. A number of CGRP analogues containing up to five amino acid substitutions showed similar potencies. In membrane binding studies at 22 degrees C in 1 mM Mg2+, the above all bound to a single site with IC50s of 0.1-0.4 nM. 3 The fragment CGRP(8-37) acted as a competitive antagonist of CGRP stimulation of adenylyl cyclase with a calculated Kd of 5 nM. The Kd determined in membrane binding assays was lower (0.5 nM). 4 The N-terminal extended human alpha-CGRP analogue Tyro-CGRP activated adenylyl cyclase and inhibited [125I]-iodohistidyl-CGRP binding less potently than human alpha-CGRP (EC50 for cyclase = 12 nM, IC50 for binding = 4 nM). 5 The pharmacological profile of the L6 CGRP receptor suggests that it most closely resembles sites on skeletal muscle, cardiac myocytes and hepatocytes. The L6 cell line should be a stable homogeneous model system in which to study CGRP mechanisms and pharmacology."

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Purpose: This paper aims to describe an investigation into how company performance can be improved by integrating internal and external customers and technology. The approach was developed, implemented and evaluated in the operations of the building components industry. The research was carried out in the precast concrete division of a Singapore company. Design/methodology/ approach: For the purpose of undertaking the investigation an exploratory case study approach was used. This was divided into conceptual and action research stages. The action research was also used to implement the changes in the company. Questionnaire surveys were carried out among company employees and external customers to assess the effect of these changes. Results of the investigation were derived using content and statistical analysis. Triangulation between three sources was used for validating the data. Findings: The exploratory case study strategy resulted in rich research data, which provided evidence of the changes taking place and integration happening, leading to improved performance. The action research approach proved a powerful tool where the uncertainty of outcomes makes it near impossible to make accurate forecasts. Another output of the research was the development of an "integrated customer orientation" (ICO) model. Research limitations/implications: The research in this paper used a single site action research investigation so should be interpreted within the specific company and industry context. There are implications for theory and practice in a number of areas of production and marketing as well as contributions to understanding about productivity improvement and organisational development. The investigation also fulfils the dual objectives of action research by contributing to both knowledge and practice. Originality/value: The paper describes a unique approach towards improving productivity, quality and service through the use of action research to implement changes, as well as providing the research evidence to evaluate both the process of implementation and results achieved. © Emerald Group Publishing Limited.

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A comparison of medicines management documents in use by NHS organisations in the West Midlands confirms that there are important differences between the primary care and hospital sectors in respect to medicines management interface issues. Of these, two aspects important to paediatric patients have been studied. These are the transfer of information as a patient is admitted to hospital, and access to long-term medicines for home-patients. National guidance provided by NICE requires medication reconciliation to be undertaken on admission to hospital for adults. A study of paediatric admissions, reported in this thesis, demonstrates that the clinical importance of this process is at least as important for children as for adults, and challenges current UK guidance. The transfer of essential medication information on hospital admission is central to the medication reconciliation process. Two surveys of PCTs in 2007 and again in 2009 demonstrate that very few PCTs provide guidance to GPs to support this process. Provision of guidance is increasing slowly but remains the exception. The provision of long-term medicines for children at home is hindered by this patient population often needing unlicensed drugs. Further studies demonstrate that primary care processes regularly fail to maintain access to essential drugs and patients and their carers frequently turn to hospitals for help. Surveys of hospital medical staff (single site) and hospital nurses (six UK sites) demonstrates the activity these healthcare workers perform to help children get the medicines they need. A similar survey of why carers turn to a hospital pharmacy department for urgent supplies (usually termed rescue-medicines) adds to the understanding of these problems and supports identifying service changes. A large survey of community pharmacies demonstrates the difficulties they have when dispensing hospital prescriptions and identifies practical solutions. This programme concludes by recommending service changes to support medication management for children.

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We introduce models of heterogeneous systems with finite connectivity defined on random graphs to capture finite-coordination effects on the low-temperature behaviour of finite-dimensional systems. Our models use a description in terms of small deviations of particle coordinates from a set of reference positions, particularly appropriate for the description of low-temperature phenomena. A Born-von Karman-type expansion with random coefficients is used to model effects of frozen heterogeneities. The key quantity appearing in the theoretical description is a full distribution of effective single-site potentials which needs to be determined self-consistently. If microscopic interactions are harmonic, the effective single-site potentials turn out to be harmonic as well, and the distribution of these single-site potentials is equivalent to a distribution of localization lengths used earlier in the description of chemical gels. For structural glasses characterized by frustration and anharmonicities in the microscopic interactions, the distribution of single-site potentials involves anharmonicities of all orders, and both single-well and double-well potentials are observed, the latter with a broad spectrum of barrier heights. The appearance of glassy phases at low temperatures is marked by the appearance of asymmetries in the distribution of single-site potentials, as previously observed for fully connected systems. Double-well potentials with a broad spectrum of barrier heights and asymmetries would give rise to the well-known universal glassy low-temperature anomalies when quantum effects are taken into account. © 2007 IOP Publishing Ltd.

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Foley [J. Opt. Soc. Am. A 11 (1994) 1710] has proposed an influential psychophysical model of masking in which mask components in a contrast gain pool are raised to an exponent before summation and divisive inhibition. We tested this summation rule in experiments in which contrast detection thresholds were measured for a vertical 1 c/deg (or 2 c/deg) sine-wave component in the presence of a 3 c/deg (or 6 c/deg) mask that had either a single component oriented at -45° or a pair of components oriented at ±45°. Contrary to the predictions of Foley's model 3, we found that for masks of moderate contrast and above, threshold elevation was predicted by linear summation of the mask components in the inhibitory stage of the contrast gain pool. We built this feature into two new models, referred to as the early adaptation model and the hybrid model. In the early adaptation model, contrast adaptation controls a threshold-like nonlinearity on the output of otherwise linear pathways that provide the excitatory and inhibitory inputs to a gain control stage. The hybrid model involves nonlinear and nonadaptable routes to excitatory and inhibitory stages as well as an adaptable linear route. With only six free parameters, both models provide excellent fits to the masking and adaptation data of Foley and Chen [Vision Res. 37 (1997) 2779] but unlike Foley and Chen's model, are able to do so with only one adaptation parameter. However, only the hybrid model is able to capture the features of Foley's (1994) pedestal plus orthogonal fixed mask data. We conclude that (1) linear summation of inhibitory components is a feature of contrast masking, and (2) that the main aftereffect of spatial adaptation on contrast increment thresholds can be assigned to a single site. © 2002 Elsevier Science Ltd. All rights reserved.

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The civil engineering industry generally regards new methods and technology with a high amount of scepticism, preferring to use traditional and trusted methods. During the 1980s competition for civil engineering consultancy work in the world has become fierce. Halcrow recognised the need to maintain and improve their competitive edge over other consultants. The use of new technology in the form of microcomputers was seen to be one method to maintain and improve their repuation in the world. This thesis examines the role of microcomputers in civil engineering consultancy with particular reference to overseas projects. The involvement of civil engineers with computers, both past and present, has been investigated and a survey of the use of microcomputers by consultancies was carried out, the results are presented and analysed. A resume of the state-of-the-art of microcomputer technology was made. Various case studies were carried out in order to examine the feasibility of using microcomputers on overseas projects. One case study involved the examination of two projects in Bangladesh and is used to illustrate the requirements and problems encountered in such situations. Two programming applications were undertaken, a dynamic programming model of a single site reservoir and the simulation of the Bangladesh gas grid system. A cost-benefit analysis of a water resources project using microcomputers in the Aguan Valley, Honduras was carried out. Although the initial cost of microcomputers is often small, the overall costs can prove to be very high and are likely to exceed the costs of traditional computer methods. A planned approach for the use of microcomputers is essential in order to reap the expected benefits and recommendations for the implementation of such an approach are presented.

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Background - It is well recognised that errors are more likely to occur during transitions of care, especially medicines errors. Clinic letters are used as a communication tool during a transition from hospital (outpatient clinics) to primary care (general practitioners). Little is known about medicines errors in clinic letters, as previous studies in this area have focused on medicines errors in inpatient or outpatient prescriptions. Published studies concerning clinic letters largely focus on perceptions of patients or general practitioners in respect to overall quality. Purpose - To investigate medicines errors contained in outpatient clinic letters generated by prescribers within the Neurology Department of a specialist paediatric hospital in the UK.Materials and methods - Single site, retrospective, cross-sectional review of 100 clinic letters generated during March–July 2013 in response to an outpatient consultation. Clinic letters were conveniently selected from the most recent visit of each patient. An evaluation tool with a 10-point scale, where 10 was no error and 0 was significant error, was developed and refined throughout the study to facilitate identification and characterisation of medicines errors. The tool was tested for a relationship between scores and number of medicines errors using a regression analysis.Results - Of 315 items related to neurology mentioned within the letters, 212 items were associated with 602 errors. Common missing information was allergy (97%, n = 97), formulation (60.3%, n = 190), strength/concentration (59%, n = 186) and weight (53%, n = 53). Ninety-nine letters were associated with at least one error. Scores were in range of 4–10 with 42% of letters scored as 7. Statistically significant relationships were observed between scores and number of medicines errors (R2 = 0.4168, p < 0.05) as well as between number of medicines and number of drug-related errors (R2 = 0.9719, p < 0.05). Conclusions - Nearly all clinic letters were associated with medicines errors. The 10-point evaluation tool may be a useful device to categorise clinic letter errors.

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A University of Hawaii oceanographic cruise, Abyssal Hills 69, with the R/V Mahi, was carried out to study the association of manganese nodules with an abyssal hill. Manganese nodules from three dredge hauls on an abyssal hill located at 36°W and 157°W exhibited differences in morphology and composition between stations only three miles apart. The morphology of the nodules suggests that nodules from a single site have similar morphologies because they began growth at the same time, probably because of a volcanic event. Differences in morphology between stations indicate a local supply of elements. Atomic absorption analysis for manganese, iron, cobalt, nickel, and copper revealed that nodules nearest to a probable fault line and source of volcanism have a, lower manganese to iron ratio than nodules farther removed. This finding supports the theory that volcanism contributes to the formation of some nodules. Additional evidence showing association with volcanism consists of volcanic nuclei in nodules, crusts formed on layers of volcanic ash, and basalt encrusted to various degrees. The variation in cobalt, nickel, and copper contents Gt the nodules from a single dredge is two-to threefold, but iron content is more uniiorm. Four of the six cores from the area increased in manganese concentration with depth, suggesting that diffusion is concentrating manganese in the upper zone of the sediments or in nodules. The author concludes that volcanism is contributing to the formation of nodules by supplying nuclei and transition elements, but is not necessary for the formation of manganese nodules.

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Live (Rose Bengal stained) and dead benthic foraminifera of surface and subsurface sediments from 25 stations in the eastern South Atlantic Ocean and the Atlantic sector of the Southern Ocean were analyzed to decipher a potential influence of seasonally and spatially varying high primary productivity on the stable carbon isotopic composition of foraminiferal tests. Therefore, stations were chosen so that productivity strongly varied, whereas conservative water mass properties changed only little. To define the stable carbon isotopic composition of dissolved inorganic carbon (d13CDIC) in ambient water masses, we compiled new and previously published d13CDIC data in a section running from Antarctica through Agulhas, Cape and Angola Basins, via the Guinea Abyssal Plain to the Equator. We found that intraspecific d13C variability of all species at a single site is constantly low throughout their distribution within the sediments, i.e. species specific and site dependent mean values calculated from all subbottom depths on average only varied by +/-0.09 per mil. This is important because it makes the stable carbon isotopic signal of species independent of the particular microhabitat of each single specimen measured and thus more constant and reliable than has been previously assumed. So-called vital and/or microhabitat effects were further quantified: (1) d13C values of endobenthic Globobulimina affinis, Fursenkoina mexicana, and Bulimina mexicana consistently are by between -1.5 and -1.0 per mil VPDB more depleted than d13C values of preferentially epibenthic Fontbotia wuellerstorfi, Cibicidoides pachyderma, and Lobatula lobatula. (2) In contrast to the Antarctic Polar Front region, at all stations except one on the African continental slope Fontbotia wuellerstorfi records bottom water d13CDIC values without significant offset, whereas L. lobatula and C. pachyderma values deviate from bottom water values by about -0.4 per mil and -0.6 per mil, respectively. This adds to the growing amount of data on contrasting cibicid d13C values which on the one hand support the original 1:1-calibration of F. wuellerstorfi and bottom water d13CDIC, and on the other hand document severe depletions of taxonomically close relatives such as L. lobatula and C. pachyderma. At one station close to Bouvet Island at the western rim of Agulhas Basin, we interpret the offset of -1.5 per mil between bottom water d13CDIC and d13C values of infaunal living Bulimina aculeata in contrast to about -0.6 +/- 0.1 per mil measured at eight stations close-by, as a direct reflection of locally increased organic matter fluxes and sedimentation rates. Alternatively, we speculate that methane locally released from gas vents and related to hydrothermal venting at the mid-ocean ridge might have caused this strong depletion of 13C in the benthic foraminiferal carbon isotopic composition. Along the African continental margin, offsets between deep infaunal Globobulimina affinis and epibenthic Fontbotia wuellerstorfi as well as between shallow infaunal Uvigerina peregrina and F. wuellerstorfi, d13C values tend to increase with generally increasing organic matter decomposition rates. Although clearly more data are needed, these offsets between species might be used for quantification of biogeochemical paleogradients within the sediment and thus paleocarbon flux estimates. Furthermore, our data suggest that in high-productivity areas where sedimentary carbonate contents are lower than 15 weight %, epibenthic and endobenthic foraminiferal d13C values are strongly influenced by 13C enrichment probably due to carbonate-ion undersaturation, whereas above this sedimentary carbonate threshold endobenthic d13C values reflect depleted pore water d13CDIC values.

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The amphibian temporins, amongst the smallest antimicrobial peptides (AMPs), are α-helical, amphipathic, hydrophobic and cationic and are active mainly against Gram-positive bacteria but inactive or weakly active against Gram-negative bacteria. Here, we report two novel members of the temporin family, named temporin-1Ee (FLPVIAGVLSKLFamide) and temporin-1Re (FLPGLLAGLLamide), whose biosynthetic precursor structures were deduced from clones obtained from skin secretion-derived cDNA libraries of the European edible frog, Pelophylax kl. esculentus, by ‘shotgun’ cloning. Deduction of the molecular masses of each mature processed peptide from respective cloned cDNAs was used to locate respective molecules in reverse-phase HPLC fractions of secretion. Temporin-1Ee (MIC = 10 μM) and temporin-1Re (MIC = 60 μM) were both found to be active against Gram-positive Staphylococcus aureus, but retaining a weak haemolytic activity. To our knowledge, Single-site substitutions can dramatically change the spectrum of activity of a given temporin. Compared with temporine-1Ec, just one chemically-conservative substitution (Val8 instead of Leu8), temporin-1Ee bearing a net charge of +2 displays broad-spectrum activity with particularly high potency on the clinically relevant Gram-negative strains, Escherichia coli (MIC = 40 μM). These factors bode well for translating temporins to be potential drug candidates for the design of new and valuable anti-infective agents.

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Although health policy would suggest that day surgery is the best service for patients undergoing a surgical procedure, it is important to consider the patient and whether this type of service is what they want. This information can be generated through a service evaluation with the results used to inform local decision-making, changes to care delivery and improvements in patient care. This article describes the results of a service evaluation performed in a single-site day surgery unit.

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Une caractéristique intéressante de la protéine Bcl-xL est la présence d'un domaine en boucle non-structurée entre les hélices α1 and α2 de la protéine. Ce domaine protéique n'est pas essentiel pour sa fonction anti-apoptotique et absent chez CED-9, la protéine orthologue chez Caenorhabditis elegans. A l'intérieur de ce domaine, Bcl-xL subit une phosphorylation et déphosphorylation dynamique sur les résidus Ser49 et Ser62 en phase G2 du cycle cellulaire et lors de la mitose. Lorsque ces résidus sont mutés et les protéines exprimées dans des cellules cancéreuses, les cellules démontrent plusieurs défauts mitotiques liés à l'instabilité chromosomique. Pour analyser les effets de Bcl-xL Ser49 et Ser62 dans les cellules normales, les présentes études ont été réalisées dans des cellules diploïdes humaines normales, et in vivo chez Caenorhabditis elegans. Dans une première étude, nous avons utilisé la lignée cellulaire de cellules fibroblastiques diploïdes humaines normales BJ, exprimant Bcl-xL (type sauvage), (S49A), (S49D), (S62A), (S62D) et les double (S49/62A) et (S49/62D) mutants. Les cellules exprimant les mutants de phosphorylation ont montré des cinétiques de doublement de la population cellulaire réduites. Ces effets sur la cinétique de doublement de la population cellulaire corrèle avec l'apparition de la sénescence cellulaire, sans impact sur les taux de mort cellulaire. Ces cellules sénescentes affichent des phénotypes typiques de sénescence associés notamment à haut niveau de l'activité β-galactosidase associée à la sénescence, la sécrétion d' interleukine-6, l'activation de p53 et de p21WAF1/ Cip1, un inhibiteur des complexes kinase cycline-dépendant, ainsi que la formation de foyers de chromatine nucléaire associés à γH2A.X. Les analyses de fluorescence par hybridation in situ et des caryotypes par coloration au Giemsa ont révélé que l'expression des mutants de phosphorylation de Bcl-xL provoquent de l'instabilité chromosomique et l'aneuploïdie. Ces résultats suggèrent que les cycles de phosphorylation et déphosphorylation dynamiques de Bcl-xL Ser49 et Ser62 sont importants dans le maintien de l'intégrité des chromosomes lors de la mitose dans les cellules normales. Dans une deuxième étude, nous avons entrepris des expériences chez Caenorhabditis elegans pour comprendre l'importance des résidus Ser49 et Ser62 de Bcl-xL in vivo. Les vers transgéniques portant les mutations de Bcl-xL (S49A, S62A, S49D, S62D et S49/62A) ont été générés et leurs effets ont été analysés sur les cellules germinales des jeunes vers adultes. Les vers portant les mutations de Bcl-xL ont montré une diminution de ponte et d'éclosion des oeufs, des variations de la longueur de leurs régions mitotiques et des zones de transition, des anomalies chromosomiques à leur stade de diplotène, et une augmentation de l'apoptose des cellules germinales. Certaines de ces souches transgéniques, en particulier les variants Ser/Ala, ont également montré des variations de durée de vie par rapport aux vers témoins. Ces observations in vivo ont confirmé l'importance de Ser49 et Ser62 à l'intérieur du domaine à boucle de Bcl-xL pour le maintien de la stabilité chromosomique. Ces études auront une incidence sur les futures stratégies visant à développer et à identifier des composés qui pourraient cibler non seulement le domaine anti-apoptotique de la protéine Bcl-xL, mais aussi son domaine mitotique pour la thérapie du cancer.

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Access to new forms, conduct and practices of educational research remain elusive providing researchers stay within the narrow theoretical constructs-the static, single vista ofconventional research models. This dissertation presents the findings of an experimental study that aims to extend the discourse of educational research through a 'performative ethnographic analysis' by using a single-site case study approach. The case study is an analytical parody based on multiple discourse relevant to a 'new' and different approach to educational research so that a more comprehensive and complex process of reading and writing text becomes possible. Throughout this process, a generative methodology and interpretative base are anticipated to provide a metaphoric focus for a critical dialogue. The discourse informing the theoretical and interpretative base of the study include philosophy, science, visual arts, literary theory, critical postructuralist theory and theatre performance. The data are presented as a series of performance narratives in the form of socio-drama, interspersed with critical reflection that enables the researcher, the research participant and reader to become part ofa triadic construct. The findings from this study have major implications for informing contemporary educational research, as they demonstrate that by approaching research in 'new' and different ways, the researcher and the educational community have access to insights that are unavailable within the constraints of conventional models ofresearch.