7 resultados para external factors to the school

em Aston University Research Archive


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DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

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Data suggest that for TG2 to be secreted, an intact N-terminal FN binding site (for which TG2 has high affinity) is required, however interaction of TG2 with its high affinity binding partners presents both in the intracellular and extracellular space as well as with specific cell surface receptors may also be involved in this process. Using a site-directed mutagenesis approach, the effects of specific mutations of TG2 on its translocation to the cell surface and secretion into the ECM have been investigated. Mutations include those affecting FN binding (FN1), HSPGs binding (HS1, HS2) GTP/GDP binding site (GTP1, 2) as well as N-terminal and C-terminal domains (TG2 deletion mutants N, and C). By performing transglutaminase activity assays, cell surface protein biotinylation and verifying distribution of TG2 mutants in the ECM we demonstrated that one of the potential heparan sulfate binding site mutants (HS2 mutant) is secreted at the cell surface in a much reduced manner and is less deposited into the ECM than the HS1 mutant. The HS2 mutant showed a low affinity for binding to a heparin sepharose column demonstrating this mutation site may be a potential heparan binding site of TG2. Analogous peptides to this site were shown to have some efficiency in the inhibition of the binding of the FN-TG2 complex to cell surface heparan sulfates in a cell adhesion assay indicating the peptide to be representative of the novel heparin binding site within TG2. The GTP binding site mutants GTP1 and GTP2 exhibited low specific activity however, GTP2 showed more secretion to the cell surface in comparison to GTP1. The FN1 binding mutant did not greatly affect TG2 activity nor did it alter TG2 secretion at the cell surface and deposition into the ECM indicating that fibronectin binding at this site on the enzyme is not an important factor. Interestingly an intact N-terminus (?1-15) appeared to be essential for enzyme externalisation. Removal of the first 15 amino acids (N-terminal mutant) abolished TG2 secretion to the cell surface as well as deposition into the ECM. In addition it reduced the enzymes affinity for binding to heparin. In contrast, deletion of the C-terminal TG2 domain (?594-687) increased enzyme secretion to the cell surface. Consistent with the data presented in this thesis we speculate that TG2 must fulfill two requirements to be successfully secreted from cells. The findings indicate that the closed conformation of the enzyme as well as intact N-terminal tail and a novel HS binding site within the TG2 molecule are key elements for the enzyme’s localisation at the cell surface and its deposition into the extracellular matrix. The importance of understanding the interactions between TG2, heparan sulfates and other TG2 binding partners at the cell surface could have an impact on the design of novel strategies for enzyme inhibition which could be important in the control of extracellular TG2 related diseases.

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Coleridge, looking back at the end of the ‘long eighteenth century’, remarked that the whole of natural philosophy had been ‘electrified’ by advances in the understanding of electrical phenomena. In this paper I trace the way in which these advances affected contemporary ‘neurophysiology.’ At the beginning of the long eighteenth century, neurophysiology (in spite of Swammerdam’s and Glisson’s demonstrations to the contrary) was still understood largely in terms of hollow nerves and animal spirits. At the end of that period the researches of microscopists and electricians had convinced most medical men that the old understanding had to be replaced. Walsh, Patterson, John Hunter and others had described the electric organs of electric fish. Gray and Nollet had demonstrated that electricity was not merely static, but flowed. Franklin had alerted the world to atmospheric electricity. Galvani’s frog experiments were widely known. Volta had invented his ‘pile.’ But did ‘animal electricity’ exist and was it identical to the electricity physicists studied in the inanimate world? Was the brain a gland, as Malpighi’s researches seemed to confirm., and did it secrete electricity into the nervous system? The Monros (primus and secundus), William Cullen, Luigi Galvani, Alessandro Volta, Erasmus Darwin, Luigi Rolando and François Baillarger all had their own ideas. This paper reviews these ‘long-eighteenth century’ controversies with special reference to the Edinburgh medical school and the interaction between neurophysiology and physics.

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This thesis challenges the consensual scholarly expectation of low EU impact in Central Asia. In particular, it claims that by focusing predominantly on narrow, micro-level factors, the prevailing theoretical perspectives risk overlooking less obvious aspects of the EU?s power, including structural aspects, and thus tend to underestimate the EU?s leverage in the region. Therefore, the thesis argues that a more structurally integrative and holistic approach is needed to understand the EU?s power in the region. In responding to this need, the thesis introduces a conceptual tool, which it terms „transnational power over? (TNPO). Inspired by debates in IPE, in particular new realist and critical IPE perspectives, and combining these views with insights from neorealist, neo-institutionalist and constructivist approaches to EU external relations, the concept of TNPO is an analytically eclectic notion, which helps to assess the degree to which, in today?s globalised and interdependent world, the EU?s power over third countries derives from its control over a combination of material, institutional and ideational structures, making it difficult for the EU?s partners to resist the EU?s initiatives or to reject its offers. In order to trace and assess the mechanisms of EU impact across these three structures, the thesis constructs a toolbox, which centres on four analytical distinctions: (i) EU-driven versus domestically driven mechanisms, (ii) mechanisms based on rationalist logics of action versus mechanisms following constructivist logics of action, (iii) agent-based versus purely structural mechanisms of TNPO, and (iv) transnational and intergovernmental mechanisms of EU impact. Using qualitative research methodology, the thesis then applies the conceptual model to the case of EU-Central Asia. It finds that the EU?s power over Central Asia effectively derives from its control over a combination of material, institutional and ideational structures, including its position as a leader in trade and investment in the region, its (geo)strategic and security-related capabilities vis-à-vis Central Asia, as well as the relatively dense level of institutionalisation of its relations with the five countries and the positive image of the EU in Central Asia as a more neutral actor.

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Nuisance growths of Cladophora have been associated with eutrophication. A review of the literature, however, reveals a scarcity of relevant experimental growth studies. Sampling experimental streams reveals that the addition of sewage effluent to good quality water alters the flora from that dominated by Potamogetan crispus to one dominated by CLadophora. Spatial and temporal differences in biomass of taxa present are discussed in the context of accompanying physicochemical data. In laboratory batch culture, growth of unialgal C. glomerata was accompanied by elevation of medium pH - considered largely responsible for the poor growth in such culture. However, appropriate experimental conditions and indices of growth were selected and the effects of various herbicides assessed. Diquat and terbutryne were shown to possess algicidal activity towards Cladophora. A closed continuous culture apparatus was developed: growth proceeded through lag, logarithmic and linear phases. Inoculum size and medium flow rate had significant effects on growth, and were standardized. In continuous culture, specific growth rate increased linearly with increased duration of light per day, up to 24 hours, and increased light intensity, up to 6000 lux - the highest intensity tested. Comparison of field and laboratory results suggests that ammonia toxicity is attributable to the undissociated form. In the laboratory, 185 µg/1 undissociated ammoniacal nitrogen reduced specific growth rate to 50% of that at 10 µg/1 undissociated ammcniacal nitrogen. 0.077-1.057 mg/1 NO2-N had no significant effect on growth. 7.2-15.2 mg/1 NO3-N had no significant effect on specific growth rate. Neither was any nitrate/phosphate interaction significant. At 4.9 mg/1 PO4-1, specific growth rate was only 48% of that at 1.9 g/1 P04-P. The critical medium PO4-P concentration was <0.1 mg/i. Specific growth rate was reduced to 50% of that in natural water by 0.036 mgCu/l, 0.070 mgzn/1 and 1.03 mgPb/l. Metal uptake was evaluated.

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In the absence of adequate visual stimulation accommodation adopts an intermediate resting position, appropriately termed tonic accommodation (TA). A period of sustained fixation can modify the tonic resting position, and indicate the adaptation properties of TA. This thesis investigates various factors contributing to the accommodative response during sustained visual tasks, in particular the adaptation of TA. Objective infra-red optometry was chosen as the most effective method of measurement of accommodation. This technique was compared with other methods of measuring TA and the results found to be well correlated. The inhibitory sympathetic input to the ciliary muscle provides the facility to attenuate the magnitude and duration of adaptive changes in TA. This facility is, however, restricted to those individuals having relatively high levels of pre-task TA. Furthermore, the facility is augmented by substantial levels of concurrent parasympathetic activity. The imposition of mental effort can induce concurrent changes in TA which are predominantly positive and largely the result of an increase in parasympathetic innervation of the ciliary muscle although there is some evidence for sympathetic attentuation at higher levels of TA. In emmetropes sympathetic inhibition can modify the effect of mental effort on the steady-state accommodative response at near. Late-onset myopes (onset after the age of 15 years) have significantlylower values of TA then emmetropes. Similarly, late-onset myopes show lower values of steady-state accommodative response for nearstimuli. The imposition of mental effort induces concurrent increases in TA and steady-state accommodative response in the myopic group which are significantly greater than those for emmetropes. Estimates of TA made under bright empty-field conditions are well correlated with those made under darkroom conditions. The method by which the accommodative loop is opened has no significant effect on the magnitude and duration of post-task shifts in TA induced by a near vision task. Significant differences in the post-task shifts in TA induced by a near vision task exist between emmetropes and late-onset myopes, the post-task shifts being more sustained for the myopic group.