Teacher participation in school management : an analysis of some major issues, background factors, and the use of an attitude scale to study and compare teacher attitudes to participation

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Factors important to the secretion and matrix deposition of tissue transglutaminase

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.

'Animal electricity' in the long eighteenth century with special reference to the Edinburgh medical school

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.

Factors affecting the growth of Cladophora in relation to river pollution

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.

Factors affecting the accommodative response to sustained visual tasks

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.

Determining which factors influence the optimum multifocal contact lens correction for presbyopia

Presbyopia is a consequence of ageing and is therefore increasing inprevalence due to an increase in the ageing population. Of the many methods available to manage presbyopia, the use of contact lenses is indeed a tried and tested reversible option for those wishing to be spectacle free. Contact lens options to correct presbyopia include multifocal contact lenses and monovision.Several options have been available for many years with available guides to help choose multifocal contact lenses. However there is no comprehensive way to help the practitioner selecting the best option for an individual. An examination of the simplest way of predicting the most suitable multifocal lens for a patient will only enhance and add to the current evidence available. The purpose of the study was to determine the current use of presbyopic correction modalities in an optometric practice population in the UK and to evaluate and compare the optical performance of four silicone hydrogel soft multifocal contact lenses and to compare multifocal performance with contact lens monovision. The presbyopic practice cohort principal forms of refractive correction were distance spectacles (with near and intermediate vision providedby a variety of other forms of correction), varifocal spectacles and unaided distance with reading spectacles, with few patients wearing contact lenses as their primary correction modality. The results of the multifocal contact lens randomised controlled trial showed that there were only minor differences in corneal physiology between the lens options. Visual acuity differences were observed for distance targets, but only for low contrast letters and under mesopic lighting conditions. At closer distances between 20cm and 67cm, the defocus curves demonstrated that there were significant differences in acuity between lens designs (p < 0.001) and there was an interaction between the lens design and the level of defocus (p < 0.001). None of the lenses showed a clear near addition, perhaps due to their more aspheric rather than zoned design. As expected, stereoacuity was reduced with monovision compared with the multifocal contact lens designs, although there were some differences between the multifocal lens designs (p < 0.05). Reading speed did not differ between lens designs (F = 1.082, p = 0.368), whereas there was a significant difference in critical print size (F = 7.543, p < 0.001). Glare was quantified with a novel halometer and halo size was found to significantly differ between lenses(F = 4.101, p = 0.004). The rating of iPhone image clarity was significantly different between presbyopic corrections (p = 0.002) as was the Near Acuity Visual Questionnaire (NAVQ) rating of near performance (F = 3.730, p = 0.007).The pupil size did not alter with contact lens design (F = 1.614, p = 0.175), but was larger in the dominant eye (F = 5.489, p = 0.025). Pupil decentration relative to the optical axis did not alter with contact lens design (F = 0.777, p =0.542), but was also greater in the dominant eye (F = 9.917, p = 0.003). It was interesting to note that there was no difference in spherical aberrations induced between the contact lens designs (p > 0.05), with eye dominance (p > 0.05) oroptical component (ocular, corneal or internal: p > 0.05). In terms of subjective patient lens preference, 10 patients preferred monovision,12 Biofinity multifocal lens, 7 Purevision 2 for Presbyopia, 4 AirOptix multifocal and 2 Oasys multifocal contact lenses. However, there were no differences in demographic factors relating to lifestyle or personality, or physiological characteristics such as pupil size or ocular aberrations as measured at baseline,which would allow a practitioner to identify which lens modality the patient would prefer. In terms of the performance of patients with their preferred lens, it emerged that Biofinity multifocal lens preferring patients had a better high contrast acuity under photopic conditions, maintained their reading speed at smaller print sizes and subjectively rated iPhone clarity as better with this lens compared with the other lens designs trialled. Patients who preferred monovision had a lower acuity across a range of distances and a larger area of glare than those patients preferring other lens designs that was unexplained by the clinical metrics measured. However, it seemed that a complex interaction of aberrations may drive lens preference. New clinical tests or more diverse lens designs which may allow practitioners to prescribe patients the presbyopic contact lens option that will work best for them first time remains a hope for the future.