High resolution wide field surface plasmon microscopy

This thesis presents the development of a high resolution wide field speckle illuminated interferometric surface plasmon microscope. This system is based on a Linnik interferometer and uses a high NA oil immersion objective for the excitation of surface plasmons. The confocal response of the microscope and high surface field enhancement due to surface plasmon excitation lead to high resolution and high contrast of weak surface structures and films. The microscope was also demonstrated in two other modes of operation, a sensing mode where the distributions seen in the back focal plane of the sample objective could be used to determine the optical parameters of the sample and a conventional surface plasmon microscope mode where image enhancement was created through the use of polarizers and optical masks. Results are presented that show the microscope as capable of imaging results comparable or better than that in the literature and without the need to scan. Hence the system is shown to be wholly suitable to biological and research fields interested in thin films and surface reactions

High resolution wide field surface plasmon microscopy

This thesis presents the development of a high resolution wide field speckle illuminated interferometric surface plasmon microscope. This system is based on a Linnik interferometer and uses a high NA oil immersion objective for the excitation of surface plasmons. The confocal response of the microscope and high surface field enhancement due to surface plasmon excitation lead to high resolution and high contrast of weak surface structures and films. The microscope was also demonstrated in two other modes of operation, a sensing mode where the distributions seen in the back focal plane of the sample objective could be used to determine the optical parameters of the sample and a conventional surface plasmon microscope mode where image enhancement was created through the use of polarizers and optical masks. Results are presented that show the microscope as capable of imaging results comparable or better than that in the literature and without the need to scan. Hence the system is shown to be wholly suitable to biological and research fields interested in thin films and surface reactions

Air transport liberalisation and airport dependency: developing a composite index

Air transport liberalisation in Europe has produced some major changes to the networks operated by airlines and the services available at airports. Within this context the degree of airport dependency in terms of market, spatial and temporal concentration is important to know from an economic geography and risk management perspective. A composite index called the Airport Dependency Index (ADI) is developed to measure airport dependency based on the concept of the relative Gini coefficient. Liberalisation has had varying impacts depending on the size and type of airport and so a comparison is made of the degree of dependency at a large sample of European airports using the ADI. The ADI has the potential to provide insight on the sustainability and worthiness of financing airport projects, and on whether airports should diversify further their activities by investing in the growth and expansion of their network

Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium

A genome comparison of non-epidemic and epidemic strains of Clostridium difficile reveals gene gains that could explain how a hypervirulent strain has emerge

The Heat Shock Response of Mycobacterium Tuberculosis: Linking Gene Expression, Immunology and Pathogenesis

The regulation of heat shock protein (HSP) expression is critically important to pathogens such as Mycobacterium tuberculosis and dysregulation of the heat shock response results in increased immune recognition of the bacterium and reduced survival during chronic infection. In this study we use a whole genome spotted microarray to characterize the heat shock response of M. tuberculosis. We also begin a dissection of this important stress response by generating deletion mutants that lack specific transcriptional regulators and examining their transcriptional profiles under different stresses. Understanding the stimuli and mechanisms that govern heat shock in mycobacteria will allow us to relate observed in vivo expression patterns of HSPs to particular stresses and physiological conditions. The mechanisms controlling HSP expression also make attractive drug targets as part of a strategy designed to enhance immune recognition of the bacterium

Semiquantitative Analysis of Clinical Heat Stress in Clostridium difficile Strain 630 Using a GeLC/MS Workflow with emPAI Quantitation.

<div><p><i>Clostridium difficile</i> is considered to be the most frequent cause of infectious bacterial diarrhoea in hospitals worldwide yet its adaptive ability remains relatively uncharacterised. Here, we used GeLC/MS and the exponentially modified protein abundance index (emPAI) calculation to determine proteomic changes in response to a clinically relevant heat stress. Reproducibility between both biological and technical replicates was good, and a 37°C proteome of 224 proteins was complemented by a 41°C proteome of 202 proteins at a 1% false discovery rate. Overall, 236 <i>C. difficile</i> proteins were identified and functionally categorised, of which 178 were available for comparative purposes. A total of 65 proteins (37%) were modulated by 1.5-fold or more at 41°C compared to 37°C and we noted changes in the majority of proteins associated with amino acid metabolism, including upregulation of the reductive branch of the leucine fermentation pathway. Motility was reduced at 41°C as evidenced by a 2.7 fold decrease in the flagellar filament protein, FliC, and a global increase in proteins associated with detoxification and adaptation to atypical conditions was observed, concomitant with decreases in proteins mediating transcriptional elongation and the initiation of protein synthesis. Trigger factor was down regulated by almost 5-fold. We propose that under heat stress, titration of the GroESL and dnaJK/grpE chaperones by misfolded proteins will, in the absence of trigger factor, prevent nascent chains from emerging efficiently from the ribosome causing translational stalling and also an increase in secretion. The current work has thus allowed development of a heat stress model for the key cellular processes of protein folding and export.</p></div

Exile

Byron rehearsed going into exile in 1809, when he was twenty-one years old. Before setting sail for Lisbon, he wrote, “I leave England without regret, I shall return to it without pleasure. – I am like Adam the first convict sentenced to transportation, but I have no Eve, and have eaten no apple but what was sour as a crab and thus ends my first Chapter” (BLJ 1: 211). Byron’s sardonic perception of himself as a biblical exile foreshadowed the allusive character of his second longer-term exile at the age of twenty-eight, when his carefully staged exit required an audience (some of the same friends and servants), expensive props (a replica of Napoleon’s carriage) and a literary precursor. On his last evening in England, Byron visited the burial place of the satirist Charles Churchill, and lay down on his grave. It was a performance of immense weariness with life and solidarity with an embittered outcast.Postprin

The Lake Poets

“If Southey had not been comparatively good,” writes Herbert F. Tucker, “he would never have drawn out Byron’s best in those satirical volleys that were undertaken, at bottom, in order to reprehend not the want of talent but its wastage.” And if Wordsworth and Coleridge had not been dangerously talented, Byron might have spared them some of his stinging sallies. In Table Talk Coleridge proclaimed the conclusion of the “intellectual war” Byron threatened in Don Juan (XI. 62: 496), declaring Wordsworth the poet who “will wear the crown,” triumphing over Byron and his ilk for the poetic laurels of the Romantic period. But Byron was not simply an opponent of his contemporaries. His responses to the Lake poets, particularly to Wordsworth, ran the gamut from “reverence” (HVSV, 129) then “nausea” (Medwin, 237) to Don Juan’s comical though cutting disdain, in under a decade. Focusing on Byron’s relationship with Wordsworth and Coleridge, I will show how Byron’s poetry and drama reveal the range and complexity of his dialogue with his older peers, where, even at their most apparently divergent, the conversation between the poets reveals the depth of the engagement across their works

Gene-enhanced tissue engineering for dental hard tissue regeneration: (1) overview and practical considerations

Gene-based therapies for tissue regeneration involve delivering a specific gene to a target tissue with the goal of changing the phenotype or protein expression profile of the recipient cell; the ultimate goal being to form specific tissues required for regeneration. One of the principal advantages of this approach is that it provides for a sustained delivery of physiologic levels of the growth factor of interest. This manuscript will review the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. Part 2 will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries