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Clostridium difficile: Infection and Immunity
Get PDFClostridium difficile is a Gram positive pathogen of significant importance in the UK, Europe and the USA. No vaccine has been developed and current treatments are focused on hospital management and the use of antibiotics. The disease is spread in hospitals in the spore form and the role of spores in C. difficile infecton is poorly understood. In this project spores of C. difficile have been characterised. The proteins from the outermost layers of the spore were identified and the genes cloned. Three of these surface proteins have unique enzymatic properties that maybe important for symptoms of disease. The ability of C. difficile spores to adhere to intestinal cells was found to be far greater than with live cells and through this we have identified that the spore may play an important role in colonisation. The regulation of spore coat gene expression during sporulation was also examined and temporal phases of genes expression identified. A major part of this project was to develop a mucosal vaccine to C. difficile. The approach used was to clone the C-terminus of toxin A onto the surface of Bacillus subtilis spores and use these recombinant spores to immunise mice and hamsters. We found that oral delivery of these spores conferred 75% protection to C. difficile infection in a hamster model of infection. Further, parenteral immunisation of the same antigens (toxin A and B) failed to generate mucosal responses and this showed that mucosal immunisation is critical for good protection. Finally, we found that antibodies to the C-terminus of toxin A were cross reactive to the C-terminus of toxin B. This showed that mucosal delivery of just the C-terminus of toxin A is sufficient to confer protection in an animal model of infection. The outcome of this work is that we have shown the parameters for successful immunisation and vaccination against C. difficile
Superconducting phase coherent electron transport in nano-engineered ferromagnetic vortices
Get PDFThis thesis presents an experimental study of the superconducting proximity effect in sub-micrometer sized ferromagnetic discs. Such discs belong to a class of mesoscopic ferromagnets intermediate between microscopic magnets with dimensions below about 10nm that behave as single giant spins and macroscopic structures that are larger than approximately 1 micrometer where domains are formed to minimise stray fields. The magnetic structure of mesoscopic magnets is strongly dependent on their geometric shape, allowing for purposeful engineering of magnetic structures using modern lithographic techniques. The ground magnetic state of mesoscopic ferromagnetic discs is the magnetic vortex where unusual time-asymmetric triplet superconductivity is predicted to exist and survive up to the non-magnetic coherence length, that is orders in magnitude larger than the ferromagnetic singlet coherence length. Magnetic Force Microscopy (MFM) was used to directly study the magnetic structure of the discs. To detect the proximity effect in the vortices, Andreev interferometers were used with normal parts replaced with mesoscopic ferromagnetic discs in the magnetic vortex state. The samples were fabricated using electron-beam lithography and a modified shadow evaporation technique developed within this project, allowing the whole structure to be made with highly precise alignment, without breaking vacuum and avoiding redundant ferromagnetic elements disturbing the magnetic vortices. Observations were made of superconducting phase periodic oscillations in the conductance of the Andreev interferometers. Such oscillations provide unambiguous evidence of phase coherent electron transport through the ferromagnetic vortex. Finally, further experiments are discussed that would provide a more detailed understanding of the long range proximity effect in SFS junctions
Don’t mention Europe: a study of the Europeanisation of party organisation in the British Labour Party, the French Socialist Party and the German Social Democratic Party.
Get PDFThis thesis examines how the British Labour Party, the French Socialist Party (PS) and the German Social Democratic Party (SPD) have ‘Europeanised’ their organisations in three different arenas: (1) in the electorate and party system; (2) in central government and parliament; and (3) in their internal procedures and activities. ‘Europeanisation’ is defined as ‘a shorthand term for a complex process whereby national actors (in this case, parties) adapt to, and also seek to shape, the trajectory of European integration in general, and EU policies and processes in particular’ (Bomberg: 2002, 32). The underlying argument is that social democratic parties have to respond to challenges created by the European Single Market, which demands the reduction of state subsidies, and by the Economic and Monetary Union (EMU), which sets limits to public spending. Social democratic parties are expected to react to these challenges by Europeanising their organisations.
This thesis draws on the academic literature, party documents and contemporary newspaper articles, together with insights gained from 70 semi-structured interviews with EU experts at the European and national levels.
The central claim is that Labour, the PS and SPD have not become as Europeanised as might have been supposed for three ostensibly pro-European parties. Whilst successive party leaderships have paid lip service to the increasing importance of European integration, their party organisations have barely been involved in the formulation of European policy. The findings have serious implications for the three parties and domestic politics in Britain, France and Germany, since the memberships lack the enthusiasm and expertise to lead well-informed, critical, Europeanised debates and election campaigns
Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy
No full textTissue-conserving surgery is used increasingly in cancer treatment. However, one of the main challenges in this type of surgery is the detection of tumor margins. Histopathology based on tissue sectioning and staining has been the gold standard for cancer diagnosis for more than a century. However, its use during tissue-conserving surgery is limited by time-consuming tissue preparation steps (1–2 h) and the diagnostic variability inherent in subjective image interpretation. Here, we demonstrate an integrated optical technique based on tissue autofluorescence imaging (high sensitivity and high speed but low specificity) and Raman scattering (high sensitivity and high specificity but low speed) that can overcome these limitations. Automated segmentation of autofluorescence images was used to select and prioritize the sampling points for Raman spectroscopy, which then was used to establish the diagnosis based on a spectral classification model (100% sensitivity, 92% specificity per spectrum). This automated sampling strategy allowed objective diagnosis of basal cell carcinoma in skin tissue samples excised during Mohs micrographic surgery faster than frozen section histopathology, and one or two orders of magnitude faster than previous techniques based on infrared or Raman microscopy. We also show that this technique can diagnose the presence or absence of tumors in unsectioned tissue layers, thus eliminating the need for tissue sectioning. This study demonstrates the potential of this technique to provide a rapid and objective intraoperative method to spare healthy tissue and reduce unnecessary surgery by determining whether tumor cells have been removed
Accountability and performance management systems within private and public sector organisational change processes
No full textThis paper examines organisational change processes that occur when accountability demands from powerful external stakeholders change. It investigates, firstly, whether these external accountability demands impact on the performance management systems of two different types of organisations. Secondly, it considers whether the goals for improved performance contained within the external accountability demands are realised. The paper derives its primary insights from analysing in-depth interviews with managers working in a private sector company and in public sector organisations. The analyses reveal complex organisational responses. In the public sector case study, the organisations tended to reorient their performance management systems towards the external accountability demands; whilst in the private sector organisation, pressures from falling share prices forced managers to focus their decision making on the preferred performance measures contained in shareholders’ accountability demands. However, whilst there is some evidence of performance management system changes, the desires for improved performance subsumed by the external accountability demands are not necessarily realised through the performance management system changes
An Exploration of the Identities and Gender Discourses of a Taiwanese Woman: A Case Study of a Working Mother
No full textThis exploratory study sets out to examine the identities of a Taiwanese woman in the 21st century. Adopting the case study as a research strategy, I probe into a working mother’s life story to understand firstly a Taiwanese working mother’s perspectives on her family roles as a wife, mother and daughter-in-law. Secondly, I investigate how social institutions, which transmit different and often-conflicting Confucian and non-Confucian “gender discourses” influence her identities. This thesis adopts narrative interviews as the major method to probe into the life story of a Taiwanese working mother. The dimensions of domestic work and childcare, verbal communication, marital sex and looking after parents-in-law are examined in order to understand how she has taken on gender discourses and developed identities through her contact with different social institutions. Informed by post-structuralism and feminist theories, I consider the Taiwanese working mother as an individual who has “agency”, meaning she recognizes and values her ability to use and integrate gender discourses into her sense of self through the process of self-attribution. My research results found that “differentiation” “reflection” and “reflexivity” are themes that play important roles in affecting how a Taiwanese working mother perceives herself as an individual and defines her social and family roles. The findings also show that a working mother is able to negotiate different gender discourses. Despite the influence of the Taiwanese Confucian gendered binary, her interactions with different social institutions, especially her native family, counselling services and women’s self-help groups, enable her to develop a sense of “who I am”. She is able to reflect on her life experiences and perceive gender discourses in a critical manner and thus take on gender discourses that she identifies with to develop her own identities
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