A study of the morphological development of some filamentous fungi in tower fermenter culture, with particular reference to Aspergillus niger

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

Strategy making process, its content and context in small professional football clubs

This thesis examines the phenomenon of strategy. Making as practised by small professional football clubs. The study was undertaken because football clubs were perceived to have problems with strategy-making and because it was believed that the specific circumstances of football clubs could be outside the range of views covered by conventional views of strategy-making. The characteristics of the club environment are its uncertainty and unpredictability, simultaneous competition and co--operation, strong regulations, and a not-for-profit orientation. Small clubs in particular face a constant struggle for financial viability and survival, due in part to split business and playing objectives. The study was designed to establish the extent and nature of the difficulties clubs experience with a view to preparing the way for creating practical guidance on ways to overcome them. Clearly, in order to survive in the long term, small professional football clubs require very effective strategic decisions. This study has addressed this issue by inquiring into the nature of strategy making for these organisations with the objective to establish the general direction in which the football clubs in question should be moving. As a result, the main research question to guide this investigation was determined as: Why do small professional football clubs have difficulties making strategies. The investigation was based on an analysis the concept of strategy and its elements, the strategic vision and objectives, the process by which strategic action comes about, the strategic action itself, and the context within which this action occurs. Data has been collected, analysed and interpreted in relation to each of these elements. Together with a wide variety of published material, 20 small football clubs have been sampled and personal interviews were conducted with board members of those clubs. The findings indicate that small football clubs do indeed experience considerable difficulties in making strategies, the reasons for which lie both in the characteristics of their competitive environment and their approaches to strategy-making. The competitive environment is characterised by a cartel-like structure with a high degree of regulation, high levels of uncertainty, little control over the core product or the production process, short-term business cycles and a close geographical link between a club with its local market. The management of clubs is characterised by the need to balance conflicting sporting and business objectives. Formal planning techniques are of little use in the small football club context as decision-making processes have a strong political character and the development of novel strategies is hindered by a strong conservative, industry paradigm and a lack of financial and managerial resources. It is concluded that there is no simple advice to be given to clubs, as they must re-examine the relationship between their playing and business objectives to create a unified and workable approach.

The evaluation and development of the lead authority partnership scheme as a central intervention strategy for health and safety enforcement by local authorities

The research comprises a suite of studies that examines and develops the Lead Authority Partnership Scheme (LAPS) as a central intervention strategy for health and safety by local authority (LA) enforcers. Partnership working is a regulatory concept that in recent years has become more popular but there has been little research conducted to investigate, explore and evaluate its practical application. The study reviewed two contrasting approaches to partnership working between LAs and businesses, both of which were intended to secure improvements in the consistency of enforcement by the regulators and in the health and safety management systems of the participating businesses. The first was a well-established and highly prescriptive approach that required a substantial resource commitment on the part of the LA responsible for conducting a safety management review (SMR) of the business. As a result of his evaluation of the existing ‘full SMR’ scheme, the author developed a second, more flexible approach to partnership working. The research framework was based upon a primarily qualitative methodology intended to investigate and explore the impact of the new flexible arrangements for partnership working. The findings from this study of the flexible development of the scheme were compared and contrasted with those from studies of the established ‘full SMR’ scheme. A substantial degree of triangulation was applied in an attempt to strengthen validity and broaden applicability of the research findings. Key informant interviews, participant observation, document/archive reviews, questionnaires and surveys all their particular part to play in the overall study. The findings from this research revealed that LAPS failed to deliver consistency of LA enforcement across multiple-outlet businesses and the LA enforced business sectors. Improvement was however apparent in the safety management systems of the businesses participating in LAPS. Trust between LA inspector and safety professional was key to the success of the partnerships as was the commitment of these key individuals. Competition for precious LA resources, the priority afforded to food safety over health and safety, the perceived high resource demands of LAPS, and the structure and culture of LAs were identified as significant barriers to LA participation. Flexible approaches, whilst addressing the resource issues, introduced some fresh concerns relating to credibility and delivery. Over and above the stated aims of the scheme, LAs and businesses had their own reasons for participation, notably the personal development of individuals and kudos for the organisation. The research has explored the wider implications for partnership working with the overall conclusion it is most appropriately seen as a strategic level element within a broader structured intervention strategy.

Teacher logs and interactive decision-making:a case study of contingencies in an EFL organizational culture and the implications for teacher development for part-time teachers

This is a case study of a program of native speaker part-time EFL (English as a Foreign Language) teachers in a junior college in Japan. It has grown out of a curiosity to ascertain how the teachers have formed and continue to maintain a coordinated program in what would seem to be a disadvantageous national context where as part-time foreign teachers they are expected to do little more than just teach a few classes of mainly oral English. This study investigates the organizational culture the teachers have formed for themselves within their staffroom, and looks at the implications of this for part-time teachers in such an environment. More specifically, the study highlights that central to the program is an interactive decision-making function engaged in by all the teachers which has not only created but also continually enables an identifiable staffroom culture. This organizational culture is contingent on college and staffroom conditions, program affordances such as shared class logs and curriculum sharing, and on the interactive decision-making itself. It is postulated that the contingencies formed in this created and continually creating shared world not only offer the teachers a proficient way to work in their severely time-constricted environment, but also provide them with fertile ground for the self-regulation of a thus created zone of covert staffroom ‘on-the-job’ teacher development.

Development of a multicellular co-culture model of normal and cystic fibrosis human airways in vitro

Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians and arises due to mutations in a chloride channel, called cystic fibrosis transmembrane conductance regulator. A hallmark of this disease is the chronic bacterial infection of the airways, which is usually, associated with pathogens such as Pseudomonas aeruginosa, S. aureus and recently becoming more prominent, B. cepacia. The excessive inflammatory response, which leads to irreversible lung damage, will in the long term lead to mortality of the patient at around the age of 40 years. Understanding the pathogenesis of CF currently relies on animal models, such as those employing genetically-modified mice, and on single cell culture models, which are grown either as polarised or non-polarised epithelium in vitro. Whilst these approaches partially enable the study of disease progression in CF, both types of models have inherent limitations. The overall aim of this thesis was to establish a multicellular co-culture model of normal and CF human airways in vitro, which helps to partially overcome these limitations and permits analysis of cell-to-cell communication in the airways. These models could then be used to examine the co-ordinated response of the airways to infection with relevant pathogens in order to validate this approach over animals/single cell models. Therefore epithelial cell lines of non-CF and CF background were employed in a co-culture model together with human pulmonary fibroblasts. Co-cultures were grown on collagen-coated permeable supports at air-liquid interface to promote epithelial cell differentiation. The models were characterised and essential features for investigating CF infections and inflammatory responses were investigated and analysed. A pseudostratified like epithelial cell layer was established at air liquid interface (ALI) of mono-and co-cultures and cell layer integrity was verified by tight junction (TJ) staining and transepithelial resistance measurements (TER). Mono- and co-cultures were also found to secrete the airway mucin MUC5AC. Influence of bacterial infections was found to be most challenging when intact S. aureus, B. cepacia and P. aeruginosa were used. CF mono- and co-cultures were found to mimic the hyperinflammatory state found in CF, which was confirmed by analysing IL-8 secretions of these models. These co-culture models will help to elucidate the role fibroblasts play in the inflammatory response to bacteria and will provide a useful testing platform to further investigate the dysregulated airway responses seen in CF.

Development of a co-culture model of the human lungs for toxicity testing and identification of biomarkers of inhalation toxicity

The airway epithelium is the first point of contact in the lung for inhaled material, including infectious pathogens and particulate matter, and protects against toxicity from these substances by trapping and clearance via the mucociliary escalator, presence of a protective barrier with tight junctions and initiation of a local inflammatory response. The inflammatory response involves recruitment of phagocytic cells to neutralise and remove and invading materials and is oftern modelled using rodents. However, development of valid in vitro airway epithelial models is of great importance due to the restrictions on animal studies for cosmetic compound testing implicit in the 7th amendment to the European Union Cosmetics Directive. Further, rodent innate immune responses have fundamental differences to human. Pulmonary endothelial cells and leukocytes are also involved in the innate response initiated during pulmonary inflammation. Co-culture models of the airways, in particular where epithelial cells are cultured at air liquid interface with the presence of tight junctions and differentiated mucociliary cells, offer a solution to this problem. Ideally validated models will allow for detection of early biomarkers of response to exposure and investigation into inflammatory response during exposure. This thesis describes the approaches taken towards developing an in vitro epithelial/endothelial cell model of the human airways and identification biomarkers of response to exposure to xenobiotics. The model comprised normal human primary microvascular endothelial cells and the bronchial epithelial cell line BEAS-2B or normal human bronchial epithelial cells. BEAS-2B were chosen as their characterisation at air liquid interface is limited but they are robust in culture, thereby predicted to provide a more reliable test system. Proteomics analysis was undertaken on challenged cells to investigate biomarkers of exposure. BEAS-2B morphology was characterised at air liquid interface compared with normal human bronchial epithelial cells. The results indicate that BEAS-2B cells at an air liquid interface form tight junctions as shown by expression of the tight junction protein zonula occludens-1. To this author’s knowledge this is the first time this result has been reported. The inflammatory response of BEAS-2B (measured as secretion of the inflammatory mediators interleukin-8 and -6) air liquid interface mono-cultures to Escherichia coli lipopolysaccharide or particulate matter (fine and ultrafine titanium dioxide) was comparable to published data for epithelial cells. Cells were also exposed to polymers of “commercial interest” which were in the nanoparticle range (and referred to particles hereafter). BEAS-2B mono-cultures showed an increased secretion of inflammatory mediators after challenge. Inclusion of microvascular endothelial cells resulted in protection against LPS- and particle- induced epithelial toxicity, measured as cell viability and inflammatory response, indicating the importance of co-cultures for investigations into toxicity. Two-dimensional proteomic analysis of lysates from particle-challenged cells failed to identify biomarkers of toxicity due to assay interference and experimental variability. Separately, decreased plasma concentrations of serine protease inhibitors, and the negative acute phase proteins transthyretin, histidine-rich glycoprotein and alpha2-HS glycoprotein were identified as potential biomarkers of methyl methacrylate/ethyl methacrylate/butylacrylate treatment in rats.

Creating a culture for critical and situated technology use through effective learning design

The purpose of this concise paper is to propose, with evidence gathered through a systematic evaluation of an academic development programme in the UK, that training in the use of new and emerging learning technologies should be holistically embedded in every learning and training opportunity in learning, teaching and assessment in higher education, and not only as stand-alone modules or one-off opportunities. The future of learning in higher education cannot afford to allow Universities to disregard that digital literacy is an expected professional skill for their entire staff.

Development of a neurotoxicity test-system, using human post-mitotic, astrocytic and neuronal cell lines in co-culture

Astrocytes are essential for neuronal function and survival, so both cell types were included in a human neurotoxicity test-system to assess the protective effects of astrocytes on neurons, compared with a culture of neurons alone. The human NT2.D1 cell line was differentiated to form either a co-culture of post-mitotic NT2.N neuronal (TUJ1, NF68 and NSE positive) and NT2.A astrocytic (GFAP positive) cells (∼2:1 NT2.A:NT2.N), or an NT2.N mono-culture. Cultures were exposed to human toxins, for 4 h at sub-cytotoxic concentrations, in order to compare levels of compromised cell function and thus evidence of an astrocytic protective effect. Functional endpoints examined included assays for cellular energy (ATP) and glutathione (GSH) levels, generation of hydrogen peroxide (H2O2) and caspase-3 activation. Generally, the NT2.N/A co-culture was more resistant to toxicity, maintaining superior ATP and GSH levels and sustaining smaller significant increases in H2O2 levels compared with neurons alone. However, the pure neuronal culture showed a significantly lower level of caspase activation. These data suggest that besides their support for neurons through maintenance of ATP and GSH and control of H2O2 levels, following exposure to some substances, astrocytes may promote an apoptotic mode of cell death. Thus, it appears the use of astrocytes in an in vitro predictive neurotoxicity test-system may be more relevant to human CNS structure and function than neuronal cells alone. © 2007 Elsevier Ltd. All rights reserved.

A framework of best practice of continuing professional development for the accounting profession

The International Accounting Education Standards Board (IAESB) places a strong emphasis on individual professionals taking responsibility for their Continuing Professional Development (CPD). On the other hand, the roles performed by professional accountants have evolved out of practical necessity to 'best' suit the diverse needs of business in a global economy. This diversity has meant that professional accountants are seen in highly specialised roles requiring diverse skill sets. In order to enhance the contribution of the accountant as a knowledge professional for business, it follows that CPD that leverages off an individual's experience should be designed to meet the needs of professionals across the different specialised roles within the profession. In doing so the project identifies how CPD should differ across roles and levels of organisational responsibility for accounting professionals. The study also makes a number of policy recommendations to IAESB and IFAC. © 2013 © 2013 Taylor & Francis.

A quantitative approach for understanding small-scale human mesenchymal stem cell culture - implications for large-scale bioprocess development

Human mesenchymal stem cell (hMSC) therapies have the potential to revolutionise the healthcare industry and replicate the success of the therapeutic protein industry; however, for this to be achieved there is a need to apply key bioprocessing engineering principles and adopt a quantitative approach for large-scale reproducible hMSC bioprocess development. Here we provide a quantitative analysis of the changes in concentration of glucose, lactate and ammonium with time during hMSC monolayer culture over 4 passages, under 100% and 20% dissolved oxgen (dO2), where either a 100%, 50% or 0% growth medium exchange was performed after 72h in culture. Yield coefficients, specific growth rates (h-1) and doubling times (h) were calculated for all cases. The 100% dO2 flasks outperformed the 20% dO2 flasks with respect to cumulative cell number, with the latter consuming more glucose and producing more lactate and ammonium. Furthermore, the 100% and 50% medium exchange conditions resulted in similar cumulative cell numbers, whilst the 0% conditions were significantly lower. Cell immunophenotype and multipotency were not affected by the experimental culture conditions. This study demonstrates the importance of determining optimal culture conditions for hMSC expansion and highlights a potential cost savings from only making a 50% medium exchange, which may prove significant for large-scale bioprocessing. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.