37 resultados para System levels

em Aston University Research Archive


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Purpose - To develop a systems strategy for supply chain management in aerospace maintenance, repair and overhaul (MRO). Design/methodology/approach - A standard systems development methodology has been followed to produce a process model (i.e. the AMSCR model); an information model (i.e. business rules) and a computerised information management capability (i.e. automated optimisation). Findings - The proof of concept for this web-based MRO supply chain system has been established through collaboration with a sample of the different types of supply chain members. The proven benefits comprise new potential to minimise the stock holding costs of the whole supply chain whilst also minimising non-flying time of the aircraft that the supply chain supports. Research limitations/implications - The scale of change needed to successfully model and automate the supply chain is vast. This research is a limited-scale experiment intended to show the power of process analysis and automation, coupled with strategic use of management science techniques, to derive tangible business benefit. Practical implications - This type of system is now vital in an industry that has continuously decreasing profit margins; which in turn means pressure to reduce servicing times and increase the mean time between them. Originality/value - Original work has been conducted at several levels: process, information and automation. The proof-of-concept system has been applied to an aircraft MRO supply chain. This is an area of research that has been neglected, and as a result is not well served by current systems solutions. © Emerald Group Publishing Limited.

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In order to survive in the increasingly customer-oriented marketplace, continuous quality improvement marks the fastest growing quality organization’s success. In recent years, attention has been focused on intelligent systems which have shown great promise in supporting quality control. However, only a small number of the currently used systems are reported to be operating effectively because they are designed to maintain a quality level within the specified process, rather than to focus on cooperation within the production workflow. This paper proposes an intelligent system with a newly designed algorithm and the universal process data exchange standard to overcome the challenges of demanding customers who seek high-quality and low-cost products. The intelligent quality management system is equipped with the ‘‘distributed process mining” feature to provide all levels of employees with the ability to understand the relationships between processes, especially when any aspect of the process is going to degrade or fail. An example of generalized fuzzy association rules are applied in manufacturing sector to demonstrate how the proposed iterative process mining algorithm finds the relationships between distributed process parameters and the presence of quality problems.

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To meet changing needs of customers and to survive in the increasingly globalised and competitive environment, it is necessary for companies to equip themselves with intelligent tools, thereby enabling managerial levels to use the tactical decision in a better way. However, the implementation of an intelligent system is always a challenge in Small- and Medium-sized Enterprises (SMEs). Therefore, a new and simple approach with 'process rethinking' ability is proposed to generate ongoing process improvements over time. In this paper, a roadmap of the development of an agent-based information system is described. A case example has also been provided to show how the system can assist non-specialists, for example, managers and engineers to make right decisions for a continual process improvement. Copyright © 2006 Inderscience Enterprises Ltd.

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Purpose – The purpose of the paper is to use a case study setting involving the implementation of an enterprise resource planning (ERP) system to expose and analyze the conflicts in the characterizations of the post bureaucratic organisation (PBO) in the literature. ERP implementations are often accompanied by increasing levels of stress in organizations that place pressures on organizational relationships and structures. Additionally, ERPs are regarded as introducing their own techno-logic of centralization, standardization and formalization that provides an apparent contrast to the exhortations about employee empowerment. Design/methodology/approach – A case study of ERP implementation in a medium-sized entity is presented. The paper explores aspects of ERP and PBO from the context of postmodern organization theory. Findings – Some concerns about PBO identified in the literature are reflected in the case situation. For example, there is a commitment to give up private time and work flexibly by some employees. The paper also provides evidence of the way the management team substitute their reliance on a key individual knowledge worker for that of an ERP system and external vendor support. Paradoxically, trust in that same knowledge worker and between core users of the system is essential to enable the implementation of the system. Originality/value – This paper adds empirical insight to a predominantly theoretical literature. The case evidence indicates some conflicting implications in the concurrent adoption of PBO and ERP.

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Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

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As levels of investment in advanced manufacturing systems increase, effective project management becomes ever more critical. This paper demonstrates how the model proposed by Mintzberg, Raisinghani and Theoret in 1976, which structures complicated strategic decision processes, can be applied to the design of new production systems for both descriptive and analytical research purposes. This paper sets a detailed case study concerning the design and development of an advanced manufacturing system within the Mintzberg decision model and so breaks down the decision sequence into constituent parts. It thus shows how a structured model can provide a framework for the researcher who wishes to study decision episodes in the design of manufacturing facilities in greater depth.

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Apoptosis, programmed cell death, is used by multicellular organisms to remove cells that are in excess, damaged or diseased. Activation of the apoptosis programme generates "eat me" signals on the surface of the apoptotic cell that mediate recognition and clearance by the innate immune system. CD14, a pattern recognition receptor expressed on macrophages, is widely known for its ability to recognise the pathogen-associated molecular pattern lipopolysaccharide (LPS) and promote inflammation. However, CD14 has also been shown to mediate binding and removal of apoptotic cells in a process that is anti-inflammatory suggesting CD14 is capable of producing two distinct, ligand-dependent macrophage responses. Whilst the molecular basis for this dichotomy has yet to be defined it is clear that CD14 defines a point of interest on the macrophage surface where we may study ligand-specific responses of macrophages. Our work seeks to define the molecular mechanisms underlying the involvement of CD14 in the non-inflammatory clearance of apoptotic cells. Here we used three different differentiation strategies to generate macrophages from the monocytic cell line THP-1. The resultant macrophage models were characterised to assess the expression and function of CD14 within each model system. Whilst each macrophage model shows increased levels of surface CD14 expression, our results demonstrate significant differences in the various models’ abilities to respond to LPS and clear apoptotic cells in a CD14-dependent manner. TLR4 levels correlated positively with LPS responsiveness but not CD14-dependent apoptotic cell clearance or anti-inflammatory responses to apoptotic cells. These observations suggest CD14-dependent apoptotic cell clearance is not dependent on TLR4. Taken together our data support the notion that the CD14 ligand-dependent responses to LPS and apoptotic cells derive from changes at the macrophage surface. The nature and composition of the CD14-co-receptor complex for LPS and apoptotic cell binding and responses is the subject of further study.

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The adjuvanticity of liposomes can be directed through formulation to develop a safe yet potent vaccine candidate. With the addition of the cationic lipid dimethyldioctadecylammonium bromide (DDA) to stable neutral distearoylphosphatidylcholine (DSPC):cholesterol (Chol) liposomes, vesicle size reduces while protein entrapment increases. The addition of the immunomodulator, trehalose 6,6-dibehenate (TDB) to either the neutral or cationic liposomes did not affect the physiochemical characteristics of these liposome vesicles. However, the protective immune response, as indicated by the amount of IFN-? production, increases considerably when TDB is present. High levels of IFN-? were observed for cationic liposomes; however, there was a marked reduction in IFN-? release over time. Conversely, for neutral liposomes containing TDB, although the initial amount of IFN-? was slightly lower than the cationic equivalent, the overall protective immune responses of these neutral liposomes were effectively maintained over time, generating good levels of protection. To that end, although the addition of DSPC and Chol reduced the protective immunity of DDA:TDB liposomes, relatively high protection was observed for the neutral counterpart, DSPC:Chol:TDB, which may offer an effective neutral alternative to the DDA:TDB cationic system, especially for the delivery of either zwitterionic (neutral) or cationic molecules or antigens.

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Computer-Based Learning systems of one sort or another have been in existence for almost 20 years, but they have yet to achieve real credibility within Commerce, Industry or Education. A variety of reasons could be postulated for this, typically: - cost - complexity - inefficiency - inflexibility - tedium Obviously different systems deserve different levels and types of criticism, but it still remains true that Computer-Based Learning (CBL) is falling significantly short of its potential. Experience of a small, but highly successful CBL system within a large, geographically distributed industry (the National Coal Board) prompted an investigation into currently available packages, the original intention being to purchase the most suitable software and run it on existing computer hardware, alongside existing software systems. It became apparent that none of the available CBL packages were suitable, and a decision was taken to develop an in-house Computer-Assisted Instruction system according to the following criteria: - cheap to run; - easy to author course material; - easy to use; - requires no computing knowledge to use (as either an author or student) ; - efficient in the use of computer resources; - has a comprehensive range of facilities at all levels. This thesis describes the initial investigation, resultant observations and the design, development and implementation of the SCHOOL system. One of the principal characteristics c£ SCHOOL is that it uses a hierarchical database structure for the storage of course material - thereby providing inherently a great deal of the power, flexibility and efficiency originally required. Trials using the SCHOOL system on IBM 303X series equipment are also detailed, along with proposed and current development work on what is essentially an operational CBL system within a large-scale Industrial environment.

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The national systems of innovation (NIS) approach focuses on the patterns and the determinants of innovation processes from the perspective of nation-states. This paper reports on continuing work on the application of an NIS model to the development of technological capability in Turkey. Initial assessment of the literature shows that there are a number of alternative conceptualisations of NIS. An attempt by the Government to identify a NIS for Turkey shows the main actors in the system but does not pay sufficient attention to the processes of interactions between agents within the system. An operational model should be capable of representing these processes and interactions and assessing the strengths and weaknesses of the NIS. For industrialising countries, it is also necessary to incorporate learning mechanisms into the model. Further, there are different levels of innovation and capability in different sectors which the national perspective may not reflect. This paper is arranged into three sections. The first briefly explains the basics of the national innovation and learning system. Although there is no single accepted definition of NIS, alternative definitions reviewed share some common characteristics. In the second section, an NIS model is applied to Turkey in order to identify the elements, which characterise the country’s NIS. This section explains knowledge flow and defines the relations between the actors within the system. The final section draws on the “from imitation to innovation” model apparently so successful in East Asia and assesses its applicability to Turkey. In assessing Turkey’s NIS, the focus is on the automotive and textile sectors.

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The in vivo and in vitro characteristics of the I2 binding site were probed using the technique of drug discrimination and receptor autoradiography. Data presented in this thesis indicates the I2 ligand 2-BFI generates a cue in drug discrimination. Further studies indicated agmatine, a proposed endogenous imidazoline ligand, and a number of imidazoline and imidazole analogues of 2-BFI substitute significantly for 2-BFI. In addition to specific I2 ligands the administration of NRl's (noradrenaline reuptake inhibitors), the sympathomimetic d-amphetamine, the α1-adrenoceptor agonist methoxamine, but not the β1 agonist dobutamine or the β2 agonist salbutamol, gave rise to significant levels of substitution for the 2-BFI cue. The administration of the α1-adrenoceptor antagonist WB4101, prior to 2- BFI itself significantly reduced levels of 2-BFI appropriate responding. Administration of the reversible MAO-A inhibitors moclobemide and Ro41-1049, but not the reversible MAO-B inhibitors lazabemide and Ro16-6491, gave rise to potent dose dependent levels of substitution for the 2-BFI cue. Further studies indicated the administration of a number of β-carbolines and the structurally related indole alkaloid ibogaine also gave rise to dose dependent significant levels of substitution. Due to the relationship of indole alkaloids to serotonin the 5-HT releaser fenfluramine and a number of SSRI's (selective serotonin reuptake inhibitor) were also administered and these compounds gave rise to significant partial (20-80% responses to the 2-BFI lever) levels of substitution. The autoradiographical studies reported here indicate [3H]2-BFI labels I2 sites within the rat arcuate nucleus, area postrema, pineal gland, interpeduncular nucleus and subfornical organ. Subsequent experiments confirmed that the drug discrimination dosing schedule significantly increases levels of [3H]2-BFI 12 binding within two of these nuclei. However, levels of [3H]2-BFI specific binding were significantly reduced within four of these nuclei after chronic treatment with the irreversible MAO inhibitors deprenyl and tranylcypromine but not pargyline, which only reduced levels significantly in two. Further autoradiographical studies indicated that the distribution of [3H]2-BFI within the C57/B mouse compares favourably to that within the rat. Comparison of these levels of binding to those from transgenic mice who over-express MAO-B indicates two possibly distinct populations of [3H]2-BFI 12 sites exist in mouse brain. The data presented here indicates the 2-BFI cue is associated with the selective activation of α1-adrenoceptors and possibly 5-HT receptors. 2-BFI trained rats recognise reversible MAO-A but not MAO-B inhibitors. However, data within this thesis indicates the autoradiographical distribution of I2 sites bears a closer resemblance to that of MAO-B not MAO-A and further studies using transgenic mice that over-express MAO-B suggests a non-MAO-B I2 site exists in mouse brain.

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The human NT2.D1 cell line was differentiated to form both a 1:2 co-culture of post-mitotic NT2 neuronal and NT2 astrocytic (NT2.N/A) cells and a pure NT2.N culture. The respective sensitivities to several test chemicals of the NT2.N/A, the NT2.N, and the NT2.D1 cells were evaluated and compared with the CCF-STTG1 astrocytoma cell line, using a combination of basal cytotoxicity and biochemical endpoints. Using the MTT assay, the basal cytotoxicity data estimated the comparative toxicities of the test chemicals (chronic neurotoxin 2,5-hexanedione, cytotoxins 2,3- and 3,4-hexanedione and acute neurotoxins tributyltin- and trimethyltin- chloride) and also provided the non-cytotoxic concentration-range for each compound. Biochemical endpoints examined over the non-cytotoxic range included assays for ATP levels, oxidative status (H2O2 and GSH levels) and caspase-3 levels as an indicator of apoptosis. although the endpoints did not demonstrate the known neurotoxicants to be consistently more toxic to the cell systems with the greatest number of neuronal properties, the NT2 astrocytes appeared to contribute positively to NT2 neuronal health following exposure to all the test chemicals. The NT2.N/A co-culture generally maintained superior ATP and GSH levels and reduced H2O2 levels in comparison with the NT2.N mono-culture. In addition, the pure NT2.N culture showed a significantly lower level of caspase-3 activation compared with the co-culture, suggesting NT2 astrocytes may be important in modulating the mode of cell death following toxic insult. Overall, these studies provide evidence that an in vitro integrated population of post-mitotic human neurons and astrocytes may offer significant relevance to the human in vivo heterogeneous nervous system, when initially screening compounds for acute neurotoxic potential.

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This research aimed to provide a comparative analysis of South Asian and White British students in their academic attainment at school and university and in their search for employment. Data were gathered by using a variety of methodological techniques. Completed postal questionnaires were received from 301 South Asian and White British undergraduates from 12 British universities, who were in their final year of study in 1985. In depth interviews were also conducted with 49 graduates who were a self selected group from the original sample. Additional information was also collected by using diary report forms and by administering a second postal questionnaire to selected South Asian and White British participants. It was found that while the pre-university qualifications of the White British and South Asian undergraduates did not differ considerably, many members in the latter group had travelled a more arduous path to academic success. For some South Asians, school experiences included the confrontation of racist attitudes and behaviour, both from teachers and peers. The South Asian respondents in this study were more likely than their White British counterparts, to have attempted some C.S.E. examinations, obtained some of their `O' levels in the Sixth Form and retaken their `A' levels. As a result the South Asians were on average older than their White British peers when entering university. A small sample of South Asians also found that the effects of racism were perpetuated in higher education where they faced difficulty both academically and socially. Overall, however, since going to university most South Asians felt further drawn towards their `cultural background', this often being their own unique view of `Asianess'. Regarding their plans after graduation, it was found that South Asians were more likely to opt for further study, believing that they needed to be better qualified than their White British counterparts. For those South Asians who were searching for work, it was noted that they were better qualified, willing to accept a lower minimum salary, had made more job applications and had started searching for work earlier than the comparable White British participants. Also, although generally they were not having difficulty in obtaining interviews, South Asian applicants were less likely to receive an offer of employment. In the final analysis examining their future plans, it was found that a large proportion of South Asian graduates were aspiring towards self employment.

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This thesis considers the visual electrophysiological effects of vigabatrin (an anti-epileptic drug, which acts by increasing the levels of the inhibitory neurotransmitter GABA on the retina of the eye compared to the concentric visual field defects which have been found associated with the drug. Flash and pattern ERG's, EOG's multifocal ERG's (VERIS), flash and pattern VEP's and visual fields were tested. Although VEP's have been shown not to be affected by vigabatrin, these were recorded to complete the testing. Initially, of the eight vigabatrin patients with known visual field defects, 7 showed abnormally delayed 30Hz flicker a-wave latencies, 5 abnormally delayed 30Hz b-wave latencies and 6 abnormally low 30Hz amplitudes. Also 7 showed an abnormally prolonged latency of oscillatory potential 1 (OP1). The two patients taking vigabatrin at the time of testing showed low EOG Arden index values. The VERIS results correlated well with the severity of the visual field defects. Following this finding, eleven healthy subjects received vigabatrin over a 10-day period. No changes were seen in the visual fields, however, the photopic ERG b-wave latency significantly increased (although not to abnormal values). A matched pairs study with eleven vigabatrin, patients and eleven epileptic patients, who had never taken vigabatrin supported the findings of abnormal 30Hz flicker b-wave and OP latencies associated with vigabatrin, again with the VERIS results correlating to the severity of the visual field defect. The abnormal 30Hz flicker and VERIS responses indicate involvement of the cone photoreceptors and the OP's show an effect on the amacrine cells. The ERG increase in the photopic b-wave latency also suggests involvement of the bipolar cells, however, this effect and the reversible effect on the Arden index after cessation of the drug may be unrelated to the visual field defect. To conclude this thesis, a field specific VEP stimulus was developed to assess the retinal function in the peripheral field of paediatric patients. It comprises of a dartboard stimulus with a central 0-5 degree black and white chequered stimulus, a blank 5-30 degree annulus and a 30-60 degree peripheral chequered stimulus. When optimised on four vigabatrin patients it was found that no peripheral response can be evoked with a field loss exceeding 30-35 degrees. Co-operation was found to be successful in children as young as four years old.