The N-terminus of CD14 acts to bind apoptotic cells and confers rapid-tethering capabilities on non-myeloid cells:CD14 and rapid tethering of apoptotic cells

Cell death and removal of cell corpses in a timely manner is a key event in both physiological and pathological situations including tissue homeostasis and the resolution of inflammation. Phagocytic clearance of cells dying by apoptosis is a complex sequential process comprising attraction, recognition, tethering, signalling and ultimately phagocytosis and degradation of cell corpses. A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within this process. The role of myeloid cell CD14 in mediating apoptotic cell interactions with macrophages has long been known though key molecules and residues involved have not been defined. Here we sought to further dissect the function of CD14 in apoptotic cell clearance. A novel panel of THP-1 cell-derived phagocytes was employed to demonstrate that CD14 mediates effective apoptotic cell interactions with macrophages in the absence of detectable TLR4 whilst binding and responsiveness to LPS requires TLR4. Using a targeted series of CD14 point mutants expressed in non-myeloid cells we reveal CD14 residue 11 as key in the binding of apoptotic cells whilst other residues are reported as key for LPS binding. Importantly we note that expression of CD14 in non-myeloid cells confers the ability to bind rapidly to apoptotic cells. Analysis of a panel of epithelial cells reveals that a number naturally express CD14 and that this is competent to mediate apoptotic cell clearance. Taken together these data suggest that CD14 relies on residue 11 for apoptotic cell tethering and it may be an important tethering molecule on so called 'non-professional' phagocytes thus contributing to apoptotic cell clearance in a non-myeloid setting. Furthermore these data establish CD14 as a rapid-acting tethering molecule, expressed in monocytes, which may thus confer responsiveness of circulating monocytes to apoptotic cell derived material. © 2013 Thomas et al.

Goal orientation and its relationship to the business family, and family business performance, within the UK’s family owned and managed mid-sized businesses

Mid-Sized Businesses (MSBs) are defined by the Department for Business, Innovation and Skills (BIS) as having a sales turnover of between £25 million and £500 million. A key gap in family firm/business research and literature to date is, understanding the role and importance of non-financial objectives (such as family harmony, tradition and business longevity), and the role the family plays in creating a wide set of business performance objectives (both financial and non-financial) in these businesses. This dissertation contributes to filling this knowledge gap by drawing on Family Systems Theory applied in a business context, and within an overarching Resource Based View (RBV) of the firm.

A study of the impact of lean on UK manufacturing organisations that view it as a philosophy

There were three principal research aims: primarily, Lean is and always should be regarded as a business model as depicted by Toyota who is dedicated towards finding better ways of producing cars; consequently an investigation of whether organisations embracing Lean as a philosophy were indeed more triumphant. An adapted balanced scorecard was used which embraced strategic, operation and indices focused towards the future prospects of an organisation. Secondly, it was obligatory to explicitly and precisely determine whether an organisation espoused Lean as a philosophy as opposed to another process or strategy. Thirdly, since Lean has to be envisaged as a never-ending journey; it was important to map out the Lean journey and to be able to categorize the juncture an organisation occupies at any particular phase of its overall implementation. This affords an opportunity to advise an organisation of specific requirements it needs to satisfy should it wish to embrace Lean as a philosophy. The methodological approach focused on the effective deployment of survey questionnaires in sixty-eight organisations and seven extensive case studies in manufacturing organisations of varying sizes. The CIMA organisational classification, the Puttick grid and the Product-Process matrix were used to analyse the range of organisations used in this investigation. Whilst there was a requirement to investigate whether Lean indeed equates to success, pertinent performance measurement was considered decisive; the DMP Model (Maltz et al., 2003) was modified to perform this role. An unremitting theme both in literature concerning the implementation of Lean and in the research evolves around the notion of corporate cultures. Its relevance is explored further within the analysis. In accepting the premise that Lean incorporates a journey, it was fundamental to identify the voyage. Prevalent frameworks are deficient in identifying the sustainability and ideological facets of Lean. Consequently, an extensive Lean audit was developed and piloted in twenty disparate organisations.

Understanding and improving the manufacturing and changeover process in Saudi Arabian business - a multiple case study approach

The importance of the changeover process in the manufacturing industry is becoming widely recognised. Changeover is a complete process of changing between the manufacture of one product to manufacture of an alternative product until specified production and quality rates are reached. The initiatives to improve changeover exist in industry, as better changeover process typically contribute to improved quality performance. A high-quality and reliable changeover process can be achieved through implementation of continuous or radical improvements. This research examines the changeover process of Saudi Arabian manufacturing firms because Saudi Arabia’s government is focused on the expansion of GDP and increasing the number of export manufacturing firms. Furthermore, it is encouraging foreign manufacturing firms to invest within Saudi Arabia. These initiatives, therefore, require that Saudi manufacturing businesses develop the changeover practice in order to compete in the market and achieve the government’s objectives. Therefore, the aim of this research is to discover the current status of changeover process implementation in Saudi Arabian manufacturing businesses. To achieve this aim, the main objective of this research is to develop a conceptual model to understand and examine the effectiveness of the changeover process within Saudi Arabian manufacturing firms, facilitating identification of those activities that affect the reliability and high-quality of the process. In order to provide a comprehensive understanding of this area, this research first explores the concept of quality management and its relationship to firm performance and the performance of manufacturing changeover. An extensive body of literature was reviewed on the subject of lean manufacturing and changeover practice. A research conceptual model was identified based on this review, and focus was on providing high-quality and reliable manufacturing changeover processes during set-up in a dynamic environment. Exploratory research was conducted in sample Saudi manufacturing firms to understand the features of the changeover process within the manufacturing sector, and as a basis for modifying the proposed conceptual model. Qualitative research was employed in the study with semi-structured interviews, direct observations and documentation in order to understand the real situation such as actual daily practice and current status of changeover process in the field. The research instrument, the Changeover Effectiveness Assessment Tool (CEAT) was developed to evaluate changeover practices. A pilot study was conducted by examining the CEAT, proposed for the main research. Consequently, the conceptual model was modified and CEAT was improved in response to the pilot study findings. Case studies have been conducted within eight Saudi manufacturing businesses. These case studies assessed the implementation of manufacturing changeover practice in the lighting and medical products sectors. These two sectors were selected based on their operation strategy which was batch production as well as the fact that they fulfilled the research sampling strategy. The outcomes of the research improved the conceptual model, ultimately to facilitate the firms’ adoption and rapid implementation of a high-quality and reliability changeover during the set-up process. The main finding of this research is that Quality’s factors were considering the lowest levels comparing to the other factors which are People, Process and Infrastructure. This research contributes to enable Saudi businesses to implement the changeover process by adopting the conceptual model. In addition, the guidelines for facilitating implementation were provided in this thesis. Therefore, this research provides insight to enable the Saudi manufacturing industry to be more responsive to rapidly changing customer demands.

A configuration framework of manufacturing strategy paradigm in state owned enterprises within China's petrochemical industry:building context-embedded configurations for the paradigm of strategic manufacturing management from exploratory case studies

The role of the production system as a key determinant of competitive performance of business operations- has long been the subject of industrial organization research, even predating the .explicit conceptua1isation of manufacturing, strategy in the literature. Particular emergent production issues such as the globalisation of production, global supply chain management, management of integrated manufacturing and a growing e~busjness environment are expected to critically influence the overall competitive performance and therefore the strategic success of the organization. More than ever, there is a critical need to configure and improve production system and operations competence in a strategic way so as to contribute to the long-term competitiveness of the organization. In order to operate competitively and profitably, manufacturing companies, no matter how well managed, all need a long-term 'strategic direction' for the development of operations competence in order to consistently produce more market value with less cost towards a leadership position. As to the long-term competitiveness, it is more important to establish a dynamic 'strategic perspective' for continuous operational improvements in pursuit of this direction, as well as ongoing reviews of the direction in relation to the overall operating context. However, it also clear that the 'existing paradigm of manufacturing strategy development' is incapable of adequately responding to the increasing complexities and variations of contemporary business operations. This has been factually reflected as many manufacturing companies are finding that methodologies advocated in the existing paradigm for developing manufacturing strategy have very limited scale and scope for contextual contingency in empirical application. More importantly, there has also emerged a deficiency in the multidimensional and integrative profile from a theoretical perspective when operationalising the underlying concept of strategic manufacturing management established in the literature. The point of departure for this study was a recognition of such contextual and unitary limitations in the existing paradigm of manufacturing strategy development when applied to contemporary industrial organizations in general, and Chinese State Owned Enterprises (SOEs) in particular. As China gradually becomes integrated into the world economy, the relevance of Western management theory and its paradigm becomes a practical matter as much as a theoretical issue. Since China markedly differs from Western countries in terms of culture, society, and political and economic systems, it presents promising grounds to test and refine existing management theories and paradigms with greater contextual contingency and wider theoretical perspective. Under China's ongoing programmes of SOE reform, there has been an increased recognition that strategy development is the very essence of the management task for managers of manufacturing companies in the same way as it is for their counterparts in Western economies. However, the Western paradigm often displays a rather naive and unitary perspective of the nature of strategic management decision-making, one which largely overlooks context-embedded factors and social/political influences on the development of manufacturing strategy. This thesis studies the successful experiences of developing manufacturing strategy from five high-performing large-scale SOEs within China’s petrochemical industry. China’s petrochemical industry constitutes a basic heavy industrial sector, which has always been a strategic focus for reform and development by the Chinese government. Using a confirmation approach, the study has focused on exploring and conceptualising the empirical paradigm of manufacturing strategy development practiced by management. That is examining the ‘empirical specifics’ and surfacing the ‘managerial perceptions’ of content configuration, context of consideration, and process organization for developing a manufacturing strategy during the practice. The research investigation adopts a qualitative exploratory case study methodology with a semi-structural front-end research design. Data collection follows a longitudinal and multiple-case design and triangulates case evidence from sources including qualitative interviews, direct observation, and a search of documentations and archival records. Data analysis follows an investigative progression from a within-case preliminary interpretation of facts to a cross-case search for patterns through theoretical comparison and analytical generalization. The underlying conceptions in both the literature of manufacturing strategy and related studies in business strategy were used to develop theoretical framework and analytical templates applied during data collection and analysis. The thesis makes both empirical and theoretical contributions to our understanding of 'contemporary management paradigm of manufacturing strategy development'. First, it provides a valuable contextual contingency of the 'subject' using the business setting of China's SOEs in petrochemical industry. This has been unpacked into empirical configurations developed for its context of consideration, its content and process respectively. Of special note, a lean paradigm of business operations and production management discovered at case companies has significant implications as an emerging alternative for high-volume capital intensive state manufacturing in China. Second, it provides a multidimensional and integrative theoretical profile of the 'subject' based upon managerial perspectives conceptualised at case companies when operationalising manufacturing strategy. This has been unpacked into conceptual frameworks developed for its context of consideration, its content constructs, and its process patterns respectively. Notably, a synergies perspective towards the operating context, competitive priorities and competence development of business operations and production management has significant implications for implementing a lean manufacturing paradigm. As a whole, in so doing, the thesis established a theoretical platform for future refinement and development of context-specific methodologies for developing manufacturing strategy.

Aspects of the design and control of manufacturing systems subject to demand uncertainty

The recent explosive growth in advanced manufacturing technology (AMT) and continued development of sophisticated information technologies (IT) is expected to have a profound effect on the way we design and operate manufacturing businesses. Furthermore, the escalating capital requirements associated with these developments have significantly increased the level of risk associated with initial design, ongoing development and operation. This dissertation has examined the integration of two key sub-elements of the Computer Integrated Manufacturing (CIM) system, namely the manufacturing facility and the production control system. This research has concentrated on the interactions between production control (MRP) and an AMT based production facility. The disappointing performance of such systems has been discussed in the context of a number of potential technological and performance incompatibilities between these two elements. It was argued that the design and selection of operating policies for both is the key to successful integration. Furthermore, policy decisions are shown to play an important role in matching the performance of the total system to the demands of the marketplace. It is demonstrated that a holistic approach to policy design must be adopted if successful integration is to be achieved. It is shown that the complexity of the issues resulting from such an approach required the formulation of a structured design methodology. Such a methodology was subsequently developed and discussed. This combined a first principles approach to the behaviour of system elements with the specification of a detailed holistic model for use in the policy design environment. The methodology aimed to make full use of the `low inertia' characteristics of AMT, whilst adopting a JIT configuration of MRP and re-coupling the total system to the market demands. This dissertation discussed the application of the methodology to an industrial case study and the subsequent design of operational policies. Consequently a novel approach to production control resulted. A central feature of which was a move toward reduced manual intervention in the MRP processing and scheduling logic with increased human involvement and motivation in the management of work-flow on the shopfloor. Experimental results indicated that significant performance advantages would result from the adoption of the recommended policy set.

Buyer-supplier relationships in advanced manufacturing technology acquisition and implementation : a study in Malaysia

This thesis reports the results of research into the connections between transaction attributes and buyer-supplier relationships (BSR) in advanced manufacturing technology (AMT) acquisitions and implementation. It also examines the impact of the different patterns of BSR on performance. Specifically, it addresses the issues of how the three transaction attributes; namely level of complexity, level of asset specificity, and level of uncertainty, can affect the relationships between the technology buyer and suppler in AMT acquisition and implementation, and then to see the impact of different patterns of BSR on the two aspect of performance; namely technology and implementation performance. In understanding the pohenomena, the study mainly draws on and integrates the literature of transaction cost economics theory,buyer-supplier relationships and advanced manufacturing technology as a basis of theoretical framework and hypotheses development.data were gathered through a questionnaire survey with 147 responses and seven semi-structured interviews of manufacturing firms in Malaysia. Quantitative data were analysed mainly using the AMOS (Analysis of Moment Structure) package for structural equation modeling and SPSS (Statistical Package for Social Science) for analysis of variance (ANOVA). Data from interview sessions were used to develop a case study with the intention of providing a richer and deeper understanding on the subject under investigation and to offer triangulation in the research process. he results of the questionnaire survey indicate that the higher the level of technological specificity and uncertainty, the more firms are likely to engage in a closer relationship with technology suppliers.However, the complexity of the technology being implemented is associated with BSR only because it is associated with the level of uncertainty that has direct impact upon BSR.The analysis also provides strong support for the premise that developing strong BSR could lead to an improved performance. However, with high levels of transaction attribute, implementation performance suffers more when firms have weak relationships with technology suppliers than with moderate and low levels of transaction attributes. The implications of the study are offered for both the academic and practitioner audience. The thesis closes with reports on its limitations and suggestions for further research that would address some of these limitations.

The release of nicotine from chewing gum formulations

The first clinically proven nicotine replacement product to obtain regulatory approval was Nicorette® gum. It provides a convenient way of delivering nicotine directly to the buccal cavity, thus, circumventing 'first-pass' elimination following gastrointestinal absorption. Since launch, Nicorette® gum has been investigated in numerous studies (clinical) which are often difficult to compare due to large variations in study design and degree of sophistication. In order to standardise testing, in 2000 the European Pharmacopoeia introduced an apparatus to investigate the in vitro release of drug substances from medical chewing gum. With use of the chewing machine, the main aims of this project were to determine factors that could affect release from Nicorette® gum, to develop an in vitro in vivo correlation and to investigate formulation variables on release of nicotine from gums. A standard in vitro test method was developed. The gum was placed in the chewing chamber with 40 mL of artificial saliva at 37'C and chewed at 60 chews per minute. The chew rate, the type of dissolution medium used, pH, volume, temperature and the ionic strength of the dissolution medium were altered to investigate the effects on release in vitro. It was found that increasing the temperature of the dissolution media and the rate at which the gums were chewed resulted in a greater release of nicotine, whilst increasing the ionic strength of the dissolution medium to 80 mM resulted in a lower release. The addition of 0.1 % sodium Jauryl sulphate to the artificial saliva was found to double the release of nicotine compared to the use of artificial saliva and water alone. Although altering the dissolution volume and the starting pH did not affect the release. The increase in pH may be insufficient to provide optimal conditions for nicotine absorption (since the rate at which nicotine is transported through the buccal membrane was found to be higher at pH values greater than 8.6 where nicotine is predominately unionised). Using a time mapping function, it was also possible to establish a level A in vitro in vivo correlation. 4 mg Nicorette® gum was chewed at various chew rates in vitro and correlated to an in vivo chew-out study. All chew rates used in vitro could be successfully used for IVIVC purposes, however statistically, chew rates of 10 and 20 chews per minute performed better than all other chew rates. Finally a series of nicotine gums was made to investigate the effect of formulation variables on release of nicotine from the gum. Using a directly compressible gum base, in comparison to Nicorette® the gums crumbled when chewed in vitro, resulting in a faster release of nicotine. To investigate the effect of altering the gum base, the concentration of sodium salts, sugar syrup, the form of the active drug, the addition sequence and the incorporation of surfactant into the gum, the traditional manufacturing method was used to make a series of gum formulations. Results showed that the time of addition of the active drug, the incorporation of surfactants and using different gum base all increased the release of nicotine from the gum. In contrast, reducing the concentration of sodium carbonate resulted in a lower release. Using a stronger nicotine ion-exchange resin delayed the release of nicotine from the gum, whilst altering the concentration of sugar syrup had little effect on the release but altered the texture of the gum.

A review of research in manufacturing prognostics

With the fast changing global business landscape, manufacturing companies are facing increasing challenge to reduce cost of production, increase equipment utilization and provide innovative products in order to compete with countries with low labour cost and production cost. On of the methods is zero down time. Unfortunately, the current research and industrial solution does not provide user friendly development environment to create “Adaptive microprocessor size with supercomputer performance” solution to reduce downtime. Most of the solutions are PC based computer with off the shelf research software tools which is inadequate for the space constraint manufacturing environment in developed countries. On the other hand, to develop solution for various manufacturing domain will take too much time, there is lacking tools available for rapid or adaptive way of create the solution. Therefore, this research is to understand the needs, trends, gaps of manufacturing prognostics and defines the research potential related to rapid embedded system framework for prognostic.

Towards the strategic adoption of Lean in aviation Maintenance Repair and Overhaul (MRO) industry:an empirical study into the industry's Lean status

Purpose - Despite many Maintenance Repair and Overhaul (MRO) organisations alluding their positive business performances to the adoption Lean initiatives, there is a paucity of direct literature that validates this assertion. Thus, the purpose of this paper is to study empirically via the use of an industry-wide survey to establish and extent of Lean adoption and to verify its suitability in mitigating prevalent MRO challenges. Design/methodology/approach - The empirical study contained in this paper is facilitated by an industry-wide survey to collect data from several firms across the MRO spectrum. The analysed responses from industry leaders, professionals and executives synthesised with existing literature was used in ascertaining the extent of Lean adoption within the operational framework of the industry. Findings - The empirical study helped in validating the suitability of Lean in MRO context. However, it was also observed that the focus of its application was skewed towards its production-orientated functions more than its service-orientated functions. Nonetheless, this paper presents results of the positive influence of Lean in MRO context. Research limitations/implications - This empirical study presented in this paper was carried out within a framework of key characteristics of operation. Although this approach is sufficient in assessing the industry's Lean status, further assessment can also be achieved within the context of relevant performance metrics which was not included in this paper. Practical implications - By exploring the industry's Lean status within the context of operational characteristics of operation, this study provides MRO practitioners with more awareness into some of the critical factors required for successful holistic Lean realisation. Social implications - The state-of-the-art of Lean within the aviation MRO context established through this research also contributes to the wider product-centric service environment by providing a platform that facilitates strategy development which ensures Lean success within this environment. Originality/value - Apart from validating the suitability of Lean in MRO contexts, by establishing the extent of Lean adoption within the context of the operational framework, this paper provides a clearer insight as to how successful Lean implementation can be achieved via a holistic implementation strategy balanced between the product-centric and service-centric aspects of the industry.

A survey of continuous improvement practices in the United Kingdom and Mexico

With the advent of globalisation companies all around the world must improve their performance in order to survive. The threats are coming from everywhere, and in different ways, such as low cost products, high quality products, new technologies, and new products. Different companies in different countries are using various techniques and using quality criteria items to strive for excellence. Continuous improvement techniques are used to enable companies to improve their operations. Therefore, companies are using techniques such as TQM, Kaizen, Six-Sigma, Lean Manufacturing, and quality award criteria items such as Customer Focus, Human Resources, Information & Analysis, and Process Management. The purpose of this paper is to compare the use of these techniques and criteria items in two countries, Mexico and the United Kingdom, which differ in culture and industrial structure. In terms of the use of continuous improvement tools and techniques, Mexico formally started to deal with continuous improvement by creating its National Quality Award soon after the Americans began the Malcolm Baldrige National Quality Award. The United Kingdom formally started by using the European Quality Award (EQA), modified and renamed as the EFQM Excellence Model. The methodology used in this study was to undertake a literature review of the subject matter and to study some general applications around the world. A questionnaire survey was then designed and a survey undertaken based on the same scale, about the same sample size, and the about the same industrial sector within the two countries. The survey presents a brief definition of each of the constructs to facilitate understanding of the questions. The analysis of the data was then conducted with the assistance of a statistical software package. The survey results indicate both similarities and differences in the strengths and weaknesses of the companies in the two countries. One outcome of the analysis is that it enables the companies to use the results to benchmark themselves and thus act to reinforce their strengths and to reduce their weaknesses.

A systems methodology for analysing and simulating manufacturing systems

The Systems Engineering Group (SEG) at De Montfort University are developing the Boardman Soft Systems Methodology (BSSM) which allows complex human systems to be modelled, this work builds upon Checkland's Soft Systems Methodology (1981). The BSSM has been applied to the modelling of the systems engineering process as used in design and manufacturing companies. The BSSM is used to solicit information from a company and this data is then transformed into systemic diagrams (systemigrams). These systemigrams are posited to be accurate and concise representations of the system which has been modelled. This paper describes the collaboration between SEG and a manufacturing company (MC) in Leicester, England. The purpose of this collaboration was twofold. First, it was to create an objective view of the MC's processes, in the form of systemigrams. It was important to get this modelled by a source outside of the company, as it is difficult for people within a system being modelled to be unbiased. Secondly, it allowed a series of systemigrams to be produced which can then be subjected to simulation, for the purpose of aiding risk management decisions and to reduce the project cycle time

Knowledge acquisition in international strategic alliances among Malaysian manufacturing firms

This thesis examines the process of knowledge acquisition by Malaysian manufacturing firms through their involvement in international strategic alliances. The strategic alliances can be with or without equity involvement. Firms involved with a foreign partner with equity involvement are joint venture firms while non-equity involvement are firms that engaged in contractual agreements. Using empirical evidence from 65 international alliances gathered through a survey conducted in high-technology manufacturing sectors, several factors that influence the process of knowledge acquisition are examined. The factors are: learning capacity, experience, goals, active involvement and accessibility to the foreign knowledge. Censored regression analysis and ordered probit analysis are used to analyse the effects of these factors on knowledge acquisition and its determinant parts, and the effects of knowledge acquisition and its determinants on the performance of the alliances. A second questionnaire gathered evidence relating to the factors, which encouraged tacit knowledge transfer between the foreign and Malaysian partners in international alliances. The key findings of the study are: knowledge acquisition in international strategic alliances is influenced by five determining factors; learning capacity, experience, articulated goals, active involvement and accessibility; new technology knowledge, product development knowledge and manufacturing process knowledge are influenced differently by the determining factors; knowledge acquisition and its determinant factors have a significant impact on the firm’s performance; cultural differences tend to moderate the effect on the firm’s performance; acquiring tacit knowledge is not only influenced by the five determinant factors but also by other factors, such as dependency, accessibility, trust, manufacturing control, learning methods and organisational systems; Malaysian firms involved in joint ventures tend to acquire more knowledge than those involved in contractual agreements, but joint ventures also exhibit higher degrees of dependency than contractual agreements; and the presence of R&D activity in the Malaysian partner encourages knowledge acquisition, but the amount of R&D expenditure has no effect on knowledge acquisition.