Transglutaminase 2 null macrophages respond to lipopolysaccharide stimulation by elevated proinflammatory cytokine production due to an enhanced αvβ3 integrin-induced Src tyrosine kinase signaling

Transglutaminase 2 (TG2) is a protein crosslinking enzyme with several additional biochemical functions. Loss of TG2 in vivo results in impaired phagocytosis of apoptotic cells and altered proinflammatory cytokine production by macrophages engulfing apoptotic cells leading to autoimmunity. It has been proposed that TG2 acts as an integrin ß(3) coreceptor in the engulfment process, while altered proinflammatory cytokine production is related to the lack of latent TGFß activation by TG2 null macrophages. Here we report that TG2 null macrophages respond to lipopolysaccharide treatment by elevated IL-6 and TNFa production. Though TGFß has been proposed to act as a feed back regulator of proinflammatory cytokine production in LPS-stimulated macrophages, this phenomenon is not related to the lack of active TGFß production. Instead, in the absence of TG2 integrin ß(3) maintains an elevated basal Src family kinase activity in macrophages, which leads to enhanced phosphorylation and degradation of the I?Ba. Low basal levels of I?Ba explain the enhanced sensitivity of TG2 null macrophages to signals that regulate NF-?B. Our data suggest that TG2 null macrophages bear a proinflammatory phenotype, which might contribute to the enhanced susceptibility of these mice to develop autoimmunity and atherosclerosis.

Benchmarking project management practices of Caribbean organizations using analytic hierarchy process

Effective management of projects is becoming increasingly important for any type of organization to remain competitive in today’s dynamic business environment due to pressure of globalization. The use of benchmarking is widening as a technique for supporting project management. Benchmarking can be described as the search for the best practices, leading to the superior performance of an organization. However, effectiveness of benchmarking depends on the use of tools for collecting and analyzing information and deriving subsequent improvement projects. This study demonstrates how analytic hierarchy process (AHP), a multiple attribute decision-making technique, can be used for benchmarking project management practices. The entire methodology has been applied to benchmark project management practice of Caribbean public sector organizations with organizations in the Indian petroleum sector, organizations in the infrastructure sector of Thailand and the UK. This study demonstrates the effectiveness of a proposed benchmarking model using AHP, determines problems and issues of Caribbean project management in the public sector and suggests improvement measures for effective project management.

Integrated analytic hierarchy process and its applications:a literature review

Due to its wide applicability and ease of use, the analytic hierarchy process (AHP) has been studied extensively for the last 20 years. Recently, it is observed that the focus has been confined to the applications of the integrated AHPs rather than the stand-alone AHP. The five tools that commonly combined with the AHP include mathematical programming, quality function deployment (QFD), meta-heuristics, SWOT analysis, and data envelopment analysis (DEA). This paper reviews the literature of the applications of the integrated AHPs. Related articles appearing in the international journals from 1997 to 2006 are gathered and analyzed so that the following three questions can be answered: (i) which type of the integrated AHPs was paid most attention to? (ii) which area the integrated AHPs were prevalently applied to? (iii) is there any inadequacy of the approaches? Based on the inadequacy, if any, some improvements and possible future work are recommended. This research not only provides evidence that the integrated AHPs are better than the stand-alone AHP, but also aids the researchers and decision makers in applying the integrated AHPs effectively.

A genetic algorithm to optimise the component placement process in the PCB assembly

In printed circuit board (PCB) assembly, the efficiency of the component placement process is dependent on two interrelated issues: the sequence of component placement, that is, the component sequencing problem, and the assignment of component types to feeders of the placement machine, that is, the feeder arrangement problem. In cases where some components with the same type are assigned to more than one feeder, the component retrieval problem should also be considered. Due to their inseparable relationship, a hybrid genetic algorithm is adopted to solve these three problems simultaneously for a type of PCB placement machines called the sequential pick-and-place (PAP) machine in this paper. The objective is to minimise the total distance travelled by the placement head for assembling all components on a PCB. Besides, the algorithm is compared with the methods proposed by other researchers in order to examine its effectiveness and efficiency.

Improvement of bio-oil stability in wood pyrolysis process

Pyrolysis is one of several thermochemical technologies that convert solid biomass into more useful and valuable bio-fuels. Pyrolysis is thermal degradation in the complete or partial absence of oxygen. Under carefully controlled conditions, solid biomass can be converted to a liquid known as bie-oil in 75% yield on dry feed. Bio-oil can be used as a fuel but has the drawback of having a high level of oxygen due to the presence of a complex mixture of molecular fragments of cellulose, hemicellulose and lignin polymers. Also, bio-oil has a number of problems in use including high initial viscosity, instability resulting in increased viscosity or phase separation and high solids content. Much effort has been spent on upgrading bio-oil into a more usable liquid fuel, either by modifying the liquid or by major chemical and catalytic conversion to hydrocarbons. The overall primary objective was to improve oil stability by exploring different ways. The first was to detennine the effect of feed moisture content on bio-oil stability. The second method was to try to improve bio-oil stability by partially oxygenated pyrolysis. The third one was to improve stability by co-pyrolysis with methanol. The project was carried out on an existing laboratory pyrolysis reactor system, which works well with this project without redesign or modification too much. During the finishing stages of this project, it was found that the temperature of the condenser in the product collection system had a marked impact on pyrolysis liquid stability. This was discussed in this work and further recommendation given. The quantity of water coming from the feedstock and the pyrolysis reaction is important to liquid stability. In the present work the feedstock moisture content was varied and pyrolysis experiments were carried out over a range of temperatures. The quality of the bio-oil produced was measured as water content, initial viscosity and stability. The result showed that moderate (7.3-12.8 % moisture) feedstock moisture led to more stable bio-oil. One of drawbacks of bio-oil was its instability due to containing unstable oxygenated chemicals. Catalytic hydrotreatment of the oil and zeolite cracking of pyrolysis vapour were discllssed by many researchers, the processes were intended to eliminate oxygen in the bio-oil. In this work an alternative way oxygenated pyrolysis was introduced in order to reduce oil instability, which was intended to oxidise unstable oxygenated chemicals in the bio-oil. The results showed that liquid stability was improved by oxygen addition during the pyrolysis of beech wood at an optimum air factor of about 0.09-0.15. Methanol as a postproduction additive to bio-oil has been studied by many researchers and the most effective result came from adding methanol to oil just after production. Co-pyrolysis of spruce wood with methanol was undertaken in the present work and it was found that methanol improved liquid stability as a co-pyrolysis solvent but was no more effective than when used as a postproduction additive.

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.

Investigation into improving efficiency in a domestic drying process

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The application of robotics to the turbine blade encapsulation process

A survey of the existing state-of-the-art of turbine blade manufacture highlights two operations that have not been automated namely that of loading of a turbine blade into an encapsulation die, and that of removing a machined blade from the encapsulation block. The automation of blade decapsulation has not been pursued. In order to develop a system to automate the loading of an encapsulation die a prototype mechanical handling robot has been designed together with a computer controlled encapsulation die. The robot has been designed as a mechanical handling robot of cylindrical geometry, suitable for use in a circular work cell. It is the prototype for a production model to be called `The Cybermate'. The prototype robot is mechanically complete but due to unforeseen circumstances the robot control system is not available (the development of the control system did not form a part of this project), hence it has not been possible to fully test and assess the robot mechanical design. Robot loading of the encapsulation die has thus been simulated. The research work with regard to the encapsulation die has focused on the development of computer controlled, hydraulically actuated, location pins. Such pins compensate for the inherent positional inaccuracy of the loading robot and reproduce the dexterity of the human operator. Each pin comprises a miniature hydraulic cylinder, controlled by a standard bidirectional flow control valve. The precision positional control is obtained through pulsing of the valves under software control, with positional feedback from an 8-bit transducer. A test-rig comprising one hydraulic location pin together with an opposing spring loaded pin has demonstrated that such a pin arrangement can be controlled with a repeatability of +/-.00045'. In addition this test-rig has demonstrated that such a pin arrangement can be used to gauge and compensate for the dimensional error of the component held between the pins, by offsetting the pin datum positions to allow for the component error. A gauging repeatability of +/- 0.00015' was demonstrated. This work has led to the design and manufacture of an encapsulation die comprising ten such pins and the associated computer software. All aspects of the control software except blade gauging and positional data storage have been demonstrated. Work is now required to achieve the accuracy of control demonstrated by the single pin test-rig, with each of the ten pins in the encapsulation die. This would allow trials of the complete loading cycle to take place.

A process framework for selecting supply system architecture in manufacturing supply chains and networks

The process framework comprises three phases, as follows: scope the supply chain/network; identify the options for supply system architecture and select supply system architecture. It facilitates a structured approach that analyses the supply chain/network contextual characteristics, in order to ensure alignment with the appropriate supply system architecture. The process framework was derived from comprehensive literature review and archival case study analysis. The review led to the classification of supply system architectures according to their orientation, whether integrated; partially integrated; co-ordinated or independent. The classification was combined with the characteristics that influence the selection of supply system architecture to encapsulate the conceptual framework. It builds upon existing frameworks and methodologies by focusing on structured procedure; supporting project management; facilitating participation and clarifying point of entry. The process framework was initially tested in three case study applications from the food, automobile and hand tool industries. A variety of industrial settings was chosen to illustrate transferability. The case study applications indicate that the process framework is a valid approach to the problem; however, further testing is required. In particular, the use of group support system technologies to support the process and the steps involving the participation of software vendors need further testing. However, the process framework can be followed due to the clarity of its presentation. It considers the issue of timing by including alternative decision-making techniques, dependent on the constraints. It is useful for ensuring a sound business case is developed, with supporting documentation and analysis that identifies the strategic and functional requirements of supply system architecture.

Improved production of industrially relevant recombinant proteins: application of multi-factorial design of experiments and scalable process modelling

The work described in this thesis focuses on the use of a design-of-experiments approach in a multi-well mini-bioreactor to enable the rapid establishments of high yielding production phase conditions in yeast, which is an increasingly popular host system in both academic and industrial laboratories. Using green fluorescent protein secreted from the yeast, Pichia pastoris, a scalable predictive model of protein yield per cell was derived from 13 sets of conditions each with three factors (temperature, pH and dissolved oxygen) at 3 levels and was directly transferable to a 7 L bioreactor. This was in clear contrast to the situation in shake flasks, where the process parameters cannot be tightly controlled. By further optimisating both the accumulation of cell density in batch and improving the fed-batch induction regime, additional yield improvement was found to be additive to the per cell yield of the model. A separate study also demonstrated that improving biomass improved product yield in a second yeast species, Saccharomyces cerevisiae. Investigations of cell wall hydrophobicity in high cell density P. pastoris cultures indicated that cell wall hydrophobin (protein) compositional changes with growth phase becoming more hydrophobic in log growth than in lag or stationary phases. This is possibly due to an increased occurrence of proteins associated with cell division. Finally, the modelling approach was validated in mammalian cells, showing its flexibility and robustness. In summary, the strategy presented in this thesis has the benefit of reducing process development time in recombinant protein production, directly from bench to bioreactor.

Computer simulation for tube-making by the cold roll-forming process

The conventional design of forming rolls depends heavily on the individual skill of roll designers which is based on intuition and knowledge gained from previous work. Roll design is normally a trial an error procedure, however with the progress of computer technology, CAD/CAM systems for the cold roll-forming industry have been developed. Generally, however, these CAD systems can only provide a flower pattern based on the knowledge obtained from previously successful flower patterns. In the production of ERW (Electric Resistance Welded) tube and pipe, the need for a theoretical simulation of the roll-forming process, which can not only predict the occurrence of the edge buckling but also obtain the optimum forming condition, has been recognised. A new simulation system named "CADFORM" has been devised that can carry out the consistent forming simulation for this tube-making process. The CADFORM system applied an elastic-plastic stress-strain analysis and evaluate edge buckling by using a simplified model of the forming process. The results can also be visualised graphically. The calculated longitudinal strain is obtained by considering the deformation of lateral elements and takes into account the reduction in strains due to the fin-pass roll. These calculated strains correspond quite well with the experimental results. Using the calculated strains, the stresses in the strip can be estimated. The addition of the fin-pass roll reduction significantly reduces the longitudinal compressive stress and therefore effectively suppresses edge buckling. If the calculated longitudinal stress is controlled, by altering the forming flower pattern so it does not exceed the buckling stress within the material, then the occurrence of edge buckling can be avoided. CADFORM predicts the occurrence of edge buckling of the strip in tube-making and uses this information to suggest an appropriate flower pattern and forming conditions which will suppress the occurrence of the edge buckling.

Evaluation of options for energy recovery from municipal solid waste in India using the hierarchical analytical network process

In this paper a Hierarchical Analytical Network Process (HANP) model is demonstrated for evaluating alternative technologies for generating electricity from MSW in India. The technological alternatives and evaluation criteria for the HANP study are characterised by reviewing the literature and consulting experts in the field of waste management. Technologies reviewed in the context of India include landfill, anaerobic digestion, incineration, pelletisation and gasification. To investigate the sensitivity of the result, we examine variations in expert opinions and carry out an Analytical Hierarchy Process (AHP) analysis for comparison. We find that anaerobic digestion is the preferred technology for generating electricity from MSW in India. Gasification is indicated as the preferred technology in an AHP model due to the exclusion of criteria dependencies and in an HANP analysis when placing a high priority on net output and retention time. We conclude that HANP successfully provides a structured framework for recommending which technologies to pursue in India, and the adoption of such tools is critical at a time when key investments in infrastructure are being made. Therefore the presented methodology is thought to have a wider potential for investors, policy makers, researchers and plant developers in India and elsewhere. © 2013 Elsevier Ltd. All rights reserved.

The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Process improvement and quality management systems in the financial services industry:the case for the OPEX quality management system and framework

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The opportunity recognition process:the mechanisms by which entrepreneurial opportunities are recognised and the role played by social networks in this process

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