Engineering enzyme systems by recombination

Homologous recombination is a source of diversity in both natural and directed evolution. Standing genetic variation that has passed the test of natural selection is combined in new ways, generating functional and sometimes unexpected changes. In this work we evaluate the utility of homologous recombination as a protein engineering tool, both in comparison with and combined with other protein engineering techniques, and apply it to an industrially important enzyme: Hypocrea jecorina Cel5a.

Chapter 1 reviews work over the last five years on protein engineering by recombination. Chapter 2 describes the recombination of Hypocrea jecorina Cel5a endoglucanase with homologous enzymes in order to improve its activity at high temperatures. A chimeric Cel5a that is 10.1 °C more stable than wild-type and hydrolyzes 25% more cellulose at elevated temperatures is reported. Chapter 3 describes an investigation into the synergy of thermostable cellulases that have been engineered by recombination and other methods. An engineered endoglucanase and two engineered cellobiohydrolases synergistically hydrolyzed cellulose at high temperatures, releasing over 200% more reducing sugars over 60 h at their optimal mixture relative to the best mixture of wild-type enzymes. These results provide a framework for engineering cellulolytic enzyme mixtures for the industrial conditions of high temperatures and long incubation times.

In addition to this work on recombination, we explored three other problems in protein engineering. Chapter 4 describes an investigation into replacing enzymes with complex cofactors with simple cofactors, using an E. coli enolase as a model system. Chapter 5 describes engineering broad-spectrum aldehyde resistance in Saccharomyces cerevisiae by evolving an alcohol dehydrogenase simultaneously for activity and promiscuity. Chapter 6 describes an attempt to engineer gene-targeted hypermutagenesis into E. coli to facilitate continuous in vivo selection systems.

Ink-jet printing for patterning engineering surfaces

This work explored the use of industrial drop-on-demand inkjet printing for masking steel surfaces on engineering components, followed by chemical etching, to produce patterned surfaces. A solvent-based ink was printed on to mild steel samples and the influences of substrate topography and substrate temperature were investigated. Contact angle measurements were used to assess wettability. Regular patterns of circular spots (∼60 /on diameter) and more complex mask patterns were printed. Variation of the substrate temperature had negligible effect on the final size of the printed drops or on the resolution achieved. Colored optical interference fringes were observed on the dried ink deposits and correlated with film thickness measurements by whitelight interferometry.

Developing a framework for mapping industrial emergence

The industrial landscape is becoming increasingly complex and dynamic, with innovative technologies stimulating the emergence of new industries and business models. This paper presents a preliminary framework for mapping industrial emergence, based on roadmapping principles, in order to understand the nature and characteristics of such phenomena. The focus at this stage is on historical examples of industrial emergence, with the preliminary framework based on observations from 20 'quick scan' maps, one of which is used to illustrate the framework. The learning from these historical cases, combined with further industrial consultation and literature review, will be used to develop practical methods for strategy and policy application. The paper concludes by summarising key learning points and further work needed to achieve these outcomes. © 2009 PICMET.

Proceedings of an international workshop on the value of computer-based engineering tools, held in Cambridge in April 1997

There is increasing adoption of computer-based tools to support the product development process. Tolls include computer-aided design, computer-aided manufacture, systems engineering and product data management systems. The fact that companies choose to invest in tools might be regarded as evidence that tools, in aggregate, are perceived to possess business value through their application to engineering activities. Yet the ways in which value accrues from tool technology are poorly understood.

This report records the proceedings of an international workshop during which some novel approaches to improving our understanding of this problem of tool valuation were presented and debated. The value of methods and processes were also discussed. The workshop brought together British, Dutch, German and Italian researchers. The presenters included speakers from industry and academia (the University of Cambridge, the University of Magdeburg and the Politechnico de Torino)

The work presented showed great variety. Research methods include case studies, questionnaires, statistical analysis, semi-structured interviews, deduction, inductive reasoning, the recording of anecdotes and analogies. The presentations drew on financial investment theory, the industrial experience of workshop participants, discussions with students developing tools, modern economic theories and speculation on the effects of company capabilities.

A workbook-based methodology for implementing concurrent engineering

Concurrent Engineering demands a new way of working and many organisations experience difficulty during implementation. The research described in this paper has the aim to develop a paper-based workbook style methodology that companies can use to increase the benefits generated by Concurrent Engineering, while reducing implementation costs, risk and time. The three-stage methodology provides guidance based on knowledge accumulated from implementation experience and best practitioners. It encourages companies to learn to manage their Concurrent Engineering implementation by taking actions which expose them to new and valuable experiences. This helps to continuously improve understanding of how to maximise the benefits from Concurrent Engineering. The methodology is particularly designed to cater for organisational and contextual uniqueness, as Concurrent Engineering implementations will vary from company to company. Using key actions which improve the Concurrent Engineering implementation process, individual companies can develop their own 'best practice' for product development. The methodology ensures that key implementation issues, which are primarily human and organisational, are addressed using simple but proven techniques. This paper describes the key issues that the majority of companies face when implementing Concurrent Engineering. The structure of the methodology is described to show how the issues are addressed and resolved. The key actions used to improve the Concurrent Engineering implementation process are explained and their inclusion in the implementation methodology described. Relevance to industry. Implementation of Concurrent Engineering concepts in manufacturing industry has not been a straightforward process. This paper describes a workbook-style tool that manufacturing companies can use to accelerate and improve their Concurrent Engineering implementation. © 1995.

Managing global network operations along the engineering value chain

Purpose: This paper aims to improve understanding of how to manage global network operations from an engineering perspective. Design/methodology/approach: This research adopted a theory building approach based on case studies. Grounded in the existing literature, the theoretical framework was refined and enriched through nine in-depth case studies in the industry sectors of aerospace, automotives, defence and electrics and electronics. Findings: This paper demonstrates the main value creation mechanisms of global network operations along the engineering value chain. Typical organisational features to support the value creation mechanisms are captured, and the key issues in engineering network design and operations are presented with an overall framework. Practical implications: Evidenced by a series of pilot applications, outputs of this research can help companies to improve the performance of their current engineering networks and design new engineering networks to better support their global businesses and customers in a systematic way. Originality/value: Issues about the design and operations of global engineering networks (GEN) are poorly understood in the existing literature in contrast to their apparent importance in value creation and realisation. To address this knowledge gap, this paper introduces the concept of engineering value chain to highlight the potential of a value chain approach to the exploration of engineering activities in a complex business context. At the same time, it develops an overall framework for managing GEN along the engineering value chain. This improves our understanding of engineering in industrial value chains and extends the theoretical understanding of GEN through integrating the engineering network theories and the value chain concepts. © Emerald Group Publishing Limited.

Industrial ecology at factory level: A prototype methodology

The concept of sustainable manufacturing is a form of pollution prevention that integrates environmental considerations in the production of goods while focusing on efficient resource use. Taking the industrial ecology perspective, this efficiency comes from improved resource flow management. The assessment of material, energy and waste resource flows, therefore, offers a route to viewing and analysing a manufacturing system as an ecosystem using industrial ecology biological analogy and can, in turn, support the identification of improvement opportunities in the material, energy and waste flows. This application of industrial ecology at factory level is absent from the literature. This article provides a prototype methodology to apply the concepts of industrial ecology using material, energy and waste process flows to address this gap in the literature. Various modelling techniques were reviewed and candidates selected to test the prototype methodology in an industrial case. The application of the prototype methodology showed the possibility of using the material, energy and waste resource flows through the factory to link manufacturing operations and supporting facilities, and to identify potential improvements in resource use. The outcomes of the work provide a basis to build the specifications for a modelling tool that can support those analysing their manufacturing system to improve their environmental performance and move towards sustainable manufacturing. © IMechE 2012.

Requirements-based development of an improved engineering change management method

Engineering changes (ECs) are essential in complex product development, and their management is a crucial discipline for engineering industries. Numerous methods have been developed to support EC management (ECM), of which the change prediction method (CPM) is one of the most established. This article contributes a requirements-based benchmarking approach to assess and improve existing methods. The CPM is selected to be improved. First, based on a comprehensive literature survey and insights from industrial case studies, a set of 25 requirements for change management methods are developed. Second, these requirements are used as benchmarking criteria to assess the CPM in comparison to seven other promising methods. Third, the best-in-class solutions for each requirement are investigated to draw improvement suggestions for the CPM. Finally, an enhanced ECM method which implements these improvements is presented. © 2013 © 2013 The Author(s). Published by Taylor & Francis.

Understanding and navigating industrial emergence

Industrial emergence is a broad and complex domain, with relevant perspectives ranging in scale from the individual entrepreneur and firm with the business decisions and actions they make to the policies of nations and global patterns of industrialisation. The research described in this article has adopted a holistic approach, based on structured mapping methods, in an attempt to depict and understand the dynamics and patterns of industrial emergence across a broad spectrum from early scientific discovery to large-scale industrialisation. The breadth of scope and application has enabled a framework and set of four tools to be developed that have wide applicability. The utility of the approaches has been demonstrated through case studies and trials in a diverse range of industrial contexts. The adoption of such a broad scope also presents substantial challenges and limitations, with these providing an opportunity for further research. © IMechE 2013.

Industrial development and land use/cover change and their effects on local environment: a case study of Changshu in eastern coastal China

The interactions among industrial development, land use/cover change (LUCC), and environmental effects in Changshu in the eastern coastal China were analyzed using high-resolution Landsat TM data in 1990, 1995, 2000, and 2006, socio-economic data and water environmental quality monitoring data from research institutes and governmental departments. Three phases of industrial development in Changshu were examined (i.e., the three periods of 1990 to 1995, 1995 to 2000, and 2000 to 2006). Besides industrial development and rapid urbanization, land use/cover in Changshu had changed drastically from 1990 to 2006. This change was characterized by major replacements of farmland by urban and rural settlements, artificial ponds, forested and constructed land. Industrialization, urbanization, agricultural structure adjustment, and rural housing construction were the major socio-economic driving forces of LUCC in Changshu. In addition, the annual value of ecosystem services in Changshu decreased slightly during 1990-2000, but increased significantly during 2000-2006. Nevertheless, the local environmental quality in Changshu, especially in rural areas, has not yet been improved significantly. Thus, this paper suggests an increased attention to fully realize the role of land supply in adjustment of environment-friendly industrial structure and urban-rural spatial restructuring, and translating the land management and environmental protection policies into an optimized industrial distribution and land-use pattern.

Engineering design of a bioprocess for the production of natural red colourants by submerged fermentation of the thermophilic fungus Penicillium purpurogenum GH2

The development of a new bioprocess requires several steps from initial concept to a practical and feasible application. Industrial applications of fungal pigments will depend on: (i) safety of consumption, (ii) stability of the pigments to the food processing conditions required by the products where they will be incorporated and (iii) high production yields so that production costs are reasonable. Of these requirements the first involves the highest research costs and the practical application of this type of processes may face several hurdles until final regulatory approval as a new food ingredient. Therefore, before going through expensive research to have them accepted as new products, the process potential should be assessed early on, and this brings forward pigment stability studies and process optimisation goals. Only ingredients that are usable in economically feasible conditions should progress to regulatory approval. This thesis covers these two aspects, stability and process optimisation, for a potential new ingredient; natural red colour, produced by microbial fermentation. The main goal was to design, optimise and scale-up the production process of red pigments by Penicillium purpurogenum GH2. The approach followed to reach this objective was first to establish that pigments produced by Penicillium purpurogenum GH2 are sufficiently stable under different processing conditions (thermal and non-thermal) that can be found in food and textile industries. Once defined that pigments were stable enough, the work progressed towards process optimisation, aiming for the highest productivity using submerged fermentation as production culture. Optimum production conditions defined at flask scale were used to scale up the pigment production process to a pilot reactor scale. Finally, the potential applications of the pigments were assessed. Based on this sequence of specific targets, the thesis was structured in six parts, containing a total of nine chapters. Engineering design of a bioprocess for the production of natural red colourants by submerged fermentation of the thermophilic fungus Penicillium purpurogenum GH2.

Modelling of industrial multi-physics processes—a key role for computational mechanics.

In the analysis of industrial processes, there is an increasing emphasis on systems governed by interacting continuum phenomena. Mathematical models of such multi-physics processes can only be achieved for practical simulations through computational solution procedures—computational mechanics. Examples of such multi-physics systems in the context of metals processing are used to explore some of the key issues. Finite-volume methods on unstructured meshes are proposed as a means to achieve efficient rapid solutions to such systems. Issues associated with the software design, the exploitation of high performance computers, and the concept of the virtual computational-mechanics modelling laboratory are also addressed in this context.