Editorial

This special issue of the Journal of the Operational Research Society is dedicated to papers on the related subjects of knowledge management and intellectual capital. These subjects continue to generate considerable interest amongst both practitioners and academics. This issue demonstrates that operational researchers have many contributions to offer to the area, especially by bringing multi-disciplinary, integrated and holistic perspectives. The papers included are both theoretical as well as practical, and include a number of case studies showing how knowledge management has been implemented in practice that may assist other organisations in their search for a better means of managing what is now recognised as a core organisational activity. It has been accepted by a growing number of organisations that the precise handling of information and knowledge is a significant factor in facilitating their success but that there is a challenge in how to implement a strategy and processes for this handling. It is here, in the particular area of knowledge process handling that we can see the contributions of operational researchers most clearly as is illustrated in the papers included in this journal edition. The issue comprises nine papers, contributed by authors based in eight different countries on five continents. Lind and Seigerroth describe an approach that they call team-based reconstruction, intended to help articulate knowledge in a particular organisational. context. They illustrate the use of this approach with three case studies, two in manufacturing and one in public sector health care. Different ways of carrying out reconstruction are analysed, and the benefits of team-based reconstruction are established. Edwards and Kidd, and Connell, Powell and Klein both concentrate on knowledge transfer. Edwards and Kidd discuss the issues involved in transferring knowledge across frontières (borders) of various kinds, from those borders within organisations to those between countries. They present two examples, one in distribution and the other in manufacturing. They conclude that trust and culture both play an important part in facilitating such transfers, that IT should be kept in a supporting role in knowledge management projects, and that a staged approach to this IT support may be the most effective. Connell, Powell and Klein consider the oft-quoted distinction between explicit and tacit knowledge, and argue that such a distinction is sometimes unhelpful. They suggest that knowledge should rather be regarded as a holistic systemic property. The consequences of this for knowledge transfer are examined, with a particular emphasis on what this might mean for the practice of OR Their view of OR in the context of knowledge management very much echoes Lind and Seigerroth's focus on knowledge for human action. This is an interesting convergence of views given that, broadly speaking, one set of authors comes from within the OR community, and the other from outside it. Hafeez and Abdelmeguid present the nearest to a 'hard' OR contribution of the papers in this special issue. In their paper they construct and use system dynamics models to investigate alternative ways in which an organisation might close a knowledge gap or skills gap. The methods they use have the potential to be generalised to any other quantifiable aspects of intellectual capital. The contribution by Revilla, Sarkis and Modrego is also at the 'hard' end of the spectrum. They evaluate the performance of public–private research collaborations in Spain, using an approach based on data envelopment analysis. They found that larger organisations tended to perform relatively better than smaller ones, even though the approach used takes into account scale effects. Perhaps more interesting was that many factors that might have been thought relevant, such as the organisation's existing knowledge base or how widely applicable the results of the project would be, had no significant effect on the performance. It may be that how well the partnership between the collaborators works (not a factor it was possible to take into account in this study) is more important than most other factors. Mak and Ramaprasad introduce the concept of a knowledge supply network. This builds on existing ideas of supply chain management, but also integrates the design chain and the marketing chain, to address all the intellectual property connected with the network as a whole. The authors regard the knowledge supply network as the natural focus for considering knowledge management issues. They propose seven criteria for evaluating knowledge supply network architecture, and illustrate their argument with an example from the electronics industry—integrated circuit design and fabrication. In the paper by Hasan and Crawford, their interest lies in the holistic approach to knowledge management. They demonstrate their argument—that there is no simple IT solution for organisational knowledge management efforts—through two case study investigations. These case studies, in Australian universities, are investigated through cultural historical activity theory, which focuses the study on the activities that are carried out by people in support of their interpretations of their role, the opportunities available and the organisation's purpose. Human activities, it is argued, are mediated by the available tools, including IT and IS and in this particular context, KMS. It is this argument that places the available technology into the knowledge activity process and permits the future design of KMS to be improved through the lessons learnt by studying these knowledge activity systems in practice. Wijnhoven concentrates on knowledge management at the operational level of the organisation. He is concerned with studying the transformation of certain inputs to outputs—the operations function—and the consequent realisation of organisational goals via the management of these operations. He argues that the inputs and outputs of this process in the context of knowledge management are different types of knowledge and names the operation method the knowledge logistics. The method of transformation he calls learning. This theoretical paper discusses the operational management of four types of knowledge objects—explicit understanding; information; skills; and norms and values; and shows how through the proposed framework learning can transfer these objects to clients in a logistical process without a major transformation in content. Millie Kwan continues this theme with a paper about process-oriented knowledge management. In her case study she discusses an implementation of knowledge management where the knowledge is centred around an organisational process and the mission, rationale and objectives of the process define the scope of the project. In her case they are concerned with the effective use of real estate (property and buildings) within a Fortune 100 company. In order to manage the knowledge about this property and the process by which the best 'deal' for internal customers and the overall company was reached, a KMS was devised. She argues that process knowledge is a source of core competence and thus needs to be strategically managed. Finally, you may also wish to read a related paper originally submitted for this Special Issue, 'Customer knowledge management' by Garcia-Murillo and Annabi, which was published in the August 2002 issue of the Journal of the Operational Research Society, 53(8), 875–884.

Enhancing vaccine design strategies:applications for protein science, proteomics and adjuvants

Editorial

Editorial overview:new protein production tools for structural biology

Full text: The idea of producing proteins from recombinant DNA hatched almost half a century ago. In his PhD thesis, Peter Lobban foresaw the prospect of inserting foreign DNA (from any source, including mammalian cells) into the genome of a λ phage in order to detect and recover protein products from Escherichia coli [ 1 and 2]. Only a few years later, in 1977, Herbert Boyer and his colleagues succeeded in the first ever expression of a peptide-coding gene in E. coli — they produced recombinant somatostatin [ 3] followed shortly after by human insulin. The field has advanced enormously since those early days and today recombinant proteins have become indispensable in advancing research and development in all fields of the life sciences. Structural biology, in particular, has benefitted tremendously from recombinant protein biotechnology, and an overwhelming proportion of the entries in the Protein Data Bank (PDB) are based on heterologously expressed proteins. Nonetheless, synthesizing, purifying and stabilizing recombinant proteins can still be thoroughly challenging. For example, the soluble proteome is organized to a large part into multicomponent complexes (in humans often comprising ten or more subunits), posing critical challenges for recombinant production. A third of all proteins in cells are located in the membrane, and pose special challenges that require a more bespoke approach. Recent advances may now mean that even these most recalcitrant of proteins could become tenable structural biology targets on a more routine basis. In this special issue, we examine progress in key areas that suggests this is indeed the case. Our first contribution examines the importance of understanding quality control in the host cell during recombinant protein production, and pays particular attention to the synthesis of recombinant membrane proteins. A major challenge faced by any host cell factory is the balance it must strike between its own requirements for growth and the fact that its cellular machinery has essentially been hijacked by an expression construct. In this context, Bill and von der Haar examine emerging insights into the role of the dependent pathways of translation and protein folding in defining high-yielding recombinant membrane protein production experiments for the common prokaryotic and eukaryotic expression hosts. Rather than acting as isolated entities, many membrane proteins form complexes to carry out their functions. To understand their biological mechanisms, it is essential to study the molecular structure of the intact membrane protein assemblies. Recombinant production of membrane protein complexes is still a formidable, at times insurmountable, challenge. In these cases, extraction from natural sources is the only option to prepare samples for structural and functional studies. Zorman and co-workers, in our second contribution, provide an overview of recent advances in the production of multi-subunit membrane protein complexes and highlight recent achievements in membrane protein structural research brought about by state-of-the-art near-atomic resolution cryo-electron microscopy techniques. E. coli has been the dominant host cell for recombinant protein production. Nonetheless, eukaryotic expression systems, including yeasts, insect cells and mammalian cells, are increasingly gaining prominence in the field. The yeast species Pichia pastoris, is a well-established recombinant expression system for a number of applications, including the production of a range of different membrane proteins. Byrne reviews high-resolution structures that have been determined using this methylotroph as an expression host. Although it is not yet clear why P. pastoris is suited to producing such a wide range of membrane proteins, its ease of use and the availability of diverse tools that can be readily implemented in standard bioscience laboratories mean that it is likely to become an increasingly popular option in structural biology pipelines. The contribution by Columbus concludes the membrane protein section of this volume. In her overview of post-expression strategies, Columbus surveys the four most common biochemical approaches for the structural investigation of membrane proteins. Limited proteolysis has successfully aided structure determination of membrane proteins in many cases. Deglycosylation of membrane proteins following production and purification analysis has also facilitated membrane protein structure analysis. Moreover, chemical modifications, such as lysine methylation and cysteine alkylation, have proven their worth to facilitate crystallization of membrane proteins, as well as NMR investigations of membrane protein conformational sampling. Together these approaches have greatly facilitated the structure determination of more than 40 membrane proteins to date. It may be an advantage to produce a target protein in mammalian cells, especially if authentic post-translational modifications such as glycosylation are required for proper activity. Chinese Hamster Ovary (CHO) cells and Human Embryonic Kidney (HEK) 293 cell lines have emerged as excellent hosts for heterologous production. The generation of stable cell-lines is often an aspiration for synthesizing proteins expressed in mammalian cells, in particular if high volumetric yields are to be achieved. In his report, Buessow surveys recent structures of proteins produced using stable mammalian cells and summarizes both well-established and novel approaches to facilitate stable cell-line generation for structural biology applications. The ambition of many biologists is to observe a protein's structure in the native environment of the cell itself. Until recently, this seemed to be more of a dream than a reality. Advances in nuclear magnetic resonance (NMR) spectroscopy techniques, however, have now made possible the observation of mechanistic events at the molecular level of protein structure. Smith and colleagues, in an exciting contribution, review emerging ‘in-cell NMR’ techniques that demonstrate the potential to monitor biological activities by NMR in real time in native physiological environments. A current drawback of NMR as a structure determination tool derives from size limitations of the molecule under investigation and the structures of large proteins and their complexes are therefore typically intractable by NMR. A solution to this challenge is the use of selective isotope labeling of the target protein, which results in a marked reduction of the complexity of NMR spectra and allows dynamic processes even in very large proteins and even ribosomes to be investigated. Kerfah and co-workers introduce methyl-specific isotopic labeling as a molecular tool-box, and review its applications to the solution NMR analysis of large proteins. Tyagi and Lemke next examine single-molecule FRET and crosslinking following the co-translational incorporation of non-canonical amino acids (ncAAs); the goal here is to move beyond static snap-shots of proteins and their complexes and to observe them as dynamic entities. The encoding of ncAAs through codon-suppression technology allows biomolecules to be investigated with diverse structural biology methods. In their article, Tyagi and Lemke discuss these approaches and speculate on the design of improved host organisms for ‘integrative structural biology research’. Our volume concludes with two contributions that resolve particular bottlenecks in the protein structure determination pipeline. The contribution by Crepin and co-workers introduces the concept of polyproteins in contemporary structural biology. Polyproteins are widespread in nature. They represent long polypeptide chains in which individual smaller proteins with different biological function are covalently linked together. Highly specific proteases then tailor the polyprotein into its constituent proteins. Many viruses use polyproteins as a means of organizing their proteome. The concept of polyproteins has now been exploited successfully to produce hitherto inaccessible recombinant protein complexes. For instance, by means of a self-processing synthetic polyprotein, the influenza polymerase, a high-value drug target that had remained elusive for decades, has been produced, and its high-resolution structure determined. In the contribution by Desmyter and co-workers, a further, often imposing, bottleneck in high-resolution protein structure determination is addressed: The requirement to form stable three-dimensional crystal lattices that diffract incident X-ray radiation to high resolution. Nanobodies have proven to be uniquely useful as crystallization chaperones, to coax challenging targets into suitable crystal lattices. Desmyter and co-workers review the generation of nanobodies by immunization, and highlight the application of this powerful technology to the crystallography of important protein specimens including G protein-coupled receptors (GPCRs). Recombinant protein production has come a long way since Peter Lobban's hypothesis in the late 1960s, with recombinant proteins now a dominant force in structural biology. The contributions in this volume showcase an impressive array of inventive approaches that are being developed and implemented, ever increasing the scope of recombinant technology to facilitate the determination of elusive protein structures. Powerful new methods from synthetic biology are further accelerating progress. Structure determination is now reaching into the living cell with the ultimate goal of observing functional molecular architectures in action in their native physiological environment. We anticipate that even the most challenging protein assemblies will be tackled by recombinant technology in the near future.

Guest editorial:special issue on digitial enterprise technology

Full text This Proceedings volume contains selected papers from the Fourth International CIRP-sponsored, Conference on Digital Enterprise Technology (DET2007), which was held at the University of Bath, UK, 19–21 September 2007. All selected papers have been suitably enhanced for publication in the Journal and have undergone full review. Digital enterprise technology (DET) is ‘the collection of systems and methods for the digital modelling and analysis of the global product development and realization process, in the context of lifecycle management.’ The principal aim of the DET concept is to provide a coherent context for the development and integration of the various digital technologies that underpin modern design and manufacturing. These technologies can be classified according to the following five key areas. 1. Distributed and collaborative design. 2. Process modelling and process planning. 3. Advanced factory design and modelling. 4. Physical-to-digital environment integrators–verification. 5. Enterprise integration technologies. This special issue is representative of the wide breadth of the DET concept including; a comprehensive review of digital engineering, design processes, digital modelling of machine tools, forming, robotics and machining processes, verification and metrology, and dynamic networks. It is particularly pleasing to see the development of metrology as a key aspect of modern manufacturing technology, linking design intent to process capability. The papers published herein will facilitate the exploration of new and evolving research concepts by the international research community and will influence the development of international standards for the application of DET technologies.