Strategic ambiguity as a rhetorical resource for enabling multiple interests

The literature on ambiguity reflects contradictory views on its value as a resource or a problem for organizational action. In this longitudinal empirical study of ambiguity about a strategic goal, we examined how strategic ambiguity is used as a discursive resource by different organizational constituents and how that is associated with collective action around the strategic goal. We found four rhetorical positions, each of which drew upon strategic ambiguity to construct the strategic goal differently according to whether the various constituents were asserting their own interests or accommodating wider organizational interests. However, we also found that the different constituents maintained these four rhetorical positions simultaneously over time, enabling them to shift between their own and other’s interests rather than converging upon a common interest. These findings are used to develop a conceptual framework that explains how strategic ambiguity might serve as a resource for different organizational constituents to assert their own interests whilst also enabling collective organizational action, at least of a temporary nature.

Action research in a collective organisation:Developing an education programme in a pressure group

The aim of this project was to develop the education work of an environmental pressure group. The research devised and implemented a project to produce multi-media teaching packs on the urban environment. Whilst this involved understanding environmental education it was necessary to research beyond this to include the various structural and dynamic constraints on change in the field. This presented a number of methodological difficulties; from the resolution of which a model of the research process involved in this project has been developed. It is argued that research oriented towards practical change requires the insights of an experienced practitioner to be combined with the rigours of controlled systematic enquiry. Together these function as a model-building process encompassing intuition, induction and deduction. Model testing is carried out through repeated intervention in the field; thus an interplay between researcher and client ensues such that the project develops in a mutually acceptable direction. In practice, this development will be both unpredictable and erratic. Although the conclusions reached here are based on a single case study they address general methodological issues likely to be encountered in different field settings concerned with different practical problems.

Constructing institutional change: emergence, contestation and convergence of business models in the field of Java application servers

How are innovative new business models established if organizations constantly compare themselves against existing criteria and expectations? The objective is to address this question from the perspective of innovators and their ability to redefine established expectations and evaluation criteria. The research questions ask whether there are discernible patterns of discursive action through which innovators theorize institutional change and what role such theorizations play for mobilizing support and realizing change projects. These questions are investigated through a case study on a critical area of enterprise computing software, Java application servers. In the present case, business practices and models were already well established among incumbents with critical market areas allocated to few dominant firms. Fringe players started experimenting with a new business approach of selling services around freely available opensource application servers. While most new players struggled, one new entrant succeeded in leading incumbents to adopt and compete on the new model. The case demonstrates that innovative and substantially new models and practices are established in organizational fields when innovators are able to refine expectations and evaluation criteria within an organisational field. The study addresses the theoretical paradox of embedded agency. Actors who are embedded in prevailing institutional logics and structures find it hard to perceive potentially disruptive opportunities that fall outside existing ways of doing things. Changing prevailing institutional logics and structures requires strategic and institutional work aimed at overcoming barriers to innovation. The study addresses this problem through the lens of (new) institutional theory. This discourse methodology traces the process through which innovators were able to establish a new social and business model in the field.

Parabolic optical pulses under the action of the third-order dispersion

Recent developments in nonlinear optics reveal an interesting class of pulses with a parabolic intensity profile in the energy-containing core and a linear frequency chirp that can propagate in a fiber with normal group-velocity dispersion. Parabolic pulses propagate in a stable selfsimilar manner, holding certain relations (scaling) between pulse power, width, and chirp parameter. In the additional presence of linear amplification, they enjoy the remarkable property of representing a common asymptotic state (or attractor) for arbitrary initial conditions. Analytically, self-similar (SS) parabolic pulses can be found as asymptotic, approximate solutions of the nonlinear Schr¨odinger equation (NLSE) with gain in the semi-classical (largeamplitude/small-dispersion) limit. By analogy with the well-known stable dynamics of solitary waves - solitons, these SS parabolic pulses have come to be known as similaritons. In practical fiber systems, inherent third-order dispersion (TOD) in the fiber always introduces a certain degree of asymmetry in the structure of the propagating pulse, eventually leading to pulse break-up. To date, there is no analytic theory of parabolic pulses under the action of TOD. Here, we develop aWKB perturbation analysis that describes the effect of weak TOD on the parabolic pulse solution of the NLSE in a fiber gain medium. The induced perturbation in phase and amplitude can be found to any order. The theoretical model predicts with sufficient accuracy the pulse structural changes induced by TOD, which are observed through direct numerical NLSE simulations.

Shaping strategic action through the rhetorical construction and exploitation of ambiguity

This paper extends existing understandings of how actors' constructions of ambiguity shape the emergent process of strategic action. We theoretically elaborate the role of rhetoric in exploiting strategic ambiguity, based on analysis of a longitudinal case study of an internationalization strategy within a business school. Our data show that actors use rhetoric to construct three types of strategic ambiguity: protective ambiguity that appeals to common values in order to protect particular interests, invitational ambiguity that appeals to common values in order to invite participation in particular actions, and adaptive ambiguity that enables the temporary adoption of specific values in order to appeal to a particular audience at one point in time. These rhetorical constructions of ambiguity follow a processual pattern that shapes the emergent process of strategic action. Our findings show that (1) the strategic actions that emerge are shaped by the way actors construct and exploit ambiguity, (2) the ambiguity intrinsic to the action is analytically distinct from ambiguity that is constructed and exploited by actors, and (3) ambiguity construction shifts over time to accommodate the emerging pattern of actions.

Deindustrialisation:lessons from the structural outcomes of post-Communist transition

Theoretical and empirical studies show that deindustrialisation, broadly observed in developed countries, is an inherent part of the economic development pattern. However, post-communist countries, while being only middle-income economies, have also experienced deindustrialisation. Building on the model developed by Rowthorn and Wells (1987) we explain this phenomenon and show that there is a strong negative relationship between the magnitude of deindustrialisation and the efficiency and consistency of market reforms. We also demonstrate that reforms of the agricultural sector play a significant role in placing a transition country on a development path that guarantees convergence to EU employment structures.

Parabolic optical pulses under the action of the third-order dispersion

Recent developments in nonlinear optics reveal an interesting class of pulses with a parabolic intensity profile in the energy-containing core and a linear frequency chirp that can propagate in a fiber with normal group-velocity dispersion. Parabolic pulses propagate in a stable selfsimilar manner, holding certain relations (scaling) between pulse power, width, and chirp parameter. In the additional presence of linear amplification, they enjoy the remarkable property of representing a common asymptotic state (or attractor) for arbitrary initial conditions. Analytically, self-similar (SS) parabolic pulses can be found as asymptotic, approximate solutions of the nonlinear Schr¨odinger equation (NLSE) with gain in the semi-classical (largeamplitude/small-dispersion) limit. By analogy with the well-known stable dynamics of solitary waves - solitons, these SS parabolic pulses have come to be known as similaritons. In practical fiber systems, inherent third-order dispersion (TOD) in the fiber always introduces a certain degree of asymmetry in the structure of the propagating pulse, eventually leading to pulse break-up. To date, there is no analytic theory of parabolic pulses under the action of TOD. Here, we develop aWKB perturbation analysis that describes the effect of weak TOD on the parabolic pulse solution of the NLSE in a fiber gain medium. The induced perturbation in phase and amplitude can be found to any order. The theoretical model predicts with sufficient accuracy the pulse structural changes induced by TOD, which are observed through direct numerical NLSE simulations.

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.

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner.

Modes of action of antibacterial agents

This chapter describes the modes of action of the major antibiotics and synthetic agents used to treat bacterial infections. Particular attention is given to the biochemical mechanisms by which the agents interfere with biosynthetic processes and the basis for their selective antibacterial action. Interference with the biosynthesis and assembly of structural components of the bacterial cell wall provides the basis for many important groups of antibiotics, including the agents targeting steps in peptidoglycan synthesis. Other agents exploit more subtle differences between bacteria and mammalian cells in fundamental processes such as DNA, RNA and protein synthesis.