16 resultados para Critical challenges

em Aston University Research Archive


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The goal of this roadmap paper is to summarize the state-of-the-art and to identify critical challenges for the systematic software engineering of self-adaptive systems. The paper is partitioned into four parts, one for each of the identified essential views of self-adaptation: modelling dimensions, requirements, engineering, and assurances. For each view, we present the state-of-the-art and the challenges that our community must address. This roadmap paper is a result of the Dagstuhl Seminar 08031 on "Software Engineering for Self-Adaptive Systems," which took place in January 2008. © 2009 Springer Berlin Heidelberg.

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Re-emphasizing the need to examine human resource management (HRM) in context, this article builds around four themes. First, it analyses the main issues discussed in the existing literature regarding HRM in the Asian context. Second, it highlights the critical challenges facing HRM function in the region. Third, along with the analysis, it presents an agenda for future research. Fourth, it presents a framework useful for highlighting the context specific nature of Asian HRM functions and the main determinants of HRM policies and practices from a cross-national comparative perspective.

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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.

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The fabrication precision is one of the most critical challenges to the creation of practical photonic circuits composed of coupled high Q-factor microresonators. While very accurate transient tuning of microresonators based on local heating has been reported, the record precision of permanent resonance positioning achieved by post-processing is still within 1 and 5 GHz. Here we demonstrate two coupled bottle microresonators fabricated at the fiber surface with resonances that are matched with a better than 0.16 GHz precision. This corresponds to a better than 0.17 Å precision in the effective fiber radius variation. The achieved fabrication precision is only limited by the resolution of our optical spectrum analyzer and can be potentially improved by an order of magnitude.

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In this article, we highlight the significance and need for conducting context-specific human resource management (HRM) research, by focusing on four critical themes. First, we discuss the need to analyze the convergence-divergence debate on HRM in Asia-Pacific. Next, we present an integrated framework, which would be very useful for conducting cross-national HRM research designed to focus on the key determinants of the dominant national HRM systems in the region. Following this, we discuss the critical challenges facing the HRM function in Asia-Pacific. Finally, we present an agenda for future research by presenting a series of research themes.

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This paper departs from this point to consider whether and how crisis thinking contributes to practices of affirmative critique and transformative social action in late-capitalist societies. I argue that different deployments of crisis thinking have different ‘affect-effects’ and consequences for ethical and political practice. Some work to mobilize political action through articulating a politics of fear, assuming that people take most responsibility for the future when they fear the alternatives. Other forms of crisis thinking work to heighten critical awareness by disrupting existential certainty, asserting an ‘ethics of ambiguity’ which assumes that the continuous production of uncertain futures is a fundamental part of the human condition (de Beauvoir, 2000). In this paper, I hope to illustrate that the first deployment of crisis thinking can easily justify the closing down of political debate, discouraging radical experimentation and critique for the sake of resolving problems in a timely and decisive way. The second approach to crisis thinking, on the other hand, has greater potential to enable intellectual and political alterity in everyday life—but one that poses considerable challenges for our understandings of and responses to climate change...

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This paper takes a critical and evaluative stance toward micro-activity-based approaches to understanding strategy. It argues that such approaches bring with them important theoretical and empirical challenges. The paper argues against a tendency to reductionism without equal emphasis to the contextual influences that bound micro-strategising. Finally, the paper argues for a more international and comparative approach to micro-strategy studies than has currently been the case.

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Systematic review has developed as a specific methodology for searching for, appraising and synthesizing findings of primary studies, and has rapidly become a cornerstone of the evidence-based practice and policy movement. Qualitative research has traditionally been excluded from systematic reviews, and much effort is now being invested in resolving the daunting methodological and epistemological challenges associated with trying to move towards more inclusive forms of review. We describe our experiences, as a very diverse multidisciplinary group, in attempting to incorporate qualitative research in a systematic review of support for breastfeeding. We show how every stage of the review process, from asking the review question through to searching for and sampling the evidence, appraising the evidence and producing a synthesis, provoked profound questions about whether a review that includes qualitative research can remain consistent with the frame offered by current systematic review methodology. We conclude that more debate and dialogue between the different communities that wish to develop review methodology is needed, and that attempts to impose dominant views about the appropriate means of conducting reviews of qualitative research should be resisted so that innovation can be fostered. Copyright © 2006 SAGE Publications.

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In this editorial, the authors respond to the 2011 article in the Journal of Management by Becker, Cropanzano, and Sanfey, titled “Organizational Neuroscience: Taking Organizational Theory Inside the Neural Black Box.” More specifically, the authors build on the ideas of Becker et al. first to clarify and extend their work and then to explore the critical philosophical issues involved in drawing inferences from neuroscientific research. They argue that these problems are yet to be solved and that organizational researchers who wish to incorporate neuroscientific advances into their work need to engage with them.

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Face-to-face meetings may be invaluable, but they are not a panacea for the challenges facing teams spread around the globe - managers must also prioritize activities before and after these meetings to help team members stay connected.

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Academia has followed the interest by companies in establishing industrial networks by studying aspects such as social interaction and contractual relationships. But what patterns underlie the emergence of industrial networks and what support should research provide for practitioners? Firstly, it seems that manufacturing is becoming a commodity rather than a unique capability, which accounts especially for low-technology approaches in downstream parts of the network, for example in assembly operations. Secondly, the increased tendency to specialize forces other parts of industrial networks to introduce advanced manufacturing technologies for niche markets. Thirdly, the capital market for investments in capacity and the trade in manufacturing as a commodity dominates resource allocation to a larger extent. Fourthly, there will be a continuous move toward more loosely connected entities forming manufacturing networks. More traditional concepts, like keiretsu and chaibol networks, do not sufficiently support this transition. Research should address these fundamental challenges to prepare for the industrial networks of 2020 and beyond.

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Women remain in a small minority as business leaders in both Middle Eastern (ME) and Western European (WE) regions, and indeed, past research indicates that ME women face even greater challenges as leaders than their Western counterparts. This article explores sample findings from two separate case studies, the first of a ME woman leader and the second of a WE woman leader, each conducting a management meeting with their teams. Using interactional sociolinguistic analysis, we examine the 'contextualisation cues' that index how each woman performs leadership in their respective meetings. We found that both women utilise relational practices in order to enact leadership with their subordinates, but with varying results. Whereas the ME leader deploys a confident and commanding interactional style with her colleagues, the WE leader's style is evasive and uncertain. On the basis of these two cases, the WE leader appears to face greater challenges in a male-dominated business world than the ME leader. Whereas the ME leader can rely on long-established ties of loyalty and organisation-as-family, the Western leader, within an apparently more open, democratic context, has to negotiate overwhelming turbulence and change within her company. © 2014, equinox publishing.

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Strategic sourcing plays an important role in organisations' performance. Strategic sourcing has been researched extensively using empirical studies as well as review work, such as strategic sourcing importance, issues and challenges, processes, source selection criteria and framework. However, there is no research on critical success factors for strategic sourcing specific to industry and country. This research aims to qualitatively evaluate and understand the current role of strategic sourcing, the critical success factors for business performance and its relationship with strategic sourcing, and strategic supplier evaluation criteria from multiple stakeholders' perspectives specific to industry and country. This research studies twenty organisations from Germany and the United Kingdom (UK) covering two industry sectors - electronics manufacturing and construction. We consider five organisations from each industry sector and each country. The findings from twenty case studies reveal comparative analysis of strategic sourcing practices of two countries and two industries.

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The Global Dimensions in Higher Education module is a fully online open course for educators, jointly developed by three UK universities through a process of consultation and inquiry involving colleagues within the global education sector. The purpose of the module is two-fold. Firstly, to engage academics within and beyond the partner institutions in a critical exploration of transnational and global issues within higher education. Secondly, to provide the project partners with an opportunity to understand and address the challenges of jointly developing and delivering an online course that is to be offered both openly as well as integrated within credit-bearing and continued professional development provision for academics in the partner institutions. This short paper describes progress to date in developing the Global Dimensions in Higher Education module, our current activity focused on validating and implementing the module, and lessons learned to be considered for the collaborative development of open online courses.

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Existing political theory, particularly which deals with justice and/or rights, has long assumed citizenship as a core concept. Noncitizenship, if it is considered at all, is generally defined merely as the negation or deprivation of citizenship. As such, it is difficult to examine successfully the status of noncitizens, obligations towards them, and the nature of their role in political systems. This article addresses this critical gap by defining the theoretical problem that noncitizenship presents and demonstrating why it is an urgent concern. It surveys the contributions to the special issue for which the article is an introduction, drawing on cross-cutting themes and debates to highlight the importance of theorising noncitizenship due to both the problematic gap that exists in the theoretical literature, and the real world problems created as a result of noncitizenship which are not currently successfully addressed. Finally, the article discusses key future directions for the theorisation of noncitizenship.