Enzymatic characterization and homology model of a catalytically active recombinant West Nile virus NS3 protease

West Nile Virus (WNV) is a mosquito-borne flavivirus with a rapidly expanding global distribution. Infection causes severe neurological disease and fatalities in both human and animal hosts. The West Nile viral protease (NS2B-NS3) is essential for post-translational processing in host-infected cells of a viral polypeptide precursor into structural and functional viral proteins, and its inhibition could represent a potential treatment for viral infections. This article describes the design, expression, and enzymatic characterization of a catalytically active recombinant WNV protease, consisting of a 40-residue component of cofactor NS2B tethered via a noncleavable nonapeptide (G(4)SG(4)) to the N-terminal 184 residues of NS3. A chromogenic assay using synthetic para-nitroanilide (pNA) hexapeptide substrates was used to identify optimal enzyme-processing conditions (pH 9.5, I < 0.1 M, 30% glycerol, 1 mM CHAPS), preferred substrate cleavage sites, and the first competitive inhibitor (Ac-FASGKR- H, IC50 &SIM; 1 μM). A putative three-dimensional structure of WNV protease, created through homology modeling based on the crystal structures of Dengue-2 and Hepatitis C NS3 viral proteases, provides some valuable insights for structure-based design of potent and selective inhibitors of WNV protease.

Adenosine triphosphate acts as both a competitive antagonist and a positive allosteric modulator at recombinant N-methyl-D-aspartate receptors

ATP and glutamate are fast excitatory neurotransmitters in the central nervous system acting primarily on ionotropic P2X and glutamate [N-methyl-D-aspartate (NMDA) and non-NMDA] receptors, respectively. Both neurotransmitters regulate synaptic plasticity and long-term potentiation in hippocampal neurons. NMDA receptors are responsible primarily for the modulatory action of glutamate, but the mechanism underlying the modulatory effect of ATP remains uncertain. In the present study, the effect of ATP on recombinant NR1a + 2A, NR1a + 2B, and NR1a + 2C NMDA receptors expressed in Xenopus laevis oocytes was investigated. ATP inhibited NR1a + 2A and NR1a + 2B receptor currents evoked by low concentrations of glutamate but potentiated currents evoked by saturating glutamate concentrations. In contrast, ATP potentiated NR1a + 2C receptor currents evoked by nonsaturating glutamate concentrations. ATP shifted the glutamate concentration-response curve to the right, indicating a competitive interaction at the agonist binding site. ATP inhibition and potentiation of glutamate-evoked currents was voltage-independent, indicating that ATP acts outside the membrane electric field. Other nucleotides, including ADP, GTP, CTP, and UTP, inhibited glutamate-evoked currents with different potencies, revealing that the inhibition is dependent on both the phosphate chain and nucleotide ring structure. At high concentrations, glutamate outcompetes ATP at the agonist binding site, revealing a potentiation of the current. This effect must be caused by ATP binding at a separate site, where it acts as a positive allosteric modulator of channel gating. A simple model of the NMDA receptor, with ATP acting both as a competitive antagonist at the glutamate binding site and as a positive allosteric modulator at a separate site, reproduced the main features of the data.

Measuring market power in electricity generation: A long-term perspective using a programming model

This paper focuses on measuring the extent to which market power has been exercised in a recently deregulated electricity generation sector. Our study emphasises the need to consider the concept of market power in a long-run dynamic context. A market power index is constructed focusing on differences between actual market returns and long-run competitive returns, estimated using a programming model devised by the authors. The market power implications of hedge contracts are briefly considered. The state of Queensland Australia is used as a context for the analysis. The results suggest that generators have exercised significant market power since deregulation.

Do organizational climate and competitive strategy moderate the relationship between human resource management and productivity?

This study examined whether the effectiveness of human resource management (HRM)practices is contingent on organizational climate and competitive strategy The concepts of internol and external fit suggest that the positive relationship between HRM and subsequent productivity will be stronger for firms with a positive organizational climate and for firms using differentiation strategies. Resource allocation theories of motivation, on the other hand, predict that the relationship between HRM and productivity will be stronger for firms with a poor climate because employees working in these firms should have the greatest amount of spare capacity. The results supported the resource allocation argument.

Offspring size effects mediate competitive interactions in a colonial marine invertebrate

Over the past 30 years, numerous attempts to understand the relationship between offspring size and fitness have been made, and it has become clear that this critical relationship is strongly affected by environmental heterogeneity. For marine invertebrates, there has been a long-standing interest in the evolution of offspring size, but there have been very few empirical and theoretical examinations of post-metamorphic offspring size effects, and almost none have considered the effect of environmental heterogeneity on the offspring size/fitness relationship. We investigated the post-metamorphic effects of offspring size in the field for the colonial marine invertebrate Botrylloides violaceus. We also examined how the relationship between offspring size and performance was affected by three different types of intraspecific competition. We found strong and persistent effects of offspring size on survival and growth, but these effects depended on the level and type of intraspecific competition.. Generally, competition strengthened the advantages of increasing maternal investment. Interestingly, we found that offspring size determined the outcome of competitive interaction: juveniles that had more maternal investment were more likely to encroach on another juvenile's territory. This suggests that mothers have the previously unrecognized potential to influence the outcome of competitive interactions in benthic marine invertebrates. We created a simple optimality model, which utilized the data generated from our field experiments, and found that increasing intraspecific competition resulted in an increase,in predicted optimal size. Our results suggest that the relationship between offspring size and fitness is highly variable in the marine environment and strongly dependent on the density of conspecifics.

RatSLAM: A hippocampal model for simultaneous localisation and mapping

The work presents a new approach to the problem of simultaneous localization and mapping - SLAM - inspired by computational models of the hippocampus of rodents. The rodent hippocampus has been extensively studied with respect to navigation tasks, and displays many of the properties of a desirable SLAM solution. RatSLAM is an implementation of a hippocampal model that can perform SLAM in real time on a real robot. It uses a competitive attractor network to integrate odometric information with landmark sensing to form a consistent representation of the environment. Experimental results show that RatSLAM can operate with ambiguous landmark information and recover from both minor and major path integration errors.

Creating and sustaining competitive advantage in collaborative systems:the what and the how

Initially this paper asks two questions: In order to create and sustain competitive advantage through collaborative systems WHAT should be managed? and HOW should it be managed? It introduces the competitive business structure and reviews some of the global trends in manufacturing and business, which leads to focus on manage processes, value propositions and extended business processes. It then goes on to develop a model of the collaborative architecture for extended enterprises and demonstrates the validity of this architecture through a case study. It concludes that, in order to create and sustain competitive advantage, collaborative systems should facilitate the management of: the collaborative architecture of the extended enterprise; the extended business processes and the value proposition for each extended enterprise through a meta level management process. It also identifies areas for further research, such as better understanding of: the exact nature and interaction of multiple strategies within an enterprise; how to manage people/teams working along extended business processes; and the nature and prerequisites of the manage processes.

Attainment of competitive advantage by the exporter-importer dyad:the role of export offering and import objectives

Although experience shows that the exporter and importer jointly contribute towards the attainment of competitive advantage, past studies have separately examined export-related characteristics or import barriers. This article identifies a subset of critical factors that illustrate how the exporter–importer (E-I) dyad creates and maintains competitive advantage. Based on a sample of Greek importers, a path analytic model was developed that empirically demonstrates that product technology sophistication (PTS), product and service quality and importer strategic objectives are important for the attainment of competitive advantage while price competitiveness and trust upon the exporter are not.

Meta-analytic model comparisons of surface- and deep-level relational diversity effects on social integration and individual effectiveness

While diversity might give an organization a competitive advantage, individuals have a tendency to prefer homogenous group settings. Prior research suggests that group members who are dissimilar (vs. similar) to their peers in terms of a given diversity attribute (e.g. demographics, attitudes, values or traits) feel less attached to their work group, experience less satisfying and more conflicted relationships with their colleagues, and consequently are less effective. However, prior empirical findings tend to be weak and inconsistent, and it remains unclear when, how and to what extent such differences affect group members’ social integration (i.e. attachment with their work group, satisfaction and conflicted relationships with their peers) and effectiveness. To address these issues the current study conducted a meta-analysis and integrated the empirical results of 129 studies. For demographic diversity attributes (such as gender, ethnicity, race, nationality, age, functional background, and tenure) the findings support the idea that demographic dissimilarity undermines individual member performance via lower levels of social integration. These negative effects were more pronounced in pseudo teams – i.e. work groups in which group members pursue individual goals, work on individual tasks, and are rewarded for their individual performance. These negative effects were however non-existent in real teams - i.e. work groups in which groups members pursue group goals, work on interdependent tasks, and are rewarded (at least partially) based on their work group’s performance. In contrast, for underlying psychological diversity attributes (such as attitudes, personality, and values), the relationship between dissimilarity and social integration was more negative in real teams than in pseudo teams, which in return translated into even lower individual performance. At the same time however, differences in underlying psychological attributes had an even stronger positive effect on dissimilar group member’s individual performance, when the negative effects of social integration were controlled for. This implies that managers should implement real work groups to overcome the negative effects of group member’s demographic dissimilarity. To harness the positive effects of group members’ dissimilarity on underlying psychological attributes, they need to make sure that dissimilar group members become socially integrated.

Utilising online shopping environment attributes holistically to create competitive advantage

As more consumers shop online, it becomes crucial for marketers to know how online shopping environments (OSEs) can be used to gain competitive advantage. This dissertation aims to explain theoretically how OSE attributes work together holistically to produce desirable consumer responses, applying and extending a theory from the environmental psychology literature to the online context. Firstly, the study conceptualises OSEs as virtual environments which may be perceived and experienced both cognitively and affectively through a technology-mediated interaction with a computer screen. A multi-disciplinary approach identifies key characteristics of OSEs: they involve consumers; they are more complex than their offline counterparts; they are likely first apprehended holistically; and they can elicit high levels of emotions and cognition. Secondly, the research uses a gestalt approach and extends Kaplan and Kalan’s (1982) Preference Framework, taking account of the specific characteristics of OSEs, which one visits specifically to obtain product information. The results support the proposition that OSEs are perceived in terms of their Sense-making and Exploratory attributes. Thirdly, the research explains how OSE attributes work together to produce desirable consumer responses. As hypothesised, Exploratory potential produces both Hedonic and Utilitarian value, and both kinds of value contribute to Site commitment. An unexpected result is that Sense-making potential does not produce Utilitarian value directly, but only through the mediation of Exploratory potential. The research contributes to marketing theory by: (1) identifying ways the internet has changed the nature of the shopping experience; (2) extending Kaplan and Kaplan’s Preference Framework to explain how consumers perceive OSEs holistically; (3) identifying the distinction between page-level and site-level perceptions, and (4) distinguishing between different sources of information (marketer vs. non-marketer). Managerially, the research provides a model for marketers to conceive and design retail websites whose attributes work together to create competitive advantage.

The right time and place:strategic positioning for competitive manufacture

Increasingly in the UK, companies that have traditionally considered themselves as manufacturers are being advised to now see themselves as service providers and to reconsider whether to have any production capability. A key challenge is to translate this strategy into a selection of product and service-centred activities within the company's supply chain networks. Strategic positioning is concerned with the choice of business activities a company carries out itself, compared to those provided by suppliers, partners, distributors and even customers. In practice, strategic positioning is directly impacted by such decisions as outsourcing, off-shoring, partnering, technology innovation, acquisition and exploitation. If companies can better understand their strategic positioning, they can make more informed decisions about the adoption of alternative manufacturing and supply chain activities. Similarly, they are more likely to reject those that, like off-shoring, are currently en vogue but are highly likely to erode competitive edge and business success. Our research has developed a new concept we call 'competitive space' as a means of appreciating the strategic positioning of companies, along with a structured decision process for managing competitive space. Our ideas about competitive space, along with the decision process itself, have been developed and tested on a range of manufacturers. As more and more manufacturers are encouraged to move towards system integration and a serviceable business model, the challenge is to identify the appropriate strategic position for their organisations, or in other words, to identify their optimum competitive space for manufacture.

A flexible cost function model with risk

In examining bank cost efficiency in banking inclusion of risk-taking of banks is very important. In this paper we depart from the standard modeling approach and view risk intimately related to the technology. Thus, instead of controlling for risk by viewing them as covariates in the standard cost function we argue that the technology differs with risk, thereby meaning that the parameters of the parametric cost function changes with risk in a fully flexible manner. This is accomplished by viewing the parameters of the cost function as nonparametric functions of risk. We also control for country-specific effects in a fully flexible manner by using them as arguments of the nonparametric functions along with the risk variable. The resulting cost function then becomes semiparametric. The standard parametric model becomes a special case of our semiparametric model. We use the above modeling approach for banks in the EU countries. Actually, European financial integration is seen as a stepping stone for the development of a competitive single EU market that promotes efficiency and increases consumer welfare, changing the risk profile of the European banks. Particularly, financial integration allows more risk diversification and permits banks to use more advanced risk management instruments and systems, however it has at the same time increased the probability of systematic risks. Financial integration has increased the risk of contagion and changed its nature and scope. Consequently the bank’s risk seems to be an important issue to be investigated.

Competition, competitive advantage, and clusters:the ideas of Michael Porter

Comprehensive coverage of all aspects of Michael Porter's works Contributions from leading authorities across the disciplines Contains response from Porter Harvard professor, Michael Porter has been one of the most influential figures in strategic management research over the last three decades. He infused a rigorous theoretical framework of industrial organization economics with the then still embryonic field of strategic management and elevated it to its current status as an academic discipline. Porter's outstanding career is also characterized by its cross-disciplinary nature. Following his most important work on strategic management, he then made a leap to the policy side and dealt with a completely different set of analytical units. More recently he has made a foray into inner city development, environmental regulations, and health care services. Throughout these explorations Porter has maintained his integrative approach, seeking a road that links management case studies and the general model building of mainstream economics. With expert contributors from a range of disciplines including strategic management, economic development, economic geography, and planning, this book assesses the contribution Michael Porter has made to these respective disciplines. It clarifies the sources of tension and controversy relating to all the major strands of Porter's work, and provides academics, students, and practitioners with a critical guide for the application of Porter's models. The book highlights that while many of the criticisms of Porter's ideas are valid, they are almost an inevitable outcome for a scholar who has sought to build bridges across wide disciplinary valleys. His work has provided others with a set of frameworks to explore in more depth the nature of competition, competitive advantage, and clusters from a range of vantage points.

Modeling competitive reaction effects

In this study I critically review models that specify competitive reaction effects. I discuss different model structures and summarize my findings on competitive reaction effects and factors that explain competitive reactions. I discuss the many models of competitive market response that have been developed and classify them into twelve sets of models that are related to each other in a logical manner through the evolutionary model-building concept.

Competitive edge through operations management

A view has emerged within manufacturing and service organizations that the operations management function can hold the key to achieving competitive edge. This has recently been emphasized by the demands for greater variety and higher quality which must be set against a background of increasing cost of resources. As nations' trade barriers are progressively lowered and removed, so producers of goods and service products are becoming more exposed to competition that may come from virtually anywhere around the world. To simply survive in this climate many organizations have found it necessary to improve their manufacturing or service delivery systems. To become real ''winners'' some have adopted a strategic approach to operations and completely reviewed and restructured their approach to production system design and operations planning and control. The articles in this issue of the International journal of Operations & Production Management have been selected to illustrate current thinking and practice in relation to this situation. They are all based on papers presented to the Sixth International Conference of the Operations Management Association-UK which was held at Aston University in June 1991. The theme of the conference was "Achieving Competitive Edge" and authors from 15 countries around the world contributed to more than 80 presented papers. Within this special issue five topic areas are addressed with two articles relating to each. The topics are: strategic management of operations; managing change; production system design; production control; and service operations. Under strategic management of operations De Toni, Filippini and Forza propose a conceptual model which considers the performance of an operating system as a source of competitive advantage through the ''operation value chain'' of design, purchasing, production and distribution. Their model is set within the context of the tendency towards globalization. New's article is somewhat in contrast to the more fashionable literature on operations strategy. It challenges the validity of the current idea of ''world-class manufacturing'' and, instead, urges a reconsideration of the view that strategic ''trade-offs'' are necessary to achieve a competitive edge. The importance of managing change has for some time been recognized within the field of organization studies but its relevance in operations management is now being realized. Berger considers the use of "organization design", ''sociotechnical systems'' and change strategies and contrasts these with the more recent idea of the ''dialogue perspective''. A tentative model is suggested to improve the analysis of different strategies in a situation specific context. Neely and Wilson look at an essential prerequisite if change is to be effected in an efficient way, namely product goal congruence. Using a case study as its basis, their article suggests a method of measuring goal congruence as a means of identifying the extent to which key performance criteria relating to quality, time, cost and flexibility are understood within an organization. The two articles on production systems design represent important contributions to the debate on flexible production organization and autonomous group working. Rosander uses the results from cases to test the applicability of ''flow groups'' as the optimal way of organizing batch production. Schuring also examines cases to determine the reasons behind the adoption of ''autonomous work groups'' in The Netherlands and Sweden. Both these contributions help to provide a greater understanding of the production philosophies which have emerged as alternatives to more conventional systems -------for intermittent and continuous production. The production control articles are both concerned with the concepts of ''push'' and ''pull'' which are the two broad approaches to material planning and control. Hirakawa, Hoshino and Katayama have developed a hybrid model, suitable for multistage manufacturing processes, which combines the benefits of both systems. They discuss the theoretical arguments in support of the system and illustrate its performance with numerical studies. Slack and Correa's concern is with the flexibility characteristics of push and pull material planning and control systems. They use the case of two plants using the different systems to compare their performance within a number of predefined flexibility types. The two final contributions on service operations are complementary. The article by Voss really relates to manufacturing but examines the application of service industry concepts within the UK manufacturing sector. His studies in a number of companies support the idea of the ''service factory'' and offer a new perspective for manufacturing. Harvey's contribution by contrast, is concerned with the application of operations management principles in the delivery of professional services. Using the case of social-service provision in Canada, it demonstrates how concepts such as ''just-in-time'' can be used to improve service performance. The ten articles in this special issue of the journal address a wide range of issues and situations. Their common aspect is that, together, they demonstrate the extent to which competitiveness can be improved via the application of operations management concepts and techniques.