From optimized monovalent ligands to size-controlled dendrimers : an efficient strategy towards high-activity DC-SIGN antagonists

This short review describes our work on the development of dendrimeric antagonists of DC-SIGN, a dendritic cells (DCs) receptor recognizing highly mannosylated structures and primarily involved in the recognition of viruses such as HIV. The structure of pseudo-di-mannoside and pseudo-tri-mannoside compounds was first finely modified to obtain DC-SIGN ligands that were more stable and selective than mannose. Their DC-SIGN affinity differences were amplified once presented on multivalent dendrimer-like scaffolds, including poly-alkyne terminated and phenylene-ethynylene rod-like ones. Libraries of mannosylated dendrimers were synthesized, improving their stability and maximizing their monodispersity. The effect of the dendrimers valency, structure, and size on DC-SIGN affinity and antiviral potency was investigated. Both the valency and the topology of the architectures were revealed as key parameters for activity optimization, together with the intrinsic affinity of the monovalent ligand. The stability, rigidity, and length of the scaffolds were also tuned. The design of geometrically adapted scaffolds afforded one of the most potent inhibitors of DC-SIGN mediated HIV infections to date. This monodispersed, not cytotoxic, and highly active compound was also tested with DCs; its internalization into endolysosomal compartments and its ability to induce the overexpression of signaling molecules makes it a good precursor to produce pathogen-entry inhibitors with immunomodulant properties

The ‘T-Shaped Buyer’: a transactional perspective on supply chain relationships

This paper challenges the normative view of interdependent buyer-seller relationships and provides a more holistic perspective of the contextual reality that shapes buyer behaviour. By proposing an innovative qualitative methodology, which focusses on boundary-spanning, pre-sales interactions, the research penetrates complex and commercially sensitive buyer-seller relationships. The longitudinal research design uses web-based diaries and follow-up interviews to explore conditions of power based interdependence between buyers and sellers. The ensuing data is mapped using qualitative content analysis and the results are aggregated graphically for assessment. Using this approach the study develops a nuanced view of the dominant patterns of buyer behaviour, and challenges the opinion that a search for competitive advantage will strengthen cooperative relationships in conditions of power based interdependence. The paper introduces the metaphor of the 'T-Shaped Buyer' to explain the empirical findings and, while acknowledging the contextual limits of the study, suggests that this metaphor may cause both academics and practitioners to reflect on normative thinking

'Let's make lots of money': the determinants of performance in the recorded music sector

This research analyzes the performance of 467 record labels in eight European countries over a period of 13 years (2003-2015). The main goal is to explain a relative measure of profitability in terms of observed variables, although the nature of the dataset also allows us to include non-observed firm and country effects. To this end alternative models are estimated and three main research questions are tested, namely: (1) the effect of the dual structure of the recorded music market, in which a competitive segment and an oligopoly coexist; (2) the extent and source of the volatility of profits in record labels; and (3) the nonlinear impact of size on performance

Barriers to women entrepreneurship. Different methods, different results?

Building on research by Akehurst et al. (Serv Ind J 32:2489-2505, 2012), this study analysed internal and external factors in women entrepreneurship and linked these factors to the barriers that women face when starting businesses. To do so, two contrasting statistical techniques were used: PLS and QCA. After analysing results from each of these techniques, we observed that family duties and difficulties in obtaining financing (both internal and external) were the main factors related to barriers faced by women entrepreneurs

Reward-Based Crowdfunding Research and Practice

publishedVersio

Delivering better outcomes through customer-led project management: the case of the major project BT 21st Century Network in the UK

Traditional approaches of major project management take the strategy of selecting a supplier-led prime/systems integrator. Although this strategy pushes a significant amount of risk to the supplier, project performance may suffer due to lower engagement of the customer in the anticipation of potential issues involving a major project. Thus, this research investigates the implications of the customer, as opposed to a selected external supplier, assuming the role of systems/prime integrator, as a Problem Structuring Method (PSM) to better deal with the soft side and uncertainties of the project. A case study approach is conducted on the major project BT 21st Century Network (BT21CN) to demonstrate that customer-led systems integration projects may provide more balance in the relationship and distribution of risks between supplier and customer, having a positive impact on project performance, accelerating the development of BT’s organisational capabilities, and producing better project outcomes in the long term

Sport policy convergence: a framework for analysis

This is an Accepted Manuscript of an article published by Taylor & Francis Group in European Sport Management Quarterly on 30th April 2012, available online at: http://www.tandfonline.com/10.1080/16184742.2012.669390The growth in the comparative analysis of sport management processes and policy has led to an increased interest in the concept of convergence. However, the concept is too often treated as unproblematic in definition, measurement and operationalisation. It is argued in this paper that a more effective framework for examining claims of convergence is one that analyses the concept in terms of seven dimensions which can be explored through a mix of quantitative and qualitative methods of data collection. It is also argued that a deeper understanding of the process of convergence can be gained by operationalising the concept in the context of a selected range of meso-level theories of the policy process or of specific aspects of the process. The proposed analytic framework provides not only a definition of convergence but also the basis for a more nuanced investigation of hypotheses of convergence