PSEUDO-GLYCODENDRIMERS CONTAINING A MOLECULAR ROD CORE: SYNTHESIS, CHARACTERIZATION AND DC-SIGN ANTAGONISM

Human immunodeficiency virus (HIV) is still a huge health problem, causing the death of over 1 million people per year. The search for HIV-entry inhibitors represents a promising challenge to prevent HIV infection. In this field, DC-SIGN, a carbohydrate-recognizing receptor expressed at the surface of the mucosal dendritic cells and involved in the early stages of HIV infection, is an important cellular target. The use of artificial molecules presenting multivalent carbohydrate moieties, able to interact with DC-SIGN with good affinity, should represent a therapeutic strategy in order to prevent HIV attachment to dendritic cells. Here we present a library of multivalent pseudo-glycodendrimers characterized by rigid molecular rods that rationally space active ligands, with the aim to exploit both the statistical rebinding and the chelating binding modes. Compounds were synthesised by varying the length of the rigid rod, the nature as well as the valency of the sugar moieties and the linkers flexibility. The optimal combination of active monovalent ligand, scaffold and valency led to a nanomolar inhibitor of DC-SIGN-mediated adhesion of HIV on cells. Compounds' biological performances were evaluated through Surface Plasmon Resonance Inhibition assays and trans-infection inhibition assays; the interaction between artificial compounds and DC-SIGN expressing cells was evaluated through confocal micoscopy, given the intrinsic fluorescence of the rods. Morphological behaviour of glycodendrimers was investigated using several analytical techniques, demonstrating that they are mainly monomers in solution, despite their amphiphilic structure. Finally, modifications of monovalent ligands were performed in order to improve compounds selectivity vs Langerin

PSEUDO-GLYCODENDRIMERS CONTAINING A MOLECULAR ROD CORE: SYNTHESIS, CHARACTERIZATION AND DC-SIGN ANTAGONISM

Human immunodeficiency virus (HIV) is still a huge health problem, causing the death of over 1 million people per year. The search for HIV-entry inhibitors represents a promising challenge to prevent HIV infection. In this field, DC-SIGN, a carbohydrate-recognizing receptor expressed at the surface of the mucosal dendritic cells and involved in the early stages of HIV infection, is an important cellular target. The use of artificial molecules presenting multivalent carbohydrate moieties, able to interact with DC-SIGN with good affinity, should represent a therapeutic strategy in order to prevent HIV attachment to dendritic cells. Here we present a library of multivalent pseudo-glycodendrimers characterized by rigid molecular rods that rationally space active ligands, with the aim to exploit both the statistical rebinding and the chelating binding modes. Compounds were synthesised by varying the length of the rigid rod, the nature as well as the valency of the sugar moieties and the linkers flexibility. The optimal combination of active monovalent ligand, scaffold and valency led to a nanomolar inhibitor of DC-SIGN-mediated adhesion of HIV on cells. Compounds' biological performances were evaluated through Surface Plasmon Resonance Inhibition assays and trans-infection inhibition assays; the interaction between artificial compounds and DC-SIGN expressing cells was evaluated through confocal micoscopy, given the intrinsic fluorescence of the rods. Morphological behaviour of glycodendrimers was investigated using several analytical techniques, demonstrating that they are mainly monomers in solution, despite their amphiphilic structure. Finally, modifications of monovalent ligands were performed in order to improve compounds selectivity vs Langerin

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

Measuring the Digital Divide: A Framework for the Analysis of Cross-Country Differences

This article proposes a new model for measuring the digital divide within a set of countries or geographical areas. Starting from a series of elementary indicators the methodology groups these indicators into six factors of digitalization and, subsequently, aggregates the factors in a synthetic index called the synthetic index of digitalization. The dispersion in the distribution of the synthetic indexes of digitalization constitutes the measure of the digital divide. This method is based upon a measurement approach, which is different from the ones previously developed, since it uses principal components analysis for aggregating the variables and avoids many of the problems and limits shown by existing models. In the article an application of the methodology is provided within a set of ten developed countries for 2000 and 2001. The measurement framework for the digital divide presented here reveals new policy implications for public institutions and highlights opportunities and risks for managers working in the ‘digital economy’ environment

Free upgrades with costly consequences: can preferential treatment inflate customers’ entitlement and induce negative behaviors?

Purpose Companies often provide preferential treatment, such as free upgrades, to customers. The present study aims to identify a costly consequence of such preferential treatment (i.e. opportunistic behavior) and reveal which type of customer is most likely to engage in that negative behavior (i.e. new customers). Design/methodology/approach Across two experimental studies, the authors test whether preferential treatment increases customers’ entitlement, which in turn increases their propensity to behave opportunistically. Moderated mediation analysis further tests whether that mediated effect is moderated by customers’ prior relationship with the company. Findings Preferential treatment increases feelings of entitlement, which consequently triggers customers’ opportunistic behaviors. New customers are more likely to feel entitled after preferential treatment than repeat customers, and hence new customers are more likely to behave opportunistically. Preferential treatment also increases customers’ suspicion of the company’s motives, but suspicion was unrelated to opportunistic behavior. Research limitations/implications Future research may focus on other marketplace situations that trigger entitlement and explore whether multiple occurrences of preferential treatment provide different effects on consumers. Practical implications Present findings demonstrate that preferential treatment can evoke opportunistic behaviors among customers. The authors suggest that preferential treatment should be provided to customers who previously invested in their relationship with a company (i.e. repeat customers) rather than new customers. Originality/value Prior research has focused more on the ways companies prioritize their repeat customers than how they surprise their new customers. The present research instead examines preferential treatment based on customers’ relationship with a firm (i.e. both repeat and new customers) and demonstrates behavioral and contextual effects of entitlement

Complex polymeric architectures self-assembling in unimolecular micelles: Preparation, characterization and drug nanoencapsulation

Unimolecular polymeric micelles are a class of single-molecule amphiphilic core-shell polymeric architectures, where the hydrophobic core is well stabilized by the hydrophilic shell, avoiding intermolecular core-core interactions. Multi-arm copolymers with a dendritic core, as well as hyperbranched and comb-like polymers, can form unimolecular micelles easily. In this review, examples of polymers able to form detectable unimolecular micelles will be presented, summarizing the analytical techniques used to characterize the unimolecular micelles and discriminate them from other supramolecular aggregates, such as multi-micelle aggregates. Unimolecular micelles are suitable for the nanoencapsulation of guest molecules. Compared to traditional supramolecular micelles, unimolecular micelles do not disassemble under dilution and are stable to environmental modifications. Recent examples of their application as drug delivery systems, endowed with increased stability and transport properties, will be discussed

Mixing rich and asynchronous communication for new service development performance

This article explores the nature of relationships between internal communication modes, new service development (NSD) competencies (specifically learning and development competencies) and NSD performance. To do so, it draws on and advances communication theory by comparing and contrasting the contingent approach, favoured by media richness theory and media synchronicity theory, with the multiplicative manner of dual coding theory. Antecedent roles of rich and asynchronous communication modes for two NSD competencies are investigated, and their function as critical contingency variables affecting the competencies–performance link is unravelled. An empirical quantitative study of senior managers of leading service firms was conducted, with a survey-based methodology. Results show that a learning competency drives development competency which in turn drives NSD performance. Asynchronous communication is essential for learning competency but not for development competency. In contrast, rich communication underpins development but has no direct effect on learning competency. Rich communication is essential for NSD performance when a firm has a low development competency. The interaction between asynchronous and rich communication is shown to be positive for learning, whereas surprisingly it is negative for development competency

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

Success factors for service innovation: a meta-analysis

Service sectors form a considerable part of the world economy. Contrary to the logical assumption that service innovation research should represent a significant share of all innovation research, the vast majority of innovation studies focus on products as opposed to services. This research presents a meta-analysis of the antecedents of service innovation performance conducted on 92 independent samples obtained from 114 articles published between 1989 and 2015. This research contributes to our understanding of service innovation in three major ways. First, this is the first meta-analysis that specifically assesses the relative importance of antecedents of service innovation performance, while also pinpointing the differences in meta-analytic findings between antecedents of service and product innovation performance. Whilst there are some universal success factors that transcend the boundaries between services and products, the presence of marked differences implies that it would be wrong to treat the development of new services and new products as the same. Second, the meta-analysis demonstrates that the antecedents of service innovation performance are contingent on the sector context (i.e., explicit versus tacit services). Comparing results between products and services, and between tacit and explicit services, there appears to be a continuum where explicit services sit interstitial between tacit services on one side and products on the other. Third, the meta-analysis compares and contrasts the antecedents of two dimensions of service innovation performance (i.e., commercial success and strategic competitive advantage). Previous meta-analyses treated these two dependent variables collectively, which falls short of identifying issues that may affect management decisions when faced with different objectives. Additionally, this research investigates the effect of several other moderators (i.e., culture, unit of analysis, journal quality, and year of publication) on the relationships between the antecedents and service innovation performance. The results are discussed in relation to their implications for research and managerial practice

'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