21 research outputs found

    Water in Cavity−Ligand Recognition

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    We use explicit solvent molecular dynamics simulations to estimate free energy, enthalpy, and entropy changes along the cavity-ligand association coordinate for a set of seven model systems with varying physicochemical properties. Owing to the simplicity of the considered systems we can directly investigate the role of water thermodynamics in molecular recognition. A broad range of thermodynamic signatures is found in which water (rather than cavity or ligand) enthalpic or entropic contributions appear to drive cavity-ligand binding or rejection. The unprecedented, nanoscale picture of hydration thermodynamics can help the interpretation and design of protein-ligand binding experiments. Our study opens appealing perspectives to tackle the challenge of solvent entropy estimation in complex systems and for improving molecular simulation models

    Formulation, stabilisation and encapsulation of bacteriophage for phage therapy

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    Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don’t present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal studies have shown the importance of using phage cocktails rather than single phage preparations to achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy outcomes, given the need for phage cocktails, where each phage within a cocktail may require significantly different formulation to retain a high enough infective dose. This review firstly looks at the clinical needs and challenges (informed through a review of key animal studies evaluating phage therapy) associated with treatment of acute and chronic infections and the drivers for phage encapsulation. An important driver for formulation and encapsulation is shelf life and storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to document approaches used in the published literature on the formulation and stabilisation of phage for storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles, nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the review concludes by looking at promising new approaches for micro- and nanoencapsulation of phages and how these may address gaps in the field

    eWOM: The Impact of Customer-To-Customer Online Know-How Exchange On Customer Value and Loyalty

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    This paper investigates the effects of a specific form of electronic word-of-mouth (eWOM) communication, customer-to-customer know-how exchange, on customer perceptions of value and customer loyalty intentions. In addition, the paper explores the antecedents of customer-to-customer know-how exchange overlooked in prior research: motivation, opportunity, and ability. The survey results from 616 participants of an online forum suggest that customer know-how exchange impacts customer perceptions of product value and likelihood to recommend the product, but does not influence customer repurchase intentions. Interestingly, opportunity did not impact know-how exchange, whereas motivation and ability did have a significant effect. Implications for managers and future research directions are discussed. (c) 2005 Elsevier Inc. All rights reserved

    Customer-to-Customer Exchange: Its MOA Antecedents and Its Impact on Value Creation and Loyalty

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    Value creation through customer-to-customer exchange occurs when the perceived benefits of a company\u27s offering are increased as a result of customers\u27 interaction with one another. C2C exchange exists in a wide variety of service environments, both online and face-to-face. Drawing on the motivation, opportunity, and ability (MOA) framework, this research presents and tests a theoretical model that examines antecedents and outcomes of C2C exchange in the context of face-to-face networking behaviors at professional association meetings. Data were obtained from a survey of conference attendees, and the hypotheses were tested using moderated regression and path analysis. The results show a three-way interaction effect among the MOA factors, that the MOA model does predict the level of C2C exchange, and that C2C exchange does enhance service value perceptions and customer loyalty intentions

    Leveraging First-Mover Advantages In Internet-Based Consumer Services

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    The role of first movers in various Internet-based consumer service markets in developing a market leadership through strategic management concepts is discussed. The value proposition of Google to meet the consumer surfing needs and of Yahoo focused on personal portal model resulted in services such as Yahoo! groups and music and Google scholar and Earth respectively. The strategic pattern and dependability of Amazon.com, with a dominant share for Internet retailing with 38% share, offers the ability to search through and choose from various consumer options. First-movers also have an advantage as a well known brand in on-line auctions category, while e-auction companies can expect to gain pioneering advantages by identifying consumer perception of service quality
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