Synthesis and evaluation of polystyrene based soluble polymeric supports for organic synthesis

Several copolymers of linear polystyrene were prepared for evaluation as soluble polymeric supports for organic synthesis. These polymers were utilized for the synthesis of ?2-isoxazoline compounds. The target compounds were synthesized via 1,3-dipolar cycloaddition reactions between polymer bound alkenes and nitrile oxides generated in situ from their corresponding aldoximes. The cleaved ?2-isoxazoline compounds were tested for biological activity against Mycobacterium fortuitum. To compare the success of these linear polystyrene copolymers, some of the ?2-isoxazoline compounds synthesized on soluble polymeric supports were also prepared via traditional crosslinked polymer supports. The polymer-bound ?2-isoxazolines were also tested for antimicrobial activity. In addition attempts were made to prepare polymers containing the ?2-isoxazolines but anchored by non-hydrolysable bonds. Although the copolymers of polystyrene gave good loading capacity in mmol/g, and being soluble in chlorinated solvents it was possible to monitor the reactions by 1H NMR spectroscopy, the cleavage of the polymer bound products proved to be quite troublesome. Product purification was not as straightforward as it was anticipated. Isolation of the cleaved target compounds proved to be time consuming and laborious when compared to the traditional organic synthesis and solid phase organic synthesis (SPOS). Polymer-bound ?2-isoxazolines close to the polymer backbone exhibited some biological activity against Staphylococcus aureus. Polymers with substitution at the para-position of the aryl substituent at position 3 of isoxazoline ring showed antimicrobial activity.

Development and formulation of wax-based transdermal drug delivery systems

Topical and transdermal formulations are promising platforms for the delivery of drugs. A unit dose topical or transdermal drug delivery system that optimises the solubility of drugs within the vehicle provides a novel dosage form for efficacious delivery that also offers a simple manufacture technique is desirable. This study used Witepsol® H15 wax as a abase for the delivery system. One aspect of this project involved determination of the solubility of ibuprofen, flurbiprofen and naproxen in the was using microscopy, Higuchi release kinetics, HyperDSC and mathematical modelling techniques. Correlations between the results obtained via these techniques were noted with additional merits such as provision of valuable information on drug release kinetics and possible interactions between the drug and excipients. A second aspect of this project involved the incorporation of additional excipients: Tween 20 (T), Carbopol®971 (C) and menthol (M) to the wax formulation. On in vitro permeation through porcine skin, the preferred formulations were: ibuprofen (5% w/w) within Witepsol®H15 + 1% w/w T; flurbiprofen (10% w/w) within Witepsol®H15 + 1% w/w T; naproxen (5% w/w) within Witepsol®H15 + 1% w/w T + 1% C and sodium diclofenac (10% w/w) within Witepsol®H15 + 1% w/w T + 1% w/w T + 1% w/w C + 5% w/w M. Unit dose transdermal tablets containing ibuprofen and diclofenac were produced with improved flux compared to marketed products; Voltarol Emugel® demonstrated flux of 1.68x10-3 cm/h compared to 123 x 10-3 cm/h for the optimised product as detailed above; Ibugel Forte® demonstrated a permeation coefficient value of 7.65 x 10-3 cm/h compared to 8.69 x 10-3 cm/h for the optimised product as described above.

Rough-terrain groundspeed measurement:a radar-based commercial solution

Off-highway motive plant equipment is costly in capital outlay and maintenance. To reduce these overheads and increase site safety and workrate, a technique of assessing and limiting the velocity of such equipment is required. Due to the extreme environmental conditions met on such sites, conventional velocity measurement techniques are inappropriate. Ogden Electronics Limited were formed specifically to manufacture a motive plant safety system incorporating a speed sensor and sanction unit; to date, the only such commercial unit available. However, problems plague the reliability, accuracy and mass production of this unit. This project assesses the company's exisiting product, and in conjunction with an appreciation of the company history and structure, concludes that this unit is unsuited to its intended application. Means of improving the measurement accuracy and longevity of this unit, commensurate with the company's limited resources and experience, are proposed, both for immediate retrofit and for longer term use. This information is presented in the form of a number of internal reports for the company. The off-highway environment is examined; and in conjunction with an evaluation of means of obtaining a returned signal, comparisons of processing techniques, and on-site gathering of previously unavailable data, preliminary designs for an alternative product are drafted. Theoretical aspects are covered by a literature review of ground-pointing radar, vehicular radar, and velocity measuring systems. This review establishes and collates the body of knowledge in areas previously considered unrelated. Based upon this work, a new design is proposed which is suitable for incorporation into the existing company product range. Following production engineering of the design, five units were constructed, tested and evaluated on-site. After extended field trials, this design has shown itself to possess greater accuracy, reliability and versatility than the existing sensor, at a lower unit cost.

Integrated manufacturing systems design in a multi-product company

Using a hydraulic equipment manufacturing plant as the case study, this work explores the problems of systems integration in manufacturing systems design, stressing the behavioural aspects of motivation and participation, and the constraints involved in the proper consideration of the human sub-system. The need for a simple manageable modular organisation structure is illustrated, where it is shown, by reference to systems theory, how a business can be split into semi-autonomous operating units. The theme is the development of a manufacturing system based on an analysis of the business, its market, product, technology and constraints, coupled with a critical survey of modern management literature to develop an integrated systems design to suit a specific company in the current social environment. Society currently moves through a socio-technical revolution with man seeking higher levels of motivation. The transitory environment from an autocratic/paternalistic to a participative operating mode demands systems parameters only found to a limited extent in manufacturing systems today. It is claimed, that modern manufacturing systems design needs to be based on group working, job enrichment, delegation of decision making and reduced job monotony. The analysis shows how negative aspects of cellular manufacture such as lack of flexibility and poor fixed asset utilisation are relatively irrelevant and misleading in the broader context of the need to come to terms with the social stresses imposed on a company operating in the industrial environment of the present and the immediate future.

Product-service systems revisited

There is a growing interest around the potential value of service-led competitive strategies to UK based manufacturers. A Product Service-System (PSS) is one form of such a strategy and is based on integrated combination of products and services. This concept also embraces environmental sustainability. This paper aims to summarise the state-of-the-art of PSS research by presenting a review of literature currently available on this topic. The literature search is described and the major outcomes of the study are presented. On this basis, this paper defines the PSS concept, reports on its origin and features.

PSS as a service based strategy for western manufacturers

A product-service system (PSS) is a subtle blend of products and services that are offered as an integrated solution to customers. Much existing work on PSS has originated from Scandinavia and has been motivated by a sustainability agenda. Although valuable, this form has limited appeal to western manufacturers. However, by expanding the concepts of PSS to also embrace leading thinking on large scale complex service systems and informated products and services, it is possible to put forward the basis of a service business model that offers the means to differentiate from competitors who simply offer lower priced products. This paper aims to build this case. It reports the state-of-the-art of PSS, defines the concept, reports on its origin and features, discusses examples of applications, and finally proposes a research strategy for future work on this topic.

Reporter ion-based mass spectrometry approaches for the detection of non-enzymatic protein modifications in biological samples

Development of mass spectrometry techniques to detect protein oxidation, which contributes to signalling and inflammation, is important. Label-free approaches have the advantage of reduced sample manipulation, but are challenging in complex samples owing to undirected analysis of large data sets using statistical search engines. To identify oxidised proteins in biological samples, we previously developed a targeted approach involving precursor ion scanning for diagnostic MS3 ions from oxidised residues. Here, we tested this approach for other oxidations, and compared it with an alternative approach involving the use of extracted ion chromatograms (XICs) generated from high-resolution MSMS data using very narrow mass windows. This accurate mass XIC data methodology was effective at identifying nitrotyrosine, chlorotyrosine, and oxidative deamination of lysine, and for tyrosine oxidations highlighted more modified peptide species than precursor ion scanning or statistical database searches. Although some false positive peaks still occurred in the XICs, these could be identified by comparative assessment of the peak intensities. The method has the advantage that a number of different modifications can be analysed simultaneously in a single LC-MSMS run. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. Biological significance: The use of accurate mass extracted product ion chromatograms to detect oxidised peptides could improve the identification of oxidatively damaged proteins in inflammatory conditions. © 2013 Elsevier B.V.

The innovation value chain in new technology-based firms:evidence from the U.K.

Innovation is central to the survival and growth of firms, and ultimately to the health of the economies of which they are part. A clear understanding both of the processes by which firms perform innovation and the benefits which flow from innovation in terms of productivity and growth is therefore essential. This paper demonstrates the use of a conceptual framework and modeling tool, the innovation value chain (IVC), and shows how the IVC approach helps to highlight strengths and weaknesses in the innovation performance of a key group of firms-new technology-based firms. The value of the IVC is demonstrated in showing the key interrelationships in the whole process of innovation from sourcing knowledge through product and process innovation to performance in terms of the growth and productivity outcomes of different types of innovation. The use of the IVC highlights key complementarities, such as that between internal R&D, external R&D, and other external sources of knowledge. Other important relationships are also highlighted. Skill resources matter throughout the IVC, being positively associated with external knowledge linkages and innovation success, and also having a direct influence on growth independent of the effect on innovation. A key benefit of the IVC approach is therefore its ability to highlight the roles of different factors at various stages of the knowledge-innovation-performance nexus, and to show their indirect as well as direct impact. This in turn permits both managerial and policy implications to be drawn. © 2012 Product Development & Management Association.

Integrating strategic groups and the resource based perspective:understanding the competitive process

Although the strategic group and resource based perspectives are frequently presented as mutually exclusive, we argue otherwise. The resource based view informs strategic group analysis through a firm's product or service portfolio by offering a richer perspective on strategy and an additional lens for competitive group interpretation. Products act as the locus and bedrock for corporate decisions and form the backbone upon which market strategies are constructed. A "corporate genome" analogy is presented to illustrate how this process occurs within the U.K. pharmaceutical industry. © 2005 Elsevier Ltd. All rights reserved.

Success factors of product innovation:an updated meta-analysis

Assessing factors that predict new product success (NPS) holds critical importance for companies, as research shows that despite considerable new product investment, success rates are generally below 25%. Over the decades, meta-analytical attempts have been made to summarize empirical findings on NPS factors. However, market environment changes such as increased global competition, as well as methodological advancements in meta-analytical research, present a timely opportunity to augment their results. Hence, a key objective of this research is to provide an updated and extended meta-analytic investigation of the factors affecting NPS. Using Henard and Szymanski's meta-analysis as the most comprehensive recent summary of empirical findings, this study updates their findings by analyzing articles published from 1999 through 2011, the period following the original meta-analysis. Based on 233 empirical studies (from 204 manuscripts) on NPS, with a total 2618 effect sizes, this study also takes advantage of more recent methodological developments by re-calculating effects of the meta-analysis employing a random effects model. The study's scope broadens by including overlooked but important additional variables, notably “country culture,” and discusses substantive differences between the updated meta-analysis and its predecessor. Results reveal generally weaker effect sizes than those reported by Henard and Szymanski in 2001, and provide evolutionary evidence of decreased effects of common success factors over time. Moreover, culture emerges as an important moderating factor, weakening effect sizes for individualistic countries and strengthening effects for risk-averse countries, highlighting the importance of further investigating culture's role in product innovation studies, and of tracking changes of success factors of product innovations. Finally, a sharp increase since 1999 in studies investigating product and process characteristics identifies a significant shift in research interest in new product development success factors. The finding that the importance of success factors generally declines over time calls for new theoretical approaches to better capture the nature of new product development (NPD) success factors. One might speculate that the potential to create competitive advantages through an understanding of NPD success factors is reduced as knowledge of these factors becomes more widespread among managers. Results also imply that managers attempting to improve success rates of NPDs need to consider national culture as this factor exhibits a strong moderating effect: Working in varied cultural contexts will result in differing antecedents of successful new product ventures.

Agent-based simulation of lock-in dynamics in a duopoly

Lock-in is observed in real world markets of experience goods; experience goods are goods whose characteristics are difficult to determine in advance, but ascertained upon consumption. We create an agent-based simulation of consumers choosing between two experience goods available in a virtual market. We model consumers in a grid representing the spatial network of the consumers. Utilising simple assumptions, including identical distributions of product experience and consumers having a degree of follower tendency, we explore the dynamics of the model through simulations. We conduct simulations to create a lock-in before testing several hypotheses upon how to break an existing lock-in; these include the effect of advertising and free give-away. Our experiments show that the key to successfully breaking a lock-in required the creation of regions in a consumer population. Regions arise due to the degree of local conformity between agents within the regions, which spread throughout the population when a mildly superior competitor was available. These regions may be likened to a niche in a market, which gains in popularity to transition into the mainstream.

A near real-time water surface detection method based on HSV transformation of MODIS multi-Spectral time series data

In the face of global population growth and the uneven distribution of water supply, a better knowledge of the spatial and temporal distribution of surface water resources is critical. Remote sensing provides a synoptic view of ongoing processes, which addresses the intricate nature of water surfaces and allows an assessment of the pressures placed on aquatic ecosystems. However, the main challenge in identifying water surfaces from remotely sensed data is the high variability of spectral signatures, both in space and time. In the last 10 years only a few operational methods have been proposed to map or monitor surface water at continental or global scale, and each of them show limitations. The objective of this study is to develop and demonstrate the adequacy of a generic multi-temporal and multi-spectral image analysis method to detect water surfaces automatically, and to monitor them in near-real-time. The proposed approach, based on a transformation of the RGB color space into HSV, provides dynamic information at the continental scale. The validation of the algorithm showed very few omission errors and no commission errors. It demonstrates the ability of the proposed algorithm to perform as effectively as human interpretation of the images. The validation of the permanent water surface product with an independent dataset derived from high resolution imagery, showed an accuracy of 91.5% and few commission errors. Potential applications of the proposed method have been identified and discussed. The methodology that has been developed 27 is generic: it can be applied to sensors with similar bands with good reliability, and minimal effort. Moreover, this experiment at continental scale showed that the methodology is efficient for a large range of environmental conditions. Additional preliminary tests over other continents indicate that the proposed methodology could also be applied at the global scale without too many difficulties

Reconfiguration of supply chain network:an ISM-based roadmap to performance

Purpose: Short product life cycle and/or mass customization necessitate reconfiguration of operational enablers of supply chain (SC) from time to time in order to harness high levels of performance. The purpose of this paper is to identify the key operational enablers under stochastic environment on which practitioner should focus while reconfiguring a SC network. Design/methodology/approach: The paper used interpretive structural modeling (ISM) approach that presents a hierarchy-based model and the mutual relationships among the enablers. The contextual relationship needed for developing structural self-interaction matrix (SSIM) among various enablers is realized by conducting experiments through simulation of a hypothetical SC network. Findings: The research identifies various operational enablers having a high driving power towards assumed performance measures. In this regard, these enablers require maximum attention and of strategic importance while reconfiguring SC. Practical implications: ISM provides a useful tool to the SC managers to strategically adopt and focus on the key enablers which have comparatively greater potential in enhancing the SC performance under given operational settings. Originality/value: The present research realizes the importance of SC flexibility under the premise of reconfiguration of the operational units in order to harness high value of SC performance. Given the resulting digraph through ISM, the decision maker can focus the key enablers for effective reconfiguration. The study is one of the first efforts that develop contextual relations among operational enablers for SSIM matrix through integration of discrete event simulation to ISM. © Emerald Group Publishing Limited.

A taxonomy of measures for consumer-based brand equity:drawing on the views of managers in Europe

Purpose: The purpose of this paper is to identify the components of consumer-based brand equity from the perspective of experts in brand management in the UK, Germany and Greece. Design/methodology/approach: Data were collected from semi-structured interviews with senior brand consultants and managers, five in the UK, five in Germany and five in Greece. Findings: The findings suggested four categories of measures which can be used to define brand equity. These are the consumers' understanding of brand characteristics; consumers' brand evaluation; consumers' affective response towards the brand; and consumers' behaviour towards the brand. Specific dimensions are identified as indicators of each category. Research limitations/implications: Although the focus of this study is Europe, data were only collected from the UK, Germany and Greece, countries representing three of the five European cultural clusters. The resultant taxonomy adds to the fragmented literature on brand equity measurement by proposing four categories to gauge brand equity. Practical implications: The suggested taxonomy provides indicators of a framework managers could use when assessing brand equity. Originality/value: There is little agreement on what constitutes brand equity and therefore measures of brand equity are fragmented. To date, the views of practicing managers have not been taken into account in research. This paper draws on the views of practitioners and academics to suggest a taxonomy of categories of measures for brand equity. © Emerald Group Publishing Limited.

Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2-10 μm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. © 2014 Al-khattawi et al.