The formation and impact of hazard control policy:a study of the regulation of white lead paint in Britain

Government regulation of industrial hazards is examined in the context of the economic and technical processes of industrial development. Technical problems and costs of control are considered as factors in both the formation and impact of regulation. This thesis focuses on an historical case-study of the regulation of the hazard to painting workers from the use of lead pigments in paint. A regulatory strategy based on the prohibition of lead paints gained initial acceptance within the British state in 1911, but was subsequently rejected in favour of a strategy that allowed continued use of lead paint subject to hygiene precautions. The development of paint technology and its determinants, including concern about health hazards, are analysed, focusing on the innovation and diffusion into the paint industry of the major white pigments: white lead (PbC03 .PB(OH)2)and its substitutes. The process of regulatory development is examined, and the protracted and polarised regulatory d~bate contrasted to the prevailing 'consensual' methods of workplace regulation. The rejection of prohibition is analysed in terms of the different political and technical resources of those groups in conflict over this policy. This highlights the problems of consensus formation around such a strategy, and demonstrates certain constraints on state regulatory activity, particularly regarding industrial development. Member-states of the International Labour Organisation agreed to introduce partial prohibition of lead paint in 1921. Whether this was implemented is related to the economic importance of lead and non-lead metal and pigment industries to a nation. An analysis is made of the control of lead poisoning. The rate of control is related to the economic and technological trajectory of the regulated industry. Technical and organisational characteristics are considered as well as regulatory factors which range from voluntary compliance and informal pressures to direct legal requirements. The implications of this case-study for the analysis of the development and impacts of regulation are assessed.

Identification and analysis of moderator variables:investigating the customer satisfaction-loyalty link

Purpose – Research on the relationship between customer satisfaction and customer loyalty has advanced to a stage that requires a more thorough examination of moderator variables. Limited research shows how moderators influence the relationship between customer satisfaction and customer loyalty in a service context; this article aims to present empirical evidence of the conditions in which the satisfaction-loyalty relationship becomes stronger or weaker. Design/methodology/approach – Using a sample of more than 700 customers of DIY retailers and multi-group structural equation modelling, the authors examine moderating effects of several firm-related variables, variables that result from firm/employee-customer interactions and individual-level variables (i.e. loyalty cards, critical incidents, customer age, gender, income, expertise). Findings – The empirical results suggest that not all of the moderators considered influence the satisfaction-loyalty link. Specifically, critical incidents and income are important moderators of the relationship between customer satisfaction and customer loyalty. Practical implications – Several of the moderator variables considered in this study are manageable variables. Originality/value – This study should prove valuable to academic researchers as well as service and retailing managers. It systematically analyses the moderating effect of firm-related and individual-level variables on the relationship between customer satisfaction and loyalty. It shows the differential effect of different types of moderator variables on the satisfaction-loyalty link.

Particulate delivery systems for vaccines

This review focuses on the use of particulate delivery systems for the purposes of immunization. This includes poly(lactide-co-glycolide) (PLGA), ISCOMs, liposomes, niosomes, virosomes, chitosan, and other biodegradable polymers. These systems are evaluated in terms of their use as carriers for protein subunit and DNA vaccines. There is an extensive focus on recent literature, the understanding of biological interactions, and relation of this to our present understanding of immunological mechanisms of action. In addition, there is consideration of formulation techniques including emulsification, solvent diffusion, DNA complexation, and entrapment. The diversity of formulation strategies presented is a testament to the exponential growth and interest in the area of vaccine delivery systems. A case study for the application of particulate vaccine carriers is assessed in terms of vaccine development and recent insights into the possible design and application of vaccines against two of the most important pathogens that threaten mankind and for which there is a significant need: Mycobacterium tuberculosis and human immunodeficiency virus. This review addresses the rationale for the use of particulate delivery systems in vaccine design in the context of the diversity of carriers for DNA- and protein-based vaccines and their potential for application in terms of the critical need for effective vaccines. © 2005 by Begell House, Inc.

Celiac disease patient IgA antibodies induce endothelial adhesion and cell polarization defects via extracellular transglutaminase 2

We have recently found that celiac disease patient serum-derived autoantibodies targeted against transglutaminase 2 interfere with several steps of angiogenesis, including endothelial sprouting and migration, though the mechanism involved remained to be fully characterized. This study now investigated the processes underlying the antiangiogenic effects exerted by celiac disease patient antibodies on endothelial cells, with particular regard to the adhesion, migration, and polarization signaling pathway. We observed that celiac IgA reduced endothelial cell numbers by affecting adhesion without increasing apoptosis. Endothelial cells in the presence of celiac IgA showed weak attachment, a high susceptibility to detach from fibronectin, and a disorganized extracellular matrix due to a reduction of protein cross-links. Furthermore, celiac patient IgA led to secretion of active transglutaminase 2 from endothelial cells into the culture supernatants. Additionally, cell surface transglutaminase 2 mediated integrin clustering in the presence of celiac IgA was coupled to augmented expression of ß1-integrin. We also observed that celiac patient IgA-treated endothelial cells had migratory defects and a less polarized phenotype when compared to control groups, and this was associated with the RhoA signaling pathway. These biological effects mediated by celiac IgA on endothelial cells were partially influenced but not completely abolished by R281, an irreversible extracellular transglutaminase 2 enzymatic activity inhibitor. Taken together, our results imply that celiac patient IgA antibodies disturb the extracellular protein cross-linking function of transglutaminase 2, thus altering cell-extracellular matrix interactions and thereby affecting endothelial cell adhesion, polarization, and motility. © 2013 Springer Basel.

E-business adoption and its impact on performance

Organizations today face intense competitive and economic pressures leading to large scale transformation of existing business operations and transactions. In addition, organizations have adopted automated business processes to deal with partners and customers. E-business diffusion is a multi-phase process, moving from initiation through to routinisation and an insight into the adoption processes helps organizations to adopt e-business more effectively. It is imperative that organizations effectively manage the e-business environment, and all associated changes to accommodate the changing relationships with customers and business partners and more importantly, to improve performance. This chapter discusses the process of e-business implementation, usage and diffusion (routinisation stage) on business performance. © 2010, IGI Global.

Effect of incorporating cholesterol into DDA:TDB liposomal adjuvants on Bilayer properties, biodistribution, and immune responses

Cholesterol is an abundant component of mammalian cell membranes and has been extensively studied as an artificial membrane stabilizer in a wide range of phospholipid liposome systems. In this study, the aim was to investigate the role of cholesterol in cationic liposomal adjuvant system based on dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) which has been shown as a strong adjuvant system for vaccines against a wide range of diseases. Packaging of cholesterol within DDA:TDB liposomes was investigated using differential scanning calorimetery and surface pressure-area isotherms of lipid monolayers; incorporation of cholesterol into liposomal membranes promoted the formation of a liquid-condensed monolayer and removed the main phase transition temperature of the system, resulting in an increased bilayer fluidity and reduced antigen retention in vitro. In vivo biodistribution studies found that this increase in membrane fluidity did not alter deposition of liposomes and antigen at the site of injection. In terms of immune responses, early (12 days after immunization) IgG responses were reduced by inclusion of cholesterol; thereafter there were no differences in antibody (IgG, IgG1, IgG2b) responses promoted by DDA:TDB liposomes with and without cholesterol. However, significantly higher levels of IFN-gamma were induced by DDA:TDB liposomes, and liposome uptake by macrophages in vitro was also shown to be higher for DDA:TDB liposomes compared to their cholesterol-containing counterparts, suggesting that small changes in bilayer mechanics can impact both cellular interactions and immune responses. © 2013 American Chemical Society.

Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor:implications for adrenomedullin and calcitonin gene-related peptide pharmacology

Background and Purpose Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear. Experimental Approach Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants. Key Results An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide. Conclusions and Implications RAMP-dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N-terminus. RAMP3 appears to alter the role of specific residues at the CLR-RAMP interface compared with RAMP1 and RAMP2. © 2013 The Authors. British Journal of Pharmacology published by John Wiley &. Sons Ltd on behalf of The British Pharmacological Society.

Proteomic analysis of phosphorylation, oxidation and nitrosylation in signal transduction

Signal transduction pathways control cell fate, survival and function. They are organized as intricate biochemical networks which enable biochemical protein activities, crosstalk and subcellular localization to be integrated and tuned to produce highly specific biological responses in a robust and reproducible manner. Post translational Modifications (PTMs) play major roles in regulating these processes through a wide variety of mechanisms that include changes in protein activities, interactions, and subcellular localizations. Determining and analyzing PTMs poses enormous challenges. Recent progress in mass spectrometry (MS) based proteomics have enhanced our capability to map and identify many PTMs. Here we review the current state of proteomic PTM analysis relevant for signal transduction research, focusing on two areas: phosphorylation, which is well established as a widespread key regulator of signal transduction; and oxidative modifications, which from being primarily viewed as protein damage now start to emerge as important regulatory mechanisms.

Purchasing consortia and electronic markets:a procurement direction in integrated supply chain management

In supply chain management literature, there has been little empirical research investigation on purchasing consortium issues focusing on a detailed analysis of information and communication (ICT) based procurement strategies. Based on the exploration of academic literature and two surveys among purchasing organisations as well as e-Marketplaces / procurement service providers (PSPs) in the automotive and electronics industry sectors, the research methodology follows a positivistic approach in order to assess the overall statement: ‘Effective participation in electronic purchasing consortia (EPC) can have the potential to enhance competitive advantage. Implementation therefore requires a clear and detailed understanding of the major process structures and drivers, based upon thetechnology-organisation-environment framework.’ Key factors and structures that affect the adoption and diffusion of EPC and the performance impact of adoption are investigated. The empirically derived model for EPC can be a valuable starting point to EPC research.

Pair breaking and bound states in disordered superconductors

We study the effects of inhomogeneous pairing interactions and impurities in short-coherence-length superconductors. Within the Born approximation, the effects of pairing disorder and magnetic impurities are identical. The T-matrices for pairing disorder sites with and without an impurity give rise to bound states within the BCS (Bardeen-Cooper-Schrieffer) gap, consistent with scanning tunnelling microscopy results on Bi2Sr2CaCu2O8+δ with Zn or Ni impurities.

Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis

Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies.

Effect of incorporating cholesterol into DDA:TDB liposomal adjuvants on Bilayer properties, biodistribution, and immune responses

Cholesterol is an abundant component of mammalian cell membranes and has been extensively studied as an artificial membrane stabilizer in a wide range of phospholipid liposome systems. In this study, the aim was to investigate the role of cholesterol in cationic liposomal adjuvant system based on dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) which has been shown as a strong adjuvant system for vaccines against a wide range of diseases. Packaging of cholesterol within DDA:TDB liposomes was investigated using differential scanning calorimetery and surface pressure-area isotherms of lipid monolayers; incorporation of cholesterol into liposomal membranes promoted the formation of a liquid-condensed monolayer and removed the main phase transition temperature of the system, resulting in an increased bilayer fluidity and reduced antigen retention in vitro. In vivo biodistribution studies found that this increase in membrane fluidity did not alter deposition of liposomes and antigen at the site of injection. In terms of immune responses, early (12 days after immunization) IgG responses were reduced by inclusion of cholesterol; thereafter there were no differences in antibody (IgG, IgG1, IgG2b) responses promoted by DDA:TDB liposomes with and without cholesterol. However, significantly higher levels of IFN-gamma were induced by DDA:TDB liposomes, and liposome uptake by macrophages in vitro was also shown to be higher for DDA:TDB liposomes compared to their cholesterol-containing counterparts, suggesting that small changes in bilayer mechanics can impact both cellular interactions and immune responses. © 2013 American Chemical Society.

How organizational cognitive neuroscience can deepen understanding of managerial decision-making:a review of the recent literature and future directions

There is growing interest in exploring the potential links between human biology and management and organization studies, which is bringing greater attention to bear on the place of mental processes in explaining human behaviour and effectiveness. The authors define this new field as organizational cognitive neuroscience (OCN), which is in the exploratory phase of its emergence and diffusion. It is clear that there are methodological debates and issues associated with OCN research, and the aim of this paper is to illuminate these concerns, and provide a roadmap for rigorous and relevant future work in the area. To this end, the current reach of OCN is investigated by the systematic review methodology, revealing three clusters of activity, covering the fields of economics, marketing and organizational behaviour. Among these clusters, organizational behaviour seems to be an outlier, owing to its far greater variety of empirical work, which the authors argue is largely a result of the plurality of research methods that have taken root within this field. Nevertheless, all three clusters contribute to a greater understanding of the biological mechanisms that mediate choice and decision-making. The paper concludes that OCN research has already provided important insights regarding the boundaries surrounding human freedom to act in various domains and, in turn, self-determination to influence the workplace. However, there is much to be done, and emerging research of significant interest is highlighted.

Coordinating expertise across knowledge boundaries in offshore-outsourcing projects:the role of codification

The coordination of effort within and among different expert groups is a central feature of contemporary organizations. Within the existing literature, however, a dichotomy has emerged in our understanding of the role played by codification in coordinating expert groups. One strand of literature emphasizes codification as a process that supports coordination by enabling the storage and ready transfer of knowledge. In contrast, another strand highlights the persistent differences between expert groups that create boundaries to the transfer of knowledge, seeing coordination as dependent on the quality of the reciprocal interactions between groups and individuals. Our research helps to resolve such contested understandings of the coordinative role played by codification. By focusing on the offshore-outsourcing of knowledge-intensive services, we examine the role played by codification when expertise was coordinated between client staff and onsite and offshore vendor personnel in a large-scale outsourcing contract between TATA Consultancy Services (TCS) and ABN AMRO bank. A number of theoretical contributions flow from our analysis of the case study, helping to move our understanding beyond the dichotomized views of codification outlined above. First, our study adds to previous work where codification has been seen as a static concept by demonstrating the multiple, coexisting, and complementary roles that codification may play. We examine the dynamic nature of codification and show changes in the relative importance of these different roles in coordinating distributed expertise over time. Second, we reconceptualize the commonly accepted view of codification as focusing on the replication and diffusion of knowledge by developing the notion of the codification of the “knower” as complementary to the codification of knowledge. Unlike previous studies of expertise directories, codification of the knower does not involve representing expertise in terms of occupational skills or competences but enables the reciprocal interrelating of expertise required by more unstructured tasks.

The big 4 in Bangladesh:caught between the global and the local

Purpose- This article explores the work practices of Big 4 firms in Bangladesh with the aim of exploring the extent to which Global Professional Service Firms can be thought of as being genuinely ‘global’. Methodology/Approach- Interviews were undertaken with the vast majority of Big 4 partners in Bangladesh. These interviews explored a number of themes related to the professional service work context in Bangladesh and the relationship between local and global firms. Findings- The central finding of this paper is that although the Big 4 have a long-established presence in Bangladesh, local societal factors heavily influence the realities of work for accountants there. In most cases the Big 4 firms establish correspondent firms (instead of full member firms) in Bangladesh and tend to offer restricted service lines. Additionally, the paper identifies professional, commercial and cultural barriers to greater Big 4 involvement in the local market. Conceptually, the chief contribution of this paper is to explore how the effects of globalising capitalism and standardised ‘best practices’ in global professional service work are mediated through the societal effects of Bangladeshi society, resulting in the Big 4 having only a tentative presence in the Bangladeshi market. Research implications- The findings cast doubt on the extent to which self-styled Global Professional Service firms are truly ‘global’ in nature. Future work examining the Big 4, or accounting more generally, in the context of globalization, would do well to pay greater attention to the experience of professionals in emerging markets. Originality/Value- Whilst there has been much work looking at accounting and accountants in the context of globalization, this work has tended to privilege ‘core’ western empirical settings. Very little is known about Professional Service Firms in ‘peripheral’ or emerging markets. Furthermore, this study extends the application of the System, Society and Dominance framework by mapping the interactions and dynamics of these three sources of influence in the setting of PSFs.